pathophysiology and management of cardiogenic shock

PATHOPHYSIOLOGY AND MANAGEMENT OF CARDIOGENIC

SHOCK

WILLIAM P. DOLE, M.D. ROBERT A. O’ROURKE, M.D.

014%2806183:06-OOl-072-$9.95 ( 1983. Year Rook Medical Publishers. Inc.

TABLE OF CONTENTS

SELF-ASSESSMENT QUESTIONS ................

SELF-ASSESSMENT ANSWERS .................

DEFINITION AND ETIOLOGY. .................

PATHOPHYSIOLOGY OF CARDIOGENIC SHUCK ..........

HEMODYNAMICS AND PROGRESSIVE NATURE OF

CARDIOGENK SHUCK ........

MECHANICAL COMPLICATIONS OF MYOCARDIAI. INFARCTION

EXTRAMYOCARDIAL FACTORS IN THE PATHOPHYSIOLOGY OF SHOCK

CARUIOGENIL SHOCK WITHOUT CC)RONARY ARTERI’ DISEASE. ..

FEEDBACK MECHANISMS AND THE PERIPHERAL CIRCL~LATION

IN CARDIOGENIC SHOCK ..................

CLINICAL ASSESSMENT OF CARDIOGENIC SHOCK ......

CARDIOVASCULAR EXAMINATION ...............

HEMODYNAMIC MONITORING CARDIOGENIC SHOCK .......

HEMODYNAMIC INDICES OF PROGNOSIS IN CARDIOGENIC SHOCK

ADDITIONAL DIAGNOSTIC USES OF HEMODYNAMIC MONITORING

IN CARDIOGENIC SHOCK ..................

MANAGEMENT OF CARDIOGENIC SHOCK ............

DRUG THERAPY FOR CARDIOGENIC SHOCK ...........

VASODILATOR THERAPY IN CARDIOGENIC SHOCK ........

MECHANICAL CIRCULATORY ASSISTANCE ...........

ROLE OF EMERGENCY SURGERY IN CARDIOGENIC SHUCK .....

Sbj1\ik~t\K’I AND FUTURE DIREC.~IONS. .............

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Editorial Board (from fop to bottom, leff to right): W. Proctor Harvey, Antonio C. de Leon, Jr., Mary Allen Engle, Robert A. CSRourke, William C. Roberts, Robert Schlant. and Robert B. Wallace

SELF-ASSESSMENT QUESTIONS

1. The single most important pathophysiologic feature which characterizes circulatory shock is: a. Hypotension with systolic pressure of less than 90 mm

His b. Weak thready pulses. c. Inadequate tissue blood flow. d. Metabolic acidosis.

2. Which of the following is not an important compensatory feedback mechanism in shock? a. Increased activity of the sympathetic nervous system. b. Increased adrenal medullary synthesis of catechol-

amines. c. Decrease in oxygen utilization by vital organs. d. ADH release from the posterior pituitary. e. Secretion of renin from the juxtaglomerular apparatus.

3. Which of the following is not true of the nervous system during shock? a. Enhancement of sympathetic tone is mediated mainly by

inhibition of baroreceptor activity. b. Enhancement of sympathetic tone is mediated in part by

relative inhibition of parasympathetic activity. c. Sympathetic nervous system may influence intravascular

volume regulation. d. Sympathetically mediated vasoconstriction results in a

decrease in the ratio of precapillary to postcapillary resistance.

4. Which of the following statements about local vasoregulatory mechanisms in shock is false? a. Tissue ischemia results in metabolite accumulation,

causing a decrease in vascular resistance. b. Autoregulation of blood flow is strongest in the skin and

skeletal muscle, which have the largest tissue mass. c. Blood flow to a given organ is primarily determined by

perfusion pressure and regional vascular resistance. d. Excessive sympathetic vasoconstriction can lead to a re-

duction in intravascular volume. 5. Which of the following is/are a major determinant(s) of myo-

cardial oxygen consumption? a. Heart rate. b. Contractile state. c. Systolic aortic pressure. d. End-diastolic volume. e All of the above.

d

6. Which of the following statements regarding the clinical assessment of cardiogenic shock is/are true? a. The earliest hemodynamic signs of a reduced cardiac out-

put include tachycardia and a decrease in arterial pulse pressure.

b. A weak thready pulse always results from a reduction in arterial pressure.

c. The skin temperature in the shock state reflects the intensity of the sympathoadrenal discharge.

d. Urinary sodium concentration can provide an earlier indication of reduced renal perfusion before oliguria de- velops.

e. All of the above. 7. Which of the following statements is/are true about hemo-

dynamic monitoring in cardiogenic shock? a. The sphygmomanometer may be used to assess the blood

pressure in shock, provided the cuff pressure is greater than 90160.

b. Pulmonary capillary wedge pressure is influenced only by intravascular volume and therefore provides a useful index of left ventricular filling pressure.

c. Pulmonary artery end-diastolic pressure may underesti- mate left ventricular end-diastolic pressure during tachycardia (heart rates greater than 124 beats/minute).

d. The optimal pulmonary capillary wedge pressure in cardiogenic shock for a patient with a colloid oncotic pressure of 10 mm Hg is 14 to 18 mm Hg.

e. None of the above. 8. Papillary muscle rupture or severe dysfunction and rupture

of the muscular interventricular septum after acute infarction are characterized by sudden clinical deterioration with hypotension, pulmonary edema, and shock. Which one of the following is not true about these conditions? a. A holosystolic murmur along the lower left sternal bor-

der is diagnostic of ventricular septal rupture and ex- cludes the possibility of mitral regurgitation.

h. Severe mitral regurgitation may occur in cardiogenic shock in the absence of a heart murmur.

c. A systolic thrill along the lower left sternal border is highly suggestive of ventricular septal rupture.

d. Definitive differential diagnosis of these two conditions requires right-sided catheterization.

9. The two most useful sympathomimetic drugs in the treatment of cardiogenic shock are: a. Epinephrine and dobutamine. b. Norepinephrine and dopamine. c. Isoproterenol and epinephrine. d. Dopamine and phenylephrine.

e. Epinephrine and norepinephrine. 10. Which of the following statements about the current surgi-

cal approach to patients with cardiogenic shock is/are true? a. When shock is due entirely to extensive myocardial dam-

age (ejection fraction less than 25%) adequate revascularization is likely to reverse the shock syndrome.

b. Adequate hemodynamic function can be maintained with excision of 50% of left ventricular muscle mass.

c. Surgery for mechanical complications of acute infarction combined with myocardial revascularization has improved the mortality associated with cardiogenic shock in selected patients.

d. Most patients with papillary muscle rupture or ventricular septal rupture can be stabilized with aggressive medical therapy for several weeks prior to elective surgery.

e. All of the above.

SELF-ASSESSMENT ANSWERS

1. c 6. b 7e

3”:: EL 4. b 9: b 5. e 10. c

is Assistant Professor of Medicine at the University of Texas Health Science Center and Audie Murphy Veterans Administra- tion Hospital, San Antonio. Dr. Dole received his B.A. degree from Columbia Uni- versity in 1969 and his M.D. degree from the New York University School of Medi- cine in 1973. He had postgraduate training in internal medicine and clinical pharma- cology at the University Hospitals of Cleveland, Case Western Reserve Univer- sity, and completed training in clinical cardiology at the University of Texas Health Science Center, San Antonio, where he was also an NHLBI Cardiovas- cular Research Fellow. Dr. Dole’s primary research interests involve basic mechanisms of coronary blood flow regulation during physiologic conditions and pathophysiologic states.

is Professor of Medicine and Director of Cardiovascular Division at the University of Texas Health Science Center in San An- tonio, and also Chairman of the American Heart Association’s Council on Clinical Cardiology. He received his medical degree from Creighton University School of Med- icine and completed his residency at Georgetown University Hospital in Wash- ington, D.C. Dr. O’Rourke’s current scien- tific interests are the effects of calcium blockers on cardiac function, coronary heart disease, and complement-mediated injury of ischemic myocardium. Dr. O’Rourke is on the editorial board of the American Heart Journal and is also the Associate Editor of Current Problems in Cardiology.

CARDIOGENIC SHOCK is an extreme form of circulatory failure related to primary impairment of the heart to function adequately as a pump in meeting tissue requirements for blood flow,

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Most commonly, cardiogenic shock presents as a catastrophic complication of acute myocardial infarction (AMI), but it can result from end-stage cardiac disease of any etiology, and it may also occur transiently following cardiopulmonary bypass surgery. With early recognition and treatment of potentially fatal arrhythmias complicating myocardial infarction, cardiogenic shock has emerged as the most common cause of death in patients admitted to the coronary care unit. Despite advances in hemodynamic monitoring and newer pharmacologic agents, the incidence of shock following acute infarction remains at lO%- 15% and carries a mortality of 80%-100%.1-5 This high mortality is chiefly related to extensive irreversible loss of left ventricular myocardium. Recent observations are compatible with the concept that cardiogenic shock represents a self-perpetuating cycle of progressive ischemic damage culminating in irreversible myocardial dysfunction.6-s Since prognosis is related to infarction size, the ultimate success of therapy depends largely on reducing myocardial ischemia and limiting permanent cardiac damage. To achieve this goal, therapeutic interventions must be instituted at an early stage in the course of complicated myocardial infarction before fully developed shock occurs. Once shock becomes evident, efforts must be directed at treating any reversible hemodynamic or metabolic derangements that could result in progressive ischemia and cardiac failure.

This monograph discusses the pathophysiology and clinical assessment of cardiogenic shock with particular emphasis on early recognition. The role of hemodynamic monitoring is considered in the context of providing a physiologic basis for specific modes of therapy and assessing their efficacy. The current use of various vasoactive and inotropic drugs, mechanical circulatory assistance, and the indications for emergency cardiac surgery are reviewed.

DEFINITION AND ETIOLOGY

Circulatory shock is a complex pathophysiologic state characterized by a reduction in tissue blood flow and oxygen delivery below levels required to meet metabolic demands, despite compensatory mechanisms.g3 lo If it is left untreated, progressive circulatory failure and impaired cellular metabolism develop, leading to organ dysfunction and eventual death. A critical reduction in tissue perfusion may result from a derangement in any one of the basic components of the circulation-the heart, blood volume, or vascular system. The term cardiogenic shock is used to describe the shock syndrome that results directly from severely impaired ventricular pump function. However, other mechanisms such as hypovolemia and vasomotor and microcir- culatory dysfunction may contribute to progressive cardiovascular deterioration, particularly in the late stages.

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The clinical diagnosis of cardiogenic shock is based on evidence of inadequate cardiac output as manifested by decreased blood flow to the brain, kidneys, and skin that is directly attributable to myocardial pump dysfunction (Table 1). It is worth stressing that the diagnosis of cardiogenic shock should be made only after extramyocardial causes of hypotension and reduced cardiac output have been corrected. These include a variety of conditions such as arrhythmias, hypoxemia and acidosis, drug- induced hypotension, and hypovolemia, which are frequently en- countered in patients admitted to the coronary care unit. Any one of these conditions alone may not be sufficient to cause shock, but in the setting of depressed myocardial function they may further impair coronary perfusion and reduce cardiac output, thus potentiating the shock syndrome. One of the first priorities in managing the patient who presents with cardiogenic shock is to immediately recognize and correct these contributing factors.

The cardinal feature of circulatory shock, regardless of etiology, is inadequate tissue blood flow. Shock is not equivalent to low blood pressure, although hypotension is usually present. The distinction between shock and hypotension has important physiologic significance. Blood flow depends not only on perfusion pressure, but on vascular resistance as well. Flow may fall below critical levels required for cellular viability and yet arterial pressure can be maintained by an increase in total systemic resistance. Thus shock can occur without severe hypotension, which is actually a relatively late sign indicating inadequate reflex vasoconstriction. ‘The distinction between shock and hypotension also has important therapeutic implications. The major goal in treating shock is rapid restoration of tissue perfusion. If systemic pressure is raised by increasing vascular resistance to vital organs, then tissue blood flow may decrease, resulting in further ischemia and organ dysfunction.

The etiologic classification of cardiogenic shock is summarized in Table 2. Although shock may complicate any form of severely advanced heart disease, it most commonly occurs following AMI. In this setting, the immediate abnormality is reduced coronary blood flow and oxygen delivery with secondary impairment of

TABLE L-CLINICAL DEFINITION OF CARDIOGENIC SHOCK

1. Peak systolic pressure < 90 mm Hg or 30 mm Hg below previous basal levels.

2. Altered sensorium (confusion, lethargy, coma, agitation). 3. Peripheral vasoconstriction manifested by cool, clammy skin, often with

cyanosis. 4. Urine output < 20 ml/hour. 5. Persistence of shock after correction of extramyocardial factors contributing

to hypotension and reduced cardiac output (arrhythmias, pain, vasovagal reactions, hypoxemia, acidosis, hypovoiemia, etc.).

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TABLE 2.-ETIOLOGY OF CARDIOGENIC SHOCK

1. Acute myocardial infarction Loss of critical muscle mass Mechanical complications

Papillary muscle rupture or dysfunction Perforated inter-ventricular septum Cardiac rupture Ventricular aneurysm

2. End-stage cardiomyopathy Congestive (idiopathic, alcoholic, hypertensive, ischemic,

myocarditis, amyloid, etc. J Hypertrophic Restrictive

3. Valvular heart disease Severe valvular stenosis Acute valvular regurgitation

4. Following cardiopulmonary bypass surgery

pump function.l’, l2 When cardiogenic shock occurs in association with diseases other than coronary atherosclerosis (e.g., cardiomyopathy), impairment of cardiac contractility is related to primary myocardial disease, while coronary blood flow is generally normal. The remaining discussion will deal primarily with cardiogenic shock related to AMI.

PATHOPHYSIOLOGY OF CARDIOGENIC SHOCK

Proper management of the patient in cardiogenic shock requires a basic understanding of pathophysiology of myocardial infarction and of the shock syndrome. The primary defect in shock following myocardial infarction is severely depressed ventricular function, which results in reduced cardiac output and inadequate tissue perfusion. The magnitude of the hemodynamic impairment is primarily related to the total amount of myocardial damage, which in turn is related to the extent of coronary artery disease and the balance between oxygen supply and demand. 5, i3-16 The majority of patients exhibit significant athero- sclerotic narrowing of all three major coronary vessels with extensive involvement of the left anterior descending artery.i7 The development of the shock syndrome has been correlated with destruction of 40% or more of the left ventricular myocardium. An important but frequently overlooked point is that the amount of ventricular damage associated with shock represents cumulative loss of myocardium. 16* l8 Thus, cardiogenic shock may be precip- itated by a seemingly small infarction in the setting of prior myocardial damage, as well as by a single massive infarction. In addition, extension of an uncomplicated infarct may result in cardiogenic shock. Pathologic studies of hearts obtained at au- topsy from nonsurvivors of cardiogenic shock have confirmed that the extensive loss of left ventricular myocardium is due to

new as well as old infarction, and that marginal extension of recent infarction is common.16* l8 Following infarction in experimental animals, three myocardial regions may be defined histo- logically, biochemically, and functionally (Fig lL1*, 1g-22 There is a zone of central necrosis surrounded by an area of ischemia (border zone), outside of which is normal uninvolved myocardium. The central necrotic zone is irreversibly damaged and un- amenable to any current forms of therapy. The ischemic zone is comprised of depressed but still viable myocardial cells, the fate of which depends on the fine balance between oxygen supply and demand. Factors that increase oxygen demand in excess of supply result in additional myocardial damage and enlargement of the necrotic zone. Progression of the ischemic zone to necrosis results in further hemodynamic impairment, which initiates a vicious positive feedback cycle leading to intractable pump failure and irreversible shock. It is apparent that the immediate clinical course of patients who initially survive AM1 will depend on whether the ischemic zone recovers its structural and functional integrity or enlarges and goes on to necrosis. This in turn depends on the myocardial oxygen supply-demand relationship. To be effective, any treatment for cardiogenic shock should favorably influence the balance between oxygen supply and demand in the ischemic zone.

The major determinants of myocardial oxygen consumption are heart rate, myocardial wall tension (determined by systolic pressure and end-diastolic volume), and myocardial contractility (Fig 2).23 That th e endocardium is more vulnerable than the ep- icardium to tissue dam’age in ischemic heart disease has been attributed to the higher intramyocardial wall tension and lower

Fig l.-Following experimental coronary artery occlusion, 3 myocardial regions can be defined: a zone of central necrosis surrounded by an ischemic zone, and normal myocardium. The ischemic zone consists of depressed but still viable myocardial cells, the fate of which depends on the balance between oxygen supply and demand. With longer occlusion durations (3 and 96 hours) there is progression of the ischemic zone to necrosis beginning in the subendocardial region and extending to the subepicardium. (From Reimer K.A., Jennings RR.: The “wavefront phenomenon” of myocardial ischemic cell death. Lab. invest 40:633, 1979. Reproduced by permission.)

40 Minutes 3 Hours

07 Nonrxhemic : lschemic I Viable I

96 Hours

a= Necrotic

OXYGEN DEMAND OXYGEN SUPPLY

FREQUENCY OF PRESSURE DEVELOPMENT ,+ I=[----

RATE OF PRESSURE DEVELOPMENT !Ll

VENTRICULAR VOLUME 4

PRESSURE DEVELOPED

I EXTRAVASCULAR I

PERFUSION PRESSURE

PERIPHERAL ARTERIAL TONE

VENOUS TONE, ATRIAL TRANSPORT

CORONARY ARTERIAL TONE

Fig 2.---Determinants of myocardial oxygen utilization. interactions, positive or negative, between factors are indicated by arrows. (From Pantridge J.F., et al.: The Acute Coronary Attack. New York, Grune & Stratton, 1975, Tunbridge Wells, En- gland, Pitman Medical. Reproduced by permission of Pitman Books Ltd., London.)

oxygen content in the deeper layers of the myocardium.“4-26 Cardiogenic shock associated with coronary artery disease generally results in predominantly left ventricular impairment. This is because the left ventricular systolic pressure load and thus wall tension are much greater than those of the right ventricle, resulting in higher metabolic demands and oxygen consumption. Any reduction in coronary blood flow would more likely cause ischemic damage to the left ventricle. In addition, the total myocardial mass supplied by the left coronary artery is greater than that supplied by the right, so more cumulative left ventricular muscle damage could occur with proximal occlusive disease. The role of right ventricular dysfunction in cardiogenic shock is not well established. Rarely, patients with right ventricular infarction and predominantly right ventricular failure develop cardiogenic shock.27

Myocardial oxygen supply is related to coronary blood flow and oxygen extraction. Since oxygen of normal aerobic cardiac metabolism is supplied by a relatively low flow and high extraction ratio (60%-65%), any change in myocardial oxygen demands must be met mainly by regulating coronary blood flow. In the normal heart, coronary blood flow is regulated by changes in coronary vascular resistance, which are controlled b z3 metabolic, mechanical, neural, and humoral factors (Fig 3). Coro- nary flow is relatively independent of changes in perfusion pressure over physiologic ranges (autoregulation). In the setting of coronary artery disease, however, a severe proximal stenosis

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Fig 3.--Regulation of coronary blood flow. Coronary flow is dependent on coronary perfusion and vascular resistance. In the normal heart coronary flow is regulated by changes in coronary vascular resistance, which are controlled by metabolic, neurohumoral, and mechanical factors. HR, heart rate; SV, stroke volume; CO, cardiac output; SBP, systemic blood pressure; SW, systemic vascular resistance; CW, coronary blood flow; CPP, coronary perfusion pressure; CVR, coronary vascular resistance.

may lim it flow despite maximum arteriolar vasodilation. Under these circumstances perfusion pressure becomes a ma jor deter- m inant of coronary blood flow since the ma jor resistance to flow is the fixed proximal stenosis rather than the arteriolar bed, which is already maximally dilated. Since pressure falls beyond a stenotic lesion, distal coronary perfusion pressure may be considerably lower than aortic pressure, and any slight decrease in systemic pressure could reduce coronary pressure and flow below critical levels.2g

Collateral coronary flow probably plays an important role in the pathophysiology of cardiogenic shock, but this remains controversial. The potential significance of collaterals is based on

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the observation that the histologic size of an infarct is often smaller than the total area supplied by the occluded vessel. In a recent angiographic study of patients with complicated myocardial infarction, the hemodynamic dysfunction, incidence of shock, and mortality were significantly less in patients with de- monstrable collateral vessels to the area of infarction.30 Other postmortem studies, however, have not demonstrated any relationship between collateral vessels and extent of myocardial infarction.

HEMODYNAMICS AND PROGRESSIVE NATURE OF CARDIOGENIC SHOCK

The marked depression of ventricular performance in cardiogenic shock usually results in severe derangement of all hemodynamic parameters of cardiac function. The initial hemodynamic abnormality is a reduction in stroke volume and cardiac output, generally less than 2.0 L/minute/m’ (Fig 4).l, 4, ’ Such a low cardiac output may be seen in patients without evidence of

Fig 4.-Pathophysiology of cardiogenic shock. SV, stroke volume; HR, heart rate; CO, cardiac output. In the early stages of shock, compensatory negative feedback mechanisms operate to restore perfusion pressure and nutritive flow to vital organs. If adequate tissue flow is not restored, positive feedback mechanisms eventually lead to progressive shock and irreversible cellular damage. (From Dole W.P., O’Rourke PA.: Circulatory shock, in Stein J. (ed.): Internal Medicine, Boston, Little, Brown & Co., 1982. Reproduced with permission.)

shock, reemphasizing the importance of regional distribution of flow and energy utilization in the pathogenesis of the shock syndrome. A reduction in cardiac output without a compensatory increase in total vascular resistance will result in hypotension and decreased tissue flow unless regional vascular resistance also decreases. If blood flow and oxygen delivery fall below a critical level, cellular ischemia and ultimately irreversible damage will occur.

The effects of prolonged hypotension following AM1 are particularly detrimental to cardiac function because of the pressure dependency of myocardial blood flow in the presence of severe occlusive coronary artery disease.” Thus, any reduction in diastolic pressure to hypotensive levels may severely impair coronary perfusion, resulting in further ischemia and necrosis. This causes additional impairment in cardiac pump function, which in turn further reduces cardiac output, blood pressure, and coronary flow. This positive feedback cycle, in which cardiac pump dysfunction leads to progressive myocardial ischemia and intractable circulatory failure, may explain the high mortality and the relative ineffectiveness of traditional drug therapy in cardiogenic shock. Recent histologic and biochemical data in man are consistent with this concept of continuous, self-perpetuating ischemic injur resulting in progressive, irreversible myocardial dysfunction. 27 Consequently, major therapeutic consideration should be directed toward improving myocardial perfusion and oxygenation.

The reduced cardiac output and systemic hypotension charac- teristic of cardiogenic shock usually occur in association with elevated left ventricular filling pressure.i’ 2, 33 31 In fact, the very presence of an elevated end-diastolic pressure in the setting of shock should immediately suggest an element of cardiac dysfunction as an underlying etiologic factor. Although an increase in left ventricular end-diastolic volume is frequently observed in patients with congestive heart failure, a normal heart size is not uncommon following AMI, even when complicated by failure or shock. Thus the increase in end-diastolic pressure cannot be taken as evidence for cardiac enlargement. While part of the elevated filling pressure may be related to reduced systolic function and an increase in end-diastolic volume, a more important contributing factor is decreased compliance and distensibility of the ischemic myocardium. Because of diminished ventricular compliance, even slightly elevated end-diastolic pressure may not reflect an adequate preload following acute infarction.32-34 It may be necessary in such instances to increase filling pressure above normal to achieve an optimal cardiac output. In terms of the Frank-Starling principle, which relates cardiac performance to ventricular filling, the function curve in cardiogenic shock is depressed, flattened, and shifted to the right (Fig 5). At any given filling pressure, cardiac output is severely reduced but

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1 I i I I LVEDP, mmHg -

Fig B.-Ventricular function curves in normal subject, acute uncomplicated transmural myocardial infarction (M/), acute MI with congestive heart faiure (CHF), and acute MI with cardiogenic shock. Points A, t3, and C all represent the same cardiac output, but each is at a different level of left ventricular end-diastolic pressure (LVEDP) shown by the verticel broken lines. In shock, despite operation of the ventricle at the peak of its function curve (point D) with marked elevation of LVEDP, an adequate cardiac output cannot be delivered and hypotension results. (From Mason D.T., Amsterdam E.A., et al.: Diagnosis and management of myocardial infarction shock, in Eliot R.S. (ed.): Cardiac Emergencies. Mount Kisco, N.Y., Futura Publish- ing Co., 1982. Reproduced with permission.)

may be augmented somewhat by increasing ventricular filling. The elevated left ventricular end-diastolic pressure (LVEDP) is passively transmitted to the left atrium and pulmonary veins. The increase in pulmonary venous pressure results in transudation of fluid, which may precipitate pulmonary edema. Arte- rial hypoxemia is a consistent finding in cardiogenic shock and is related to both pulmonary venous congestion and ventilation- perfusion abnormalities.35 Pulmonary artery pressure is also elevated in cardiogenic shock as a result of passive transmission of the elevated LVEDP and increased pulmonary vascular resistance due to hypoxia and acidosis. Right ventricular failure may result from significant pulmonary hypertension or from infarction involving the right ventricle. Under these conditions, central venous pressure (CVP) may be elevated. However, it is important to recognize that in the absence of right ventricular failure, CVP may be normal despite profound left ventricular failure or cardiogenic shock.

Other hemodynamic parameters used to assess cardiac function such as cardiac or stroke work, and isovolumetric and ejection phase indices of contractility, are also markedly depressed in cardiogenic shock.36-38 Stroke work appears to correlate best with the severity of the shock syndrome. This is because stroke work is derived from stroke volume, systolic pressure, and heart rate, each of which has independent prognostic significance following myocardial infarction.“”

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MECHANICAL COMPLICATIONS OF MYOCARDIAL INFARCTION

Mechanical complications of AM1 may significantly contribute to already impaired cardiac function by exacerbating congestive failure or precipitating shock. 3g-42 These structural defects include acute mitral regurgitation, ventricular septal rupture, and ventricular aneurysm (Fig 6). Recognition of these entities is important because aggressive medical treatment and possible surgical intervention may be lifesaving.

Mitral regurgitation following AM1 is generally due to papillary muscle dysfunction and less commonly to actual rupture or infarction of the body of the papillary muscle or one of its heads. Ventricular wall motion abnormalities and cardiac dilatation are important contributing factors. The major hemodynamic consequences of acute mitral regurgitation include a reduction in forward stroke volume, volume overload of the left ventricle, and elevation of atria1 and pulmonary venous pressures. Papil- lary muscle rupture presents as a catastrophic event characterized by fulminant pulmonary edema, low cardiac output, and early death. Papillary muscle dysfunction produces varying de- grees of mitral regurgitation ranging from mild to severe. The consequences of this additional hemodynamic burden superim-

Fig 6.-Major complications of acute myocardial infarction. (From Crawford M.H., O’Rourke R.A.: The bedside diagnosis of the complications of myocardial infarction, in Eliot R.S. (ed.): Cardiac Emergencies. Mount Kisco, N.Y., Futura Publishing Co., 1982. Reproduced with permiqion.)

Pericarditis

posed on an already damaged left ventricle depend on the severity of regurgitation and extent of ischemic myocardial damage.

Ventricular septal rupture is usually associated with extensive transmural infarction involving the anteroseptal region and left ventricular free wall. The hemodynamic sequelae are dependent on the size of the defect and relative systemic and pulmonary vascular resistances. Although the magnitude of the lefjt- to-right shunt may vary, in most cases it is usually large, with a ratio of pulmonary to systemic flow of greater than 2 : 1. The additional hemodynamic burden results in rapid biventricular failure, pulmonary edema, shock, and death. Clinical differentiation of septal rupture from acute mitral regurgitation usually requires right heart catheterization. Rupture of the left ventricular free wall close to the interventricular septum occurs more commonly than isolated septal rupture. Death generally occurs within minutes to hours, due to hemopericardium and tamponade. Occasionally patients survive due to the formation of a pseudoaneurysm.

Dyskinesis refers to the paradoxical outward systolic bulging of an infarcted region of myocardium, which is referred to as an aneurysm. The passive expansion of an aneurysm can result in trapping of enough blood volume to substantially reduce cardiac output. This occurs when dyssynergy involves 25% or more of the surface area of the left ventricle. Additional cardiac dysfunction may result from elevated end-diastolic pressure and volume, papillary muscle dysfunction with resulting mitral regurgitation, and ventricular arrhythmias.

EXTRAMYOCARDIAL FACTORS IN THE PATHOPHYSIOLOGY OF SHOCK

Although the shock syndrome following AM1 is related primarily to the extent of total myocardial damage, a number of extramyocardial factors may further impair cardiovascular function and thus play a major role in precipitating or perpetuating the shock state (Table 3).43-45 It is particularly important to recognize these specific contributing factors since they are usually amenable to therapy and their prompt correction may prevent progressive myocardial necrosis and deteriorating circulatory function.

Relative or absolute hypovolemia following AM1 is well docu- mented even in the presence of severe left ventricular dysfunction.46’ 47 Hypovolemia in this setting is frequently related to excessive water and electrolyte losses from inadequate fluid intake, sweating, vomiting, diarrhea, hyperventilation, or prior diuretic use. In addition, transudation of fluid from the intravascular to the extravascular space may occur as a result of reflex activation of the sympathetic nervous system or use of exoge- nous sympathomimetic drugs.4A, 4g Loss of intravascular fluid

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TABLE 3.--NONMYOCARDIAL FACTORY IN THE PATHOGENESIS OF CARDIOGENIC SHOCK

Hypovolemia Inadequate fluid and salt intake Excessive sweating, vomiting, diarrhea Diuretics and sodium restriction Blood loss Excessive postcapillary vasoconstriction (ieflrx sympathetic stimulation,

sympathomimetic drugs) Arrhythmias and conduction disturbances

Tachyarrhythmias Bradyarrhythmias Bundle-branch block, intraventricular conduction delays and heart block AV dissociation

Acidosis, hypoxemia Cardiovascular depressant drugs

Propranolol Antiarrhythmics tdisopyramide, lidocaine, quinidine and procainamide m

high doses) Barbiturates, anesthetic agents Narcotics and tranquilizers. in excess doses Antihypertensive drugs Vasodilator drugs (nitrates, nitroprusside, o-blocking agents)

Circulating toxic substances Pain, vasovagal reactions Fever Impaired reflex sympathetic vasoconstriction Additional etiology for shock (hemorrhage, sepsis, adrenal insufficiency, etc.) Miscellaneous conditions

Pulmonary embolus Cardiac tamponade Pneumothorax or hemothorax

and protein may also result from ischemic endothelial damage, which increases capillary permeability. Slight reductions in intravascular volume will not usually affect cardiac output with otherwise normal myocardial function due to reflex increases in ejection fraction and heart rate. However, with extensive myocardial infarction the ejection fraction is depressed and a larger than normal end-diastolic volume may be needed to maintain stroke volume. Under these circumstances even mild hypovolemia may contribute significantly to a reduced cardiac output by not allowing the optimal hemodynamic response according to the Frank-Starling mechanism.

While hypovolemia may accompany complicated myocardial infarction, more frequently the left ventricular filling pressure is elevated. Transmission of an excessively high filling pressure to the pulmonary veins can precipitate pulmonary edema, resulting in hypoxemia, which further impairs oxygen delivery to an already ischemic heart. In addition, ventricular filling pressure is transmitted through the ventricular wall during diastole, particularly in the subendocardium. This may reduce the effective pressure gradient for coronary perfusion and result in further subendocardial ischemia.

Arrhythmias, which are common in the immediate peri-infarction period, may also contribute to circulatory dysfunction by further reducing cardiac output and increasing myocardial ischemia. Since stroke volume is limited by primary myocardial damage, severe bradycardia may critically reduce cardiac output. 5o Tachycardia, by reducing the diastolic ventricular filling period, may also limit stroke volume. Additionally, the increased oxygen demands and reduced diastolic coronary perfusion period associated with excessive tachycardia may potentiate myocardial ischemia and extend the zone of myocardial necrosis. The contribution of atria1 contraction to left ventricular filling and cardiac output is relatively greater in the setting of reduced left ventricular compliance and impaired myocardial contractility. Thus loss of the atria1 “kick” due to atria1 fibrillation or infarction or atrioventricular dissociation may result in further hemodynamic deterioration.51

The accumulation of metabolic acids and toxic humoral factors produced by severely ischemic tissue may also impair cardiac function in shock. Metabolic acidosis results from excess lactate production associated with anerobic metabolism and also from impaired renal excretion of organic acids. The increased hydro- gen ion concentration exerts a direct depressant effect on myocardial contractility.52 Besides metabolic acids, one or more “myocardial depressant factors” may be involved in the pathophysiology of progressive shock. One such factor is produced by ischemia-mediated disruption of lysosomes in the pancreas with release of proteases and enzymatic hydrolysis of cellular pro- teins to form a peptide with potent negative inotropic properties. The role of this myocardial depressant factor in shock is still not fully understood.

A variety of drugs used in the treatment of ischemic heart disease may result in direct myocardial depression. Propranolol, commonly used to treat angina, may decrease contractility. The antiarrhythmic drugs, particularly disopyramide, in high doses may exert a negative inotropic effect. Narcotics, tranquilizers, and antihypertensive and vasodilator drugs in excessive doses will reduce vascular resistance, resulting in undesirable hypotension. This is not to suggest that drugs such as morphine and lidocaine should not be used in cardiogenic shock, but rather that the dose must be carefully titrated and the smallest effective dose should be employed.

Following a reduction in cardiac output and blood pressure, reflex activation of the sympathetic nervous system results in an integrated cardiovascular response which operates to restore blood flow to vital organs. Impairment of sympathetic reflex vasoconstriction has been shown experimentally and clinically in AMI.53-55 This has been attributed to activation of mechanore- ceptors or chemoreceptors in the ischemic myocardium mediated by vagal or sympathetic afferent pathways. Inability to increase

20

systemic vascular resistance appropriately in the face of a decreasing cardiac output will result in a fall in blood pressure. Since coronary blood flow is dependent on perfusion pressure in the presence of obstructive coronary artery disease, failure to maintain blood pressure by elevating resistance could lead to further myocardial ischemia and necrosis, thus perpetuating the hemodynamic abnormalities in cardiogenic shock.

In some patients, especially with acute posterior or inferior myocardial infarction, a vagal reflex similar to the experimental Bezold-Jarisch reflex may be operative.56 In such instances ischemic stimulation of cholinergic ganglia at the posterior mar- gin of the atrioventricular node may reflexly produce sinus bradycardia, heart block, depressed atria1 and ventricular function, and hypotension. Rarely, cardiogenic shock has been associated with evidence of increased vagal tone. Atropine may be helpful in partly reversing the hemodynamic abnormalities under these circumstances.

Low-grade fever is a common accompaniment of myocardial infarction. Fever of greater than 39 C may be associated with mild hypotension, reduced peripheral vascular resistance, tachycardia, and an increase in cardiac output. Hypotension and tachycardia may worsen myocardial ischemia, while the increase in cardiac output is mainly distributed to the skin. Thus, fever may contribute to circulatory dysfunction following AMI.

The possibility of concurrent or alternative etiologies for shock in the setting of AM1 should always be kept in mind since they may be readily treatable. Sepsis, particularly with the widespread use of invasive hemodynamic monitoring, remains a constant threat in the intensive care unit. Pulmonary emboli are more likely to occur in bedridden patients with low cardiac output. Cardiac tamponade may result as a complication of pace- maker insertion or the use of anticoagulants. Pneumothorax or hemothorax may be produced by internal jugular or subclavian vein catheterization.

CARDIOGENIC SHOCK WITHOUT CORONARY ARTERY DISEASE

The pathophysiology of cardiogenic shock in the absence of coronary artery disease differs in several important respects from shock following AMI. The basic abnormality in coronary shock is impaired myocardial blood flow due to obstructive ath- erosclerotic disease of the coronary arteries. If a given stenosis is flow-limiting despite compensatory vasodilation, then oxygen delivery and energy production are reduced below metabolic requirements and ischemic cell damage results. In addition, since the vascular bed distal to a severe proximal stenosis may be maximally vasodilated, autoregulation is not possible and flow :\iecomes dependent on pressure. In contrast, in noncoronary

21

shock the primary abnormality is in the myocardial muscle cell itself, not in blood flow or oxygen delivery. The reduced contractility is probably related to a defect in energy utilization rather than production. Autoregulation of coronary blood flow is intact, as is the response of coronary resistance vessels to changes in metabolic state and hypoxemia. In fact, coronary blood flow may be considerably greater than normal despite reduced cardiac output and systemic pressure. The precise cellular defects responsible for poor myocardial function are not well understood.

FEEDBACK MECHANISMS AND THE PERIPHERAL CIRCULATION IN CARDIOGENIC SHOCK

There are a number of negative compensatory feedback mechanisms in the early stages of shock which operate to restore blood flow to vital organs following a reduction in cardiac output and blood pressure (see Fig 4). These compensatory adjustments are mediated through the sympathetic nervous system, release of endogenous vasoconstrictor and hormonal substances, and local vasoregulatory mechanisms.57 A reduction in mean arterial pressure, pulse pressure, or rate of pressure rise will inhibit baroreceptor activity, resulting in enhancement of sympathetic tone and reduction in vagal tone. This integrated cardiovascular response augments cardiac output by increasing heart rate, myocardial contractility, and venous tone, and maintains systemic pressure through arterial vasoconstriction.58 In addition, increased sympathetic activity increases adrenal medullary synthesis and release of catecholamines. If blood pressure falls to extremely low levels, resulting in tissue ischemia, a chemore- ceptor reflex is activated that further augments sympathoadrenal activity. It is important to realize that sympathoadren- ally mediated arteriolar constriction, although widespread, is not a homogeneous response. Vasoconstriction is most pronounced in skeletal muscle, splanchnic, and cutaneous vascular beds, while the coronary and cerebral circulations are least affected. This allows a reduced cardiac output to be redistributed to organs essential for immediate survival. In addition to maintaining blood pressure and cardiac output, the sympathoadrenal system also influences intravascular volume regulation.4g Sym- pathetically mediated vasoconstriction results in an increase in the ratio of precapillary to postcapillary resistance and a fall in capillary hydrostatic pressure. This facilitates the osmotic movement of interstitial fluid into the vascular compartment to restore blood volume. When pump failure secondary to AM1 is the initiating mechanism in shock, there may be an impairment of sympathetic baroreflexes. Inability to maintain coronary perfusion pressure in this setting often leads to further myocardial ischemia and necrosis and progressive cardiovascular deterioration.

22

The renin-angiotensin-aldosterone system also contributes to the maintenance of blood pressure and intravascular volume.58’ 5g The reduction in renal perfusion pressure and the sympathetic stimulation of renal nerves both result in secretion of renin from the juxtaglomerular apparatus which converts the circulating globulin angiotensinogen to angiotensin I, the latter enzymatically transformed to angiotensin II by converting enzyme. Angiotensin II is the most potent vasoconstrictor com- pound made in the body and also stimulates the release of aldosterone by the adrenal cortex. Aldosterone, in turn, stimulates sodium and water reabsorption by the renal tubules which help maintain intravascular volume. Another hormonal system which plays a role in volume regulation during shock is antidi- uretic hormone (ADH), which is released from the posterior pituitary after activation of baroreceptor reflexes in response to hypotension. ADH increases the permeability of the renal tubular cells, resulting in increased water reabsorption.

Several local vasoregulatory mechanisms also act to maintain tissue blood flow during circulatory shock (see Figs 3 and 4). According to the metabolic theory of local flow regulation, tissue ischemia leads to an accumulation of vasoactive metabolites (e.g., adenosine) which act on arterioles and precapillary sphinc- ters to cause vasodilation.28, 6o The reduction in arteriolar resistance increases regional blood flow (metabolic hyperemia). The decrease in precapillary sphincter tone increases total capillary surface area, which facilitates blood-tissue exchange. Hypoxia is another stimulus that relaxes arteriolar smooth muscle and increases blood flow. Experimental data support the possible involvement of several local mechanisms in addition to the direct effect of low tissue PO, on the vasculature. Autoregulation is a third local vascular response in which changes in perfusion pressure cause changes in vascular smooth muscle tone independent of neurogenic or humoral factors. In shock states, the lowered perfusion pressure would elicit a vasodilatory response, resulting in increased flow. Since the coronary, cerebral, and renal circulations demonstrate strong autoregulation, whereas skeletal muscle and skin exhibit weak autoregulation, relative differences in regional autoregulation favor redistribution of blood flow to the vital organs.

The shock syndrome may develop rapidly or more gradually, depending on the severity of the initial insult and the adequacy of compensatory mechanisms to restore blood flow. If the negative feedback mechanisms are able to maintain adequate pressure and cardiac output, a compensated “preshock” state may exist. If compensatory mechanisms are insufficient to restore effective perfusion to vital organs, either because of the severity of the initial insult or because of its prolonged duration, clinical evidence of reduced organ perfusion or shock will be apparent, 1.f aggressive therapy is instituted at this point, the shock syn.

23

drome may still be reversible. If, however, severe reductions in tissue perfusion continue, eventually irreversible cellular changes occur and death will ensue.

The negative feedback mechanisms activated in cardiogenic shock are the same as those operative in advanced congestive heart failure (see Fig 4).61 However, a major pathophysiologic difference is that the compensatory mechanisms in severe congestive heart failure are able to maintain a reasonably stabl”e although depressed circulatory function. Cardiogenic shock, on the other hand, is an unstable syndrome in which vital organ dysfunction, through positive feedback mechanisms, leads to further reductions in blood pressure and cardiac output and progressive cardiovascular deterioration.45T 62

The most deleterious vicious cycle is that of progressive myocardial ischemia and necrosis occurring when pressure-dependent coronary flow is decreased with perfusion pressures below 60 mm Hg, resulting in further cardiac dysfunction (Fig 7). The accumulation of metabolic acids and toxic humoral factors produced by severely ischemic tissue may also further depress cardiac function.52

A critical reduction in cardiac output and systemic pressure also results in ischemic injury to the microvascular system, causing functional and structural impairment, which can per- petuate the shock state. Prolonged hypoxia, acidosis, and accumulation of vasodilatory metabolites may counteract sympathetic vasoconstriction, resulting in systemic hypotension and a decrease in blood flow to vital organs. Excessive venodilation increases the capacitance bed, decreasing venous return and cardiac filling. In addition, hypoxic and metabolic vasodilation may open up anatomical arteriovenous channels, leading to a decrease in capillary or nutritive flow. This is most pronounced in the mesenteric circulation in shock. The vasodilator effect of ischemia is more pronounced in the precapillary resistance vessels, and thus the ratio of precapillary to postcapillary resistance may actually decrease in the course of shock.4g The resulting increase in capillary hydrostatic pressure leads to movement of fluid out of the intravascular compartment, which reduces cardiac output. Loss of intravascular fluid and protein may also result from ischemic endothelial injury, which increases capillary permeability. The decrease in intravascular volume further reduces blood pressure and cardiac output, which reflexly increases sympathetic activity, causing more severe vasoconstriction and thus perpetuating the shock state.

Other deleterious positive feedback mechanisms in shock are initiated by ischemic damage to the lungs, gastrointestinal tract, kidney, and reticuloendothelial system. Damage to the pulmonary capillary endothelial cells causes an increase in capillary permeability, interstitial and alveolar edema, hemor- rshage, and impaired gas exchange (“shock 1ung”i.‘” The result-

24

Obstructron of Motor Coronory Artery

I Myocordtol Ischemto

Mtcroclrc

Fig 7.-Positive feedback mechanism by which coronary artery obstruction results in progressive myocardial ischemia and cardiogenic shock. (From Ross R.S., Lesch M., Braunwald E.: Acute myocardial infarction, in Thorn G.W. (ed.): Harrison’s &in- Q/es of internal Medicine. New York, McGraw-Hill Book Co., 1977. Reproduced with permission.)

ing hypoxemia and respiratory acidosis further reduce tissue oxygen delivery and vital organ function. Ischemic damage to the intestinal mucosa allows bacteria and bacterial toxins to en- ter the bloodstream, causing sepsis and further circulatory dysfunction. Renal ischemia causes acute tubular necrosis, which results in fluid, electrolyte, and metabolic disturbances.64 The reticuloendothelial system may be damaged by ischemia, which will impair the patient’s ability to withstand infection.

A final positive feedback mechanism in severe shock involves intravascular clottin due to formation of microthrombi and platelet aggregates. 6$ Precipitating events include low cardiac output and stasis, capillary endothelial damage with fibrin dep- osition, and catecholamine-induced platelet aggregation. The resulting obstruction to arterioles and capillaries further reduces nutrient blood flow.

CLINICAL ASSESSMENT OF CARDIOGENIC SHOCK

The clinical diagnosis of well-advanced cardiogenic shock is usually quite apparent. The diagnostic criteria for shock are based on evidence of cardiovascular dysfunction resulting in in-

25

adequate tissue blood flow and impairment of vital organ function (see Table 1). The classic signs include hypotension, cool and clammy skin, altered mentation, oliguria, and metabolic acidosis.

Evidence of acute or recent myocardial infarction and correction of any extramyocardial factors that could contribute to circulatory dysfunction are essential before a definitive diagnosis of cardiogenic shock can be made. Hypotension and clinical sigris of ischemic organ failure occur late in the course of fully developed, progressive shock and are associated with a very high mortality, despite aggressive medical therapy. Thus, the importance of recognizing early cardiovascular dysfunction is evident, and prompt treatment at this early stage, before progressive or irreversible tissue damage occurs, greatly improves the patient’s chances of survival.

The initial assessment of the cardiovascular system in suspected shock states involves careful evaluation of several important clinical parameters that reflect the adequacy of blood flow

HEART RATE AND BLOOD PRESSURE The earliest hemodynamic signs of a reduced cardiac output,

which may occur before any significant reduction in blood pressure, include tachycardia and a decrease in the arterial pulse pressure. A relatively small reduction in cardiac output and blood pressure will reflexly trigger the sympathoadrenal system, which tends to restore systemic pressure b rate, contractility, and systemic ir increasing heart

resistance.5 * “, 66 This results in a tachycardia and an increase in diastolic pressure. The systolic pressure may be slightly decreased or unchanged, depending on whether or not stroke volume is maintained. Since stroke volume is one of the determinants of pulse pressure, a reduction in cardiac output may be suspected by a decrease in pulse pressure before systolic pressure is significantly reduced. With more severe reductions in cardiac output, blood pressure will fall despite compensatory mechanisms.

PERIPHERAL AND CENTRAL PULSES The pulsations felt over an artery depend on the ability to

detect differences in vessel caliber during systole and diastole. This will depend not only on intra-arterial pressure but also on extremity blood flow and the distensibilit ter depending on vascular resistance.“73 6 2 of the vessel, the lat-

Weak, thready, or ab- sent pulses in shock are often due to a reduced arterial pressure, but also may result from high peripheral resistance with decreased flow and reduced vessel distensibility despite normal intravascular pressure. When the skin is warm, reduced pulses

26

usually reflect hypotension in the absence of peripheral vascular disease. The carotid and femoral pulses provide better information about central pressure since there is greater flow and less constriction of these larger vessels.

SKIN TEMPERATURE

The temperature of the skin in the absence of fever is an in- dicator of the adequacy of cutaneous blood flow. Warm skin indicates adequate cutaneous flow, while cool, clammy skin indicates reduced flow. In shock, reflex sympathetic vasoconstriction frequently results in reduced cutaneous flow. Thus, the skin temperature reflects the intensity of the sympathoadrenal discharge in shock.6g Not all patients in shock, however, demonstrate cutaneous vasoconstriction. For example, warm skin can occur following myocardial infarction despite inadequate cardiac output, presumably due to pathologic reflexes from the ischemic myocardium.

SENSORIUM

A reduction in cerebral perfusion pressure and blood flow will be reflected by altered mentation. In the early stages this will be manifested by restlessness, agitation, and confusion. With further reduction in cerebral perfusion, lethargy and obtunda- tion occur.

URINE OUTPUT

The urine output in shock, in the absence of diuretic therapy, correlates reasonably well with the renal blood flow, which is dependent on cardiac output.70 A urine flow of less than 20 ml/ hour in the absence of obstruction is an indication of inadequate renal flow and decreased cardiac output. Urinary sodium concentration and osmolality can provide earlier indication of reduced renal perfusion in shock before oliguria actually devel- ops. ‘l, 72 A decrease in glomerular filtration and activation of the renin-angiotensin-aldosterone system will cause an increase in sodium and water reabsorption. As a result, urinary sodium concentration will be low (-c 20 mEq/L) and osmolality will be high iurine to serum osmolality ratio b1.2 to 1).

CARDIOVASCULAR EXAMINATION

Examination of the heart in patients with cardiogenic shock frequently does not reveal the extensive nature of the myocardial damage or the severity of the resulting circulatory dysfunc- iion. The precordium may he entirely normal on palpation, but

27

more commonly there is evidence of abnormal wall motion. If infarction involves the anterior wall, a prominent systolic impulse may be palpated medial to the cardiac apex in the third to fifth left intercostal space, indicating ventricular dyskinesis. In some patients, the dyskinetic impulse is diffuse and not easily separated from the apex impulse. In patients with previous cardiac dilation the apical impulse will be displaced downward and laterally. A systolic thrill along the lower left sternal border OF apex may be detected with rupture of the interventricular septum or severe mitral regurgitation.

The heart sounds are frequently decreased in intensity and may be inaudible due to the marked reduction in myocardial contractility. With severe left ventricular dysfunction the pre- ejection period may exceed the shortened ejection time, resulting in paradoxical splitting of the second heart sound. A fourth heart sound is virtually always present following AM1 but is common with decreased left ventricular compliance from any cause.

A third heart sound is also quite common following AM1 and usually signifies an increased left ventricular filling pressure. Although frequently associated with ventricular failure, an S3 gallop in the immediate postinfarction period may be due to reduced ventricular compliance in the absence of heart failure.73

Systolic murmurs are frequently heard in patients with AM1 and generally result from mitral regurgitation secondary to papillary muscle dysfunction. The sudden appearance of a loud holosystolic murmur and thrill at the lower left sternal border or apex associated with abrupt hemodynamic deterioration is char- acteristic of severe mitral regurgitation due to papillary muscle rupture or ventricular septal rupture. Clinical differentiation may be difficult or impossible.42 Definitive diagnosis usually requires right heart catheterization.

The character of the jugular venous pulse reflects right atria1 and right ventricular hemodynamics. In predominantly left ventricular failure, the jugular venous pulse is normal in height and contour. In right ventricular infarction or failure secondary to left ventricular dysfunction with pulmonary hypertension, the jugular veins may be distended to more than 5 cm above the sternal angle. The arterial pulses in shock have already been discussed.

Examination of the lungs in myocardial infarction shock usually discloses fine rales over the lower lung fields or diffusely, indicating alveolar edema. Wheezing without rales may occur with predominantly interstitial edema. If cardiogenic shock occurs with relative hypovolemia, the lung fields may appear clear despite evidence of severe tissue hypoperfusion.

The clinical diagnosis of cardiogenic shock is made from a con- stellation of physical findings, and no single sign is diagnostic of the shock state.

28

HEMODYNAMIC MONITORING IN CARDIOGENIC SHOCK

Accurate continuous hemodynamic monitoring plays an essential role in the management of any patient in shock but particularly in patients with shock complicating myocardial infarction. The information obtained is invaluable in establishing the pathophysiologic mechanisms causing or perpetuating the shock syndrome and in quickly evaluating the adequacy of therapy. Hemodynamic monitoring is by no means a substitute for careful clinical evaluation but does provide additional data with which to make complex therapeutic decisions.

HEARTRATE AND CARDIAC RHYTHM Continuous monitoring of heart rate and rhythm is useful for

early detection of changes in cardiopulmonary status and reflex autonomic function. A gradual increase in heart rate may alert, the physician to the possibility of worsening cardiac performance or of decreasing intravascular volume. Electrocardi- ographic (ECG) monitoring instantly detects any ventricular premature beats which, if left untreated, may precipitate more serious ventricular dysrhythmias. Other dysrhythmias as well as conduction disturbances can be promptly identified and appropriate treatment instituted before progressive cardiovascular deterioration occurs.

BLOOD PRESSURE Accurate measurement of the blood pressure in shock is criti-

cal since the level of systemic pressure greatly influences the adequacy of coronary blood flow, as well as myocardial oxygen demands. It is important to recognize that the auscultatory blood pressure measured with a sphygnomanometer in the setting of shock may be grossly inaccurate, especially when reflex vasoconstriction is prominent.68 In the presence of reflex sympathetic vasoconstriction, the forearm resistance may be high enough to prevent adequate peripheral flow. Since the Korotkoff sounds are dependent on flow and vessel distensibility, the cuff pressure may be grossly underestimated or even unobtainable despite a normal or even high intra-arterial pressure. Failure to appreciate this could lead to inappropriate administration of vasoconstrictor drugs, which could further reduce tissue perfusion. Intra-arterial pressure can be measured by cannulating the radial, brachial, or femoral arteries. Cannulation of the radial artery is least likely to cause ischemic damage to the extremity. An N-gauge cannula can be quickly inserted percutaneously if a pulse is palpable or by cutdown when no pulse can be felt. The arterial cannula also allows frequent determination of blood gases and pH.

29

CARDIAC FILLING PRESSURE AND VENTRICULAR PERFORMANCE

Once the diagnosis of cardiogenic shock has been established and the patient has been initially stabilized, the very next step is to determine the left ventricular filling pressure so that appropriate therapy can be immediately instituted to optimize ventricular performance and cardiac output.

PULMONARY CAPILLARY WEDGE PRESSURE

Measurement of LVEDP provides two critical pieces of hemodynamic information in cardiogenic shock. First, filling pressure is an index of left ventricular function; second, it reflects the level of pulmonary capillary hydrostatic pressure, a factor related to the propensity for developing pulmonary edema. This information provides a rational basis for planning specific therapy and assessing the adequacy of that therapy. Left ventricular filling pressure can be indirectly determined safely at the bedside by measuring pulmonary capillary wedge pressure (PCWP) using a flow-directed balloon tip catheter. The pressure measured at the catheter tip with the balloon inflated in the peripheral pulmonary artery is the PCWP and reflects left atria1 pressure, which is transmitted retrograde through the pulmonary veins. In patients with diminished ventricular compliance, atria1 systole can substantially augment LVEDP without altering mean PCWP, which then underestimates the ventricular filling pressure. On the other hand, an increased mean PCWP in mitral stenosis or regurgitation may result in overestimation of LVEDP. Despite these limitations, PCWP has proved to be a very reliable and useful index of left ventricular filling pressure in the critically ill patient in shock following myocardial infarction.‘5 Correct interpretation of the PCWP should take into account that a given value will be influenced not only by intravascular volume and myocardial contractility, but also by left ventricular and venous compliance and the diastolic filling period.

When PCWP cannot be obtained, the pulmonary artery end- diastolic pressure (PAEDP) may be used as an index of left ventricular filling.78 There are several limitationF6 however, to using PAEDP to assess left ventricular function. In conditions in which pulmonary vascular resistance is elevated, PAEDP may greatly exceed mean PCWP and LVEDP. In the setting of reduced ventricular compliance, the atria1 contribution to LVEDP may not be totally transmitted across the pulmonary bed so that PAEDP would be lower than LVEDP. During tachycardia with heart rates greater than 124 beats/minute, PAEDP may overestimate LVEDP because of shortening of the diastolic filling period as well as contraction of the atrium against a partially closed mitral valve.“’

The usefulness of CVP as an index of left ventricular filling pressure is limited to situations in which left ventricular function and pulmonary vascular resistance are both normal. For example, in patients with pneumonia, pulmonary embolus, or predominant right ventricular infarction, CVP may be quite high while left ventricular filling pressure is low, and fluid replacement may be required. On the other hand, in patients with acute left ventricular infarction, LVEDP is usually higher than CVP, which may be normal or very low. Fluid administration in this setting could result in pulmonary edema and critically worsen cardiac performance. Thus, CVP should not be used to assess left ventricular hemodynamics in cardiogenic shock. Fail- ure to appreciate this point could lead to inappropriate and potentially hazardous treatment.

Although measurement of cardiac filling pressures is extremely useful in the diagnosis and management of shock, it does not provide a direct index of blood flow. Mental status and urine output clinically reflect the adequacy of cardiac output but do not provide quantitative information which may be useful in assessing the immediate efficacy of a specific therapy. There is no single optimal cardiac filling pressure for every patient with cardiogenic shock. However, simultaneous measurements of PCWP and cardiac outyut can be used to construct left ventricular function curves,75- 7 and in this way the PCWP which max- imizes cardiac output without causing pulmonary edema can be determined. Serial measurement of cardiac output can be quickly and reproducibly done with a flow-directed thermodilution catheter.8 A thermistor at the end of the catheter records changes in pulmonary artery blood temperature produced by a right atria1 bolus injection of cold 5% glucose. Cardiac output is calculated from a “negative heat” dilution curve using a small digital computer.

In studies of ventricular function curves following AMI, maximum cardiac output was generally achieved with a PCWP between 14 and 18 mm Hg and a PAEDP of 20-24 mm Hg.75* 77 Raising filling pressures above these levels did not further improve cardiac output and only increased the risk of developing pulmonary edema. A more sensitive index of the risk of pulmonary edema than PCWP alone may be obtained by relating the PCWP to plasma colloid osmotic pressure and calculating the oncotic-hydrostatic pressure gradient. When this gradient (nor- mally 10 mm Hg) is less than 4 mm Hg the likelihood of pulmonary edema is quite high. Recently a clinical oncometer has been developed for routine measurement of plasma colloid osmotic pressure.

Within certain limitations. arterial-mixed venous oxygen dif- 31

ference may be used as a rough index of cardiac output. The arteriovenous oxygen difference is determined from simultaneous blood samples drawn from a systemic artery and the pulmonary artery. Since oxygen consumption shows such wide variation in the critically ill patient in shock, absolute values have less meaning than overall trends. In general, an arteriovenous oxygen content greater than 5.2 ml/d1 is associated wit& a reduced cardiac output. The arteriovenous oxygen differenee may overestimate cardiac output when arteriovenous shunting is prominent.

HEMODYNAMIC INDICES OF PROGNOSIS IN CARDIOGENIC SHOCK

Initial measurements of left ventricular filling pressure and cardiac index have provided useful information on the prognosis of patients with cardiogenic shock.77 An initial PAEDP greater than 28 mm Hg or a PCWP greater than 15 mm Hg with a cardiac index of less than 2.3 L/minute/m2 have been associated with 100% mortality despite intensive medical therapy. Such hemodynamic abnormalities may identify patients who are candidates for mechanical circulatory assistance and possibly surgical intervention. In patients with relatively low filling pressures (about 20% of patients with cardiogenic shock), the response to volume expansion has been shown to have prognostic value. Survivors usually respond to volume augmentation with a greater increase in cardiac output than in left ventricular filling pressure, while nonsurvivors show a proportionately greater increase in filling pressure. Indices derived from cardiac output have also been used to estimate prognosis. For example, a stroke volume greater than 25 ml/beat/m2 was found to predict survival with over 70% reliability.82 Perhaps the best single hemodynamic index of survival is stroke work (over 80% reliability), since this parameter is derived from cardiac output, heart rate, and arterial pressure, each of which has independent prognostic significance.’ 2 84

ADDITIONAL DIAGNOSTIC USES OF HEMODYNAMIC MONITORING IN CARDIOGENIC SHOCK

Although shock following AM1 is usually related to extensive loss of contractile muscle mass, occasionally severe damage to mechanically vital structures such as the inter-ventricular septum or papillary muscles may be the major factor precipitating the shock state. Early diagnosis of these conditions is important since they may respond to aggressive medical or surgical intervention. Papillary muscle rupture or severe dysfunction and rupture of the muscular interventricular septum after AM1 are both characterized by sudden clinical deterioration, with hypo-

32

tension, pulmonary edema, and shock. Differentiation of these two serious complications is often difficult since their clinical presentations are similar and the associated systolic murmurs cannot be reliably distinguished (Table 4). In addition, severe mitral regurgitation may occur in cardiogenic shock in the absence of a murmur. Definitive diagnosis of septal rupture and mitral regurgitation in these instances requires catheterization of the right side of the heart?‘, 85 This can be safely and rapidly performed at the bedside using a flow-directed balloon-tipped catheter. The diagnosis of septal rupture is made by demonstrat- ing a significant step-up in oxygen saturation (> 5%) at the level of the right ventricle. The degree of shunting may be estimated using the oxygen content of blood samples from a systemic artery, the pulmonary artery, and the venae cavae or right atrium. Using the Fick principle, the pulmonary to systemic flow rate, QpiQs, is given by:

Qp/Qs = (Ao, - PAo,Y(Ao, - MVo,) where A02 and PAo, are the arterial and pulmonary artery oxygen contents and MVoz is the mixed venous oxygen content. The diagnosis of mitral regurgitation is made by finding a large V wave in the pulmonary artery wedge pressure tracing. Since existing mitral regurgitation will produce elevated V waves, it is important to exclude septal rupture with oximetry. The degree of mitral regurgitation can be quantitated accurately only with left ventricular angiography.

The diagnosis of acute rupture of the ventricular free wall must be established immediately for emergency treatment to be effective. The clinical picture is usually characterized by sudden recurrence of pain, hypotension, signs of pericardial tamponade, and new ST segment elevation on the ECG.3g-41 This presentation may be easily confused with extension of a recent myocardial infarction. The hemodynamic diagnosis of tamponade is made by finding a diastolic pressure plateau with equalization of mean right atria1 pressure, right ventricular and pulmonary artery diastolic pressures, and PCWP.

When predominant right ventricular dysfunction occurs in the setting of acute inferior myocardial infarction, the ability of the right ventricle to maintain adequate left ventricular filling is impaired. Recognition of this condition as a contributing factor in cardiogenic shock is important since careful volume expansion despite elevated venous pressure may improve left ventricular performance and cardiac output. The finding of distended neck veins often leads to the use of diuretics, which further reduces left ventricular filling pressure in this situation, resulting in hemodynamic deterioration

Right ventricular infarction may be clinically suspected when elevated venous pressure occurs with clear lung fields. However, pulmonary hypertension due to hypoxia, pulmonary embolus, or

33

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obstructive lung disease could also cause the same clinical picture.

When predominant right ventricular dysfunction occurs in the setting of cardiogenic shock, the mean right atria1 and right ventricular end-diastolic pressures are higher than left ventricular filling pressure.86 Since right ventricular systolic function is impaired, there is little increase in mean pressure from the right atrium to the pulmonary artery, allowing differentiation from conditions causing pulmonary hypertension. Thus, hemodynamic monitoring is of great value in recognizing patients with predominant right ventricular dysfunction in cardiogenic shock who may benefit from volume expansion.

MANAGEMENT OF CARDIOGENIC SHOCK

The onset of cardiogenic shock is usually delayed for hours and sometimes days after the initial symptoms. This suggests that progressive myocardial damage rather than a single massive insult is responsible for the shock state and points to the need for early recognition and treatment of circulatory dysfunction following AMI. The importance of early diagnosis and immediate therapy is further emphasized by the rapidly lethal course followed once shock is established within 6 hours. The median survival time is about 10 hours.ie3

The primary goal in treating circulatory shock of any etiology is to rapidly restore adequate tissue blood flow to meet existing metabolic requirements. The major dilemma in achieving this goal in cardiogenic shock is that the standard inotropic and vasoconstrictor drugs used to augment cardiac output and maintain systemic pressure also increase myocardial oxygen demands, which can exacerbate ischemic myocardial damage. This has led to the development of newer pharmacologic agents, the use of circulatory assistance devices, frequently in conjunction with drug therapy, and a more aggressive surgical approach to the patient in cardiogenic shock.

The management of cardiogenic shock may be considered under four general categories: (1) initial resuscitation and general supportive measures, (2) specific pharmacologic therapy to maintain adequate blood volume, systemic pressure, cardiac output, and vital organ flow, (31 mechanical cardiac assistance, and (4) emergency cardiac surgery. The specific approach to any single case will depend on repeated evaluation of the patient’s clinical status and hemodynamic function.

RESUSCITATION AND GENERAL MEASURES

In any critically ill patient, the first priority in resuscitation is establishing an adequate airway with effective ventilation and oxygenation. Respiratory function is best assessed by mea-

35

suring arterial blood gases. The level of Pacoz reflects the adequacy of ventilation. A Paces greater than 50 mm Hg, with a reduction in arterial pH, indicates hypoventilation. The adequacy of blood oxygenation is reflected by the arterial Paz, oxygen saturation, and hemoglobin concentration. Maintenance of adequate oxygenation (Pao, of at least 70 mm Hg) in cardiogenic shock requires supplemental oxygen administration. An oxygqn concentration of 28%-40% delivered through a Venturi fa&e mask is usually adequate for maintaining arterial Pas. If respiratory function is seriously compromised, endotracheal intuba- tion and mechanical ventilation will be required. Positive end- expiratory pressure (PEEP) may also be needed to improve blood oxygenation in cases of advanced cardiopulmonary failure. The concentration of inspired oxygen should not exceed 60% for prolonged periods because of the potential for oxygen toxicity.

R.B. WALLACE: When positive end expiratory pressure ventilation is used, it is important that its effect on hemodynamics is appreciated. Systemic venous return may be compromised especially in the hypovolemic state and optimal values for PCWP and PAEDP will have to be adjusted upward to account for the degree of PEEP.

The authors have presented in detail the etiology, pathophysiology, method of assessment, therapeutic modalities, and the general prognosis of cardiogenic shock. It is readily apparent that therapy of any kind is not effective in reducing mortality in patients with cardiogenic shock, except in those instances where a correctable mechanical defect is present. This clearly suggests the importance of identifying patients who are at risk for cardiogenic shock, prior to the time that left ventricular function has been compromised to such an extent that cardio- genie shock occurs. This would require the identification of patients at an early stage in the course of their disease, so that prophylactic and therapeutic measures may be initiated to prevent progression to this lethal stage. This unquestionably would require a more aggressive approach to the evaluation of patients who have sustained seemingly uncomplicated myocardial infarctions.

Since marked reduction of central pulses and profound hypotension may cause rapid irreversible cerebral and myocardial damage, immediate therapy to restore perfusion pressure is indicated. The patient should be placed in the horizontal position with the legs slightly elevated to increase venous return. In the presence of obvious circulatory collapse, inotropic vasoconstrictor drugs such as dopamine (200-2,000 pg/minute) or norepinephrine (2-20 pg/minute) should be given intravenously while the patient is being clinically evaluated and arterial and venous catheters are being inserted. These drugs will rapidly raise systemic vascular resistance, augment myocardial contractility, and increase central perfusion pressure. Continuous infusion of the miltimum dose required to establish a viable pulse should be done until an accurate blood pressure can be obtained. ECG monitoring is also begun for detection of rhythm or conduction

36

disturbances. Blood samples are sent for determination of hematocrit and electrolyte determinations.

Disturbances of acid-base balance are diagnosed from the arterial pH and Pacoz. Respiratory acidosis requires more effective ventilation, while significant respiratory alkalosis is usually corrected by sedation. Metabolic acidosis, the most common acid- base abnormality in advanced shock, is best treated by restoring effective tissue blood flow. Since severe acidosis (pH < 7.2) de- presses myocardial contractility and predisposes to arrhythmias, prompt correction with sodium bicarbonate may be indicated. It is important to realize however, that infusion of hypertonic sodium bicarbonate may be hazardous, as excess sodium increases the risk of pulmonary edema and of hyperosmolar states.s7 In addition, overcorrection of pH will cause alkalosis, which impairs oxygen release from hemoglobin at the tissue levelE8 and also predisposes to arrhythmias. Bicarbonate administration should be guided by repeated measurements of arterial pH to avoid this.

Arrhythmias and conduction disturbances are important contributing factors in cardiogenic shock. Ectopic tachycardias such as ventricular tachycardia or atria1 fibrillation may lead to rapid deterioration of cardiac function as well as to increasing ischemic myocardial damage. The treatment of choice in the setting of rapid hemodynamic deterioration is electric cardioversion. Antiarrhythmic drug therapy may be employed first when hemodynamic status is not seriously compromised and following cardioversion for preventing recurrence. Severe brachycardia accompanied by hypotengion and low cardiac output may be due to excess vagotonia and can be corrected with intravenous administration of atropine sulfate, 1.5-2 mg.” In individuals unresponsive to atropine or in cases of infranodal disease and high- degree atrioventricular block, transvenous ventricular pacing will be required to establish an adequate cardiac output. In the setting of reduced ventricular compliance, atria1 systole may contribute significantly to stroke volume, and in such cases se- quential atrioventricular pacing may be needed to attain optimal cardiac output.80, ‘*

The pain of myocardial infarction contributes to excessive activity of the autonomic nervous system. Increased sympathetic activity augments myocardial metabolic demands, which could potentiate myocardial ischemia, while increased parasympathetic activity may cause bradycardia and hypotension (vasovagal response), which could lead to rapid deterioration of cardiovascular function. The drug of choice for treating pain associated with myocardial infarction is morphine sulfate administered intravenously at a dose of 4-8 mg and repeated at intervals of 5- 15 minutes until pain is relieved or toxic side effects (hypotension, respiratory depression, etc.) are observed. In addition to relieving pain and anxiety, morphine also causes peripheral ar-

37

terial and venous dilation, which may be useful in reducing elevated pulmonary venous pressure in patients with pulmonary edema. Hypotension following morphine administration may be minimized by keeping the patient in the supine position and by concomitant administration of atropine to block the vagomi- metic effects of morphine.

Other general measures that are helpful in treating the pat tient in cardiogenic shock include reducing fever, vigorous treat4 ment of nausea and vomiting, and correction of any electrolyte abnormalities.

INTRAVASCULARVOLUME IN CARDIOGENIC SHOCK

Since preload is a major determinant of cardiac performance (Starling relation), maintenance of optimal left ventricular filling pressure is critical in managing the patient in cardiogenic shock. A suboptimal filling pressure indicates relative hypovolemia, and in such instances cautious volume expansion frequently results in an increase in cardiac output and blood pressure with improvement in tissue perfusion. In addition, the efficacy of concomitant vasoactive drug therapy is enhanced after ventricular filling pressure is first maximized by fluid administration. Changes in cardiac output in response to fluid challenge may be used as a measure of cardiac reserve. An increase in cardiac output suggests a more favorable prognosis, while no change or a decrease in output with marked elevation in filling pressure indicates a much poorer prognosis. Unfortu- nately, ventricular filling pressure is frequently excessive in cardiogenic shock, and volume expansion in this circumstance is contraindicated. Instead, diuretic therapy to reduce pulmonary congestion may be required.

The rationale for hemodynamic monitoring of PCWP or PAEDP in the setting of cardiogenic shock has already been discussed. It should be reemphasized that CVP has little value in assessing volume status and guiding fluid therapy following AMI. Because ventricular compliance following AM1 is reduced, the end-diastolic pressure-volume relationship is shifted to the right. This means that higher than normal end-diastolic pressures are required to achieve optimal ventricular filling. The relationship between left ventricular filling pressure and cardiac output should be measured for each patient. In general, following AMI, a PCWP of 14-18 mm Hg or a PAEDP of 20-24 mm Hg is required to maximize cardiac output.75-77

The hemodynamic response to rapid volume challenge using small graded increments of fluid is quite helpful in evaluating the efficacy of volume therapy. Initial volume therapy should consist of 50-100 ml increments of fluid over 5-10 minutes with continuous hemodynamic monitoring and observation of signs of improvement, in tissue perfusion. If beneficial effects are ob-

38

served without evidence of pulmonary edema, further fluids are given with careful hemodynamic monitoring. If volume expansion increases filling pressures without increasing cardiac output and vital organ flow, further volume expansion is unlikely to be helpful and only increases the risk of precipitating pulmonary edema. It should be noted that although raising PCWP much above 20 mm Hg is likely to result in pulmonary edema, pulmonary edema may also occur at much lower PCWPs. The risk of pulmonary edema is dependent not only on pulmonary venous pressure but on colloid osmotic pressure as well.” If PCWP approaches or exceeds osmotic pressure, pulmonary edema will usually develop. Measurement of colloid osmotic pressure is relatively inexpensive and very useful in the fluid management of shock states.

The type and amount of fluid used in treating shock depend on the specific clinical situation. For example, when blood loss is apparent or the hematocrit is less than 30, whole blood or packed cells is the most effective agent for restoring pressure and tissue perfusion.

Acellular fluids used in the treatment of cardiogenic shock include crystalloids and colloids.g3 Dextrose solutions are not effective volume expanders because water distributes in 60% of body weight and plasma volume is only about 10% of this. Crystal- loids include isotonic saline solutions (normal saline, Ringer’s lactate) and distribute in the extracellular space, of which 25% is plasma volume.g4 In critically ill patients with increased capillary permeability and reduced oncotic pressure, less than 25% of an infused volume of saline will remain in the intravascular space. To better restrict the distribution of fluid therapy to the blood volume and to shift interstitial fluid into the intravascular space, large molecular weight colloids may be used. These include human serum albumin, plasma substitutes, and glucose polymers (dextrans, hydroxyethyl starch). Human serum albumin (5 gm/lOO ml) is an excellent volume expander, particularly in the edematous hypovolemic patient with low serum albumin. Use of plasma to increase blood volume carries the risk of trans- mitting hepatitis. Purified plasma protein derivatives do not transmit hepatitis but they do contain vasoactive contaminants, which can cause hypotensive reactions. Dextrans are glucose polymers produced by streptococci. A 6% solution of dextran 70 (molecular weight 70,000) expands blood volume by 130% of in- jected volume and remains intravascular for longer periods than crystalloid solutions. The effects of dextran 40 (MW 40,000) are dissipated within 90 minutes. g3 Toxic side effects of the dextrans include bleeding due to interference with platelet function and coagulation, and anaphylactic reactions. Dextran 40 may cause renal failure by increasing urine viscosity. Hydroxyethyl starch is another polysaccharide colloid similar to dextran 70 in its capacity to augment blood volume but with several advan-

39

tages.g5’ ” It is relatively nonallergenic, causes much less bleeding (in doses less than 1,500 ml), and does not cause renal failure.

DRUG THERAPY FOR CARDIOGENIC SHOCKg7-102

lT~~~~~~~~~~~~~~ AND INOTROPIC AGENTS

In most cases of cardiogenic shock, optimization of left ventricular filling pressure (preload) alone will not restore adequate tissue perfusion, and drugs that raise systemic vascular resistance and augment myocardial contractility are usually necessary to support the circulation. The importance of maintaining adequate coronary perfusion pressure early in the course of shock complicating myocardial infarction cannot be overem- phasized. Continued arterial hypotension results in progressive myocardial ischemia, further deterioration of ventricular function, and perpetuation of the shock state. However, it should also be emphasized that the use of vasoconstrictor drugs to maintain blood pressure should be considered temporary therapy. Extensive and unnecessary vasoconstriction will increase central blood pressure but at the expense of decreasing tissue perfusion and increasing myocardial oxygen demands.

SYMPATHOMIMETIC AMINES

The most commonly used cardiovascular drugs in the treatment of cardiogenic shock are the sympathomimetic amines. The effects of these agents are mediated through action on (Y- and p- adrenergic receptors (Table 5).103, lo4 Stimulation of a-receptors causes vasoconstriction, while stimulation of P-receptors causes vasodilation. Activation of myocardial P-receptors increases heart rate and contractility. The various adrenergic drugs differ with respect to their relative CY and p effects (Table 6). In addi-

TABLE 5.-SOME RECEPTOR ACTIONS OF CATECHOLAMINES*

‘4T)RENERGIC RECEPTOR SITE

-- ____--_____

PI Myocardium

Sinoatrial node Atrioventricular conduction

system I% Arterioles

Lungs a Peripheral arterioles

ACTION

Increase atria1 and ventricular contractility

Increase heart rate Enhance atrioventricular conduction+

Vasodilation Bronchodilation Vasoconstriction

*From Sonnenblick E.H., et al.: Dobutamine: A new synthetic cardioactive sym- jiathetic amine N. Engl. d. Med. 300:18. 1979 Reproduced with permission

40

TABLE 6.-ADRENERGIC-RECEWOR ACTIVITY OF SYMPATHOMIMETIC AMINES

a Pl Pz PERIPHERAL CARDIAC PERIPHERAL

Norepinephrine ++++ ++++ 0 Epinephrine ++++ ++++ ++ Dopamine* L 1. A .! i- t ” ! I + Isoproterenol 0 ++++ +-i-i-+ Dobutamine + ++++ ++ Methoxamine ++++ 0 0

*Causes renal and mesenteric dilation by stimulating dopaminergic receptors.

From Sonnenblick E.H., et al.: Dobutamine. A new synthetic cardioactive sympathetic amine. N. Engl. J. Med. 300:18, 1979. Reproduced with permission.

tion, the cardiovascular effects of any single drug depend on the dose and the specific vascular bed on which the drug acts. The rationale for using drugs with positive inotropic and vasoconstrictor properties in cardiogenic shock is to increase cardiac output by augmenting myocardial contractility and to improve blood flow to vital organs by increasing perfusion pressure. A necessary hemodynamic consequence of increasing perfusion pressure by elevating total vascular resistance is that blood flow will be reduced through some vascular beds. Ideally, selective vasoconstriction of nonvital structures would increase systemic resistance and provide the elevated pressure needed to improve perfusion to more vital organs. Unfortunately, most sympathomimetic amines are nonspecific with respect to their vasoconstrictor action. Several drugs, notably dopamine, do have relatively selective constrictor and dilator activity which results in a more favorable redistribution of flow to the heart, brain, kidney, and splanchnic organs.lo5 Another hemodynamic consequence of vasoconstrictor-inotropic drug therapy is that any increase in systemic pressure and cardiac contractility will also be associated with an increase in myocardial oxygen demand, which could worsen myocardial ischemia. However, the increase in coronary blood flow due to the rise in arterial pressure and the decrease in left ventricular end-diastolic chamber size associated with augmented contractility tend to offset this increase in oxygen requirements. The desired net effect is to improve overall tissue blood flow by increasing perfusion pressure and enhancing cardiac function while favorably affecting the balance of myocardial oxygen supply to demand.

NoREPINEPHRINE.-Norepinephrine increases myocardial contractility by stimulating &-receptors and causes arteriolar and venous constriction by stimulating o-receptors.lo6 The actual effect on cardiac output depends on the dose employed. In small doses, the p effect predominates and cardiac output and blood

41

pressure are increased. In very high doses, however, extensive vasoconstriction causes a marked increase in systemic resistance and a fall in cardiac output despite the positive inotropic effect. Such an adverse hemodynamic effect can also occur when norepinephrine is given in lower doses to patients with initially high systemic vascular resistance. The vasoconstrictor effects of norepinephrine are most prominent in the cutaneous, skeletal muscle, and splanchnic beds. In the heart, the relative I3 effect results in vasodilation. Thus, norepinephrine may exert beneficial effects in cardiogenic shock by increasing cardiac output and redistributing blood flow to the heart and brain. Careful metabolic and hemodynamic studies have shown that the increases in systemic pressure and coronary blood flow produced by norepinephrine in cardiogenic shock are associated with an actual reduction in myocardial ischemia, as indicated by decreased lactate production or change to lactate extraction.i2 The average initial dose of norepinephrine bitartrate is 2-8 p,g/minute. Nor- epinephrine is best administered through an indwelling catheter in a large vein since extravasation can result in severe subcu- taneous tissue necrosis. Undesirable pharmacologic effects of norepinephrine include renal vasoconstriction with resulting impairment of renal perfusion and oliguria; hypovolemia, usually after prolonged administration, due to postcapillary venoconstriction; excessive tachycardia and ventricular arrhythmias; and potentiation of myocardial ischemia in excessive doses.

DOPAMINE.-Dopamine, a naturally occurring precursor of norepinephrine, is currently one of the most widely used drugs in the treatment of cardiogenic shock because it possesses several uni ue properties that offer major hemodynamic advantages. lo’- lo The precise cardiovascular effects are dependent on P the dose used. In low doses (2-5 Kg/kg/minute), it produces non- adrenergic vasodilation of renal, mesenteric, coronary, and cerebral vascular beds.“‘, lo8 In higher doses (6-15 pg/kg/minute), it increases contractility and cardiac output through pi-stimulation. In very large doses (20 p.g/kg/minute), generalized o-mediated vasoconstriction predominates, which opposes the selective beneficial vasodilation seen at lower doses.lo7’ ‘11 In the usual therapeutic doses (2-15 pg/kg/minute) dopamine increases cardiac output and blood pressure with little change or slight reduction in peripheral vascular resistance. The increase in blood pressure is due to enhanced cardiac output and is accompanied by a fall in LVEDP and little change in heart rate. In addition, the vasodilatory action of dopamine on the renal vasculature increases renal blood flow and urine out ut, which is of major benefit to the oliguric patient with shock.’ ’ It is im- Jl portant to realize that systemic hemodynamics may improve at the expense of myocardial oxygenation. In one study of patients in cardiogenic shock, dopamine (8-28 pglkgiminute) improved

42

cardiac performance but increased myocardial oxygen consumption and lactate production.‘13 It seems advisable to use the low- est dose that results in an acceptable hemodynamic response. Another potentially serious adverse effect of dopamine treatment is ventricular arrhythmias. Other undesirable effects include angina, nausea, vomiting, tachycardia (less so than with other sympathomimetic amines), hypotension at low doses, and excessive vasoconstriction at high doses.

DOBuTAMINE.-Dobutamine is a newly developed, relatively cardioselective catecholamine clinically approved for intravenous use in the short-term treatment of acute cardiac failure characterized bv low cardiac output and elevated diastolic filling pressures.114-11 Dobutamine acts directly on Pi-adrenergic receptors in the myocardium to produce a dose-related increase in cardiac output. The increase in cardiac output is accompanied by a significant reduction in the left ventricular diastolic pressure. Since dobutamine exhibits minimal p2 and a-adrenergic effects, augmentation of cardiac contractility occurs without major changes in arterial pressure. Although systemic vascular resistance is modestly reduced, the improvement in stroke volume is adequate to maintain arterial pressure. In addition, the chronotropic and arrhythmogenic effects of dobutamine are considerably less than those of other catecholamines in clinical use. In normotensive patients with AM1 complicated by cardiac failure, dobutamine has been shown to increase cardiac output ap- preciably without affecting heart rate or blood pressure, while simultaneously decreasing both preload and afterload. These beneficial hemodynamic effects might be expected to favorably influence myocardial metabolism. Although such data are not presently available, dobutamine has been shown to improve ventricular performance in patients with AM1 without exacerbating enzymatically determined ischemic injury and without increasing ventricular arrhythmias. Dobutamine appears to offer several advantages over other catecholamines when the desired goal is to improve ventricular function by direct inotropic stimulation. Both dopamine and norepinephrine in moderate to high doses increase systemic vascular resistance, which can offset the increase in cardiac output due to augmented contractility and can also increase myocardial oxygen demands. In addition, dopamine in small to moderate doses does not lower left ventricular filling pressure as effectively as dobutamine.

Dobutamine has not been systematically evaluated in cardiogenic shock. In mild hypotension, augmentation of cardiac output may increase pressure. However, in cardiogenic shock with severe hypotension, an increase in systemic vascular resistance may be essential in maintaining adequate coronary perfusion pressure. In such cases, norepinephrine or dopamine would appear to be more efficacious than dobutamine. Additional studies

43

are needed to define the role of dobutamine in the management of AM1 and cardiogenic shock.

Other sympathomimetic amines have also been used in the treatment of cardiogenic shock but, in most cases, are hemodynamically less advantageous than dopamine or norepinephrine.

EPINEPHRINE.-This potent (3 inotropic and chronotropic catecholamine causes vasodilation of skeletal muscle beds and vi- soconstriction of splanchnic and renal beds. Although epinephrine increases cardiac output, the effects on regional resistance do not favor redistribution of flow to vital organs.“’ In addition, serious cardiac arrhythmias resulting from increased automa- ticity are potential hazards with epinephrine. Epinephrine thus appears to be hemodynamically less advantageous than norepinephrine.

ISOPROTERENOL.-Isoproterenol, a synthetic sympathomimetic amine, is a pure P-adrenergic agonist that augments myocardial contractility and heart rate and causes peripheral vasodilation. In patients with moderate to severe shock and hypotension, the drug is not beneficial because the fall in systemic resistance frequently exceeds the increase in cardiac output, resulting in a further reduction in blood pressure.“’ In addition, its inotropic and chronotropic effects substantially increase myocardial oxygen demands, which can exacerbate myocardial ischemia and lead to extension of necrosis. Although cardiac performance is improved with isoproterenol, deterioration of myocardial metabolism despite an increase in coronar& blood flow has been demonstrated in clinical cardiogenic shock. This indicates that myocardial oxygen demands exceeded an overall improvement in oxygen delivery. In addition, isoproterenol frequently induces ventricular arrhythmias. For these rea- sons, isoproterenol is not recommended in the treatment of cardiogenic shock.

PURE WADRENERGIC AGONISTS.-Drugs such as phenylephrine and methoxamine have no inotropic activity and increase systemic resistance without favorably redistributing blood flow to vital organs.12’ Although blood pressure is usually increased, cardiac output is generally reduced and myocardial oxygen demands augmented. Such drugs have no place in the management of cardiogenic shock.

Extreme caution is required when drugs with potent vasoconstrictor properties are used in the treatment of cardiogenic shock. Although some vasoconstriction may be beneficial initially to maintain adequate perfusion pressure to vital organs, excessive or prolonged vasoconstriction is potentially harmful. This is especially true if vasoconstrictor drugs are given to maintain pressure in relatively hypovolemic patients. In addition, excessive elevation of systemic resistance and pressure will increase myocardial oxygen demands and may reduce cardiac

44

output. Unfortunately, there is no optimal blood pressure for all patients in cardiogenic shock, because the extent of atheroscle- rotic narrowing of various vascular beds, which influences regional perfusion pressure, is unknown, as are the relative effects of changing afterload on myocardial oxygen supply and demand. As a general guide, however, a mean arterial pressure of 65-70 mm Hg is required to perfuse adequately the brain, kidney and splanchnic organs and a diastolic pressure of 60 mm Hg to perfuse the heart. The dosage of drug employed, then, should be titrated to maintain systolic pressure at 80-90 mm Hg and diastolic pressure at 60-70 mm Hg.

In summary, the vasoactive drugs of choice in the initial treatment of cardiogenic shock are norepinephrine and dopamine because of their favorable redistribution of blood flow away from skin and muscle and toward the heart and brain. Dopa- mine has the added advantage of redistributing blood to the kidney and splanchnic beds. The possible role of dobutamine in cardiogenic shock requires further investigation. Although these agents in appropriate doses may improve cardiovascular function without augmenting myocardial oxygen demands, there is no evidence to date that the ultimate course of cardiogenic shock is favorably affected. However, their use is often successful in temporarily improving systemic pressure and cardiac output, which is important in stabilizing the patient for possible cardiac catheterization and institution of other modes of therapy, in- cluding mechanical cardiac assistance or emergency surgery. Perhaps earlier recognition and institution of pharmacologic therapy for circulatory failure following myocardial infarction might favorably alter eventual prognosis.

DIURETICS

The most effective means of establishing an adequate urine output in the patient in shock is by correcting reduced intravascular volume and restoring renal perfusion pressure. Treatment of the hypovolemic, hypotensive patient with potent diuretics is dangerous and will only worsen tissue perfusion. The intravenous diuretics furosemide and ethacrynic acid are useful in the patient in cardiogenic shock with high PCWP and pulmonary venous congestion, although vasodilator therapy may, in certain cases, be even more advantageous. If diuretics are used, the smallest effective dose should be employed to maintain a urine output of at least 40-50 ml/hour with careful monitoring of blood pressure and cardiac filling pressure. It should be noted that furosemide, by increasing venous capacitance, may reduce PCWP before it actually induces diuresis.121 In addition to reducing pulmonary congestion and improving blood oxygenation, diuretic therapy may also reduce myocardial oxygen demands by decreasing heart size.

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DIGITALIS GLYCOSIDES

Despite the salutory effects of digitalis on ventricular function in chronic congestive heart failure, data from clinical studies indicate that digitalis is of no benefit and rnaJ actually be deleterious in patients with cardiogenic shock.12 ’ 123 As an inotropic agent in this clinical setting, it is relatively weak compared to the more potent sympathomimetic amines. Attenuation of t& positive inotropic effect of digitalis in ischemic myoeardium has been demonstrated experimentally. Intravenous digitalis may also produce transient peripheral and coronary vasoconstriction, which could be hemodynamically detrimental in cardiogenic shock because of the increase in afterload and reduction in coronary blood Aow.‘~~ In addition, the hypoxia, acidosis, and impaired renal function, common in shock states, predispose to potentially dangerous digitalis-induced arrhythmias. The uses of digitalis in cardiogenic shock are lim ited to the treatment of su- praventricular tachyarrhythmias unresponsive to vagal maneu- vers and of m ild to moderate pump failure when the patient is being weaned from more potent inotropic agents.

VASODILATOR THERAPY IN CARDIOGENIC SHOCK

Although generalized sympathetic vasoconstriction is a useful compensatory mechanism for maintaining systemic pressure in shock, excessive arteriolar and precapillary constriction can reduce tissue flow and oxygen delivery despite adequate or even high perfusion pressure. In addition, progressively increasing postcapillary resistance results in an increase in capillary hydrostatic pressure and loss of intravascular volume; the latter reduces cardiac output and reflexly increases sympathetic activity even further.4g The rationale for using vasodilator therapy in shock is to break the deleterious positive feedback cycle in which widespread vasoconstriction causes a decrease in cardiac output and blood pressure, resulting in further sympathetically induced vasoconstriction. The potential beneficial effects of vasodilators include (1) dilation of arterioles, precapillary sphinc- ters, and venules, which improves capillary flow; (2) reduction in capillary hydrostatic pressure due to a greater decrease in postcapillary resistance, which favors movement of fluid into the intravascular space; and (3) reduction in myocardial oxygen demands by decreasing both preload and afterload. The vasodilator drugs have no direct inotropic action on the heart. Their effects on increasing cardiac output are entirely mediated by changes in preload and afterload.

Despite the beneficial hemodynamic effects produced by these agents in selected patients in chronic congestive heart failure, 124, 125S 137 their exact role in the management of AMI and cardiogenic shock remains controversial.” Some reports have

46

demonstrated hemodynamic improvement in cardiogenic shock in the absence of severe hypotension when systemic vascular resistance and left ventricular filling pressures were elevated.iz6, 13’ Long-term prognosis, however, has not been shown to be favorably altered, and even short-term hemodynamic improvement has not been consistently obtained. It should be appreciated that the use of vasodilators in myocardial infarction, particularly when shock occurs, is potentially dangerous. The major hazard is that a reduction in preload and afterload could further decrease diastolic arterial pressure, resulting in extension of ischemic myocardial injury. The possibility of improving coronary blood flow to ischemic zones with vasodilators has not been demonstrated in the clinical setting. In some experimental studies vasodilators have actually increased infarct size by redistributing collateral flow away from the ischemic region C’coronary steal”). 127-130

Although vasodilators cannot be recommended routinely in the management of cardiogenic shock, they may be of benefit in selected patients without severe hypotension who show evidence of excessive vasoconstriction and poor tissue perfusion despite adequate volume replacement. In addition, afterload reduction has been of temporary benefit in cardiogenic shock associated with severe mitral regurgitation, where decreasing peripheral vascular resistance reduces the regurgitation and enhances cardiac output4’, 132, 133

The vasodilator agents most common11 used in these settings are nitroprusside and phentolamine.134, ’ 5 Nitroprusside acts directly on vascular smooth muscle to cause both arteriolar and venous dilation.136, 137 The drug is administered intravenously beginning with a dose of 0.5 pg/kg/minute, which is gradually increased if improvement in hemodynamics and overall tissue perfusion is observed. Additional volume replacement may be required if filling pressure falls excessively. Prolonged use of nitroprusside, particularly in the setting of renal impairment, can cause thiocyanate toxicity. Phentolamine is an a-adrenergic blockii$f Fgent with no depressant effects on myocardial contractility. ’ Phentolamine inhibits venoconstriction relatively more than arteriolar constriction. This can cause a rapid decrease in cardiac filling pressure, so adequate volume replacement is essential before starting therapy. Phentolamine is given intravenously at a dosage of 0.1-2 mg/minute. The importance of careful hemodynamic monitoring of arterial and ventricular filling pressures prior to and during vasodilator therapy should be emphasized. The drug dose must be titrated so that systemic pressure does not fall more than 10 mm Hg or below 80-90 mg systolic. The presence of severe hypotension is a contraindica- tion to using vasodilator drugs. The potential role of vasodilator therapy in conjunction with other treatment modalities such as inechanical cardiac assistance to augment diastolic pressure ap-

47

pears to merit further investigation. The combined use of external counter-pulsation and nitroprusside was shown to be more effective than either alone in a small group of patients with myocardial infarction, shock. 13’

some of whom were in cardiogenic

MECHANICAL CIRCULATORY ASSISTANCE

The high mortality associated with cardiogenic shock despite optimal medical therapy has led to the development of a variety of mechanical circulatory assistance devices designed to support left ventricular function temporarily. A major reason for the failure of conventional pharmacologic therapy to reverse the shock syndrome associated with myocardial infarction is that drugs that increase systemic pressure and cardiac output also increase myocardial oxygen demands, which can exacerbate ischemic cardiac injury. Mechanical circulatory assistance techniques were developed in an attempt to improve left ventricular function in the failing heart while favorably affecting the balance between myocardial oxygen supply and demand. This has the advantage of restoring effective circulation while potentially limiting ischemic myocardial damage. The two basic approaches that have been used entail (1) modifications of cardiopulmonary bypass techniques used in open heart surgery, and (2) counterpulsation in which phasic displacement of arterial blood volume synchronized with the cardiac cycle is employed to increase proximal aorti~~r~~~ure during diastole and to reduce afterload during systole.

BYPASS TECHNIQUES

Although total cardiopulmonary bypass has been used in the treatment of cardiogenic shock, blood cell destruction severely limits the time period over which this method may be safely employed. Another disadvantage is that perfusion is nonpulsa- tile, and so arterial pressure is constant throughout the cardiac cycle. This means that increases in coronary blood flow achieved by raising diastolic pressure are also accompanied by an increase in cardiac work, since left ventricular systolic pressure is also raised.

Partial bypass techniques that have been used in the treatment of cardiogenic shock include left atrial-arterial bypass (transseptal cannulation, Debakey pump) and left ventricular- arterial bypass (transarterial left ventricular cannulation, left ventricle-aorta bypass pump). Modifications of these techniques have incorporated the principle of counterpulsation. Presently, none of these approaches has achieved widespread acceptance, being limited by technical complexities, relatively high complication rat.es. and excessive costs,

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COUNTERPULSATION

Presently, counterpulsation is the most frequently used method of mechanical circulatory assistance in the treatment of cardiogenic shock. The principle of counterpulsation involves augmentation of aortic pressure during diastole with subsequent reduction of afterload. The increase in aortic diastolic pressure improves coronary blood flow to pressure-dependent ischemic regions. The decrease in afterload enhances systolic emptying of the left ventricle, which augments cardiac output and reduces myocardial oxygen consumption. The reduction in oxygen demands is due to diminished myocardial wall tension through systolic pressure unloading, as well as to decreased ventricular volume. In the setting of severe hypotension, the efficacy of the technique is related more to increasing diastolic coronary perfusion than to reducing myocardial oxygen demands, since systolic pressure is already very low. The net effect of counterpulsation is to improve the ratio of myocardial oxygen supply to demand, providing optimal potential for reducing ischemic cardiac damage while restoring effective circulation to vital organs.

Counterpulsation may be achieved by intravascular techniques which include arterioarterial pump, the intra-aortic balloon pump, and the dynamic aortic patch, as well as by noninvasive methods which include external synchronous compression and synchronized body acceleration. Although the results of the arterioarterial pump and dynamic aortic patch are encouraging, these methods are limited by technical difficulties and complications that include blood element destruction, clotting, and infection. The remainder of this section will deal with intra-aortic balloon counterpulsation, which is currently the most widely used form of mechanical circulatory assistance, and external counterpulsation.

INTRA-AORTIC BALLOON COUNTERPULSATION. 142-145-In this technique, a catheter with a distal balloon is advanced retrograde from the femoral artery to the descending thoracic aorta just distal to the left subclavian artery. An external control system, using the ECG for synchronization, inflates a 30- or 40-cc balloon during diastole and immediately deflates the balloon just prior to left ventricular ejection. Balloon inflation increases coronary blood flow by augmenting diastolic perfusion pressure and balloon deflation decreases myocardial oxygen demands and improves cardiac output by reducing afterload (Fig 8). Balloon counterpulsation has been carried out safely for up to several days with very little discomfort to the patient. In the past, catheter design required insertion by a surgical cutdown of the common femoral artery and attachment of a prosthetic graft to allow safe passage of the balloon. Modification of the standard balloon catheter by addition of a central lumen for pressure monitoring, injection of contrast, medium, and passage of a guide wire ap-

49

Fig 8.--Relationship between the cardiac cycle and balloon inflation during intra- aortic balloon counterpulsation (IAW). During diastole (A) the balloon is inflated, augmenting the prevailing pressure in the proximal aorta and hence coronary arterial perfusion pressure. During systole (B) the left ventricular chamber dimension decreases, with antegrade ejection of blood into the proximal aorta. During this portion of the cardiac cycle the balloon is deflated, facilitating ejection of blood into the periphery, where systemic arterial resistance vessels are dilated maximally because of the preceding inhibition of perfusion by the inflated balloon during diastole. As shown in the inset on the right, utilization of IABP results in augmentation of diastolic arterial blood pressure (PAo) with a modest reduction in systolic left ventricular pressure (PLv). (From Sobel B.E.: Cardiac and noncardiac forms of acute circulatory collapse (shock), in Braunwald E. (ed.): Heart Disease: A Textbook of Cardiovas- w/a; Medicine..Philadelphia, W.B. Saunders Co., 1980. Original figure from Bolooki H.: Clinical Applications of Ma-aortic Balloon Pump. New York, Futura Publishing Co., 1977. Reproduced with permission.)

pears to increase the efficacy and safety of insertion. Recently a new balloon catheter has been developed that can be introduced percutaneously by Seldinger technique using a No. 12 F Teflon sheath, which facilitates catheter insertion and removal.146, 147 Intra-aortic balloon counterpulsation offers the advantages of rapid implementation, technical simplicity, and a relatively low complication rate. Reported complications include lower extremity ischemia requiring balloon removal, emergency vascular surgery, and, rarely, amputation; femoral and renal arterial emboli, usually in nonanticoagulated patients; trauma to the aortic wall, rarely with dissection or actual rupture; thrombocytopenia and hemolysis; deep vein thrombosis; groin hematoma and wound infection; and mechanical failure such as balloon rupture.‘48 Contraindications to balloon counterpulsation include moderate to severe aortic regurgitation and the presence of an aortic aneurysm. Since the duration of balloon inflation and deflation are fixed, counterpulsation is less efficient with irregular rhythms such as atria1 fibrillation, since pressure augmentation may occur during early systole and balloon deflation may occur before the end of diastole. In addition, tachyarrhythmias must be controlled before institution of balloon counterpulsation for maximum benefit. Peripheral vascular disease may be a limiting or complicating factor and prevents successful catheter insertion 11’ IO%-15% of patients. > 1

50

The results of intra-aortic balloon counterpulsation in cardiogenic shock have demonstrated that tern ora

14g 144 Y?2%Fodynamic improvement can usually be achieved. ’ ’ Hemody- namic changes include an increase in cardiac output (lO%- 40%), a slight increase or no change in mean aortic pressure, decrease in left ventricular filling pressure, and slowing of the heart rate. These changes are associated with signs of improved tissue blood flow, as indicated by decreased cutaneous vasoconstriction, improvement in mental status, increased urine output, and correction of metabolic acidosis. In addition, pulmonary venous congestion is diminished, as indicated by improvement in arterial oxygenation. Data on the effects of balloon counterpulsation on coronary blood flow and myocardial metabolism in clinical cardiogenic shock are limited and variable. In one study, coronary blood flow increased by about 30% while myocardial oxygen consumption was unchanged and lactate production con- verted to extraction, indicating a reduction in myocardial ischemia. 157 In another study in which the patients had been stabilized for 14 hours with counter-pulsation before coronary hemodynamics were measured, coronary blood flow and myocardial oxygen consumption decreased in most patients, with no change in lactate metabolism.‘5s The effects of counter-pulsation on coronary blood flow and myocardial metabolism depend on the extent and severity of coronary artery disease, the magnitude of diastolic pressure augmentation, and changes in myocardial oxygen consumption.

Despite temporary reversal of many of the hemodynamic and metabolic abnormalities associated with cardiogenic shock, intra-aortic balloon counter-pulsation has had little impact on long-term survival in myocardial infarction once the shock syndrome has already developed. Although some studies have shown a reduction in mortality to 75% with balloon counterpulsation alone (small improvement over the 85%-100% mortality with conventional medical therapy), in most instances survival is confined to the period of actual mechanical circulatory assist. The failure to permanently reverse the shock syndrome following acute infarction may be explained by the extensive myocardial damage already in existence at the time therapy is instituted.

The transient nature of the hemodynamic benefits of balloon counterpulsation and the frequent deterioration observed following discontinuation of mechanical assistance (“balloon dependence”) have led to the use of emergency cardiac surgery in selected patients with cardiogenic shock.‘45V 156 As a result of recent advances, successful surgical correction of mechanical myocardial defects in conjunction with emergency revascularization has reduced the mortality in cardiogenic shock to 60% at some institutions. A major use of intra-aortic balloon counterpulsation in emergency cardiac surgery is to support left ven-

51

tricular function temporarily during diagnostic cardiac catheterization and angiography to identify surgically remedial lesions. In surgical candidates, balloon counterpulsation is of further benefit in maintaining adequate circulation during induction of anesthesia and in further supporting ventricular function in the immediate postoperative period.

Since intra-aortic balloon counterpulsation has been shown @ reduce experimental infarct size, 15’, 16’ it may be useful in pre venting cardiogenic shock in the early stages of myocardial infarction with mild to moderate ventricular dysfunction. Al- though there is little clinical data to support the routine use of “prophylactic mechanical cardiac assistance,” the available data do indicate that balloon counterpulsation alone, once shock is evident, is usually too late.

PRACTICAL USE OF BALLOON COUNTERPULSATION.-The major indication for intra-aortic balloon counterpulsation in cardiogenic shock is the failure of conventional medical therapy to reverse the shock syndrome in an otherwise salvageable patient. This includes correction of all reversible factors that could contribute to shock (arrhythmias, hypoxia, acidosis, etc.), achieve- ment of an optimal left ventricular filling pressure, and the use of appropriate pharmacologic agents. Balloon counterpulsation is initially maintained for 12-24 hours. At this point mechanical assistance is discontinued and the patient’s hemodynamic and clinical status reassessed. If improvement is noted, additional periods of counterpulsation are attempted until maximum hemodynamic benefit is achieved. Then the patient may be gradually weaned off the pump by applying counterpulsation first to every other cardiac cycle, then to every third cycle, etc. If deterioration occurs while the patient is on the pump or if the patient cannot be weaned from the pump, emergency cardiac catheterization is indicated to determine if a surgically remedial lesion is present.

EXTERNAL COUNTERPULSATION External counterpulsation is a noninvasive form of diastolic

pressure augmentation and afterload reduction that produces phasic displacement of blood by applying synchronous intermit- tent positive and negative pressure to the extremities.161-‘64 The most widely used device for this purpose consists of a water- filled, trouser-like bladder that encloses the legs and is surrounded by a rigid plastic case with an airtight seal. A mechanical pump synchronized with the ECG rapidly inflates the bladder during diastole and deflates it during systole. This technique delivers a positive external pressure of up to 250 mm Hg and a maximum negative external pressure of - 100 mm Hg. During diastole, external compression applied uniformly to the lower

52

extremities reduces the capacity of the arterial system, displac- ing blood into the proximal aorta. Augmentation of diastolic aortic pressure increases coronary blood flow, thereby improving myocardial oxygen delivery. During systole, negative external pressure increases the arterial capacity of the lower extremities, which pulls arterial blood peripherally, lowering central aortic pressure and afterload. This augments cardiac output while reducing myocardial oxygen demands. The precise synchronization, duration, and magnitude of the externally applied pressure can be varied to achieve the desired changes in aortic pressure. A modification of this technique involves sequenced external pulsation on all four extremities.165

The major advantages of external counterpulsation over invasive approaches are (1) it is nontraumatic and (2) it can be rapidly implemented for prolonged periods without the vascular complications of the intra-aortic balloon or the technical complexities of bypass procedures. The only common untoward side effect of external compression is mild local discomfort in the legs, particularly after prolonged periods of pumping. Although the potential for dislodging lower-extremity venous thrombi and precipitating pulmonary emboli exists, large-scale clinical studies have not shown any increased risk of this complication. Ex- ternal counterpulsation is contraindicated in patients with aortic regurgitation and severe peripheral vascular disease.

Although there are no data that conclusively demonstrate that external counter-pulsation reduces mortality in cardiogenic shock, a number of studies have shown very definite transient hemodynamic improvement.166-168 In a comparative study on patients with cardiogenic shock, increases in cardiac output with external counterpulsation were comparable to those obtained with intra-aortic balloon counterpulsation. 16’ However, external counterpulsation is generally less efficient in augmenting diastolic pressure and less effective in reducing left ventricular filling pressure than is balloon counterpulsation. The failure of external counterpulsation to consistently lower left ventricular diastolic pressure is due to the increase in venous return produced by leg vein compression during systole.

The use of vasodilator therapy in conjunction with external cardiac assistance is a useful means of achieving diastolic pressure augmentation while simultaneously reducing left ventricular preload and afterload. In a study on patients with AMI, some with cardiogenic shock, the combination of external counterpulsation and nitroprusside resulted in greater hemodynamic improvement than was achieved by either treatment modality alone.13’ External counterpulsation reversed the diastolic hypotension produced by nitroprusside and increased cardiac index further in most patients than nitroprusside alone. The use of nitroprusside enabled left ventricular filling pressure to be substantially reduced.

53

External counter-pulsation has been shown to increase coronary blood flow and lactate extraction in patients with AM1 complicated by heart failure.‘7o3 17’ The potential for reducing myocardial ischemia suggests that external counterpulsation could potentially be useful in limiting infarct size and perhaps preventing cardiogenic shock. In this regard, a cooperative trial reported that external counterpulsation was beneficial in red c- Y-2 ing the mortality rate in patients with Killip class II AM1.J Treated patients also showed a decrease in the incidence of recurrent chest pain, progression of heart failure, and occurrence of ventricular fibrillation, and an improvement in functional status at the time of discharge. Hemodynamic measurements, however, were not reported. Although noninvasive circulatory assistance has not improved survival in myocardial infarction once shock has developed, the possibility that shock might be prevented by early use of external counterpulsation in selected hemodynamic subsets requires further investigation.

ROLE OF EMERGENCY SURGERY IN CARDIOGENIC SHOCK

The finding that pharmacologic therapy and mechanical circulatory assistance generally result in only temporary hemodynamic improvement in cardiogenic shock and that long-term survival is not greatly affected, stimulated the development of more definitive surgical approaches in the treatment of severe pump failure complicating myocardial infarction. Technical advances in open heart surgery and the use of intra-aortic balloon counter-pulsation for supporting left ventricular function during cardiac catheterization and anesthesia induction have made the ble. P ossibility of surgery in selected patients quite feasi-

145, 173- 7g The two major goals of surgery in AM1 with refractory shock are (1) to increase coronary blood flow to ischemic potentially viable myocardium and (2) to correct mechanical defects that contribute to hemodynamic deterioration. The surgical procedures that have been used include myocardial revascularization, infarctectomy or aneurysmectomy, repair of ventricular septal defect, and mitral valve replacement.

PATIENT SELECTION Although there are no widely accepted, well-defined criteria

for selection of patients in cardiogenic shock for emergency surgery, several general guidelines have been established. When shock complicating myocardial infarction is not rapidly reversed by conventional therapy (l-2 hours), mechanical circulatory assistance should be promptly instituted. If at this point hemodynamic and clinical parameters show no significant improvement or deteriorate further, then cardiac catheterization is under- taken and surgery considered in patients with correctable le-

54

sions. Experience with intra-aortic balloon counterpulsation has shown that hemodynamic improvement generally occurs within 12-24 hours, with maximum effects attained at 24-48 hours. Based on this observation, the following guidelines have been recommended for cardiac catheterization in patients in cardiogenic shock treated with balloon counter-pulsation: (1) failure to show hemodynamic improvement within 12-24 hours with optimal drug therapy and balloon counterpulsation, (2) increasing requirement for vasoconstrictor agents during treatment with balloon counterpulsation, (3) dependence on balloon counterpulsation after 24 hours, or (4) recurrent hemodynamic deterioration after being weaned from mechanical assistance.“’ De- pendence on intra-aortic balloon counterpulsation has been defined as the failure to maintain a mean aortic pressure of 60 mm Hg, a cardiac index of greater than 2 L/minute/m2, and a pulmonary wedge pressure of less than 20 mm Hg on temporary interruption of mechanical assistance. In most studies 50% of patients will be balloon dependent and will be candidates for cardiac catheterization.

Reports from several centers have clearly shown that selective coronary and ventricular angiography can be performed quickly and safely in acutely ill patients in cardiogenic shock with mechanical circulatory support. The importance of careful angiographic evaluation in refractory cardiogenic shock is reflected by studies showing that 40%-65% of patients undergoing catheterization in this setting will be surgical candidates. Surgically remedial lesions in cardiogenic shock include (1) obstructive coronary artery disease, (2) acute mitral regurgitation, (3) acute ventricular septal rupture, and (4) discrete region of myocardial dyssynergy. Unfortunately, the most common cause of cardiogenic shock is diffuse left ventricular dyssynergy involving more than 40% of the left ventricle, which is usually not amenable to conventional surgical therapy. When myocardial damage is this extensive, the only possible treatment modality appears to be total heart replacement. Although the risk of cardiac surgery in the immediate postinfarction period is very high, the majority of patients in cardiogenic shock die within 24-48 hours after onset of infarction. Thus, if surgery is to be effective, it must be performed early because of the rapidly progressive nature of ischemic myocardial injury.

CORONARY ARTERY BYPASS GRAFTING

The goal of myocardial revascularization in cardiogenic shock is to improve ventricular function and limit infarct size by restoring blood flow to ischemic but viable periinfarction tissue. Segmental left ventricular wall motion abnormalities and pump function have been reversed following bypass surgery in certain patients with angina as well as AMI. Several groups of investi-

55

gators have reported survival rates of up to 44%-74% in small numbers of selected patients with cardiogenic shock treated with mechanical assistance and emergency revascularization formed within 24 hours of hemodynamic deterioration. 162, 16l%

Candidates for revascularization must have patent distal vessels and demonstrate some vascularity of the dyssynergic left ventricular wall with a bypassable major coronary branch supplying the area. This approach, however, has not received widespread acceptance because of the very high mortality associated with bypass surgery within the first 24 hours after AMI.18*-ls7 In some instances, acute revascularization has resulted in intramyocardial hemorrhage and edema in the infarcted area associated with decreased left ventricular compliance and function.ls3 In addition, the operative mortality is high when revascularization alone is performed for heart failure secondary to coronary artery disease.“’ i8’ Successful surgical intervention is more likely when a part of the pump failure is attributable to a major mechanical disturbance of ventricular function, such as segmental dyssynergy, ventricular septal defect, or mitral regurgitation. When shock is due entirely to extensive myocardial damage with an ejection fraction of less than 25%, emergency bypass surgery carries a high risk and, as the only procedure, is unlikely to reverse the shock syndrome.

INFARCTECTOMY AND ANEURYSMECTOMY

The basis for excision of acutely infarcted myocardium or aneurysm in cardiogenic shock is that regional myocardial dyssynergy contributes to hemodynamic impairment not only through direct loss of contractile mass but also by secondarily affecting the function of adjacent viable myocardium.1g0-1g3 This large dyskinetic area may sequester blood volume by passive expansion during systole and reduce forward stroke volume. As a result, end-diastolic volume increases to maintain cardiac output, which augments myocardial oxygen demands by increasing wall tension. In addition, distortion of diastolic ventricular ge- ometry can cause mitral regurgitation. Dyssynergy in the setting of AM1 may also precipitate medically refractory ventricular arrhythmias. Infarctectomy in experimental myocardial infarction has been demonstrated to improve hemodynamic function and increase survival.“*, lg5 The major limitation is the mass of myocardial tissue that can safely be excised without causing hemodynamic deterioration. Adequate hemodynamic function cannot be maintained with excision of more than 35%- 40% of left ventricular muscle mass.1g6 ig7

Clinical experience with infarctectomy and aneurysmectomy in refractory cardiogenic shock is limited. The major indication for surgery in this setting is the presence of a relatively discrete dyskinetic segment constituting less than 350/c-40% of the left

56

ventricular wall which appears to significantly interfere with pump function. Another less common indication is the presence of a localized area of infarction with recurrent ventricular arrhythmias refractory to drug therapy. The major preoperative determinants of survival are the pumping capacity of the non- involved myocardium and the extent of coronary artery disease. 1g*-200 Infarctectomy and aneurysmectomy are usually performed in conjunction with coronary bypass grafting when possible. Concomitant myocardial revascularization is important to reverse ischemia in areas adjacent to and distant from the actual infarct. Since most late deaths after aneurysmectomy are due to infarction at sites remote from the aneurysm, long-term prognosis may also be improved. In one study of 10 patients with refractory cardiogenic shock, infarctectomy combined with myocardial revascularization resulted in a 40% long-term survival rate.162 Results of infarctectomy for medically refractory arrhythmias have been variable.

MITRAL VALVE REPLACEMENT

Papillary muscle dysfunction due to AM1 may result in mitral regurgitation which can vary from mild to massive in severity. Papillary muscle rupture is relatively rare and presents with acute severe mitral regurgitation, pulmonary edema, and shock.3g, 40, l’s The hemodynamic burden imposed by acute mitral regurgitation is due to reduction in forward stroke volume and to pulmonary venous congestion with impaired gas exchange.201 When superimposed on an already ischemic left ventricle, even mild to moderate mitral regurgitation can precipitate the shock syndrome. Surgical correction of hemodynamically significant mitral regurgitation complicating AM1 consists of mitral valve replacement. The operative risk can be considerably reduced if surgery can be delayed for 4 weeks or more. This is only possible if there is rapid and sustained hemodynamic improvement with vasodilators and balloon counterpulsation. Unfortunately, this is rarely the case, and emergency valve replacement in combination with myocardial revascularization or infarctectomy offers the only chance for survival. Sev- eral reports have demonstrated the potential for reversing the shock syndrome associated with cardiogenic shock and acute mitral regurgitation in small numbers of selected patients.202-205

CARDIAC RUPTURE

Septal rupture is usually associated with extensive infarction and often aneurysms of the adjacent free wall. The hemodynamic burden resulting from the left-to-right shunt is due to sudden reduction in cardiac output and the imposition of a volume load on the left ventricle previously damaged by acute in-

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farction. 3g, *‘I ‘7’s 205-207 In most cases the magnitude of the shunt is large and treatment with inotropic drugs combined with balloon counter-pulsation offers only temporary hemodynamic improvement. Although surgical results are most successful when repair is performed 2 or more months after infarction, progressive clinical deterioration usually precludes any delay. Surgical repair of the septal defect is carried out through w incision directly into the infarcted, often dyskinetic, left ventricular free wall. Small defects may be closed with sutures, while larger defects require prosthetic grafts of woven Teflon. Surgical correction is frequently difficult because of technical problems in suturing friable, often necrotic, tissue. Septal repair may be combined with aneurysmectomy and myocardial revascularization in selected cases.208-213 Early surgery for septal rupture in AM1 has resulted in survival in about 50% of patients, which is encouraging considering, that the majority of such patients die within 1 week.

Acute rupture of the ventricular free wall is a more common complication of myocardial infarction than septal rupture and is the cause of death in 8%-10% of autopsied cases. The clinical presentation is characterized by sudden recurrence of chest pain, followed by acute hypotension and signs of pericardial tamponade. This complication usually occurs in elderly patients with persistent hypertension and severe left ventricular dysfunction. 214-217 Emergency pericardiocentesis is indicated when the diagnosis is suspected. Removal of a small quantity of blood may be temporarily therapeutic. Cardiopulmonary bypass should then be instituted immediately without angiography. The surgical approach involves infarctectomy with suturing or patch repair of the defect. Intraoperative angiography may be possible to determine if myocardial revascularization would be of benefit. There have been several reports of successful surgery for cardiac rupture with long-term surviva1.218-221

SUMMARY AND FUTURE DIRECTIONS

Cardiogenic shock is a rapidly progressive syndrome characterized by severe left ventricular dysfunction and generalized circulatory failure. It is the leading cause of death in patients hospitalized with AMI. The high mortality associated with cardiogenic shock is related primarily to extensive loss of left ventricular myocardium. Extramyocardial factors and mechanical defects may also contribute to the shock syndrome. Optimal treatment of this disorder requires a detailed understanding of the pathophysiology of ischemic heart disease and shock and considerable clinical expertise in the use of hemodynamic monitoring, vasoactive inotropic drugs, and mechanical circulatory assistance. Despite aggressive medical therapy combined with

58

intra-aortic balloon counterpulsation, the mortality from cardiogenic shock remains high. Evaluation for potentially correctable mechanical cardiac defects in selected patients has identified a significant subset of patients who may benefit from emergency surgery. Successful cardiac catheterization and surgical therapy for cardiogenic shock requires the combined efforts of an expe- rienced, well-coordinated team of cardiologists and cardiovascular surgeons. Unfortunately, only slightly more than 50% of patients who undergo catheterization will be found to have surgically remediable lesions, and of these, at best, 60% will be long-term survivors. The overall survival rate in cardiogenic shock despite this aggressive therapeutic approach is still only 30%.

It would appear that any further reduction in mortality associated with pump failure following AM1 will require therapy which can prevent progression of ischemic damage and the development of cardiogenic shock. The rationale for the concept of “infarct size reduction”‘*’ 22, 222, 223 is based on two physiologic observations: (1) AM1 is a dynamic process which is influenced by the balance between myocardial oxygen supply and demand, and (2) cumulative infarct size is a major determinant of ultimate prognosis. Extensive experimental studies have evaluated the efficacy of various interventions that could reduce myocardial necrosis following coronary occlusion. The basic approaches currently being investigated include the use of various pharmacologic agents to (1) decrease myocardial oxygen demands, (2) increase myocardial oxygen supply, (3) augment anaerobic metabolism, (4) facilitate diffusion of oxygen and substrates, and (5) protect against autolytic and heterolytic processes (Table 7). While the potential benefits of these approaches have been demonstrated experimentally, conclusive proof of the efficacy of specific interventions to salvage ischemic myocardium in man is not yet available. Although encouraging preliminary results have been obtained in clinical studies using 13-blockers,224-228 nitrates 22g-231 hyaluronidase,232 and glucose-insulin-potassium infusibn,233-235 routine use of any of these measures cannot be recommended at this time.

Most recently, studies have shown that myocardial reperfusion can be rapidly and safely achieved in a large percentage of patients with acutely evolving myocardial infarction by lysing fresh coronary thrombus with intracoronary and also intravenous infusion of the thrombolytic agent, streptokinase.236-243 Percutaneous transluminal coronary $r&o+asty244-247 immediately after intracoronary thrombolysis * may also contribute to the reperfusion of ischemic myocardium and decrease the risk of reocclusion. While initial experience with streptokinase alone and in combination with percutaneous coronary angioplasty strongly indicates that myocardial ischemia and left ventricular

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TABLE 7.-INTERVENTIONSTHATREDUCE MYOCARDIAL INJURY AFTERCORONARYARTERY OCCLUSION*

DECREASE MYOCARDIALOXYGEN REQUIREMENTS 6-Adrenergic blockadet Digitalis (in the failing heart) Counterpulsation

Intra-aortic balloon? External?

Nitroglycerint Decreasing afterload in patients with hypertension+ Reducing intracellular free fatty acid levels

Antilipolytic agents, e.g., 8-pyridyl carbinol Lipid-free albumin infusions Glucose-insulin-potassium+ (presumed)

Pentobarbital INCREASE MYOCARDIAL OXYGENSUPPLY

Directly Coronary artery reperfusioni- Elevating arterial oxygen tension; Thrombolytic agents? Heparint (presumed)

Through collateral vessels Elevation of coronary perfusion pressure by methoxamine,

phenylephrine, norepinephrine Intra-aortic balloon counterpulsation+ External counterpulsationt Hyaluronidaset

Increasing plasma osmolality Mannitol Hypertonic glucose

AUGMENT ANAEROBIC METABOLISM (PRESUMED) Glucose-insulin-potassium Hypertonic glucose 1-Carnitine Sodium dichloroacetate

PROTECT AGAINST AUTOLYTIC AND HETEROLYTIC PROCESSES (PRESUMED) Corticosteroidst Cobra venom factor Aprotinin Ibuprofen

*From Braunwald E., Sobel B.F.: Coronary blood flow and myocardial ischemia, in Braunwald E. (ed.1: Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia, W.B. Saunders Co., 1980. Reproduced with permission.

tIntervention has been applied to patients in pilot studies.

performance may be improved, the long-term effects on ventricular function and survival remain to be determined. Future advances in the treatment and prevention of cardiogenic shock will require more basic knowledge of the pathophysiologic mechanisms of acute myocardial ischemia as well as large-scale patient trials with appropriate control data, well-defined clinical subsets, and reliable quantitative techniques to measure regional left ventricular function and infarct size.

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REFERENCES

1. Scheidt S., Ascheim R., Killis T.: Shock after acute myocardial infarction: A clinical and hemodvnamic orofile. Am. J. Cardiol. 26:556. 1970.

2. Loeb H.S., Johnson S:A., Guniar R.M.: Cardiogenic shock. Triangle 13:121, 1974.

3. Rackley C.E., Russell R.O. Jr., Mantle J.A., et al.: Cardiogenic shock: Rec- ognition and management. Cardiovasc. Clin. 71251, 1975.

4. Amsterdam E.A., Demaria A.N., Hughes J.L., et al.: Myocardial infarction shock: Mechanisms and management, in Mason D.T. (ed.1: Congestive Heart Failure: Mechanisms, Evaluations and Treatment. New York, Dun-Don- nelly, 1976.

5. Swan H.J.C., Forrester J.S., Danzig R., et al.: Power failure in acute myocardial infarction. Progr. Cardiovasc. Dis. 12:568, 1970.

6. Page D.L., Caulfield J.B., Kastor J.A., et al.: Myocardial changes associated with cardiogenic shock. N. Engl. J. Med. 285:133, 1971. -

7. Gutovitz A.L.. Sobel B.E.. Roberts R.: Prozzressive nature of mvocardial injury in selected patients’with cardiogenii shock. Am. J. Carkol. 41:409, 1978.

8 Geddes J.S., Adgey A.A.J., Pantridge J.F.: Prevention of cardiogenic shock. Am. Heart J. 99:243, 1980.

9. Thal A.P., Kinney J.M.: On the definition and classification of shock. Progr. Cardiovasc. Dis. 9:527, 1967.

10. Jacobson E.D.: A physiologic approach to shock. N. Engl. J. Med. 278:834, 1968.

11. Hamosh P., Cohn J.N.: Left ventricular function in acute myocardial infarction. J. Clin. Invest. 50:523, 1971.

12. Mueller H., Ayres S.M., Gregory J.J., et al.: Hemodynamics, coronary blood flow and myocardial metabolism in coronary shock: Response to L-norepi- neohrine and isoproterenol. J. Clin. Invest. 49:1885. 1970.

13. Weber K.T., RatLhin R.A., Janicki J.S.: Left ventricular dysfunction following acute myocardial infarction: A clinico-pathologic and hemodynamic orofile of shock and failure. Am. J. Med. 54:697. 1973.

14. haroko P.R., Kjekshus i.K., Sobel B.E.: Fact&s influencing infarct size following experimental coronary artery occlusions. Circulation 43:67, 1971.

15. Harnarayan C., Bennett M.A., Pentecost B.L., et al.: Quantitative study of infarcted myocardium in cardiogenic shock. Br. Heart J. 32~728, 1970.

16. Page D.L., Caulfield J.B., Kastor S.A., et al.: Myocardial changes associated with cardiogenic shock. N. Engl. J. Med. 285:133, 1971.

17. Wackers F.J., Lie K.I., Becker A.E., et al.: Coronary artery disease in patients dying from cardiogenic shock or congestive heart failure in the setting of acute myocardial infarction. Br. Heart J. 32~728, 1970.

18. Alonso D.R., Scheidt S., Post M., et al.: Pathophysiology of cardiogenic shock: Quantification of myocardial necrosis, clinical, pathologic and electrocardiographic correlations. Circulation 48:588, 1973..

19. Cox J.L.. McLaughlin V.W.. Flowers NC.. et al.: The ischemic zone sur- rounding acute gyocardial infarction: Its morphology as detected by dehy- drogenase staining. Am. Heart J. 76:650, 1968.

20. Jennings R.B., Ganate C.E., Reimer A.: Ischemic tissue injury. Am. J. Pa- thol. 81:179, 1975.

21. Reimer K.A., Jennings R.B.: The wavefront phenomenon of myocardial ischemic cell death. Lab. Invest. 40:633, 1979.

22. Protection of the ischemic myocardium, Braunwald E. (ed.): Circulation 53 (suppl. I):l-228, 1976.

23. Sonnenblick E.H., Skelton C.L.: Oxygen consumption of the heart: Physio- logical principles and clinical implications. Mod. Concepts Cardiovasc. Dis. 40:9, 1971.

24 Buckberg G.D., Kattus A.A. Jr.: Factors determining the distribution and adequacy of left ventricular myocardial blood flow. in Bloor C.M., Olsson

61

R.A. (eds.): Current Topics in Coronary Research. New York, Plenum Press, 1973. Brazier J., Cooper N., Buckberg G.: The adequacy of subendocardial oxygen delivery: The interaction of determinants of flow, arterial oxygen content and myocardial oxygen need. Circulation 49:968, 1974. Hoffman J.I.E.: Determinants and prediction of transmural myocardial perfusion. Circulation 58:381, 1978. Guiha N.H., Lumas C.J., Broder MI., et al.: Predominant right ventricular failure in clinical and experimental right ventricular infarction. Clin. Res., 201375, 1972. Beme R.M., Rubio R.: Coronary circulation, in Beme R.M. (ed.1: The Car- diovascular System, The Heart. Handbook of Physiology, Bethesda, Md., American Physiological Society, 1979. Klocke F.J., Mates R.E., Codley D.P., et al.: Physiology of the coronary circulation in health and coronary artery disease, in Yu P., Goodwin J.F. (eds.): Progress in Cardiology. Philadelphia, Lea & Febiger, 1976. Williams D.O., Amsterdam E.A., Miller R.R.: Functional significance of coronary collateral vessels in patients with acute myocardial infarction: Re- lation to pump performance, cardiogenic shock and survival. Am. J. Car- dial. 37~345, 1975. Bleifeld W., Hanrath P., Mathey D., et al.: Acute myocardial infarction: Left and right ventricular hemodynamics in cardiogenic shock. Br. Heart J. 36~822, 1974. Diamond G., For-rester J.S.: Effect of coronary artery disease and acute myocardial infarction on left ventricular compliance in man. Circulation 45:11, 1972. Russell R.O. Jr., Rackley C.E., Pombo J., et al.: Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction. J. CZin. Invest. 49:1539, 1970. Cohn J.N., Luria M.H., Daddario R.C., et al.: Studies in clinical shock and hypotension: Hemodynamic effects of dextran. Circrdation 35:316, 1967. MacKenzie G.J., Taylor S.H., Flenley DC., et al.: Circulatory and respiratory studies in myocardial infarction and cardiogenic shock. Lancet 2:825, 1964. Ratshin R.A., Rackley C.E., Russel R.O.: Hemodynamic evaluation of left ventricular function in shock complicating myocardial infarction. Circula- tion 45:127, 1972. Shubin H., Abdelmonen A.A., Rand W.M., et al.: Objective index of hemodynamic status for quantitation of severity and prognosis of shock compli- eating myocardial infarction. Cardiovasc. kes. 2:$29,1968. Cohn J.N., Franciosa J.A.: Pathophysiology of shock in acute myocardial infarction. Progr. Cardiol. 2~207-234, 1973. Logue B., Bone D., Kaplan J.: The diagnosis and management of mechanical defects due to mvocardial infarction. Cardiovasc. Rev. Rep. 1:446-459.

25.

26.

27

28

29

30

31

32

33

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

is

1980. Fox A.C., Glassman E., Isom W.O.: Surgically remediable complications of myocardial infarction. Progr. Cardiovasc. Dis. 21:461-484, 1979. Cohn L.H.: Surgical management of acute and chronic cardiac mechanical complications due to myocardial infarction. Am. Heart J. 102:1049-1060, 1981. Crawford M.H., G’Rourke R.A.: Bedside diagnosis of the complications of myocardial infarction, in Eliot R.S. (ed.): Cardiac Emergencies. New York, Futura Publishing Co., 1982. Constantin L.: Extracardiac factors contributing to hypotension during coronary occlusion. Am. J. Cardiol. 11:205-217, 1963. Mason D.T., Amsterdam E.A., Miller R.R., et al.: Pathophysiology of myocardial infarction shock, in Eliot R.S. (ed.): Cardiac Emergencies. New York, Futura Publishing Co., 1977. Cohn J.N., Franciosa J.A : Pathophysiology of shock 111 acute ntyocardiai infarction Progr Cardiol. 2:207-234, 1973

46. Loeb H.S., Pietas R.J., Tobin J.R., et al.: Hypovolemia in shock due to acute myocardial infarction. Circulation 40:653, 1969.

47. Cohn J.N., Laria M.H.: Studies in clinical shock and hypotension: V. Hemo- dynamic effects of dextran. Circulation 34~823, 1966.

48. Cohn J.N.: Relationship of plasma volume changes to resistance and capacitance vessel effects of vasopressor drugs and dextran. Clin. Sci. 30:267, 1966.

49. Nickerson M.: Vascular adjustments during the development of shock. Can. Med. Assoc. J. 103:853, 1971.

50. Miller D.E., Gleason W.L., Whalen R.E., et al.: Effect of ventricular rate on cardiac output in the dog with heart block. Circ. Res. 10:558, 1962.

51. Braunwald E.. Frahm C.J.: Studies on Starlie’s law of the heart: IV. Obser- vations on the hemodynamic functions of the left atrium in man. Circula- tion 241633, 1961.

52. Weissler A.M., Kruger F.A., Baba N., et al.: Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium. J. Clin. Invest. 47~403, 1968.

53. Kezdi P., Misra S.N., Kordenat R.K., et al.: The role of vagal afferents m acute myocardial infarction. Am. J. Cardiol. 26:642, 1970.

54. Toubes D.D., Brady M.J.: Inhibition of reflex vasoconstriction after experimental coronary embolization in the dog. Circ. Res. 26:211, 1970.

55. Pantridge J.F.: Autonomic disturbance at the onset of acute myocardial in. farction, in Schwartz P.J., Brown A.M., Malliani A., et al. (eds.): Neural Mechanisms in Cardiac Arrhythmias. New York, Raven Press, 1978.

56. Mark A.L.: The Bezold-Jarisch reflex revisited: Clinical implications of in- hibitory reflexes originating in the heart. J. Am. Coil. Cardiol. 1:90, 1983.

57. Dole W.P., O’Rourke R.A.: Hypotension and cardiogenic shock, in Stein J.H. (ed.): Internal Medicine. Boston, Little, Brown & Co, 1983.

58. Abboud F.M., Heistad D.D., Mark A.L., et al.: Reflex control of the peripheral circulation. Progr. Cardiovasc. Dis. 18:371, 1976.

59. Errington M.L., Rocha e Silva M. Jr.: On the role of vasopressin and angiotensin in the development of irreversible shock. J. Physiol. 242:119, 1974.

60. Belloni F.L.: The local control of coronary blood flow. Cardiovusc. Res. 13:63, 1979.

61. Braunwald E., Ross J. Jr., Sonnenblick E.H.: Mechanisms of Contractions in the Normal and Failing Heart, ed. 2. Boston, Little, Brown & Co., 1976.

62. Guyton A.C.: Cardiovascular Physiology. Baltimore, University Park Press, 1976.

63. Ayres S.M., Mueller H.,, Giannelli S. Jr., et al.: The lung in shock. Am. J. Cardiol. 26:588, 1970.

64. Tristani F.E., Cohn J.N.: Studies in clinical shock and hypotension: VII. Renal hemodynamics before and during treatment. Circulation 42:839, 1970.

65. Lasch H.G.: Coagulation disturbances in shock. Postgrad. Med. J. 45:539, 1969.

66. Cohn J.N., Luria M.: Studies in clinical shock and hypotension: IV. Varia- tions in reflex vasoconstriction and cardiac stimulation. Circulation 34:823, 1966.

67. Cohn J.N., Luria M.: Studies in clinical shock and hypotension: The value of bedside hemodynamic observations. JAMA 190:891, 1964.

68. Cohn J.N.: Blood pressure measurement in shock: Mechanisms of inaccu- racy in auscultatory and palpatory methods. JAMA 199:972, 1967.

69. tJoly H.R., Weil M.H.: Temperature of the great toe as an indication of the severity of shock. Circulation 39:131, 1969.

70. Garfinkel H.J., Sziden J.P., Hirsch L.J., et al.: Renal performance in experimental cardiogenic shock. Am. J. Physiol. 222:1260, 1972.

7i. Stein J.H., Lifschitz M.D., Barnes L.D.: Current concepts in the pathophys. iology of acute renal failure. Am. J. Physiol. 334:F171, 1978.

T’.! Reubi F.C., Vorburger C.: Renal hemodynamics and pathophysiology of :tcute renal failure and shock in man, in Giovannetti S Ronomini 1’. D‘A-

63

mica G. (eds.): Advances in Nephrology: Physiology, Hypertension, Renal Disease, Renal Failure, Dialysis, and Transpkzntation, Sixth Znterna- tional Congress of Nephrology. Basel, S. Karger, 1975.

73. Hull J.C., G’Rourke R.A., Lewis R.P., et al.: The diagnostic value of the

74.

75

76.

77

78

i9.

80

81.

82.

83.

84.

85.

86.

87.

88.

89.

90.

91.

92.

93.

94.

atria1 gallop in acute myocardial infarction. Am. HeaiJ. 78:194, 1969. Swan H.J.C., Ganz W., Forrester J.S., et al.: Catheterization of the heart in man with use of a flow directed balloon-tipped catheter. N. Engl. J. Med. 283~447, 1970. Crexells C., Chattejee K., Forrester J.S., et al.: Optimal level of fill& pressure in the left side of the heart in acute myocardial infarction. N. Engl. J. Med. 289:1263, 1973. Cohn J.N., Luria M.H., Daddario R.C., et al.: Studies in clinical shock and hypotension: V. Hemodynamic effects of dextran. Circulation 35:316, 1967. Ratshin R.A., Rackley C.E., Russell R.O.: Hemodynamic evaluation of left ventricular function in shock complicating myocardial infarction. Circula- tion 45:127, 1972. Scheinman M., Evans T.A., Weiss A., et al.: Relationship between pulmonary artery end-diastolic pressure and left ventricular filling pressure in patients in shock. Circulation 471317, 1973. Bouchard R.J., Gault J.H., Ross J. Jr.: Evaluation of pulmonary arterial end-diastolic pressure as an estimate of left ventricular end-diastolic pressure in patients with normal and abnormal left ventricular performance. Circulation 44:1072, 1971. Braunwald E., Frahm C.J.: Studies on Starling’s law of the heart IV. Ob- servations on the hemodynamic functions of the left atrium in man. Circu- lation 24:633, 1961. Ganz W., Swan H.J.C.: Measurement of blood flow by thermodilution. Am. J. Card&l. 29:241, 1972. Afifi A., Chang P.C., Liu V.Y., et al.: Prognostic indexes in acute myocardial infarction complicated by shock. Am. J. Cardiol. 33:826, 1974. Parmley W.W., Diamond G., Tomoda H., et al.: Clinical evaluation of left ventricular pressures in myocardial infarction. Circulation 45:358, 1972. Scheidt S., Fillmore S., Ascheim R., et al.: Objective assessment of prognosis after acute myocardial infarction. Circulatbn 42(suppl. III): 196,~1970 Meister S.G.. Helfant R.H.: Ranid bedside differentiation of runtured interventricular septum from acute mitral insufficiency. N. Engl. J. Med. 16:1024, 1972. Cohn J.N., Guiha N.H., Broder M.J., et al.: Right ventricular infarction: Clinical and hemodynamic features. Am. J. Cardiol. 33:209, 1974. Matlar J.A., Weil M.H., Shubin H., et al.: Cardiac arrest in the critically ill: II. Hyperosmolar states following cardiac arrest. Am. J. Med. 56:162, 1974. da Luz P.L., Cavanilles J.M., Michaels S., et al.: Oxygen delivery, anoxic metabolism and P50 in patients with acute myocardial infarction and shock. Am. J. Cardiol. 36:148, 1975. Warren J.V., Lewis R.P.: Beneficial effects of atropine in the pre-hospital phase of coronary care. Am. J. Cardiol. 37:68, 1976. Ogawa S., Dreifus L.S., Shenoy P.N., et al.: Hemodynamic consequences of atrioventricular and ventricular pacing. Pace 1:8, 1978. Vismara L.A., Leaman D.M., Zelis R.: The effects of morphine on venous tone in patients with acute pulmonary edema. Circulation 54:335, 1976. da Luz P.L., Shubin H., Weil M.H., et al.: Pulmonary edema related to changes in colloid osmotic pressure and pulmonary artery wedge pressure in patient8 after acute myocardial infarction. Circulation 51:350, 1975. Thompson W.L.: Rational use of albumin and plasma substitutes. Johns Hopkins Med. J. 136:220, 1975. Moore F.D., Daher F.J., Boyden C.M., et al.: Hemorrhage in normal man: Distribution and dispersal of saline infusions following acute blood loss: clinical kinetics of blood volume support. Ann. Surg. 163:485, 1966

64

95. Thompson W.L., Britton J.J., Walton R.P.: Persistence of starch derivatives and dextran when infused after hemorrhage. J. Phnrmncol. Exp. Ther. 136:125, 1962.

96. Solanke T.F., Khwaja J.S., Madejemu E.I.: Plasma volume studies with four different plasma volume expanders. J. Surg. Res. 11:140, 1971.

97. Perloth M.G., Harrison DC.: Medical therapy for shock in acute myocardial infarction. Progr. Cardiol. 2:235, 1973.

98. da Luz P.L., Weil M.H., Shubin H.: Current concepts on mechanisms and treatment of cardiogenic shock. Am. Heart J. 92:103, 1976.

99. Kuhn L.A.: Management of shock following acute myocardial infarction. Am. Heart J. 95529, 1978.

100. Geddes J.S., Adgey A.A.J., Pantridge J.F.: Prevention of cardiogenic shock. Am. Heart J. 99:243, 1980.

101. Gunnar R.M., Loeb H.S.: Use of drugs in cardiogenic shock due to acute myocardial infarction. Circulation 45:211, 1972.

102. Mason D.T., Amsterdam E.A., Low R.I., et al.: Diagnosis and management of myocardial infarction shock, in Eliot R.S. (ed.): Cardiac Emergencies. New York, Futura Publishing Co., 1982.

103. Weiner N.: Norepinephrine, epinephrine, and the sympathomimetic amines, in Gilman A.G., Goodman L.S., Gilman A. (eds.): The Phurmuco- logic Basis of Therapeutics. New York, Macmillan Publishing Co., 1980.

104. Moran N.C.: Evaluation of the pharmacologic basis for the therapy of circulatory shock. Am. J. Cardiol. 26:570, 1970.

105. Goldberg L.I., Hsieh Y., Resnekov L.: Newer catecholamines for treatment of heart failure and shock: An update on dopamine and a first look at dobutamine. Progr. Cardiovasc. Dis. 191327, 1977.

106. Udjojii V.N., Weil M.H.: Circulatory effects of angiotensin, levarterenol and metaraminol in the treatment of shock. N. Engl. J. Med. 270:501, 1964.

107. Goldberg L.I.: Cardiovascular and renal actions of dopamine: Potential clinical applications. Pharmucol. Rev. 24:1, 1972.

108. Hollenberg N.K., Adams D.F., Mendell P., et al.: Renal vascular responses to dopamine: Hemodynamics and angiographic observations in normal man. Clin. Sci. Molec. Med. 451733, 1973.

109. Velasco M., Tjandramaga’ T.B., McNay J.L.: Differential dose related effects of dopamine on systemic and renal hemodynamics in hypertensive patients. Clin. Res. 22~308, 1974.

110. Rosenblum R., Tai A.R., Lawson D.: Dopamine in man: Cardiorenal hemodynamics in patients with heart disease. J. Phurmacol. Exp. Ther. 183:256, 1972.

111. Allwood M.J., Ginsburg J.: Peripheral vascular and other effects of dopamine in man. Clin. Sci. 271271, 1964.

112. McDonald R.H. Jr., Goldberg L.I., McNay J.L., et al.: Effect of dopamine in man: Augmentation of sodium excretion, glomerular filtration rate and renal plasma flow. J. Clin. Invest. 43:1116, 1964.

113. Mueller H.S., Evans R., Ayres SM.: Effect of dopamine on hemodynamics and myocardial metabolism in shock following acute myocardial infarction in man. Circulation 57:361, 1978.

1 14. Tuttle R.R., Mills J.: Development of a new catecholamine to selectively increase cardiac contractility. Circ. Res. 36~185, 1975.

115. Sonnenblick E.H., Frishman W.H., LeJemtel T.H.: Dobutamine: A new synthetic cardioactive sympathetic amine. N. Engl. J. Med. 300:17, 1979.

116. Leier C.V., Heban P.T., Huss P., et al.: Comparative systemic and regional hemodynamic effects of dopamine and dobutamine in patients with car- diomyopathic heart failure. Circulation 58:466, 1978.

117. Gillespie T.A., Ambos H.D., Sobel B.E., et al.: Effects of dobutamine in patients with acute myocardial infarction. Am. J. Cardiol. 39:588, 1977.

118. Goldberg L.I.: Dopamine-clinical uses of an endogenous catecholamine. N Engl. J. Med. 291:707, 1974.

119. Kuhn L.A., Kline H.J., Goodman P., et al.: Effects of isoproterenol on 65

hemodynamic alterations, myocardial metabolism and coronary flow in acute myocardial infarction with shock. Am. Heart J. 771772, 1969. Mason D.T., DeMaria A.N., Lee G., et al.: Congestive heart failure and cardiogenic shock due to acute myocardial infarction, in Mason D.T. (ed.): Cardiac Emergencies. Baltimore, Will iams 8z Wilkins Co., 1978. Dikshit K.. Vvden J.K.. Forrester J.S.. et al.: renal and extrarenal hemodynamic eke& of furosemide in congestive heart failure after acute myocardial infarction. N. Engl. J. Med. 288:1087, 1973. Cohn J.N., Tristani F.E., Khatri 1-M.: Cardiac and peripheral vascular ef:, fects of digitalis in clinical cardiogenic shock. Am. Heart J. 178:318, 1969. Gunner R.M., Loeb H.S., Pietras R.J., et al.: The hemodynamic effects of myocardial infarction and results of therapy. Med. Clin. North Am. 54:235, 1970.

120.

121.

122.

123.

124.

125.

126.

127.

128.

129.

130.

131.

132.

133.

134.

135.

136.

137.

138.

139.

140.

i&i

Cohn J.N., Franciosa J.A.: Vasodilator therapy of cardiac failure. N. Engl. J. Med. 297127, 254, 1977. Parmley W.W., Chattejee K.: Vasodilator therapy. Curr. Probl. C’ardiol. 2:1, 1978. Chatterjee K., Parmley W.W., Ganz W., et al.: Hemodynamic and metabolic responses to vasodilator therapy in acute myocardial infarction. Circulation 48:1183, 1973. Luz P.L., Forrester J.S., Wyatt H.L., et al.: Hemodynamic and metabolic effects of sodium nitroprusside on the performance and metabolism of regional ischemic myocardium. Circulation 52:400, 1975. Maroko P.R., Braunwald E.: Assessment of interventions designed to reduce myocardial ischemic damage: Effects of metabolic and pharmacologic interventions on myocardial infarct size following coronary occlusion. Cir- culation 53csuppl. I): 162-168, 1973. Becker L.C.: Conditions for vasodilatory-induced coronary steal in experimental myocardial ischemia. Circulation 57:1103, 1978. Warltier DC., Gross G.J., Brooks H.L.: Coronary steal-induced increase in myocardial infarct size after pharmacologic coronary vasodilation. Am. J. Cardiol. 46~83, 1980. Cohn J.N., Mathew J.K., Franciosa J.A., et al.: Chronic vasodilator therapy in the management of cardiogenic shock and intractable left ventricular failure. Ann. Intern. Med. 81~777, 1974. Yoran C., Yellin E.L., Becker R.M., et al.: Mechanism of reduction of mitral regurgitation with vasodilator therapy. Am. J. Cardiol. 43~773, 1979. Chatterjee K., Parmley W.W., Swan H.J.C., et al.: Beneficial effects of vasodilator agents in severe mitral regurgitation due to dysfunction of sub- valvular apparatus. Circulation 48~684, 1973. Chattejee K., Parmley W.W.: Role of vasodilator therapy in heart failure. Progr. Cardiovasc. Dis. 19:301, 1977. Mason D.T.: Symposium on vasodilator and inotropic therapy of heart failure. Am. J. Mkd.65:101, 1978.

__

Palmer R.F., Lasseter K.C.: Drug therapy: Sodium nitroprusside. N. Engl J. Med. 292:294, 1975. Guiha N.H., Cohn J.N.,, Mikulic E., et al.: Treatment of refractory heart failure with infusion of nitrourusside. N. Encl. J. Med. 291:587. 1974. Stern M.A., Gohlke H.K., Ldeb H.S., et al.: hemodynamic effedts of intravenous phentolamine in low output cardiac failure: Dose response relation- ships. Circulation 58:157, 1978. Parmley W.W., Chatterjee K., Charuzi Y., et al.: Hemodynamic effects of noninvasive systolic unloading (nitroprusside) and diastolic augmentation (external counterpulsation) in patients with acute myocardial infarction. Am. J. Cardiol. 33:819, 1974. Corday E., Swan H.J.C., Lang T.L., et al.: Physiologic principles in the application of circulatory assist for the failing heart. Am. J. Cardiol, 26:595, 1970. Amsterdam E.A.. DeMaria A.N,, Granett L., et al,: Mechanical circulatory assist in acute ischemic heart disease. Adt’. Cnrdiol. 23: 142, 1978.

142. Bolooki H.: Clinical Applications of Intra-aortic Balloon Pump. New York, Futura Publishing Co., 1977.

143. Weber R.T., Janicki J.S.: Intra-aortic balloon counterpulsation: A review of physiological principles, clinical results, and device safety. Ann. Thorac. Surg. 17:602, 1974.

144. Breaman D.: Assessment of intra-aortic balloon counteroulsation in cardi-

145

146.

147

148.

149

150.

151.

152.

153.

154.

155.

156.

157.

158.

159.

160.

161.

162.

ogeiic shock. Crit. Care Med. 3:90, 1975. I

Mundth E.D., Buckley M.J., Daggett W.M., et al.: Intra-aortic balloon pump assistance and early surgery in cardiogenic shock. Ado, Cardiol 15:159, 1975. Bregman D., Weiss M.B., Casarella W.J.: Percutaneous intra-aortic balloon pumping. Am. J. Cardiol. 45:395, 1980. Grayzel J.: Clinical evaluation of the Percor percutaneous intra-aortic balloon: Cooperative study of 711 cases. Circulation 66(suppl. 11):223, 1981. Ismer J.M., Cohen S.R., Virmani R., et al.: Complications of the intra-aortic balloon counterpulsation device: Clinical and morphologic observations in 45 necropsy patients. Am. J. Cardiol. 45:260, 1980. Kantrowitx A., Tjnnelard S., Freed P.S., et al.: Initial clinical experience with intra-aortic balloon pumping in cardiogenic shock. JAMA 203:135, 1968. Scheidt S., Wilner G., Mueller H., et al.: Intra-aortic balloon counterpulsation in cardiogenic shock. N. Enpl. J. Med. 288:979. 1973. Bardet J., M&uet C., Kahn C.: et al.: Clinical and hemodynamic results of intra-aortic balloon counterpulsation and surgery for cardiogenic shock. Am. Heart J. 93:280, 1977. Leinbach R.C., Dinsmore R.E., Mundth E.D., et al.: Selective coronary and left ventricular cineangiography during intra-aortic balloon pumping for cardiogenic shock. Circulation 45:845, 1972. Scheidt S., Wilner G., Mueller H., et al.: Intra-aortic balloon counterpulsation in cardiogenic shock: Report of a cooperative clinical trial. N. Engl. J. Med. 288,979,1973. Willerson J.T., Curry G.C., Watson J.T., et al.: Intra-aortic balloon counterpulsation in patients in cardiogenic shock, medically refractory left ventricular failure and/or recurrent ventricular tachycardia. Am. J. Med. 58183, 1975. Dilley R.B., Ross J. Jr., Bernstein E.F.: Serial hemodynamics during intra- aortic balloon counterpulsation for cardiogenic shock. Circulation 47, 48fsuppl. III):99, 1973. DeWood M.A., Notske R.N., Hensley G.R., et al.: Intra-aortic balloon counterpulsation with and without reperfusion for myocardial infarction shock. Circulation 61:1105, 1980. Mueller H., Ayres SM., Giannelli S. Jr., et al.: Effects of isoproterenol, L- norepinephrine and intra-aortic counterpulsation on hemodynamics and myocardial metabolism in shock following acute myocardial infarction. Cir- culation 45:335, 1972. Leinbach RX., Buckley M.J., Austen W.G., et al.: Effects of intra-aortic balloon pumping on coronary flow and metabolism in man. Circulation 43csuppl. 1):77, 1971. Sugy W.L., Webb W.R., Ecker R.R.: Reduction of extent of myocardial in- far&on by counterpulsation. Ann. Thorac. Surg. ‘7:310, 1969. Maroka P.R.. Bernstein E.F.. Libbv P.. et al.: Effects of intra-aortic balloon counterpulsation on the severity bf myocardial ischemic injury following acute coronary occlusion. Circulation 4%1150, 1972. - Soroff H.S.. Ruiz U.. Birtwell W.C.: Assisted circulation bv external nres- sure variation. Zsr. J. Med. Sci. 5506, 1969. Sanders CA., Buckley M.J., Leinbach RX., et al.: Mechanical circulatory assistance: Current status and experience with combining circulatory assistance, emergency coronary angiography, and acute myocardial revascularization. Circulation 45:129, 1972. Ruiz U., Soroff H.S., Birtwell W.C.. et al.: External synchronous assisted

67

circulation: Experimental and clinical evaluation. Surg. Forum 19:127, 1968.

164. Amsterdam E.A., DeMaria A.N., Garrett L., et al.: Mechanical circulatory assist in acute ischemic heart disease. Adu. Cardiol. 23:142, 1978.

165. Cohen L.S., Mullins C.B., Mitchell J.H.: Sequenced external counterpulsation and intra-aortic balloon numning in cardioeenic shock. Circulation

166.

167

168

169

170.

171

172.

173.

174.

175.

176.

177.

178.

179.

180.

181.

182.

183.

- - - 42(suppl. 111):81, 1970. Soroff H.G., Giron F., Ruiz V., et al.: Physiologic support of heart action. N. Engl. J. Med. 280:693, 1964. Messer J.V., McDowell J.W., Bing O.H.L., et al.: Hemodynamic evaluation of external counterpulsation in human cardiogenic shock. Clin. Res. 21:439, 1973. Soroff H.S., Cloutier C.T., Birtwell W.C., et al.: Clinical evaluation of external counterpulsation in cardiogenic shock. Circulation 4Xsuppl. 111):297, 1972. Beckman C.B., Romero L.H., Shatney C.H., et al.: Clinical comparison of the intra-aortic balloon pump and external counterpulsation for cardiogenic shock. Trans. Am. Sot. Artif Internal Organs 29:414, 1973. Michael T.D., Bassan M., Chattejee K., et al.: Hemodynamic and metabolic effects of noninvasive circulatory assist (Cardiassist). Circulation 45(suppl. 11):761, 1972. Mueller H., Ayres S., Grace W., et al.: External counterpulsations: A noninvasive method to protect ischemic myocardium in man. Circulation (suppl. 11):195, 1972. Amsterdam E.A., Banas J., Criley J.M., et al.: Clinical assessment of external pressure circulatory assist in acute myocardial infarction: Report of a cooperative clinical trial. Am. J. Cardiol. 45:349, 1980. Amsterdam E.A., Miller R.R., Hughes J.L., et al.: Emergency surgical therapy of complicated acute myocardial infarction: Indications and results in cardiogenic shock, intractable ventricular tachycardia, and extending infarction, in Russek H.I. (ed.): Cardiovascular Problems. Baltimore. Univer- sity Park Press, 1976. Buckley M.J., Mundth E.D., Daggett W.M., et al.: Surgical therapy for early complications of myocardial infarction. Surgery 70:814-820, 1971. Miller R.R., Amsterdam E.A., Lurie A.J., et al.: Surgical treatment of myocardial infarction shock. Arch. Cardiol. 23:163-172, 1978. Bunkman W.B., Leinbach R.C., Buckley M.J., et al.: Clinical and hemodynamic results of intra-aortic balloon pumping and surgery for cardiogenic shock. Circulation 46:465, 1972. Amsterdam E.A., Hughes J.L., Iben A., et al.: Surgery for acute myocardial infarction, in Gunnar R.M., Loeb H.S., Rahimtoola S.H. (eds.): Shock in Myocardial Infarction. New York, Grune & Stratton, 1974. Cohn L.H.: Surgical management of acute and chronic cardiac mechanical complications due to myocardial infarction. Am. Heart J. 102:1049-1060, 1981. Johnson S.A., Scanlon P.J., Loeb H.S., et al.: Treatment of cardiogenic shock in myocardial infarction by intra-aortic balloon counterpulsation and surgery. Am. J. Med. 62:687, 1977. Leinbach R.C., Mundth E.D., Dinsmore R.E., et al.: Selective coronary and left ventricular cineangiography during intra-aortic balloon assist for cardiogenic shock. Am. J. Cardiol. 261644, 1970. Mundth E.D., Buckley M.J., Daggett W.M., et al.: Surgery for complications of acute myocardial infarction. Circulation 45:1279, 1972. Chattejee K., Swan H.J.C., Parmley W.W., et al.: Depression of left ventricular function due to acute myocardial &hernia and its reversal after aorto-coronary saphenous-vein bypass. N. Engl. J. Med. 286:1117, 1972. Abbas S.Z., Shankar K.R.. Cohen G., et al.: Medical versus sureical management of cardiogenic shbck. Am. J. Cardiol. 29:250. 1972. -

184. Dawson F.T., Hall., R.J., Hallman G.L.: Mortality in patients undergoing coronary artery bypass surgery after myocardial infarction. Am. J. Cardiol. 33:483, 1974.

185. Lang T., Corday E., Meerbaum S.: Is early revascularization following acute coronary occulsion a safe and effective surgical procedure? Cardio- uasc. Clin. 8:65, 1977.

186. Mathur VS., Guinn G.A.: Early revascularization in acute infarction, help or hazard: A randomized study: Am. J. Cardiol. 33:156, 1974.

la7. Mundth E.D.. Bucklev M.J.. Daeeett W.M.. et al.: Intra-aortic balloon pump assistance and surgical inn&ention in’the management of ischemic pump failure, in 2nd Henry Ford Hospital International Symposium on Cardiac Surgery. New York, Appleton-Century-Crofts, 1976.

188. Spencer F.C., Green G.E., Tice D.A., et al.: Coronary artery bypass grafts for congestive heart failure: A report of experiences with 40 patients. J. Thorac. Cardiovasc. Surg. 62529, 1971.

189. Kouchoukas N.T., Doty D.B., Buettner L.E., et al.: Treatment of postinfarction cardiac failure by myocardial excision and revascularization. Circula- tion 45(suppl. 1):72, 1972.

190. Klein M.D., Herman M.V., Gorlin R.: A hemodynamic study of left ventricular aneurysm. Circulation 35614, 1967.

191. Janz R.F., Waldron R.V.: Predicted effect of chronic apical aneurysms on the passive stiffness of the human left ventricle. Circ. Res. 42:255, 1978.

192. Herman M.V., Heinle R.A., Klein M.D., et al.: Localized disorders in myocardial contraction: Asynergy and its role in congestive heart failure. N. Engl. J. Med. 277~222, 1967.

193. Miller R.R., Olson H.G., Vismara L.A., et al.: Pump dysfunction after myocardial infarction: Importance of location, extent and pattern of abnormal left ventricular segmental contraction. Am. J. Cardiol. 37:340, 1976.

194. Glass B.A., Carter R.L., Albert H.M., et al.: Excision of myocardial infarcts, Arch. Surg. 97:940, 1968.

195. Heimbecker R.O.: Surgery for massive myocardial infarction. Progr. Car- diouasc. Dis. 11:338, 1969.

196. Stein M.D., Cordell A.R.: Arrhythmias and left ventricular efficiency following infarction and infarctectomy. Arch. Surg. 99:802, 1969. -

197. Liedtke A.J.. Hughes H.C.. Zelis R.: Functional reductions in left ventricular volume; Minimum chamber size consonant with effective hemodvnamic performance. J. Thorac. Cardiouasc. Surg. 71:195, 1976.

198. Watson L.E.. Dickhaus D.W.. Martin R.H.: Left ventricular aneurvsm: Pre- operative hemodynamics, chamber volume, and results of aneurysmectomy. Circulation 52:868, 1976.

199. Lee D.C., Johnson R.A., Boucher C.A., et al.: Angiographic predictors of survival following left ventricular aneurvsmectomv. Circulation 56(sunnl. 11):12, 1977. -

_.

200. Loop F.D., Effler D.B., Navia J.A., et al.: Aneurysms of the left ventricle: Survival and results of a a 10 year surgical experience. Ann. Surg. 178:399. 1973.

201. Vlodaver Z., Edwards J.E.: Rupture of ventricular septum or papillary muscle complicating myocardial infarction. Circulation 55:815, 1977.

202. Austen W.G., Sanders C.A., Averill J.H., et al.: Ruptured papillary muscle: Report of a case with successful mitral valve replacement. Circulation 32597, 1965.

203. Cohen L.S., Morrow A.G., Braunwald N.S., et al.: Severe mitral regurgitation following acute myocardial infarction and ruptured papillary muscle: Hemodynamic findings and results of mitral valve replacement in four patients. Circulation 36(suppl. 11):87, 1967.

204. Austen W.G., Sokol D.M., DeSanctis R.W., et al.: Surgical treatment of papillary muscle rupture complicating myocardial infarction. N. Engl. J. Med. 2731137, 1968.

69

205.

206.

207.

m3.

209.

210.

211.

212.

213.

214.

215.

Buckley M.J., Mundth E.D., Daggett W.M., et al.: Surgical management of ventricular septal defects and mitral regurgitation complicating acute myocardial infarction. Ann. Thorac. Surg. 16:598, 1973. Seizer A., Gerbode F., Kerth W.J.: Clinical, hemodynamic and surgical consideration of rupture of the ventricular septum after myocardial infarction. Am. Heart J. 78:598, 1969. Brendt B.B., Gerbode F., Kerth W.J.: Ventricular septal defect following myocardial infarction. Ann. Thoruc. Surg. 27:580, 1978. Kitamura S.. Mendez A.. Kav J.H.: Ventricular seotal defect followind myocardial infarction: Experience with surgical repair through a left ven-’ triculotomy and review of literature. J. Thoruc. Cardiouasc. Surg. 61:186, 1971. Javid H., Hunter J.A., Najafi H., et al.: Left ventricular approach for the repair of ventricular septal perforation and infarctectomy. J. Thoruc. Cur- diouasc. Surg. 63:14, 1972. Kouchoubos W.T.: Infarction ventricular septal defect, in Cohn L.H. ted.): Modern Techniques in Surgery-Cardiothoracic Surgery, Mt. Kisco, N.Y , Futura Publishing Co., 1979. Daggett W.M., Buckley M.G.: The surgical treatment of post-infarction ventricular septal defect: Indications, techniques and results, in Moran J.M., Michaels L.L. (eds.1: Surgery for the Complications of Myocardial Zn- farction. New York, Grune & Stratton, 1980. Montoya A., McKeever L., Scanlon P., et al.: Early repair of ventricular septal rupture after infarction. Am. J. Cardiol. 45:345, 1980. Iben A.B., Muller R.R., Amsterdam E.A., et al.: Successful immediate repair of acquired ventricular septal defect and survival in patients with acute myocardial infarction shock using a new double patch technique. Chest 66:665, 1974. Naeim F., De La Maza L.M., Robbins S.L.: Cardiac rupture during myocardial infarction: A review of 44 cases. Circulation 45:1231, 1972. Friedman H.S.: Cardiac rupture following myocardial infarction: A review. Cardiol. Dig. 8:10, 1973.

216. Rasmussen S., Leth A., Kjoller E., et al.: Cardiac rupture in acute myocardial infarction: A review of 72 consecutive cases. Actu Med. Stand. 205:11, 1979.

217. Roberts W.C., Ronan J.A. Jr., Harvey W.P.: Rupture of the left ventricular free wall or ventricular septum secondary to acute myocardial infarction (AMI): An occurrence virtually limited to the first transmural AM1 in a hypertensive individual. Am. J. Cardiol. 35:166, 1975.

218. Fitzgibbon G.M., Hooper G.D., Heggtveit H.A.: Successful surgical treatment of postinfarction external cardiac rupture. J. Thorac. Cardiouusc. Surg. 63:622, 1972.

219. Montegut F.J. Jr.: Left ventricular rupture secondary to myocardial infarction: Report of survival wth surgical repair. Ann. Thoruc. Surg. 14:75, 1972.

220. Cobbs B.W., Hatcher C.R. Jr., Robinson P.H.: Cardiac rupture: Three op- erations with two long-term survivals. JAMA 223:532, 1973.

221. Calick A., Kerth W., Barbour D., et al.: Successful surgical therapy of ruptured myocardium. Chest 66:188, 1974.

222. Braunwald E., Maroko P.: The reduction of infarct size: An idea whose time (for testing) has come. Circulation 50:206, 1974.

‘223. Meerbaum S., Corday E.: Is it possible to salvage acutely ischemic myocardium, in Brest A.N.ced.1: Controversies in Cardiology. Cardiovasc. Clin. Philadelphia, F.A. Davis Co., 1977.

224, Norris R.M.: Beta adrenoreceptor blockade in acute myocardial infarction. Am. Heart J. 99:683, 1980.

325. Mueller H.: Propranolol in acute myocardial infarction in man: Effects of hemodynamics and myocardial oxygenation. Acfa Med, Stand. Suppl =i87-177. 1976

226. Peter T., Norris R.M., Clarke E.D., et al.: Reduction of enzyme levels by propranolol after acute myocardial infarction. Circulation 57:1091, 1978.

227. Maroko P.R., Kloner R.A., Gold H.K., et al.: Propranolol in acute myocardial infarction: Experimental and clinical considerations, in Braunwald E. (ed.): Beta-Adrenergic Blockade: A New Era in Cardiovascular Medicine. New York, Excerpta Medica, 1978.

228. Mueller H.S., Ayres, SM.: The role of propranolol in the treatment of acute myocardial infarction. Progr. Cardiovasc. Dis. 19:405, 1977.

229. Derrida J.P., Sal R., Chiche P.: Nitroglycerin infusion in acute myocardia! infarction. N. Engl. J. Med. 297:36, 1977.

230. Awan N.A., Amsterdam E.A., Zakuddin V., et al.: Reduction of ischemic injury by sublingual nitroglycerin in patients with acute myocardial infarction. Circulation 54:761, 1976.

231. Borer J.S., Redwood D.R., Levi H.B., et al.: Reduction in myocardial ischemia with nitroglycerin or nitroglycerin plus phenylephrine administered during acute myocardial infarction. N. Engl. J. Med. 293:1008, 1975.

232. Maroko P.R., Hillis L.D., Muller J.E., et al.: Favorable effects of hyaluronidase on electrocardiographic evidence of necrosis in patients with acute mvocardial infarction. N. Engl. J. Med. 296. 898. 1977.

243 R&sell R.O. Jr., Rogers W.j., Mantle J.A:. et gl,: Glucose-insulin-potassium, free fatty acids and acute myocardial infarction in man. Circulation 53fsuppl. U-107, 1975.

234. Heng M.K., Norris R.M., Singh B.N., et al.: Effects of glucose and glucose- insulin-potassium on hemodynamics and enzyme release after acute myocardial infarction. Br. Heart J. 39:748, 1977.

235. Rogers W.J., Segall P.H., McDaniel H.G., et al.: Prospective randomized trial of glucose-insulin-potassium in acute myocardial infarction. Am. J. Cardiol. 43:801, 1979.

236. Rentrop P., Blank H., Kostering H., et al.: Acute myocardial infarction: Intracoronary application of nitroglycerin and streptokinase in combination with transluminal recanalization. Clin. Cardiol. 2:354, 1979.

237. Rentrop P., Blank H., Karsch H., et al.: Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circula- tion 63:307, 1981.

238. Ganz W., Buchbinder N., Marcus H., et al.: Intracoronary thrombolysis in evolving myocardial infarction. Am. Heart J. 101:4, 1981.

239.

240.

241.

242.

243.

844.

245.

246

Mathey-D.G., Kuck K.H., Tilsner V., et al.: Nonsurgical coronary artery recanalization in acute transmural mvocardial infarction. Circulation 63:489, 1981. Schwarz F.. Schuler G., Katus H., et al.: Intracoronarv thrombolvsis in acute myocardial infarction: Correlations among serum enzyme scinti- graphic and hemodynamic findings. Am. J. Cardiol. 50:32, 1982. Schuler G., Schwartz F., Hofmann M., et al.: Thrombolysis in acute myocardial infarction using intracoronary thallium-201 scintigraphy. Circula- tion 66:658, 1982. Rentrop P., Blank H., Karsch R.K., et al.: Changes in left ventricular function after intracoronary streptokinase infusion in clinically evolving myocardial infarction. Am. Heart J. 102:1188, 1981. Reduto L.A., Freund G.C., Gaeta J.M., et al.: Coronary artery reperfusion in acute myocardial infarction: Beneficial effects of intracoronary streptokinase of left ventricular salvage and performance. Am. Heart J. 102:1168. 1981. Gruntzig A.R., Senning A., Sieyenthaler W.E.: Nonoperative dilation of coronary artery stenosis. N. Engj. J. Med. 302:61, 1965. 49:2011, 1982. Kent K.. Bentivoelio L.. Block P.. et al.: Percutaneous transluminal coronary an&oplasty:kepoA from the’ NHLBI Registry. Am. J. Cardiol. Cowley M.J., Vetrove G., Wolfgang F.C.: Efficacy of percutaneous translu minal angioplasty: Technique, patient selection, salutory results. limita- !)ons and complications. Am Henrt J 101:272. 1981

247. Williams D.O., Riley R.S., Singh A.K., et al.: Restoration of normal coronary hemodynamics and myocardial metabolism after percutaneous transluminal coronary angioplasty. Circulation 62:653, 1980.

248. Meyer J.M., Merx W., Schmitz H., et al.: Percutaneous transluminal coronary angioplasty immediately after intracoronary streptolysis of transmural myocardial infarction. Circulation 66:905, 1981.

249. Meyer J., Merx W., Dorr R., et al.: Successful treatment of acute myocardial infarction shock by combined percutaneous transluminal coronary recanalization and percutaneous tr anslumina! coronary angioplasty -4~ Heart J. 103:132, 1982.

pathophysiology and management of cardiogenic shock

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