intracoronary thrombolysis in acute myocardial infarction: correlations among serum enzyme,...

Intracoronary Thrombolysis in Acute Myocardial Infarction :Correlations Among Serum Enzyme, Scintigraphic andHemodynamic Findings

FRANZ SCHWARZ, MDGERHARD SCHULER, MDHUGO KATUS, MDHELMUTH C. MEHMEL, MDKLAUS von OLSHAUSEN, MDMANFRED HOFMANN, MDHANS-JOACHIM HERRMANN, MDWOLFGANG KUBLER, MD, FACC

Heidelberg, West Germany

From the Abteilung Innere Medizin III(Kardiolo-gie)und Strahlenklinik der Universitat Heidelberg,West Germany. This study was supported by agrant from the Deutsche Forschungsgemein-schaft, Bonn-Bad Godesberg . within the SFB 90Kardiovaskulares System der Universitat Heidel-berg, Heidelberg, West Germany . Manuscript re-ceived September 14, 1981 ; revised manuscriptreceived January 12, 1982, accepted January 22,1982 .

Address for reprints : Franz Schwarz, MD, Ab-teilung Innere Medizin lll(Kardiologie)der Mediz-inischen Universitatsklinik, Bergheimer Strasse58, 6900 Heidelberg, West Germany .

32 July 1982 The American Journal of CARDIOLOGY Volume 50

The effect of early reperfusion after intracoronary infusion of streptokinasein patients with acute myocardial infarction was assessed in 27 patientsby serial analysis of serum creatine kinase (CK) activity, thallium-201scintigraphy (seven pinhole technique) and left ventricular and coronaryangiography. Serial serum CK activity determinations were carried outat hourly intervals. Thallium-201 tomographlc scintigrams were obtainedbefore and 24 hours after recanalization . The size of the perfusion defectwas measured from eight scintigraphic cross sections of the left ventricle .Regional ejection fraction was determined from the left ventricular an-glogram before and 4 weeks after recanalization . The results in threegroups of patients are presented : group A, 10 patients with successfulrecanalizatlon and a peak serum CK activity of less than 1,000 U/liter ;group B, 9 patients with successful recanalization and a peak serumCK activity of more than 1,000 U/liter and group C, 8 patients with un-successful recanalization . Patients in group A showed an increase in CKactivity (from 46 to 603 U/liter p <0 .001), a reduction in the thalliumperfusion defect (from 115 to 49 ° , p <0.01) and an augmentation of re-gional ejection fraction (from 24 to 38 percent, p <0 .05). Patients in groupB had an increase in serum CK activity (from 46 to 1,562 U/liter, p<0.001), only a moderate reduction in the thallium perfusion defect (from141 to 87 ° , p <0.01) and no change In regional ejection fraction (from25 to 27 percent, p >0 .05) . Patients in group C had an increase in serumCK activity (from 43 to 1,756 U/liter, p <0 .001), no change in the thalliumperfusion defect (from 145 to 147 ° , p >0.05) and no change in regionalejection fraction (from 32 to 26 percent, p >0 .05). Compared with patientsin group B, those in group A had a shorter duration of ischemia (3 .9 versus4.8 hours), more frequently adequate collateral supply to the infarctingarea before recanalizatlon (40 versus 0 percent of patients) and a smallerarea supplied by the occluded vessel (115 versus 141 ° ) . Although alldifferences were not at the level of significance (p >0 .05), conditions fortolerating ischemia were better in group A than in group B .

The study shows that early reperfuslon has a beneficial effect on theextent of myocardial necrosis as estimated from serum enzyme deter-minations, thallium-201 scintigraphy and contrast ventriculography . Thebeneficial effect depends on the duration of myocardial ischemia and onthe blood supply to the ischemlc area by collateral vessels .

Coronary reperfusion after acute myocardial infarction may limit theextent of myocardial necrosis.' --5 Recently, early reperfusion was es-tablished with use of intracoronary infusion of streptokinase in patientswith acute myocardial infarctions-9 The success of early recanalizationof an obstructed coronary artery in acute myocardial infarction is notyet established, because evaluation of the ischemic left ventricularsegment has yielded inconsistent results .--9 In this study, we report theresults of intracoronary thrombolysis in 27 patients with acute

transmural myocardial infarction. Our aim was to cor-relate data on serum enzyme, scintigraphic and hemo-dynamic changes after early reperfusion and thus clarifythe extent to which myocardial damage can be limitedby intracoronary thrombolysis .

Methods

Study patients: In 27 patients with acute transmuralmyocardial infarction, intracoronary infusion of streptokinasewas performed during the acute stage of infarction in orderto recanalize the obstructed coronary artery . Symptoms andsigns of acute myocardial infarction included (1) acute chestpain lasting for more than 30 minutes, and (2) persistent S-Tsegment elevation for more than 30 minutes progressing to Qwaves in the standard 12 lead electrocardiogram. The average(± standard deviation) age of the patients (1 woman and 26

TABLE I

Serum Enzyme, Scintigraphic and Hemodynamic Data Before and After Recanalization

INTRACORONARY THROMBOLYSIS IN INFARCTION-SCHWARZ ET AL,

men) was 55 ± 11 years . Patients 4, 13 and 26 had clinical andelectrocardiographic evidence of a previous myocardial in-farction . Patients with symptoms for more than 8 hours beforeentry into the coronary care unit were not included in thestudy .

At the initial clinical investigation, 18 patients were in Killipfunctional class I, 5 were in class II and 3 were in class III ; 1patient was in class IV ." Anterior, anteroseptal and antero-lateral infarctions, categorized as anterior infarction, werefound in 12 patients; inferior, inferoposterior, posterior andinferolateral infarctions, categorized as inferior infarction,were found in 15 patients (Table 1) . All patients gave writteninformed consent to the study after receiving a detailed ex-planation of the procedure, its possible hazards and possiblebeneficial effects . Successful recanalization of the obstructedvessel was achieved in 19 of the 27 patients ; in 8 patients, thevessel remained occluded .

Percent occlusion of luminal diameter .a = adequate collateral supply to infarct vessel ; CK = serum creatine kinase activity (U/liter) (Post = peak value) ; EF = total left ventricular

ejection fraction (percent) ; i = inadequate collateral supply to infarct vessel ; LAD = anterior descending branch of the left coronary artery ; LCx= circumflex branch of the left coronary artery; n = no collateral supply to infarct vessel ; NS = not significant (p >0 .05): p = probability value ;post = after recanalization ; pre = before recanalizatlon ; REFI = regional ejection fraction of infarct area (percent) ; REFn = regional election fractionof normal area (percent) : RCA = right coronary artery : SD = standard deviation ; time = time between onset of symptoms and repertusion (hours) ;? = contralateral coronary artery not injected before recanalization; TI-201 = thallium-201 scintigram, perfusion defect expressed as degreesof left ventricular circumference ; t-1 = time interval (hours) between the onset of symptoms and the start of cardiac catheterization ; t-2 = timeinterval (hours) between the onset of symptoms and recanalization .

July 1982 The American Journal of CARDIOLOGY Volume 50

33

CaseInfarct Vessel`

Pre

Postt-1

t-2(hours)

CKPre Post

TI-201Pre

PostEF(%) REFi(%) REFn(%)

Pre Post Pre Post Pre Post

Group A (canalization successful, peak CK <1,000 Uliner)

1 LAD 99n 75n 2.0 3 .0 38 256 53 67 28 58 45 272 LAD loon 90n 0.5 1 .5 70 300 184 47 60 71 42 59 42 403 RCA loci 50n 2 .5 3 .5 20 400 58 0 - 64 - 32 - 704 RCA 100a 100a 3.0 4 .0 60 500 144 21 33 39 7 17 41 535 RCA loon 90n 4.0 4 .5 60 500 50 22 54 52 22 30 58 426 RCA 100a - 5.0 5 .5 45 715 47 29 49 - 24 - 58 -7 LAD loon 90n 2 .5 4 .0 29 800 63 53 37 26 49 448 LAD 99a 900 6.5 7 .5 70 830 178 65 37 58 13 44 35 449 RCA tool 50n 4 .0 4 .5 24 850 104 68 46 68 20 38 51 6010 LAD 100a 90n 1 .0 1 .5 40 880 155 137 46 49 23 30 20 27

Mean 81 3 .1 3 .9 46 603 115 49 49.0 57 .1 24.0 37 .8 42 .6 42 .1f SD 18 1 .8 1 .8 19 239 58 43 10 .5 11 .0 11 .6 15 .1 11 .5 11 .4p <0.001 <0.01 NS <0.05 NS

Group B (canalization successful, peak CK > 1,000 U/liter)

11 RCA 99n 50n 3 .5 4 .5 45 1150 40 11 61 67 27 41 66 6512 LAD 100? 90n 2 .0 2 .5 25 1200 166 130 52 43 29 24 32 3213 RCA 1001 90n 3 .0 3 .5 80 1300 187 79 25 42 12 22 32 4614 LCx loon 75n 4 .0 5 .0 30 1540 54 25 47 39 31 27 38 3715 LAD 100? 90n 6.0 8 .0 30 1580 39 58 22 33 21 4416 LAD 99n - 4.0 5 .0 40 1580 169 68 48 20 - 30 -17 LAD 1001 - 2.5 3 .5 25 1780 220 158 44 - 20 - 46 -18 LAD loon 50n 5.0 6 .0 30 1850 191 180 50 39 37 25 24 1719 RCA tool 75n 4.0 5 .0 110 2080 104 43 47 37 20 17 57 59

Mean 74 3.8 4 .8 46 1562 141 87 45.9 46 .4 25 .4 27 .0 38 .6 42 .9f SD 18 1 .2 1 .6 29 310 67 63 11 .3 11 .5 8 .2 7 .9 16 .8 16 .2P <0 .001 <0.01 NS NS NS

Group C (recanalizatlon unsuccessful)

20 LCx loci 100a 3.0 62 1016 56 58 39 37 46 4721 LAD loci - 5.0 14 3800 194 194 56 - 23 - 45 -22 LCx loon - 3.5 30 1550 97 112 54 33 - 52 -23 LAD loon loon 3.0 70 1800 151 144 41 30 25 7 28 3224 RCA loci 100i 2 .0 30 1350 83 79 60 54 29 29 52 4725 RCA fool 100a 3.5 60 1400 52 48 28 27 46 4926 RCA 1001 - 2.5 28 1550 202 205 26 - 5 - 35 -27 RCA 1001 100a 3.0 49 1580 65 62 37 31 68 66

Mean 3 .2 43 1756 145 147 54.8 50 .4 31 .6 26.2 48.0 48 .2± SD 0 .9 20 856 54 53 9 .1 12 .5 6 .1 11 .4 14 .4 12 .1p <0 .001 NS NS NS NS

INTRACORONARY THROMBOLYSIS IN INFARCTION-SCHWARZ ET AL .

degrees

FIGURE 1 . Schematic illustration showing how the size of the perfusiondefect was measured on thallium-201 scintigraphy . After the geometriccenter of the left ventricular cross section was defined, the area showingdecreased thallium-201 uptake was identified and the number of de-grees in the left ventricular circumference with the detect were de-termined .

Thallium-201 myocardial scintigraphy- After the initialclinical examination of the patient in the coronary care unit,2.0 mCi of thallium-201 was injected into a peripheral vein .The patient was transferred to the cardiac catheterizationlaboratory, and imaging was begun 10 minutes after injectionof the radioisotope . All studies were performed with a mobilegamma camera (Picker Dynamo) equipped with a seven pin-hole collimator .' 1 The camera head was positioned over thecardiac apex in a 40 to 450 left lateral projection in order toalign it with the long axis of the left ventricle . Two and a halfmillion counts were collected, usually in 10 minutes or less .Twenty-four hours later, a second dose of thallium-201 (1 .0to 1 .5 mCi) was injected and a second set of two images ob-tained. To assess the effect of residual thallium on scintigramsobtained 24 hours after the initial dose of thallium, two imageswere obtained in five patients . The first image utilizedequilibrated thallium still present in the patient from theprevious day; the second scintigram was obtained after in-jection of an additional dose of thallium . Apart from the betterquality and shorter collection time of the second image, nosignificant differences were observed between the two scin-tigrams; in particular, the size of the perfusion defect wasidentical in both images . All scintigraphic data were trans-ferred on line to a small computer for storage and evalua-tion.

Eight cross-sectional planes through the left ventricularmyocardium, perpendicular to the long axis, were recon-structed from the original data stored on magnetic disc usinga commercially available computer algorithm . 72 To estimatethe size of the perfusion defect all reconstructed myocardialcross sections were analyzed by a semiquantitative programdescribed by Vogel et al . 12 After the geometric center of eachcross section is defined, 60 radii, spaced at equal angles, areprojected outward from this point. A search is made along eachradius for peak count rate, which is normalized to the maximalcount rate in each patient. The results are displayed as a cir-cumferential plot over 360° . Abnormal myocardial sectionsare identified by comparing each plot with the lower limit ofnormal as defined by data from 15 patients free of cardiacabnormalities (mean ± 2 standard deviations), who weresimilarly studied . Once a section was identified to show de-creased thallium-201 uptake no attempt was made to gradethe degree of abnormality . Finally, the defect was calculatedfor each cross section and was expressed in degrees of leftventricular circumference (Fig. 1) ; for each patient the resultsof eight cross sections were averaged. The intraobserver

34


variability was 5 percent, and the interobserver variability 9percent .

Cardiac catheterization : Patients were studied with se-lective coronary arteriography using the femoral percutaneoustechnique. Patients received heparin, 7,500 U intraarterially,as well as prednisolone, 250 mg intravenously, in order to avoidallergic reactions to streptokinase . Diazepam, 10 mg, andmorphine sulfate . 10 mg, were administered intravenouslywhen necessary . Before use of contrast medium, left ventric-ular pressures were recorded during midinspiratory apnea (8Fcatheter, Statham P23 db transducer) . Single plane left ven-tricular cineangiography was performed in the 300 right an-terior oblique projection (40 ml Urografin-76 ®, 35 mm cine-film, 50 frames/s, Philips dual field 9 and 5 inch (22 .9 and 12 .7cm) image intensifier system . Selective arteriography of theright and left coronary artery (manual injection of 6 to 8 mlof Urografin-76) was performed in six projections includingthree hetniaxial projections . When a coronary occlusion wasclearly visualized, intracoronary injection of 0 .2 to 0 .4 mg ofnitroglycerin was performed to exclude spastic occlusion andthereafter continuous intracoronary streptokinase infusionwas begun (2,000 IT/min) . Injections of contrast medium wererepeated every 15 minutes and the infusion was stopped 15minutes after coronary recanalization . The patient was thentransferred to the coronary care unit . Heparin was given in-travenously according to plasma thrombin time to achieve fullanticoagulation (thrombin time was prolonged to between twoand three times normal value) . Blood samples were takenhourly for 12 hours and every 4 hours for the following 36hours for determination of serum creatine kinase WK) ac-tivity. l s Left ventriculography and coronary angiography wererepeated 4 weeks later using premeditation with diazepam,10 mg orally.From the coronary arteriograms obstructions mere assessed

and collateral circulation to the distal vessel segment wascarefully noted. As described by Levin, 14 the size and degreeof opacification of the distal vessel segments, as seen angio-graphically, were taken as an indication of the adequacy ofcollateral circulation . The latter was considered adequate ifthe average caliber of the distal vessel segment measured morethan 1 .0 mm in diameter (after correction for angiographicmagnification) . When inflow to the distal vessel segment wasso reduced that its average caliber was only 1 .0 mm or less,collateral circulation was considered inadequate .

Front the left ventricular angiograms, end-diastolic, end-systolic and stroke volumes were determined,' ,' and ejectionfraction and regional ejection fractions were calculated . Re-gional ejection fraction was determined using the area methodas shown diagrammatically in Figure 2 . 16 The area systemmeasured systolic change as segmental ejection fraction . Areascorresponding to the perfusion area of the occluded vessel(infarct area) were averaged (anterior infarction, areas 1, 2 and3; inferior infarction, areas 3, 4 and 5) . Normal areas were alsoaveraged (anterior infarction, areas 4 and 5; inferior infarction,areas I and 2) . Left ventricular end-diastolic pressure wasmeasured at the junction of the a wave with the upstroke ofthe left ventricular systolic pressure .

Statistical analysis: Paired and unpaired t tests, analysisof variance and the chi-square test were used . Significance wasaccepted at the 5 percent probability level (p <0 .05). Meanvalues ± standard deviation are given in the Tables and in theResults section. In the figures mean values t standard errorof the mean are shown .

Results

Patient groups (Table 1) : The patients were clas-sified into three groups: group A, 10 patients with re-

FIGURE 2 . Schematic drawing for calculating regional ejection fractionfrom the left ventriculogram (right anterior oblique projection) . Theventriculogram was divided into five areas and the segmental ejectionfraction was calculated for each area . Areas 1, 2 and 3 were averagedfor anterior myocardial Infarction, and areas 3, 4 and 5 for inferior in-farction .

opening of the occluded coronary artery who manifestedpeak CK activity of less than 1,000 U/liter after recan-alization ; group B, 9 patients with recanalization of theoccluded coronary artery who manifested peak CK ac-tivity greater than 1,000 U/liter after recanalization, andgroup C, 8 patients in whom the attempt to recanalizethe occluded artery was unsuccessful .

In group A before recanalization, eight patients hadtotal occlusion and the remaining two patients hadsubtotal occlusion of the vessel supplying the infarctingmyocardial area . Adequate collateral supply was ob-served in four patients. In group B before recanalization,


seven patients revealed total and two patients subtotalocclusion of the vessel supplying the infarcting myo-cardial area. Adequate collateral supply was not seenin any patient in group B . All patients in group C hadtotal occlusion of the vessel supplying the infarctingmyocardium . No patient in this group had collateralsupply to the obstructed coronary artery .

The number of anterior and inferior infarctions didnot. differ among the three groups (p >0 .05). The timeinterval between the onset of symptoms and the startof cardiac catheterization was 3 .1 ± 1 .8 hours in groupA, 3.8 ± 1.2 hours in group B and 3 .2 ± 0 .9 hours ingroup C (all p >0 .05) . The time interval between theonset of symptoms and recanalization was 3 .9 ± 1 .8hours in group A and 4 .8 ± 1.6 hours in group B (p>0.05). The dose of streptokinase administered was145,000 ± 51,000 U in group A, 191,000 ± 30,000 U ingroup B and 196,000 :k 48,000 U in group C (p >0 .05) .The average duration of streptokinase infusion was 70f 26 minutes in group A (range 30 to 120), 75 f 35minutes in group B (range 30 to 150) and 103 ± 29minutes in group C (range 60 to 150) (all p >0 .05). Therewere no significant group differences in heart rate(group A 82 f 22, group B 83 ± 19, group C 77 f 15heats/min), left ventricular systolic pressure (group A125 ± 13, group B 116 t 24, group C 1311 11 mm Hg),left ventricular end-diastolic pressure (group A 20 ± 7,group B 22 ± 8, group C 17 t 8 mm Hg), ejection frac-tion, regional ejection fraction, serum CK activity orthallium-201 perfusion defect before recanalizationattempt (p >0.05) .

Early study after recanalization attempt : Figure3 illustrates two thallium-201 scintigrams from a patientin group A (before and after successful recanalization) .

FIGURE 3 . Thallium-201 scintigrams of a cross section of the left ventricle in a patient in group A. A defect of the anterior and septal walls seenbefore recanalization (left panel) disappeared 24 hours after reperfusion (right panel) .


35


before recanalizalion 4weeks after recanalizationFIGURE 4 . Left ventriculogram (right anterior oblique projection) froma patient in group A . The interrupted line denotes the end-diastolicframe and the cross-hatched area the end-systolic frame . The anteriordyskinesia run before recanalization disappeared 4 weeks after re-canalization .

After 24 hours the perfusion defect of the anterior wallhas disappeared . Figure 4 shows the left ventricularangiogram from a patient in group A before and 4 weeksafter successfulrecanalization .In this patient anteriordyskinesia was considerably lessened 4 weeks afterthrombolysis .Serum CK activity increased in group A from 46 f

19 to 603 ± 239 U/liter (p <0 .001), in group B from 461 29 to 1,562 ± 310 U/liter (p <0 .001) and in group Cfrom 43 + 20 to 1,756 1956 TI/liter (p <0 .001) (Fig . 5) .The peak value in group A was lower than correspond-ing value in the other two groups (p <0 .05). Peak CKactivity was reached 15 .7 t 4 .3 hours after the onset ofsymptoms in group A, at 12 .9 ± 4.8 hours in group B (p>0.05) and at 23.6 17.4 hours in group C (p <0 .05 ver-sus group A, p <0.01 versus group B) .

The thallium-201 perfusion defect decreased from115 158 to 49 f 43° (p <0 .01) in group A (Fig . 5), from141 + 67 to 87 + 63° (p <0.01) in group B, but remainedunchanged in group C (145 ± 54 to 147 153', p >0.05) .The thallium-201 defect was smaller after 24 hours ingroup A than in group C (p <0.05) .

Late study: Four weeks after recanalization total leftventricular ejection fraction was unchanged in all threegroups (Table I) . The regional ejection fraction of theinfarct area increased significantly (p <0 .05) in groupA but remained unchanged in groups B and C (Fig . 5) .The regional ejection fraction after 4 weeks was higherin group A than in the other two groups ; however, thedifference was not significant (p >0 .05). The regionalejection fraction of the normal area remained essentiallyunchanged in all three groups . No patient in group A orB had clinical, serum enzyme or electrocardiographicevidence of recurrence of acute myocardial infarctionbetween the early and the late study . Patient 4 mani-fested reocclusion of the recanalized vessel in the secondstudy .Complications; Minor bleeding occurred at the site

of the arterial puncture in three patients and gastroin-testinal bleeding, seen in one patient, was treatedmedically . Three patients died within 4 weeks of theintervention (Cases 21, 22 and 26) . Two deaths weresudden (outside the coronary care unit) and one death

36


YU

y 1000c0.

500

0

200

100

50

0

40

10

Successful recanalizatlon

JIon

Group A Group B Group C

I

I I I

SEM

I I

II II I

before alter

before alter

before afterFIGURE 5 . Mean serum enzyme, scintigraphic and hemodynamic valuesin the three groups . after = after recanalization ; before = before re-canalization ; CK = creatine kinase ; TL = thallium-201 ; * = probability(p) value <0.05 ; ` • = p <0 .01 or 0.001 (when comparing the valuesbefore and after recanalization); SEM = standard error of the mean ;Unsucc. = unsuccessful .

was due to developing cardiogenic shock 4 days after anunsuccessful recanalization attempt.

Discussion

Control group : W e use serum enzyme, scintigraphicand hemodynamic criteria to evaluate the effect ofsuccessful early reperfusion due to intracoronarythrombolysis in patients with acute myocardial in-farction . The group with an unsuccessful attempt atrecanalization (group C) is considered the control group,indicating the natural course of acute myocardial in-farction . This control group fulfilled the following cri-teria: (1) The patients were studied invasively at iden-tical time intervals (early and late) after the onset ofsymptoms to those in the other two groups; (2) thesepatients were comparable at the initial study with pa-tients in the other groups regarding initial serum ere-atine kinase activity, thallium-201 perfusion defect, left

ventricular ejection fraction, regional ejection fraction,left ventricular hemodynamics and dose of streptoki-nase administered; and (3) during the study interval theinfarct vessel did not recanalize spontaneously (nospontaneous reperfusion) . In this group serum creatinekinase activity increased to a peak value of 1,756 U/liter24 hours after the onset of symptoms, thallium-201scintigraphy revealed no change in the perfusion defect24 hours after admission and the regional ejectionfraction of the infarct area decreased slightly 4 weeksafter the early intervention .Recanalization groups: The two groups with suc-

cessful reopening of the obstructed vessel due to intra-coronary thrombolysis (groups A and B) were separatedon the basis of peak serum CK activity . Patients ingroup A had a peak value below 1,000 U/liter ; those ingroup B had a peak value above 1,000 U/liter (Fig. 5) .

The size of the thallium-201 defect decreased in bothgroups, but the reduction was greater in group A . Theregional ejection fraction of the infarct area increasedsignificantly in group A only, whereas a slight but notsignificant increase was seen in group B . It is evidentthat patients in group A had the most favorable courseafter acute myocardial infarction when compared withpatients in groups B and C . Serum enzyme, scintigra-phic and hemodynamic data demonstrate a significantsalvage of jeopardized myocardium in group A but a lessfavorable result in group B .Serum CK activity as a measure of infarct size :

Serum peak CK activity was used in this study to esti-mate the size of the area of myocardial necrosis.17-19

Vatner et al." showed in dog experiments that the en-zyme estimate of infarct size (serum CK analysis) andthe pathologic estimate correlated significantly (r =0.94) when the coronary vessel was permanently oc-cluded. They also reported that these estimates corre-lated significantly (r = 0 .90) even after reperfusion ofthe infarcted area, although the enzyme values overes-timated infarct size,19 because early reperfusion mayfacilitate enzyme washout from damaged cells . Thus,after reperfusion, CK activity may be disproportion-ately elevated at a given infarct size . Among our patientswith successful recanalization, on the basis of peak CKactivity we established two subgroups (groups A and B)in order to define the prerequisites for the optimal re-covery of left ventricular function after recanalization .In these two groups the peak CK levels after recanali-zation were lower than or even equal to values in thecontrol group, thus indicating smaller areas of ne-crosis .Myocardial thallium uptake as a measure of

myocardial perfusion and preserved myocardium :The intracellular uptake of thallium is determined byregional myocardial blood flow and by the integrity ofthe myocardial cells . 20 Necrotic tissue fails to accumu-late thallium, whereas restoration of flow to an ischemicarea before tissue damage occurs will normalize thalliumuptake. 21 . 22 Similar observations were reported 2s ,24 inseveral patients undergoing intracoronary fibrinolysisusing intracoronary injection of thallium-201 . Hence,changes in thallium uptake early after reperfusion re-flect recovery from ischemia .

INTRACORONARV THROMBOLYSIS IN INFARCTION- SCHWARZ ET AL .

We used the seven pinhole tomographic technique inour study. With this technique we took great care toalign the collimator exactly with the long axis of the leftventricle . The technique is very sensitive to patientpositioning; therefore, great care was also taken to re-produce the position as closely as possible in the sub-sequent studies: All raw data were screen for clippededges or off center position in order to eliminate re-construction artifacts . In some instances it was neces-sary to readjust the position and to record a secondimage. Because of its limited angle aperture of less than180° the Z axis resolution of the seven pinhole colli-mator deteriorates with increasing distance from thecollimator face (that is, toward the base of the heart) .Thus, the thickness of individual cross sections throughthe myocardium is not identical at all levels; sections arethinner at the apex than at the base, resulting in anoverrepresentation of the apical versus basilar slices .Because coronary occlusion affects the apex and the midportion of the left ventricle this overrepresentation mayproduce an overestimation of ischemic area. However,because each patient was his or her own control, actualchanges in infarct size should have been recorded ade-quately. The reproducibility of the method has beenfound to be excellent 25

Regional contraction function: Improvement inregional contractile function was observed in group Aand was documented by significant augmentation of theregional ejection fraction of the infarct area in the leftventriculogram. Contractile function in both groups Band C showed no recovery, although patients in groupB had successful reperfusion in contrast to those ingroup C. Experimental studies2c 2i revealed improve-ment of contractile function when reperfusion was es-tablished within 2 to 3 hours after coronary occlusion,the beneficial effect being critically dependent on theduration of ischemia .

Factors affecting beneficial influence of reper-fusion: Patients in group A (those with the most fa-vorable result) had a shorter interval between the onsetof symptoms and reperfusion (3 .9 hours) than did pa-tients in group B (4 .8 hours) . In addition, angiographi-cally estimated collateral blood flow to the occludedcoronary artery seemed to be adequate in 40 percent ofpatients in group A but in no patient in group B . Finally,the initial size of the thallium perfusion defect wasslightly smaller in patients in group A than in those ingroup B, signifying a smaller infarcting area at risk ingroup A. Heart rate and left ventricular systolic pressureas determinants of myocardial oxygen consumption atthe time of recanalization did not differ in groups A andB. The favorable result in group A can be explained byan additive effect of the modifying factors of ischemia :time of ischemia and severity of ischemia (residual flowto infarct area and size of area at risk) .

Our data suggest that in acute transmural infarctionreopening of the occluded coronary artery due to in-tracoronary thrombolysis limits infarct size as estimatedfrom serum enzyme, scintigraphic and hemodynamicmeasurements. The therapeutic success of the proce-dure is affected by the duration and severity of isch-emia.


37


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intracoronary thrombolysis in acute myocardial infarction: correlations among serum enzyme,...

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