NEUROGENIC SHOCK

I. THE EFFECTS OF PROLONGED LOWERING OF BLOOD PRESSURE BYCONTINUOUS STIMULATION OF THE CAROTID SINUS IN DOGS

DALLAS B. PHEMISTER, M.D.,AND

RUBIN J. SCHACHTER, Ph.D.CHICAGO, ILL.

FROM THE DEPARTMENT OF SURGERY, UNIVERSITY OF CHICAGO, CHICAGO, ILL.

DURING THE PAST CENTURY AND A HALF, in which the word shock hasbeen used medically to indicate a state of acute circulatory embarrassmentor failure associated with wounds, hemorrhage and other accidents, therehas existed a marked tendency on the part of the medical profession toconsider it brought about somehow through the nervous system.

Psychic activity incident to the accident and resulting in the passage ofimpulses from the brain to the vasomotor centers in the medulla may playa variable r6le and may be difficult to evaluate. That vasodepressor centersexist in the cerebral cortex was shown recently by Hoff and Green,' who pro-duced a decline in blood pressure by electrical stimulation of the lateral, supra-sylvian, ectosylvian and sylvian gyri in cats and occasionally the marginal gyrusand a small area of cortex near the anterior tip of the superior precentralsulcus in monkeys. Fainting frequently accompanies a variety of suddenaccidents and may send the blood pressure to very low levels.2 If thereaction is marked and prolonged, as is rarely the case, and if combined withother shock-producing factors such as hemorrhage, it may be of importancein initiating or prolonging a state of shock. Fear has been considered byFreeman,3 Cannon,4 and others, to be an exciting factor in shock by in-creasing the output of adrenalin, producing vasoconstriction with damage toand increase of permeability of capillaries, hemoconcentration, and secondaryfall of blood pressure.

Injury to sensory nerves of the traumatized field resulting in afferentimpulses to the vasomotor centers in the medulla is the method of actionthat has been most generally considered. The sensory stimuli are generallyassumed to inhibit vasoconstrictor impulses and lower blood pressure al-though the possibility exists that vasodilator impulses may simultaneouslybe augmented. The most serious objection to this theory is that whilevasodepressor responses may be elicited by electrical stimulation or bymechanical stimulation (as by cutting, pinching or stretching) of cerebro-spinal nerves during operations on man or experiments on animals, theyare usually absent in most of these instances, and if present are practicallynever of a degree that results in shock or even in marked and prolongedlowering of blood pressure.

610

Volume 116Number 4 NEUROGENIC SHOCK

The carotid sinus and cardio-aortic nerves are special afferent modulatornerves for the blood pressure with centers in the medulla and axonal endingsin the walls of the blood vessels and in case of the cardiac division of thecardio-aortic nerve in the left heart. Stimulation of these nerves resultsin lowering of the blood pressure which varies to some extent in degreeand duration with the nature, strength and length of the stimulus. Theexistence of similar modulator nerves has been postulated for other arteries,such as those of the abdomen, but never definitely proven. It has been thegeneral observation that falls of blood pressure often to shock levels (70Mm. of mercury or under) may usually be produced within a period of oneto three minutes by appropriate stimulation of either the carotid sinus or thecardio-aortic nerves. The pressure may be maintained at a low level for anindefinite period or it may rise to varying levels as a result of varying degreesof exhaustion of the reflex. However, no reports have been found in theliterature of very prolonged stimulation of these nerves in an endeavor todetermine whether or not the blood pressure can be maintained at lowlevels for a sufficiently long time to become the sole or an important factorin the causation of shock. Freeman3 lowered blood pressure in five cats bycardio-aortic nerve stimulation maintaining it between 6o and 8o Mm. ofmercury for 95 minutes in one case. The accompanying blood changes werenegligible and the pressure promptly returned to the original level on re-moval of the stimulus.

Experiments have been conducted in an effort to determine the effectof continuous and prolonged stimulation of the carotid sinus of the dogand of the cardio-aortic nerves of the rabbit. Also, an attempt has beenmade to determine whether or not there are similar nerves supplying bloodvessels within the abdomen which on stimulation lower the blood pressure.The results of carotid sinus stimulation are reported here.

The vasodepressor effect of stimulation of the carotid sinus was dis-covered by Hering,5 and Koch, and has since been considerably elaboratedby Heymans and coworkers,7 and others. Short to medium periods ofstimulation in dogs have not been found to bring on a state of shock althoughsudden reflex death has occasionally resulted during dissection or mechanicalor electrical stimulation of the carotid sinus or its nerve.

EXPERIMENTAL METHODS

Dogs weighing from 7 to I5 Kg. were anesthetized with sodium barbital,300 mg. per Kg. body-weight, intravenously. When smaller doses weretried there was usually struggling and disruption of the set-up especially onelectrical stimulation. The experiment was also set up under evipal anes-thesia, and the animal allowed to recover. Stimulation then also producedstruggling and disruption of the set-up. Kymographic tracings of bloodpressure were recorded from a cannula in the femoral artery. Stimulationwas produced in some cases mechanically by distention of the carotid sinus,in others electrically by an induced current passing through a bipolar elec-

611

PHEMISTER AND SCHACHTER Annals of SurgeryOctober, 1942

trode applied to the sinus in one form externally and in another form intra-vascularly. Erythrocyte counts, hematocrit, and in some cases hemoglobinand serum protein determinations, by the Barber-Hamilton method, weremade before and at intervals in the course of the stimulation. Blood wasdrawn from the exposed femoral vein in most experiments but more recentlyfrom the femoral artery.

Mechanical Stimulation.-For mechanical stimulation the technic of Hey-mans was used. An inverted jugular vein sac was attached to the end of acannula which was then inserted and tied in the carotid artery, so that thesac rested in the sinus. The external carotid artery was ligated near itsorigin. By distention of the sac with water the pressure was raised to thedesired levels. Sac pressures ranging between 175 and 275 Mm. of mercurywere found to give the greatest falls in blood pressure.

There were eight experiments of this kind. Sinus distention promptlylowered the blood pressure to some degree in seven but in only three didthe level reach 70 Mm. of mercury or lower. Usually, regardless of thelevel of descent the pressure began to rise within a few minutes and reachedthe previous level in from 10 tO 40 minutes. After periods of rest there wouldusually be a response to stimulation of the same character. One dog whichshowed falls of blood pressure of 20 to 40 Mm. lasting up to 30 minutes,died suddenly when the pressure was released at 120 Mm. mercury. In onedog there was failure of response despite repeated and varied elevations ofpressure in the sinus. Section of the vagi in three cases after failure tohold the pressure at low levels by stimulation made little difference in results.The remaining animals were sacrificed after 4 to 13 hours while stimulationwas not being carried out. Their blood pressures were at or only slightlybelow the levels before stimulation was begun and there were no changes inR. B. C. counts or hematocrits, or other evidences to indicate a state ofimpending or existing shock. The method of stimulation was consequentlyabandoned as being inadequate.

Electrical Stinmtulation with Electrode Applied Externally.-In a secondgroup of 14 experiments the region of bifurcation of the common carotidartery was dissected free of surrounding soft parts. One wire of a bipolarelectrode was hooked about the internal carotid and the other about the com-mon carotid near the bifurcation. In addition, five animals died suddenlyduring the dissection in an attempt to carry out this procedure, from reflexrespiratory and/or cardiac arrest, it being difficult to say which.

Stimulation was from a Harvard inductorium with 6 to i i cm. separationof the secondary coil from the zero point. Leakage of current to the sur-

rounding soft parts was troublesome. In IO experiments there were falls ofblood pressure but the degree and duration were very variable. Five animalsshowed moderate short responses but died suddenly at the onset or within 12

minutes to 2 hours in the course of stimulation, probably from current leak-age to the adjacent vagus. Only two dogs had prolonged falls of pressure.

612

Volume 116 NEUROGENIC SHOCKNumber 4

In one, the initial pressure was I50oMm., and under almost continuousstimulation for 6 hours it ranged between 8o and ioo Mm. and the erythro-cytes increased gradually from 6,480,ooo to 8,020,000, and the hematocritfrom 53 to 59. Death occurred suddenly from vagus arrest of the heart.In a second dog the pressure fell initially fromi- 145 Mm. and fluctuated be-tween 75 and 125 Mm. under continuous stimulation for ii hours. Whenthe stimulus was removed for '2 to 2 minutes, the pressure always boundedupward to I40-i6o Mm. and when released at the end, before killing, itwas 155 Mm. The erythrocytes were 6,o8o,ooo and the hematocrit 43before stimulation. After 5' 2 hours they were 6,8oo,ooo and 48, respec-tively. Estimations IO minutes before the stimulus was stopped showed12,000,000 erythrocytes (inaccurate ? ) and a hematocrit of 6o. Thus,despite the fact that the stimlulus was removed after i i hours, the bloodpressure rose as high as it was at the beginniing, showing that vasomotorcontrol was still normal. Hemoconcentratioin had developed during the last4 hours.

Electrical Stinndation with a Cannula Electrode.-In an endeavor toimprove the method of stimulation, a bipolar cannula electrode was devised.It is inserted and tied in the comiimon carotid artery, the distal pole beingcarried into the first portion of the internal carotid leaving the proximalpole in the carotid sinus. The cannula anid the method of insertion areshown in Figure i. For the prevention of leakage of current, the carotidartery is tied and divided proximally, the freed surrounding soft parts retractedby two Farr automatic retractors anid one ribbon retractor anchored to across bar. The set-up of the experiment is shown in Figure 2. In fourexperiments, both carotids were cannulated but the results of bilateralstimulation were little different from those of unilateral stimulation.

The results of cannula electrode stimulation in I9 experiments were agreat improvement over those obtained by previous methods, as the cir-culation of the sinus was well preserved, and it responded to stimulationfor long periods. By avoiding dissection about the carotid sinus nerve,there was no death during the preparation of the experiments. In everyexperiment there was at some time a response to stimulation but therewas variation in the intensity, duration and time at which it was obtained.With initial blood pressures varying from iiO to i6o Mm. mercury, therewas usually a fall at the onset of stimulation with the secondary coilio to 8 cm. from the zero poinlt. In the majority of the experiments thepressure fell from 25 to 50 Mm. of mercury, leaving it at suprashocklevels and sometimes much stronger stimuli were necessary. However ina minority of cases the fall was to 70 Mm. of mercury, or lower. The mostmarked falls were usually in animals showing little or no embarrassmentof respiration. In experiments giving the most marked and persistentresponse it was possible to lower the blood pressure to shock levels eitherimmediately or relatively sooIn after the onlset of stimulation and maintain

613

PHEMISTER AND SCHACHTER

TABLE I

CAROTID SINUS STIMULATION MAINTAINING BLOOD PRESSURE ALMOST CONTINUOUSLYAT SHOCK LEVELS UNTIL DEATH

Stimu-lation

E sper. Survival PeriodNo. Hours Hours

0

0.11.0

114 7.5 2.03.55.57.5

0

0.2119 9.5 1.0

2.53.56.59.25

0

0.11.0

129 8 3.06.257. 75

B. P.Mm.Hg.110666050707035

13076

10074836541

1065074707544

PulseRate120

124142138134

Res-pira- R. B.C.tion Millions20 7.14

24 7.1420 7.5228 8.7222 9.60

9.14

120 16 5.44 37

Hemat-ocrit% Pathology48 Lung: Congestion of capillaries and venules,

little hemorrhage and protein precipitate in47 alveoli. Liver: Extreme stasis in both51 hepatic and portal systems. Liver cords57 either vacuolated or granulated in places.61 Some lymphatics markedly distended with59 lyniph coagulum. Kidneys: Marked conges-

tion and acute granular degeneration ofepithelium of tubules. Adrenals: Markedcongestion, some hemorrhage and degenera-tion of cells of fasciculate zone. Littlecortical and medullary change. Lymphaticganglion near adrenal: Extensive degenera-tion of nuclei of some cells. Changes in otherviscera negligible.

116 22 7.28 40

96 8 7.12 4084 8 6.88 39132 7 6.08 39

126 36

120 20140 28136 26144 48

5.28

5.767.567.36

Average 8. 3

33 Necropsy: Moderate edema and atelectasisof lungs. Aspirated vomitus in some bronchi.

30 Central congestion and slight granular de-39 generation in cords of liver lobules. Slight36 degeneration of fasciculate zone of adrenal

cortex. Nuclear degeneration in convolutedtubules of kidneys. Spleen small andanemic, as in collapse. Other visceralchanges negligible.

it continuously or almost at such levels until circulatory exhaustion and deathoccurred. A summary of the results of three experiments is given in Table I.

The average survival time after beginning the continuous stimulation was

8.3 hours. As the blood pressure gradually declined there was a tendencyto hemoconcentration as shown by the erythrocyte counts and the hematocrit.This was slight in Experiments I I9 and I29. Necropsy in ExperimentsII4 and I29 revealed congestion and- acute degenerative changes in mostof the viscera. The hemoconcentration and pathologic changes were most

marked in Experiment I I4, in which the blood pressure was most con-

sistently at low levels, and in which death occurred earliest after 7.5 hours.Graph i shows the early blood pressure tracing with the rise and fall ofpressure from clamping and releasing the common carotid arteries, the fallof pressure from short stimulation with the inductorium at 9 cm. and theearly part of the prolonged period of continuous stimulation. Release of thestimulus for 2 minutes three hours after the beginning with a pressure of62 Mm. of mercury resulted in a rise of 30 Mm. However, a similar re-

lease 55 minutes before death resulted in only an 8 Mm. rise in pressure,

showing that the circulation was so badly damaged that an almost irreversible614

Annals of SurgeryOctober, 1942

Volume 116Number 4 NEUROGENIC SHOCK

state was present. Graph 2 shows the further decline during the final 35minutes of life. Photomicrographs show the blood and lymph stasis in theliver (Fig. 3), the cell necrosis in the convoluted tubules of the kidney(Fig. 4) and the disappearance of nuclei in sympathetic ganglion cells(Fig. 5).

GRAPH I.

CAROTID ARTERIESCLAMPED

N, RELEASED

ELECTRICAL STIM. OF CAROTID SINUS

U -MINUTES I

B.P.MM

RESRSTO PPED

m _ '^~~~~~~~~~~~~~~~

CONTINUOUS STIMULATION

MINUTESI I TI I I I I l I 1111111 111111111111111111 111111111

GRAPH 2.

GRAPH i.-Experiment 114: Showing carotid sinus reflex from clamping and releasingcarotid arteries and electrical stimulation of right carotid sinus.

GRAPH 2.-Experiment II4: Blood pressure tracing before death, following 7Y2 hoursof stimulation, with maintenance at shock levels.

In the larger group of experiments in which, for a long period, the reduc-tion in blood pressure was to irregular suprashock levels, the general effecton the animals was relatively slight, and on release of the stimulus thepressure would mount to approximately the prestimulation levels. At times

615

PHEMISTER AND SCHACHTER Annals of SurgeryOctober, 1942

A

B

Z/ I * lZFInt.carotid \ COmmOn5inus nerve

FIG. T.-A. Insulated bipolar cannula electrode. B. Electrode inserted through right carotidartery with distal pole in internal carotid artery and proximal in carotid sinus.

_- . . . i.::::zE _

FIG. 2.-Experiment set-up for stimulation. Cannula inserted in carotid sinus and held in theclear by clamp. Surrounding soft parts retracted by one anchored ribbon retractor and two Farrautomatic retractors.

616

ME

.... .... .....

.3A

OF

Noumber 4 NEUROGENIC SHOCK

the reflex would be exhausted and the pressure would rise to previous levels.Following a brief rest period, the pressure would again fall on stimulation.

E

TABLE I IBLOOD PRESSURE LOWERED TO SUPRASHOCK LEVELS DURING ABOUT THE

FIRST TWO-THIRDS OF PERIOD OF CAROTID SINUS STIMULATIONB. P. Hemato-

:xper. Survival Time Mm. Pulse Resp. R. B. C. critNo. Hours Hours Hg. Rate Rate Millions % Patholog

0 120 138 16 6.96 35 Operative wounds infecte0.3 80 static congestion of lung0.6 80 128 20 5.52 31 alveoli. Lymphatics dist

131 26 1.6 90 136 20 5.78 35 agulun. Central venous2.6 100 168 20 5.48 34 liver with degeneration ii5.0 84 162 28 4.32 26 Sone degeneration in cort9.0 82 176 26 3.84 generation and hyperen13.0 80 150 36 5.68 35 zone of adrenals. Extens

(over night) and sloughing of convol22.5 72 172 28 6.4 39 kidney. Moderate hyperer24. 6 68 170 28 6. 24 40 spleen. Subepicardial v;25.6 45 5.59 41 ment, with lymphatics dis

coagulum. Slight waxymyocardiurn. Pancreas,skeletal muscle normal. S(in peripancreatic sympat

y*d. M arked hypo-,s. Some blood in;tended with co-;engorgement inin adjacent cords.tical zone and de-nia in fascicularsive degenerationluted tubules ofmia of kidney andrascular engorge-stended by lymphdegeneration ofjejunum and

,ome degenerationthetic ganglio'n.

00.11.0

132 14.75 1.21.653.04.06.59.09.510.013.0

00.251.0

133 18.3 2.04.59.09.7511.515.516.518.0

Average 19.7

170140140

128135859090907054

130909810011511010580706026

180 22 9.04 48 Operative wounds infected. 'Hypostaticcongestion and beginning pneumonia in

163 20 8.96 55 posterior lobe of lung. Passive congestionof liver and degeneration of cord cells.Acute necrosis of cells of convolutedtubules and marked congestion of kidney.

160 24 9. 76 51 Congestion and moderate degeneration in180 16 10.38 53 intermediary zone of the a'drenals. Pan-

creas, spleen, jejunum and skeletal muscle184 28 9. 68 normal. So-ne fragmentation of myocardial

fibers.160 24 9.14 51

138 24 6.90 47

160 28 8.00168 32 7.44176 19 6.56

8.40144 24144 32 7.28160 16 6.72

514544

44

4642

Operative wounds infected. Hypostaticcongestion and slight atelectasis of lungs.Engorgement of central lobe veins andnecrosis of cords of liver. Slight hyperemiaand necrosis or tubules of kidney. Moder-ate hyperemia, necrosis and leukocyticinfiltration of intermediary zone oof adrenals.Other viscera and cardiac muscle essential-ly normal.

However, after IO to 20 hours of continuous, or almost continuous stimula-tion, the blood pressure would decline to shock levels and then death wouldresult in a shorter time than in the animals whose pressures fell to shocklevels at -the onset of the stimulation. The results of three experiments aregiven in Table II.

The average survival period was I9.7 hours. There was relatively littlefluctuation in the erythrocyte counts and hematocrit, either before or afterthe blood pressure descended to shock levels. The experiments ran longenough for wound infection to be established and to play a part in thecausation of death.

617

PHEMISTER AND SCHACHTER

FIG. 3.

Annals of StorgeryOctober, 1942

FIG. 4. FIG. 5.

FIG. 3.-Experiment II4: Engorgement of veins and capillaries with blood, and of lymphaticswith lymph coagulum.

FIG. 4.-Rxperiment I 14: Necrosis of cells of kidney tubules.FIG. 5.-Experiment II4: Necrosis of cells of sympathetic ganglion.

In Experiment I3I the animal lived 26 hours. The duration and degreeof fall during the first I3 hours varied considerably. Graph 3 shows thedecline of pressure on initial stimulation with the inductorium at 6 cm.and the rapid return to a higher level despite continuation of the stimulus.After moving the secondary coil to 4 cm. the pressure again fell and withthat strength unchanged it remained at irregularly low levels until death.During the long period that the pressure remained at suprashock levels,the rise of pressure on temporary release of the stimulus was very markedas shown at the end of 3.2 hours by Graph 3b, and at the end of II.3 hoursand 22.5 hours as shown by Graph 4c and d, respectively. However, afterthe pressure had been at shock levels for one hour, the elevation ofpressure on release was very slight (Graph 4e) and after another hour itfailed to occur.

For comparison with these two groups of stimulation experiments, athird or control group was run, in which the procedure was the same exceptthe electrical stimulus was not applied to the sinus. The results are shownin Table III. The average duration of life was 28.7 hours. The blood pres-sure did not drop to shock levels until an average of about 4 hours before

618

S-

NEUROGENIC SHOCK

EXPERIMENT NO. 131

I I, II**I,, I** If . I I I I ..I I

A - ONSET OF STIMULATION. REFLEX QUICKLY EXHAUSTED.

e - 40 SEC. RELEASE AFTER 3.2 HRS. CONTINUOUS STIM.

GRAPH 3.-Experiment I31: A. Showing fall in blood pressure to suprashocklevels, with recovery during carotid sinus stimulation. B. Elevation of blood pressureon release of stimulus, while pressure is maintained at suprashock level for 3.2 hours.

MINUTES

E

-r-T- I .

C - 45 SEC. RELEASE AFTER 11.3 HRS. CONTINUOUS STIM.D - 3 MIN. " " 2265" "E - 20 SEC. " 23.5 " " "

GRAPH 4.-Experiment 13I: Showing marked pressor responseon release of stimulus after maintenance at suprashock levels for(C) i I4 hours. Response still good when shock level reached(D) after 22X2 hours, but feeble (E) after 23¼2 hours.

619

Volumiie 116Number 4

MM

160

120-

80O70-

BASE LINE

INDUCTORIUMx 6CM.

A

STIMUL

MINUTE

.u

PHEMISTER AND SCHACHTER Annals of SurgeryOctober, 1942

TABLE IIICONTROL EXPERIMENTS FOR CAROTID SINUS STIMULATION

Sur- B. P. Res-Exper. vivaNo. Hour

134 26.3

1 Time Mm. Pulse pira- R. B. C.rs Hours Hg. Rate tion MilliQns

0 145 88 28 9.605 2.3 150 180 24 9.12

8 150 205 24 10.2410.25 140 10.32

(over night)22 80 88 12 8.7224 70 138 20 8.8826 40 8.80

0 160 180 22 7.76135 31 2 160 180 20 7.84

8 160 180 20 8.6414 130 170 28 8.0820 90 144 10 8.1625 70 150 12 7.6830 50 164 10 6.90

0 120 144187 29 1.6 110 140

4 126 1608 120 180

12 100 180(over night)

20 86 19024 80 18028 60 160

2440444448

365488

5.686.085.846.806.94

7.207.686.72

Hemato-crit Serum% Proteins Pathology56 5.61 Necropsy: Early infection of60 5.48 wounds. Early pneumonia. Early60 5.78 necrosis of mrany cells of convo-57 5.61 luted and collecting tubules of kid-

neys. Central congestion of liver53 5.48 lobules, degeneration of liver cells.54 5.48 Degeneration and nuclear frag-52 5. 65 mentation of adrenal cortex. Slight

waxydegenerationof heartmuscles.Other viscera and skeletal muscleshowed no changes.

51 5.58 Necropsy: Moderate ate!ectasis53 6.26 and congestion of lungs. Degener-54 6.35 ation of glomerular zone and of50 6.22 cells of cords of adrenal cortex.52 5.65 Slight degeneration and sloughing49 under 5.58 of cells ot convoluted tubules of48 under 5.58 kidney. Congestion of liver

lobules. Otber viscera show nochange. Infection of wounds.

Hb.45 84 Hypostatic congestion of lungs and47 5.31 86 early pneumonia. Necrosis of cells50 5.48 85 of tubules of kidneys. Hyperemia.49 92 Necrosis and lehkocytic infiltra-49 5.48 96 tion of intermediary zone of

adrenal. Marked engorgerrent of49 5.24 102 liver veins and necrosis and leuko-49 4.97 104 cytic infiltration of liver cells.47 5.24 95 Other viscera and skeletal muscle

show negligible change. Infectionof experimental wounds.

Average 28.7

death. There was no significant change in the erythrocyte counts, hematocritor plasma proteins. Infection of the operative wounds was more markedthan in the group of cases represented in Table II.

DISCUSSION.-The factors to be considered in the causation of death ofthe animals in which the carotid sinus was stimulated electrically, with theuse of the bipolar cannula electrode, are the effects of the stimulus, theanesthetic, the experimental wounds, and the possible late complicationsfrom infection and dehydration.

In the group of animals represented in Table I, in which the bloodpressure was maintained at shock levels during nearly all of the period of.stimulation, there was death after an average of 8.3 hours, with a tendencyto hemoconcentration, which was marked in one case and slight in the othertwo cases. In the two necropsied cases there were acute congestive and de-generative changes in the cells of parenchymatous organs compatible withchanges resulting from low blood pressure and failure of the circulation. Theanesthetic produced sound narcosis, but there was no evidence that it wasan important -factor in the cause of early death. The experimental woundswere made with very little blood-loss, and death occurred before there wastime for the appearance of toxic effects of their infection. Consequently, it

620

Volume 116 NEUROGENIC SHOCKNumber 4

appears justifiable to conclude that the prolonged maintenance of the bloodpressure near or below 70 Mm. of mercury was the most important factorin the production of death from acute circulatory failure.

In the group of animals represented in Table II, in which, during con-tinuous or almost continuous stimulation, the blood pressure remained de-pressed but at irregular levels, above 70 Mm. of mercury, the animals didnot present a tendency to hemoconcentration, and on temporary release ofthe stimulus, the blood pressure quickly rose to high levels over a period ofIO to 20 hours. Finally, the blood pressure sank to 70 Mm. or below, afterwhich the animals died in an average of four to five hours showing a slighttendency to hemoconcentration during the period. Infection, prolonged an-esthesia, and dehydration appeared to be the most important lethal agentsand circulatory damage from lowering of blood pressure to suprashock levelsby sinus stimulation was of much less significance.

In the third group of control experiments, which lived on an average of28.7 hours, the prolonged anesthesia and infection of the wounds, and ofthe respiratory tract were the factors of greatest importance in causingdeath. The blood showed little change, with a slight tendency to hemo-dilution, and the blood pressure fell to low levels late in the course of theexperiments.

SUMMARY

By electrical stimulation of the carotid sinus in dogs under sodiumbarbital anesthesia using a bipolar cannula electrode, it was possible tomaintain the blood pressure at reduced levels for long periods of time andto observe the effects of the lowered blood pressure upon the body andthe general circulation.

In one set of experiments, in which the pressure was held continuouslyor nearly so at 70 Mm. of mercury or below, the blood became concentratedand death occurred after the lapse of an average of 8.5 hours. At necropsy,there was congestion and acute necrosis of the cells of many of the viscera,and the picture was compatible with shock produced principally by thevasodepressor nerve stimulation.

In a second set of experiments, in which the pressure was lowered bystimulation but remained above 70 Mm. of mercury, there was relativelylittle damage to the circulation for many hours, as revealed by the absenceof hemoconcentration and by prompt elevation of the pressure on temporaryrelease of the stimulus. Finally, the pressures fell to shock levels, and deaththen followed in 4 to 5 hours with a total survival period averaging I9hours. The anesthetic and the infections of the wounds and of the respiratory'tract were important factors in the causation of death. However, that deathwas hastened by the blood pressure lowering effects of the stimulation isindicated by the fact that a set of control animals lived an #verage of 28.7hours, or 9 hours longer than those of the second group, dying mainly fromthe effects of anesthesia and infection.

While neurogenic shock has been produced by carotid sinus stimulation621

PHEMISTER AND SCHACHTER Annals of SurgeryOctober. 1942

in anesthetized dogs it has only indirect bearing on human shock, sincesimilar stimulation would scarcely be encountered as a result of injury orduring operation in man.

The pathology of the experiments has been kindly reviewed by Dr. EleanorHumphreys.

REFERENCES

1 Hoff, E. C., and Green, H. D.: Cardiovascular Reactions Induced by Electrical Stimu-lation of the Cerebral Cortex. Amer. Jour. of Phys., 117, 411, I936.

2 Phemister, D. B., and Livingstone, H.: Primary Shock. ANNALS OF SURGERY, 100,7I4, I934.

3 Freeman, N. E.: Mechanism and Management of Surgical Shock. Penn. Med. Journ.,42, I449-I452, 1939. Idemn: Decrease in Blood Volume after Prolonging Hyper-activity of the Sympathetic Nervous System. Amer. Jour. of Physiology, 103,I85, I933.

4 Cannon, Walter B.: A Consideration of Possible Toxic and Nervous Factors in theProduction of Traumatic Shock. ANNALS OF SURGERY, 100, 704-713, I934.

5 Hering, H. E.: Wien. med. Wchnschr., 73, No. i6, 729, I923.6 Koch, E.: Munchen. med. Wchnschr., 70, 13I6, I923. Idem, ibid., 71, 704, I924.'Heymans, C., Bouckaert, J. J., and Regniers, C.: Le sinus Carotidien et la Zone

Homologue Cardioaortique. G. Doin et Cie., Paris, I933.

622