The mechanism and treatment of shock in acute myocardial infarction

The Mechanism and Treatment of Shock in Acute Myocardial Infarction

By h'~AX~VELLJ.

BINDZn

HE MILD DECREASE in blood pressure which frequently accompanies cute myocardial infarction does not alter the mortality rate in this disease. Severe shock, on the other hand, occurs in approximately 12 per cent of patients hospitalized for acute myocardial infarction and is associated with a mortality rate of 80 per cent or more t'r (table 1). There are man)' gradations between these two extremes which do not lend themselves to clear-cut definition. Severe shock, however, pre3ents a distinct clinical picture characterized by: (1) Marked hypotension, e. g., fall in systolic blood pressure to 80 mm. Hg or below. Patients who have had significant hypertension prior to infarction may develop shock when the systolic blood pressure is higher than 80 mm. (Hg. (2) Confirmatory clinical signs such as anuria or severe oligdria, cold sw~'aty skin, pallor or cyanosis or both, and dulled sensorium. The urinary output is a very sensitive index of slmck. Thus, the response of the kidney is of critical importance in differentiating shock from simple hypotension. In general, the degree of dep~'ession of the sensorium correlates least with the severity of shock. Severe shock occurring subsequent to acute myocardial infarction need not be due to the infarction per se. It may be due to such complications as hemorrhage, embolism, extra-cardiac thrombosis, infection, acidosis or to the rapid intravenous administration of analgesic drugs. These conditions should, if possible, be ruled out before the shock state is attributed to the acute myocardial infarction (coronary shock), inasmuch as they are associated with a different mechanism, prognosis and treatment. Similar consideration should be given to the presence of severe pain, cardiac arrhythmias or frank Congestive heart failure. Shock has also been reported with clinical states that simulate myocardial infarction. These include acute pericarditis, s,9 dissecting aortic aneurysm 1~ and acute cor pulmonale produced by pulmonary emboli.15-1s MECtlANIS.Xl OF CORONARYSIIOCK Until recent years, knowledge of tile mechanism of coronary shock was limited by the failure to reproduce it in animals and by the lack of hemo: dynamic data in human coronary shock. It was therefore possible only to speculate about the nature of the physiologic changes present in coronary shock. Thus, in 1934 Fishberg et al. TM stated that shock following myocardial infarction was due to heart failure and to peripheral circulatory failure. From the Cardiology Section, Medical Service, Veterans Administration Hospital, and the Department of Medicine,School of Medicine, University of California, Los Angeles, California. 206

207

S H O C K I N A C U T E .'klYOCAI1DIAL I N F A R C T I O N

TAmaLE1.--Coronary Shock: Incidence and Mortality Rates

Year

1941 1947 1949 1952 1952 1954 1955

Author

Rosenbaumand Levine Mintz and Katz Epstein and Relman Seizer tlellersteinet al. Griffith et al. Binder et al.

Incidence o f Shock in C o r o n a r y Occlusion (%)

No. o f Cases Reported

Mortality

7 7 15 13 10 20 9

14 36. 20 69 10 161 57

13 (93,%) 28 (78%) 17 (85%) 48 (70%) 8 (80%) 128 (80%) 51 (89%)

Several years later, Fishberg changed his opinion and concluded that coronary shock was due entirely to heart failure. -~~ Boyerel similarly felt that heart failure was the sole cause of coronary shock, an opinion which he has recently 9 o,) reiterated.-Experimental studies: Ttle heart has been injured experimentally in many ways without lowering the blood pressure significantly. The method of coronary artery ligation first used by Samuelson in 1881,-"'~has been associated with a mild drop in blood pressure,-0;-29" ventricular fibrillation "-'~,eT.29-al or with heart failure.2a,-or,'~l Shock has not resulted from hyperthermal injury of the myocardium with electrocautery32,'~'~ or with heated metal, ~4 nor has it followed hypothermal injury of the myocardium with ethyl chloridezz or with expanding carbon dioxide.~ Lohman in 1908ar and many investigators subsequently have produced myocardial necrosis by direct injection of chemicals into the heart 36 without producing significant lowering of blood pressure, except for Meyers et al. 3s who produced hypotension by injecting necrotizing zinc hydroxide into the myocardium (mainly septum). Embolie occlusion of the coronary arteries was attempted by Itamburger et al. with lycopodium sporesf '~ by Herrmann and Decherd with metallic mercury4~ and by Roos and Smith with a starch suspension, at In some of the animals observed by Roos and Smith, heart failure and significant hypotension occurred 10 minutes prior to death. In 1952, Agress et al. reported a method for embolizing the coronary arteries in the closed-chest dog, utilizing plastic microspheres.4-~ This procedure avoided the trauma and hemorrhage inherent in the open chest technic. In an appreciable number of these dogs it was possible to produce coronary shock meeting the following criteria: (1) reduction in mean arterial pressure (MAP) by 30 per cent; (2) maintenance of this reduction with no upward trend for at least 30 minutes; (3) electrocardiograpldc evidence of severe myocardial injury; (4) absence of cardiac arrhythmias. Other dogs showed no significant change in MAP despite repeated coronary embolization and severe myocardial injury. "Figure 1 illustrates the hemodynamic changes observed ~3,43 in those animals which developed coronary shock. Cardiac output (CO), stroke volume and MAP fell to approximately 60 per cent of control values, but, significantly, no change occurred in the total peripheral resistance (TPR). In those dogs

208

~[AX~VELL

J. BINDER

which maintained their MAP desp!te repeated coronary embolization (fig. 2), it was found that tlle CO anti stroke volume fell to 40 to 50 per cent of control values. However, this was associated with a rise in TPR of 100 per cent and little change in the MAP. In these experiments, the degree of myocardial injury and reduction in cardiac output was similar in both groups; tile critical factor in the production of shock was the response of the TPR. When a compensatory rise in TPR failed to occur, coronary shock was produced. Other data reported in these animals indicated that the central venous pressure was normal at the onset of shock and tended to rise with the passage of time. Heart failure might thus be added to shock, but it was not necessary for the production of sheck. A mild reduction in blood volume occurred hfter shock had developed, reaching 16 per cent below control values in several / hours. These changes in blood volume do not appear to be important in the development of shock, inasmuch as it has been shown that a reduction in blood volnme of approximately 40 per cent is necessary to produce hypovolemie shock. 4~-4G Failure of the TPR to rise in the shocked animals suggested inhibition of vasoconstrictor reflexes which appeared to be intact in the nonshoeked group. It x'vas theorizea that such inhibition could result from reflexes arising in the injured myocardium. The known afferent cardiac pathways were then studied. After it was found tlmt bilateral cervical vagotomy did not prevent 120

I00

80

g/ 60

\\\

V

STROKVOL ~

CARDIACOUTPUT MEAN ARTERIALPREss.

40

tJJ Z

>tr

80

=_, z

CONTROL

I hI.

2 hrs.

3 I~rs.

Fic. 1 . - - H e m o d y n a m i e s in coronary slmck.

SIIOCK IN ACUTE .XIYOCAI1DIAL INFARCTION

ZOO

009

/

TOT.P[R.R[S.

18C 160 140 PULSEP,ATE 120

(

A

IOO J

NARTERIAP L.RESS.

8O

40

CARC4AG OUTPUT STROKEVOLUME

~ao ~

C~'~TRO~_-

I~l

2~.

~[s.

Fro. 2.--Hemodynamies after myocardial damage without shock. or alleviate coronary shock,43 attention was directed to tlm afferent cardiac sympathetic fibers. Figure 3 demonstrates the rise in TPR and MAP which occurred after section of tile posterior dorsal roots from C 7 to T 6 in an animal previously injured by coronary embolism. Figure 4 shows that epidural analgesia of this same region produced a similar rise in TPR and MAP in an animal which had been maintained on levarterenol (Levophed) after coronary embolism. Thus, tile available data suggest that coronary shock, experimentally produced, is related to inhibition of homeostatic vasoconstrictor responses in the presence of a reduced cardiac output.' While the experiments cited above support the concept that such inhibition results from reflexes that arise in the injured myocardium and are carried by the afferent cardiac sympathetic fibers, they do not eliminate the possibility that hormonal factors may play a role as well. Clinical st,dies: Blood volume determinations in patients with severe coronary shock 4r'49 indicate that little or no change occurs in the first few hours of the development of slmck. By the end of 24 hours, the blood volume may be reduced by 15 per cent. With further passage of time, heart failure

210

.'%IAXV4ELL

MEAN B.R (ram. Hg.)

EXPERIMENTAL MYOCARDIAL INFARGTION

J.

BINDER

I C.O. T.P.R. (I,,/mkl.) D----e 1500

140 -

//

1.4 1200

120 - ~ \ \ I00

//

0".-..~_.~ \ ",,.

_

t,2

riO0

//

1.2 9O0 0.8

80

700 60 40

0.6

.,r-

DORSAL ROOTS 0.4 SECTIONED

-TT i CORONARY

20 I

+

I

,

I

I

I

I-,I

,

80

40 66 TIME (rain.)

Z0

30O

0.2

EMBOLISM 0

500

I IO0

Fie. 3.--Experimental myocardial infarction. Heinodynamlcs before and after dorsal root section.

C 0 T.P.R. I/rain units

MEAN I B.P. I

mm_H~,

O----O ,C----~C )00

140 120 _

\

~

~

iI

3.0

K)O

-

'50

2.5 _ 60O \\

80 ~0~ 0 ~ -

""

T

40_ 920'_

-(3-

]L

11

--0

-

EPIDURAL ANALGESIA

_ I.O

EMBOUSM I

i

1

I

_

I

20 40 TIME - Minutes 0

60

80

I00

120

140

'-~

160

~

0.5 --I

~

5O

180

F*c. 4.--Experhnental myocardial infarction. Hemodynamics before and after epidural analgesia.

211

SHOCK IN ACUTE 3,IYOCARDIAL INFARCs

may supervene and the blood volume may increase. As in the animal studies cited above, these blood volume changes are too small and occur too late to be significant in tile production of coronary shock. Data relating to CO and TPR changes in clinical coronary shock are available in four reports 47,4~.z~ on 14 patients (table 2). The cardiac output was low in each of tlmse patients. However, in other patients with acnte myocardial infarction, equally low cardiac outputs were found in the absence of shock. The TPR was elevated in 8 of tile 14 patients with coronary shock and was normal in the other 6 patients. In 2 of the 14 patients (Cases 1 and 3) measurements were made before and after the development of shock. Despite significant reduction in MAP and CO, there was little change in the TPR, / suggesting failure of homeostatic vasoconstrictor responses. The venous pressure was measured in 12 patients (table 2); it was normal in 6 patients and above 200 mm. water in only 2 patients. The modest elevations of venous pressure (up to 200 mm. water) found in the remaining four patients may have been due to the venoconstriction associated with shock, rather than to congestive heart failure. 4~',.~2 The hemodynamic studies in human coronary shock ifldicate that these patients fall into one of t w o groups,~i.'e.,-(1) those patients in whom the degree of myocardial damage and resultant fall in cardiac output is so great that even marked vasoconstriction cannot maintain the blood pressure and (2) those patients with myocardial infarction and reduced cardiac output in whom homeostatic vasoconstriction does not occnr. Neither the animal experiments nor the human data have shown evidence of "peripheral vascular collapse" if this term is used to mean an appreciable fall in TPR. The abnormality which has been demonstrated is the failure of the T P R to rise as tim cardiac ontput and blood pressure fall. TABLE 2.--ttemodynamic Changes in Clinical Coronan.I Shock

Authors

Year

Freis et al.

1952

Smith et al.

1954

Gilbert et al.

1954

Patient Number

Mean Arterial Pressure (mm.Hg)

Cardiac Index (L./M.-~/Min.)

1 2 3 4 5 6 7 8 9 10 11 12

72 83 73 52 58 54 60 84 70 81 54 25

2.4 1.5 1.5 1.6 1.9 1.3 1A 1.5 1.3 0.8 0.8 0.6

13

90

**

Total* Peripheral Resistance (Dynes Sec./cm. ~)

Gammill et al. 1955 14 85 ** *Average normal TPR values in these cases are 1,400. **Only stroke volume reported: Patient 13, 43 ce.; Patient 14, 22 ***No data given.

1,300 2,450 2,100 1,200 1,280 1,360 2,080 2,480 2,160 3,900 3,400 1,600 1,432 2,367 CC.

Venous Pressure (rnm.H:O)

115 90 140 270 88 176 74 81 149 220 65 175 * ** ** *

212

~XIAX~,VELL j. BINDER TREAT.~IENT OF CORONARY StlOCK

The most significant advance in the treatment of severe coronary shock in recent years has been the use of potent vasopressor drugs. Thus, an evaluation of the levarterenol treatment in 131 patients with severe coronary shock r revealed that the mortality rate was lowered from 80 per cent to 60 per cent when this drug was used. However, the fact that three out of five patients with this syndrome still die indicates the need for other and more effective forms of therapy. The presence of severe chest pain may be directly related to tile development of shock in some patients with acute myocardial infarction. In such patients, relief of pain promptly relieves the shock and most of these patients survive. 4 Inasmuch as it has been shown that absorption from depot sites is delayed when shock is present, ~3 all analgesic agents should be given intravenously. Tim most effective are morphine in doses of 10 to 30 mg. or Dilandid in doses of 2 to 4 rag. Either drug is dissolved in 10 cc. of sterile water and given slowly. Too rapid intravenous injection may produce postural hypotension, particularly if the higher doses are used. 54 The early, administration of oxygen has helped to relieve shock in some patients. 55 It should be given at a rate of 6 to 8 liters per minute by means of a nasal catheter or a well-fitting face mask. When pulmonary edema is absent, positive pressure should be avoided because it interferes with venous return and thus leads to further decrease in cardiac output and a fall in blood pressure. Whether the patient should be placed in the "shock position" usually depends on the presence or absence of left ventricular failure. If pulmonary congestion and orthopnea are absent, the foot of the bed is elevated. If this position is not tolerated, the patient is allowed to lie fiat. On the other hand, if pulmonary edema is present, the head of the bed is elevated to the position of maximum comfort for the patient. If shock persists in spite of the above measures, vasopressor drugs are administered via an arm vein if possible or via the femoral vein if necessary. An indwelling urinary catheter is then inserted and the urine flow measured every 30 minutes. This is a simple and sensitive method for following the conrse 9of shock. A satisfactory response to treatment consists of a rise in systolic blood pressure to approximately 100 ram. Hg or more, a pulse pressure of 20 ram. Hg or more, clearing of the visible signs of shock and, in addition, a urinary output of at least x/~ cc. per minute. Unless the latter is obtained, the prognosis remains grave. Levarterenol (Levophed) is the most potent and most rapidly acting of the available vasopressor dr;~gs. 7 It is started in a concentration of 8 rag. per liter of 5 per cent glucose in water. The rate of administration and the concentration are quickly adjusted to obtain a satisfactory pressor response. The rate of flow is then maintained at 1,4 to I c e . per minute, depending on the urinary output. Upward adjustments in the amount of levarterenol infused per unit time are accomplished by increasing the concentration of

SttOCK IN ACUTE XIYOCAI1DIAL INFARCTION

0],~ ~

solution rather than tlle rate of flow. An), concentration of levarterenol solution necessary to produce a pressor effect may b~ nsed, but little added benefit is likely to be seen with concentrations above 24 rag. per liter. If levarterenol is required for more than a few hours, it is best given via a polyethylene catheter which has been inserted into an anteeubital vein and passed centrally as far as possible. Should extravasation of levarterenol solution occur, tissue sloughs may be prevented by tile prompt injection of liberal amounts of procaine hydrochloride solution into tile area. ffevarterenol sloughs may also be prevented by injecting phentolamine (Regitine) or piperoxan (Benodaine) in a concentration of 5 mg. ill 20 ce. of water into tile involved region. 5G-'~s When levarterenol is discontinued, it should be done gradually, for sudden withdrawal may result in a rapid fall in blood pressure. 13 Metaraminol (Aramine) is an effective vasopressor agent which has been reported to produce favorable results in coronary shock. ~9-61 When this drug is given intravenously, a pressor effect begins in 1 to 2 minutes, is maximal in 5 minutes and persists for 20 to 25 minutes. 62 Thus, while inetaraminol does not raise the blood pressure as promptly as levarterenol, its duration of action is considerably, longer. This permits greater ease of control of the blood pressure during prolonged inffaVenous infusion. In contrast to levarterenol, metaraminol does not cause local injury to tissue. 5~ It may therefore be given subcutaneously and intramuscularly as well as intravenously. In potency, 20 to 25 rag. of metaraminol are equivalent to 1 rag. of levarterenol. ~9 Metaraminol may be given intravenously in intermittent doses of 3 to 10 rag. or as a continuous infusion containing 100 to 500 nag. per liter of 5 per cent glucose in water. It may subsequently be given subcutaneously or intramuscularly in doses o f 3 to 25 mg. Metaraminol has much in its favor when prolonged vasopressor therapy is needed. Other vasopressor drugs that have been used for coronary shock are phenylephrine (Neosynephrine), c'a methoxamine (Vasoxyl) C* and mephentermine (Wyamine). ~ Phenylephrine has been used intravenously in doses of 2 to 7 mg. Methoxamine has been given intravenously in doses of 5 to 15 mg. or in an intravenous infusion containing 85 rag. per 250 ce. of 5 per cent glucose in water. Mephentermine has been administered intravenously in doses of 5 to 20 rag. or in intravenous infusion given at a rate of 1 rag. per minute. In our experience and those of others 14,G'~ none of these has been as etfeetive as levarterenol or metaraminol. Both of the latter drugs, as well as mephentermine, act directly on the myoeardiurn to increase its contractility; neither phenylephrine nor methoxamine do this',cc,c'9 In the absence of congestive heart failure, digitalis does not improve the effects of tile vasopressor drugs, r It is, however, indicated when flank congestive heart failure is added to coronary shock. Under these circumstances, it is best given intravenously in divided doses. An electrocardiographic strip is taken before each dose in order to detect early evidence of digitalis toxicity. Ouabain provides a means of rapid digitalization, starting with 0.5 rag. intravenously, followed by 0.1 nag. every hour until approximately 0.8 rng. is given. Lanatoside

214

~IAX~VELL J. BINDER

C ( C e d i l a n i d ) m a y be used if less rapid digitalization is desired, starting with 0.8 mg. intravenously, followed by 0.4 mg. at 2 hour intervals; the average digitalizing dose is 1.6 mg. Cardiac arrhythmias, particularly ventricular tachycardia, may contribute to the development and perpetuation of the shock syndrome. Their elimination is frequently necessary before shock can be relieved. This may, at times, be accomplished by vasopressor therapy alone. If ventricular tachycardia persists, it may be abolished by procaine amide (Pronestyl) given intravenously under electrocardiographic control. We have used ouabain intravenously when other measures failed and have, in a few patients been able to convert ventricular tachycardia to sinus rhythm with this drug. When marked sinus bradycardia complicates coronary shock, atropine sulfate given intravenously in doses of 1 mg. may increase the ventricular rate and may thus potentiate the effect of the vasopressor drugs. A similar effect may occur when isopropylarterenol (Isuprel) is used to treat complete heart block which persists during vasopressor therapy. Isopropylarterenol may be given intravenously in an infusion containing 1 mg. in 250 ce. of 5 per cent glucose in water, in intermittent doses of 0.02 to 0.04 mg., or it may be used sublingually in doses of 15 mg. Parenterally adhainistered steroids have been reported to alleviate complete heart block in two patients who lind acute myocardial infarction3 ~ We have also used thoracie epidural analgesia in patients with severe coronary shock who failed to respond to all other measures. This approach was based on tile hemodynamie data reported in experimental and clinical coronary shock and followed the demonstration that thoracic epidural analgesia potentiated the pressor effect of levarterenol in experimental coronary shock. While our experience with this procedure has been limited, it lms been encouraging. In three out of four patients so treated, the blood pressure rose to satisfactory levels even though tile dose of lew~rterenol was not changed. One of these patients survived. Figure 5 shows the early course of this patient, who remained in severe shock for 12 hours despite large doses of levarterenol as well as intravenously administered ouabain and hydrocortisone. Shock disappeared when epidural analgesia was instituted and reappeared when the analgesia wore off. Reinstitntion of epidural analgesia relieved shock and allowed reduction in the amonnt of levarterenol given. In contrast to these results, thoracic epidural analgesia did not potentiate the effect of levarterenol in patients in whom severe congestive heart failure and coronary shock coexisted. Other therapeutic measures for coronary shock have been disappointing. A mortality rate of 90 per cent was obtained in 59 patients treated ~vith intravenous transfusion r and one of 81 per cent was obtained in 42 patients treated with intra-arterial transfusion. 7 Disappointing results were obtained with corticosteroids by Grifflth et al. ~ and by Sampson. 14 Our results have been similar. Hydrocortisone, given intravenously to 15 patients at a rate of 100 mg. per 2 hours, failed to improve a poor response to levarterenol. Little information is available on the use of hypothermia in coronary shock, but our results with this procedure in four patients have not encouraged us to pursue it further.

SIIOCKIN ACUTE3,IYOCABDIALINFAItCTION CLN IC I ALsHoCK

F-

215

YES

,~176

)l X NOx~"YES~K NO

BLOOD eOj- ~

~

PRESSURE60' (mm.Hg.)40 1 II

~~

olu.

~

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

''~ "~80

/

150

\

40[ URINARYouTPUT 20I-~

~~. ~ . ~ ~ 2~04 0

AOJUNGTI THERAPYVE[

ouABAIN HYDROCORTISONE E,,~A

]

E~A

LEVOPHED {ixg./min.I 200f I

2 20 2

4

6

8

10

12

TIME(HOURS)

14

16

18

Fxc. 5.--Thoracic epidural analge~ (E A) in clinical coronary shock. SURIRfARY 1. Hemodynamie studies in experimental and clinical coronary shock indicate that the degree of reduction in cardiac output does not ahvays correlate with the occurrence of shock. When the coronary arteries of the closed-chest dog were embolized, the fall in cardiac output was approximately the same in those animals which developed shock and in those which did not. The two groups differed in the response of tile total peripheral resistance. When a compensatory rise in total peripheral resistance occurred, no shock resulted; when this rise failed to occur, shock was produced. These findings suggest that the development of experimental coronary shock is related to inhibition of homeostatic vasoconstrictor responses in the presence of a reduced cardiac output. While hormonal factors have not been ruled out, the available data suggest that this inhibition results from reflexes arising in the injured myocardium and that these reflexes fire carried by the afferent cardiac sympathetic fibers. The data reported on clinical coronary shock are consistent with the findings in the experimental animal. They indicate that patients with severe coronary shock fall into one of two groups: those patients in whom the reduction in cardiac output is so great that shock occurs in spite of marked vasoconstriction, and those patients with reduced cardiae output in whom homeostatie vasoconstriction does not occur. No data have been reported in lmmans or in the experimental animal to indicate that tlle total peripheral resistance falls appreciably in coronary shock or that congestive heart failure is necessary for tlle production of this type of shock. The development of coronary shock has been found to antecede any appreciable change in blood volume. 2. Vasopressor drugs, notably ]evarterenol and metaraminol, have reduced

216

~I~AXXVELL J. BINDEH

the mortality rate in severe c o r o n a r y shock from 80 per cent to tile present rate of 60 p e r cent. Tile relief of severe chest pain with intravenously infnsed analgesic agents a n d the earl), administration of oxygen h a v e at times resulted in the relief of c o r o n a r y sheck. T h o r a c i c epidural analgesia has given enc o u r a g i n g results in a few patients w h o failed to r e s p o n d to all other measures. T h e p r e s e n c e of congestive h e a r t failure, ventricnlar t a c h y c a r d i a or c o m p l e t e heart block m a y p e r p e t u a t e the shock s y n d r o m e and requires tile a p p r o p r i a t e therapy. D i s a p p o i n t i n g results have b e e n o b t a i n e d in severe c o r o n a r y shock with intravenous or intra-arterial transfusions, with intravenous infusion of corticosteroids a n d with h y p o t h e r m i a . REFERENCES 1. Rosenbaum, F. F. and Levine, S. A.: Prognostic value of various clinical and electrocardiographic features of acute myocardial infarction: immcdiate prognosis. Arch. Int. Med. 68:913, 1941. 2. Mintz, S. S. and Katz, L. N.: Recent lnyocardial infarction. Arch. Int. Sled. 80:205, 1947. 3. Epstein, F. H. and Relman, A. S.: Transfusion treatment of shock due to myocardial infarction. New England J. Med. 241:889, 19t9. 4. Seizer, A.: The hypotc~nsive.state following acute myocardial infarction. I. Am. Iteart J. 44:1, 1952. 5. ttellerstein, II. K., Brofinan, B. L., and Caskey, W. ti.: Shock accompanying myocardial infarction: treatment with pressor amines. Am. Ilcart J. 44:407, 1952. 6. Gritilth, G. C., Wallace, W. B., Cochran, B., Jr., Nerlich, W. E., and Frasher, W. G.: The treatment of shock associated with myocardial infarction. Circulation 9:527, 1954. 7. Binder, M. J., Ryan, J. A., Jr., Marcus, S., Muglcr, F., Jr., Strange, D. and Agress, (3. M.: Evahmtion of therapy in shock following acute myocardial infarction. Am. J. Med. 18:622, 1955. 8. Burchell, H. B.: Acute nonspecifie pericarditis. Slod. Concepts Cardiovascular Dis. 16: No. 3, 1947. 9. Witherbee, H. R., Jr. and Pearce, SI. L.: Shock and acute abdominal symptoms complicating acute idiopathic pericarditis. Ann. Int. Med. (in press). 1O. Galbraith, B. T. and Norman, S. L.: Dissecting anenrysm of the aorta. New England J. Sled. 250:670, 1954. 11. David, P., McPeak, E. M., Vivas-Salas, E., and White, P. D.: Dissecting aneurysm of the aorta. Ann. Int. Med. 27:405, 1947. 12. Zendel, J. F. and Paulin, C.: Prolonged shock in dissecting aortic ancnrysm. Arch. Int. Med. 98:106, 1956. 13. Agress, C. M. and Binder, M. J.: Cardiogcnic shock. Am. Heart J. 54:458, 1957. 14. Sampson, J. J.: Shock of cardiac origin. Mod. Concepts Cardiovascular Dis. 26:No. 3, 1957. 15. Hunter, R. B.: Puhnonary embolism. Brit..X.l.J. 1:1424, 1955. 16. Wolff, F. \V.: Shock due to pulntonary cnaholism. Lancet 2:72, 1954, 17. De Takats, G., Beck, W. C., and Fcnn, G. K.: Pnhnonary embolism; experimental and clinical study. Surgery 6:339, 1939. 18. Seizer, A. and Bradley, H. W.: Obserw~.tions concerning the origin of shock associated with acute cor pulmonale. Am. J. Sled. 22:163, 1957. 19. Fishberg, A. M., Hitzig, W. M., and King, F. H.: Circulatory dynamics in myocardial infarction. Arch. Int. Sled. 54:997, 1934. 20. : Heart Failure. Philadelphia, Lea and Febiger, 1940, ed. 2. 21. Boyer, N. H.: Cardiogenic shock. New England J. Med. 230:226, 256, 1944. 22. .: Digitalis in acute myocardial infarction. New England J. Med. 252:536, 1955.

SHOCK IN ACUTE ,~IYOCAItDIALINFARCTION

L9]-7

23. Samuelson, B.: Uber den einfluss tier coronar-arterien-versehliessung auf die herzaktlon. Ztschr. klin. Med. 2:12, 1881. 24. Manning, G. W., McEachern, C. G., and Hall, G. E.: Reflex coronary artery spasm following sudden occlusion of other coronary branches. Arch. Int. Med, 64:661, 1939. 25. Gross, L., Mendlowitz, hl., and Schauer, G.: Hcmodynamic studies in experinaental coronary occlusion. I. Open chest experiments. Am. Heart J. 13:647, 1937. 26. Mendlowitz, M., Schauer, G., and Gross, L.: ttemodynamie studies in experimental coronary occlusion. II. Closed chest experiments. Am. Heart J. 13:664, 1937. 27. Orias, O.: The dynamic changes in the ventricles following ligation of the taurus dcscendens anterior. Am. J. Physiol. 100:629, 1932. 28. Corday, E., Bergman, H. C., Schwartz, L. L., Spritzlcr, R. J., a n d Prinzmetal, hi.: Studies on the coronary circulation. IV. The effect of shock on the heart and its treatment. Am. Heart J. 37:560, 1949. 29. Wegria, R., Frank, C. W., Misrahy, G. A., Wang, H., Miller, R., and Case, R. B.: Immediate hemodynamic effects of acute coronary artery occlusion. Am. J. Physiol. 177:123, 1954. 30. Blumgart, H. L., Zoll, P. hi., Frecdbcrg, A. S., and Gilligan, D. R.: The experimental production of intercoronar), arterial anastomoses and their functional significance. Circulation 1:10, 1950. 31. Johnston, F, D., tlill, I. G. W., and Wilson, F. N.: The form of the electrocardiogram in experimental myocardial infarction. The early effects produced by ligation of the anterior descending branch of the I d t .coronary artery. Am. Iteart J. 10:889, 1935. 32. Bakos, A. C. P.: The question (;f the function o'f the right ventrlcular myocardium: an experimental study. Circulation 1:724, 1950. 33. Kagan, A.: Dynamie responses of tile right ventricle following extensive damage by cauterization. Circulation 5:816, 1952. 34. Starr, I., Jeffers, W. A., and Meade, R. H., Jr.: The absence of conspicuous increments of venous pressure after severe damage to the right ventricle of the dog, with a discussion of the relation between clinical congestive failure and heart disease. Am. Heart J. 26:291, 1943. 35. Eppinger, H. and Rothberger, C. J.: Zur analyse des elektrokardiogramms. Wien. klin. Wchnsclar. 22:1091, 1909. 36. Taylor, C. B., Davis, C. B., Jr., Vawter, G. F., and Hass, G. M.: Controlled myocardial injury produced by a hypothennal method. Circulation 3:239, 1951. 37. Lohman, A.: Uber die funktion der hruekenfasern die anstelle der grossen venen die fuhrung der herztatigkeit beim saugetiere zn ubernelnnen. Arch. f.d.ges. Physiol. 123: 628, 1908, 38. Meyers, F. H., Schoolar, J. C., and Overman, R. R.: Characteristics of shock following acute reduction of cardiac output in dogs. Circulation Res. 2:304, 1954. 39. Hamburger, W. W., Priest, W. S., and Bettman, R. B.: Experimental coronary embolism. Am. J. hi. Sc. 171:168, 1926. 40. Herrmann, G." and Decherd, G.: Creatine lnohilization in myocardial damage. Proe. Soc. Exper. Biol. & Med. 32:477, 1934. 41. Boos, A. and Smith, J. R.: Production of experimental heart failure in dogs with intact circulation. Am. J; Physiol. 153:558, 1948. 42. Agress, C. hl., Rosenburg, hi. J., Jacobs, tt. I., Binder, hi. J., Schneiderman, A., and Clark, W. G.: Protracted shock in the closed-chest dog following coronary embolization with graded microspheres. Am. J. Physiol. 170:536, 1952. ,13. , Glassner, H. F., Binder, hi. J., and Fields, J.: Hemodynamie measur6ments in experimental coronary shock. J. Appl. Physiol. I0:469, 1957. 44. ~Viggers, C. J.: Physiology of Shock. New York, Tile Commonwealth Fund, 1950. 45. Walcott, W. W.: Blood volume in experimental hemorrhagic shock. Am. J. Physiol. 143:247, 1945. ~46. Cournand, A., Riley, R. L., Bradley, S. E., Breed, E. S., Noble, R. P., Lauson, H. D.,

218

47. 48. 49. 50. 51.

52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66.

67.

68.

69.

70. 71.

,XIAX~,VELL ]. BINDER Gregersen, M. I., and Richards, D. W.: Studies of the circulation in clinical shock. Surgery 13:964, 1943. Freis, E. D., Sehnaper, tt. W., Johnson, R. L., and Schreiner, G. E.: Hemodynamie alterations in acute myocardial infarction. J. Clin. Invest. 31:131, 1952. Smith, ~V. W., Wikler, N. S., and Fox, A. C.: Hemodynamic studies of patients with myocardial infarction. Circulation 9:352, 1954. Agress, C. M., Rosenburg, M., Schneidenaaan, A., and Brotman, E. J.: Blood volume studies in shock resulting from myocardial infarction. J. Clin. Invest. 29:1267, 1950. Gilbert, R. P., Goldberg, M., and Griffin, J.: Circulatory clmnges in acute myocardial infarction. Circulation 9:847, 1954. Gammill, J. F., Applegarth, J. J., Reed, C. E., Fernald, J. D., and Antenucci, A. J.: Hemodynamic changes following acute myocardial infarction using the dye injection method for cardiac output determination. Ann. Int. Mcd. 43:100, 1955. Kohlstaedt, K. G. and Page, I. H.: Terminal hemorrhagic shock: circulatory dynamics, recognition and treatment. Surgery 16:430, 1944. Bauer, F. K.: Some observations on the peripheral circnlation in patients with myocardial infarction. Angiology 6:505, 1955. Altschule, M. D.: ttazards in the treatment of cardiac decompensation. New England J. Med. 248:493, 1953. Blumgart, 1t. L.: Treatment of acute myocardial infarction with particular reference to shock. J.A.M.A. 154:107, 1954. McGinn,.J.T., Schluger, J., and Di Gregorio, N. J.: Prevention of lewlrterenol sloughs: preliminary report. New York J. Mcd. 56:1950, 1956. Zucker, G.:Use of phentolamine to prevent necrosis due to levarterenol. J.A.M.A. 163: 1477, 1957. Pelner, L.: Treatment of local ischemia due to levarterenol (Levophed) leakage with piperoxan. J.A.M.A. 165:444, 1957. Moyer, J. H. and Beazley, H. L.: Effectiveness of Aramine in the treatment of shock. Am. Heart J. 50:136, 1955. Stechel, G. H., Fishman, S. I., Schwartz, G., Turkowitz, H., Madonia, P. F., and Fankhauser, A.: The use of Aramine in clinical shock. Circulation 13:834, 1956. Well, M. H.: Clinical studies on a vasopressor agent: mctaraminol (Aramine) II. Ohservations on its use in the management of shock. Am. J. M. Se. 230:357, 1955. : Current concepts on the management of shock. Circulation 16:1097, 1957. Gootnick, A. and Knox, F. H., Jr.: Management of shock in acute myocardial infarction. Circulation 7:511, 1953. Council on Pharmacy and Chemistry: Use of methoxamine hydrochloride in shock accompanying myocardial infarction. J.A.M.A. 159:1634, 1955. Oblath, R. W. and Griflith, G. C.: Complications of myocardial infarction. Postgrad Med. 14:531, 1953. Gazes, P. C., Goldberg, L. I., and Darh~', T. I).: Heart force effects of sympathomimetic amines as a basis for their use in shock accompanying myocardial infarction. Circulation 8:883, 1953. Sarnoff, S. J., Case, R. B., Bcrghmd, E., and Sarnoff, L. C.: Ventricular function. V. The circulatory effects of Aramine; mcclaanism of action of "vasopressor'" drugs in cardiogenic shock. Circulation 10:84, 1954. Denison, A. B., Jr., Bardhanabaedya, S., and Green, H. D.: Adrenergic drugs and blockade on coronary arterioles and myocardial contraction. Circulation Res. 4:653, 1956. Binion, J. T., Morgan, W. J., Jr., Welch, G. H., and Samoff, S. J.: Effect of sympathomimetie drugs in acute experimental cardiac tamponade. Circulation Res. 4:705, 1956. Prinzmetal, M. and Kennamer, R.: Emergency treatment of cardiac arrhythmias. J.A.M.A. 154:1049, 1954. Phelps, M. D., Jr. and Lindsay, J. D., Jr.: Cortisone in Stokes-Adams disease secondary to myocardial infarction. New England J. Med. 256:204, 1957.