Acute Coronary Insufficiency Due to Acute Hemorrhage:

Acute Coronary Insufficiency Due to Acute Hemorrhage:An Analysis of One Hundred and Three Cases

By ARTHUR M. MASTER, M.D., SiMoN DACK, M.1)., HENRY hORN, M.D.,BERNARD I. FREEDMAN, M.D., AND LEONARD E. FIELD, M.D

The occurrence of 59 cases of acute coronaiy insufficiency among 103 patients with acute hemor-

rhage, chiefly from the gastrointestinal tract, emphasizes the frequency and gravity of this gener-

ally unrecognized complication of bleeding. Clinical, electrocardiographic abncd anatomic manifes-tations of mvocardial ischemia and subendocardial necrosis are prone to appeal in previously(liseased hearts, although they may develop in otherwise normal hearts. Consequently, promptand adequate blood replacement is required in patients with coronary arteriosclerosis, enlargedhearts, valvular heart disease, etc. to prevent as *vell as to treat coronary insufficien(y secondary

to hemorlhage.

T HE CONCEPT of acute coronary in-

sufficiency has become well establishedon the basis of clinical and pathologic

observations.' 13 It has been shown that myo-

cardial ischemia results from a disproportionbetween the oxygen requirements of the myo-

cardium and the coronary blood flow, and isprovoked by factors which either increase thework of the heart, decrease coronary blood flowor decrease the quantity of oxygen carried bythe blood. When cardiac ischemia is severe or

protracted, myocardial necrosis may develop inthe absence of acute coronary occlusion. Thenecrosis following acute coronary insufficiencyis focal, disseminated an(l usually localized tothe subendocardial region of the left ventricle,especially within the papillary muscle. The elec-trocardiogram is characterized by the presence

of RS-T segment depression and T-wave inver-sion in one or more leads and often in all leads.These changes are usually transient and disap-pear rapidly following subsidence of the ische-mia. Deep Q waves and elevations of the RS-Tsegment almost never occur, thus differentiat-ing this condition from massive infarction dueto acute coronary artery occlusion."'The clinical factors which may lead to acute

coronary insufficiency have been enumeratedpreviously." We have found hemorrhage to beone of the most frequent and important precip-itating causes of acute coronary insufficiency.In a patient, whose coronary circulation is al-

From the Cardiograph e Department, _Mount SinaiHospital, New York, N. Y.

ready impaired by arteriosclerosis or by cardiachypertrophy, hemorrhage from any source of-fers dangerous potentialities. It is not suffi-ciently appreciated that bleeding is important,not only because of loss of an essential transportagent for oxygen and food but also because ofthe cardiac damage which may ensue.

MATERIAL AND RESULTS

This report is hase(1 on a clinical analysis of 193consecutive cases of mo(lerate or severe hemorrhageadmitted to the M\ount Sinai hospital. Includedin the senrs were those patients in whom evidencesof heniorrhage were considered to be of sufficientdegree to requite treatment ani(l from whom oneor more electrocardiogramis were made (uring thebout of hemorrhage.The gastrointestinal tract was the source of bleed-

ing in 95 patients, the uterus in 4, the plrostategland in 2, and a rupturedl aorta in 2. The mostcommon etiologic factor for massive gastrointestinalhemorrhage was peptic ulcer (64 cases). Less com-mnon causes were esophageal varices (10 cases),ulcerative colitis (8 cases) and hemorrhoids (8 cases).The clinical course of each patient was stu(lie(l

wvith particular regarl to the amount and rapi(lityof hemorrhage, hemoglobin level, heart rate, bloodpressure, presence of shock, and the electrocar(lio-graphic findings. The 103 cases were divided intotwo general groups. Group I consisted of 59 cases(57 per cent) with clinical or electrocar(liograplhicsigns of acute coronary insufficiency. Group II coin-prisedl 44 cases (43 per cent) with neither clinicdlnor cleetrocardiographic evidence of coronary in-sufficiency. Group I could be subdivided into 32cases with an electrocardiographic pattern of acutecoronaryl insufficiency but no clinical stigmata, 6cases with clinical findings of coronary insufficiencybut normal electrocardiograms and 21 inistanc(}s

1302

by guest on January 31, 2018http://circ.ahajournals.org/

Dow

nloaded from

http://circ.ahajournals.org/

MASTER, DACK, HORN, FREEDMAN, AND FIELD

with both clinical and electrocardiographic abnor-malities.

Twenty-two patients died of the effects of thehemorrhage; of these, 18 presented clinical or elec-trocardiographic signs of acute coronary insuffi-ciency. Four of the 13 autopsied cases presentedcardiae alterations characteristic of acute coronaryinsufficiency; namely, myocaidial necrosis in the ab-sence of recent coronary artery occlusion.

DISCUSSION

Clinical, Electrocardiographic and A natomicFeatures

Clinical Signs of Coronary Insufficiency. Clin-ical signs of acute coronary insufficiency werenoted in 27 patients, in 21 of whom acute elec-trocardiographic changes were observed. Theelectrocardiogram in the other 6 remained unal-tered. Precordial or substernal pain occurred in15 cases, congestive heart failure developed in8, and both pain and cardiac failure togetherappeared in 3 instances.The precordial pain often resembled that seen

in coronary artery disease. In 6 patients, severeprecordial pain in association with shock, tach-ycardia and drop in blood pressure which fol-lowed the hemorrhage closely simulated acutecoronary artery occlusion. Indeed, this diagno-xis was entertained not infrequently before itwas recognized that precordial pain could be amanifestation of acute coronary insufficiencyprecipitated by hemorrhage.

Heart failure during or following hemorrhagewas observed in 11 cases and was manifestedby dyspnea, pulmonary congestion or edema,peripheral venous engorgement and galloprhythm. Acute pulmonary edema of suddenonset was not uncommon and constituted stillanother feature which caused the clinical pic-ture to resemble that of acute coronary arteryocclusion.

Precordial pain and heart failure occurred,as a rule, in the patients with severe acute ane-mia or shock. The average hemoglobin level inthese cases was 44 per cent (Sahli), while theactual drop in hemoglobin averaged 37 per centfrom control levels. Similarly, shock, togetherwith a marked fall in blood pressure and tach-ycardia, occurred in over two-thirds of thepatients (69 per cent).The precordial pain and the heart failure

were generally transient, subsiding as the hem-orrhage ceased or was actively treated and asthe shock diminished and the blood hemoglobinrose toward normal levels, usually after one ormore transfusions. The response to treatmentwas particularly striking in several cases of re-current hemorrhage in which each bout of bloodloss had precipitated an episode of severe an-gina pectoris. It was significant that anginapectoris was absent or mild in the periods be-tween the occurrence of hemorrhage, and ineach instance subsided rapidly following activetreatment of the bleeding.

Electrocardiographic Findings. Significantacute changes in the electrocardiogram werepresent in 33 of the 103 patients. These con-sisted generally of flattening or inversion of theT wave, with or without depression of the lRS-Tsegment. Abnormal T waves alone aswere ob-served in 24 cases, ItS-T depression alone in 4and combined RS-T and T changes in 25 cases.The mortality rate of the 24 cases showing T-wave changes alone was only 17 per cent ascompared with a rate of 40 per cent in the 25patients who had presented 1{S-T depression inassociation with T-wave changes. It seems,therefore, that a combination of RS-T segmentdepression and T-wave inversion represents amore profound degree of coronary insufficiencythan a change in the T wave alone. There werebut 4 patients in whom changes were limited tothe I{S-T segment, and 3 of these patients died(fig. 1).The most common lead combinations show-

ing the RS-T and T wave changes were 1, 11and IV; l, 11 and III; and 1, 11,II, IVr; respec-tively. Abnormalities were disclosed most fre-quently in Leads I and II.The T-wave changes consisted of flattening

and partial or complete inversion. The 1RS-Tsegment was depressed from 0.5 to 2.0 milli-meters. RS-T elevation was observed infre-quently in Lead III but never in any of theother leads. Deep Q waves were also extremelyrare and developed in but 3 cases. Occasionallya deep Q wave was present prior to the episodeof hemorrhage, and was the result of infarctiondue to a former coronary artery occlusion. Therelative rarity of RS-T elevation and deep Qwlaves was of aid in differentiating the electro-

1303


Dow

nloaded from


CORONARY INSUFFICIENCY DUE TO HEMORRHAGE

cardiogram of acute coronary insufficiencyfrom that of myocardial infarction due to acutecoronary artery occlusion.

Influence of Sex and Age. The series included78 men and 25 women. Forty-one of the former(53 per cent) and 18 of the latter (72 per cent)developed evidence of acute coronary insuffi-ciency. The mortality rate in each sex groupwas exactly the same.The ages of the patients with hemorrhage who

developed acute coronary insufficiency variedgreatly (from 18 to 79 years). Similarly, the

I

II

in

IY

FIG. 1-L. F., a man of 54 years with no antecedentcardiac disease. Profuse gastrointestinal bleedingproduced shock, severe acute coronary insufficiency,myocardial ischemia and death. The electrocardio-gram the first day of the hemorrhage disclosedpronounced RS-T depressions in all leads; no digitalishad been given.

ages of those without coronary insufficiencyranged from 22 to 89 years. It appeared thatage itself did not significantly influence the in-cidence of acute coronary insufficiency in thisseries. Acute coronary insufficiency developed,not infrequently, in the very young if the hem-orrhage was sufficiently severe or protracted.Thus, one instance of myocardial necrosis was

observed in a girl of 19 in whom the coronaryarteries were perfectly normal. On the otherhand, some of the elderly patients presentedno significant signs of coronary insufficiencyeven after fairly severe hemorrhage. The aver-

age age of the men who developed coronary

insufficiency was 52, and that of the women was45 years.

Antecedent Cardiac Disease. Antecedent car-diovascular disease proved to be a more sig-nificant factor than age in the occurrence ofcoronary insufficiency following hemorrhage.Thirty-eight of the 103 patients presentedclinical or electrocardiographic evidence of pre-vious cardiovascular disease, generally of the hy-pertensive or arteriosclerotic variety. Seventy-one per cent of these 38 patients developedacute coronary insufficiency as compared withan incidence of 49 per cent in the group withoutpreceding cardiovascular disease. Further anal-ysis revealed that the association of antecedentcardiovascular disease was approximately twiceas great in the coronary insufficiency group(47 and 25 per cent, respectively). These ob-servations indicate that chronic coronary in-sufficiency incident to coronary arteriosclerosisor cardiac hypertrophy renders the heart morevulnerable to the hemodynamic effects of hem-orrhage.

Blood Hemoglobin Level. The blood hemoglo-bin concentration at the time that the clinicalor electrocardiographic signs of coronary in-sufficiency had developed were tabulated andthe actual decrease in hemoglobin determinedby comparison with the level prior to the hem-orrhage or following recovery. The averagehemoglobin concentration for the group withevidence of coronary insufficiency was 54 percent of normal (Sahli). That of the noncoronaryinsufficiency group was 63 per cent. When onlythose cases were considered in which symptomsof coronary insufficiency had developed, theaverage hemoglobin level was found to havebeen 44 per cent of normal. The number ofpatients who had sustained a drop in hemoglo-bin level of 20 to 30 per cent or more was dis-tinctly greater in the coronary insufficiencygroup. Conversely, it was found that when thehemoglobin level had decreased 30 per cent ormore, acute coronary insufficiency appeared infour-fifths of the patients.

In general, therefore, acute coronary insuffi-ciency occurred when the hemorrhage effecteda significant drop in blood hemoglobin. Never-theless, acute coronary insufficiency was noted,not infrequently, before any significant anemia

1304


Dow

nloaded from


MASTER, DACK, HORN, FREEDMAN. AND FIELD

had developed and, occasionally, even if suchhad never appeared. Thus, severe precordialpain associated with acute electrocardiographicchanges occurred in 3 patients whose hemo-globin level dropped only 10 per cent or less.In these patients the hemoglobin level mightnot have been an accurate measure of the se-verity of hemorrhage because of hemoconcen-tration. It is evident, accordingly, that acuteanemia is an important but not an essentialforce for the production of acute coronary in-sufficiency in hemorrhage. In the absence ofanemia, the factors of shock, drop in bloodpressure and tachycardia take on additionalimportance in precipitating coronary insuffi-ciency.The electrocardiogram seemed to be a sensi-

tive indicator of the intensity of bleeding. Al-terations in the electrocardiogram often werenoted long before clinical manifestations of coro-nary insufficiency appeared and in some caseseven when other clinical signs were wanting.

Blood Pressitre. The average fall in bloodpressure at the time the electrocardiogram wasobtained was 27 mm. Hg in the coronary in-sufficiency group as contrasted with only 9 mm.in the group without signs of coronary insuffi-ciencv. Further, one-third of the former hadshown a drop in blood pressure of 40 mm. ormore as compared with only 5 per cent of thelatter group. A significant drop in blood pres-sure following a bleeding episode proved to bean important precipitating factor of coronaryinsufficiency. This belief is supported by theobservation that the incidence of coronary in-sufficiency was 84 per cent when the bloodpressure fell 20 mm. or more and 90 per centwhen the fall was 40 mm. or more. A drop inblood pressure was thus directly related to thepresence of coronary insufficiency as indicatedby electrocardiograms and by clinical signs.

Tachycardia. Tachycardia of 100 beats ormore per minute was noted in 52 per cent of thepatients with coronary insufficiency and in only14 per cent of the other group. Conversely, 82per cent of the patients with heart rates of 100or more manifested stigmata of coronary in-sufficiency. Evidence of coronary insufficiencywas noted in the 10 instances (17 per cent of thegroup) in which the heart rate rose to 125 or

more. Such a rapid rate never occurred in thosepatients without signs of myocardial ischemia.

In the coronary insufficiency group, tachy-cardia generally accompanied a marked dropin blood pressure. Although tachycardia repre-sents a compensatory mechanism for the main-tenance of cardiac output following blood pres-sure fall, the combination of hypotension andtachycardia apparently led more readily to thedevelopment of coronary insufficiency.

Shock. Clinical manifestations of shock (syn-cope, prostration, feeble pulse, clammy skin,etc.) were observed in 38 per cent of the coro-nary insufficiency group but only in 20 per centof Group II. The incidence of shock was foundto be as high as 69 per cent in the 27 patientswith signs of coronary insufficiency. Moreover,of the 43 patients who developed signs of shock,79 per cent manifested myocardial ischemia.These figures emphasize the close relationshipbetween shock and coronary insufficiency fol-lowing hemorrhage. The coexistence of a fallin blood pressure and tachycardia was notedfrequently in the majority of patients withshock. As one would expect, shock was morecommon in the patients with coronary insuffi-ciency who succumbed (82 per cent) than inthose who recovered (48 per cent).

In summary it can be said that a fall in bloodhemoglobin and blood pressure, tachycardiaand shock are all significant forces in precipi-tating coronary insufficiency following hemor-rhage. When the bleeding episodes were accom-panied by any one or more of these clinicalfindings, acute coronary insufficiency devel-oped in at least four out of every five cases.

A typical example of coronary insufficiencyeis illustrated in the following case.

Case 2. H. C., a 38 year old mnan with a duo-denal ulcer, was hospitalized because of a moderategastrointestinal hemorrhage of two weeks' (luratioin.For one week prior to entry he had experiencedclysl)nea and squeezing precordial pain which hadradiated to the left shoulder and arm following exei-tion. Hypertension had been present for eight yearswith no diminution of cardiae reserve; blood pies-sure varied between 150-170 nmim. systolic anld 100-1 10 mm. Hg diastolic.Upon admission, July 19, 1941, there was no

shock, tachycardia or fall in blood pressure. Thehemoglobin level was 65 pel cent. The electiocaid(lio-

130.


Dow

nloaded from



gram (fig. 2), July 21, showed inversion of the Twave in Leads I, II, and III. With cessation of thebleeding and as the hemoglobin level rose, anginapectoris disappeared and the electrocardiogramshowed a gradual return to normal. On July 23 thehemoglobin was 74 per cent; the electrocardiogramdisclosed the T wave to be low in Leads I and IIand upright in Lead III. On July 28, the hemo-globin was 78 per cent while the electrocardiographicpattern was normal. Subsequent to discharge fromthe hospital, the 2-step test electrocardiogram wasalso normal.

sufficiency due to other causes.'4 The degree ofmorphologic changes depends upon the severityand rapidity of the hemorrhage and the natureof the underlying predisposing factors.'3 Fol-lowing acute severe hemorrhage, the myocar-dium of patients with coronary arteriosclerosis,cardiac hypertrophy or aortic valvular disease,for example, will be more seriously affectedthan that of a patient with no previous heartdisease. The rate of blood loss, duration of the

FIG. 2.-H. C., a man of 38 years. Transient anginal syndrome and acute coronary insufficiencyduring gastro-intestinal hemorrhage. Hemoglobin fell only to 65 per cent. Upon admission to hospital,July 21, 1941, the T wave in Leads I, II, and III was inverted; normal within a week.

Comment: A case of acute coronary insuffi-ciency with clinical and electrocardiographicmanifestations occurring in a hypertensive manduring the course of a moderately severe andprotracted gastrointestinal hemorrhage. Fol-lowing treatment of the anemia, there was rapiddisappearance of angina pectoris and restora-tion of the electrocardiogram to normal.Anatomic Findings. The myocardium in pa-

tients with coronary insufficiency due to acuteblood loss presents a pathologic picture similarto that seen in instances of acute coronary in-

anemia, degree of associated shock, work of theheart, and other factors previously discussed,directly influence the alterations in the cardiacmusculature.The myocardial ischemia that occurs after

acute blood loss, however, may be mild andtransient, and anatomic lesions entirely absent.In more protracted instances, on the otherhand, focal subendocardial microscopic lesionsbecome apparent. These may vary from tinc-torial changes in the muscle fibers, loss ofstriations, smudginess of fibrillar outline and

1306


Dow

nloaded from



nuclear degeneration to actual necrosis withreactive cellular infiltration. Finally, in themost pronounced cases, confluent zones of sub-endocardial necrosis are grossly recognizable.

Thirteen cases came to autopsy, but only7 hearts were available for re-examination bythe writers. These included all 4 positive cases

and 3 of the negative cases. All grossly visiblecoronary arteries were studied by transversesections at intervals of 2 to 3 mm. In no in-stance was an acute coronary artery occlusionfound. Microscopic studies were made routinelyfrom all representative portions of heart wall;namely, anterior, posterior and lateral walls,septum, apex, anterior and posterior papillarymuscles of the left ventricle, anterior and pos-

terior walls of the right ventricle, and auricleswhen indicated. In addition, any area disclosingdiscoloration or mottling was examined histo-logically.The variety of cardiac lesions may be noted

in the following illustrative cases.

Case 3. H. S., a 67 year old woman with clini-cally recognized aortic stenosis presented the mostextensive myocardial changes we have observed, inthe absence of an acute coronary artery occlusion,following gastrointestinal hemorrhage. Since 1940the patient had experienced angina pectoris pre-cipitated by repeated bouts of gastrointestinal hem-orrhage. During these periods the blood hemoglobinlevel dropped to 40-50 per cent, and the electro-cardiogram would disclose plronounce(l RS-T seg-ment depression and T-wave inversion (fig. 3, A).When the hemoglobin rose above 60 per cent follow-ing therapy, the angina pectoris subsided and theelectrocardiogram would improve. The patient was

again hospitalized on November 1, 1942, because ofgastrointestinal bleeding for eight days and pie-cordial pain for four days. Her blood pressure uponentry was 90/60, pulse mate 120 and hemoglobin 42per cent. On the following (lay she suddenly (level-oped the clinical picture of shock an(l pulmonaryedema and died. The electrocardiogram disclosed a

sul)raventricular tachycardia of 170; marked RS-Tdepression in Leads 1, II and IV; and a deep Q3.

Cardiac Findings: The heart weighed 575 gramsand was dilated. The left ventricle was moderatelyhypertrophied. Widespread necrosis was notedgrossly in all portions of the left ventricle, includingthe papillary muscles. The zone of necrosis involvedthe inner third of the thickness of the ventricularwall, while the outer two-thirds of the wall, includ-ing the epicardium, were intact. The endocardiumitself appearled normal, and no mural thrombi were

observed. The affected areas disclosed yellowish

mottling with scattered red foci, the latter especiallynoticeable within the septum and posterior wall.The right ventricle showed merely slight fatty in-filtration.The aortic valve was rigidly thickened, irregularly

nodular and calcified; the aortic orifice severelystenotic. The mitral valve leaflets were moderatelythickened; the mitral ring was markedly calcified.The coronary ostia were patent. The left circumflexcoronary artery and its branches to the anterior leftventricle were moderately narrowed by arterioscle-rotic plaques, while the remaining major branchesof the coronary arteries disclosed only slight muralthickening. Detailed transverse sectioning of theentire coronary artery tree revealed no evidence ofeither a recent or old occlusion.

The microscopic picture was similar in all the in-vxolved regions (fig. 3, B). The endoctardium wasunaltered. Disseminated focal and often confluentareas of myonecrosis were present in the subendo-cardial layer, among which many islands of normalheart muscle remained. Frequently a very thinstrip of uninvolved muscle was interposed betweenthe endocardium and the zone of mvonecrosis. Thealtered portions of myocardium disclosed hemogeni-zation, loss of striations, tinctorial changes, karyol-ysis, loss of nuclei, and conspicuous necrosis ofmuscle fibers. Interspersed were foci of hemorrhageand scattered cellular infiltrates consisting of poly-morphonuclear leukocytes, lymphocytes and histio-cvtes.The anatomic diagnoses were: acute, widespread,

focal and confluent subendocardial necrosis of leftventricle; inactive rheumatic aortic and mitral val-vulitis with severe aortic stenosis and moderateinitral stenosis and insufficiency; moderate coronaryarteriosclerosis with narrowing of the lumen.

Comment: A patient in whom angina pec-toris occurred during episodes of gastrointes-tinal bleeding developed extensive subendo-cardial necrosis of the myocardium. Rheumaticcardiovalvular disease, as well as coronary arte-riosclerosis, acted as predisposing factors.Hemorrhage, with resulting hypotension, tach-yeardia and shock, occurred and precipitatedacute coronary insufficiency.

Case 4. S. S., a 60 year old man was observedin two bouts of severe hematemesis due to a chronicpeptic ulcer. The first episode occurred on Septemn-ber 10, 1945, and was accompanied by shock, ablood pressure of 80/40, pulse rate of 120, poorheart sounds and hemoglobin of 30 per cent. Theelectrocardiogram on the day after admissioni showedsemi-inversion of the T wave in Leads I and IV.On September 19, following several transfusions,the tracing was normal. In the second bout of hem-orrhage, which took place on January 17, 1946,

1307


Dow

nloaded from


FIG. 3A

FIG. 3B1308


Dow

nloaded from



there was shock with a blood pressure of 90/50,tachycardia, poor heart sounds and a hemoglobinof 23 per cent. An electrocardiogram on January 21revealed a low T wave in Lead I (fig. 4). On January

Slight hypertrophy of the left and slight dilatationof both ventricles were noted but there were nogross myocardial changes. Moderate thickening ofthe mitral and tricuspid leaflets and slight thicken-

FIG. 4.-S. S., a man of 60 years with two bouts of hematemesis resulting from peptic ulcer. Atautopsy, moderate coronary arteriosclerosis and acute, focal, subendocardial necrosis in both papil-lary muscles and posterior wall of left ventricle. On September 11, 1945, the hemoglobin was 30 per

cent; the electrocardiogram disclosed inversion of the T wave in Leads I and IV. Following trans-fusions, clinical recovery and normal electrocardiogram resulted. On January 21, 1946, followinghematemesis with shock and hemoglobin of 23 per cent, the electrocardiogram showed the T wave

low inr ]Leads I and IV. Five days later, the patient experienced agonizing substernal pain, and theRS-T segment was depressed in Lead IV; death followed.

26 the patient developed agonizing substernal pain,dyspnea, cyanosis and severe shock and died withinseveral hours. Electrocardiograms during this epi-sode disclosed depression of the RS-T segment inLead IV.

Cardiac Findings: The heart weighed 450 grams.

ing of the aortic cusps were present. The coronaryostia were patent. Slight to moderate arteriosclerosiswas noted in the greater portion of the coronaryartery tree. However, no narrowing of the lumenwas evident; in fact, the lumen of the anterior de-scending branch of the left coronary artery was

FIG. 3.-H. S., a 67 year old woman with antecedent aortic and mitral valve disease, as well ascoronary artery disease. Recurrent episodes of gastrointestinal bleeding precipitated seizures ofangina pectoris. Extensive subendocardial myocardial necrosis of left ventricle at autopsy.

A. (Top) Electrocardiograms during the bouts of bleeding disclosed RS-T depressions and T-waveinversions in Leads I and II. During the second hemorrhage the T wave in Lead III and, duringthe third attack, in Lead IV, was, in addition, transiently inverted. The final episode of hemorrhageproduced a supraventricular tachycardia, marked depressions of RS-T segment in Leads I, II, andIV and large Q wave in Lead III.

B. (Bottom) Photomicrograph of section from left ventricle. Subendocardial layer revealed dis-seminated focal and often confluent areas of acute myonecrosis. Occasionally a thin strip of unin-volved muscle was present immediately beneath the endocardium, interposed between the intactendocardium and the involved muscle. Homogenization, loss of striation, tinctorial changes, lossof nuclei, profound necrosis of muscle fibers, scattered hemorrhages and reactive cellular infiltra-tion were observed.

1309


Dow

nloaded from



dilated, as occasionally occurs despite the presenceof arteriosclerotic plaques.l5

Histologic changes were pronounced in scatteredportions. The involved areas were focal and limitedto the papillary muscles and subendocardial regionof the posteriorIwall of the left ventricle. Theseconsisted of tinctorial alterations, loss of striation,hemogenization and necrosis of myocardial fibers,together with a reactive infiltration composed prin-cipally of polymorphonuclear leukocytes.

III

Ivu-l..

matic valvular disease were predisposing fac-tors to coronary insufficiency while severebleeding, hypotension and shock constitutedthe precipitating mechanisms.

Case 5.-T. L., a 19 year old housewife withmoderate rectal bleeding for two months due toulcerative colitis, had had fever of 101 to 105 F. forthree weeks, and a spontaneous miscarriage with

FIG. 5.-T. L., a 19 year old woman with ulcerative colitis and intestinal bleeding. Followingmassive hemorrhage, death occurred. The heart was not enlarged; the coronary arteries werenormal; there was focal, acute myonecrosis of anterior and posterior walls and papillary muscles ofleft ventricle. The electrocardiogram disclosed depression of RS-T segment in Leads I, II, and IIIand low T waves in all leads.

The anatomic diagnoses were: acute, focal, sub-endocardial mvonecrosis of posterior wall and papil-larv muscles of the left ventricle; focal myofibrosis;coronary arteriosclerosis without narrowing; inac-tive, moderate rheumatic valvulitis of the mitral,aortic and tricuspid valves.

Comment: Although the clinical picture dur-ing periods of severe gastrointestinal hemor-rhage suggested acute coronary artery occlu-sion, the electrocardiograms were consideredcharacteristic of acute coronary insufficiency.This impression was confirmed at autopsy bythe presence of microscopic areas of focal, acutemyonecrosis in the absence of acute coronary

occlusion. Coronary arteriosclerosis and rheu-

moderate uterine hemorrhage one week prior to ad-mission. She was disoriented, semistuporous andpale. The pulse rate was 128; respiratory rate variedfrom 30 to 40. The systolic blood pressure was 130;the diastolic could not be determined. The heartwas not enlarged, the sounds were forceful, therhythm regular; an apical presystolic gallop and aprecordial systolic murmur were audible. Bilateralbasal pulmonary raMes were heard. The hemoglobinw-as 14 per cent, red blood cell count 885,000 percu. mm., and leukocyte count 23,700 per cu. mm.of which 69 per cent were neutrophiles. The electro-cardiogram (fig. 5) showed a depressed RS-T seg-ment in Leads I, II and III and flattened T wavesin all leads. The patient improved slowly followingtransfusions; the hemoglobin rose to 32 per cent.However, one week after admission she suddenlypassed numerous tarry stools and succumbed.

1310


Dow

nloaded from



At autopsy, the heart weighed 225 grams. Beneaththe endocardium of the trabeculae carneae andwithin the papillary muscles of the left ventriclewere pale yellow streaks, while on section scatteredareas of the musculature showed similar involve-ment. MXlicroscopically, minute disseminated areasof ischemic change were noted within the subendo-cardial layers of the anterior and posterior wallsof the left ventricle and within the papillary muscles.These were focal, pin-point areas of myocardial de-generation consisting of disappearance of nuclei, ob-scuration of myofibril outlines, foci of hemorrhage,necrosis and reactive acute and subacute inflamma-tion.

Comment: Massive intestinal hemorrhage ina 19 year old girl suffering from anemia second-ary to ulcerative colitis, resulted in focal myo-necrosis in the wall of the left ventricle in thepresence of normal coronary arteries and anotherwise normal heart.Physiologic and Biochemical Considerations

It is pertinent to consider briefly the physio-logic effects of hemorrhage upon the coronarycirculation. Moderate blood loss causes a dimi-nution in cardiac output, arterial blood pres-sure, circulating blood volume and venousreturn to the heart. These constitute the initiat-ing factors in the vascular readjustmentsfollowing acute hemorrhage.'6-24 These altera-tions effect the vasopressor reflex, which in turnproduces compensatory peripheral vasocon-striction, accelerates heart rate and tends toreturn blood pressure to normal. It is signifi-cant, however, that following the initial stageof reduced cardiac output and lowered bloodpressure, a compensatory increase in cardiacoutput often occurs despite a decreased bloodvolume.25 This mechanism helps deliver a nor-mal oxygen supply to the peripheral tissues byincreasing circulation rate and oxygen utiliza-tion. It has been well established on clinicaland experimental grounds that uncomplicated,severe hemorrhage may also produce astate of shock similar to that due to othercauses.17, 19, 26-28

Vasoconstriction generally is beneficial, helpsmaintain blood pressure and effect an adequateblood flow to vital organs.22' 29 , 30 The questionwhether the coronary arteries participate in thegeneralized reflex vasoconstriction is of clinicalimportance. To such a possibility has beenascribed the development of acute coronary

insufficiency as evidenced by electrocardio-graphic abnormalities, particularly followinghemorrhage from the gastrointestinal tract.", 32However, conclusive proof of such effect hasnot been adduced experimentally.

In continued bleeding all compensatory re-adjustments ultimately fail, the cardiac outputis reduced strikingly with resultant irreparabledamage to the cerebral vasomotor centers andcardiac muscle, and irreversible shock super-venes.That the state of the myocardium contrib-

utes significantly to recovery from shock hasbeen re-emphasized by Wiggers33- swho hassuggested that myocardial impairment ratherthan peripheral circulatory failure was respon-sible for the state of irreversible shock followinghemorrhage. Lawson and Rehm36 have shownthat when hemodilution has occurred in theterminal phases of post-hemorrhagic shock, theblood volume and venous pressure may be in-creased and the heart dilated, denoting myo-cardial damage and failure. Kohlstaedt andPage20 considered that cardiac dilatation is thecritical point at which irreversible changes ap-pear following hemorrhage, for up to this pointinfusion was therapeutically successful in theiranimals. In view of these observations, it wouldappear that the heart muscle is particularlysusceptible to change in the presence of hemor-rhagic shock and, in turn, exerts considerableinfluence in recovery.An important consideration in a study of the

effect of hemorrhage on the circulation is thequantity and rapidity of blood loss. It has beendemonstrated that in the normal, average-sizedman no serious effects appear if the hemorrhageis less than 30 per cent of the blood volume orless than 3 per cent of the body weight, i.e.,less than 1,500 cc. of blood.'8' 22, 23, 37 On theother hand, in patients with organic heart dis-ease, pulmonary disease, chronic anemia, etc., aloss of even 500 cc. of blood is tolerated poorly.The amount of blood loss, furthermore, hasbeen related to electrocardiographic changes.Thus, Scherf and Klotz32 found no electrocar-diographic abnormalities in two normal personsfrom whom 850 cc. and 400 cc. of blood, respec-tively, had been withdrawn. However, loss ofeven smaller quantities of blood proved to be

1311


Dow

nloaded from


CORONARY INSUFFICIENCY DUE TO HEMORRHAGIE

very significant in the presence of coronaryartery disease or other factors predisposing tocoronary insufficiency.The rapidity of the fall may be of greater

significance than the actual decrease in hemo-globin. In patients with chronic anemia whoremain at rest, for example, the hemoglobinmay fall to very low levels without producingevidences of coronary insufficiency. The com-pensatory mechanisms usually suffice to main-tain normal coronary blood flow at rest. Inactive hemorrhage, on the other hand, if thehemoglobin concentration rapidly decreases 20per cent or more, acute electrocardiographicchanges frequently appear and occasionally an-atomic myocardial alterations occur.

Biochemical studies following hemorrhagehave yielded evidence of marked disturbancesin tissue metabolism, involving electrolyte pat-terns and acid-base balance, with deleteriouseffects upon the coronary circulation and myo-cardium.9' 38 4)2 In posthemorrhage shock thereis also a striking reduction in tissue oxygen con-sumption, a mechanism which may be as im-portant a cause of tissue anoxia as the reducedblood flow.11

Clinical Observations of Coronary Insufficiencyand Myocardial Involvement following Hemor-rhage

As long ago as 1842, Hall44 wrote: "Hemor-rhage not only induces syncope, but occasion-ally sudden death, due to interruption of thecoronary blood supply.... Impaired coronarycirculation may arise from impeded flow ofblood through arteries contracted by ossifica-tion, or impeded by adipose substances...orfrom an insufficient condition of blood itself incases of hemorrhage and anemia."The significance of the relationship between

hemorrhage and cardiac sequelae, first sugges-ted by Hall, was not generally recognized untilthe 1930's, when Dietrich and Schwiegk,iBiichner,5 and Goldenberg and Rothberger45showed that anoxemia constituted an impor-tant precipitating cause of acute coronaryinsufficiency. Hicks46 later demonstrated thatcardiac muscle, unlike skeletal muscle, is unableto go into temporary oxygen debt when thecoronary circulation is impaired. Since that

time the importance of cardiac muscle damagefollowing blood loss has been emphasized re-peatedly by investigators abroad and in thiscountry."' -8, 13 Friedberg and Horn' foundhemorrhage to be responsible for myocardialnecrosis in 2 of their 34 cases of myocardialinfarction without coronary artery occlusionand offered the opinion that the factor of shockwas most important. MWaster, Jaffe and Dack47described an instance of extensive myocardialinfarction following severe gastrointestinalhemorrhage. Similar experiences were reportedby Bean,48 Gross and Sternberg,7 McLaughlin,Baker and Sharpe,49 and _Master, Gubner, Dackand Jaffe.9 On the basis of these and his ownobservations, Master50 emphasized the impor-tance of hemorrhage as a cardiac emergencyand urged early and repeated transfusions toforestall the development of coronary insuffi-ciency. Additional clinical reports have ap-peared more recently.dl-57The belief that hemorrhage exerts an impor-

tant deleterious effect upon the myocardium isfortified by the clinical observations that heartfailure either may be induced or worsened byhemorrhage.9' 13, 7 7 Heart failure was precip-itated in 10 per cent of the cases included inthis report. These observations emphasize thefact that hemorrhage is dangerous in patientswith heart disease, and is of especially seriousomen in those already in cardiac failure. Hereboth the cardiac failure and hemorrhage de-mand energetic treatment.

Electrocardiographic ConsiderationsThe Electrocardiogram and Experimentally

Induced Coronary Insufficiency. A number ofobservers3-5 58-62 have reported that, followingsevere or repeated bleeding of normal dogs andrabbits, flattening and inversion of the T wavesand depression of the RS-T segments appeared.Tachycardia often developed. These changeswere found similar to those observed in manduring an attack of angina pectoris and in in-duced anoxemia." 58, 59 62 Presumably both di-minished coronary flow and anoxemia mightbe responsible for the abnormal electrocardio-gram following experimental bleeding in ani-mals.

Electrocardiographic Changes duer to S ubendo-

1312


Dow

nloaded from



,cardial Involvement. In acute coronary insuffi-ciency due to any cause, proof has been estab-lished of the relationship of the characteristicelectrocardiographic changes, i.e., RS-T de-pressions and T-wave inversions, to localizationof the myocardial necrosis within the subendo-cardium and papillary muscles.2'3 9 ,31 32, 63-72Pruitt, Barnes and Essex,7' and Pruitt andVTalencia72 described RS-T depression associatedwith experimentally produced lesions in thesubendocardium of animals. Scherf and his col-leagues3" 32 reported transient T-wave and RS-*T changes in cases of profuse gastric hemor-rhage, which they attributed to reflex coronaryartery spasm. The occurrence of focal necrosislimited to the subendocardium and papillarymuscle was postulated since the electrocardio-graphic patterns resembled those produced byexperimental injury to the inner surface of theheart.64 These investigators observed that themore acute the loss of blood, the more markedwere the electrocardiographic changes. It wastheir belief, moreover, that the electrocardio-graphic changes after acute hemorrhage werelimited usually to the T wave and that only insevere cases did depression of the RS-T segmentoccur. They showed, further, that RS-T seg-ment depression is regularly observed whenanoxemia of the myocardium is widespread.Oerning, Sommerfelt and Fredriksen73 describedT-wave changes and RS-T depressions in morethan one-third of their 74 patients in whomhemorrhage had occurred and thought that theelectrocardiographic alterations were due tovasomotor reflexes affecting the coronary circu-lation and the myocardial anoxemia which fol-lowed. Our studies confirm the belief that theabnormal electrocardiographic pattern is due,primarily, to the involvement of the subendo-cardial region of the left ventricle.The electrocardiogram may afford sensitive

and objective evidence of coronary insuffi-ciency. Alterations in the T wave appear readilyfollowing blood loss in bed patients, and itappears that especially when RS-T depressionsco-exist, the presence of acute coronary insuffi-ciency is to be assumed whether or not clinicalsigns have been detected. We have observedpatients showing RS-T segment depressionswho gave no other indication of cardiac impair-

ment and, yet, in whom an unusual physicaleffort induced myocardial collapse.

Additional details of our electrocardiographicfindings will be reported subsequently. How-ever, one observation seems worthy of commenthere. Although T-wave inversion and depres-sion of the RS-T segment are characteristic ofthe electrocardiogram following hemorrhage,as in other forms of acute coronary insuffi-ciency, in 3 instances a deep Q wave ultimatelyappeared. These patients died. Permission foran autopsy examination was obtained in onecase only (Case 3); widespread subendocardialnecrosis was found in the absence of a recentartery occlusion. On the basis of this and otherexperiences, it is reasonable to assume thatthe coronary circulation had been reduced tosuch a degree previously that widespread myo-cardial necrosis followed the massive hemor-rhage, and was responsible for the appearanceof large Q waves in the electrocardiogram.In bleeding patients, the development of largeQ waves in a tracing hitherto distinguishedonly by the presence of RS-T depression andT-wave inversions may signify extensive myo-cardial necrosis and antecedent heart disease.

Active therapeutic measures are indicatedas soon as T-wave or RS-T segment alterationsappear in the electrocardiogram. In our opiniona progressive decrease in amplitude of the Twave is sufficient proof that the loss of bloodhas produced a harmful effect upon the myo-cardium.

TherapyThe treatment for hemorrhage is, of course,

adequate blood transfusion. Whole bloodshould be given especially early to those pa-tients in whom a predisposing factor of coro-nary insufficiency is suspected. Coronary arte-riosclerosis, valvular disease, hyperthyroidism,congestive heart failure, and chronic anemiaare factors which predispose to the occurrenceof acute coronary insufficiency and constitutedangerous potentialities.Treatment should be instituted before the

myocardium is impaired, since in such stateintravenous infusion will be to little or noavail.20' 33, 34, 50, 62 The value of the daily elec-trocardiogram lies in the fact that not only

1313


Dow

nloaded from



is it an objective sign of coronary insufficiencybut also that it will reveal RS-T depressionsand T-wave inversions which may precede theappearance of clinical evidence of coronaryinsufficiency. Blood should be administered un-til bleeding has ceased and pulse rate, bloodpressures, hemoglobin determinations and elec-trocardiograms have been restored to normalvalues.The treatment of the angina pectoris which

appears during hemorrhage is blood replace-ment.74-76 The occurrence of chest pain orthe aggravation of pain ordinarily experiencedby the patient constitutes an urgent indicationfor therapy. It is significant that chest painhad appeared in 18 of our patients and ineach instance blood transfusion effected eitheramelioration or disappearance of this com-plaint. The advisability of repeated transfu-sions may be questioned in patients withorganic heart disease, in view of the possibilityof inducing left ventricular failure. Such even-tuality is readily admitted. However, we firmlybelieve that the occurrence of this complica-tion can be prevented, or its severity mini-mized, even when frequently repeated trans-fusions are indicated, by careful and slowadministration of blood. Constant and studiedclinical supervision is imperative.

SUMMARY

1. Hemorrhage is one of the most frequentand important precipitating causes of acutecoronary insufficiency and assumes grave sig-nificance in patients whose coronary circulationis already imparied by antecedent heart diseasesuch as coronary arteriosclerosis, aortic steno-sis, enlarged heart. In such patients acute hem-orrhage may be followed by myocardialischemia of sufficient severity and durationto produce clinical, electrocardiographic andanatomic evidence of acute coronary insuffi-ciency.

2. A review has been presented of 103 casesof acute, moderate and severe hemorrhage withreferences to the amount of rapidity of hemor-rhage, blood hemoglobin level, heart rate, bloodpressure, presence of shock and electrocardio-graphic changes. The gastrointestinal tract wasthe source of bleeding in 95 cases. Fifty-nine

cases (57 per cent) presented clinical or elec-trocardiographic evidence of acute coronaryinsufficiency; of these, 32 showed electrocardio-graphic changes alone, 6 only clinical findingsand 21 had both clinical and electrocardio-graphic evidence. The age of patients whodeveloped coronary insufficiency ranged from18 to 79 years.

3. Twenty-two patients succumbed to theeffects of hemorrhage; 18 of these presentedclinical or electrocardiographic features of acutecoronary insufficiency. In 4 of 13 autopsiedcases, pathologic examination disclosed sub-endocardial myocardial necrosis in the absenceof recent coronary artery occlusion.

4. Of the 27 patients with clinical evidenceof coronary insufficiency, substernal or pre-cordial pain occurred in 15 instances, congestiveheart failure in 8, and both together in 3.Precordial pain varied from mild to severein nature. In 6 instances its association withshock, tachycardia, and fall in blood pressuresimulated massive myocardial infarction dueto acute coronary artery occlusion. These symp-toms and signs were transient and respondedrapidly to therapy. This was especially strikingin several cases of recurrent hemorrhage inwhich each bout of hemorrhage precipitatedan episode of severe angina pectoris.

5. Significant electrocardiographic changesoccurred in 53 patients. These consisted offlat or inverted T waves in 24 instances, RS-Tdepression in 4 cases, and combined RS-T andT changes in 25 cases. The latter findingsrepresented the severest degree of coronaryinsufficiency. Although alterations occurred inall leads, Leads I, II and IN' were most fre-quently affected. Reduced coronary blood flowresulting in anoxia, particularly of the sub-endocardium, was responsible for tbe JS-Tdepressions and T-wave inversions.

6. The changes in circulatory dynamics whichwere found to be associated with coronaryinsufficiency following hemorrhage include theshock state, tachycardia, drop in blood pres-sure and decreased blood volume. Althoughanoxemia due to fall in hemoglobin was im-portant, it was observed that coronary insuf-ficiency occurred in the absence of anemiawhen the clinical features of shock predomi-

1314


Dow

nloaded from



nated. This emphasizes that rapidity of bloodloss may be more significant than the actualamount.

7. The morphologic myocardial changes,when present, varied from tinctorial changes,smudginess of myofibrils and focal necrosis togrossly recognizable confluent zones of infarc-tion. The ischemic lesions were usually notedin the subendocardial region of the posteriorwall, septum and papillary muscles of the leftventricle. Pericarditis and mural thrombosiswere conspicuously absent. Although coronaryarteriosclerosis and varying degrees of stenosisof the lumen were often present, acute coronaryocclusion was not found.

8. Hemorrhage exerts a deleterious effectupon the myocardium and was responsible forthe production of heart failure in 10 per centof the cases herein reported. By the samemechanism, hemorrhage may intensify the car-diac failure already present.

9. The proper therapy of shock and anemiafollowing acute hemorrhage in essential for pro-phylaxis and therapy of coronary insufficiency.Blood should be administered promptly andadequately, particularly in patients with pre-disposing factors of coronary insufficiency.

REFERENCES1 DIETRICH, S., AND SCHWIEGK, H.: Angina pectoris

und Anoxie des Herzmuskels. Ztschr. f. klin.Med. 125: 195, 1933.

W'EBER, A.: Die klinische Bedeutung der Verander-ungen von S-T und T im Extremitatenelectro-kardiogramm. Deutsche med. Wchnschr. 63:430, 1937.

.3BtCHNER, F.: Die Zeichen der Herzmuskelscha-digung durch Koronarinsuffizienz im histolo-gischen Bild und im Elektrokardiogramm. Zen-tralbl. f. inn. Med. 58: 497, 1937.

4 --:Die Deutung des Elektrokardiogramms beiden Durchblutungsstdrungen des Herzmuskelsvom Standpunkt des Pathologen. Klin. Wchn-schr. 17: 1713, 1745, 1938.

5--: Experimente ilber Koronarinsuffizienz undihre morphologische und elektrokardiograph-ische Manifestierung. Verhandl. d. deutsch.Gesellsch. f. inn. Mled. 50: 73, 1938.

6 FRIEDBERG, C. K., AND HORN, H.: Acute myo-cardial infarction not due to coronary arteryocclusion. J.A.MI.A. 112: 1675, 1939.

7GROSS, H., AND STERNBERG, W. H.: Mlyocardialinfarction without significant lesions of coronaryarteries. Arch. Int. MIed. 64: 249, 1939.

£ MASTER, A. M., AND JAFFE, H. L: Coronary in-

sufficiency and myocardial necrosis due to acutehemorrhage. J. MIt. Sinai Hosp. 7: 26, 1940.

9 , GUBNER, R., DACK S., AND JAFFE, H. L.:Differentiation of acute coronary insufficiencywith myocardial infarction from coronary oc-clusion. Arch. Int. Med. 67: 647, 1941.

10 , JAFFE, H. L., DACK, S., AND GRISHMAN, A.:Coronary occlusion, coronary insufficiency, andangina pectoris. Am. Heart J. 27: 803, 1944.

: Progress in acute coronary artery diseases;acute coronary insufficiency with and withoutacute occlusion. -New York -Med. 2: 19, 1946.

12 Acute coronary diseases. History, incidence,differential diagnosis and occupational signifi-cance. Am. J. 1Med. 2: 501, 1947.

13 , )DACK, S., GRISHMAN, A., FIELD, L. IE., ANDHORSN, H1.: Acute coronary insufficiency: anentity. Shock, hemorrlhage and pulmonary em-bolism as factors in its production. J. Mt.Sinai Hosp. 14: 8, 1947.

11 HORN, H., FIELD, L. I., DACK, S., AND MASTER,A. A1.: Acute coronary insufficiency: Pathologicand physiologic aspects. Presented before Sec-tion on Pathology and Physiology, A. AM. A.Convention. Atlantic City, N. J., June 9, 1949.Am. Heart J. In Press.

5 , AND FINKELISTotoN, L. E.: Arteriosclerosis ofthe coronary arteries anAI the mechanism oftheir occlusion. Am. Heart J. 19: 655, 1940.

16 HARRISON, T. R.: Failure of the Circulation, ed. 2.Baltimore, Williams & Wilkins, 1939. P. 19.

17 BLALOCK, A.: Principles of Surgical Care. Shockand Other Problems. St. Louis, C. V. _MosbyCo., 1940. P. 126.

18 FISHBERG, A. MI.: Heart Failure, ed. 2. Philadel-phia, Lea & Febiger, 1940. Pp. 616, 640.

19 MOON, V. H., MORGAN, D. R., LIEBER, MI. M.,AND MCGREW, D.: Similarities andl distinc-tions between shock and effects of hemorrhage.J.A.'M.A. 117: 2024, 1941.

20 KOHLSTAEDT, K. G., AND PAGE, I. H.: Terminalhemorrhagic shock; Circulatory dynamics, rec-ognition and treatment. Surgery 16: 430, 1944.

21 NEUMANN, C., FOSTER, A. D., JR., AND ROVEN-STINE, E. A.: Peripheral circulatory responseto hemorrhage and shock. Proc. Am. Federa-tion Clin. Research (1944) 2: 11, 1945.

22 BEST, C. H., AND TAYLOR, N. B.: The Physio-logical Basis of Medical Practice, ed. 4. Balti-more, Williams & Wilkins, 1945. P. 21.

23 BRANNON, E. S., STEAD, E. A., JR., WARREN, J.V., AND MERRILL, A. J.: Hemodynamics ofacute hemorrhage in man. Am. Heart J. 31:407, 1946.

24 PETERS. J. P.: Water balance in health and indisease: Chapter VI in: DUNCAN, G. G.: Dis-eases of Metabolism, ed. 2. Philadelphia &London, W. B. Saunders, 1947. P. 317.

25 SHARPEY-SCHAFER, E. P.: Cardiac output in severeanemia. Clin. Sc. 5: 125, 1944.

1315


Dow

nloaded from



26 WERLE, J. L., AND COSBY, R. S.: Initiation ofshock through loss of blood or plasma. Am. J.Physiol. 133: 487, 1941.

27 WIGGERS, C. J.: Applicability of experimental re-sults to the shock problem in man. J.A.-M.A.117: 1143, 1941.

28 iIOON, V. H.: Early recognition of shock and itsdifferentiation from hemorrhage. Ann. Surg.110: 260, 1939.

29 FREEMAN, N. E., SCHAFFER, S. A., SCHECTER, A.E., AND HOLLING, H. E.: The effect of totalsympathectomy on the occurrence of shockfrom hemorrhage. J. Clin. Investigation, 17:359, 1938.

30 GOLLWITZER-AIEIER, KL.: DeI Kr~eisla,1ufkollaps(Experimentelle Pathologie). Verhandl. d.deutsch. Gesellsch. f. Kreislaufforsclh. 11: 15,1938.

31 SCHERF, D., REINSTEIN, H., AND KLOTZ, S.: Elec-trocardiographic changes following hematemesisin peptic ulcer. Rev. Gastroenterol. 345: 350,1941.

32 , AND KLOTZ, S.: Electrocardiographic changesafter acute loss of blood. Ann. Int. M\led. 20:438, 1944.

33 AIGGERS, C. J., AND WERLE, J. M.: Cardiac andperipheral resistance factors as determinants ofcirculatory failure in hemorrhagic shock. Am.J. Physiol. 136: 421, 1942.

34-~~ : Failure of transfusions in irreversible hem-orrhagic shock (study of central venous pIes-sures). Am. J. Physiol. 144: 91, 1945.

35 -- AMyocardial depression in shock. A surveyof cardiodynamic studies. Am. Heart J. 33:633, 1947.

36 LAWSON, H., AND REHM, W. S.: The reversibilityof the cardiovascular damage done by nearlycomplete exsanguination. Am. J. Physiol. 144:206, 1945.

3 ACLEOD, J. J. R.: Physiology and Biochemistryin MIodern Medicine. The Factors Concernedin M1aintenance of the Blood Pressure ed. 6.St. Louis, C. V. M\losby Co., 1930. P. 357.

38 LAMSON, P. D., AND GREIG, M. E1.: Certain bio-chemical aspects of shock from hemorrhage,Tr. A. Am. Physicians 58: 182, 1944.

39DAVIDSON, C. S., LEWIS, JESSICA H., FAGNON,H. J., ADAMS, MARGARET A., AND TAYLOR, F.H. L.: Medical shock; Abnormal biochemicalchanges in patients with severe, acute medicalillnesses, with and without peripheral vascularfailure. New England J. Med. 234: 279, 1946.

40 SELIGMAN, A. M., FRANK, H. A., ALEXANDER, B.,AND FINE, J.: Traumatic shock. XV. Carbohy-drate metabolism in hemorrhagic shock in thedog. J. Clin. Investigation, 26: 536, 1947.

41 SCHRUMPF, A.: Azotemia in gastro-intestinal hem-orrhage. Am. J. Digest. Dis. 14: 169, 1947.

42 DENNIS, J., AND AIoORE, R. AiI.: Potassiumchanges in functioning heart under conditions

of ischemia and of congestion. Am. J. Physiol123: 443, 1938.

41 BURDETTE, W. J., AND WILHELAI, A. E.: Respira-tion of heart muscle slices from rats in terminalstage of hemorrhagic shock. Proc. Soc. ExperoBiol. & Med. 61: 411, 1946.

44 HALL, MI.: On the mutual relation between anat-omy, physiology, pathology and therapeuticsan(l the practice of medicine: Being the Gal-stonian Lectures for 1842. London, Bailliere,1842. P. 55.

45 GOLDENBERG, M., AND ROTHBERGER, C. J.: UbereAngina pectoris bei Koronarstenose. Ztschr. f.klin. i\led. 123: 490, 1933.

46 HICKS, S.: Hamilton Russel Memnorial Lecture:Physiology of acute circulatory failure clue tohemorrhage and shock. Australian & New Zea-land J. Surg. 7: 99, 1937.

47 M\ASTER, A. M., JAFFE, H. L., AND DACK, S.:Sudden profound acrocyanosis as the present-ing sign in mv-ocardial infarction. J. Mt. SinaiHosp. 4: 21, 1937.

48 BEAN, W,. B.: Infarction of the heart; A morpho-logical and clinical appraisal of three hundredcases. Part I. Predisposing and precipitatingconditions. Am. Heart J. 14: 684, 1937.

19 MCLAUGHLIN, C. W., BAKER, C. P., AND SHARPE,J. C.: Bleeding duodenal ulcer complicated bym ocardial infarction. Nebraska 1M. J. 25: 266,1940.

50 MASTER, A. M.: Treatment of cardiovasculatremergencies. U. S. Nay. AM. Bull. 39: 190, 1941.

51 ASCHENBRENNER, R.: Mlagenblutung und Anoxiedes Herzmuskels. Ztschr. f. klin. Med. 127:160, 1934.

52ELLIOT, A. H.: Anemia as the cause of anginapectoris in the presence of healthy coronaryarteries and aorta: Report of a case. Am. J. MI.SC. 187: 185, 1934.

53 FLAUM, E., AND VON JAGIC, N.: Uber Erschein-ungen von Mlyokardischqnmie in einem Fallevon Ulkusblutung. Wien. Arch. f. inn. Mled-27: 113, 1935.

54 DAVIS, H. A.: Pathology of shock in man; Visceraleffects of trauma, hemorrhage, burns and sur-gical operations. Arch. Surg. 41: 123, 1940.

55 PRIEST, W. S.: Sudden fall in arterial pressure as.a precipitating factor in acute coronary throm-bosis and myocardial infarction. Modern Con-cepts Cardiovascular Iis., Am. Heart A., Vol.11, No. 2, 1942.

56 \ICKINLAY, C. A.: Coronary insufficiency, l)e-cipitated by hemorrhage from duo(lenal ulcer.Journal Lancet 63: 31, 1943.

67 KINNEY, T. D., AND MALLORY, G. K.: Cardiacfailure associated with acute anemia. New Eng-land J. iIed. 232: 215, 1945.

58 DIETRICH, S.: Blutversorgung und Aktionsstromndes Herzens. Ztschl. f. cl. ges. exper. M\ed. 90:689, 1933.

1316


Dow

nloaded from



RADNAI, P.: Uber das elektrokardiographischeBild der durch akute Anarmie verursachtenHerzmuskelanoxiimie, Ztschr. f. klin. _Med. 128:401, 1935.

60 MARCHAL, G., SOULIE, P., AND BAUGE, C.: Modi-fications 6lectrocardiographiques au cours de lasaign6e experimentale. Arch. d. mal. du coeur31: 303, 1938.

61 LEPESCHKIN, E. AA.: Uber das Electrokardio-gramm bei experimenteller Koronarinsuffizienz.Versuche mit Einblutung und Reinfusion. Car-diologia 2: 236, 1938.

62 IZQUIETA, J. M\1., AND PASTERNACK, B.: Electro-cardiographic changes in hemorrhage and is-chemic compression shock. Proc. Soc. Exper.Biol. & M\leci. 61: 407, 1946.

63 SCHiiTZ, E.: Der monophasische Aktionsstrom.Verhandl. d. deutsch. Gesellsch. f. Kreislauf-forsch. 12: 15, 1939.

61 BOYD, L. J., AND SCHERF, D.: The electrocardio-gram after mechanical injury of inner surfaceof heart. Bull. Newr York MI. Coll., Flower &Fifth Ave. Hosps. 3: 1, 1940.

65 KISCH, B., NAHUM, L. H., AND HOFF, H. E.: Thepredominance of surface over deep cardiac in-jury in producing changes in the electrocardio-gram. Am. Heart J. 20: 174, 1940.

66 W"OLFERTH, C. C., BELLET, S., LIVEZEY, MARYM., AND MURPHY, F. D.: Negative displace-ment of RS-T segment in electrocardiogramand its relationships to positive displacement;Experimental study. Am. Heart J. 29: 220,1945.

67 :The clinical significance of precordial leadsin the diagnosis of heart disease. 1lodern Con-cepts Cardiovascular Dis., Am. Heart A., Vol.15, No. 1, 1946.

68 PRICE, R. K., AND JANES, L. R.: Case of subendo-car(lial infarction. Brit. Heart J. 5: 134, 1943.

69 BAYLEY, R. H.: The electrocardiographic effectsof injury at endocardial surface of left ven-tricle. Am. Heart J. 31: 677, 1946.

70 VAN BUCHEM, F. S. P.: Extensive calcification inthe heart at an early age. Acta med. Scandinav.125: 182, 1946.

71 PRUITT, R., BARNES, A. R., AND ESSEX, H. E.:Electrocardiographic changes associated withlesions in deeper layers of the myocardium;Experimental study. Am. J. MI. Sc. 210: 100,1945.

72 , AND VALENCIA, F.: The immediate electro-cardiographic effects of circumscribed myocar-(ial injuries: An experimental study. Am. HeartJ. 35: 161, 1948.

7OOERNING, K., SOMMERFELT, C., AND FREDRIKSEN,M.: Electrocardiographic findings in patientswith peptic ulcer. Acta med. Scandinav. 124:564, 1946.

74BLOCH, C.: Angina 1)ectolis und Animie. Wien.Arch. f. inn. MIed. 26: 143, 1934.

75 BERNSTEIN, S. S., AND GINZBURG, L.: Status angi-nosus due to profound anemia. Complete relieffollowing resection of gastric and sigmoid car-cinomata. J. _Mt. Sinai Hosp. 9: 142, 1942.

76 MIASTER, A. M/I., DACK, S., FIELD L. E., ANDHORN, H.: Diagnosis and treatment of acute.coronary diseases. J.A.M\1.A. 141: 887, 1949.

1317


Dow

nloaded from


LEONARD E. FIELDARTHUR M. MASTER, SIMON DACK, HENRY HORN, BERNARD I. FREEDMAN and

and Three CasesAcute Coronary Insufficiency Due to Acute Hemorrhage: An Analysis of One Hundred

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1950 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/01.CIR.1.6.1302

1950;1:1302-1317Circulation.

http://circ.ahajournals.org/content/1/6/1302the World Wide Web at:

The online version of this article, along with updated information and services, is located on

http://circ.ahajournals.org//subscriptions/

is online at: Circulation Information about subscribing to Subscriptions:

http://www.lww.com/reprints Information about reprints can be found online at: Reprints:

document.

Permissions and Rights Question and Answer Further information about this process is available in therequested is located, click Request Permissions in the middle column of the Web page under Services.the Editorial Office. Once the online version of the published article for which permission is being

can be obtained via RightsLink, a service of the Copyright Clearance Center, notCirculationpublished in Requests for permissions to reproduce figures, tables, or portions of articles originallyPermissions:


Dow

nloaded from

http://circ.ahajournals.org/content/1/6/1302

http://www.ahajournals.org/site/rights/

http://www.lww.com/reprints

http://circ.ahajournals.org//subscriptions/


Acute Coronary Insufficiency Due to Acute Hemorrhage:

Documents