Pathophysiology of Cardiogenic ShockQuantification of Myocardial Necrosis, Clinical, Pathologic

and Electrocardiographic Correlations

By DANIEL R. ALONSO, M.D., STEPHEN SCHEIDT, M.D., MARTIN POST, M.D.,

AND THOMAS KILLIP, M.D.

SUMMARYClinical and pathologic data were correlated in 22 patients with cardiogenic shock and 10 "con-

trol" patients who died suddenly after infarction without shock. A pathologic technique of ven-

tricular mapping allowed quantification of recent as well as old infarction. Total left ventricular(LV) damage averaged 51% (range 35-68%) in the shock patients and 23% (range 14-31%) inthe control group. Shock was associated with recent infarction (all 22 patients), old infarction(21 patients) and extension of infarction (18 patients). Extension, often in a subepicardial man-

ner, averaged 6% of LV mass (range 3-10%) in 18 patients with shock; it preceded shock infour, coincided with the onset of shock in six, and followed shock in seven patients with shock.In contrast, small extensions averaging 2% of LV mass were found in three, and multiple recentinfarctions in two control patients. Although progressive myocardial damage was a common

pathologic finding, it was infrequently recognized clinically. The electrocardiogram reflected evi-dence of recent infarction in 56%, old infarction in 31%, and extension in only 30% of patients.These data suggest that appropriate early therapeutic intervention might limit myocardial dam-age by preventing extension or reinfarction. Since shock was best correlated with total LV dam-age, such limitation of infarction might reduce the incidence and mortality of cardiogenic shock.

Additional Indexing Words:Myocardial infarction Quantification of infarct size

CARDIOGENIC shock remains the major causeof death among patients hospitalized with

acute myocardial infarction.' Mortality is high inspite of pharmacologic agents, mechanical circula-tory assistance and surgery. Development ofoptimal therapy requires better understanding ofthe pathophysiology of the cardiogenic shocksyndrome.We present herein a detailed clinical-pathologic

study of patients who died with cardiogenic shock.The data demonstrate that shock is associated withmassive myocardial damage and that myocardialinjury frequently occurs in a stepwise or progressivefashion. Interruption of the cycle of clinicaldeterioration and progressive damage through

From the Departments of Pathology and Medicine, theNew York Hospital-Cornell Medical Center, New York, NewYork.

Supported by USPHS Contract PH 43-67-1439.Address for reprints: Daniel R. Alonso, M.D., Department

of Pathology, The New York Hospital-Cornell MedicalCenter, 525 East 68th Street, New York, New York 10021.

Received February 26, 1973; revision accepted forpublication April 25, 1973.

588

Extension of infarction

therapy directed at limiting the amount of myocar-dial damage during the episode of acute infarctionmight reduce the incidence and mortality ofcardiogenic shock.

Methods

Clinical, physiologic and postmortem studies havebeen obtained in 32 patients over a two-year period.Twenty-two patients died with cardiogenic shockcomplicating acute myocardial infarction. All had intra-arterial systolic pressure less than 90 mm Hg andabnormal renal or cerebral perfusion manifested byhourly urine flow less than 20 ml or abnormalities ofmental status. Hypovolemia was excluded either bymeasurement of left ventricular filling pressure, whichexceeded 12 mm Hg whenever obtained, or by trialexpansion of intravascular volume. Severe pain, signi-ficant arrhythmias, disorders of electrolyte or acid basebalance, and abnormalities of ventilation or oxygenationwere corrected whenever possible.The findings in the patients with shock were

compared to those of a control group, composed of tenpatients who died suddenly and unexpectedly duringconvalescence in the hospital following acute myocar-dial infarction.

Table 1 lists characteristics of the shock and controlgroups. Differences in age, time of admission to theCardiac Care Unit and total duration of illness between

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Table 1

Comparison of Patient Groups

Suddendeath after

Cardiogenic myocardialshock infarction

NMaleFemaleAge, mean (range)Median time fromclinical "moment of infarction"to CCU admission, hrMedian survival after infarction,hrNumber of patients withcomplications at CCU admission

nonemild or moderate CHFpulmonary edemacardiogenic shock

Median time from infarction toonset of shock, hr, (range)Median survival after onset ofshock, hr

22 1014 68 466 (50-85) 70 (57-89)

6 13

100 172

9624

4600

66 (0-331)

42

Abbreviations: CCU = Cardiac Care Unit,gestive heart failure.

CHF = con-

the two groups are not statistically significant. Patientswho developed shock did so at varying times afteradmission. Only seven of the 22 patients developedshock within 24 hr of the acute myocardial infarct.

In the group who died suddenly two patients hadventricular rupture and eight had unexpected cardiacarrest.

Pathologic StudiesThe heart was removed intact from the chest. A

radiograph was obtained in various projections, and thecoronary arteries were then perfused with a mixture ofbarium sulfate and gelatin through polyethylenecatheters placed in each coronary ostium and securedby a ligature around the origin of the vessel. Anonpulsatile perfusion pressure of 100 mm Hg wasapplied until all visible epicardial branches were filled.At the completion of the perfusion, the heart was fixedby immersion in a solution of 20% formalin for 48 hr.Care was taken to fill the cardiac chambers withformalin to complete fixation. The heart was weighedbefore and after fixation; no significant difference in theweights was found.

After 48 hr of fixation radiographs of the heart wereobtained in four projections. The coronary arteries werethen dissected free from the epicardial surface. Theentire length of major vessels was resected. The arterieswere decalcified in 7% nitric acid for 24-48 hr,according to the amount of calcium present in eachvessel. Radiographs were taken of isolated coronaryarteries by placing them directly on mammography X-ray film.

Quantification of infarcted ventricular myocardiumCirculation, Volume XLVIII, September 1973

589

was accomplished by sectioning the heart in astandardized manner, determining the degree ofnecrosis in each standard segment and calculating totaldamage through comparison with data obtained fromnormal hearts. The method employed is a modificationof one originally devised by Dr. Donald B. Hackel ofDuke University Medical Center.The method is as follows: After completion of

arteriography the crux of the heart was identified. A cutwas made 2 cm below the crux parallel to theatrioventricular groove (fig. 1). Thus, the heart wasdivided into a basal and a ventricular portion. Thelatter was then cut into six equal and parallel coronalslices. These coronal slices were labelled A through F,from the apex to the base. The ventricular myocardiumof the basal portion was separated by sharp dissectionfrom the atria along the atrioventricular groove andlabelled G.Each of the seven coronal slices (A through G) was

then cut into six radial segments in a standard manner.The interventricular septum was divided into equalanterior and posterior halves (segments 5 and 1respectively). The perimeter of the epicardial aspect ofthe remaining free wall of the left ventricle wasmeasured with a flexible plastic ruler and divided intothree equal segments. The segments were labelled 4(anterior), 3 (lateral) and 2 (diaphragmatic). Theentire free wall of the right ventricle was separated andassigned number 6, but was not included in thecalculation to follow. Thus a total of 35 segments (5

sulcus

3 L

Figure 1

(Top) Method of sectioning the heart for quantification otventricular myocardial damage. (Bottom) Method of divid-ing each coronal slice of myocardium into radial segments.Five radial segments (1-5) in each of 7 coronal slices (A-G)provide 35 standard segments comprising the entire mass ofthe left ventricular myocardium.

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ALONSO ET AL.

radial segments in each of 7 coronal slices) ofmyocardium of left ventricular wall and interventricularseptum was obtained.

In the hearts from patients with shock or suddendeath, areas of myocardial infarction and fibrosis wereidentified grossly and mapped in each coronal section.Microscopic sections were then obtained from areas ofobvious infarction as well as from grossly normalmyocardium. A minimum of 20 large blocks of leftventricular myocardium were studied microscopically ineach heart.The technique of sectioning the heart in a standard

manner was performed in 25 normal adult heartsobtained at autopsy from patients who died fromnoncardiac causes. The percent contribution of eachstandard segment to the total left ventricular weight ofthe normal heart is shown in figure 2.

In hearts with infarction, viable myocardium in eachstandard segment was estimated by gross and micro-scopic observations. If viable myocardium was totallyabsent, either due to recognizable recent necrosis or asa result of old infarction with subsequent fibrosis andloss of mass, the percent of left ventricular massrepresented by that standard segment (as determinedfrom the expected percent in the 25 normal hearts)was subtracted from 100%. If, for example, the anteriorseptal segment in section G (fig. 2) was totallyinfarcted, the necrosis represented 5.5% of ventricularmass. Loss of myocardium in part of a standard

A nterior

segment was subtracted in proportion to the amount ofdamage or loss of tissue in the segment. Thus thismethod accounts for not only recognizable recentdamage, but also old necrosis which has resulted in lossof ventricular mass.The age of infarcts was estimated by conventional

histopathologic criteria.2-4 Three categories were estab-lished: recent infarct (less than 2 weeks old),intermediate infarct (2 weeks to 3 months old) and oldinfarct (more than 3 months old). While this separationaccording to age was both workable and useful, it isrecognized that aging of a myocardial infarct is not aprecise process.

ResultsThe hearts of patients who died with cardiogenic

shock showed massive left ventricular destructionand the extent of infarction was significantly greaterthan in the patients who died without shock. Thusthe total mass of left ventricular infarction averaged51% (range 35-68%) in the 22 patients with shockand 23% (range 14-31%) in the ten patients withsudden death (fig. 3). The mass of old orintermediate infarction was not different in theshock and sudden death groups; the highlysignificant difference in total infarction between thetwo groups was explained by the difference in massof recent infarction which averaged 31% in the

DEATH DUE TO ACUTE MYOCARDIAL INFARCT:SUMMARY OF LEFT VENTRICULAR DAMAGE

60wLU

- 50

U-1

Z 40X

DU 30

zlit

20LLJ

-, 10K')

A

Figure 2

Mean percent of left ventricular myocardial mass containedin each of the 35 standard segments as determined from25 normal hearts.

CARDIOGENICSHOCK n=22

HISTOLOGICAGE OF INFARCT

RECENTINTERMEDIATE

. 2 WEEKS TO 3 MONTHS)

OLD

' p<.001

p< 001 \

ns

DIED SUDDENLY(NON-SHOCK) n = 10

Figure 3

Mass of left ventricular infarction in 22 patients who diedfrom cardiogenic shock compared to 10 with sudden death.There is no significant difference in mass of old (clear portionof bar) or intermediate (lightly stippled) infarction. Thehighly significant difference in mass of total infarction isexplained by the much larger recent infarction (dark stip-pling) in the shock patients.

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shock group but only 12% in the sudden deathgroup.

Figure 4 depicts the distribution of damage byage of infarct in each of the patients with shock andsudden death. The relative proportions of old,intermediate and recent damage are highly vari-able. In 16 of the 32 patients most of the myocardialdamage was due to recent necrosis. Six patients,only two of whom died from shock, had relativelysmall recent infarcts combined with larger old orintermediate infarets. In general, the appearance ofshock seems best correlated with total left ventricu-lar damage.

Duration of Shock

The 22 patients with shock were divided into twogroups according to the clinical duration of shock.Group 1 consisted of patients in shock longer than24 hr. Group 2 was comprised of patients who diedwithin 24 hr of the onset of shock. The meanduration of shock was 88 hr for Group 1 and 12 hrfor Group 2. The two groups do not differ

70 DEATH DUE TO ACUTE M)LEFT VENTRICULAR

60LUU

CLi50

U-

z 40

U30-

zLUJ> 20-U-LU

~10

significantly with respect to the total or recent massof left ventricular infarction, the frequency or massof extension, or the extent of coronary arterythrombosis (table 2). Figure 5 demonstrates thatthere is no relationship between the mass of leftventricular infarct and the duration of shock. Thuslength of survival following the onset of shock doesnot appear to influence the pathologic findings.

Extension of InfarctionAn infarct was considered to have extended when

myocardial necrosis of a more recent vintage wasdemonstrated at the edges of an established infarct.This was distinguished from "multiple recentinfarction" (hereafter "reinfarction"), where severaldiscrete infarcts in scattered locations were appar-ent.Two patterns of extension, type A and type B,

were observed. Type A extension occurred at theedges of a subendocardial infarct, usually involvingthe subepicardial aspect of the ventricular wall.Type B extension developed at the lateral margins

(OCARDIAL INFARCT:DAMAGE

AGE OF INFARCT

RECENTINTERMEDIATE(2 WEEKS TO 3 MONTHS)

OLD

CARDIOGENIC SHOCK n =22 DIED SUDDENLY(NON -SHOCK) n = 10

Figure 4

Mass of left ventricular infarction in individual patients.

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ALONSO ET AL.Table 2

Influence of Duration of Si

NMlean duration of shock,

onset to death, hrMass of LV inifarct,

%7C of LV\lass of recent LV infarct.,% of LV

Extension of infarction,patients

Mass of extension,%c of LV

Recent coronary arterythrombosis, patients

sudden death group, comprising 2, 2 and 3% of lefth~ock on Pathologic Findings ventricular mass, respectively.Grouip 1 Groulp 2 Seven of the patients in the shock group and oneProlonged Rapidshock demise in the sudden death group had two or more(duiration (dturation>24 hrs) <24 hrs) p anatomically distinct reinfarctions.9 12 The pathologic determination of the infarets

recognized at autopsy was correlated with clinical88 12 <.001 events as described in the medical record. Chrono-

logic relationships for the 22 patients are depicted54t 47 NS in figure 7 and table 3. Extension or reinfarction36 32 NS followed the onset of shock in seven patients. In six

patients an extension or reinfarction clearly pre-8 (89%0/) 10 (83%) NS ceded and perhaps precipitated shock. In six

instances the onset of shock and extension or5.4 4. 7 NS reinfarction occurred at about the same time, so6 (67%) 10 (83%c) NS that the pathophysiologic sequence could not be

determined.Abbreviations: LV = left, ventricle, NS = not significant

of transmural infarcts since no viable subepicardialmyocardium remained (fig. 6).

Extension of infarction was observed in 18 of the22 shock patients but in only 3 of the 10 suddendeath patients (P < .005). Type A extensionoccurred in 9 and type B extension in 9 of the 18patients with shock in whom extension wasdocumented. The mass of left ventricle involved byextension averaged 6% (range 3-10%) in the shockgroup. There were three small extensions in the

60

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40

z> 30

0e 20

10

RELATIONSHIP BETWEEN MASS OF LEFT VENTRICULAR- INFARCT AND DURATION OF CARDIOGENIC SHOCK

S

.0

000* S0

0- 0

0

00

.* e

0

I10 20 40 60 80 100 120

DURATION OF SHOCK, HOURS

Figure 5

140 160

Mass of left ventricular infarct plotted against the durationof cardiogenic shock. Apparent lack of any relationship sug-

gests that shock itself is not responsible for the pathologicfindings.

Figure 6

Schematic representation of two types of extension of myo-cardial infarction. Type A (top) was observed at the edgesof an infarct, usually subepicardially. Type B (bottom)occurred at the lateral margins.

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1

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PATHOPHYSIOLOGY OF CARDIOGENIC SHOCK

200 180 160 140 120 100 80 60 40 20 0

HOURS BEFORE DEATHFigure 7

Chronologic relationships between clinical and pathologic events in the 22 patients dying from cardio-genic shock. The age of infarction, extension or reinfarction was estimated by standard pathologic tech-niques and is shown as a range of minimum to maximum estimated age. Original infarcts have beenomitted where they occurred long before the clinical onset of shock. Table 3 s-ummarizes the relation-ships shown here.

Arranging the data in another way, the onset ofshock was related to the original infarct in 9episodes of shock, followed extension or reinfarctionin 6, occurred simultaneously with extension orreinfaretion in 6, and was not closely related to anobvious pathologic event in 3 instances.

Coronary Artery PathologyThrombosis was common. in both groups of

patients. Recent occlusive thrombosis of majorcoronary arteries was found in 16 of the 22 (72%)patients with shock and 6 of the 10 (60%) patientswith sudden death. The thrombi averaged 18.4 mm

Table 3

Chronologic Relationships between Infarction, Extension, Reinfarction and Shock

Extension or reinfarction(patients)

Followed shockPreceded shockOccurred simultaneously with theonset of shockNo extension or reinfarction

76

63

22

Clinical onset of shock:(episodes of shock)

Related to original infarctFollowed extension or reinfarctionOccurred simultaneously with extensionor reinfarctionNo obvious pathologic event

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(range 2.0 to 52.0 mm) in length in the shockgroup, and 28.6 mm (range 13.0 to 47.0 mm) in thesudden death group. The presence and size ofrecent thrombi could not be correlated with theduration of shock, survival after the onset of acutemyocardial infarction or the presence, type or mass

of extension.Table 4 compares the distribution of major

coronary artery stenoses ( >75% of luminal area) inthe shock and sudden death patients. Extensivethree-vessel disease was the dominant finding inpatients who died with cardiogenic shock, but 3patients had involvement of one vessel only (leftanterior descending coronary artery in two, rightcoronary artery in one).

Electrocardiographic Correlations

Scalar electrocardiograms were evaluated forevidence of old and new myocardial infarctionusing standard criteria.5 Forty discrete old infarctswere identified pathologically in the 32 patients.Electrocardiographic diagnosis was not possible insix instances because of left bundle branch block,acute infarction in the same location as oldinfarction (thus obscuring any old changes) or

inadequate electrocardiograms. Of the remaining 34old infarctions, only 12 (35%) could be diagnosedfrom the scalar electrocardiogram (fig. 8).Of the 38 discrete recent infarcts identified

pathologically, chronologically suitable electrocar-diograms were available in 33 instances. Nineteenof the 33 acute infarctions (58%) could bediagnosed from the electrocardiogram.

In 19 instances of acute transmural infarction, an

average of 32% of left ventricular mass was

destroyed. Of these transmural infarcts, only threecould not be diagnosed from the electrocardiogram,for a diagnostic accuracy of 84%. In contrast, 19acute nontransmural infarcts were small, averaging12.5% of left ventricular mass. Only four nontrans-mural infarcts were apparent from the electrocar-diogram, for a diagnostic accuracy of 21% (fig. 8).

Table 4

Coronary Artery Pathology in PatientsSudden Death

Major coronary vesselswxith > 75 c,,c stenosis

1 vessel2 vessels3 vessels

Shockpts Co

3 14

7 32

12 54

with Shock and

Sudden deathpts %

2

6

2

20

60

20

Abbreviation. pts = patients.

ELECTROCARDIOGRAPHIC DIAGNOSISAND EXTENT OF INFARCTION

o TRANSMURAL INFARCTA CENTRAL 1 NON-TRANSMURALO SUBENDOCARDIAL J INFARCT

70r

zLUJUW

U

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z

:DU

zLU

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OLD INFARCTION

60k

50k

0040H

30k

20h 0

0

0

00

0

0

0

00

0

10

0:0

0

0

0

00

0*:0

00000

00v

ECG DIAGNOSTICNON- DiAGNOSTIC

Figure

RECENT INFARCTION

0

0

0

0

0

00

0

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0

0

8

A

aa

ECG DIAGNOSTICNON- DIAGNOSTIC

Diagnostic utility of the standard scalar electrocardiogramaccording to mass and type (transmural, central or subendo-cardial) of infarction. Transmural infarctions were larger andusually produced diagnostic electrocardiographic changes.

In ten instances an electrocardiogram was

available after the presumed chronologic time ofextension of infarction. In only three of theseinstances could acute injury (new ST-segmentelevation or Q wave) be recognized electrocardio-graphically.

Discussion

This study demonstrates that when cardiogenicshock complicates acute myocardial infaretion,massive left ventricular infarction is to be expected.Furthermore, the extent of myocardial damage ismuch greater in patients who die from shock thanin those who die unexpectedly while convalescingin the hospital from acute infarction. Our observa-tions are in agreement with recent clinical-patholog-ic studies in which the mass of left ventricular

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infarction was established by other pathologictechniques.6' 7, 8 The difference in mass of infarctedleft ventricle between the cardiogenic shock andsudden death groups is highly significant and is notrelated to the duration of shock, the use of drugs orof mechanical circulatory assistance with the intra-aortic counterpulsating balloon.On the average, more than half of the left

ventricular mass is destroyed in patients who diefrom cardiogenic shock. Stated another way, in thepatients with cardiogenic shock less than half of theleft ventricular myocardium remains to maintainventricular function. The theoretical consequencesof such loss of myocardium are considered withreference to a conceptual model by Swan et al.9Under certain circumstances, loss of half of the leftventricular myocardium is sufficient to explain thehemodynamic and clinical consequences of shock,and contractility of the remaining viable tissue neednot be impaired. One implication of this analysis isthat preservation of functioning myocardium is ofparamount importance. Current and past experi-ence have amply demonstrated that therapy di-rected at the remaining viable tissue (which isalready functioning at normal or perhaps above-normal levels of contractility) does little to improvesalvage.We have further shown that patients dying

during hospitalization from myocardial infarctionoften have a stepwise increase or progression ofmyocardial necrosis, usually from marginal exten-sion of infarction. Thus, extension was found in 18of 22 patients with shock but in only three of tenwith sudden death. Multiple recent infarctions werefound in seven patients with shock and two withsudden death. Page et al. observed extension to bepresent only in patients with shock and suggestedthat extension was a consequence of the shockstate.8 In our patients, although extension followedthe onset of shock in some, it clearly preceded (andperhaps caused) shock in others. These observa-tions indicate that extension is an importantmechanism resulting in progressive myocardialnecrosis following acute myocardial infarction.

Extension of infarction is often a process whichgoes unrecognized clinically. None of the threeextensions recognized pathologically in the patientswith sudden death were suspected despite closeobservation in a cardiac care unit. In the patientswith shock, only three of ten electrocardiogramsavailable after the presumed time of extensiondemonstrated an acute injury pattern. Only three ofthe 18 extensions were suspected clinically becauseCirculation, Volume XLVIII, September 1973

of renewed or protracted chest pain. Althoughdiagnosis of extension is infrequent, the processmay not be silent. Perhaps more frequent recordingof electrocardiograms, serial precordial ST-segmentmaps or assay of serum enzymes several times dailywould improve diagnostic accuracy.The limitations of the standard scalar electrocar-

diogram in the diagnosis of myocardial infarctionhave been previously recognized.10' 11 In our study,after excluding patients with left bundle branchblock and intraventricular block, old infarctioncould be diagnosed in only 31% and acute infarctionin only 59% of hearts with pathologically confirmedareas of myocardial necrosis. Our findings closelyparallel those of Levine and Phillips.12 Infarcts thatare nontransmural, diaphragmatic and posterior, orthose that comprise less than 10% of left ventricularmass are often not apparent electrocardiographical-ly. At least part of the difficulty is due to the factthat a significant Q wave, evidence of a transmuralscar, is generally necessary for diagnostic certainty.Others have noted the inadequacies of the electro-cardiogram in the diagnosis of purely subendocar-dial infarction.10' 13 It must be recognized therefore,that although cardiogenic shock is usually temporal-ly related to acute infarction or recent extension,the electrocardiogram will be of diagnostic valueonly about half of the time.There was a preponderance of patients with

disease of all three major coronary arteries in theshock group, although three patients developedshock with a single major coronary artery occlusion.The frequency of coronary thrombosis encounteredin our patients with shock is comparable to thatreported by Page.8 The incidence of thrombi in thesudden death group, higher than that reported inother studies of sudden death,'4 is probablyexplained by the fact that our group comprisedhospitalized patients who died suddenly duringconvalescence, often many days following acuteinfarction. Other studies of sudden death generallydeal with patients dying within a short time of theonset of symptoms. Our inability to determine theage of thrombus precludes any attempt to establisha causal relationship between thrombosis andinfarction or extension of the original injury.The apparent temporal association between

extension of infarction and the clinical onset ofshock suggests that progression of myocardialdamage plays an important role in the pathogenesisof shock. Extension probably represents loss ofviability of an ischemic zone which surrounds theinitial infarct.'5-17 Infarction of this zone of

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marginal viability could be precipitated by anyfactor that unfavorably influences its metabolicmilieu. The balance of factors which regulatemetabolic demands and the supply of nutrients tothe myocardium becomes crucial in controlling theprogressive necrosis which may follow the initialinsult. Perhaps treatment designed to improveoxygenation and substrate utilization or to reducemyocardial oxygen needs can enhance the viabilityof the marginal ischemic zone. The hypothesis thatprogressive loss of functioning myocardium follow-ing acute infarction is preventable requires furtherinvestigation as specific therapeutic interventionsare critically evaluated. Limitation of myocardialdamage, rather than intensive therapy after cardio-genic shock is manifest, may succeed in reducingboth the incidence and mortality of progressivepower failure complicating acute myocardial infarc-tion.

References1. SCHEIDT S, ASCHEIM R, KILLIP T: Shock after acute

myocardial infarction. Amer J Cardiol 26: 556,1971

2. MALLORY GK, WHITE PD, SALCEDO-SALGAR J: Thespeed of healing of myocardial infarction: A study ofthe pathologic anatomy in seventy-two cases. AmerHeart J 18: 647, 1939

3. LODGE-PATCH I: The ageing of cardiac infarcts and itsinfluence on cardiac rupture. Brit Heart J 13: 37,1951

4. WHO SCIENTIFIC GROUP: The pathologic diagnosis ofacute ischemic heart disease. WHO Technical ReportSeries No. 441. Geneva, World Health Organization,1970

5. BLACKBURN H, KEYS A, SIMONSON E, RAUTAHARJU P,PUSAR S: The electrocardiogram in populationstudies: A classification system. Circulation 21: 1160,1960

6. BOOLOOKI H, LEMBERG L, GHAHRAMANI A,ECONOMIDES C, CALDWELL T, JUDE JR: The clinical,surgical and pathologic correlations in patients withacute myocardial infarction and pump failure.Circulation 44: 1034, 1971

7. HARNARAYAN C, BENNETT MA, PE-NTECOST BL, BREWERDB: Quantitative study of infarcted myocardium incardiogenic shock. Brit Heart J 32: 728, 1970

8. PAGE DL, CAULFIELD JB, KASTOR JA, DESANCTIS RW,SANDERS CA: Myocardial changes associated withcardiogenic shock. New Eng J Med 285: 133,1971

9. SWAN HJC, FORRESTER JS, DIAMOND G, CHATTERJEEK, PARMILEY WW: Hemodynamic spectrum ofmyocardial infarction and cardiogenic shock. Aconceptual model. Circulation 45: 197, 1972

10. PRUITT RD, DENNIS EW, KINARD SA: The difficultelectrocardiographic diagnosis of myocardial infarc-tion. Progr Cardiovasc Dis 6: 85, 1963

11. ANDERSSEN N, SKJAEGGSTAD 0: The electrocardiogramin patients with previous myocardial infarction. ActaMed Scand 176: 123, 1964

12. LEVINE H, PHILLIPS E: An appraisal of the newelectrocardiography in one hundred and fifty consec-utive autopsied cases. New Eng J Med 245: 833,1951

13. GEORAS CS, DAHLQUIST E, CUTTS FB: Subendocardialinfarction. Arch Intern Med 111: 488, 1963

14. ROBERTS WC, BUJA LM: The frequency and signifi-cance of coronary arterial thrombi and otherobservations in fatal acute myocardial infarction. Astudy of 107 patients. Amer J Med 52: 425, 1972

15. MAROKO PR, LIBBY P, COVELL JW, SOBEL BE, Ross J,BRAUNWALD E: Precordial ST segment elevationmapping: An atraumatic method for assessingalterations in the extent of myocardial ischemicinjury. Amer J Cardiol 29: 223, 1972

16. MAROKO PR, KJEKSHUS JK, SOBEL BE, WATANABE T,COVELL JW, Ross J, BRAUNWALD E: Factorsinfluencing infarct size following experimental coro-nary artery occlusion. Circulation 43: 67, 1971

17. HOOD WB JR: Salvage of myocardium in acuteischemia. Circulation 43: 11, 1971

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DANIEL R. ALONSO, STEPHEN SCHEIDT, MARTIN POST and THOMAS KILLIPPathologic and Electrocardiographic Correlations

Pathophysiology of Cardiogenic Shock: Quantification of Myocardial Necrosis, Clinical,

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1973 American Heart Association, Inc. All rights reserved.

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