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Experimental myocardial infarction
EXPERIMENTAL
STUDIES
Experimental Myocardial Infarction XII. Dynamic Changes in Segmental Mechanical Infarcted and Non-infarcted Myocardium
PANTEL FAROUK
S. VOKONAS, A. PIRZADA,
WILLIAM
B. HOOD,
Boston,
Massachusetts
Jr.,
MD MD MD
Behavior of
The mechanical behavior of ischemic myocardium was studied in anesthetized open chest dogs. In each animal, a small well localized myocardial infarction was produced by ligation of a single ventricular branch of the left circumflex coronary artery. Serial in situ measurements of segment length were made by mercury-in-Silastic gauges sutured directly to the left ventricular surface. After coronary ligation, systolic aneurysmal bulging of the ischemic segment was uniformly noted. This was quantified as follows: normalized segment length change in this region, expressed in muscle lengths (where muscle lengths = phasic segment length amplitude/end-diastolic segment length), immediately increased from 0.06 f 0.01 (standard error of the mean) to 0.10 f 0.02 muscle lengths (i-67 percent, P <0.02). Over a 6 hour period, muscle lengths progressively declined to near control values, but retained an aneurysmal contour. End-diastolic segment length increased 5 percent above control values after coronary occlusion and remained fixed at this level for 6 hours. In contrast, noninfarcted myocardium exhibited no significant changes in muscle length or end-diastolic segment length. These studies demonstrate that the degree of systolic aneurysmal bulging in infarcted myocardium, although initially great, resolves within 6 hours but retains an aneurysmal contour. These findings are consistent with either partial return of contractility or diminished local compliance, but persistence of an aneurysmal shape favors the latter mechanism. The fixed increase in end-diastolic segment length suggests that “stress-relaxation” takes place in the infarcted region. It is possible that diminished compliance in zones of infarction, previously noted after several days, begins within a few hours after the onset of ischemia.
From the Cardiology Division of the Thorndike Memorial Laboratory and the Department of Medicine, Boston City Hospital, Boston University School of Medicine, Boston, Mass. This study was supported by U. S. Public Health Service Grants HL 14646, HE 07299, Contract 712498 and Training Grant 5TOl HL 05986 from the National Institutes of Health, Bethesda, Md. and Grant 71-1016 from the American Heart Association, Dallas, Texas. Manuscript accepted September 10. 1975. Address for reprints: Pantel S. Vokonas, MD, Cardiology Division, Boston City Hospital, Boston. Mass. 02118.
The mechanical behavior of ischemic myocardium after coronary arterial occlusion and its relation to cardiac performance have been the subject of recent investigations in experimental animals and in patients with acute myocardial infarction. l-s Immediately after experimental coronary occlusion, aneurysmal systolic bulging of the ischemit portion of the left ventricular wall is uniformly observed, and is responsible at least in part for the immediate depression in cardiac function that ensues. Previous studies have demonstrated that this dyskinesia resolves within a few days after coronary occlusion and is a result of decreased compliance of the infarcted segment.7 Left ventricular performance in acute myocardial infarction is determined by a complex interrelation between the loss of functioning myocardium, the dissipation of contractile force to maintain tension in the ballooning segment and the contractile response of the nonischemic portion of the myocardium.1,2.s We therefore elected to
May 1976
The American
Journal
of CARDIOLOGY
Volume
37
653
MECHANICAL
BEHAVIOR
OF INFARCTED MYOCARDIUM-VOKONAS
ET AL.
Segment
Gauge
Gauge
..tY
\
,,
FIGURE 1. Schematic drawing of the anterior surface of the canine left ventricle, showing the position of two mercury-in-Silastic segment length gauges attached transversely to normal epicardium (control gauge) and to the area perfused by the ligated branch of the left circumflex coronary artery (infarct gauge). Pressure was measured with use of a short catheter attached directly to a strain gauge and placed through the left ventricular apex. LA = left atrium: LAD = left anterior descending coronary artery; LCf = circumflex coronary artery.
study the extent and time course of these segmental mechanical changes in a model of canine myocardial infarction not characterized by either an extensive loss of functioning myocardium or a serious deterioration in hemodynamic performance. These experiments were carried out to assess the early phase of experimental ischemia, to determine whether resolution of the aneurysmal bulge is noted at this stage, and if so, to relate such changes to changes ih compli-
Data Analysis and Calculations Phasic recordings of segment length were analyzed to determine end-diastolic segment length and the total amplitude of the phasic segment length oscillation during each cardiac cycle (Fig. 2). To permit a comparison of changes in segment length in both normal and ischemic myocardial segments in the same animal and among animals using gauges that necessarily differed in initial length, each phasic segment length amplitude (ZSL) was normalized to its respective end-diastolic segment length (EDsrJ as shown:
ance. Methods
Studies were performed in eight mongrel dogs weighing
Normalized segment length amplitude = KSL/EDat
17 to 23 kg and anesthetized with 30 mg/kg body weight sodium pentobarbital given intravenously. After endotracheal intubation, positive pressure ventilation was maintained by a Bennett model PR-1 respirator with use of room air supplemented with 40 percent oxygen. A left thoracotomy was performed and the exposed heart was supported in a pericardial cradle. A single ventricular branch of the left circumflex artery was carefully dissected free near its origin and a ligature passed beneath the vessel (Fig. 1). After control measurements were obtained, the artery was occluded by tying the ligature at this point. Using this technique, a small well circumscribed myocardial infarction 1 to 2 cm in diameter was consistently produced (see later).
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Length and Other Measurements
Measurements of segment length were made by short mercury-in-Silastic length gauges” (inner and outer diameter 0.012 and 0.025 inch, respectively [0.036 and 0.064 cm]; Parks Electronics, Beaverton, Ore.) positioned directly over the anterolateral left ventricular surface in a transverse orientation (Fig. 1). Each end of the segment length gauge was anchored in place by means of a small (8 mm diameter) Teflon@ button sutured directly to the epicardium. Two gauges were implanted, one positioned over the myocardial region to be made ischemic and the other over an adjacent segment of normal myocardium. The gauges positioned over the area to be made ischemic were specially constructed to be short enough (1 to 2 cm) to sample primarily ischemic muscle. Each gauge was calibrated before and after each experiment and showed stable gain and linearity. Simultaneous left ventricular pressure measurements were made with use of a short polyethylene cannula inserted into the left ventricle at the apex and attached directly to a Statham P23Db pressure transducer. The zero point for pressure measurements was set at the level of the midleft ventricle. In addition, the electrocardiogram and aortic pressure were recorded. Simultaneous phasic recordings of all signals were made on a direct-writing recorder (Brush 480). Serial measurements were performed under control conditions 5, 15, 30 and 60 minutes after coronary ligation, and at hourly intervals thereafter for a total of 6 hours. An external drip infusion of physiologic saline solution was used to keep the ventricular surface moist throughout the period of study to prevent drying of the epicardium. After these studies, the gauges were removed, the thoracotomy closed and the animal permitted to recover. Twenty-four hours after coronary ligation, the animal was killed by injection of an overdose of sodium pentobarbital. The heart was excised, and full thickness sections of the ventricular wall through both normal and infarcted regions of the myocardium were removed for gross and histologic study. The presence of a well circumscribed zone of myocardial necrosis directly underlying the previous position of the infarct gauge was thereby objectively confirmed in each animal.
Hereafter, this dimensionless normalized value is referred to as muscle lengths since it defines fractional shortening or lengthening in the epicardial muscle segment to which the gauge is attached. In this study, changes in measurements of both phasic segment length amplitudes and corresponding muscle lengths were used to assess the degree of aneurysmal bulging observed after coronary occlusion. Pressure-length loops were derived by constructing continuous plots of normalized segment length (infarct gauge) versus simultaneous left ventricular pressures at 20 msec intervals throughout the cardiac cycle in representative beats before and after coronary ligation.
37
MECHANICAL BEHAVIOR OF INFARCTED MYOCARDIUM-VOKONAS
PRE 40
*
200
20 -
100
ET AL.
POST
LV
PRESSURE /mmHg/
O17.8
FIGURE 2. Top, high gain (rapid paper speed) and low gain (slow paper speed) tracings of left ventricular (LV) pressure before (pre) and immediately after (post) coronary occlusion. Center, segment length tracings from the infarct gauge. Bottom, tracings from the control gauge. The aneurysmal bulge appears in the infarct gauge tracings after occlusion, but is absent in the control gauge tracings. The latter also show no changes in left ventricular systolic peak or end-diastolic pressures. ilSL = phasic segment length amplitude: EDsL = enddiastolic segment length.
TABLE
SEGhfEN7 L ENGTtfINFARCT
r
15.6 E,&L
t
/mm)
1n
13.4 66.1 r
SEGh4EN T LENGTHCONTROL
55.2 c
/mm/
I 16.2 r
Hemodynamic Measurements Before and After Coronary Occlusion (mean values f standard error of the mean)
SEGMENT L ENGTtl/NfARCT
Left Ventricular
Control Postocclusion 15 Minutes 30 Minutes 1 Hour 2 Hours 3 Hours 4 Hours 5 Hours 6 Hours
Aortic Mean Pressure (mm Hg)
End-Diastolic Pressure (mm Hg)
Heart Rate (beats/min)
4.4 i 1.8
152 2 8
101+4
5.1 4.6 5.1 5.3 4.9 4.4 4.6 4.0
14829 147 i 9 147 + 10 144 f 10 149 f 10 149 f 10 151 i8 152 f 9
105 r4 106zk 4 110+6 109+5 109 i 4 105 r 5 107 f 4 107 *4
t + i fi + * + i-
2.0 1.8 2.1 2.0 1.9 1 .9 1 .9 1.7
SL
Control
1 1 Hr
2 Hrs
4 Hrs
1
6th
, 3.8
/mm/
FIGURE 3. Segment length tracings of single complexes recorded at a rapid paper speed from the ischemic area before, during and 1, 2, 4 and 6 hours after coronary occlusion. The aneurysmal contour noted after occlusion persists throughout the study, despite a decrease in the overall amplitude of the segment length tracings with passage of time.
Results Mechanical effects of acute coronary arterial occlusion: The effects of acute coronary occlusion on left ventricular pressure and segment length in the ischemic myocardial segment and in a segment of normal myocardium are shown in Figure 2. Before coronary occlusion, phasic recordings of segment length during the cardiac cycle were characterized by lengthening during the isovolumic period. Systolic shortening followed during the left ventricular ejection period and phasic segment length amplitude further decreased during isovolumic relaxation. Immediately after coronary occlusion there was a marked increase in the phasic segment length amplitude and the development of systolic aneurysmal bulging, as indicated by the rounded systolic contours, during the period of left ventricular ejection. End-diastolic segment length showed a small but consistent increase after coronary occlusion (see later). In comparison, no significant segment length changes were observed in the normal myocardial seg-
ment after coronary occlusion (Fig. 2) or in measured values of left ventricular end-diastolic pressure, heart rate or aortic pressure (Table I). Time course of change in segmental mechanical characteristics: Figure 3 shows representative phasic segment length tracings in the ischemic segment sequentially recorded at rapid speed during the 6 hour period. Segment length amplitude increased in comparison with control values for 1 to 2 hours after coronary occlusion. By 6 hours, however, phasic segment length amplitude had progressively decreased, approaching values observed in the control period. The rounded aneurysmal systolic contour that occurred immediately after coronary occlusion typically persisted for the remainder of the experiment. This suggests that active systolic contraction during left ventricular ejection does not return during this period. Mean values for muscle lengths (normalized segment length amplitude) were determined throughout the experimental period (Fig. 4). A significant increase in muscle lengths occurred immediately after occlusion, but values gradually returned to control levels over 6 hours, whereas no significant changes occurred in the nonischemic segments.
May 1976
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0.125 r -.
ASL
I
1
, ASL; I
k--=--l I I I
0
2
1
3
4
5
6
HOURS FIGURE 4. Muscle lengths (normalized segment length amplitude) for both infarcted and control segments throughout the course of the experiment. Horizontal bars indicate the standard error of themean. Significant increases in muscle lengths over the initial value are noted up to the 3rd hour after coronary occlusion (P <0.05, paired differences). No significant changes were noted in the control segment. Muscle length = phasic segment length amplitude (ASL)/enddiastolic segment length (EDsL). 0 Control rl l
I 0
I
I
I
0
1
2
3
I
I
4
5
6
clockwise loop inscription indicating active shortening during the ejection period and the performance of mechanical work by the muscle segment. One hour after coronary occlusion, the end-diastolic segment length is displaced rightward to a longer resting length, whereas the loop is displaced to the right and is inscribed in a clockwise direction, indicating lengthening during the ejection period. Six hours after coronary occlusion, the pressurelength loop continues to be inscribed in a clockwise direction, indicating the continuing absence of work performance by the segment. But the loop is now to the left of the position at 1 hour. The end-diastolic length remains elongated. These changes in configuration are in agreement with the findings of an initial increase followed by a decrease in phasic segment length amplitude observed in our 6 hour study period (Fig. 3 and 4).
HOURS FIGURE 5. Percent changes in end-diastolic segment length (EDsL) throughout the course of experiment, using the preocclusion enddiastolic segment length value as the reference value. Horizontal bars indicate standard error of the mean. End-diastolic segment length in the ischemic segment increased significantly (P (0.05) immediately after occlusion and remained stable thereafter. There were no significant changes in the control segment.
Mean values for end-diastolic segment length were also computed (Fig. 5). There was an immediate increase in end-diastolic segment length in the ischemit myocardium, and this higher value continued throughout the experiment even though there were no signficant increases in left ventricular end-diastolic pressure (Table I) and no changes occurred in the control segment. Pressure-length relations in the ischemic segment: To provide an additional frame of reference for analyzing segmental changes, instantaneous pressure-length loops obtained from the ischemic segment in one experiment are shown in Figure 6. The control beat shown is characterized by a counter-
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I 0.10
FIGURE 6. Pressure-length loops reconstructed by plotting instantaneous pressure versus segment length from single cardiac cycles, recorded in a representative experiment. Open circles show a control (preocclusion) loop, triangles a loop recorded 1 hour after occlusion and closed circles a loop recorded at 6 hours. Arrows show the direction of loop inscription. In this example values of muscle lengths are referenced to the control value of end-diastolic segment length (EDsL), designated as zero. ASL = phasic segment-length amplitude; LV = left ventricular. See text for discussion.
Control
kc’
I 0.05
Hr 6 Hrs
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of CARDIOLOGY
Volume
Discussion The development of aneurysmal systolic bulging of the ischemic portion of the left ventricular wall immediately after coronary occlusion has been shown
37
MECHANICAL BEHAVIOR OF INFARCTED MYOCARDIUM-VOKONAS
experimentally by several investigators utilizing various techniques.1J0m16 Similar focal abnormalities of left ventricular contraction have been observed in patients after acute myocardial infarction in clinical studies using such techniques as ventriculography,‘7 radarkymography,18 apex cardiographylg and echocardiography.20 Previous studies have also demonstrated that acute depression in left ventricular performance after myocardial infarction is determined by a complex interrelation between at least three factors: (1) primary loss of functioning myocardium as determined by infarct size measured before or after death,21J2 (2) systolic bulging of the infarcted area, which permits local sequestration of blood and thereby reduces effective stroke volume,1,6,7 and (3) the contractile response of the nonischemic portion of the myocardium.s It has also been demonstrated that systolic aneurysmal bulging of the infarcted region usually resolves within 3 to 5 days after coronary occlusion and is related to increased stiffness of the infarcted segment.7 Such a mechanism could in part explain the time-dependent improvement in hemodynamic performance noted in the 1st week after myocardial infarction.2,6 In this invkstigation we studied segment length changes in the early stages of ischemia and infarction to determine the time of onset of alteration in the aneurysmal bulge. We studied animals with small focal ischemic lesions, so that extensive loss of functioning myocardium and secondary hemodynamic changes would not complicate interpretation of the results. Thus, the changes observed reflect changes in the intrinsic mechanical properties of ischemic myocardium and are not influenced by other mechanical factors such as changes in preload and afterload. Phasic segment length changes of ischemic myocardium: Before coronary occlusion, control phasic recordings of epicardial segment length (Fig. 2) show during the isovolumic period lengthening that is related to thickening of the ventricular shell as tension is developed.‘Z There is then a progressive downward slope reflecting active systolic shortening during the period of left ventricular ejection and a further more rapid decrease in phasic segment length amplitude during isovolumic relaxation as the ventricular shell becomes dynamically thinner. Aneurysmal systolic bulging of the ischemic segment is observed immediately after coronary occlusion (Fig. 2). Similar immediate changes after ischemia have been observed previously by other investigators’,:~JO and more recently by Banka and Helfant*:’ in a study using epicardial segment length gauges. In our study these observations were extended for 6 hours after coronary occlusion. Thus, our findings indicate that the amplitude of the aneurysma1 bulge noted immediately after coronary ligation gradually diminishes over 6 hours and returns to control values by the end of the experiment (Fig. 3 and 4). However, phasic recordings of segment length throughout the cardiac cycle show that a rounded or
ET AL.
aneurysmal contour is retained for the 6 hour period. These changes are accompanied by a fixed increase in end-diastolic segment length in the ischemic segment despite unchanged left ventricular end-diastolic pressures (Fig. 5, Table I), thus further suggesting the presence of viscous behavior (“creep”) in the ischemit segment during the relaxation phase of the cardiac cycle.24 Changes in contractility versus compliance: It is clear that resolution of the aneurysmal bulge begins within hours after experimental coronary occlusion. Two interpretations of this change are possible: (1) There may be a gradual return of local contractility, or (2) there may be a progressive increase in local stiffness. These possibilities are clarified by the diagrams shown in Figure 6, in which representative results from one experiment are presented in the form of pressure-length loops. In the control (preocclusion) loop, inscribed in a counterclockwise direction, active work is being performed by the segment. Amplitude along the length scale reflects primarily shortening during ejection. One hour after occlusion, a clockwise nonworking loop is inscribed; that is, the muscle segment no longer performs work, but now external mechanical work is being performed on the segment. l6 Phasic segment length amplitude now reflects the degree to which ischemic noncontractile myocardium is dynamically stretched by intracavitary pressure during systole. The increase in resting end-diastolic length, despite absence of an increase in end-diastolic pressure, may represent the effects of repeated stretching of muscle during systole and may indicate the presence of “stress-relaxation.” These effects of ischemia are initially due to loss of contractility since aneurysmal bulging may be abolished in the early phases of ischemia by infusion of inotropic agents directly into the ischemic segment.l Six hours after occlusion, a clockwise nonworking loop configuration persists, but the amplitude along the length scale is reduced; that is, the extent of aneurysmal bulging is diminished. Since there is no change in the overall loop configuration, and no decrease in the resting end-diastolic length, the results suggest that increased stiffness of the ischemic segment is responsible for reduction in amplitude of the aneurysmal bulge. Some information is available concerning compliance changes in acute experimental myocardial ischemia. An early increase in overall compliance of the focally ischemic left ventricle, measured from postmortem pressure-volume curves,25 has been documented.26 Our findings are compatible with this observation but also suggest that a subsequent decrease in compliance may occur over the next few hours. Presumably, these changes subsequently progress to the point of much greater stiffening, documented to occur after several days.7 Mechanism of changes in compliance of infarcted segment: The precise mechanism for these changes in the viscoelastic properties of ischemic and subsequently infarcted myocardium are uncertain. Initially, passive stretch of the noncontracting myo-
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MECHANICAL BEHAVIOR CF INFARCTED MYOCARDIUM-VOKONAS
ET AL
cardium during systole may disrupt the myofibrillar architecture or its supporting elements.2fi Subsequently stiffening occurs, perhaps as a consequence of tissue edema or the early cellular infiltration that is known to occur within hours after coronary occlusion, or possibly as a result of an intracellular process analogous to rigor mortis .27 The process of stiffening in the chronic phase may differ from that observed in the acute phase since infarcted tissue is ultimately replaced by collagenized fibrous tissue.28 Despite irreversible loss of a segment of the left ventricular wall that now no longer contracts, and that therefore does not contribute to stroke output, progressive stiffening of the infarcted segment and resolution of aneurysmal bulging may at least permit partial reversal of two of the mechanical factors that contribute to the deterioration in overall left ventricular function. Thus, contractile force would no longer be dissipated to maintain tension in the ballooning segment, and diminished displacement of blood within the ventricular chamber during systole would permit a corresponding increase in stroke volume. These mechanisms may in part explain the observed timedependent improvement in hemodynamic performance during the 1st week after myocardial infarction.2+s Clinical implications: The bearing of these experimental results upon clinical observations in acute and chronic ischemic heart disease deserves comment. Diminished left ventricular compliance has been documented in both acute myocardial infarction and the chronic phase of coronary artery disease.2gJ0 Some investigators2gv30 have also obtained evidence to suggest that an acute decrease in left ventricular
compliance accompanies the transient coronary ischemia of angina pectoris, but the mechanism may involve systolic tension prolongation of the type observed during experimental reperfusion of ischemic myocardium31,32 rather than changes in compliance as such. Thus far, a transient phase of increased compliance of ischemic tissues in the early phases of infarction in patients has not been documented. The occurrence of ventricular aneurysm in patients with symptomatic coronary artery disease and the correlation of such abnormalities with various clinical and hemodynamic indexes of left ventricular failure is now well established. l7 Less certain is the relation between left ventricular performance and the effects on segmental compliance produced by pathologic changes known to occur in infarcted myocardium, that is, progressive myocardial fibrosis during the weeks and months after an acute insult. In this regard, a recent study by Parmley et al.“” estimated the mechanical disadvantages to overall left ventricular function produced by ventricular aneurysms removed at cardiac surgery from patients with coronary artery disease. Muscular aneurysms were estimated to have a considerably greater mechanical disadvantage than either mixed fibrous and muscular or fibrous aneurysms. Since in each instance there was a significant loss of contracting myocardium, it is of interest that those aneurysms that retain the features of paradoxical systolic bulging and diminished local stiffness provide the greatest additional mechanical burden to left ventricular function. These findings are consistent with our short-term observations regarding the dynamic evolution of ventricular aneurysm after acute experimental myocardial infarction.
References I.
2.
3. 4.
5.
6.
7.
8.
9.
10.
858
Hood WB Jr, Cove16 VH, Abelmann WH, et al: Persistence of contractile behavior in acutely ischemic myocardium. Cardiovast Res 3:249-260, 1969 Kumar R, Hood WB Jr, Joison J, et al: Experimental myocardial infarction. II. Acute depression and subsequent recovery of left ventricular function: serial measurements in intact conscious dogs. J Clin Invest 49:55-62, 1970 Hood WB Jr: Pathophysiology of ischemic heart disease. Prog Cardiovasc Dis 14:297-320, 197 1 Russell RO Jr, Rackley CE, Pombo J, et al: Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction. J Clin Invest 49:1539-1550, 1970 Scheidt S, Ascheim R, Killip T Ilk Shock after acute myocardial infarction. A clinical and hemodynamic profile. Am J Cardiol 26:556-564, 1970 Swan HJC, Forrester JS, Diamond G, et al: Hemodynamic spectrum of myocardial infarction and cardiogenic shock: a conceptual model. Circulation 45:1097-l 110, 1972 Hood WB Jr, Bianco JA, Kumar R, et al: Experimental myocardial infarction. IV. Reduction of left ventricular compliance in the healing phase. J Clin Invest 49:1316-1323, 1970 Hood WB Jr: Experimental myocardial infarction. Ill. Recovery of left ventricular function in the healing phase: contribution of increased fiber shortening in non-infarcted myocardium. Am Heart J 79:531-538. 1970 Parrish D, Sirandness DE Jr, Bell JW: Dynamic response characteristics of a mercury-in-Silastic strain gauge. J Appl Physiol 19:363-365, 1964 Tennant R, Wiggers CJ: Effects of coronary occlusion on myo-
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of CARDIOLOGY
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11. 12.
13.
14.
15.
16.
17.
18.
19.
20.
37
cardial contraction. Am J Physiol 112:351-361, 1935 Tatooles CJ, Randall WC: Localized ventricular bulging after acute coronary occlusion. Am J Physiol 201:451-456, 1961 Newman WH, Walton RP: Alteration in left ventricular dimensions and mural force following coronary occlusion. Am J Physiol 214:1388-1391, 1968 Banka VS, Helfant RH: Temporal sequence of dynamic contractile characteristics in ischemic and nonischemic myocardium after acute coronary ligation. Am J Cardiol 34:158-163, 1974 Kerber RE, Abboud FM: Echocardiographic detection of regional myocardial infarction: an experimental study. Circulation 47: 997-1005, 1973 Theroux P, Franklin D, Ross J Jr, et al: Regional myocardial function during acute coronary occlusion and its modification by pharmacologic agents in the dog. Circ Res 35896-908, 1974 Tyberg JV, Forrester JS, Wyatt HL, et al: An analysis of segmental ischemic dysfunction utilizing the pressure-length loop. Circulation 46:748-754, 1974 Herman MV, Heinle RA, Klein MD, et al: Localized disorders in myocardial contraction: asynergy and its role in congestive heart failure. N Engl J Med 272:222-232, 1967 Kazamlas TM, Gander MP, Ross J Jr, et al: Detection of left ventricular wall motion disorders in coronary artery disease by radarkymography. N Engl J Med 285:63-71, 1971 Thakur MP, Venkataraman K, Madias JE, et al: Serial apexcardiograms in patients with acute myocardial infarction (abstr). Clin Res 21:955, 1973 Moue K, Smulyan H, Mookherjee S, et al: Ultrasonic measure-
MECHANICAL
21.
22.
23. 24. 25.
26.
27.
ment of left ventricular wall motion in acute myocardial infarction. Circulation 43:778-785, 1971 Maroko PR, Kjekshus JK, Sobel BE, et al: Factors influencing infarct size following experimental coronary artery occlusion. Circulation 43:67-82, 1971 Page DL, Caulfield JB, Kastor JA, et al: Myocardial changes associated with cardiogenic shock. N Engl J Med 285133-137, 1971 Rushmer RF, Crystal DK, Wagner C: The functional anatomy of ventricular contraction. Circ Res 1: 162-170, 1953 Alexander RS: Viscoelastic determinants of muscle contractility and “cardiac tone.” Fed Proc 21:1001-1005, 1962 Diamond G, Forrester JS, Hargis J, et al: Diastolic pressurevolume relationship in the canine left ventricle. Circ Res 29: 267-275, 1971 Forrester J, Diamond G, Parmley WW, et al: Early increase in left ventricular compliance following myocardial infarction. J Clin Invest 51:598-603, 1972 Szent-Gybrgyl A: Chemistry of Muscular Contraction. New
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OF INFARCTED MYOCARDIUM-VOKONAS
ET AL.
York, Academic Press, 1947, p 77-78 28. Mallory GK, White PD, Salcedo-Salgar J: The speed of healing of myocardial infarction. Am Heart J 18:647-67 1, 1939 29. Dwyer EM Jr: Left ventricular pressure-volume alterations in regional disorders of contraction during myocardial ischemia induced by atrial pacing. Circulation 42: 111 l-l 122, 1970 30. Diamond G, Forrester JS: Effects of coronary artery disease and acute myocardial infarction on left ventricular compliance in man. Circulation 45:11-19, 1972 31. Tyberg JV, Yeatman LA Jr, Parmley WW, et al: Effects of hypoxia on the mechanics of cardiac contraction. Am J Physiol 216:1780-1788, 1970 32. Bing OHL, Keefe JF, Wolk MJ, et al: Tension prolongation during recovery from myocardial hypoxia. J Clin Invest 50:660666, 1971 33. Parmley WW, Chuck L, Kfvowitz C, et al: In vitro length-tension relations of human ventricular aneurysms: the relationship of stiffness to mechanical disadvantage. Am J Cardiol 32: 889-894, 1973
May 1976
The American
Journal
of CARDIOLOGY
Volume
37
659
STUDIES
Experimental Myocardial Infarction XII. Dynamic Changes in Segmental Mechanical Infarcted and Non-infarcted Myocardium
PANTEL FAROUK
S. VOKONAS, A. PIRZADA,
WILLIAM
B. HOOD,
Boston,
Massachusetts
Jr.,
MD MD MD
Behavior of
The mechanical behavior of ischemic myocardium was studied in anesthetized open chest dogs. In each animal, a small well localized myocardial infarction was produced by ligation of a single ventricular branch of the left circumflex coronary artery. Serial in situ measurements of segment length were made by mercury-in-Silastic gauges sutured directly to the left ventricular surface. After coronary ligation, systolic aneurysmal bulging of the ischemic segment was uniformly noted. This was quantified as follows: normalized segment length change in this region, expressed in muscle lengths (where muscle lengths = phasic segment length amplitude/end-diastolic segment length), immediately increased from 0.06 f 0.01 (standard error of the mean) to 0.10 f 0.02 muscle lengths (i-67 percent, P <0.02). Over a 6 hour period, muscle lengths progressively declined to near control values, but retained an aneurysmal contour. End-diastolic segment length increased 5 percent above control values after coronary occlusion and remained fixed at this level for 6 hours. In contrast, noninfarcted myocardium exhibited no significant changes in muscle length or end-diastolic segment length. These studies demonstrate that the degree of systolic aneurysmal bulging in infarcted myocardium, although initially great, resolves within 6 hours but retains an aneurysmal contour. These findings are consistent with either partial return of contractility or diminished local compliance, but persistence of an aneurysmal shape favors the latter mechanism. The fixed increase in end-diastolic segment length suggests that “stress-relaxation” takes place in the infarcted region. It is possible that diminished compliance in zones of infarction, previously noted after several days, begins within a few hours after the onset of ischemia.
From the Cardiology Division of the Thorndike Memorial Laboratory and the Department of Medicine, Boston City Hospital, Boston University School of Medicine, Boston, Mass. This study was supported by U. S. Public Health Service Grants HL 14646, HE 07299, Contract 712498 and Training Grant 5TOl HL 05986 from the National Institutes of Health, Bethesda, Md. and Grant 71-1016 from the American Heart Association, Dallas, Texas. Manuscript accepted September 10. 1975. Address for reprints: Pantel S. Vokonas, MD, Cardiology Division, Boston City Hospital, Boston. Mass. 02118.
The mechanical behavior of ischemic myocardium after coronary arterial occlusion and its relation to cardiac performance have been the subject of recent investigations in experimental animals and in patients with acute myocardial infarction. l-s Immediately after experimental coronary occlusion, aneurysmal systolic bulging of the ischemit portion of the left ventricular wall is uniformly observed, and is responsible at least in part for the immediate depression in cardiac function that ensues. Previous studies have demonstrated that this dyskinesia resolves within a few days after coronary occlusion and is a result of decreased compliance of the infarcted segment.7 Left ventricular performance in acute myocardial infarction is determined by a complex interrelation between the loss of functioning myocardium, the dissipation of contractile force to maintain tension in the ballooning segment and the contractile response of the nonischemic portion of the myocardium.1,2.s We therefore elected to
May 1976
The American
Journal
of CARDIOLOGY
Volume
37
653
MECHANICAL
BEHAVIOR
OF INFARCTED MYOCARDIUM-VOKONAS
ET AL.
Segment
Gauge
Gauge
..tY
\
,,
FIGURE 1. Schematic drawing of the anterior surface of the canine left ventricle, showing the position of two mercury-in-Silastic segment length gauges attached transversely to normal epicardium (control gauge) and to the area perfused by the ligated branch of the left circumflex coronary artery (infarct gauge). Pressure was measured with use of a short catheter attached directly to a strain gauge and placed through the left ventricular apex. LA = left atrium: LAD = left anterior descending coronary artery; LCf = circumflex coronary artery.
study the extent and time course of these segmental mechanical changes in a model of canine myocardial infarction not characterized by either an extensive loss of functioning myocardium or a serious deterioration in hemodynamic performance. These experiments were carried out to assess the early phase of experimental ischemia, to determine whether resolution of the aneurysmal bulge is noted at this stage, and if so, to relate such changes to changes ih compli-
Data Analysis and Calculations Phasic recordings of segment length were analyzed to determine end-diastolic segment length and the total amplitude of the phasic segment length oscillation during each cardiac cycle (Fig. 2). To permit a comparison of changes in segment length in both normal and ischemic myocardial segments in the same animal and among animals using gauges that necessarily differed in initial length, each phasic segment length amplitude (ZSL) was normalized to its respective end-diastolic segment length (EDsrJ as shown:
ance. Methods
Studies were performed in eight mongrel dogs weighing
Normalized segment length amplitude = KSL/EDat
17 to 23 kg and anesthetized with 30 mg/kg body weight sodium pentobarbital given intravenously. After endotracheal intubation, positive pressure ventilation was maintained by a Bennett model PR-1 respirator with use of room air supplemented with 40 percent oxygen. A left thoracotomy was performed and the exposed heart was supported in a pericardial cradle. A single ventricular branch of the left circumflex artery was carefully dissected free near its origin and a ligature passed beneath the vessel (Fig. 1). After control measurements were obtained, the artery was occluded by tying the ligature at this point. Using this technique, a small well circumscribed myocardial infarction 1 to 2 cm in diameter was consistently produced (see later).
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Length and Other Measurements
Measurements of segment length were made by short mercury-in-Silastic length gauges” (inner and outer diameter 0.012 and 0.025 inch, respectively [0.036 and 0.064 cm]; Parks Electronics, Beaverton, Ore.) positioned directly over the anterolateral left ventricular surface in a transverse orientation (Fig. 1). Each end of the segment length gauge was anchored in place by means of a small (8 mm diameter) Teflon@ button sutured directly to the epicardium. Two gauges were implanted, one positioned over the myocardial region to be made ischemic and the other over an adjacent segment of normal myocardium. The gauges positioned over the area to be made ischemic were specially constructed to be short enough (1 to 2 cm) to sample primarily ischemic muscle. Each gauge was calibrated before and after each experiment and showed stable gain and linearity. Simultaneous left ventricular pressure measurements were made with use of a short polyethylene cannula inserted into the left ventricle at the apex and attached directly to a Statham P23Db pressure transducer. The zero point for pressure measurements was set at the level of the midleft ventricle. In addition, the electrocardiogram and aortic pressure were recorded. Simultaneous phasic recordings of all signals were made on a direct-writing recorder (Brush 480). Serial measurements were performed under control conditions 5, 15, 30 and 60 minutes after coronary ligation, and at hourly intervals thereafter for a total of 6 hours. An external drip infusion of physiologic saline solution was used to keep the ventricular surface moist throughout the period of study to prevent drying of the epicardium. After these studies, the gauges were removed, the thoracotomy closed and the animal permitted to recover. Twenty-four hours after coronary ligation, the animal was killed by injection of an overdose of sodium pentobarbital. The heart was excised, and full thickness sections of the ventricular wall through both normal and infarcted regions of the myocardium were removed for gross and histologic study. The presence of a well circumscribed zone of myocardial necrosis directly underlying the previous position of the infarct gauge was thereby objectively confirmed in each animal.
Hereafter, this dimensionless normalized value is referred to as muscle lengths since it defines fractional shortening or lengthening in the epicardial muscle segment to which the gauge is attached. In this study, changes in measurements of both phasic segment length amplitudes and corresponding muscle lengths were used to assess the degree of aneurysmal bulging observed after coronary occlusion. Pressure-length loops were derived by constructing continuous plots of normalized segment length (infarct gauge) versus simultaneous left ventricular pressures at 20 msec intervals throughout the cardiac cycle in representative beats before and after coronary ligation.
37
MECHANICAL BEHAVIOR OF INFARCTED MYOCARDIUM-VOKONAS
PRE 40
*
200
20 -
100
ET AL.
POST
LV
PRESSURE /mmHg/
O17.8
FIGURE 2. Top, high gain (rapid paper speed) and low gain (slow paper speed) tracings of left ventricular (LV) pressure before (pre) and immediately after (post) coronary occlusion. Center, segment length tracings from the infarct gauge. Bottom, tracings from the control gauge. The aneurysmal bulge appears in the infarct gauge tracings after occlusion, but is absent in the control gauge tracings. The latter also show no changes in left ventricular systolic peak or end-diastolic pressures. ilSL = phasic segment length amplitude: EDsL = enddiastolic segment length.
TABLE
SEGhfEN7 L ENGTtfINFARCT
r
15.6 E,&L
t
/mm)
1n
13.4 66.1 r
SEGh4EN T LENGTHCONTROL
55.2 c
/mm/
I 16.2 r
Hemodynamic Measurements Before and After Coronary Occlusion (mean values f standard error of the mean)
SEGMENT L ENGTtl/NfARCT
Left Ventricular
Control Postocclusion 15 Minutes 30 Minutes 1 Hour 2 Hours 3 Hours 4 Hours 5 Hours 6 Hours
Aortic Mean Pressure (mm Hg)
End-Diastolic Pressure (mm Hg)
Heart Rate (beats/min)
4.4 i 1.8
152 2 8
101+4
5.1 4.6 5.1 5.3 4.9 4.4 4.6 4.0
14829 147 i 9 147 + 10 144 f 10 149 f 10 149 f 10 151 i8 152 f 9
105 r4 106zk 4 110+6 109+5 109 i 4 105 r 5 107 f 4 107 *4
t + i fi + * + i-
2.0 1.8 2.1 2.0 1.9 1 .9 1 .9 1.7
SL
Control
1 1 Hr
2 Hrs
4 Hrs
1
6th
, 3.8
/mm/
FIGURE 3. Segment length tracings of single complexes recorded at a rapid paper speed from the ischemic area before, during and 1, 2, 4 and 6 hours after coronary occlusion. The aneurysmal contour noted after occlusion persists throughout the study, despite a decrease in the overall amplitude of the segment length tracings with passage of time.
Results Mechanical effects of acute coronary arterial occlusion: The effects of acute coronary occlusion on left ventricular pressure and segment length in the ischemic myocardial segment and in a segment of normal myocardium are shown in Figure 2. Before coronary occlusion, phasic recordings of segment length during the cardiac cycle were characterized by lengthening during the isovolumic period. Systolic shortening followed during the left ventricular ejection period and phasic segment length amplitude further decreased during isovolumic relaxation. Immediately after coronary occlusion there was a marked increase in the phasic segment length amplitude and the development of systolic aneurysmal bulging, as indicated by the rounded systolic contours, during the period of left ventricular ejection. End-diastolic segment length showed a small but consistent increase after coronary occlusion (see later). In comparison, no significant segment length changes were observed in the normal myocardial seg-
ment after coronary occlusion (Fig. 2) or in measured values of left ventricular end-diastolic pressure, heart rate or aortic pressure (Table I). Time course of change in segmental mechanical characteristics: Figure 3 shows representative phasic segment length tracings in the ischemic segment sequentially recorded at rapid speed during the 6 hour period. Segment length amplitude increased in comparison with control values for 1 to 2 hours after coronary occlusion. By 6 hours, however, phasic segment length amplitude had progressively decreased, approaching values observed in the control period. The rounded aneurysmal systolic contour that occurred immediately after coronary occlusion typically persisted for the remainder of the experiment. This suggests that active systolic contraction during left ventricular ejection does not return during this period. Mean values for muscle lengths (normalized segment length amplitude) were determined throughout the experimental period (Fig. 4). A significant increase in muscle lengths occurred immediately after occlusion, but values gradually returned to control levels over 6 hours, whereas no significant changes occurred in the nonischemic segments.
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0.125 r -.
ASL
I
1
, ASL; I
k--=--l I I I
0
2
1
3
4
5
6
HOURS FIGURE 4. Muscle lengths (normalized segment length amplitude) for both infarcted and control segments throughout the course of the experiment. Horizontal bars indicate the standard error of themean. Significant increases in muscle lengths over the initial value are noted up to the 3rd hour after coronary occlusion (P <0.05, paired differences). No significant changes were noted in the control segment. Muscle length = phasic segment length amplitude (ASL)/enddiastolic segment length (EDsL). 0 Control rl l
I 0
I
I
I
0
1
2
3
I
I
4
5
6
clockwise loop inscription indicating active shortening during the ejection period and the performance of mechanical work by the muscle segment. One hour after coronary occlusion, the end-diastolic segment length is displaced rightward to a longer resting length, whereas the loop is displaced to the right and is inscribed in a clockwise direction, indicating lengthening during the ejection period. Six hours after coronary occlusion, the pressurelength loop continues to be inscribed in a clockwise direction, indicating the continuing absence of work performance by the segment. But the loop is now to the left of the position at 1 hour. The end-diastolic length remains elongated. These changes in configuration are in agreement with the findings of an initial increase followed by a decrease in phasic segment length amplitude observed in our 6 hour study period (Fig. 3 and 4).
HOURS FIGURE 5. Percent changes in end-diastolic segment length (EDsL) throughout the course of experiment, using the preocclusion enddiastolic segment length value as the reference value. Horizontal bars indicate standard error of the mean. End-diastolic segment length in the ischemic segment increased significantly (P (0.05) immediately after occlusion and remained stable thereafter. There were no significant changes in the control segment.
Mean values for end-diastolic segment length were also computed (Fig. 5). There was an immediate increase in end-diastolic segment length in the ischemit myocardium, and this higher value continued throughout the experiment even though there were no signficant increases in left ventricular end-diastolic pressure (Table I) and no changes occurred in the control segment. Pressure-length relations in the ischemic segment: To provide an additional frame of reference for analyzing segmental changes, instantaneous pressure-length loops obtained from the ischemic segment in one experiment are shown in Figure 6. The control beat shown is characterized by a counter-
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I 0.10
FIGURE 6. Pressure-length loops reconstructed by plotting instantaneous pressure versus segment length from single cardiac cycles, recorded in a representative experiment. Open circles show a control (preocclusion) loop, triangles a loop recorded 1 hour after occlusion and closed circles a loop recorded at 6 hours. Arrows show the direction of loop inscription. In this example values of muscle lengths are referenced to the control value of end-diastolic segment length (EDsL), designated as zero. ASL = phasic segment-length amplitude; LV = left ventricular. See text for discussion.
Control
kc’
I 0.05
Hr 6 Hrs
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Discussion The development of aneurysmal systolic bulging of the ischemic portion of the left ventricular wall immediately after coronary occlusion has been shown
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MECHANICAL BEHAVIOR OF INFARCTED MYOCARDIUM-VOKONAS
experimentally by several investigators utilizing various techniques.1J0m16 Similar focal abnormalities of left ventricular contraction have been observed in patients after acute myocardial infarction in clinical studies using such techniques as ventriculography,‘7 radarkymography,18 apex cardiographylg and echocardiography.20 Previous studies have also demonstrated that acute depression in left ventricular performance after myocardial infarction is determined by a complex interrelation between at least three factors: (1) primary loss of functioning myocardium as determined by infarct size measured before or after death,21J2 (2) systolic bulging of the infarcted area, which permits local sequestration of blood and thereby reduces effective stroke volume,1,6,7 and (3) the contractile response of the nonischemic portion of the myocardium.s It has also been demonstrated that systolic aneurysmal bulging of the infarcted region usually resolves within 3 to 5 days after coronary occlusion and is related to increased stiffness of the infarcted segment.7 Such a mechanism could in part explain the time-dependent improvement in hemodynamic performance noted in the 1st week after myocardial infarction.2,6 In this invkstigation we studied segment length changes in the early stages of ischemia and infarction to determine the time of onset of alteration in the aneurysmal bulge. We studied animals with small focal ischemic lesions, so that extensive loss of functioning myocardium and secondary hemodynamic changes would not complicate interpretation of the results. Thus, the changes observed reflect changes in the intrinsic mechanical properties of ischemic myocardium and are not influenced by other mechanical factors such as changes in preload and afterload. Phasic segment length changes of ischemic myocardium: Before coronary occlusion, control phasic recordings of epicardial segment length (Fig. 2) show during the isovolumic period lengthening that is related to thickening of the ventricular shell as tension is developed.‘Z There is then a progressive downward slope reflecting active systolic shortening during the period of left ventricular ejection and a further more rapid decrease in phasic segment length amplitude during isovolumic relaxation as the ventricular shell becomes dynamically thinner. Aneurysmal systolic bulging of the ischemic segment is observed immediately after coronary occlusion (Fig. 2). Similar immediate changes after ischemia have been observed previously by other investigators’,:~JO and more recently by Banka and Helfant*:’ in a study using epicardial segment length gauges. In our study these observations were extended for 6 hours after coronary occlusion. Thus, our findings indicate that the amplitude of the aneurysma1 bulge noted immediately after coronary ligation gradually diminishes over 6 hours and returns to control values by the end of the experiment (Fig. 3 and 4). However, phasic recordings of segment length throughout the cardiac cycle show that a rounded or
ET AL.
aneurysmal contour is retained for the 6 hour period. These changes are accompanied by a fixed increase in end-diastolic segment length in the ischemic segment despite unchanged left ventricular end-diastolic pressures (Fig. 5, Table I), thus further suggesting the presence of viscous behavior (“creep”) in the ischemit segment during the relaxation phase of the cardiac cycle.24 Changes in contractility versus compliance: It is clear that resolution of the aneurysmal bulge begins within hours after experimental coronary occlusion. Two interpretations of this change are possible: (1) There may be a gradual return of local contractility, or (2) there may be a progressive increase in local stiffness. These possibilities are clarified by the diagrams shown in Figure 6, in which representative results from one experiment are presented in the form of pressure-length loops. In the control (preocclusion) loop, inscribed in a counterclockwise direction, active work is being performed by the segment. Amplitude along the length scale reflects primarily shortening during ejection. One hour after occlusion, a clockwise nonworking loop is inscribed; that is, the muscle segment no longer performs work, but now external mechanical work is being performed on the segment. l6 Phasic segment length amplitude now reflects the degree to which ischemic noncontractile myocardium is dynamically stretched by intracavitary pressure during systole. The increase in resting end-diastolic length, despite absence of an increase in end-diastolic pressure, may represent the effects of repeated stretching of muscle during systole and may indicate the presence of “stress-relaxation.” These effects of ischemia are initially due to loss of contractility since aneurysmal bulging may be abolished in the early phases of ischemia by infusion of inotropic agents directly into the ischemic segment.l Six hours after occlusion, a clockwise nonworking loop configuration persists, but the amplitude along the length scale is reduced; that is, the extent of aneurysmal bulging is diminished. Since there is no change in the overall loop configuration, and no decrease in the resting end-diastolic length, the results suggest that increased stiffness of the ischemic segment is responsible for reduction in amplitude of the aneurysmal bulge. Some information is available concerning compliance changes in acute experimental myocardial ischemia. An early increase in overall compliance of the focally ischemic left ventricle, measured from postmortem pressure-volume curves,25 has been documented.26 Our findings are compatible with this observation but also suggest that a subsequent decrease in compliance may occur over the next few hours. Presumably, these changes subsequently progress to the point of much greater stiffening, documented to occur after several days.7 Mechanism of changes in compliance of infarcted segment: The precise mechanism for these changes in the viscoelastic properties of ischemic and subsequently infarcted myocardium are uncertain. Initially, passive stretch of the noncontracting myo-
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MECHANICAL BEHAVIOR CF INFARCTED MYOCARDIUM-VOKONAS
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cardium during systole may disrupt the myofibrillar architecture or its supporting elements.2fi Subsequently stiffening occurs, perhaps as a consequence of tissue edema or the early cellular infiltration that is known to occur within hours after coronary occlusion, or possibly as a result of an intracellular process analogous to rigor mortis .27 The process of stiffening in the chronic phase may differ from that observed in the acute phase since infarcted tissue is ultimately replaced by collagenized fibrous tissue.28 Despite irreversible loss of a segment of the left ventricular wall that now no longer contracts, and that therefore does not contribute to stroke output, progressive stiffening of the infarcted segment and resolution of aneurysmal bulging may at least permit partial reversal of two of the mechanical factors that contribute to the deterioration in overall left ventricular function. Thus, contractile force would no longer be dissipated to maintain tension in the ballooning segment, and diminished displacement of blood within the ventricular chamber during systole would permit a corresponding increase in stroke volume. These mechanisms may in part explain the observed timedependent improvement in hemodynamic performance during the 1st week after myocardial infarction.2+s Clinical implications: The bearing of these experimental results upon clinical observations in acute and chronic ischemic heart disease deserves comment. Diminished left ventricular compliance has been documented in both acute myocardial infarction and the chronic phase of coronary artery disease.2gJ0 Some investigators2gv30 have also obtained evidence to suggest that an acute decrease in left ventricular
compliance accompanies the transient coronary ischemia of angina pectoris, but the mechanism may involve systolic tension prolongation of the type observed during experimental reperfusion of ischemic myocardium31,32 rather than changes in compliance as such. Thus far, a transient phase of increased compliance of ischemic tissues in the early phases of infarction in patients has not been documented. The occurrence of ventricular aneurysm in patients with symptomatic coronary artery disease and the correlation of such abnormalities with various clinical and hemodynamic indexes of left ventricular failure is now well established. l7 Less certain is the relation between left ventricular performance and the effects on segmental compliance produced by pathologic changes known to occur in infarcted myocardium, that is, progressive myocardial fibrosis during the weeks and months after an acute insult. In this regard, a recent study by Parmley et al.“” estimated the mechanical disadvantages to overall left ventricular function produced by ventricular aneurysms removed at cardiac surgery from patients with coronary artery disease. Muscular aneurysms were estimated to have a considerably greater mechanical disadvantage than either mixed fibrous and muscular or fibrous aneurysms. Since in each instance there was a significant loss of contracting myocardium, it is of interest that those aneurysms that retain the features of paradoxical systolic bulging and diminished local stiffness provide the greatest additional mechanical burden to left ventricular function. These findings are consistent with our short-term observations regarding the dynamic evolution of ventricular aneurysm after acute experimental myocardial infarction.
References I.
2.
3. 4.
5.
6.
7.
8.
9.
10.
858
Hood WB Jr, Cove16 VH, Abelmann WH, et al: Persistence of contractile behavior in acutely ischemic myocardium. Cardiovast Res 3:249-260, 1969 Kumar R, Hood WB Jr, Joison J, et al: Experimental myocardial infarction. II. Acute depression and subsequent recovery of left ventricular function: serial measurements in intact conscious dogs. J Clin Invest 49:55-62, 1970 Hood WB Jr: Pathophysiology of ischemic heart disease. Prog Cardiovasc Dis 14:297-320, 197 1 Russell RO Jr, Rackley CE, Pombo J, et al: Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction. J Clin Invest 49:1539-1550, 1970 Scheidt S, Ascheim R, Killip T Ilk Shock after acute myocardial infarction. A clinical and hemodynamic profile. Am J Cardiol 26:556-564, 1970 Swan HJC, Forrester JS, Diamond G, et al: Hemodynamic spectrum of myocardial infarction and cardiogenic shock: a conceptual model. Circulation 45:1097-l 110, 1972 Hood WB Jr, Bianco JA, Kumar R, et al: Experimental myocardial infarction. IV. Reduction of left ventricular compliance in the healing phase. J Clin Invest 49:1316-1323, 1970 Hood WB Jr: Experimental myocardial infarction. Ill. Recovery of left ventricular function in the healing phase: contribution of increased fiber shortening in non-infarcted myocardium. Am Heart J 79:531-538. 1970 Parrish D, Sirandness DE Jr, Bell JW: Dynamic response characteristics of a mercury-in-Silastic strain gauge. J Appl Physiol 19:363-365, 1964 Tennant R, Wiggers CJ: Effects of coronary occlusion on myo-
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11. 12.
13.
14.
15.
16.
17.
18.
19.
20.
37
cardial contraction. Am J Physiol 112:351-361, 1935 Tatooles CJ, Randall WC: Localized ventricular bulging after acute coronary occlusion. Am J Physiol 201:451-456, 1961 Newman WH, Walton RP: Alteration in left ventricular dimensions and mural force following coronary occlusion. Am J Physiol 214:1388-1391, 1968 Banka VS, Helfant RH: Temporal sequence of dynamic contractile characteristics in ischemic and nonischemic myocardium after acute coronary ligation. Am J Cardiol 34:158-163, 1974 Kerber RE, Abboud FM: Echocardiographic detection of regional myocardial infarction: an experimental study. Circulation 47: 997-1005, 1973 Theroux P, Franklin D, Ross J Jr, et al: Regional myocardial function during acute coronary occlusion and its modification by pharmacologic agents in the dog. Circ Res 35896-908, 1974 Tyberg JV, Forrester JS, Wyatt HL, et al: An analysis of segmental ischemic dysfunction utilizing the pressure-length loop. Circulation 46:748-754, 1974 Herman MV, Heinle RA, Klein MD, et al: Localized disorders in myocardial contraction: asynergy and its role in congestive heart failure. N Engl J Med 272:222-232, 1967 Kazamlas TM, Gander MP, Ross J Jr, et al: Detection of left ventricular wall motion disorders in coronary artery disease by radarkymography. N Engl J Med 285:63-71, 1971 Thakur MP, Venkataraman K, Madias JE, et al: Serial apexcardiograms in patients with acute myocardial infarction (abstr). Clin Res 21:955, 1973 Moue K, Smulyan H, Mookherjee S, et al: Ultrasonic measure-
MECHANICAL
21.
22.
23. 24. 25.
26.
27.
ment of left ventricular wall motion in acute myocardial infarction. Circulation 43:778-785, 1971 Maroko PR, Kjekshus JK, Sobel BE, et al: Factors influencing infarct size following experimental coronary artery occlusion. Circulation 43:67-82, 1971 Page DL, Caulfield JB, Kastor JA, et al: Myocardial changes associated with cardiogenic shock. N Engl J Med 285133-137, 1971 Rushmer RF, Crystal DK, Wagner C: The functional anatomy of ventricular contraction. Circ Res 1: 162-170, 1953 Alexander RS: Viscoelastic determinants of muscle contractility and “cardiac tone.” Fed Proc 21:1001-1005, 1962 Diamond G, Forrester JS, Hargis J, et al: Diastolic pressurevolume relationship in the canine left ventricle. Circ Res 29: 267-275, 1971 Forrester J, Diamond G, Parmley WW, et al: Early increase in left ventricular compliance following myocardial infarction. J Clin Invest 51:598-603, 1972 Szent-Gybrgyl A: Chemistry of Muscular Contraction. New
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OF INFARCTED MYOCARDIUM-VOKONAS
ET AL.
York, Academic Press, 1947, p 77-78 28. Mallory GK, White PD, Salcedo-Salgar J: The speed of healing of myocardial infarction. Am Heart J 18:647-67 1, 1939 29. Dwyer EM Jr: Left ventricular pressure-volume alterations in regional disorders of contraction during myocardial ischemia induced by atrial pacing. Circulation 42: 111 l-l 122, 1970 30. Diamond G, Forrester JS: Effects of coronary artery disease and acute myocardial infarction on left ventricular compliance in man. Circulation 45:11-19, 1972 31. Tyberg JV, Yeatman LA Jr, Parmley WW, et al: Effects of hypoxia on the mechanics of cardiac contraction. Am J Physiol 216:1780-1788, 1970 32. Bing OHL, Keefe JF, Wolk MJ, et al: Tension prolongation during recovery from myocardial hypoxia. J Clin Invest 50:660666, 1971 33. Parmley WW, Chuck L, Kfvowitz C, et al: In vitro length-tension relations of human ventricular aneurysms: the relationship of stiffness to mechanical disadvantage. Am J Cardiol 32: 889-894, 1973
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