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Myocardial revascularization after acute infarction
Myocardial Revascularization
HOOSHANG BOLOOKI, MD, FRCS (C), FACC with the assistance of MICHAEL D. KOTLER, BS LAWRENCE LOTTENBERG, BS STEPHEN DRESNICK, BS ROBERT C. ANDREWS, BS STEVEN KIPNIS, BS RICHARD M. ELLIS l
Miami, Florida
From the Division of Thoracic and Cardiovascular Surgery, University of Miami, School of Medicine, Miami, Fla. This study was supported in part by Grant HE 13978-04 from the National Institutes of Health, Bethesda, Md., and grants inaid from Eli Lilly Research Laboratories, Indianapolis, Ind. and Greater Miami Heart Association, Miami, Fla. Research Career Development Awardee, National Heart and Lung Institute, Grant HL 70670-03. Address for reprints: Hooshang Bolooki, MD, P.O. Box 675. Biscayne Annex, Miami, Fla. 33152. l
After Acute Infarction
The purpose of this study was (1) to establish the maximal interval between the onset of ischemia and reperfusion that would permit a decrease in the size of infarction, and (2) to evaluate the relation between changes in infarct size and preservation of cardiac function. Studies were carried out in 19 dogs of which 13 had temporary (1 to 3 hours) occlusion of the left anterior descending coronary artery. The hospital course of 15 patients of whom 13 underwent myocardial revascularization within 8 hours of acute infarction was also reviewed. In dogs, the eventual pathologic infarct size was significantly reduced if reperfusion was performed within 2 hours of ischemia. After 2 hours of ischemia, the revascularized segment remained dyskinetic on angiographic assessment and cardiac function was depressed. After 3 hours of ischemia, in spite of a patent coronary artery, the extent of infarct and dykinesia was greater than during ligation of the left anterior descending coronary artery. In patients, small infarcts developed with revascularization performed more than 4 hours afler infarction but with revascularization of the lefl anterior descending coronary artery the size of the dyskinetic area (as assessed with angiography) was similar to that in patients wlth a closed graft to the left anterior descending coronary artery but with a patent graft to its diagonal branch. In all patients after revascularization the extent of the left ventricular dysktnetic area was smaller and cardiac function was significantly better than in patients who did not receive revascularization for complete occlusion of the left anterior descending coronary artery. In spite of successful revascularizatton, electrocardiographic evidence of transmural infarction persisted postoperatively. It is concluded that reperfusion of an area of myocardium that has been ischemic for less than 2 hours in dogs or less than 4 hours in man may lead to a significant reduction in the extent of infarction as well as improvement in cardiac function. However, the revascularized area remains angiographically dysklnetic and electrocardiographically abnormal.
Previous experimental studies1*2 and recent clinical reports3 indicate that reperfusion of an area of myocardium after a few hours of ischemia can result in a significant reduction of the eventual size of infarct. The purpose of our research was to answer some important questions regarding the surgical treatment of acute myocardial ischemia and infarction by direct myocardial revascularization (reperfusion). First, we attempted to establish the maximal interval from ischemia to reperfusion that would permit clinically and angiographitally successful revascularization with reduction in the size of infarct. Second, we attempted to evaluate the relation between the extent of cardiac muscle preserved and cardiac function. The studies were performed simultaneously in a group of dogs and in a group of patients who underwent myocardial revascularization after acute infarction. Brief reports4-7 on the results of this work have been periodically published elsewhere.
September1975 The American Journal of CARDIOLOGY
Volume 36
395
MYOCARDIAL REVA6CULARlZATlDN APTER ACUTE INFARCTKM-BOLDDKI
II
I
Ill
AVR
AVL
v,
AVF
v3
v2
v,
v5
VE
A
II
2 (3:OO pm]
I
II
Preop.
Ill
AN
AVL
V,
AVf
V3
V,
V,
V5
V,
FIGURE 1. Case 6, Group II. Serial 12 lead electrocardiograms from a patient who was admitted with evidence of subendocardial ischemia (A). After 3 days of therapy, chest pain continued with persistent electrocardiographic changes (B). Diagnostic cardiac catheterization studies were performed at this time and within 3 hours there was acute S-T segment elevation in the precordial leads (C) concomitant with marked serum enzyme elevation. The patient was operated on within 6 hours and underwent myocardial revascularization within 8 hours of development of chest pain, sweating and hypotension. The postoperative electrocardiogram revealed evolution of anterior wall myocardial infarction (D) in spite of a patent anterior descending coronary graft (see Fig. 7). (Reprinted by permission from Bolooki et al.13)
11/Z/71 PIE-O?
III
AVR AVl AVF
Vi
V,
4
!r,
+I 4s I:
’
4
t
11/:/I I
IKT-IP 111 A’/! II
AVL
AVf
VI
VI
V,
VI
Methods Experimental Studies Studies were performed in 19 mongrel dogs of both sexes weighing 23 to 25 kg. Preoperatively a control electrocardiogram, left ventriculograms and selective left coronary arteriograms were obtained. Cardiac catheterization was performed 3 to 4 days before surgical occlusion of the left anterior descending coronary artery followed by reperfusion of the vessel or by direct revascularization with the use of left internal mammary-coronary artery anastomosis. Cardiac catheterization studies: These investigations were carried out under mild anesthesia with intravenously administered pentobarbital sodium (10 mg/kg body weight). With the dogs in the right anterior oblique position, a groin cut-down procedure was performed and a no.
396
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The American Journal of CARDIOLOGY
Vs
Vr
FIGURE 2. Case 9, Group Ill. Serial 12 lead electrocardiograms from a patient admitted with the diagnosis of preinfarction angina (A). In the course of 24 hours, the chest pain increased in frequency and severity in spite of extensive treatment. There was electrocardiographic evidence of subendocardial ischemia (B). The patient underwent emergency cardiac catheterization studies but within 2 hours presented with hypotension and sweating with electrocardiographic evidence of extensive anterior wall myocardial infarction (C) and serum enzyme elevation. He was operated upon immediately and received a bypass graft to the left anterior descending coronary artery within 4 hours of the onset of chest pain and electrocardiographic evidence of infarction. Postoperatively he remained in a low output state and required vasopressor therapy. An electrocardiogram taken 5 days postoperatively revealed further evolution of the anterior wall infarction (D).
7F Cordis catheter was threaded into the left ventricular cavity. A left ventriculogram was then obtained with hand injection of 20 cc of 90 percent Hypaquea. The left ventriculograms were recorded with Phillips equipment on 35 mm tine films at a rate of 60 frames/set. Selective coronary arteriograms were obtained with use of a Cordis left coronary arterial catheter. By hand injection of 5 to 10 ml of 90 percent Hypaque into the coronary artery, the patency of this vessel and the extent of its collateralization and runoff were assessed. Postoperative cardiac catheterization studies (ventriculography and left coronary and internal mammary artery arteriography) were performed 1 week after the operation using methods similar to those of the preoperative studies. In six dogs serial angiographic studies 2, 4 and 7 days postoperatively were performed to study the changes in left
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MYOCARDIAL Rf3’ASClJlARlZAT0N
ventricular contraction pattern and to assess patency of the left anterior descending coronary artery or internal mammary artery graft. Surgical procedure: Surgery was carried out under pentobarbital sodium anesthesia (25 mg/kg) with the dogs intubated, connected to a Bird respirator and breathing an oxygen-air mixture. The dogs were placed in the right lateral decubitus position and prepared and draped in a sterile manner. The groin was dissected, and the femoral vein and artery were exposed. The vein was used for intravenous infusion, and the artery for intraventricular pressure monitoring by a transducer tip catheter (Edwards). A left thoracotomy was then made at the fourth intercostal space and the precordium was opened vertically to develop-a cradle. The heart was examined, and communications between the left anterior descending coronary artery and the posterior branches were ligated. In 10 dogs, the left anterior descending coronary artery was ligated above the level of its first diagonal branch, and the left internal mammary artery, dissected free from the anterior chest wall, was used to anastomose to the left anterior descending coronary artery. In the remaining dogs the left anterior descending coronary artery was temporarily occluded (six dogs) or ligated (three dogs). At a desired interval (ranging between 1 and 4 hours), the occlusion of the coronary artery or of the internal mammary artery graft was released. The revascularization procedure was performed without use of cardiopulmonary bypass but every dog received 10 to 15 cc/kg of low molecular weight dextran (Rheomacrodex@).
AFTER ACUTE INFARCTION-BOLOOKI
TABLE I Clinical Data in Four Groups of Patients --
Case no. Group 1+ 2 3 4 Group 5 6 7 8 Group 9 10 11 Group 12+* 13+ 14+
Age (yr) &Sex no. of Grafts/Grafts Open -
I* 42M 47M 42M 56M
2/LAD l/LAD 2/LAD 2/LAD-RCA
46M 52M 26F 38F
l/LAD l/LAD l/LAD 2/LAD-RCA
44M 39F 62M
2/Diag 2/Diag 2/Diag
48M 56M 47M 39M
...
II*
Ill*
IV*
15*
3jNone 2/None
____
...
____
* See text for composition
of each group. + Patient receiving circulatory assistance. * Patient did not consent to operation. Diag = diagonal branch of the left anterior descending coronary artery; LAD = left anterior descending coronary artery; RCA = right coronary artery.
Patient Material
The subjects studied were 13 men and 2 women aged 42 to 64 years who were treated in the early stages of acute myocardial infarction. They were selected from among 20 such patients because of the location of a coronary lesion high in the left anterior descending coronary artery and because of availability of pre- and postoperative cardiac catheterization data. Thirteen of these 15 patients underwent myocardial revascularization. Two others did not consent to surgery but were included in this study as control subjects. Three of the 15 patients had acute infarction after cardiac catheterization for unstable angina pectoris. Two patients were admitted to the hospital early after an acute infarction. Seven patients experienced acute myocardial infarction just before scheduled coronary bypass surgery and three had an infarction in the course of administration of anesthesia for such surgery. All patients had more than 80 percent obstructive lesions of the left anterior descending coronary artery at a site proximal to its first diagonal branch. One patient had a main left coronary lesion and two others had lesions in the right coronary artery as well. Complete preoperative hemodynamic data including cardiac catheterization studies were available in these patients. In the 13 patients who underwent myocardial revascularization, the interval between infarction and surgery ranged from 2 to 8 hours, but in each case, there was electrocardiographic evidence of acute transmural infarction of the anterior wall (Fig. 1 and 2). Electrocardiographic studies were repeated after the operation and for 3 consecutive days postoperatively. In addition, serum enzyme studies (creatine phosphokinase [CPK], hydroxybutyric dehydrogenase [HBD], lactic dehydrogenase [LDH] and glutamic oxaloacetic transaminase [GOT]) were performed in all patients before revascularization and were repeated on the day of operation and for 3 consecutive postoperative days.* All 11 patients surviving
Sepkntir
the revascularization procedure underwent cardiac catheterization studies at various intervals (4 weeks to 6 months) after the operation. Two patients each had two additional studies at 2 and 3 l/2 years after the operation. Myocardial revascularization was performed under total cardiopulmonary bypass and mild to moderate hypothermia (32O to 28O C). The maximal period of total cardiac ischemia in the course of operation in any case was 5 minutes. Four patients had a single aortocoronary bypass graft to the left anterior descending coronary artery. Eight patients had two coronary grafts, one to the left anterior descending coronary artery. One patient had triple grafts, to the left anterior descending and circumflex coronary arteries and to a large diagonal branch. Interval between infarction and revascularization: Depending upon the length of time from infarction to surgical revascularization and patency of the graft to the left anterior descending coronary artery, the 15 patients in the study were classified into four groups (Table I). Group I comprised four patients who were operated upon within 4 hours from the time of chest pain and electrocardiographic evidence of anterior wall infarction. Group II comprised four patients who were operated upon within 8 hours of myocardial infarction. Cardiac catheterization in this group was performed just before or during the course of infarction. Group III (three patients) underwent revascularization within 8 hours of infarction but were found to have occlusion of both the left anterior descending coronary artery and the graft to this vessel postoperatively. All three patients had a patent vein graft to the diagonal branch of the left anterior descending coronary artery. The preoperative cardiac catheterization studies in this group were performed before the episode of infarction. Group IV comprised four patients who were seen within 8 hours after acute anterior wall myocardial infarction; two of them re-
1975
The American Journal ol CARDIOLOGY
Volume 36
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MYOCARDlAL
REVASCULARIZATICN
AFTER ACUTE lNFARCT#)N-BCLOOKI
fused surgery and two others did not survive the operation. Hemodynamic studies in these patients were performed while they were undergoing diastolic augmentation with a balloon pump (Datascope).
Evaluation of Left Ventricular Performance The left ventricular silhouette in systole and diastole in the right anterior oblique view was drawn and, with the projection factor calculated from the projected size of the catheter used for dye injection and its actual size, the left
ventricular end-diastolic and end-systolic volumes were calculated. The area-length method of Dodge et a1.,g was modified to the multiradii method and was used for this purpose by assuming the left ventricular cavity, for each bi-
section
of the longitudinal
axis, as an ellipsoid:
Microscopic sections from the edges of the infarct and the adjacent left ventricular wall were obtained to assess the extent of inclusion of areas of healthy muscle within the infarcted segment and vice versa. With careful exclusion of the areas of healthy muscle from the infarcted area in previous studies we have been able to obtain a fairly accurate determination of the size of the area of infarct.i2 In patients and in dogs: The extent of the border of the left ventricle that did not contract was calculated as desilhouette scribed by Smith et al. l1 from the left ventricular in diastole and in systole in the right anterior oblique view. The extent of dyskinetic or akinetic left ventricular border was expressed as percent of the left ventricular silhouette
in diastole. In four patients who died, the extent of infarct was assessed at autopsy by methods similar to those used in the experimental studies.
V = a4/:< L/2 (M/2 )?F where L is the longitudinal axis of the inner left ventricular silhouette from midaortic valve area to the bisected midwall radius in the right anterior oblique view, M is the short axis of the left ventricle obtained from quadrisection of L by perpendicular lines, and F is the projection factor. Usually the longitudinal axis L was divided in half and again bisected to obtain two mid-wall sections of inner left ventricular chamber for data calculation. In patients, the left ventricular volumes calculated from the right anterior oblique view were corrected for biplane cineangiography by using the formula: v’ = 0.95 v-:4 where V’ is the (biplane) volume of the left ventricle and V is the calculated volume from the right anterior oblique view.‘O Ejection fraction was calculated by subtracting the end-systolic volume from the end-diastolic volume and dividing the remainder by the end-diastolic volume. Pressure data were calculated directly from the curves obtained by the transducer tip catheter (Millar, Houston). To obtain an index of left ventricular diastolic compliance (C), the method of Smith et al.” was utilized using the formula:
where AV is the stroke volume output from left ventricular angiograms, ESV = end-systolic volume and Ap is the change in diastolic pressure from end-systole to end-diastole. Cardiac output was measured by the Fick principle. The stroke work index (SWI) in g-m/m per m2 was calculated from the formula: (mBP
-
mRA)
Sl X 1.326
where mBP and mRA are, respectively, the mean aortic and right atria1 pressures in mm Hg, and SI is the stroke index in liters/min per m2.
Evaluation of Infarct Size In experimental studies: The dogs were killed after postoperative cardiac catheterization studies (7 to 10 days after the operation). The heart was then removed and patency of the left internal mammary coronary-artery anastomosis and the left anterior descending coronary artery was confirmed. The left ventricle including the septum was then dissected free from the right ventricular muscle, aorta and left atrium. The left ventricle was weighed and the area of infarct as seen grossly was excised by sharp dissection. The infarcted area was weighed and the percent infarct size in relation to left ventricular mass was obtained.
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The American Journal of CARDIOLOGY
Results Experimental Results The period of &hernia for the 19 dogs ranged from 1 to 4 hours. Three dogs were found to have occlusion of an internal mammary artery graft and the left anterior descending coronary artery; these served as control dogs together with three other dogs with ligation of the left anterior descending coronary artery (Group IV). Of the remaining 13 dogs, 6 had 1 hour of ischemia before restoration of blood flow (Group I), 3 had 2 hours of ischemia (Group II) and 4 had 3 to 4 hours of ischemia (Group III). Hemodynamic changes: Comparison was made of changes in left ventricular end-diastolic volume, endsystolic volume and ejection fraction before and after reperfusion (Table II). The data indicated a significantly depressed left ventricular performance postoperatively in dogs of Groups II, III and IV. There was no significant hemodynamic change in dogs with 1 hour of ischemia (Group I). At the time of postoperative studies (7 to 10 days after infarction) in dogs with reperfusion after 2 hours of ischemia (Group II) the end-diastolic volume had increased and ejection fraction had decreased significantly (P <0.05). As compared with dogs in Group IV, dogs in Group III had larger end-diastolic and end-systolic volumes (P cO.05) but there was no significant difference in ejection fraction between the two groups (Table III). The average size of infarct on pathologic study and the extent of dyskinetic area determined angiographicalIy correlated well in dogs in Group IV only. In dogs in Groups I, II and III with revascularization after 1, 2 and 3 hours, respectively, the angiographic dyskinetic area was significantly larger than the pathologic infarct size. Size of myocardial infarct: Pathologic studies showed that in dogs in Group I the size of the myocardial infarct 1 week to 10 days after the insult was nil except in one dog in which the infarct was 8 percent of left ventricular mass (Table II). In dogs with 2 hours of ischemia (Group II) infarct size was 11.8 f 4.1 percent (standard error). In dogs with 3 hours of ischemia the infarct size ranged between 29 and 32 percent (mean of 31 f 0.7 percent). Dogs in Group IV (three dogs with ligation of the left anterior descending coronary artery and three with an occluded inter-
Volume 38
MYDCARDIAL
TABLE
REVABCULARIZATION
AFTER ACUTE INFARCTION-BDLDDKI
II
Experimental
Data in Four Groups of Dogs -__ EDV
(ml)
ESV (ml)
1
Dog
2
1 2 3 4 5 6 Mean *SE P value
I: Dogs with
Coronary
40
14
33 31
30 20 9
16 19 18
32 55 37
58 42 41
89 28 41 44 10
75 24 35 40 7
57 10 17 24 7
54 15 19 23 6
35 63 58 46 5
27 37 44 41 4
47 36 18 33.7 8.45
42 17 63 40.7 13.3
40 57 50 49 4.9
< 0.20
51 44 44 47 48 3
14
27 16 24 22 36 31 26 2
Coronary
18 5 42 21.7 10.8
III:
85 40 42 69 53 10
17 12 16 26 18 2
<0.20
70 22 33 54 45 21
Group
IV:
Dogs with
Coronary
LAD
< 0.05
12 19 4.5 11.8 4.19
Ligation
47 36 18 33.7 8.4
... 19 43 20 22 26 5
66 71 63 43 61 5
23 20 16 29 36 19 24 3
0 0 16 26 7 0 12 5
...
Occlusion
12 6 17 12 20 17 14 2
45 37 3.9
46 45 19 36.7 8.8
57 72 33 54 11.4
-- <0.05 32 48 22 34 42
0 0 0 8 0 0 2.8 2.8
. . . ~______ . . .
<0.05
Dogs with 3 to 4 Hours of LAD
% Dyskinesiat
Occlusion
10 11 12 13 Mean +SE P value
< 0.20
<0.20 II: Dogs with 2 Hours of LAD
% Infarct*
Occlusion
45
Group
15 16 17 18 19 Mean *SE P value
1 Hour of LAD
2
1
45
<0.20
7 8 9 Mean *SE P value
2
1 Group
___-
~_
%EF
29 31 32 32 31 0.7
47 34 36 50 40 4
..
-
..
or Closed Grafts 26 31 33 18 32 23 27 2
28 58 25 14
55 63 27 47 42 44 46 5
15 25 27 6
25 30 30 30 30 27 29 1
< 0.02
* Gross pathologic size of infarct in relation to left ventricular mass as measured at autopsy. f Extent of left ventricular wall dyskinesia over the diastolic chamber silhouette. 1 = preoperative and 2 = postoperative angiographic data; EDV = end-diastolic volume; EF = ejection fraction; ESV = endsystolic volume; LAD = left anterior descending coronary artery; P = probability value in relation to pre- and postoperative angiographic data: SE = standard error.
TABLE
III
Experimental
Studies:
Groups I with
Statistical
Compared
Analysis
of Postoperative
Data
EDV
ESV
% EF
% Dyskinesia
% Infarct
0.274 < 0.20
0.060 <0.20
1.833 <0.05
9.366
4.549
0.252 <0.20
0.192 <0.20
0.833 < 0.20
0.588 <0.20
3.173 < 0.01
1.889 <0.05
1.907 <0.05
0.0176
3.24
1.523
IV (df = 10)
t score P value II with IV (df = 7) t score P value III with IV (df = 8) t score P value df = degrees of freedom
for t tests, indicating
number
of observations
September 1975
...
minus 1; other abbreviations
as in Table
The American Journal of CARDIOLOGY
I I.
Volume 36
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MYOCARDIAL REVASCULARIZATION AFTER ACUTE INFARCTION-SOLOOK!
FIGURE 3. Dog 7. Comparison of the preoperative (top) left ventricular angiogram and postinfarction (bottom) left ventriculogram in a dog after 2 hours of coronary ischemia. The internal mammary artery (MA) graft to the left anterior descending coronary artery (LAD) is patent, but the anterior wall of the left ventricle is dyskinetic. Microscopic view of a section of the anterior wall of left ventricle of this dog is shown below. (Hematoxylin-eosin X5, reduced by 10 percent.)
nal mammary artery graft) had a mean infarct size of 27 f 2 percent of the weight of the left ventricle (Table II). Pathologic studies also revealed that 7 to 10 days after infarction in dogs in Groups I and II the infarct involved only the inner third of the left ventricular wall and superficial left ventricular fibers were preserved (Fig. 3). In dogs with 3 hours of ischemia, the infarct was transmural and usually included the interventricular septum. However, in dogs in Groups II (Fig. 3) and III, the anterior left ventricular wall was dyskinetic in spite of patency of the internal mammary-coronary artery anastomosis or of the left anterior descending coronary artery proper. As compared with dogs having reperfusion after 3 hours of ischemia (Group III with an infarct size of 31 f 0.7 percent), dogs in Group IV had smaller infarcts (27 f 2 percent) although this difference was not statistically significant (Tables II and III). However, there was a significant difference (P
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September 1975
The American Journal of CARDIOLOGY
function (data not shown) from findings in the initial postoperative studies on day 2. Clinical Results
Thirteen patients survived the operative procedure in the course of acute myocardial infarction. Postoperatively, three of these patients had severe cardiac pump failure and cardiogenic shock requiring vasopressor therapy (two patients) or intraaortic balloon counterpulsation for 48 hours (one patient). The classification of the patients into four groups was based on the success of the revascularization procedure and the interval between operation and acute myocardial infarction as assessed by electrocardiographic and serum enzyme findings evaluated after the fact. Myocardial revascularization was considered successful if there was a patent vein graft to the left anterior descending coronary artery (Groups I and II). The zero time for development of infarction was the onset of chest pain that lasted for more than 30 minutes and that during its course was accompanied by evidence of infarction (serum enzyme changes and S-T segment elevation in the electrocardiogram). The duration of ischemia was from time zero to the time of completion of the vein graft anastomosis to the aorta and the left anterior descending coronary artery. The four patients in Group IV died, the two not operated on within 3 to 5 days after acute myocardial infarction and t’ remaining two at surgery when they could not b eaned from cardiopulmonary by-
Volume 36
MYOCARDtAL REVASCULARlZATlON AFTER ACUTE INFARCTtON-SOXJOKI
FIGURE 4. Case 12, Group IV. lop, left ventricular angiograms in diistole and systole in a patient with total acute occlusion of the left anterior descending coronary artery (LAD). The right coronary artery (RC) and the circumflex artery (C) with its acute marginal branch (AM) were patent. Bottom, coronary arteriograms in the right anterior oblique (R.A.O.) and left anterior oblique (L.A.O.) views. Cardiac catheterization studies in this patient were performed during intraaortic balloon assistance. Although the patient was studied within 8 hours of acute myocardial infarction, he refused surgical intervention and died 2 days later.
pass. At autopsy these patients had 61 f 5 percent of the left ventricular mass involved in the process of infarction. A left ventricular angiogram from one of these patients (Case 12) is shown in Figure 4 and the pathologic photograph of myocardial infarction in this heart is shown in Figure 5. The four patients in Group I received seven coronary bypass grafts, of which five were patent (Table I). The four patients in Group II had five coronary grafts, all of which were patent. Patients in Group III received six coronary grafts, of which only three were patent. Thus, the total number of grafts in these three groups of patients was 18 and the total number of patent grafts was 13, giving an overall patency rate of 72 percent. One patient in Group IV received triple coronary grafts and one a double coronary graft with myocardial infarctectomy. In both of these patients the coronary bypass grafts were technically feasible and at the time of autopsy the graft anastomoses with the coronary artery were patent. There was an overall operative mortality rate of 15 percent (2 of 13 patients). Hemodynamic changes: Table IV presents the hemodynamic data for all patients. In Group I (myocardial revascularization within 4 hours of infarction), there was no significant change in most indexes. There was, however, a slight improvement in car-
FIGURE 5. Case 12. Group IV. The gross pathologic extent of the acute myocardiil infarct in the patient whose left ventricular angiograms are shown in Figure 4. The infarct involved 70 percent of the circumference of the left ventricle. The infarcted area (between arrows) is seen to have gelatinous degeneration and intracavitary clot formation (C). The left ventricular septum (S) and the right and left ventricular cavities are shown in a cross section from the middle of the infarcted area.
disc index and ejection fraction and a decrease in left ventricular end-diastolic pressure. In Group II (patients undergoing myocardial revascularization 4 to 8 hours after infarction with a pat.ent graft to the left anterior descending coronary artery), there was no significant change in most indexes of cardiac function, but end-diastolic volume increased significantly postoperatively (P <0.05). In Group III (patients undergoing myocardial revascularization within 4 hours of infarction but with occlusion of the left anterior descending coronary artery and its graft and patency of a diagonal branch graft, there was a significant increase in left ventricular end-diastolic pressure (from 9 f 0.8 [standard error] to 19 f 2 mm Hg, P CO.05). The preoperative cardiac catheterization data in this group of patients (Group III) were obtained before development of acute myocardial infarction since in all the infarct occurred just before scheduled elective coronary surgery. Group IV patients served as control subjects in order to evaluate the extent of left ventricular dysfunction and myo-
September 1975
The American Journal of CARDIOLOGY
Volume 36
401
MYOCARDIAL
REVASCULARIZATDN
AFTER ACUTE INFARCTKIN-BOLOOKI
volving 45 f 6 percent (standard error) of the diastolic silhouette of the left ventricle. This extent of dyskinesia was greater than in all other patients (P
cardial infarction after complete occlusion of the anterior descending coronary artery. The preoperative cardiac catheterization studies in these patients indicated a marked depression of left ventricular function (Tables IV and V), and .three of these patients underwent intraaortic balloon pumping in the course of cardiac catheterization (Table I). Changes in infarct size: Except for Group I (patients who underwent myocardial revascularization within 4 hours after myocardial infarction and who had a patent graft to the left anterior descending coronary artery), all patients had a large area of left ventricular dyskinesia. In patients in Group IV, which served as a control group, the preoperative data indicated the presence of left ventricular dyskinesia in-
TABLE
IV
Hemodynamic
and Angiographic
Data in Four Groups of Patients
Cl Patient
EDP
1
2
% EF
SWI
1
2
1
I
2
EDV
2
1
% Dyskynesiat
aV/ESV/aP
~_____
2
1
2
0.006 0.06 0.11
0.16 0.07 0.02 0.07 0.08 0.02
1
2
% Infarct”
Group I: Revascularization <4 Hours, LAD Open 1 2 3 4 Mean t SE P value
2.8 2.3 3.0 2.2 2.5 0.19
2.8 3.1 2.3 2.7 2.7 0.16
12 14 16 11 13 1
32 20 16 26 23 3
<0.20
0.02 0.6 0.43 . 6.35 0.17
co.10
9 10 11 Mean * SE P value
3.6 2.3 3.8 4.2 3.4 0.4
3.7 2.4 3.8 2.7 3.1 0.3
25 6 14 22 11 5 co.20
<0.20
3.1 2.2 2.2 2.5 0.2
1.8 2.1 2.4 2.1 0.1 co.20
14 18 14 8 13 2
Group
III:
11 8 10 9 0.8 *; 0.05
22 22 15 19 2
Group 12 13 14 15 Mean ? SE
1.4 2.1 2.4 1.1 1.7 0.3
.
.
42 20 30 20 28 5
27 42 68 69 56 13 / 0.20
co.20 Group
5 6 7 8 Mean 2 SE P value
0.26 0.40 0.26 0.40 0.33 0.04
II: Revascularization
0.37 0.44 0.32 0.24 0.38 0.58 0.60 0.30 0.41 0.39 0.06 0.07 I 0.20 Revascularization 0.33 0.40 0.25 0.32 0.04
IV: Control,
_.
0.03 0.24 0.13 0.04 0.11 0.03
38 38 78 51 50 52 78 63 61 51 10 5 ,‘. 0.20 LAD
40 ks 50 76 40 70 43 5 3 .. . 0.20
LAD
Closed, Anterior
. . .
150 105 224 153 158 24 co.20
-14 Hours,
,:4 Hours,
0.20 0.22 0.29 0.23 0.02 -: 0.20
61 61 65 66 63 1
25 41 30 30 31 3
LAD
146 137 177 100 140 15
< 0.20
Other
250 82 134 223 305 152 229 70 50 co.10
0.01 0.09
. . ::
0.01 0.06 0.07 0.17 0.07 0.03
d.& 0.25 0.20 I, 0.20
Wall Infarction
. _. . __.
38 5 ;; 18.3 10 co.20
38 23 21 18 25 4
.__
.
Grafts Open
.
253 245 200 250 237 12
5 0 0 0 1.2 1.2
Open
232 257 190 264 170 177 114 181 176 219 24 23 ’ 0.05 Closed,
d.bi 0.03
10 22 20 20 18 2
0.20 0.06 0.13 0.06
. 0.02 0.01 0.01 0.004
0 0 0 0 0
20 18 22 20 1
.
62 50 30 40 45 6
.
< 0.20
. :. . ...
.
>4 Hours 0.004 0.008 0.008 0.004 0.006 0.001
..
.
. ..
.
70 60 50 55 61 5
* Gross pathologic size of infarct in relation to left ventricular mass as measured at autopsy. + Extent of left ventricular wall dyskinesia over the diastolic chamber silhouette. 1 = preoperative and 2 = postoperative data; Cl = cardiac index (liters/min per m*); AV/ESV/~P (units) = compliance”; EDP = left ventricular end-diastolic pressure (mm Hg); EDV = end-diastolic volume (ml); EF = ejection fraction; ESV = endsystolic volume; LAD = left anterior descending coronary artery; P = probability (comparing pre- and postoperative data); SE = standard error; SWI = stroke work index (g-m per m’).
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MYOCARDlAL REVASCULARIZATION
ly larger than in patients in Group III, who had a closed graft. In group II there was a mean dyskinetic area of 25 f 4 percent compared with a mean value of 20 f 1 percent in Group III (Table IV). This difference was not statistically significant (P <0.20), thus indicating the similarity of the extent of left ventricular dyskinesia and possibly infarction in patients undergoing revascularization of the left anterior descending coronary artery 4 to 8 hours after infarction, and those with revascularization of only its diagonal branch. The left ventricular angiograms from two patients in Groups II and III are shown in Figures 6 and 7. Electrocardiographic changes: The electrocardiographic evidence of transmural infarction in all patients remained unchanged (Fig. 1 and 2). Evolution of infarction in the postoperative tracings was seen with persistent Q waves throughout the precordial leads and leads I and aVL. Serum enzyme changes: Preoperative serum enzyme studies in 11 patients showed an increase in creatine phosphokinase to 1,200 f 300 IU (standard error) (normal 150 IU); values for HBD, LDH and GOT were within normal limits. Postoperatively serum CPK increased markedly in all patients to a mean (13 patients) of 2,400 f 700 IU, associated with increases in HBD, LDH and GOT for 3 to 4 days after revascularization. The peak increase in serum CPK occurred 12 hours after revascularization (Fig. 8). Follow-up: In the course of 1 to 4 years of followup 11 patients have remained asymptomatic, and 9 of these have returned to work. Two patients from Group II are not working. Two other patients (one
TABLE
V
Clinical ------
Studies:
Statistical
Analysis -__
Groups Compared -____ .___ -__ I with II (df = 6) t score
I
P value with I I I (df = 5) t score P value
II with III t score
I
of Postoperative -_--~--
Cl
EDP
1.098
0.106
AFTER ACUTE INFARCTiON-BOLOOKl
each from Groups I and II) were asymptomatic but died suddenly 4 months and 1 year, respectively, after operation with cardiogenic shock and cardiac arrest due to sudden closure of the left anterior descending coronary artery graft. Two patients from Group II underwent repeated cardiac catheterization studies after revascularization. In one patient the size of infarct (left ventricular dyskinesia) decreased markedly within 9 months postoperatively.7 A third postoperative cardiac catheterization in this man showed no further changes in left ventricular contraction pattern. In the second patient, who had two postoperative hemodynamic studies, there was no change in the size of a left ventricular aneurysm that developed in spite of a patent graft to the left anterior descending coronary artery (Fig. 9). However, the patient’s cardiac function showed some improvement 3 l/2 years after revascularization (left ventricular diastolic pressure decreased from 22 to 14 mm Hg and cardiac index increased from 2.2 to 2.7 liters/min per m2). Discussion Previous experimental studies have shown that with reperfusion of an area of myocardial ischemia within 3 hours of coronary occlusion, the size of the myocardial infarct (as determined by release of CPK) decreases appreciably. ls2 Reperfusion has been employed clinically in patients who were considered to be in a phase of preinfarction13-1” or early infarction16 or to have extension of an infarct.17 It has been shownl*Jg that revascularization can be carried out with acceptable operative mortality and results in improved cardiac function and a reduced size of myo-
Data
______~______.______~__---_._ SW!
%EF
EDV -__--__
2.319
0.6979
aV/ESP/AP
% Dyskinesia
<0.20
<0.20
< 0.20
<0.05
2.806 <0.02
0.056 <0.20
5.135 < 0.001
2.648 < 0.02
2.483 <0.05
1.917
5.558
1.697 10.10
.2.198 < 0.05
11.02
1.255 <0.20
0.178 <0.20
1.845 <1.10
1.086 10.20
a.757
4.814
2.536 < 0.02
6.355 < 0.001
3.181
0.646 <0.20
.2.133 < 0.05
2.501 10.02
2.493
0.141 <0.20
1.757
3.671 10.01
(df = 5)
P value with IV*(df t score
2.699
1.980
< 0.02
1.902
= 6) 2.850
P value II with IV*(df=6) r score
<0.02
P value III with IV*(df I score
<0.02
2.760 <0.02
3.036
2.580 <0.02
3.474
= 5) 1.017
P value __________~__.__ * In Group IV
the patients
par ison. Abbreviations
as in Tables
1.455
<0.20
<0.20 died
2.268 <0.05
and had no postoperative
<0.05
___studies; their
preoperative
data were used for statistical
COm-
I I I and IV.
September 1975
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MYOCARDIAL REVASCULARIZATION AFTER ACUTE INFARCTION-BOLOCKI
cardial infarct. Although, in clinical cases, it has been difficult to calculate the extent of decrease in size of the eventual infarct, it was postulated that reversal of the clinical shock state and improvement in cardiac function were indicators of a decrease in the area of nonfunctioning myocardium and, hence, of a decrease in the size of the infarct. Effect of reperfusion on infarct size: Because of the complicated clinical setting in which emergency myocardial revascularization for an acute myocardial infarction is decided upon, it is not possible to categorize all patients into one group. For this reason we have classified our patients into four groups on the basis of several variables. For example, unlike the reported results in other studies, our data were correlated with the postoperative angiographic findings because operative survival or reversal of the shock state as such does not necessarily indicate a successful revascularization. Furthermore, in the clinical setting timing of the duration of ischemia or infarction has always been difficult. As a result, in all clinical studies related to this subject (including this investi-
gation) there have been some departures from a strict research protocol that might affect the results considerably. To clarify our results we analyzed data in a group of patients selected because they had a similar anatomic lesion in the left anterior descending coronary artery and a similar interval between the onset of infarction and revascularization. To complement the clinical study, because the extent of pathologic infarction in patients could not be evaluated, we performed some experiments in dogs. We believe that the results show clearly that reperfusion of an ischemit (or infarcted) area of the myocardium can be performed with acceptable mortality and is beneficial in man if carried out within 4 hours of the onset of myocardial infarction. Our experimental studies indicated that, with reperfusion of an infarcted area within 2 hours of coronary occlusion, it was possible to decrease the eventual size of the infarct by about 50 percent (from 27 f 2 percent to 11.8 f 4.19 percent, P
preoperative- anterior- ventricula; wall dyskinesia was due to multiple lesions in the left anterior descending coronary artery (double arrows, top right). Postoperative angiograms obtained 3 months later showed no change in the extent of anterior wall dyskinesia or ejection fraction (Table IV). The graft to the anterior descending coronary artery (dngle arrow, lower panels) is patent. There are multiple sitver clips in the postoperative angiograms.
FIGURE 7. Case1 1, Group Ill. Pm- and postoperative left ventricular angiograms (left and center panels) and coronary arteriograms (rfght panels). The patient was studied before development of acute myocardial infarction. There was no left ventricular dyskinesia. but the left anterior descending coronary artery (LAD) and diagonal branch (D) showed more than 90 percent obstructive lesions. Acute myocardiil infarction developed in this patient at the time of anesthesia induction as evidenced by electrocardiographic change and hypotension. Coronary grafts to the left anterior descending coronary artery and its diagonal branch were performed, and the patient tolerated the procedure well. Postoperative angiograms obtained 4 months later showed e&fence of dyskinesia and aneurysmal formation of the anterior wall due to closure of the graft to the left anterior descending coronary artery. The graft to the diagonal branch was patent. (Reprinted from Bolooki et al.’ by permission of the American Heart Association.)
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MYOCARDlAL REVASCULARIZATION
left ventricular dyskinesia decreased considerably (from a mean value of 18 percent to 1.2 percent, P
AFTER ACUTE INFARCTION-SOLOOKI
of an adjacent patent coronary graft contributed to limiting the extent of myocardial infarction in these patients. In patients with a patent graft (reperfusion) to the left anterior descending coronary artery, the anterior descending artery was the major anterior wall artery without a large diagonal branch or other collateral vessels. Although this anatomic variation could have played an important role in survival of these patients, it is safe to conclude that myocardial reperfusion performed more than 4 hours after myocardial infarction does not prevent development of a dyskinetic area of the left ventricle or an aneurysm (Fig. 7 and 9). In this study, we found no dyskinetic areas in three patients who underwent myocardial revascularization within 4 hours of electrocardiographic infarction. In these patients electrocardiographic
C.P.K.*ll.l.K.o--~
SuRftRY
1.B.Y.~~~~~~ S.f.K.T.~--.
‘\
Es
,
AFTER
FIGURE 9. Case 9, Group Ill. Serum enzyme curves before (top) and after (bottom) myocardial revascularization. Preoperative studies were obtained on admission (1). during day 1 in the hospital (2) and before surgical intervention (3). The postoperative studies were performed on days 1 to 10 postoperatively. This pattern of serum enzyme rise and decline was seen in most patients operated on in the course of acute myocardial infarction.
FIGURE 9. Case 6. Group II. Left ventricular angiograms (top) and coronary arteriograms (bottom) obtained 7 months postoperatively in the patient whose electrocardiograms are shown in Figure 1. A large left ventricular aneurysm involving the anterior and inferior walls has developed in spite of a patent graft to the left anterior descending coronary artery (LAD). The left circumflex coronary artery (LC) and its acute marginal branch are normal. A repeat cardiac catheterization in this man 3 l/2 years after revascularization of the infarct showed no changes in the pattern of left ventricular contraction. (Reprinted from Bolooki et al.13 by permission.)
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MVDCARDIAL REVASCULARIZATIDN AFTER ACUTE INFARCTION-BOLDOKI
evidence of acute myocardial infarction (S-T segment elevation) and hypotension developed while they were being given general anesthesia in the operating room. An interesting observation was the persistence of preoperative Q waves in the postoperative electrocardiograms (Fig. 1 and 2) in spite of successful revascularization of the infarct. This finding indicates that the revascularized transmural infarct remains abnormal electrophysiologically. In our experience with these and other patients with the so-called intermediate coronary syndrome or preinfarction angina, the only reversible electrocardiographic changes have been those of subendocardial ischemia (T wave inversion in precordial leads) regardless of the duration of these changes before operation.‘s Clinical implications: Our study shows that the duration of ischemia before reestablishment of blood flow to the distal areas of an occluded coronary artery in man must be limited to 4 hours if reperfusion is to lead to improvement in cardiac function and a decrease in the extent of the infarct. This finding is supported by our experimental results, although perhaps because of the acute conditions of the experiments, the time limit in dogs is 2 hours. This difference in time may also indicate a greater tolerance of human myocardium to ischemia and is most likely due to the presence of numerous intercoronary collateral communications and the insidious onset of coronary obstruction. In addition to a significant decrease in the extent
of dyskinetic area in patients who had successful myocardial revascularization (reperfusion) early after infarction, the overall cardiac function was better than in patients who underwent myocardial reperfusion late after infarction (Group II) or did not undergo revascularization of the left anterior descending coronary artery (Group III). However, long-term follow-up studies (1 to 4 years) in these patients demonstrated that, regardless of patency or closure of the bypass graft to the left anterior descending coronary artery, most patients undergoing revascularization for an acute infarct remained asymptomatic and many returned to their previous activities. Although a recent report by Shell and SobeP indicates the advantages of noninvasive measures to reduce infarct size in patients with myocardial infarction, perhaps a study of matched groups of patients treated by noninvasive (antihypertensive) methods and by myocardial reperfusion would further our knowledge of the effects of each of these methods. It is likely, however, that no one method will be useful for all patients and in the future the patients may be carefully selected for a specific method of therapy. Acknowledgment We express our gratitude to Drs. Ali Ghahramani, Leonard Sommer and Stephen Mallon, who performed the cardiac catheterization studies in these patients. Drs. James Jude and Richard Robinson performed surgery in two of these patients. We also appreciate the data analysis and calculations by Miss Adrianne Fried, BSN.
References I. Glnks WR, Sybers HD, Maroko PR, et al: Coronary artery reperfusion. II. Reduction of myocardial infarct size at one week after coronary occlusion. J Clin invest 51:2717-2723, 1972 2. Sobei BE, Shell WE: Jeopardized, blighted and necrotic myocardium. Circulation 47:215-217, 1973 3. Keon WJ, Bedard P, Kanakaiahnavara RS, et al: Experience with emergency aorto-coronary bypass graft in the presence of acute myocardial infarction. Circulation 48: Suppl lll:lll-151-lll155.1973 4. Boiooki H, Morales A, Goikar R, et al: The effects of revascularization of myocardial infarct size. A clinical and experimental correlation. Surg Forum 24: 137- 139, 1973 5. Boiooki H, Maiion S, Ghahramani A, et al: Objective assessment of the effects of aorto-coronary bypass operation on cardiac function. J Thorac Cardiovasc Surg 66:916-933, 1973 6. Boiooki H, Vargas A, Ghahramani A, et al: Aorto-coronary bypass graft for preinfarction angina. Chest 61:247-252, 1972 7. Boiooki H, Sommer L, Ghahramani A, et al: Complications of coronary bypass surgery. Circulation 48: Suppl III:IlC12O-B-126, 1973 6. Boiooki H, Sommer L, Faraido A, et al: The significance of serum enzyme studies in patients undergoing direct coronary artery surgery. J Thorac Cardiovasc Surg 65863-868, 1973 9. Dodge HT, Kennedy JW, Petersen JL: Valvular heart disease. IV. Quantitative angiocardiographic methods in the evaluation of valvular heart disease. Prog Cardiovasc Dis 16:1-23. 1973 10. Kennedy JW, Trenhoime SE, Kasser IS: Left ventricular volume and mass from single plane cineangiocardiograms. A comparison of anteroposterior and the right anterior oblique methods. Am Heart J 80:343-352, 1970 11. Smith M, Russell RO Jr, Feiid BJ, et al: Left ventricular compli-
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12. 13.
14.
15.
16.
17.
18. 19.
20.
21.
ante and abnormally contracting segments in postmyocardial infarction patients. Chest 65368-378, 1974 Bakhshandeh K, Kaiser GA, Boiooki H: Hemodynamic correlates of the size of infarct. Surg Forum 23:152-154, 1972 Bolookl H, Sommer L, Kaiser GA, et al: Long-term follow-up in patients receiving emergency revascularization for intermediate coronary syndrome. J Thorac Cardiovasc Surg 68:90-100. 1974 Hill JD, Kerth WJ, Kelly JK, et al: Emergency aorta-coronary bypass for impending or extending myocardial infarction. Circulation 43: Suppl l:l-105-l-I 10, 1971 Lambert CJ, Adam M, Geisier G, et al: Emergency myocardial revascularization for impending infarction and arrhythmias. J Thorac Cardiovasc Surg 62:522-628. 1971 PHarre R, Spinazroia A, Nemickas R, et al: Emergency aortocoronary bypass for acute myocardial infarction. Arch Surg 103:525-528, 1971 Mundth ED, Buckley NJ, Lefnbach RC, et al: Surgical intervention for the complications of acute myocardial ischemia. Ann Surg 178:379-390, 1973 Cheanvechai C, Effier DB, Loop FD, et al: Emergency myocardial revascularization. Am J Cardiol 32:901-908. 1973 Cohn LH, Goriin R, Herman MV, et al: Aorta-coronary bypass for acute coronary occlusion. J Thorac Cardiovasc Surg 64: 503-513. 1972 Pairolero P, Hailermann FJ, Ellis F Jr: Left ventriculogram in experimental myocardial infarction. Radiology 95:31 l-316. 1970 Shell WE, Sobei BE: Protection of jeopardized ischemic myocardium by reduction of ventricular afterload. N Engl J Med 291:481-486, 1974
Volume 36
HOOSHANG BOLOOKI, MD, FRCS (C), FACC with the assistance of MICHAEL D. KOTLER, BS LAWRENCE LOTTENBERG, BS STEPHEN DRESNICK, BS ROBERT C. ANDREWS, BS STEVEN KIPNIS, BS RICHARD M. ELLIS l
Miami, Florida
From the Division of Thoracic and Cardiovascular Surgery, University of Miami, School of Medicine, Miami, Fla. This study was supported in part by Grant HE 13978-04 from the National Institutes of Health, Bethesda, Md., and grants inaid from Eli Lilly Research Laboratories, Indianapolis, Ind. and Greater Miami Heart Association, Miami, Fla. Research Career Development Awardee, National Heart and Lung Institute, Grant HL 70670-03. Address for reprints: Hooshang Bolooki, MD, P.O. Box 675. Biscayne Annex, Miami, Fla. 33152. l
After Acute Infarction
The purpose of this study was (1) to establish the maximal interval between the onset of ischemia and reperfusion that would permit a decrease in the size of infarction, and (2) to evaluate the relation between changes in infarct size and preservation of cardiac function. Studies were carried out in 19 dogs of which 13 had temporary (1 to 3 hours) occlusion of the left anterior descending coronary artery. The hospital course of 15 patients of whom 13 underwent myocardial revascularization within 8 hours of acute infarction was also reviewed. In dogs, the eventual pathologic infarct size was significantly reduced if reperfusion was performed within 2 hours of ischemia. After 2 hours of ischemia, the revascularized segment remained dyskinetic on angiographic assessment and cardiac function was depressed. After 3 hours of ischemia, in spite of a patent coronary artery, the extent of infarct and dykinesia was greater than during ligation of the left anterior descending coronary artery. In patients, small infarcts developed with revascularization performed more than 4 hours afler infarction but with revascularization of the lefl anterior descending coronary artery the size of the dyskinetic area (as assessed with angiography) was similar to that in patients wlth a closed graft to the left anterior descending coronary artery but with a patent graft to its diagonal branch. In all patients after revascularization the extent of the left ventricular dysktnetic area was smaller and cardiac function was significantly better than in patients who did not receive revascularization for complete occlusion of the left anterior descending coronary artery. In spite of successful revascularizatton, electrocardiographic evidence of transmural infarction persisted postoperatively. It is concluded that reperfusion of an area of myocardium that has been ischemic for less than 2 hours in dogs or less than 4 hours in man may lead to a significant reduction in the extent of infarction as well as improvement in cardiac function. However, the revascularized area remains angiographically dysklnetic and electrocardiographically abnormal.
Previous experimental studies1*2 and recent clinical reports3 indicate that reperfusion of an area of myocardium after a few hours of ischemia can result in a significant reduction of the eventual size of infarct. The purpose of our research was to answer some important questions regarding the surgical treatment of acute myocardial ischemia and infarction by direct myocardial revascularization (reperfusion). First, we attempted to establish the maximal interval from ischemia to reperfusion that would permit clinically and angiographitally successful revascularization with reduction in the size of infarct. Second, we attempted to evaluate the relation between the extent of cardiac muscle preserved and cardiac function. The studies were performed simultaneously in a group of dogs and in a group of patients who underwent myocardial revascularization after acute infarction. Brief reports4-7 on the results of this work have been periodically published elsewhere.
September1975 The American Journal of CARDIOLOGY
Volume 36
395
MYOCARDIAL REVA6CULARlZATlDN APTER ACUTE INFARCTKM-BOLDDKI
II
I
Ill
AVR
AVL
v,
AVF
v3
v2
v,
v5
VE
A
II
2 (3:OO pm]
I
II
Preop.
Ill
AN
AVL
V,
AVf
V3
V,
V,
V5
V,
FIGURE 1. Case 6, Group II. Serial 12 lead electrocardiograms from a patient who was admitted with evidence of subendocardial ischemia (A). After 3 days of therapy, chest pain continued with persistent electrocardiographic changes (B). Diagnostic cardiac catheterization studies were performed at this time and within 3 hours there was acute S-T segment elevation in the precordial leads (C) concomitant with marked serum enzyme elevation. The patient was operated on within 6 hours and underwent myocardial revascularization within 8 hours of development of chest pain, sweating and hypotension. The postoperative electrocardiogram revealed evolution of anterior wall myocardial infarction (D) in spite of a patent anterior descending coronary graft (see Fig. 7). (Reprinted by permission from Bolooki et al.13)
11/Z/71 PIE-O?
III
AVR AVl AVF
Vi
V,
4
!r,
+I 4s I:
’
4
t
11/:/I I
IKT-IP 111 A’/! II
AVL
AVf
VI
VI
V,
VI
Methods Experimental Studies Studies were performed in 19 mongrel dogs of both sexes weighing 23 to 25 kg. Preoperatively a control electrocardiogram, left ventriculograms and selective left coronary arteriograms were obtained. Cardiac catheterization was performed 3 to 4 days before surgical occlusion of the left anterior descending coronary artery followed by reperfusion of the vessel or by direct revascularization with the use of left internal mammary-coronary artery anastomosis. Cardiac catheterization studies: These investigations were carried out under mild anesthesia with intravenously administered pentobarbital sodium (10 mg/kg body weight). With the dogs in the right anterior oblique position, a groin cut-down procedure was performed and a no.
396
September 1975
The American Journal of CARDIOLOGY
Vs
Vr
FIGURE 2. Case 9, Group Ill. Serial 12 lead electrocardiograms from a patient admitted with the diagnosis of preinfarction angina (A). In the course of 24 hours, the chest pain increased in frequency and severity in spite of extensive treatment. There was electrocardiographic evidence of subendocardial ischemia (B). The patient underwent emergency cardiac catheterization studies but within 2 hours presented with hypotension and sweating with electrocardiographic evidence of extensive anterior wall myocardial infarction (C) and serum enzyme elevation. He was operated upon immediately and received a bypass graft to the left anterior descending coronary artery within 4 hours of the onset of chest pain and electrocardiographic evidence of infarction. Postoperatively he remained in a low output state and required vasopressor therapy. An electrocardiogram taken 5 days postoperatively revealed further evolution of the anterior wall infarction (D).
7F Cordis catheter was threaded into the left ventricular cavity. A left ventriculogram was then obtained with hand injection of 20 cc of 90 percent Hypaquea. The left ventriculograms were recorded with Phillips equipment on 35 mm tine films at a rate of 60 frames/set. Selective coronary arteriograms were obtained with use of a Cordis left coronary arterial catheter. By hand injection of 5 to 10 ml of 90 percent Hypaque into the coronary artery, the patency of this vessel and the extent of its collateralization and runoff were assessed. Postoperative cardiac catheterization studies (ventriculography and left coronary and internal mammary artery arteriography) were performed 1 week after the operation using methods similar to those of the preoperative studies. In six dogs serial angiographic studies 2, 4 and 7 days postoperatively were performed to study the changes in left
Volume 36
MYOCARDIAL Rf3’ASClJlARlZAT0N
ventricular contraction pattern and to assess patency of the left anterior descending coronary artery or internal mammary artery graft. Surgical procedure: Surgery was carried out under pentobarbital sodium anesthesia (25 mg/kg) with the dogs intubated, connected to a Bird respirator and breathing an oxygen-air mixture. The dogs were placed in the right lateral decubitus position and prepared and draped in a sterile manner. The groin was dissected, and the femoral vein and artery were exposed. The vein was used for intravenous infusion, and the artery for intraventricular pressure monitoring by a transducer tip catheter (Edwards). A left thoracotomy was then made at the fourth intercostal space and the precordium was opened vertically to develop-a cradle. The heart was examined, and communications between the left anterior descending coronary artery and the posterior branches were ligated. In 10 dogs, the left anterior descending coronary artery was ligated above the level of its first diagonal branch, and the left internal mammary artery, dissected free from the anterior chest wall, was used to anastomose to the left anterior descending coronary artery. In the remaining dogs the left anterior descending coronary artery was temporarily occluded (six dogs) or ligated (three dogs). At a desired interval (ranging between 1 and 4 hours), the occlusion of the coronary artery or of the internal mammary artery graft was released. The revascularization procedure was performed without use of cardiopulmonary bypass but every dog received 10 to 15 cc/kg of low molecular weight dextran (Rheomacrodex@).
AFTER ACUTE INFARCTION-BOLOOKI
TABLE I Clinical Data in Four Groups of Patients --
Case no. Group 1+ 2 3 4 Group 5 6 7 8 Group 9 10 11 Group 12+* 13+ 14+
Age (yr) &Sex no. of Grafts/Grafts Open -
I* 42M 47M 42M 56M
2/LAD l/LAD 2/LAD 2/LAD-RCA
46M 52M 26F 38F
l/LAD l/LAD l/LAD 2/LAD-RCA
44M 39F 62M
2/Diag 2/Diag 2/Diag
48M 56M 47M 39M
...
II*
Ill*
IV*
15*
3jNone 2/None
____
...
____
* See text for composition
of each group. + Patient receiving circulatory assistance. * Patient did not consent to operation. Diag = diagonal branch of the left anterior descending coronary artery; LAD = left anterior descending coronary artery; RCA = right coronary artery.
Patient Material
The subjects studied were 13 men and 2 women aged 42 to 64 years who were treated in the early stages of acute myocardial infarction. They were selected from among 20 such patients because of the location of a coronary lesion high in the left anterior descending coronary artery and because of availability of pre- and postoperative cardiac catheterization data. Thirteen of these 15 patients underwent myocardial revascularization. Two others did not consent to surgery but were included in this study as control subjects. Three of the 15 patients had acute infarction after cardiac catheterization for unstable angina pectoris. Two patients were admitted to the hospital early after an acute infarction. Seven patients experienced acute myocardial infarction just before scheduled coronary bypass surgery and three had an infarction in the course of administration of anesthesia for such surgery. All patients had more than 80 percent obstructive lesions of the left anterior descending coronary artery at a site proximal to its first diagonal branch. One patient had a main left coronary lesion and two others had lesions in the right coronary artery as well. Complete preoperative hemodynamic data including cardiac catheterization studies were available in these patients. In the 13 patients who underwent myocardial revascularization, the interval between infarction and surgery ranged from 2 to 8 hours, but in each case, there was electrocardiographic evidence of acute transmural infarction of the anterior wall (Fig. 1 and 2). Electrocardiographic studies were repeated after the operation and for 3 consecutive days postoperatively. In addition, serum enzyme studies (creatine phosphokinase [CPK], hydroxybutyric dehydrogenase [HBD], lactic dehydrogenase [LDH] and glutamic oxaloacetic transaminase [GOT]) were performed in all patients before revascularization and were repeated on the day of operation and for 3 consecutive postoperative days.* All 11 patients surviving
Sepkntir
the revascularization procedure underwent cardiac catheterization studies at various intervals (4 weeks to 6 months) after the operation. Two patients each had two additional studies at 2 and 3 l/2 years after the operation. Myocardial revascularization was performed under total cardiopulmonary bypass and mild to moderate hypothermia (32O to 28O C). The maximal period of total cardiac ischemia in the course of operation in any case was 5 minutes. Four patients had a single aortocoronary bypass graft to the left anterior descending coronary artery. Eight patients had two coronary grafts, one to the left anterior descending coronary artery. One patient had triple grafts, to the left anterior descending and circumflex coronary arteries and to a large diagonal branch. Interval between infarction and revascularization: Depending upon the length of time from infarction to surgical revascularization and patency of the graft to the left anterior descending coronary artery, the 15 patients in the study were classified into four groups (Table I). Group I comprised four patients who were operated upon within 4 hours from the time of chest pain and electrocardiographic evidence of anterior wall infarction. Group II comprised four patients who were operated upon within 8 hours of myocardial infarction. Cardiac catheterization in this group was performed just before or during the course of infarction. Group III (three patients) underwent revascularization within 8 hours of infarction but were found to have occlusion of both the left anterior descending coronary artery and the graft to this vessel postoperatively. All three patients had a patent vein graft to the diagonal branch of the left anterior descending coronary artery. The preoperative cardiac catheterization studies in this group were performed before the episode of infarction. Group IV comprised four patients who were seen within 8 hours after acute anterior wall myocardial infarction; two of them re-
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MYOCARDlAL
REVASCULARIZATICN
AFTER ACUTE lNFARCT#)N-BCLOOKI
fused surgery and two others did not survive the operation. Hemodynamic studies in these patients were performed while they were undergoing diastolic augmentation with a balloon pump (Datascope).
Evaluation of Left Ventricular Performance The left ventricular silhouette in systole and diastole in the right anterior oblique view was drawn and, with the projection factor calculated from the projected size of the catheter used for dye injection and its actual size, the left
ventricular end-diastolic and end-systolic volumes were calculated. The area-length method of Dodge et a1.,g was modified to the multiradii method and was used for this purpose by assuming the left ventricular cavity, for each bi-
section
of the longitudinal
axis, as an ellipsoid:
Microscopic sections from the edges of the infarct and the adjacent left ventricular wall were obtained to assess the extent of inclusion of areas of healthy muscle within the infarcted segment and vice versa. With careful exclusion of the areas of healthy muscle from the infarcted area in previous studies we have been able to obtain a fairly accurate determination of the size of the area of infarct.i2 In patients and in dogs: The extent of the border of the left ventricle that did not contract was calculated as desilhouette scribed by Smith et al. l1 from the left ventricular in diastole and in systole in the right anterior oblique view. The extent of dyskinetic or akinetic left ventricular border was expressed as percent of the left ventricular silhouette
in diastole. In four patients who died, the extent of infarct was assessed at autopsy by methods similar to those used in the experimental studies.
V = a4/:< L/2 (M/2 )?F where L is the longitudinal axis of the inner left ventricular silhouette from midaortic valve area to the bisected midwall radius in the right anterior oblique view, M is the short axis of the left ventricle obtained from quadrisection of L by perpendicular lines, and F is the projection factor. Usually the longitudinal axis L was divided in half and again bisected to obtain two mid-wall sections of inner left ventricular chamber for data calculation. In patients, the left ventricular volumes calculated from the right anterior oblique view were corrected for biplane cineangiography by using the formula: v’ = 0.95 v-:4 where V’ is the (biplane) volume of the left ventricle and V is the calculated volume from the right anterior oblique view.‘O Ejection fraction was calculated by subtracting the end-systolic volume from the end-diastolic volume and dividing the remainder by the end-diastolic volume. Pressure data were calculated directly from the curves obtained by the transducer tip catheter (Millar, Houston). To obtain an index of left ventricular diastolic compliance (C), the method of Smith et al.” was utilized using the formula:
where AV is the stroke volume output from left ventricular angiograms, ESV = end-systolic volume and Ap is the change in diastolic pressure from end-systole to end-diastole. Cardiac output was measured by the Fick principle. The stroke work index (SWI) in g-m/m per m2 was calculated from the formula: (mBP
-
mRA)
Sl X 1.326
where mBP and mRA are, respectively, the mean aortic and right atria1 pressures in mm Hg, and SI is the stroke index in liters/min per m2.
Evaluation of Infarct Size In experimental studies: The dogs were killed after postoperative cardiac catheterization studies (7 to 10 days after the operation). The heart was then removed and patency of the left internal mammary coronary-artery anastomosis and the left anterior descending coronary artery was confirmed. The left ventricle including the septum was then dissected free from the right ventricular muscle, aorta and left atrium. The left ventricle was weighed and the area of infarct as seen grossly was excised by sharp dissection. The infarcted area was weighed and the percent infarct size in relation to left ventricular mass was obtained.
398
September 1975
The American Journal of CARDIOLOGY
Results Experimental Results The period of &hernia for the 19 dogs ranged from 1 to 4 hours. Three dogs were found to have occlusion of an internal mammary artery graft and the left anterior descending coronary artery; these served as control dogs together with three other dogs with ligation of the left anterior descending coronary artery (Group IV). Of the remaining 13 dogs, 6 had 1 hour of ischemia before restoration of blood flow (Group I), 3 had 2 hours of ischemia (Group II) and 4 had 3 to 4 hours of ischemia (Group III). Hemodynamic changes: Comparison was made of changes in left ventricular end-diastolic volume, endsystolic volume and ejection fraction before and after reperfusion (Table II). The data indicated a significantly depressed left ventricular performance postoperatively in dogs of Groups II, III and IV. There was no significant hemodynamic change in dogs with 1 hour of ischemia (Group I). At the time of postoperative studies (7 to 10 days after infarction) in dogs with reperfusion after 2 hours of ischemia (Group II) the end-diastolic volume had increased and ejection fraction had decreased significantly (P <0.05). As compared with dogs in Group IV, dogs in Group III had larger end-diastolic and end-systolic volumes (P cO.05) but there was no significant difference in ejection fraction between the two groups (Table III). The average size of infarct on pathologic study and the extent of dyskinetic area determined angiographicalIy correlated well in dogs in Group IV only. In dogs in Groups I, II and III with revascularization after 1, 2 and 3 hours, respectively, the angiographic dyskinetic area was significantly larger than the pathologic infarct size. Size of myocardial infarct: Pathologic studies showed that in dogs in Group I the size of the myocardial infarct 1 week to 10 days after the insult was nil except in one dog in which the infarct was 8 percent of left ventricular mass (Table II). In dogs with 2 hours of ischemia (Group II) infarct size was 11.8 f 4.1 percent (standard error). In dogs with 3 hours of ischemia the infarct size ranged between 29 and 32 percent (mean of 31 f 0.7 percent). Dogs in Group IV (three dogs with ligation of the left anterior descending coronary artery and three with an occluded inter-
Volume 38
MYDCARDIAL
TABLE
REVABCULARIZATION
AFTER ACUTE INFARCTION-BDLDDKI
II
Experimental
Data in Four Groups of Dogs -__ EDV
(ml)
ESV (ml)
1
Dog
2
1 2 3 4 5 6 Mean *SE P value
I: Dogs with
Coronary
40
14
33 31
30 20 9
16 19 18
32 55 37
58 42 41
89 28 41 44 10
75 24 35 40 7
57 10 17 24 7
54 15 19 23 6
35 63 58 46 5
27 37 44 41 4
47 36 18 33.7 8.45
42 17 63 40.7 13.3
40 57 50 49 4.9
< 0.20
51 44 44 47 48 3
14
27 16 24 22 36 31 26 2
Coronary
18 5 42 21.7 10.8
III:
85 40 42 69 53 10
17 12 16 26 18 2
<0.20
70 22 33 54 45 21
Group
IV:
Dogs with
Coronary
LAD
< 0.05
12 19 4.5 11.8 4.19
Ligation
47 36 18 33.7 8.4
... 19 43 20 22 26 5
66 71 63 43 61 5
23 20 16 29 36 19 24 3
0 0 16 26 7 0 12 5
...
Occlusion
12 6 17 12 20 17 14 2
45 37 3.9
46 45 19 36.7 8.8
57 72 33 54 11.4
-- <0.05 32 48 22 34 42
0 0 0 8 0 0 2.8 2.8
. . . ~______ . . .
<0.05
Dogs with 3 to 4 Hours of LAD
% Dyskinesiat
Occlusion
10 11 12 13 Mean +SE P value
< 0.20
<0.20 II: Dogs with 2 Hours of LAD
% Infarct*
Occlusion
45
Group
15 16 17 18 19 Mean *SE P value
1 Hour of LAD
2
1
45
<0.20
7 8 9 Mean *SE P value
2
1 Group
___-
~_
%EF
29 31 32 32 31 0.7
47 34 36 50 40 4
..
-
..
or Closed Grafts 26 31 33 18 32 23 27 2
28 58 25 14
55 63 27 47 42 44 46 5
15 25 27 6
25 30 30 30 30 27 29 1
< 0.02
* Gross pathologic size of infarct in relation to left ventricular mass as measured at autopsy. f Extent of left ventricular wall dyskinesia over the diastolic chamber silhouette. 1 = preoperative and 2 = postoperative angiographic data; EDV = end-diastolic volume; EF = ejection fraction; ESV = endsystolic volume; LAD = left anterior descending coronary artery; P = probability value in relation to pre- and postoperative angiographic data: SE = standard error.
TABLE
III
Experimental
Studies:
Groups I with
Statistical
Compared
Analysis
of Postoperative
Data
EDV
ESV
% EF
% Dyskinesia
% Infarct
0.274 < 0.20
0.060 <0.20
1.833 <0.05
9.366
4.549
0.252 <0.20
0.192 <0.20
0.833 < 0.20
0.588 <0.20
3.173 < 0.01
1.889 <0.05
1.907 <0.05
0.0176
3.24
1.523
IV (df = 10)
t score P value II with IV (df = 7) t score P value III with IV (df = 8) t score P value df = degrees of freedom
for t tests, indicating
number
of observations
September 1975
...
minus 1; other abbreviations
as in Table
The American Journal of CARDIOLOGY
I I.
Volume 36
399
MYOCARDIAL REVASCULARIZATION AFTER ACUTE INFARCTION-SOLOOK!
FIGURE 3. Dog 7. Comparison of the preoperative (top) left ventricular angiogram and postinfarction (bottom) left ventriculogram in a dog after 2 hours of coronary ischemia. The internal mammary artery (MA) graft to the left anterior descending coronary artery (LAD) is patent, but the anterior wall of the left ventricle is dyskinetic. Microscopic view of a section of the anterior wall of left ventricle of this dog is shown below. (Hematoxylin-eosin X5, reduced by 10 percent.)
nal mammary artery graft) had a mean infarct size of 27 f 2 percent of the weight of the left ventricle (Table II). Pathologic studies also revealed that 7 to 10 days after infarction in dogs in Groups I and II the infarct involved only the inner third of the left ventricular wall and superficial left ventricular fibers were preserved (Fig. 3). In dogs with 3 hours of ischemia, the infarct was transmural and usually included the interventricular septum. However, in dogs in Groups II (Fig. 3) and III, the anterior left ventricular wall was dyskinetic in spite of patency of the internal mammary-coronary artery anastomosis or of the left anterior descending coronary artery proper. As compared with dogs having reperfusion after 3 hours of ischemia (Group III with an infarct size of 31 f 0.7 percent), dogs in Group IV had smaller infarcts (27 f 2 percent) although this difference was not statistically significant (Tables II and III). However, there was a significant difference (P
400
September 1975
The American Journal of CARDIOLOGY
function (data not shown) from findings in the initial postoperative studies on day 2. Clinical Results
Thirteen patients survived the operative procedure in the course of acute myocardial infarction. Postoperatively, three of these patients had severe cardiac pump failure and cardiogenic shock requiring vasopressor therapy (two patients) or intraaortic balloon counterpulsation for 48 hours (one patient). The classification of the patients into four groups was based on the success of the revascularization procedure and the interval between operation and acute myocardial infarction as assessed by electrocardiographic and serum enzyme findings evaluated after the fact. Myocardial revascularization was considered successful if there was a patent vein graft to the left anterior descending coronary artery (Groups I and II). The zero time for development of infarction was the onset of chest pain that lasted for more than 30 minutes and that during its course was accompanied by evidence of infarction (serum enzyme changes and S-T segment elevation in the electrocardiogram). The duration of ischemia was from time zero to the time of completion of the vein graft anastomosis to the aorta and the left anterior descending coronary artery. The four patients in Group IV died, the two not operated on within 3 to 5 days after acute myocardial infarction and t’ remaining two at surgery when they could not b eaned from cardiopulmonary by-
Volume 36
MYOCARDtAL REVASCULARlZATlON AFTER ACUTE INFARCTtON-SOXJOKI
FIGURE 4. Case 12, Group IV. lop, left ventricular angiograms in diistole and systole in a patient with total acute occlusion of the left anterior descending coronary artery (LAD). The right coronary artery (RC) and the circumflex artery (C) with its acute marginal branch (AM) were patent. Bottom, coronary arteriograms in the right anterior oblique (R.A.O.) and left anterior oblique (L.A.O.) views. Cardiac catheterization studies in this patient were performed during intraaortic balloon assistance. Although the patient was studied within 8 hours of acute myocardial infarction, he refused surgical intervention and died 2 days later.
pass. At autopsy these patients had 61 f 5 percent of the left ventricular mass involved in the process of infarction. A left ventricular angiogram from one of these patients (Case 12) is shown in Figure 4 and the pathologic photograph of myocardial infarction in this heart is shown in Figure 5. The four patients in Group I received seven coronary bypass grafts, of which five were patent (Table I). The four patients in Group II had five coronary grafts, all of which were patent. Patients in Group III received six coronary grafts, of which only three were patent. Thus, the total number of grafts in these three groups of patients was 18 and the total number of patent grafts was 13, giving an overall patency rate of 72 percent. One patient in Group IV received triple coronary grafts and one a double coronary graft with myocardial infarctectomy. In both of these patients the coronary bypass grafts were technically feasible and at the time of autopsy the graft anastomoses with the coronary artery were patent. There was an overall operative mortality rate of 15 percent (2 of 13 patients). Hemodynamic changes: Table IV presents the hemodynamic data for all patients. In Group I (myocardial revascularization within 4 hours of infarction), there was no significant change in most indexes. There was, however, a slight improvement in car-
FIGURE 5. Case 12. Group IV. The gross pathologic extent of the acute myocardiil infarct in the patient whose left ventricular angiograms are shown in Figure 4. The infarct involved 70 percent of the circumference of the left ventricle. The infarcted area (between arrows) is seen to have gelatinous degeneration and intracavitary clot formation (C). The left ventricular septum (S) and the right and left ventricular cavities are shown in a cross section from the middle of the infarcted area.
disc index and ejection fraction and a decrease in left ventricular end-diastolic pressure. In Group II (patients undergoing myocardial revascularization 4 to 8 hours after infarction with a pat.ent graft to the left anterior descending coronary artery), there was no significant change in most indexes of cardiac function, but end-diastolic volume increased significantly postoperatively (P <0.05). In Group III (patients undergoing myocardial revascularization within 4 hours of infarction but with occlusion of the left anterior descending coronary artery and its graft and patency of a diagonal branch graft, there was a significant increase in left ventricular end-diastolic pressure (from 9 f 0.8 [standard error] to 19 f 2 mm Hg, P CO.05). The preoperative cardiac catheterization data in this group of patients (Group III) were obtained before development of acute myocardial infarction since in all the infarct occurred just before scheduled elective coronary surgery. Group IV patients served as control subjects in order to evaluate the extent of left ventricular dysfunction and myo-
September 1975
The American Journal of CARDIOLOGY
Volume 36
401
MYOCARDIAL
REVASCULARIZATDN
AFTER ACUTE INFARCTKIN-BOLOOKI
volving 45 f 6 percent (standard error) of the diastolic silhouette of the left ventricle. This extent of dyskinesia was greater than in all other patients (P
cardial infarction after complete occlusion of the anterior descending coronary artery. The preoperative cardiac catheterization studies in these patients indicated a marked depression of left ventricular function (Tables IV and V), and .three of these patients underwent intraaortic balloon pumping in the course of cardiac catheterization (Table I). Changes in infarct size: Except for Group I (patients who underwent myocardial revascularization within 4 hours after myocardial infarction and who had a patent graft to the left anterior descending coronary artery), all patients had a large area of left ventricular dyskinesia. In patients in Group IV, which served as a control group, the preoperative data indicated the presence of left ventricular dyskinesia in-
TABLE
IV
Hemodynamic
and Angiographic
Data in Four Groups of Patients
Cl Patient
EDP
1
2
% EF
SWI
1
2
1
I
2
EDV
2
1
% Dyskynesiat
aV/ESV/aP
~_____
2
1
2
0.006 0.06 0.11
0.16 0.07 0.02 0.07 0.08 0.02
1
2
% Infarct”
Group I: Revascularization <4 Hours, LAD Open 1 2 3 4 Mean t SE P value
2.8 2.3 3.0 2.2 2.5 0.19
2.8 3.1 2.3 2.7 2.7 0.16
12 14 16 11 13 1
32 20 16 26 23 3
<0.20
0.02 0.6 0.43 . 6.35 0.17
co.10
9 10 11 Mean * SE P value
3.6 2.3 3.8 4.2 3.4 0.4
3.7 2.4 3.8 2.7 3.1 0.3
25 6 14 22 11 5 co.20
<0.20
3.1 2.2 2.2 2.5 0.2
1.8 2.1 2.4 2.1 0.1 co.20
14 18 14 8 13 2
Group
III:
11 8 10 9 0.8 *; 0.05
22 22 15 19 2
Group 12 13 14 15 Mean ? SE
1.4 2.1 2.4 1.1 1.7 0.3
.
.
42 20 30 20 28 5
27 42 68 69 56 13 / 0.20
co.20 Group
5 6 7 8 Mean 2 SE P value
0.26 0.40 0.26 0.40 0.33 0.04
II: Revascularization
0.37 0.44 0.32 0.24 0.38 0.58 0.60 0.30 0.41 0.39 0.06 0.07 I 0.20 Revascularization 0.33 0.40 0.25 0.32 0.04
IV: Control,
_.
0.03 0.24 0.13 0.04 0.11 0.03
38 38 78 51 50 52 78 63 61 51 10 5 ,‘. 0.20 LAD
40 ks 50 76 40 70 43 5 3 .. . 0.20
LAD
Closed, Anterior
. . .
150 105 224 153 158 24 co.20
-14 Hours,
,:4 Hours,
0.20 0.22 0.29 0.23 0.02 -: 0.20
61 61 65 66 63 1
25 41 30 30 31 3
LAD
146 137 177 100 140 15
< 0.20
Other
250 82 134 223 305 152 229 70 50 co.10
0.01 0.09
. . ::
0.01 0.06 0.07 0.17 0.07 0.03
d.& 0.25 0.20 I, 0.20
Wall Infarction
. _. . __.
38 5 ;; 18.3 10 co.20
38 23 21 18 25 4
.__
.
Grafts Open
.
253 245 200 250 237 12
5 0 0 0 1.2 1.2
Open
232 257 190 264 170 177 114 181 176 219 24 23 ’ 0.05 Closed,
d.bi 0.03
10 22 20 20 18 2
0.20 0.06 0.13 0.06
. 0.02 0.01 0.01 0.004
0 0 0 0 0
20 18 22 20 1
.
62 50 30 40 45 6
.
< 0.20
. :. . ...
.
>4 Hours 0.004 0.008 0.008 0.004 0.006 0.001
..
.
. ..
.
70 60 50 55 61 5
* Gross pathologic size of infarct in relation to left ventricular mass as measured at autopsy. + Extent of left ventricular wall dyskinesia over the diastolic chamber silhouette. 1 = preoperative and 2 = postoperative data; Cl = cardiac index (liters/min per m*); AV/ESV/~P (units) = compliance”; EDP = left ventricular end-diastolic pressure (mm Hg); EDV = end-diastolic volume (ml); EF = ejection fraction; ESV = endsystolic volume; LAD = left anterior descending coronary artery; P = probability (comparing pre- and postoperative data); SE = standard error; SWI = stroke work index (g-m per m’).
402
September 1975
The American Journal of CARDIOLOGY
Volume 38
MYOCARDlAL REVASCULARIZATION
ly larger than in patients in Group III, who had a closed graft. In group II there was a mean dyskinetic area of 25 f 4 percent compared with a mean value of 20 f 1 percent in Group III (Table IV). This difference was not statistically significant (P <0.20), thus indicating the similarity of the extent of left ventricular dyskinesia and possibly infarction in patients undergoing revascularization of the left anterior descending coronary artery 4 to 8 hours after infarction, and those with revascularization of only its diagonal branch. The left ventricular angiograms from two patients in Groups II and III are shown in Figures 6 and 7. Electrocardiographic changes: The electrocardiographic evidence of transmural infarction in all patients remained unchanged (Fig. 1 and 2). Evolution of infarction in the postoperative tracings was seen with persistent Q waves throughout the precordial leads and leads I and aVL. Serum enzyme changes: Preoperative serum enzyme studies in 11 patients showed an increase in creatine phosphokinase to 1,200 f 300 IU (standard error) (normal 150 IU); values for HBD, LDH and GOT were within normal limits. Postoperatively serum CPK increased markedly in all patients to a mean (13 patients) of 2,400 f 700 IU, associated with increases in HBD, LDH and GOT for 3 to 4 days after revascularization. The peak increase in serum CPK occurred 12 hours after revascularization (Fig. 8). Follow-up: In the course of 1 to 4 years of followup 11 patients have remained asymptomatic, and 9 of these have returned to work. Two patients from Group II are not working. Two other patients (one
TABLE
V
Clinical ------
Studies:
Statistical
Analysis -__
Groups Compared -____ .___ -__ I with II (df = 6) t score
I
P value with I I I (df = 5) t score P value
II with III t score
I
of Postoperative -_--~--
Cl
EDP
1.098
0.106
AFTER ACUTE INFARCTiON-BOLOOKl
each from Groups I and II) were asymptomatic but died suddenly 4 months and 1 year, respectively, after operation with cardiogenic shock and cardiac arrest due to sudden closure of the left anterior descending coronary artery graft. Two patients from Group II underwent repeated cardiac catheterization studies after revascularization. In one patient the size of infarct (left ventricular dyskinesia) decreased markedly within 9 months postoperatively.7 A third postoperative cardiac catheterization in this man showed no further changes in left ventricular contraction pattern. In the second patient, who had two postoperative hemodynamic studies, there was no change in the size of a left ventricular aneurysm that developed in spite of a patent graft to the left anterior descending coronary artery (Fig. 9). However, the patient’s cardiac function showed some improvement 3 l/2 years after revascularization (left ventricular diastolic pressure decreased from 22 to 14 mm Hg and cardiac index increased from 2.2 to 2.7 liters/min per m2). Discussion Previous experimental studies have shown that with reperfusion of an area of myocardial ischemia within 3 hours of coronary occlusion, the size of the myocardial infarct (as determined by release of CPK) decreases appreciably. ls2 Reperfusion has been employed clinically in patients who were considered to be in a phase of preinfarction13-1” or early infarction16 or to have extension of an infarct.17 It has been shownl*Jg that revascularization can be carried out with acceptable operative mortality and results in improved cardiac function and a reduced size of myo-
Data
______~______.______~__---_._ SW!
%EF
EDV -__--__
2.319
0.6979
aV/ESP/AP
% Dyskinesia
<0.20
<0.20
< 0.20
<0.05
2.806 <0.02
0.056 <0.20
5.135 < 0.001
2.648 < 0.02
2.483 <0.05
1.917
5.558
1.697 10.10
.2.198 < 0.05
11.02
1.255 <0.20
0.178 <0.20
1.845 <1.10
1.086 10.20
a.757
4.814
2.536 < 0.02
6.355 < 0.001
3.181
0.646 <0.20
.2.133 < 0.05
2.501 10.02
2.493
0.141 <0.20
1.757
3.671 10.01
(df = 5)
P value with IV*(df t score
2.699
1.980
< 0.02
1.902
= 6) 2.850
P value II with IV*(df=6) r score
<0.02
P value III with IV*(df I score
<0.02
2.760 <0.02
3.036
2.580 <0.02
3.474
= 5) 1.017
P value __________~__.__ * In Group IV
the patients
par ison. Abbreviations
as in Tables
1.455
<0.20
<0.20 died
2.268 <0.05
and had no postoperative
<0.05
___studies; their
preoperative
data were used for statistical
COm-
I I I and IV.
September 1975
fhe
American
Journal of CARDIOLOGY
Volume 36
403
MYOCARDIAL REVASCULARIZATION AFTER ACUTE INFARCTION-BOLOCKI
cardial infarct. Although, in clinical cases, it has been difficult to calculate the extent of decrease in size of the eventual infarct, it was postulated that reversal of the clinical shock state and improvement in cardiac function were indicators of a decrease in the area of nonfunctioning myocardium and, hence, of a decrease in the size of the infarct. Effect of reperfusion on infarct size: Because of the complicated clinical setting in which emergency myocardial revascularization for an acute myocardial infarction is decided upon, it is not possible to categorize all patients into one group. For this reason we have classified our patients into four groups on the basis of several variables. For example, unlike the reported results in other studies, our data were correlated with the postoperative angiographic findings because operative survival or reversal of the shock state as such does not necessarily indicate a successful revascularization. Furthermore, in the clinical setting timing of the duration of ischemia or infarction has always been difficult. As a result, in all clinical studies related to this subject (including this investi-
gation) there have been some departures from a strict research protocol that might affect the results considerably. To clarify our results we analyzed data in a group of patients selected because they had a similar anatomic lesion in the left anterior descending coronary artery and a similar interval between the onset of infarction and revascularization. To complement the clinical study, because the extent of pathologic infarction in patients could not be evaluated, we performed some experiments in dogs. We believe that the results show clearly that reperfusion of an ischemit (or infarcted) area of the myocardium can be performed with acceptable mortality and is beneficial in man if carried out within 4 hours of the onset of myocardial infarction. Our experimental studies indicated that, with reperfusion of an infarcted area within 2 hours of coronary occlusion, it was possible to decrease the eventual size of the infarct by about 50 percent (from 27 f 2 percent to 11.8 f 4.19 percent, P
preoperative- anterior- ventricula; wall dyskinesia was due to multiple lesions in the left anterior descending coronary artery (double arrows, top right). Postoperative angiograms obtained 3 months later showed no change in the extent of anterior wall dyskinesia or ejection fraction (Table IV). The graft to the anterior descending coronary artery (dngle arrow, lower panels) is patent. There are multiple sitver clips in the postoperative angiograms.
FIGURE 7. Case1 1, Group Ill. Pm- and postoperative left ventricular angiograms (left and center panels) and coronary arteriograms (rfght panels). The patient was studied before development of acute myocardial infarction. There was no left ventricular dyskinesia. but the left anterior descending coronary artery (LAD) and diagonal branch (D) showed more than 90 percent obstructive lesions. Acute myocardiil infarction developed in this patient at the time of anesthesia induction as evidenced by electrocardiographic change and hypotension. Coronary grafts to the left anterior descending coronary artery and its diagonal branch were performed, and the patient tolerated the procedure well. Postoperative angiograms obtained 4 months later showed e&fence of dyskinesia and aneurysmal formation of the anterior wall due to closure of the graft to the left anterior descending coronary artery. The graft to the diagonal branch was patent. (Reprinted from Bolooki et al.’ by permission of the American Heart Association.)
404
September 1975
The American Journal of CARDIOLOGY
Volume 36
MYOCARDlAL REVASCULARIZATION
left ventricular dyskinesia decreased considerably (from a mean value of 18 percent to 1.2 percent, P
AFTER ACUTE INFARCTION-SOLOOKI
of an adjacent patent coronary graft contributed to limiting the extent of myocardial infarction in these patients. In patients with a patent graft (reperfusion) to the left anterior descending coronary artery, the anterior descending artery was the major anterior wall artery without a large diagonal branch or other collateral vessels. Although this anatomic variation could have played an important role in survival of these patients, it is safe to conclude that myocardial reperfusion performed more than 4 hours after myocardial infarction does not prevent development of a dyskinetic area of the left ventricle or an aneurysm (Fig. 7 and 9). In this study, we found no dyskinetic areas in three patients who underwent myocardial revascularization within 4 hours of electrocardiographic infarction. In these patients electrocardiographic
C.P.K.*ll.l.K.o--~
SuRftRY
1.B.Y.~~~~~~ S.f.K.T.~--.
‘\
Es
,
AFTER
FIGURE 9. Case 9, Group Ill. Serum enzyme curves before (top) and after (bottom) myocardial revascularization. Preoperative studies were obtained on admission (1). during day 1 in the hospital (2) and before surgical intervention (3). The postoperative studies were performed on days 1 to 10 postoperatively. This pattern of serum enzyme rise and decline was seen in most patients operated on in the course of acute myocardial infarction.
FIGURE 9. Case 6. Group II. Left ventricular angiograms (top) and coronary arteriograms (bottom) obtained 7 months postoperatively in the patient whose electrocardiograms are shown in Figure 1. A large left ventricular aneurysm involving the anterior and inferior walls has developed in spite of a patent graft to the left anterior descending coronary artery (LAD). The left circumflex coronary artery (LC) and its acute marginal branch are normal. A repeat cardiac catheterization in this man 3 l/2 years after revascularization of the infarct showed no changes in the pattern of left ventricular contraction. (Reprinted from Bolooki et al.13 by permission.)
September 1975
The American Journal of CARDIOLOGY
Volume 36
405
MVDCARDIAL REVASCULARIZATIDN AFTER ACUTE INFARCTION-BOLDOKI
evidence of acute myocardial infarction (S-T segment elevation) and hypotension developed while they were being given general anesthesia in the operating room. An interesting observation was the persistence of preoperative Q waves in the postoperative electrocardiograms (Fig. 1 and 2) in spite of successful revascularization of the infarct. This finding indicates that the revascularized transmural infarct remains abnormal electrophysiologically. In our experience with these and other patients with the so-called intermediate coronary syndrome or preinfarction angina, the only reversible electrocardiographic changes have been those of subendocardial ischemia (T wave inversion in precordial leads) regardless of the duration of these changes before operation.‘s Clinical implications: Our study shows that the duration of ischemia before reestablishment of blood flow to the distal areas of an occluded coronary artery in man must be limited to 4 hours if reperfusion is to lead to improvement in cardiac function and a decrease in the extent of the infarct. This finding is supported by our experimental results, although perhaps because of the acute conditions of the experiments, the time limit in dogs is 2 hours. This difference in time may also indicate a greater tolerance of human myocardium to ischemia and is most likely due to the presence of numerous intercoronary collateral communications and the insidious onset of coronary obstruction. In addition to a significant decrease in the extent
of dyskinetic area in patients who had successful myocardial revascularization (reperfusion) early after infarction, the overall cardiac function was better than in patients who underwent myocardial reperfusion late after infarction (Group II) or did not undergo revascularization of the left anterior descending coronary artery (Group III). However, long-term follow-up studies (1 to 4 years) in these patients demonstrated that, regardless of patency or closure of the bypass graft to the left anterior descending coronary artery, most patients undergoing revascularization for an acute infarct remained asymptomatic and many returned to their previous activities. Although a recent report by Shell and SobeP indicates the advantages of noninvasive measures to reduce infarct size in patients with myocardial infarction, perhaps a study of matched groups of patients treated by noninvasive (antihypertensive) methods and by myocardial reperfusion would further our knowledge of the effects of each of these methods. It is likely, however, that no one method will be useful for all patients and in the future the patients may be carefully selected for a specific method of therapy. Acknowledgment We express our gratitude to Drs. Ali Ghahramani, Leonard Sommer and Stephen Mallon, who performed the cardiac catheterization studies in these patients. Drs. James Jude and Richard Robinson performed surgery in two of these patients. We also appreciate the data analysis and calculations by Miss Adrianne Fried, BSN.
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