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Hemodynamic and ultrastructural evaluation of experimental myocardial infarctectomy
Hemodynamic and ultrastructural evaluation of experimental myocardial infarctectomy Infarcts were created in 16 pigs by ligating main branches of the left anterior descending coronary artery (LAD). Two animals died immediately; 14, in shock, were supported for 1 hour by intra-aortic balloon counterpulsation (IABCP). Injarctectomy was performed. Aortic flow and left ventricular pressure were improved by this procedure (8/14). Some animals (6/14) survived until they were put to death to obtain samples of the myocardium. Analysis of oxidative metabolism of mitochondria in the infarcted, marginal, and normal myocardium was carried out by measuring respiratory control index (RCI), adenosine diphosphate added/ oxygen consumed (ADP/O), and rate of respiration (QOz) indices. Electron microscopic studies were made in the same samples. Mitochondria exhibited marked depression in oxidative metabolism, not only in the infarcted area but also in the marginal portion. This finding suggests that the damaged area is larger than the frankly infarcted, cyanotic wall.
Raymond R. Limet, M.D., Marlene Lazarus, M.S., Arnold S. Schwartz, Ph.D., Louis A. Sordahl, Ph.D., Arnold Strashun, B.S., Rick Manning, B.S., and John H. Kennedy, M.D., Houston, Texas
Ifailure, n certain patients with progressive cardiac use of mechanical circulatory assistance permits recovery, whereas in others circulation becomes dependent upon the assist device- 6 despite an increased flow in the ischemic myocardium. 7 The present study was undertaken to assess the effect of infarctectomy in pigs which were dependent upon intra-aortic balloon counterpulsation (IABCP). The pig was chosen because of its many similarities with human beings, particularly with respect to the coronary circulation." Methods
Sixteen pigs, ranging in weight from 11 to 25 kilograms, were anesthetized with a From the Taub Laboratories for Mechanical Circulatory Support, Cora and Webb Mading Department of Surgery, Baylor College of Medicine, Houston, Texas
77025. Research supported in part by U. S. Public Health Service Grant HL-13330. Received for publication July 20, 1973.
Fluothane-oxygen mixture. Median sternotomy was performed, and a flow probe was placed around the aortic root and connected to a square-wave electronic flowmeter (Carolina Medical Electronics, Inc., Winston Salem, N. C.). Polyethylene catheters (outer diameter 0.4 mm.) were inserted in the left ventricle, aorta, and superior vena cava, and pressures were recorded with Statham P23b transducers and an Electronics for Medicine recorder. Lateral laparotomy was performed. Because of the small diameter of the femoral artery in the pig, one iliac artery was isolated and a Teflon catheter (size 18 Fr.), to which was attached a 15 c.c. polyurethan balloon, * was introduced to the level of the left subclavian artery. Heparin (3 mg. per kilogram) was given, and cannulas were inserted in the right atrium and iliac artery. Control data were recorded. 'Fabricated in the Plastics Laboratory, Baylor College of Medicine, Houston, Texas.
243
The Journal of
Limet et al.
244
Thoracic and Cardiovascular Surgery
Fig. 1. Angiocardiography of the left ventricle before (A) and after (B) infarctectomy. Bulge of the sutured wall can be seen.
Table I Venous pressure (mm. Hg)
Lett ventricular pressure (mm. Hg) A
42 60 90 60 80 120 90 64 58 76 44 72 92
76
I
B
0 24 64 40 50 35 70 10 72
50 20 80 56 62
I
C
68 30 68 26 28 60 70 36 68 68 56 60 72
48
A
10 14 10 14 14 16 6 6 8 5 10 10
I
B
I
10 14 17
14 14 18 7
Cardiac flow (per cent) C
15 17 18 16 13
10
9
11
11 11
12
8 6
10 14
A
I
B
I
C
100 100
77 83
88 20
100 100 100 100
62 69 80 55
72
88 120 100
11
Survival (min.)
15 27 12 30 5 28 15 60· 120· 60· 60· 20 60· 60·
Legend: A, Normal conditions. B, Values after infarction. C, Values after completion of the infarctectomy. 'Pigs in good condition at the time of sacrifice.
After injection of lidocaine (2 mg. per kilogram) to prevent arrhythmias, myocardial infarction was produced by ligating branches of the left anterior descending artery (LAD) while avoiding any damage to the anterior septal artery. IABCP was started a few minutes later for a period of
60 minutes; data were recorded again. Bypass was initiated and infarctectomy was carried out. The excision was made as ellipse, the apogee of which was parallel to the LAD. It was extended laterally until a pink region was reached which was assumed to be
Volume 67 Number 2 Februory, 1974
Experimental myocardial iniarctectomy
245
Fig. 2. Electron microscopic view of normal myocardium shows normal striation of the myofibrils (mf) and normal inner and outer structures of the mitochondria (m). (Original magnification x20,200.)
the limit of the infarct. The excised infarcted muscle was immediately placed in a special solution* and submitted for mitochondrial biochemical analysis. Because of the friability of the fresh infarcted muscle, walls were reapproximated by mattress sutures, which were passed through two pieces of Dacron
velour in order to avoid the sutures cutting through. Direct-current countershock was used to correct ventricular fibrillation when necessary, and bypass was discontinued. A third sample of data was recorded . Eight pigs died from the procedure a few minutes after bypass was stopped*; 6 others
"KE1G A (O.l8M KCl, lOmM ethylenediaminetetraacetic acid, O.S per cent bovine serum albumin [pH 7.2» .
"When an attempt to discontinue IABCP was made, hypotension and low cardiac output ensued.
The Journal of
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Limet et al.
Thoracic and Cardiovascular Surgery
Fig. 3. Electron microscopic view of infarcted myocardium. Contracture band (cb) can be seen. Sarcoplasmic reticulum (SR) is swollen. Some mitochondria (m) are disrupted. (Original magnification x18,300.)
remained alive until they were put to death. Then peripheral muscle neighboring the excised infarct and normal myocardial wall were immediately preserved in the special solution. A small portion was prepared at this time for fixation for electron microscopy. Mitochondria were isolated by differential centrifugation and were analyzed by polarographic methods for comparative oxidative phosphorylation and electron transfer capacity. The efficiency of the mitochondria
was expressed by three indices: ( I) the respiratory control index (ReI) , revealing the tightness of coupling between phosphorylation and electron flow; (2) the amount of adenosine diphosphate added/ oxygen consumed (ADP/ 0 ) ; and (3) the rate of respirat ion (Q02), analyzing the rate of oxygen consumption of mitochondria ." pH and blood gases were available throughout the experiment. In 1 pig (Table I), estimation of the left ventricular volume by bi-
Volume 67
Number 2
Experimental myocardial iniarctectomy
2 4 7
February, 1974
Fig. 4. Electron microscopic view of infarcted myocardium. Lesions are severe. Normal arrangement of myofibrils (mf) and mitochondria has vanished. E, Interstitial edema. g, Golgi zone. (Original magnification x36,lOO.)
plane angiography was carried out by injection of 15 c.c. sodium iodothalamate (80 per cent) into the left ventricle. Results
Hemodynamic data. In 2 of the 16 pigs, the heart did not start beating again after infarction. Immediate bypass and emergency infarctectomy did not permit resuscitation in these 2 animals. Results for the remaining 14 animals are shown in Table I. Car-
diac action appeared effective immediately after infarctectomy; aortic pressure and velocity of flow were increased, yet venous pressure and left ventricular end-diastolic pressure (LVEDP) were increased as well. Most often the cardiac output fell quickly. Consequently, severe metabolic acidosis ensued and animals died in asystole. No fatal arrhythmias occurred, but it was very often necessary to pace the heart during the experiment. In 6 animals there was a notice-
The Journal of
248
Limet et al.
Thoracic and Cardiovascular Surgery
Fig. 5. Electron microscopic view of the intermediate myocardium. Lesions are like those displayed in Fig. 4. M, Mitochondria. mj, Myofibril. E, Edema. (Original magnification x12,OOO.)
able survival time with an apparently effective heart action up to the time of sacrifice. In these animals, venous pressure was below 11 mm. Hg. From the observation of the beating heart during the experiment and from angiocardiography (Fig. 1), it would appear that the useful volume of the left ventricular chamber is seriously restricted by the procedure. Fifteen per cent of the left ventricle was excised," but the portion of the heart through which the stitches pass must be taken into account as well. Biochemical data. RCI and ADP/O were 10.6 and 4.0 in the normal myocardium, 9.8 and 4.0 in the marginal tissue, and 8.3 and 3.5 in the infarcted myocardium. Q02 was 182 nanoatoms of oxygen per minute in the normal myocardium but dropped to 133 and 107 in the marginal and infarcted myo-
cardium. Thus the experimental data from infarction studies show marked differences between normal and infarcted samples for all three indices. Normal values appeared consistent with the values of normal heart in other species. 8 Most dramatic was the extreme drop in Q02 between the normal and infarcted tissues; such results were anticipated, as mitochondrial activity was expected to be greatly impaired in the dying tissue. Not anticipated, however, was the marked drop in the Q02 of the peripheral tissue as well. It should be noted that there was little difference between values for normal and peripheral tissue for RCI and ADP/O indices. These results reveal that there is further damage from myocardial infarction than can be noted visually, i.e., the peripheral tissue
Volume 67 Number 2 February, 1974
as well as the infarcted tissue is enzymatically less active in respiration. However, the peripheral RCI and ADP/0 values still remain in the normal range. Nothing can be said about the reversibility of damage to the mitochondria of the marginal tissue. Electron microscopic studies (Figs. 2 to 5). Electron microscopic studies of the myocardium stained with 3.5 per cent uranyl acetate and 0.4 per cent lead citrate reveal a normal ultrastructure in the normal area (Fig. 2). Mitochondria are not swollen and cristae are intact. The tissues taken from infarcted areas showed changes characteristic of hypoxic tissue, but some sections displayed nearly normal architecture. In some instances, a slight dilatation of the sarcoplasmic reticulum (Fig. 3) or a complete disruption of normal myofibrillar and mitochondrial arrangement (Fig. 4) can be seen. Most interesting is the fact that tissues from the marginal areas display severe intracellular edema; mitochondria are swollen and normal cristae and membrane patterns are disrupted (Fig. 5). Cells from the marginal area display much greater injury to their ultrastructure as compared to cells from infarcted tissue due to the time of tissue sampling.
Experimental myocardial injarctectomy
undesirable consequences: The oxygen requirements were increased and the efficiency was decreased. Thus the two major difficulties encountered were changes in the cardiac chambers and mitochondrial damage in the apparently normal myocardium. Other experiments with dogs- 4," have ended with better survival rates than this study. The heart size of the dog is similar to the heart size of the bigger pigs used in this series, but the crucial factor seems to be that the heart has no time to adapt itself to this suddenly reduced volume. Hence, left ventricular bypass in the days following the operation would be expected to be of particular value. Mitochondrial damage cannot be discerned by the surgeon so that, in some ways, acute infarctectomy is still a "blind" procedure. REFERENCES
2
3
Discussion This study arouses again the same important point that Bailey and Gilman- mentioned in 1957: "How much to excise?" From the biochemical and ultrastructural results, it can be concluded that the infarcted area was larger than it appeared. The tissue surrounding the infarcted area, although pink and beating well, had important biochemical abnormalities, the reversibility of which is questionable. Besides, after excision and reconstruction of the ventricle, the diastolic volume was so restricted that the left ventricle had only two mechanisms by which to deliver the same output: either eject the same stroke volume from a much higher LVEDP because of the decrease in distensibility or eject a smaller stroke volume at a higher rate. Both conditions had the same
249
4
5
6
7
Bailey, C. D., and Gilman, R. A.: Experimental and Clinical Resection for Ventricular Aneurysm, Surg. Gynecol. Obstet. 104: 539, 1957. Danielson, K. S., Resnicoff, S. A, and DeWeese, J. A.: An Evaluation of Myocardial Infarctectomy, J. THoRAc. CARDIOVASC. SURG. 59: 723, 1970. Feola, M., Normann, N. A., Haiderer, 0., and Kennedy, J. H.: Assisted Circulation: Experimental Intra-aortic Balloon Pumping, Artificial Heart Program Conference, Washington, D. C,; June 9-13, 1969, U. S. Government Printing Office. Glass, B. A, Carter, R. L., and Albert, H. M.: Experimental Myocardial Infarction: Effect on Cardiac Output and Response of the Heart After Surgical Excision, Am. Surg. 33: 912, 1967. Jude, J. R., Mobin-Uddin, K., MartinezFarinas, L. 0., Lombardo, C. R., and Smith, P. E.: Surgical Treatment of Experimental Myocardial Infarction, J. A M. A. 203: 451, 1968. Kennedy, J. H.: Assisted Circulation: An Extended Concept of Cardiopulmonary Resuscitation, J. THoRAc. CARDIOVASC. SURG. 57: 668, 1969. Limet, R., Feola, M., Hojevac, I., Ross, J. N., Jr., and Kennedy, J. H.: Effects of Intra-aortic Balloon Counterpulsation on the Distribution of Myocardial Blood Flow in Experimental Left Ventricular Failure, J. Cardiovasc. Surg. 13: 315, 1972.
The Journal of
250
Limet et al.
Thoracic and Cardiovascular Surgery
8 Lindenmayer, G. E., Sordahl, L. A, and Schwartz, A: Re-evaluation of Oxidative Phosphorylation in Cardiac Mitochondria From Normal Animals and Animals in Heart Failure, Circ. Res. 23: 439, 1968. 9 Shacklett, R. C., and Singletary, H.: Comparative Anatomy: Human, Dog, and Swine, ill
Bustad, L. K., and McClellan, R. 0.: Swine in Biomedical Research, Richland, Wash., 1965, Pacific Northwest Laboratory, pp. 390-397. 10 Williams, C. L., and Woods, L. P.: Experimental Resection of Myocardial Infarction, Ann. Thorac. Surg. 10: 339, 1970.
Raymond R. Limet, M.D., Marlene Lazarus, M.S., Arnold S. Schwartz, Ph.D., Louis A. Sordahl, Ph.D., Arnold Strashun, B.S., Rick Manning, B.S., and John H. Kennedy, M.D., Houston, Texas
Ifailure, n certain patients with progressive cardiac use of mechanical circulatory assistance permits recovery, whereas in others circulation becomes dependent upon the assist device- 6 despite an increased flow in the ischemic myocardium. 7 The present study was undertaken to assess the effect of infarctectomy in pigs which were dependent upon intra-aortic balloon counterpulsation (IABCP). The pig was chosen because of its many similarities with human beings, particularly with respect to the coronary circulation." Methods
Sixteen pigs, ranging in weight from 11 to 25 kilograms, were anesthetized with a From the Taub Laboratories for Mechanical Circulatory Support, Cora and Webb Mading Department of Surgery, Baylor College of Medicine, Houston, Texas
77025. Research supported in part by U. S. Public Health Service Grant HL-13330. Received for publication July 20, 1973.
Fluothane-oxygen mixture. Median sternotomy was performed, and a flow probe was placed around the aortic root and connected to a square-wave electronic flowmeter (Carolina Medical Electronics, Inc., Winston Salem, N. C.). Polyethylene catheters (outer diameter 0.4 mm.) were inserted in the left ventricle, aorta, and superior vena cava, and pressures were recorded with Statham P23b transducers and an Electronics for Medicine recorder. Lateral laparotomy was performed. Because of the small diameter of the femoral artery in the pig, one iliac artery was isolated and a Teflon catheter (size 18 Fr.), to which was attached a 15 c.c. polyurethan balloon, * was introduced to the level of the left subclavian artery. Heparin (3 mg. per kilogram) was given, and cannulas were inserted in the right atrium and iliac artery. Control data were recorded. 'Fabricated in the Plastics Laboratory, Baylor College of Medicine, Houston, Texas.
243
The Journal of
Limet et al.
244
Thoracic and Cardiovascular Surgery
Fig. 1. Angiocardiography of the left ventricle before (A) and after (B) infarctectomy. Bulge of the sutured wall can be seen.
Table I Venous pressure (mm. Hg)
Lett ventricular pressure (mm. Hg) A
42 60 90 60 80 120 90 64 58 76 44 72 92
76
I
B
0 24 64 40 50 35 70 10 72
50 20 80 56 62
I
C
68 30 68 26 28 60 70 36 68 68 56 60 72
48
A
10 14 10 14 14 16 6 6 8 5 10 10
I
B
I
10 14 17
14 14 18 7
Cardiac flow (per cent) C
15 17 18 16 13
10
9
11
11 11
12
8 6
10 14
A
I
B
I
C
100 100
77 83
88 20
100 100 100 100
62 69 80 55
72
88 120 100
11
Survival (min.)
15 27 12 30 5 28 15 60· 120· 60· 60· 20 60· 60·
Legend: A, Normal conditions. B, Values after infarction. C, Values after completion of the infarctectomy. 'Pigs in good condition at the time of sacrifice.
After injection of lidocaine (2 mg. per kilogram) to prevent arrhythmias, myocardial infarction was produced by ligating branches of the left anterior descending artery (LAD) while avoiding any damage to the anterior septal artery. IABCP was started a few minutes later for a period of
60 minutes; data were recorded again. Bypass was initiated and infarctectomy was carried out. The excision was made as ellipse, the apogee of which was parallel to the LAD. It was extended laterally until a pink region was reached which was assumed to be
Volume 67 Number 2 Februory, 1974
Experimental myocardial iniarctectomy
245
Fig. 2. Electron microscopic view of normal myocardium shows normal striation of the myofibrils (mf) and normal inner and outer structures of the mitochondria (m). (Original magnification x20,200.)
the limit of the infarct. The excised infarcted muscle was immediately placed in a special solution* and submitted for mitochondrial biochemical analysis. Because of the friability of the fresh infarcted muscle, walls were reapproximated by mattress sutures, which were passed through two pieces of Dacron
velour in order to avoid the sutures cutting through. Direct-current countershock was used to correct ventricular fibrillation when necessary, and bypass was discontinued. A third sample of data was recorded . Eight pigs died from the procedure a few minutes after bypass was stopped*; 6 others
"KE1G A (O.l8M KCl, lOmM ethylenediaminetetraacetic acid, O.S per cent bovine serum albumin [pH 7.2» .
"When an attempt to discontinue IABCP was made, hypotension and low cardiac output ensued.
The Journal of
246
Limet et al.
Thoracic and Cardiovascular Surgery
Fig. 3. Electron microscopic view of infarcted myocardium. Contracture band (cb) can be seen. Sarcoplasmic reticulum (SR) is swollen. Some mitochondria (m) are disrupted. (Original magnification x18,300.)
remained alive until they were put to death. Then peripheral muscle neighboring the excised infarct and normal myocardial wall were immediately preserved in the special solution. A small portion was prepared at this time for fixation for electron microscopy. Mitochondria were isolated by differential centrifugation and were analyzed by polarographic methods for comparative oxidative phosphorylation and electron transfer capacity. The efficiency of the mitochondria
was expressed by three indices: ( I) the respiratory control index (ReI) , revealing the tightness of coupling between phosphorylation and electron flow; (2) the amount of adenosine diphosphate added/ oxygen consumed (ADP/ 0 ) ; and (3) the rate of respirat ion (Q02), analyzing the rate of oxygen consumption of mitochondria ." pH and blood gases were available throughout the experiment. In 1 pig (Table I), estimation of the left ventricular volume by bi-
Volume 67
Number 2
Experimental myocardial iniarctectomy
2 4 7
February, 1974
Fig. 4. Electron microscopic view of infarcted myocardium. Lesions are severe. Normal arrangement of myofibrils (mf) and mitochondria has vanished. E, Interstitial edema. g, Golgi zone. (Original magnification x36,lOO.)
plane angiography was carried out by injection of 15 c.c. sodium iodothalamate (80 per cent) into the left ventricle. Results
Hemodynamic data. In 2 of the 16 pigs, the heart did not start beating again after infarction. Immediate bypass and emergency infarctectomy did not permit resuscitation in these 2 animals. Results for the remaining 14 animals are shown in Table I. Car-
diac action appeared effective immediately after infarctectomy; aortic pressure and velocity of flow were increased, yet venous pressure and left ventricular end-diastolic pressure (LVEDP) were increased as well. Most often the cardiac output fell quickly. Consequently, severe metabolic acidosis ensued and animals died in asystole. No fatal arrhythmias occurred, but it was very often necessary to pace the heart during the experiment. In 6 animals there was a notice-
The Journal of
248
Limet et al.
Thoracic and Cardiovascular Surgery
Fig. 5. Electron microscopic view of the intermediate myocardium. Lesions are like those displayed in Fig. 4. M, Mitochondria. mj, Myofibril. E, Edema. (Original magnification x12,OOO.)
able survival time with an apparently effective heart action up to the time of sacrifice. In these animals, venous pressure was below 11 mm. Hg. From the observation of the beating heart during the experiment and from angiocardiography (Fig. 1), it would appear that the useful volume of the left ventricular chamber is seriously restricted by the procedure. Fifteen per cent of the left ventricle was excised," but the portion of the heart through which the stitches pass must be taken into account as well. Biochemical data. RCI and ADP/O were 10.6 and 4.0 in the normal myocardium, 9.8 and 4.0 in the marginal tissue, and 8.3 and 3.5 in the infarcted myocardium. Q02 was 182 nanoatoms of oxygen per minute in the normal myocardium but dropped to 133 and 107 in the marginal and infarcted myo-
cardium. Thus the experimental data from infarction studies show marked differences between normal and infarcted samples for all three indices. Normal values appeared consistent with the values of normal heart in other species. 8 Most dramatic was the extreme drop in Q02 between the normal and infarcted tissues; such results were anticipated, as mitochondrial activity was expected to be greatly impaired in the dying tissue. Not anticipated, however, was the marked drop in the Q02 of the peripheral tissue as well. It should be noted that there was little difference between values for normal and peripheral tissue for RCI and ADP/O indices. These results reveal that there is further damage from myocardial infarction than can be noted visually, i.e., the peripheral tissue
Volume 67 Number 2 February, 1974
as well as the infarcted tissue is enzymatically less active in respiration. However, the peripheral RCI and ADP/0 values still remain in the normal range. Nothing can be said about the reversibility of damage to the mitochondria of the marginal tissue. Electron microscopic studies (Figs. 2 to 5). Electron microscopic studies of the myocardium stained with 3.5 per cent uranyl acetate and 0.4 per cent lead citrate reveal a normal ultrastructure in the normal area (Fig. 2). Mitochondria are not swollen and cristae are intact. The tissues taken from infarcted areas showed changes characteristic of hypoxic tissue, but some sections displayed nearly normal architecture. In some instances, a slight dilatation of the sarcoplasmic reticulum (Fig. 3) or a complete disruption of normal myofibrillar and mitochondrial arrangement (Fig. 4) can be seen. Most interesting is the fact that tissues from the marginal areas display severe intracellular edema; mitochondria are swollen and normal cristae and membrane patterns are disrupted (Fig. 5). Cells from the marginal area display much greater injury to their ultrastructure as compared to cells from infarcted tissue due to the time of tissue sampling.
Experimental myocardial injarctectomy
undesirable consequences: The oxygen requirements were increased and the efficiency was decreased. Thus the two major difficulties encountered were changes in the cardiac chambers and mitochondrial damage in the apparently normal myocardium. Other experiments with dogs- 4," have ended with better survival rates than this study. The heart size of the dog is similar to the heart size of the bigger pigs used in this series, but the crucial factor seems to be that the heart has no time to adapt itself to this suddenly reduced volume. Hence, left ventricular bypass in the days following the operation would be expected to be of particular value. Mitochondrial damage cannot be discerned by the surgeon so that, in some ways, acute infarctectomy is still a "blind" procedure. REFERENCES
2
3
Discussion This study arouses again the same important point that Bailey and Gilman- mentioned in 1957: "How much to excise?" From the biochemical and ultrastructural results, it can be concluded that the infarcted area was larger than it appeared. The tissue surrounding the infarcted area, although pink and beating well, had important biochemical abnormalities, the reversibility of which is questionable. Besides, after excision and reconstruction of the ventricle, the diastolic volume was so restricted that the left ventricle had only two mechanisms by which to deliver the same output: either eject the same stroke volume from a much higher LVEDP because of the decrease in distensibility or eject a smaller stroke volume at a higher rate. Both conditions had the same
249
4
5
6
7
Bailey, C. D., and Gilman, R. A.: Experimental and Clinical Resection for Ventricular Aneurysm, Surg. Gynecol. Obstet. 104: 539, 1957. Danielson, K. S., Resnicoff, S. A, and DeWeese, J. A.: An Evaluation of Myocardial Infarctectomy, J. THoRAc. CARDIOVASC. SURG. 59: 723, 1970. Feola, M., Normann, N. A., Haiderer, 0., and Kennedy, J. H.: Assisted Circulation: Experimental Intra-aortic Balloon Pumping, Artificial Heart Program Conference, Washington, D. C,; June 9-13, 1969, U. S. Government Printing Office. Glass, B. A, Carter, R. L., and Albert, H. M.: Experimental Myocardial Infarction: Effect on Cardiac Output and Response of the Heart After Surgical Excision, Am. Surg. 33: 912, 1967. Jude, J. R., Mobin-Uddin, K., MartinezFarinas, L. 0., Lombardo, C. R., and Smith, P. E.: Surgical Treatment of Experimental Myocardial Infarction, J. A M. A. 203: 451, 1968. Kennedy, J. H.: Assisted Circulation: An Extended Concept of Cardiopulmonary Resuscitation, J. THoRAc. CARDIOVASC. SURG. 57: 668, 1969. Limet, R., Feola, M., Hojevac, I., Ross, J. N., Jr., and Kennedy, J. H.: Effects of Intra-aortic Balloon Counterpulsation on the Distribution of Myocardial Blood Flow in Experimental Left Ventricular Failure, J. Cardiovasc. Surg. 13: 315, 1972.
The Journal of
250
Limet et al.
Thoracic and Cardiovascular Surgery
8 Lindenmayer, G. E., Sordahl, L. A, and Schwartz, A: Re-evaluation of Oxidative Phosphorylation in Cardiac Mitochondria From Normal Animals and Animals in Heart Failure, Circ. Res. 23: 439, 1968. 9 Shacklett, R. C., and Singletary, H.: Comparative Anatomy: Human, Dog, and Swine, ill
Bustad, L. K., and McClellan, R. 0.: Swine in Biomedical Research, Richland, Wash., 1965, Pacific Northwest Laboratory, pp. 390-397. 10 Williams, C. L., and Woods, L. P.: Experimental Resection of Myocardial Infarction, Ann. Thorac. Surg. 10: 339, 1970.