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Survival after acute ligation of the anterior descending coronary artery in the dog
SURVIVAL AFTER DESCENDING
SOL
GELMAN,
B.S.,
LEONARD BERNARD
ACUTE CORONARY
REICH, M.
WAGNER,
LIGATION ARTERY
PHOTIS M.D., M.D.,
LIGATION of the anterior descending coronary artery in dogs has been performed by many investigators [l, 2, 4, 51 as an experimental modality in the study of the effects of coronary occlusion and in examination of methods to reduce morbidity and mortality from such occlusion. In preparation for a series of such studies a group of dogs were subjected to coronary artery ligation to determine time and rate of survival following such a procedure. In addition heparin was administered to approximately half of the dogs in order to ascertain whether or not this drug had any therapeutic value in the face of myocardial ischemia.
G. FRANK AND
OF IN
THE ANTERIOR THE DOG
PANAGOPOULOS,
M.D.,
WEISER, GABOR
M.D., KALEY,
PH.D.
endotracheal tube was inserted which was connected to a positive-pressure respirator using ambient air. The respirator delivered 10 ml . per kilogram of air at a constant rate of 18 strokes per minute. A temperature probe was introduced into the midesophagus to ascertain maintenance of normothermia (36°C. to 38°C.) for the duration of the experiment. ECG leads were attached to the animals and were connected to a cardiotachometer with an alarm to monitor the onset of fibrillation. In 28 dogs arterial blood pressure in the brachial artery was measured, using a Statham pressure transducer before, and in surviving dogs up to thirty minutes after, coronary ligation. In 45 dogs 2.5 mg. per kilogram heparin sodium was administered immediately prior to ligation,
METHODS Eighty-eight mongrel dogs of either sex, ranging in weight from 12 to 20 kg., were anesthetized with 28 mg. per kilogram of sodium pentobarbital. Each dog was placed on the operating table on its right side. An From the Departments of Surgery, Medicine, Pathology, and Physiology, New York Medical College, New York, N.Y. This work was supported by a grant from the John A. Hartford Foundation, Inc. Submitted for pubbcation May 11, 1966.
PROCEDURE
FOR LIGATION
CORONARY
The heart was approached through a left lateral thoracotomy. A three- to four-inch incision was made in the skin along the line of the fourth interspace. The muscles were then split at right angles to the skin incision and the interspace was opened into the pleural cavity. The ribs were spread with a self-retaining retractor, the left lung was retracted 177
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OF
SURGICAL
RESEARCH
VOL.
7
4,
NO.
posteriorly, and the pericardium was incised anterior and parallel to the phrenic nerve. The left atria1 appendage was caught in a lung clamp, and another clamp was used to lift up the epicardial fat pad at the superior end of the atrioventricular groove, just behind and below the pulmonary artery. The anterior descending branch of the left coronary artery was carefully dissected, a No. 2 silk suture was placed around it, and the artery was ligated 1 to 5 mm. distal to its origin. The ribs were then approximated and the incision was closed in layers around a No. 20 catheter connected to underwater drainage. The above procedure lasted no longer than fifteen minutes and blood loss was minimal. Following ligation animals were observed for a period of 3 hours, after which they were decannulated, taken off the respirator, and returned to their cages.
RESULTS In Table 1 data are presented on the survival of dogs after acute coronary ligation. Of a total of 88 animals which had undergone surgery 29 (33% ) died within forty minutes. All except one died in ventricular fibrillation, and this exception showed no arterial blood pressure even though ECG tracings showed rhythmic activity. The average time of onset of fibrillation after coronary occlusion in the above dogs was fifteen minutes. Whereas, 24 dogs (27% ) were found dead in their cages the morning after surgery, 35 (40% ) survived for more than 24 hours. Of the latter 10 were found dead at various times between two to fourteen days postoperatively, Table
Group Heparin IV 2.5 mg./kg. Control Totals
1.
Descending
DISCUSSION Previous to our work, a number of investigators had reported on methods to produce myocardial infarction in dogs with a resultant mortality rate from 10% to 93% [ 1, 2, 4,5, 61. The discrepancy in these data is undoubtedly due to differences in surgical techniques and the extent to which supportive measures were employed. It may be significant that the 72% mortality rate observed in our studies was obtained on a much larger series of dogs than
Coronary
Number of Dogs 45
Died on Table 15 (33%)
43 88
14 (33%) 29 (33%)
13 (30%) 24 (27%)
rate: 7270.
1967
while the remaining 25 were sacrificed at intervals up to 3 months after the experimental procedure. There was no significant difference between the survival time of dogs receiving heparin before coronary ligation and that of controls. The overall mortality rate for the period of two weeks after surgery was 72%. Postligation, ECG changes invariably included alterations in the S-T segment, while inversion of T wave was observed in but 15% of all animals studied. Mean arterial blood pressure of 28 dogs treated with heparin declined 10% to 25% within the first five minutes after coronary occlusion. This was followed by a slow increase and maintenance of stable blood pressure close to or equal to preligation levels, up to thirty minutes, in surviving dogs. Microscopic examination of hearts in all instances revealed areas of myocardial opacity or, in long-term survivors, patchy fibrosis in left ventricular muscle. The size and location of infarcts, however, could not be correlated with mortality.
Died Overnight 11 (25%)
a Overall mortality 178
Effect of Anterior
APRIL
Artery
Ligation
on Survival Survived Less than 2 weeks 19 (42%) 16 (37%) 35 (40%)
of Dogs Over 24 Hours Over 2 weeks 10 (22%) 15 (35%) 25 (28%)”
GELMAN
hitherto reported and that no special attempt was made to increase survival. Acute ligation of the left anterior descending coronary artery to produce myocardial infarction was employed in the course of our study, since this type of segmental occlusion corresponds more closely to the clinical situation than the diffuse plugging of coronary arteries observed after the injection of plastic microspheres. Some workers [2, 61 have attempted to standardize the degree of ischemia by ligating the left descending coronary artery at a point distal to the septal branch to assure patency of the latter vessel. However, since there is a considerable variation in size and branching-off point of the septal artery, and since the size of the infarct could not, under any circumstance, be controlled, no attempt was made in this study to ligate distal to the septal artery. In this manner the infarction was thought to be closer to the clinical condition in which occlusion occurs at random. That immediate survival was not adversely affected by ligating proximal to the origin of the septal artery was indicated by the fact that none of three animals which were fortuitously so ligated died within 24 hours. Since decreased blood flow distal to an occlusion renders the blood hypercoagulable and promotes intravascular clotting [3], it was thought that the administration of heparin might favorably influence the effects of coronary ligation. However, no significant improvement was observed with the use of heparin.
ET
AL.:
SURVIVAL
IN
DOG
AFTER
CORONARY
LIGATION
SUMMARY A simple and rapid procedure for producing coronary occlusion in the dog is described. Of 88 dogs with acute anterior descending coronary artery ligation 35 (40% ) survived over 24 hours, while mortality rate for the two-week period following ligation was 72$%; 29 animals (33% ) died, 28 in ventricular fibrillation, within forty minutes after the surgical procedure. Administration of heparin prior to ligation did not significantly influence immediate or long-term survival. REFERENCES 1. Chardack, W. M., Bolgan, F. J., Olson, K. C., Gage, A. A., and Farnsworth, W. E. Mortality following ligation of anterior descending branch of left coronary artery in dogs: Experimental study. Ann. Surg. 141:443, 1955. R. P., Davila, J. C., Kyle, R. H., Beard, 2. Glover, J. C., Jr., Trout, R. G., and Kitchell, J. R. Ligation of the internal mammary arteries as a means of increasing blood supply to the myocardium. J. Thorac. Surg. 34:561, 1957. 3. Hardaway, Robert M. Microcoagulation in shock. Amer. J. Surg. 110:298, 1965. 4. Schauer, G., Gross, L., and Blum, L. Hemodynamic studies in experimental coronary occlusion: Stellate ganglionectomy experiments. Amer. Heart J. 14:669, 1937. 5. Siderys, H., Grice, P. F., Shumaker, H. B., Jr., and Riberi, A. Occlusion of the great cardiac vein and coronary artery ligation. Surg. Gynec. Obstet. 102: 18, 1956. 6. Vansant, J. H. Technique of experimental ligation of the anterior descending coronary artery. Surgery 49:387, 1961.
179
SOL
GELMAN,
B.S.,
LEONARD BERNARD
ACUTE CORONARY
REICH, M.
WAGNER,
LIGATION ARTERY
PHOTIS M.D., M.D.,
LIGATION of the anterior descending coronary artery in dogs has been performed by many investigators [l, 2, 4, 51 as an experimental modality in the study of the effects of coronary occlusion and in examination of methods to reduce morbidity and mortality from such occlusion. In preparation for a series of such studies a group of dogs were subjected to coronary artery ligation to determine time and rate of survival following such a procedure. In addition heparin was administered to approximately half of the dogs in order to ascertain whether or not this drug had any therapeutic value in the face of myocardial ischemia.
G. FRANK AND
OF IN
THE ANTERIOR THE DOG
PANAGOPOULOS,
M.D.,
WEISER, GABOR
M.D., KALEY,
PH.D.
endotracheal tube was inserted which was connected to a positive-pressure respirator using ambient air. The respirator delivered 10 ml . per kilogram of air at a constant rate of 18 strokes per minute. A temperature probe was introduced into the midesophagus to ascertain maintenance of normothermia (36°C. to 38°C.) for the duration of the experiment. ECG leads were attached to the animals and were connected to a cardiotachometer with an alarm to monitor the onset of fibrillation. In 28 dogs arterial blood pressure in the brachial artery was measured, using a Statham pressure transducer before, and in surviving dogs up to thirty minutes after, coronary ligation. In 45 dogs 2.5 mg. per kilogram heparin sodium was administered immediately prior to ligation,
METHODS Eighty-eight mongrel dogs of either sex, ranging in weight from 12 to 20 kg., were anesthetized with 28 mg. per kilogram of sodium pentobarbital. Each dog was placed on the operating table on its right side. An From the Departments of Surgery, Medicine, Pathology, and Physiology, New York Medical College, New York, N.Y. This work was supported by a grant from the John A. Hartford Foundation, Inc. Submitted for pubbcation May 11, 1966.
PROCEDURE
FOR LIGATION
CORONARY
The heart was approached through a left lateral thoracotomy. A three- to four-inch incision was made in the skin along the line of the fourth interspace. The muscles were then split at right angles to the skin incision and the interspace was opened into the pleural cavity. The ribs were spread with a self-retaining retractor, the left lung was retracted 177
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
7
4,
NO.
posteriorly, and the pericardium was incised anterior and parallel to the phrenic nerve. The left atria1 appendage was caught in a lung clamp, and another clamp was used to lift up the epicardial fat pad at the superior end of the atrioventricular groove, just behind and below the pulmonary artery. The anterior descending branch of the left coronary artery was carefully dissected, a No. 2 silk suture was placed around it, and the artery was ligated 1 to 5 mm. distal to its origin. The ribs were then approximated and the incision was closed in layers around a No. 20 catheter connected to underwater drainage. The above procedure lasted no longer than fifteen minutes and blood loss was minimal. Following ligation animals were observed for a period of 3 hours, after which they were decannulated, taken off the respirator, and returned to their cages.
RESULTS In Table 1 data are presented on the survival of dogs after acute coronary ligation. Of a total of 88 animals which had undergone surgery 29 (33% ) died within forty minutes. All except one died in ventricular fibrillation, and this exception showed no arterial blood pressure even though ECG tracings showed rhythmic activity. The average time of onset of fibrillation after coronary occlusion in the above dogs was fifteen minutes. Whereas, 24 dogs (27% ) were found dead in their cages the morning after surgery, 35 (40% ) survived for more than 24 hours. Of the latter 10 were found dead at various times between two to fourteen days postoperatively, Table
Group Heparin IV 2.5 mg./kg. Control Totals
1.
Descending
DISCUSSION Previous to our work, a number of investigators had reported on methods to produce myocardial infarction in dogs with a resultant mortality rate from 10% to 93% [ 1, 2, 4,5, 61. The discrepancy in these data is undoubtedly due to differences in surgical techniques and the extent to which supportive measures were employed. It may be significant that the 72% mortality rate observed in our studies was obtained on a much larger series of dogs than
Coronary
Number of Dogs 45
Died on Table 15 (33%)
43 88
14 (33%) 29 (33%)
13 (30%) 24 (27%)
rate: 7270.
1967
while the remaining 25 were sacrificed at intervals up to 3 months after the experimental procedure. There was no significant difference between the survival time of dogs receiving heparin before coronary ligation and that of controls. The overall mortality rate for the period of two weeks after surgery was 72%. Postligation, ECG changes invariably included alterations in the S-T segment, while inversion of T wave was observed in but 15% of all animals studied. Mean arterial blood pressure of 28 dogs treated with heparin declined 10% to 25% within the first five minutes after coronary occlusion. This was followed by a slow increase and maintenance of stable blood pressure close to or equal to preligation levels, up to thirty minutes, in surviving dogs. Microscopic examination of hearts in all instances revealed areas of myocardial opacity or, in long-term survivors, patchy fibrosis in left ventricular muscle. The size and location of infarcts, however, could not be correlated with mortality.
Died Overnight 11 (25%)
a Overall mortality 178
Effect of Anterior
APRIL
Artery
Ligation
on Survival Survived Less than 2 weeks 19 (42%) 16 (37%) 35 (40%)
of Dogs Over 24 Hours Over 2 weeks 10 (22%) 15 (35%) 25 (28%)”
GELMAN
hitherto reported and that no special attempt was made to increase survival. Acute ligation of the left anterior descending coronary artery to produce myocardial infarction was employed in the course of our study, since this type of segmental occlusion corresponds more closely to the clinical situation than the diffuse plugging of coronary arteries observed after the injection of plastic microspheres. Some workers [2, 61 have attempted to standardize the degree of ischemia by ligating the left descending coronary artery at a point distal to the septal branch to assure patency of the latter vessel. However, since there is a considerable variation in size and branching-off point of the septal artery, and since the size of the infarct could not, under any circumstance, be controlled, no attempt was made in this study to ligate distal to the septal artery. In this manner the infarction was thought to be closer to the clinical condition in which occlusion occurs at random. That immediate survival was not adversely affected by ligating proximal to the origin of the septal artery was indicated by the fact that none of three animals which were fortuitously so ligated died within 24 hours. Since decreased blood flow distal to an occlusion renders the blood hypercoagulable and promotes intravascular clotting [3], it was thought that the administration of heparin might favorably influence the effects of coronary ligation. However, no significant improvement was observed with the use of heparin.
ET
AL.:
SURVIVAL
IN
DOG
AFTER
CORONARY
LIGATION
SUMMARY A simple and rapid procedure for producing coronary occlusion in the dog is described. Of 88 dogs with acute anterior descending coronary artery ligation 35 (40% ) survived over 24 hours, while mortality rate for the two-week period following ligation was 72$%; 29 animals (33% ) died, 28 in ventricular fibrillation, within forty minutes after the surgical procedure. Administration of heparin prior to ligation did not significantly influence immediate or long-term survival. REFERENCES 1. Chardack, W. M., Bolgan, F. J., Olson, K. C., Gage, A. A., and Farnsworth, W. E. Mortality following ligation of anterior descending branch of left coronary artery in dogs: Experimental study. Ann. Surg. 141:443, 1955. R. P., Davila, J. C., Kyle, R. H., Beard, 2. Glover, J. C., Jr., Trout, R. G., and Kitchell, J. R. Ligation of the internal mammary arteries as a means of increasing blood supply to the myocardium. J. Thorac. Surg. 34:561, 1957. 3. Hardaway, Robert M. Microcoagulation in shock. Amer. J. Surg. 110:298, 1965. 4. Schauer, G., Gross, L., and Blum, L. Hemodynamic studies in experimental coronary occlusion: Stellate ganglionectomy experiments. Amer. Heart J. 14:669, 1937. 5. Siderys, H., Grice, P. F., Shumaker, H. B., Jr., and Riberi, A. Occlusion of the great cardiac vein and coronary artery ligation. Surg. Gynec. Obstet. 102: 18, 1956. 6. Vansant, J. H. Technique of experimental ligation of the anterior descending coronary artery. Surgery 49:387, 1961.
179