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Left Circumflex Coronary Artery Division in Dogs Given Supportive Treatment
Left Circumflex Coronary Artery Division in Dogs Given Supportive Treatment David B. Skinner, M.D., William G. Davis, Jr., T/Sgt, USAF, and Thomas F. Camp, Jr., M.D.
A
n experimental model for acute myocardial infarction is needed for the evaluation of circulatory assistance and other forms of treatment. A useful preparation should be reproducible by different investigators and should cause a consistent mortality high enough to permit demonstration of the beneficial effects of treatment, but not so high that deleterious effects of treatment will be obscured. In dogs, division of the left anterior descending coronary artery has caused variable acute death rates ranging from 10 to 50% in 24 hours [l, 4, 5, 71. Left circumflex coronary artery (LCCA) division has been reported to cause 84 to 93% acute mortality [2-4, 61. Pifarrk and Hufnagel [5] observed that the mortality of LCCA division could be reduced to 65% in 48 hours by defibrillating hearts which fibrillated and providing supportive treatment during the first hours after coronary division. If reproducible, such a canine myocardial infarction preparation causing death in approximately two-thirds of the animals would be a useful experimental model. T o investigate this preparation further, two groups of dogs were studied at an interval of 9 months, so that seasonal and other selection variables could be eliminated.’ MATERIALS A N D METHODS
Mongrel dogs weighing between 10 and 28 kg. were inoculated against distemper and conditioned for at least 3 weeks to determine that they had stable hematocrit and weight and no evidence of heartworm From the Surgery Branch, USAF School of Aerospace Medicine, Brooks Air Force Base, Tex., and the Department of Surgery, The Johns Hopkins University School of Medicine, The Johns Hopkins Hospital, Baltimore, Md. Address reprint requests to Dr. Skinner, Blalock 626, The Johns Hopkins Hospital, Baltimore, Md. 21205. Accepted for publication Kov. 7, 1968. *The animals involved in this study were maintained in accordance with the “Guide for Laboratory Animals’ Facilities and Care,” published by the National Academy of Sciences, National Research Council.
242
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Coronary Artery Division with Supportive Treatment
infestation or other illness. Twelve dogs (Group I) were studied during November, 1966, and 24 (Group 11) were studied during August, 1967. Animals were anesthetized with pentobarbital (30 mg./kg.) and atropine (0.3-0.5 mg.). Femoral artery and vein catheters were inserted to monitor arterial and central venous pressures. Mechanical endotracheal respiratory assistance was provided. Through a left thoracotomy incision, the pericardium was opened and the left circumflex coronary artery was doubly ligated and divided at its origin from the main left coronary artery. T h e first atrial branch was divided in some animals when necessary for adequate mobilization of the LCCA. Each dog was given 100% oxygen through the respirator for 15 minutes after the artery was interrupted. Thereafter, a mixture of 60% air and 40% oxygen was given while the chest wound was left open for 1 hour. If ventricular fibrillation occurred during this time, the heart was defibrillated. If the arterial blood pressure fell below 90 mm. Hg systolic, 30 mg. of mephentermine was given in a slow intravenous drip during the remainder of the surgical procedure. Ringer’s lactate solution (100-200 cc.) was given intravenously during the operation. After 1 hour, the thoracotomy wound was closed with drainage. An electrocardiogram was obtained, and oxygen was blown into the endotracheal tube postoperatively at the rate of 3 to 5 liters per minute until the animal was awake and the tube was removed. After air and blood were evacuated from the hemithorax, the chest tube was removed. T h e animals were observed postoperatively to determine length of survival. Electrocardiograms were performed at 24 and 48 hours after surgery in animals which survived. Autopsies were performed on animals which died or were sacrificed to verify myocardial infarction. Those which lived 2 months or more were sacrificed. Some Group I1 animals which survived more than 24 hours were employed in a subsequent experiment. RESULTS
Survival rates of dogs for 24 hours following left circumflex coronary artery ligation were identical in Group I (4 out of 12) and Group I1 (8 out of 24). Two dogs in Group I1 died during another experiment 48 hours later. Of the remaining 10 dogs which survived more than 24 hours, 4 died from 2 weeks to 2 months later, and 6 lived until sacrificed 2 months or more after myocardial infarction. T h e hearts of 10 animals developed ventricular fibrillation within 1 hour of LCCA division and were successfully defibrillated. Three of the dogs which had ventricular fibrillation survived more than 24 hours. In 13 dogs, the systolic blood pressure fell below 100 mm. Hg, and 8 were given mephentermine. Of these severely hypotensive dogs, 4 surVOL.
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vived more than 24 hours. There was no significant difference in the incidence of fibrillation or hypotension between animals in Group I and Group 11. Electrocardiograms taken before and approximately 1 hour after coronary interruption were available for review in 32 of the 36 dogs. (2 waves developed after artery ligation in 19 tracings; T wave inversions or depressions were observed in 30; and ST-T segment elevations or depressions occurred in 30. Premature ventricular contractions were noted in 9, and ventricular tachycardia was present in 4. Each animal demonstrated electrocardiographic evidence of ischemia. ECG tracings were available for review in 10 of the 12 dogs that survived more than 24 hours. At that time, Q waves were present in 9, and T wave inversions were noted in all 10. Nine animals had runs of ventricular tachycardia recorded during the period 24 to 48 hours after coronary ligation, and all had premature ventricular contractions. Autopsy examination after death or sacrifice verified the presence of myocardial infarction in each dog. CONCLUSIONS A N D S U M M A R Y
The acute (24-hour) mortality following left circumflex coronary artery (LCCA) division was 67% in each of two groups of conditioned dogs studied 9 months apart. During surgery, animals were given supportive treatment as needed, including cardiac defibrillation, mephentermine for hypotension, oxygen, and intravenous fluids. T h e incidence of ventricular fibrillation, hypotension, and electrocardiographic changes was the same in both groups. This 67% mortality is lower than that which has generally been reported following LCCA ligation, and is in the range which should be most useful for evaluating circulatory assistance and other experimental therapy for acute myocardial infarction. T h e mortality in both groups of dogs was nearly identical to the 48-hour death rate following LCCA division in dogs given similar supportive treatment by Pifarrb and Hufnagel [5], providing further evidence that this preparation is reproducible and has validity as an experimental model. REFERENCES
1. Chardack, W. M., Bolgan, F. J., Olson, K. C., Gage, A. A., and Farnsworth, W. E. The mortality following ligation of the anterior descending branch of the left coronary artery in dogs. A n n . Surg. 141:443, 1955. 2. Fineberg, C., Foris, N., and Camishion, R. C. Revascularization of the dog myocardium. 11. Acute ligation of the circumflex coronary artery with and without hypothermia. Arch. Surg. (Chicago) 85:717, 1962. 3. Goldfarb, D., Conti, C. R., Brown, B. G., and Gott, V. L. Treatment of severe cardiogenic shock by diastolic augmentation after ligation and division of the left circumflex coronary artery in dogs. J. Thorac. Cardiovasc. Surg. 51 :783, 1966. 244
THE ANNALS OF THORACIC SURGERY
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Coronary Artery Division with Supportive Treatment
4. Lumb, G., Shacklett, R. S., and Cook, J. B., Jr. T h e results of varying degrees of narrowing the left circumflex coronary artery in dogs. Amer. J . Path. 36: 113, 1960. 5. Pifarre, R., and Hufnagel, C. A. An experimental study comparing the acute occlusion of the anterior descending and the left circumflex coronary arteries. J. Thorac. Cardiovasc. Surg. 51:761, 1966. 6. Skelton, R. B., Gergely, N., Manning, G. W., and Coles, J. C. Mortality studies in experimental coronary occlusion. J . Thorac. Cardiovasc. Surg. 44: 90, 1962. 7. Timmis, H. H., and Lehan, P. H. Local coronary A-V blood gas, carbohydrate, and enzyme gradients following acute coronary occlusion. J. Thorac. Cardiovasc. Surg. 54:856, 1967.
NOTICE FROM THE SOCIETY OF THORACIC SURGEONS T h e Fifth Annual Meeting of The Society of Thoracic Surgeons was held in San Diego, Calif., January 27-29, 1969. The third postgraduate lecture series was held on January 26 with 183 members and guests attending. At the annual business session the following officers were elected: Donald B. EfRer, President; Will C. Sealy, Vice-President; Ralph D. Alley, Secretary; and Robert G . Ellison, Treasurer. Herbert Sloan was appointed Editor of The Annals of Thoracic Surgery. Elected to honorary membership was Professor Charles DuBost of Paris, France. John D. Steele, retiring Editor of T h e Annals, was presented with the Society’s first Distinguished Service Award. One hundred and four new members were elected, increasing the membership to 807. A new committee, the Thoracic and Cardiovascular Surgery Training and Standards Committee, was established. During the coming year, the Council will select a professional management service to conduct the routine affairs of the Society. Dues are to remain unchanged at $25.00; however, the members will be charged for T h e Annals of Thoracic Surgery at the reduced subscription price of $19.00. This will increase the annual dues payment from $25.00 to $44.00. More than 700 physicians attended the various sessions. Total attendance, including exhibitors and wives, was more than 900. T h e next meeting will be held in Atlanta, Ga., January 12-14, 1970. JOHN
VOL.
7,
NO.
N. BRIGGS, Secretary
3,
MARCH,
1969
245
A
n experimental model for acute myocardial infarction is needed for the evaluation of circulatory assistance and other forms of treatment. A useful preparation should be reproducible by different investigators and should cause a consistent mortality high enough to permit demonstration of the beneficial effects of treatment, but not so high that deleterious effects of treatment will be obscured. In dogs, division of the left anterior descending coronary artery has caused variable acute death rates ranging from 10 to 50% in 24 hours [l, 4, 5, 71. Left circumflex coronary artery (LCCA) division has been reported to cause 84 to 93% acute mortality [2-4, 61. Pifarrk and Hufnagel [5] observed that the mortality of LCCA division could be reduced to 65% in 48 hours by defibrillating hearts which fibrillated and providing supportive treatment during the first hours after coronary division. If reproducible, such a canine myocardial infarction preparation causing death in approximately two-thirds of the animals would be a useful experimental model. T o investigate this preparation further, two groups of dogs were studied at an interval of 9 months, so that seasonal and other selection variables could be eliminated.’ MATERIALS A N D METHODS
Mongrel dogs weighing between 10 and 28 kg. were inoculated against distemper and conditioned for at least 3 weeks to determine that they had stable hematocrit and weight and no evidence of heartworm From the Surgery Branch, USAF School of Aerospace Medicine, Brooks Air Force Base, Tex., and the Department of Surgery, The Johns Hopkins University School of Medicine, The Johns Hopkins Hospital, Baltimore, Md. Address reprint requests to Dr. Skinner, Blalock 626, The Johns Hopkins Hospital, Baltimore, Md. 21205. Accepted for publication Kov. 7, 1968. *The animals involved in this study were maintained in accordance with the “Guide for Laboratory Animals’ Facilities and Care,” published by the National Academy of Sciences, National Research Council.
242
THE ANNALS OF THORACIC SURGERY
NOTE:
Coronary Artery Division with Supportive Treatment
infestation or other illness. Twelve dogs (Group I) were studied during November, 1966, and 24 (Group 11) were studied during August, 1967. Animals were anesthetized with pentobarbital (30 mg./kg.) and atropine (0.3-0.5 mg.). Femoral artery and vein catheters were inserted to monitor arterial and central venous pressures. Mechanical endotracheal respiratory assistance was provided. Through a left thoracotomy incision, the pericardium was opened and the left circumflex coronary artery was doubly ligated and divided at its origin from the main left coronary artery. T h e first atrial branch was divided in some animals when necessary for adequate mobilization of the LCCA. Each dog was given 100% oxygen through the respirator for 15 minutes after the artery was interrupted. Thereafter, a mixture of 60% air and 40% oxygen was given while the chest wound was left open for 1 hour. If ventricular fibrillation occurred during this time, the heart was defibrillated. If the arterial blood pressure fell below 90 mm. Hg systolic, 30 mg. of mephentermine was given in a slow intravenous drip during the remainder of the surgical procedure. Ringer’s lactate solution (100-200 cc.) was given intravenously during the operation. After 1 hour, the thoracotomy wound was closed with drainage. An electrocardiogram was obtained, and oxygen was blown into the endotracheal tube postoperatively at the rate of 3 to 5 liters per minute until the animal was awake and the tube was removed. After air and blood were evacuated from the hemithorax, the chest tube was removed. T h e animals were observed postoperatively to determine length of survival. Electrocardiograms were performed at 24 and 48 hours after surgery in animals which survived. Autopsies were performed on animals which died or were sacrificed to verify myocardial infarction. Those which lived 2 months or more were sacrificed. Some Group I1 animals which survived more than 24 hours were employed in a subsequent experiment. RESULTS
Survival rates of dogs for 24 hours following left circumflex coronary artery ligation were identical in Group I (4 out of 12) and Group I1 (8 out of 24). Two dogs in Group I1 died during another experiment 48 hours later. Of the remaining 10 dogs which survived more than 24 hours, 4 died from 2 weeks to 2 months later, and 6 lived until sacrificed 2 months or more after myocardial infarction. T h e hearts of 10 animals developed ventricular fibrillation within 1 hour of LCCA division and were successfully defibrillated. Three of the dogs which had ventricular fibrillation survived more than 24 hours. In 13 dogs, the systolic blood pressure fell below 100 mm. Hg, and 8 were given mephentermine. Of these severely hypotensive dogs, 4 surVOL.
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1969
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vived more than 24 hours. There was no significant difference in the incidence of fibrillation or hypotension between animals in Group I and Group 11. Electrocardiograms taken before and approximately 1 hour after coronary interruption were available for review in 32 of the 36 dogs. (2 waves developed after artery ligation in 19 tracings; T wave inversions or depressions were observed in 30; and ST-T segment elevations or depressions occurred in 30. Premature ventricular contractions were noted in 9, and ventricular tachycardia was present in 4. Each animal demonstrated electrocardiographic evidence of ischemia. ECG tracings were available for review in 10 of the 12 dogs that survived more than 24 hours. At that time, Q waves were present in 9, and T wave inversions were noted in all 10. Nine animals had runs of ventricular tachycardia recorded during the period 24 to 48 hours after coronary ligation, and all had premature ventricular contractions. Autopsy examination after death or sacrifice verified the presence of myocardial infarction in each dog. CONCLUSIONS A N D S U M M A R Y
The acute (24-hour) mortality following left circumflex coronary artery (LCCA) division was 67% in each of two groups of conditioned dogs studied 9 months apart. During surgery, animals were given supportive treatment as needed, including cardiac defibrillation, mephentermine for hypotension, oxygen, and intravenous fluids. T h e incidence of ventricular fibrillation, hypotension, and electrocardiographic changes was the same in both groups. This 67% mortality is lower than that which has generally been reported following LCCA ligation, and is in the range which should be most useful for evaluating circulatory assistance and other experimental therapy for acute myocardial infarction. T h e mortality in both groups of dogs was nearly identical to the 48-hour death rate following LCCA division in dogs given similar supportive treatment by Pifarrb and Hufnagel [5], providing further evidence that this preparation is reproducible and has validity as an experimental model. REFERENCES
1. Chardack, W. M., Bolgan, F. J., Olson, K. C., Gage, A. A., and Farnsworth, W. E. The mortality following ligation of the anterior descending branch of the left coronary artery in dogs. A n n . Surg. 141:443, 1955. 2. Fineberg, C., Foris, N., and Camishion, R. C. Revascularization of the dog myocardium. 11. Acute ligation of the circumflex coronary artery with and without hypothermia. Arch. Surg. (Chicago) 85:717, 1962. 3. Goldfarb, D., Conti, C. R., Brown, B. G., and Gott, V. L. Treatment of severe cardiogenic shock by diastolic augmentation after ligation and division of the left circumflex coronary artery in dogs. J. Thorac. Cardiovasc. Surg. 51 :783, 1966. 244
THE ANNALS OF THORACIC SURGERY
NOTE:
Coronary Artery Division with Supportive Treatment
4. Lumb, G., Shacklett, R. S., and Cook, J. B., Jr. T h e results of varying degrees of narrowing the left circumflex coronary artery in dogs. Amer. J . Path. 36: 113, 1960. 5. Pifarre, R., and Hufnagel, C. A. An experimental study comparing the acute occlusion of the anterior descending and the left circumflex coronary arteries. J. Thorac. Cardiovasc. Surg. 51:761, 1966. 6. Skelton, R. B., Gergely, N., Manning, G. W., and Coles, J. C. Mortality studies in experimental coronary occlusion. J . Thorac. Cardiovasc. Surg. 44: 90, 1962. 7. Timmis, H. H., and Lehan, P. H. Local coronary A-V blood gas, carbohydrate, and enzyme gradients following acute coronary occlusion. J. Thorac. Cardiovasc. Surg. 54:856, 1967.
NOTICE FROM THE SOCIETY OF THORACIC SURGEONS T h e Fifth Annual Meeting of The Society of Thoracic Surgeons was held in San Diego, Calif., January 27-29, 1969. The third postgraduate lecture series was held on January 26 with 183 members and guests attending. At the annual business session the following officers were elected: Donald B. EfRer, President; Will C. Sealy, Vice-President; Ralph D. Alley, Secretary; and Robert G . Ellison, Treasurer. Herbert Sloan was appointed Editor of The Annals of Thoracic Surgery. Elected to honorary membership was Professor Charles DuBost of Paris, France. John D. Steele, retiring Editor of T h e Annals, was presented with the Society’s first Distinguished Service Award. One hundred and four new members were elected, increasing the membership to 807. A new committee, the Thoracic and Cardiovascular Surgery Training and Standards Committee, was established. During the coming year, the Council will select a professional management service to conduct the routine affairs of the Society. Dues are to remain unchanged at $25.00; however, the members will be charged for T h e Annals of Thoracic Surgery at the reduced subscription price of $19.00. This will increase the annual dues payment from $25.00 to $44.00. More than 700 physicians attended the various sessions. Total attendance, including exhibitors and wives, was more than 900. T h e next meeting will be held in Atlanta, Ga., January 12-14, 1970. JOHN
VOL.
7,
NO.
N. BRIGGS, Secretary
3,
MARCH,
1969
245