TUESDAY MORNING, APRIL 1, 1969

8:30 A.M. Scientific Session: THORACIC SURGERY FORUM

Grand Ballroom

21. Myocardial Viability and Hypothermia

William W. Angell,* Layton Rikkers,* Eugene Dong,*

and Norman E. Shumway, Palo Alto, Calif.

Myocardial hypothermia has been used for anoxic preservation in cardiac transplantation and in several hundred other open heart procedures at the Stanford Medical Center. It permits 2 hours of total anoxia without myocardial damage. A quantitative relationship (related to organ viability) was defined between temperature and the interval of anoxia. The interval of anoxia compatible with viability (defined as survival of the transplanted heart without infarction) was determined in 40 canine hearts at 37, 30, 22, and 15°C. Function was studied by left ventricular pressure curves, heart rate, contractility, oxygen consumption, CO₂ production, enzyme liberation, edema formation, and light and electron microscopic morphology. The allowable interval of anoxia proved to be a linear function of the log of

temperature This is also permitted a prediction of viability in any

given heart undergoing anoxia at variable temperatures. ( Viability was accurately predicted in 10

human and 10 canine hearts from the formula:

Proven preoperative donor heart viability is essential to successful heart transplantation. Any heart can be definitively evaluated as a donor organ if the temperature and anoxic interval are known.

22. The Microcirculation of Transplanted Hearts

William E. Neville, Roque Pifarre,* John W. Balis,* William Cox,*

Francis Dwan,* and Edward S. Rappaport,* Hines, Ill.

The gross, histologic and ultrastructural changes of hearts, orthotopically transplanted from goat-to-dog, dog-to-dog and dog-to-goat were studied. The coronary blood flow, heart contractility, color and ultrastructure appeared normal in dog hearts transplanted to either dogs or goats. On the other hand, the goat hearts transplanted to dogs failed to contract properly, and rapidly developed bluish red discoloration with sharp diminution of coronary blood flow within one hour after transplantation. Histologic and ultrastructural studies in these hearts showed- 1) Obstruction of capillaries by agglutinated erythrocytes, and marked endothelial damage without platelet aggregates and fibrin deposits 2) Interstitial edema and extravasated erythrocytes, 3) Typical changes of acute ischemic damage of the myocardium, namely, mitochondrial swelling, loss of glycogen, clumping and margination of nuclear chromatin. Since dog erythrocytes are appreciably larger than goat erythrocytes, it is suggested that differences in size and other properties as well accounts, in part, for the rapid agglutination of these cells in the microcirculation following heterologous heart transplantation. The possibility exists that similar events in the capillary circulation may be responsible for the "acute immunologic rejection" of transplanted organs in man.

23. The Immediate Prophylactic Role of Myocardial Revascularization Following Internal Mammary Artery Implantation into Normal Myocardium

Susumu Tanaka,* William R. Rassman,* Richard Fleming,*

Robert J. Ellis,* and G. Walton Lillehei, New York, N. Y.

The functional effects of internal mammary artery implantation (I.M A.) into normal myocardium and ischemic myocardium of dogs was compared. Implantation performed in normals demonstrated 90% patency at 6 months and there was no difference in patency rate into ischemic muscle. However, I.M.A. implants into ischemic myocardium showed angiographically much more widespread connections at 3 months. However, a striking finding of these studies was demonstration that I.M.A. implants into healthy myocardium did after 6 months show, following creation of acute ischemia, an immediate (within 60 sec.) widespread opening of collateral vessels equal in size and number to those visible in animals with chronic ischemia. The following measurements were also taken: ventricular size (utilizing epicardial strain gauges), ventricular and systemic pressures, coronary artery flow and implanted I.M.A. flow. Acute ischemia was then created by coronary artery hgations. Contribution of blood from internal mammary implants significantly offset immediate effects of acute ischemia confirming the angiographic observations. Conclusion: I.M.A. implantations are capable of establishing widespread latent arterial communications without need of mvocardial ischemia. The number, size and area of distribution of these communications become immediately functional in the presence of acute ischemia.

24. Experimental Evaluation of Myocardial Tunnelization as a Method of Myocardial Revascularization

Isam N. Anabtawi,* Hubert F. Riegler,* and Robert G. Ellison,

Augusta, Ga.

The protective effect of surgically created myocardial tunnels between the left ventricular chamber and the myocardium was studied in dogs whose myocardium was rendered ischemic by ameroid constriction of left coronary artery. Four of five control dogs whose myocardium was made ischemic without benefit of tunnels died within two months of operation from extensive myocardial infarction whereas ten of 13 animals protected with tunnels were alive and well five months after operation. Tunnel communication with the left ventricular chamber could be demonstrated in the early postoperative period whereas at autopsy five months later no communications were present indicating healing closure of the endocardial entry site. The tunnels, however, remained patent as large myocardial blood channels which freely communicated with both right and left coronary artery branches. Endothelial cells could be seen lining some channels. The results indicate the feasibility of vascularizing multiple areas in the myocardium by creation of channels which promote intercoronary passage of blood between branches of both coronary arteries. This seems preferable to the limitation of two artificially implanted internal mammary arteries with their inherent risk of thrombosis.

25. The Hemodynamics and Coronary Arteriographic Patterns During Acute Myocardial Infarction

F. R. Bego,* M. A. Kooros,* G. J Magovern, E. M. Kent,

L. B. Brent,* and W. B. Gushing,* Pittsburgh, Pa.

The effects of coronary occlusion on left ventricular function have been studied extensively in the experimental laboratory but the left ventricular response during acute coronary occlusion has not been studied in man. This paper presents our findings in 51 patients who have been studied 10 hours to 4 weeks following the onset of myocardial infarction and describes 1) the coronary angiographic pattern in acute myocardial infarction and 2) the intra-ventricular pressures and angiographic assessment of left ventricular function. Five patients were studied within twenty-four hours of the onset of their myocardial damage with right and left heart catheterization, selective angiocoronary arteriographv and left ventriculography. There were no complications. The remaining forty-six patients had selective coronary artenography and left ventriculography to study the arteriographic pattern in evolving myocardial infarction. The results demonstrate that retrograde left heart catheterization with selective coronary arteriography can be successfully applied to any phase of coronary arterial disease and points put by illustrating the arteriographic pattern in all phases of myocardial infarction the potential surgical implications of acquiring this physiological and angiographic data within hours of the onset of an occlusion of the coronary artery.

26. The Effect of Excessively High Perfusion Pressures on the Histology, Histochemistry, Birefringence and Function of the Myocardium

A. Hedley Brown,* Mark V. Braimbrtdoe,* Nelson R. Niles,*

Frank Gerbode, and Mary S. Aguilar,* San Francisco, Calif.

During operations on the aortic valve, the coronary arteries may be perfused at higher pressures than normal. The purpose of this investigation is to demonstrate that high perfusion pressure does in fact damage the heart. The model was an isolated heart preparation. One group of hearts was perfused at normal aortic pressures, and another at elevated aortic pressures. Myocardial damage was assessed by the following methods: (a) Histochemistry (Succinic dehydrogenase, free phospholipids) (b) Birefringence of myocardial fibers (c) Hematoxylin and Eosin stain (d) Ventricular wall tension (e) Velocity of contraction (f) Ventricular compliance (g) Ventricular wall thickness. Perfusion was carried out for three hours. There were significant changes in both ventricular wall tension and velocity of contraction in both groups. Hearts perfused at high pressures had a significant marked loss of ventricular compliance and increase in ventricular wall thickness. Histochemistry and birefringence were not significantly altered in either group. Microscopic examination demonstrated marked difference in the two groups. Hearts perfused at normal pressure were normal. Those perfused at high pressure were congested, edematous and exhibited red cell infiltration between myocardial fibers. These results indicate that high coronary artery perfusion pressure is detrimental to the myocardium and should be accurately controlled during aortic valve surgery.

27. Postoperative Isoproterenol Ventricular Arrhythmias: Conversion with Insulin

S. A. Hoffman,* H. W. Wallace,* H. Zinsser,* Philadelphia, Pa.,

A. E. Baue, St. Louis, Mo, and W. S. Blakemore, Philadelphia, Pa.

Postoperative open heart patients who have previously received digitalis and diuretics frequently develop ventricular arrhythmias when isoproterenol is administered. To study this, hypokalemia was produced in dogs. Isoproterenol did not induce ventricular arrhythmias in nondigitalized hypokalemic dogs, while in digitalized hypokalemic dogs, the administration of isoproterenol caused ventricular arrhythmias. The administration of KGL was found to abolish these arrhythmias. When a combination of slow and rapid acting digitalis was used, the administration of KCL resulted in heart block. Isoproterenol, 2 ug./min., produced serious ventricular arrhythmias in six hyperkalemic patients in acute renal failure on long term digitalis and diuretics. The addition of regular insulin (o.05 units/ug. of isoproterenol) effectively converted the ventricular arrhythmias to a normal rhythm. This insulin supplement in addition reduced the myocardial requirements for isoproterenol by 90 per cent of its dose to 0.2 ug./min. Beta adrenergic reception stimulation by isoproterenol probably affected the relationship of cardiac glycosides and myocardial potassium. Insulin presumably altered the intracellular-extracellular potassium balance.

28. An Operative Technique for the Prevention of Reflux Following Oesophagogastrostomy

F. G. Pearson, and R. M. Parrish,* Toronto, Ontario

Oesophago-gastrostomy is the simplest method of reconstruction following oespphagectomy for carcinoma of the intrathoracic oesophagus, but results in frequent and significant disability due to gastro-oesophageal reflux. Ottosen of Denmark (1959) described a modified oesophagpgastric anastomosis in which a long segment of intrathoracic oesophagus is inya-ginated into the gastric fundus, permitting normal swallowing but preventing significant reflux. This modified anastomosis was used in 12 consecutive patients at the Toronto General Hospital with carcinoma of the middle or lower third of the oesophagus managed by resection and oesophagogastrostomy in one stage. Follow-up varies from 9 months to 3 years after operation. Nine patients are still living and 3 have died of recurrent carcinoma. The effectiveness of the modified anastomosis in preventing reflux has been evaluated by clinical assessment, detailed cine-radiographic follow-up, and oesophagoscopy. There were no operative deaths and no anastomotic leaks. None of 12 patient has developed symptomatic reflux, none have shown evidence of aspiration, and none have developed oesophagitis or stricture proximal to the anastomosis. Although the number of patients reported is small, and the follow-up period relatively short, current observations merit an optimistic preliminary report.

29. Autonomic Innervation in Achalasia of the Esophagus

D. M. Jacobowitz,* P. Berg,* S. A. Steinberg,* and P. Nemir, Jr.,

Philadelphia, Pa.

Studies were carried out on the autonomic innervation at various levels of the esophagus in the normal dog and in a group with severe naturally occurring achalasia. The parasympathetic innervation has been studied by the histochemical method for acetylcholinesterase and, for the first time, sympathetic innervation by a histpfluprometric method for the localization of catecholamines. The adrenergic innervation is seen primarily in the Auerbach"s plexus and about blood vessels and not innervating the smooth muscle as classically believed. No change in the innervation of the adrenergic and cholinergic fibers was observed in the body of the normal and dilated esophagus. In animals with achalasia the sympathetic fibers in anatomical proximity to Auerbach"s plexus are either absent or markedly reduced in the lower esophagus as compared to the normal. These findings indicate that the primary derangement in achalasia is a spasm on the basis of parasympathetic predominance rather than a failure of relaxation. Moreover, studies indicate that the effectiveness of esophagomyotomy is through restoration of autonomic balance. Since the influence of catecholamines on the esophagus may be either stimulatory or inhibitory, we are presently testing certain alpha and beta stimulator and blocking agents using cine-roentgenographic, manometric and electromyographic techniques.

30. The Experimental Treatment of Esophageal Strictures by Intralesional Steroid Injections

Keith W. Ashcraft,* and Thomas M. Holder, Kansas City, Kan.

The treatment of short esophageal strictures by dilatations has often been frustrating and unsuccessful. The demonstration that keloids, hypertrophic scars, and burn contractures resolved after intralesional injection of triamcinolone diacetate suggested a new method of management of esophageal stricture. This drug enhances the solubility of saline extractable collagen and depresses mucopolysaccharide formation in the synthesis of collagen. Short esophageal strictures were created in 15 dogs by sodium hydroxide burns. These strictures were documented by endoscopy and by cine radiography. Nine animals received intralesional injections of triamcinolone endoscopically. Six animals served as controls - three receiving no treatment and three receiving saline injections. None of the 15 strictures were dilated and all animals were maintained on a liquid diet. Repeat cine-esophagrams and esophagoscopy were performed prior to sacrifice. Of the treated animals seven demonstrated at least a four-fold increase in cross sectional area at the stricture. Two were unchanged. None of the controls improved. Four patients with short esophageal strictures were treated by this method. Three of these had undergone multiple dilatations prior to the addition of the steroid injections. All showed marked and lasting relief of the stricture functionally and radiographically.

31. Oxygen Consumption During Cardiopulmonary Bypass Circulation: Effect of Pulsatile Flow

Richard B. Shepard,* and John W. Kirklin, Birmingham, Ala.

Portions of the microcirculation may not be perfused during shock and during some types of cardiopulmonary bypass. While tolerable for short periods, this is disadvantageous over long periods. To test the hypothesis that perfusion of the microcirculation is more complete with pulsatile than with non-pulsatile flow, 23 calves were subjected to 4 hour periods of complete cardiopulmonary bypass circulation (2.1 L/min/M²; 36.5-37°C) using a disc oxygenator. A roller pump was used for non-pulsatile perfusion (NPP) (13 animals). A modified roller pump was run at pulse rates of 60-70 for pulsatile perfusion (PP) (10 animals). Phasic flow and pressure were measured in the animals. Oxygen consumption during NPP was 126 ± 25 cc/min/M²; during PP it was 159 ± 16 (p <.001). During PP, the pulsatile component of hemodynamic energy was not significantly different from that existing before and after bypass (.7 < p < .8). It was higher by 8500 ergs/cm³ blood during PP compared to NPP (.001 < p < .005). Bronchial artery flow was 128 ± 56 cc/min/M² during PP and 36 ± 11 during NPP (p <.001). The data suggest that in these calves perfusion of the microcirculation was more complete when flow was pulsatile than when it was non-pulsatile.

32. Improved Organ Function During Cardiac Bypass With a Roller Pump Modified to Deliver Pulsatile Flow

Lloyd A. Jacobs,* Edward H. Klopp,* Woodrow Seamone,*

Stephen R. Topaz,* and Vincent L. Gott, Baltimore, Md.

The importance of pulsatile flow during cardiac bypass has not been completely established. Evidence is accumulating, however, suggesting that steady flow perfusion causes greater disturbance of physiologic function than pulsatile perfusion. To further evaluate this hypothesis, a roller pump has been modified to achieve pulsatile flow by the addition of a torque motor powered by a triangular waveform. Rate and stroke volume are adjustable and pulsatile or steady flow may be selected. The femoral artery pressure waveform produced in the dog is nearly indistinguishable from that seen in the intact animal. Total left heart bypass has been performed in twenty dogs, five with steady flow and fifteen with pulsatile flow. Dogs perfused with steady flow showed immediate, large decreases (85-100%) in urine output and creatinine clearance; those perfused with pulsatile flow showed only small (10-15%) decreases in urine output and creatinine clearance during four-hour perfusions. Furthermore, those perfused with pulsatile flow showed smaller changes in peripheral resistance, less edema and somwhat lower serum lactate levels. It was possible to demonstrate unimpaired renal function, reflexes and responsiveness after twelve hours of pulsatile perfusion.

33. A Central-Flow, Low-Profile, Leaflet-Deforming Mitral Valve Prosthesis Free of Prolonged Anticoagulation Requirements

K. W. Edmark,* W. J Hill,* G. I. Thomas, and T. W. Jones,

Seattle, Wash.

Described is a new concept in artificial heart valve prosthesis which is a central-flow, leaflet-deforming valve giving normal heart sounds, free of murmurs or clicks. The advantages of this valve are its laminar central-flow characteristics with low profile and its non-thrombogenic surface coating of tetrafluoropropylene, which does not require long-term anticoagulant therapy. The anti-thrombogenic properties of this valve have been developed after four years of animal implant experimentation, with dog survival beyond two years. It has also been fatigue-tested beyond 405 million cycles, with a closing pressure of 250 mm. Hg, giving a fatigue life beyond 40 years, with a flex life beyond ten years. The presentation will include laboratory data and the clinical experience in the initial ten patient implants, beginning February, 1968, and continuing.

*By Invitation