American Association for

Thoracic Surgery

60TH ANNUAL MEETING

Scientific Program

MONDAY MORNING, APRIL 28,1980

8:30 A.M. Business Session (Limited to Members)

Continental Ballroom

8:45 A.M. Scientific Session - Continental Ballroom

1. Myocardial Energy Replenishment and Reversal of Ischemic Damage by Substrate Enhancement with Amino Acids during Reperfusion

HAROLD LAZAR*, ANDREW M. MANGANARO*,

HEINZ BECKER* and GERALD D. BUCKBERG,

Los Angeles, California

We have shown previously that ischemia depletes myocardial energy stores and limits recovery by impairing the post-ischemic oxidative metabolism which repletes them. This study tests the hypothesis that near normal post-ischemic oxidative metabolism and functional recovery is possible by adding the amino acid L-glutamte to the blood cardioplegic solution used to lower oxygen demands during reperfusion.

Methods: Of 20 dogs undergoing 45 minutes of 37°C ischemic arrest, no heart could support the systemic circulation 15 minutes after unclamping. We prolonged bypass 30 minutes in all dogs; in 13 we lowered O₂ demands further by reclamping the aorta for 10 minutes while continually infusing at 37° blood potassium cardioplegic solution. In 8 dogs, we added L-glutamate (0.026 M) to this solution. Coronary blood flow (micro-spheres), ATP, metabolism (O₂ content), and LV performance (Starling curves) were measured during control and at 15 and 45 minutes after unclamping.

Results: The lowest post-ischemic ATP (2.2 µM/gm) and least functional recovery (35% return of stroke work index) occurred in hearts not receiving cardioplegia during prolonged bypass. In contrast, adding L-glutamate to the blood cardioplegic solution allowed better ATP repletion (4.2 vs 3.2 µM/gm*), greater augmentation of LV subendocardial flow (85 vs 71%*) and O₂ uptake (108 vs 83%*) during the working state, and higher stroke work indices (1.20 vs 0.74 g-m/kg, 85 vs 55%* recovery) than with blood cardioplegia alone.

Conclusion: Adding L-glutamate to blood cardioplegia causes near complete reversal of ischemic damage, possibly through restoring ATP by stimulating oxidative metabolism and replenishing a vital Krebs cycle intermediate lost during ischemia. We believe L-glutamate will become an important component of future cardioplegic solutions.

*p < .05 from hearts receiving L-glutamate

*By invitation

2. Adenosine Metabolism and Myocardial Preservation

JOHN E. FOKER*, STANLEY EINZIG* and TING WANG*,

Minneapolis, Minnesota

Sponsored by: Robert W. Anderson, Minneapolis, Minn.

The nature of the metabolic events leading to irreversible damage of the ischemic myocardium are not known. We tested the hypothesis that catabolism of ATP precursors limits the regeneration of this high energy compound following ischemic insult. Dogs on cardiopulmonary bypass (CPB) had their aortas cross-clamped (XC) for 20 min at normothermia and 30 min later CPB was discontinued. Rapidly frozen left ventricular biopsies were assayed and control levels (um/gm) found for ATP (5.30) and creatine phosphate (CP) (6.18) and the ATP precursors ADP (0.82) and AMP (0.43). Measurable AMP degradation did not occur in the control state and adenosine (Ad), inosine and hypoxanthine/xanthine (Hx/x) were not detectable. At the end of XC, ATP had fallen to 3.60 and CP to 0.57, however, the predicted rise in the levels of ADP, AMP and Ad was not found. The levels of inosine (1.23) and Hx/x (0.24) increased indicating ADP, AMP and Ad had been further catabolised and limited the potential for ATP recovery. Following XC release, ATP levels did not increase and even 60 min off CPB were only 3.27. CP levels rose from 0.57 during XC to 10.2 within 5 min after XC, indicating high energy bonds could be formed. To test the effect of blocking Ad catabolism, EHNA (10 mg/k), an inhibitor of adenosine deaminase was used in 5 dogs. At the end of XC, tissue Ad, previously unmeasurable, was 1.60 um/gm. Nevertheless, ATP levels did not rebound after XC release; the reason was found to be cellular loss and the coronary sinus blood contained high levels of Ad. Adenosine (20 mg/k) infusion alone was used to equilibrate intra- and extracellular levels during CPB in 5 dogs. This did not alter subsequent ATP levels so we combined EHNA treatment with Ad infusion (5 dogs). ATP levels showed good recovery and 30 min after XC were 4.68 and 60 min off CPB were 4.73. We conclude that ATP regeneration after ischemia is limited by the availability of ADP, AMP and Ad. Inhibition of Ad catabolism and infusion of Ad will enhance ATP return from ischemia. Current methods of myocardial preservation, chiefly hypothermia and cardioplegia, are designed to decrease ATP utilization. Our approach, by inhibiting an important biochemical consequence of ischemia, may improve myocardial preservation by providing precursors for ATP recovery.

*By invitation

3. Relationship Between Atrio-Ventricular Arrhythmias and the Concentration of K⁽⁺⁾ Ion in Cardioplegic Solution

ROBERT ELLIS*, CONSTANTINE MAVROUDIS*,

DANIEL ULLYOT, KEVIN TURLEY* and PAUL EBERT,

San Francisco, California

Several centers have noted a high incidence of atrial arrhythmias following the use of potassium cardioplegia during cardiac surgery. A spectrum of arrhythmias such as atrio-ventricular dissocation, nodal rhythm, and either right or left hemiblock conduction defects have been observed at the termination of cardiopulmonary bypass. Although these are transient, they can have deleterious effects on the hemodynamic stability of the patient. The etiology of these arrhythmias is postulated to be due to one or a combination of the following factors: Anoxic myocardium, inadequate cooling of the right atrium, air in the A-V nodal artery or action potential changes in the conduction system induced by concentration of K⁽⁺⁾ ion. We have recently compared the incidence of intraoperative arrhythmias using Holler monitoring in three groups of patients (20 each) where the concentration of K⁽⁺⁾ ion was varied. Total revascularization was attempted with a mean of 3.2 grafts/pt and a mean cardioplegic arrest time of 55 ± 4 minutes. Patients had their cardiac jhythm taped using a Holter monitor throughout the cardiac procedure. Group I used 20meq K⁽⁺⁾/L/4°C as the perfusate with repeated infusions of this same solution. Group II used only 5meq K⁽⁺⁾/L/4°C as perfusate both initially and for subsequent infusions. Group III used 20meq K< + >/L/4°C as the initial perfusate and 5meq/L for subsequent infusions. All patients had an initial infusion of 800cc of cardioplegic fluid followed by a 400cc infusion after each distal anatomoses.

These results indicate that myocardial HEP was preserved in all three groups. The incidence of arrhythmias in the immediate post arrest period in Group I was 60% whereas it was only 5% in Groups II and III. These data suggest that after the initial infusion of high K+ solution, subsequent infusions could be with low potassium cardioplegia to avoid the arrhythmias noted with the repeated use of high potassium cardioplegic solution.

*By invitation

4. Comparison of the Effect of Blood Cardioplegia to Crystalloid Cardioplegia on Human Myocardial Contractility

NADIV SHAPIRA*, DOUGLAS BEHRENDT,

MARVIN KIRSH, and KENNETH JOCHIM*,

Ann Arbor, Michigan

Cardioplegic solutions (CP) of various compositions are advocated for myocardial protection during aortic clamping. However, no controlled quantitative measurements have been made on their comparative effect on human myocardial function.

Thirty-three patients (pts) undergoing coronary bypass grafting were randomly assigned to 1 of 3 groups: Group KCP (n = 9) received crystalloid CP (Ringers, 24 meqK VI, 12.5 gm mannitol/1, 4 meqNaHCO₃/l). Group MgKCP (n = 9) received a different crystalloid CP (Mg ^{+ +} 30 meq/1, K + 20 meq/1). Group BCP (n= 15) received blood CP (Hct 20%, K⁺ = 30 meq/1). In each patient, 1 liter of 4°C CP sol. was given followed by 500 ml every 30 min. All distal anastomosis were completed during one continuous aortic crossclamping. In each pt cardiac output (CO), LVEDP and contractile element velocity (Vpm) were recorded intraoperatively before and after aortic crossclamp period. Vpm was recorded from a Millar catheter placed in the LV through apical stabwound. Heart rate was held constant by atrial pacing during recordings. The 3 groups were comparable in regards to age, sex, ejection fraction, symptoms, propranolol use, number of bypasses performed (av. 2.6) and duration of ischemic arrest (av. 52 min).

Preoperative LV function assessed by CO, LVEDP and Vpm was similar in all 3 groups. No significant differences in myocardial function were observed after ischemia with BCP or KCP. However, pts receiving MgKCP had significant (P = 0.02) depression in Vpm (from 28.6±7.8 sec^-1 to 20.4 ±3.6 sec^-1) and increase (P<0.05) in LVEDP (from 9.4 ± 2.2 mmHg to 13.4 ± 5.2 mmHg). Postoperative Vpm of MgKCP group was also significantly depressed (P <0.05) by comparison with BCP group. 89% of pts receiving KCP or MgKCP but only 40% of BCP pts required electrical defibrillation. There were no deaths, and only one patient sustained peri-operative infarction (in KCP group).

We conclude that blood Cardioplegia offers no advantage in degree of myocardial protection compared to simple high K⁺ solution, although fewer patients required electrical defibrillation. MgKCP solution yielded inferior results.

*By invitation

5. Heart and Lung Transplantation: Auto and Allotransplantation in Primates with Extended Survival

BRUCE A. REITZ,* NELSON A. BURTON,*

STUART W. JAMIESON,* JOHN L. PENNOCK,*

EDWARD B. STINSON,* and NORMAN E. SHUMWAY

Stanford, California

A number of severely ill patients with congenital or acquired disease could be treated by transplantation of the heart and both lungs. In order to study this possibility, heart and lung transplantation (HLTx) was performed in 25 monkeys (rhesus or cynomolgous) divided into two groups.

Group I (17 animals weighing 2.6-6.5 kg) underwent HLTx with surface-induced deep hypothermia (17-20°C), circulatory arrest (58-94 min), and surface rewarming. The phrenic nerves were preserved on pedicles and anastomoses were performed to the trachea, ascending aorta, and both vena cavae. Group IA (5 animals) had auto-HLTx with one long-term survivor (now 213 days). Group IB (12 animals) had allo-HLTx with 9 resuming spontaneous respiration, 6 surviving greater than 24 hours, and one surviving 5 days before dying of rejection. Group II (8 animals weighing 4.9-8.8 kg) had HLTx with cardiopulmonary bypass. A similar .operative technique was used with all cannulations performed in the thorax. Group IIA (2 animals) had auto-HLTx with both surviving at 49 and 157 days. Group IIB (6 animals) had allo-HLTx with all surviving more than 24 hours with spontaneous and normal respiratory patterns. The 3 animals surviving more than 48 hours were started on cyclosporin A (25 mg/kg/day) and azathioprine (2 mg/kg/day for 14 days) with 2 currently surviving at 110 and 41 days without rejection. These experiments demonstrate extended survival of primates after complete heart and lung transplantation. The allografts on cyclosporin and azathioprine are the longest reported survivors after this procedure.

INTERMISSION - 45 MINUTES

VISIT EXHIBITS

*By invitation

6. Comparison of Standard Aneurysmectomy and Aneurysmectomy with Endocardial Resection for the Treatment of Recurrent Sustained Ventricular Tachycardia

ALDEN H. HARKEN*, LEONARD N. HOROWITZ*,

and MARK E. JOSEPHSON*, Philadelphia, Pennsylvania

Sponsored by Dwight E. Harken, Boston, Massachusetts

Failure of aneurysmectomy to ablate venticular tachycardia may be due to incomplete removal of the tachycardia site. We have developed an in-traoperative catheter mapping technique coupled with endocardia! resection * of sites demonstrated to be the origin of ventricular tachycardia. The value of intraoperative mapping and endocardial resection in addition to standard aneurysmectomy was compared to standard aneurysmectomy alone in 36 patients with recurrent sustained, medically refractory, ventricular tachycardia. Sixteen patients (group 1) ranging in age from 42 to 66 underwent standard aneurysmectomy alone (1971-1975) and 20 patients (group 2) ranging in age from 23 to 68 years underwent mapping and endocardial resection with or without aneurysmectomy (1976-1979). All 36 patients had coronary artery disease and prior myocardial infarction but only 85%of group 2 patients had left ventricular aneurysms. In group 1, mean ejection fraction was 32% (range 10-42%) and cardiac index was 2.2 L/Min/M². Group 2 patients had an ejection fraction of 28% (5-39%) and cardiac index of 2.0 L/Min/M². In group 1, there were 5 operative deaths (31%), 3 of recurrent ventricular tachycardia. Six survivors had recurrent ventricular tachycardia, 4 (25%) of whom subsequently died of their arrhythmia. The remaining 2 are controlled by anti-arrhythmic therapy. Five patients in group 1 have had no ventricular tachycardia in the absence of anti-arrhythmic medication. In group 2, intraoperative catheter mapping localized the origin of the tachycardia to a border of the infarction or aneurysm in all instances. At surgery, ventricular tachycardia persisted following resection of the ventricular aneurysm or ventriculotomy (prior to the endocardial resection) in 18 out of 20 patients. Following endocardial resection, 16 patients remain free of their ventricular tachycardia, 2 patients' tachycardia are now controllable on anti-arrhythmic therapy, and there were 2 (10%) operative deaths. We conclude that surgical therapy of recurrent sustained ventricular tachycardia is feasible by identification of the site of origin of the arrhythmia by intraoperative mapping and appropriately guided endocardial resection.

*By invitation

7. Left Atrial Isolation: A New Technique For The Treatment of Supraventricular Arrhythmias

J. MARK WILLIAMS*, ROSS M. UNGERLEIDER*,

GARY K. LOFLAND* and JAMES L. COX*, Durham, N.C.

Sponsored by: David C. Sabiston, Jr., Durham, North Carolina

Surgical therapy has been successful in the treatment of ectopic and re-entrant ventricular tachycardia and in re-entrant Supraventricular tachycardia. However, surgical ablation of ectopic Supraventricular arrhythmias, particularly those arising in the left atrium, has been unsuccessful. As a result, it has been necessary to cryoablate the bundle of His and insert a permanent ventricular pacemaker for control of these arrhythmias. It was the purpose of this study to develop a technique to isolate the left atrium electrically from the remainder of the heart, thereby precluding the necessity for an artificial pacemaking system.

Right atrial, left atrial, and ventricular epicardial electrograms were recorded in ten adult dogs prior to institution of cardiopulmonary bypass (CPB) and potassium cardioplegic arrest of the heart. During CPB, a standard left atriotomy was performed and was extended anteriorly across the mitral valve annulus between the right and left fibrous trigones. Posteriorly, the atriotomy was extended across the mitral valve annulus just to the left of the posterior crux and interatrial septum. The muscular interatrial fibers accompanying the coronary sinus were cryoablated at minus 60°C for two minutes. The atriotomy was closed and the animals were weaned from CPB.

Postoperatively, all animals remained in normal sinus rhythm. Neither rapid left atrial pacing nor left atrial fibrillation affected the rate or rhythm of the remainder of the heart. Preliminary hemodynamic measurements suggest that loss of the synchronous left atrial "kick" does not significantly affect left ventricular preload, afterload, or cardiac output.

This technique offers an alternative to the current surgical approach for treatment of refractory ectopic Supraventricular tachycardia arising in the left atrium. Moreover, it may ultimately become useful as an adjunctive treatment for chronic atrial fibrillation associated with mitral valve disease in patients requiring mitral valve replacement.

*By invitation