International Rallroom Center

19. Cardiopulmonary Homotransplantation

George L. Grinnan,* Walter H. Graham,* James W. Childs,*

and Richard R. Lower, Richmond, Va.

Orthotopic homotransplantation of the heart and both lungs was performed on 25 dogs to evaluate function and pathology. All had serial determinations of arterial pO₂, pCO₂, pH and EGG. The ventilatory responses, pulmonary resistance and cardiac output (C.O.) were studied in 3 animals breathing alternately 7% O₂and 5% CO₂. Immunosuppression consisted of methylprednisolone, azathioprine and antilymphocyte serum. All animals resumed spontaneous respirations and 10 survived between 1 and 10 days. Early deaths were primarily related to technical problems. Most animals initially demonstrated normal pO₂ and pCO₂ and spontaneously corrected a mild metabolic acidosis resulting from bypass In the animals studied, pulmonary resistance was normal; hypercapnia and hypoxia produced appropriate increases in tidal and minute volumes despite denervation. Changes in C.O. were unpredictable due to the unstable condition of the early postoperative period. In animals surviving over 24 hours, pulmonary edema was a frequent pathologic finding with varying degrees of mononuclear cell infiltration. Hearts were normal clinically and showed less cellular infiltrate. Total Cardiopulmonary transplantation appears technically and physiologically feasible. The denervated preparation is capable of adequate gas exchange and normal hemodynamic support of the animal. Prolonged survival is more difficult to achieve than with cardiac transplantation.

20. Effect of Anticoagulants on the Transplanted Heart

Donald R. Kahn, Edward A Carr,* Marvin M. Kirsh,*

Harold A. Oberman,* William Y. Moores,* John H. Dufek,*

and Herbert E. Sloan, Ann Arbor, Mich.

To evaluate anticoagulants in acute and chronic rejection, myocardial scans were performed after 33 pig heterotopic cardiac transplants and three human cardiac transplants. Recipient pigs received Cesium-131 chloride one to nine days after transplantation followed by myocardial scans. Samples of myocardia were counted in a scintillation well-counter and examined microscopically. One group received heparin; the second group were controls. Control pigs showed the same uptake of Cesium in the transplanted hearts despite microscopic evidence of rejection. Pigs receiving heparin had two- to three-fold increase in the uptake of Cesium and histological delay in rejection. Human cardiac transplants received heparin and coumadin in addition to azathioprine and prednisone. In two patients without evidence of rejection for one year, myocardial scans showed good uptake. In one patient who had two acute rejection episodes reversed with drug therapy and was in chronic rejection at 6 months, myocardial scans showed decreasing uptake with diffuse "cold" areas. This study supports that ischemia is not of great importance in acute rejection but does accompany chronic rejection. Heparin increases blood flow and delays rejection in the transplanted heart but does not always prevent chronic rejection. Myocardial scans may be useful in diagnosing chronic rejection.

21. Functional Evaluation of the Preserved Heart

Sidney Levitsky,* Willis H. Williams.,* Don E. Detmer,*

Charles L. McIntosh,* and Andrew G. Morrow, Bethesda, Md.

Nineteen canine hearts were perfused with filtered plasma passed through a Kolobow membrane oxygenator for 3 to 24 hours at 8-IOC. in a silicone rubber air free chamber. Active and passive length-tension curves (LTC) were obtained with an isovolumetric balloon after re-warming to 37C. with blood pumped from a support animal. Coronary perfusion pressure and heart rate were held constant. Nine additional hearts were evaluated in the same manner immediately after removal The active LTC was unchanged up to 18 hours of preservation and depressed at 24 hours. Diastolic compliance gradually decreased over the entire preservation period but myocardial edema never exceeded 5%. At a left ventricular end-diastolic pressure of 10 mm. Hg, maximum dp/dt was 1310 ± 109 and 1403 ± 435 mm. Hg/sec., tension time index was 12.4 ± .6 and 10.9 ± 3.5 g-sec./cm.² and peak pressure was 126.3 ± 9.5 and 119.9 ± 31.0 mm. Hg in controls and hearts preserved up to 18 hours respectively. During the period of preservation depressed myocardial function could be predicted by increases in perfusion pressure above 75 mm. Hg, inhibition of lactate uptake and increasing acidosis. These data show the value of the preservation system and provide a model to compare with other methods of cardiac preservation.

22. Bronchial Brushing

Willard A. Fry,* and P. Manalo-Estrella,* Evanston, Ill.

Sponsored by Dwight E. Harken

The Minnesota Impedance Cardiograph has been used to detect the accumulation of interstitial, pleural and mediastinal fluid. The impedance readings (Z₀) are based on the changes in an electric field (4 ma, rms, 100 kHz) applied and monitored via circumferential electrodes and are inversely related to the total thoracic fluid content. In patients such as anephrics undergoing dialysis, changes in Z₀ were found to correlate with clearing in the chest roentgenogram and decrease in the pulmonary extra-vascular water volume (PEWV), using tritiated water and Evans blue dye. With pleural effusion, Z₀ correlated closely with the amount of fluid aspirated (r = 0.99, p < 0.001). This technique was then applied to the clinical monitoring of eight patients undergoing mitral valve replacement. Measurements were made preoperatively and continued post-operatively until discharge. During the immediate postoperative period the Z₀ values were correlated with PEWV and the physiologic pulmonary shunt as well as with left atrial pressure, central venous pressure, blood volume and chest roentgenograms. Thoracic impedance was found to be a valuable means of following the patient's course. In addition it offers the advantages of being simple, non-invasive and adaptable to on-line monitoring systems.

24. Effect of Oxygen and Helium Mixtures upon Ventricular Fibrillation

Roque Pifarre, T.K. Raghunath,* Robert M. Vanecko*

and William E. Neville, Hines, Ill.

The influence of oxygen and helium upon ventricular fibrillation has been investigated in 55 dogs. Routine pentobarbital anesthesia, endotracheal intubation and controlled ventilation with a Harvard respirator were used. The left circumflex artery was ligated at its origin, five minutes after ventilation with the gas mixture was begun. The study was divided in five groups: Group I (26 dogs) was the control group; dogs were ventilated with room air. Group II (10 dogs) 70% oxygen and 30% helium. Group III (12 dogs) 80% oxygen and 20% helium. Group IV (18 dogs) 10% oxygen, 20% helium and 70% room air. Group V (15 dogs) 30% oxygen, 20% helium and 50% air. The incidence of ventricular fibrillation was: Group I (control): 54% Group II: 20%. Group III: 8%. Group IV: 16%. Group V: 0%. Oxygen and helium mixtures reduce significantly the incidence of ventricular fibrillation in acute myocardial infarction in dogs. The mechanism of protection is not clear. However, injection studies demonstrate faster development of collateral circulation with helium ventilation, suggesting that helium mixtures increase blood supply in infarcted areas. Although further investigation is needed, its potential clinical application in mobile coronary care units is self-evident.

5. Evaluation of Dextrose, Insulin and Potassium on Ventricular Irritability in Localized Acute Myocardial Ischemia

Kenneth S. Danielson,* James A. Deweese, and

Earle, B. Mahoney, Rochester, N.Y.

Antiarrhythmic effects of dextrose (D), potassium (K) and glucagon-free insulin (I) on canine hearts following left anterior descending artery ligation has been analyzed by the technique of ventricular fibrillation threshold (VFT) as described by Wiggers. Serial VFT's were measured prior to and over a four-hour period following ligation in all groups. In test groups of ten dogs each receiving 500 ml solution of 1) D 50 g, 2) D 50 g K 40 mEq, or 3) D 50 g, K 40 mEq and I 40 u, the VFT returned to preligation levels after one hour of infusion whereas the VFT in a control group (ten dogs) and pancreatectomized D 50 g-treated group (five dogs) did not recover until the fourth hour. In the presence of the normally-functioning pancreas, concentrated dextrose alone has an antiarrhythmic effect on the acutely localized ischemic myocardium. It is not necessary to administer potassium or potassium and insulin to observe this effect. The mode of action appears to be release of a factor from the pancreas in response to dextrose.

26. Replacement of the Aortic Valve with Molded Autogenous Grafts Grown in Response to Implanted Silastic

Alexander S. Geha,* Gustave L. Davis,* and

Arthur E. Baue, St. Louis, Mo.

Preserved homologous aortic valves virtually eliminate thromboembolic complications following replacement of the diseased aortic valve, but their supply is limited and they have a high incidence of late degeneration and failure. The late results of easily available heterografts may be even less satisfactory. The advantages of autogenous tissue for aortic valve replacement are obvious, but tailoring of fascia lata or pericardium into a valve remains a difficult engineering problem. This report is an evaluation of a method designed to easily provide valve-shaped autografts and study their late results. Aortic cusp-shaped silastic molds are implanted subcutaneously, resulting in growth of a mature acellular thin fibrous host tissue response accurately molded to the geometry and configuration of the implant and histologically similar to the normal cusp architecture. When mature, this well-differentiated tissue is easily dissected and the new "cusp" is attached to the basal rim of the excised cusp with a single row of interrupted sutures placed prior to lowering the valve into position. Autograft aortic cusps have been inserted in a series of dogs, allowing functional, gross, and microscopic examination of the valves at regular intervals up to four months postoperatively. Clinical application of this method appears to be warranted.

27. Deterioration of Formalin-Treated Aortic Valve Heterografts

Wally S. Buch,* Jon C. Kosek,* and William W. Angell,*

Palo Alto, Calif.

Sponsored by Norman E. Shumway

The superiority of fresh aortic valve homografts has been demonstrated by their low failure rate and lack of thromboembolic complications without adjunctive anticoagulant therapy. Difficulties in procurement and storage of this viable tissue prevent widespread use. Heterograft valves treated with 4% formalin have been used elsewhere with good initial results. We implanted supported formalinized porcine heterograft valves into the mitral position of 50 dogs. These valves functioned well initially. This prompted trial in 27 patients. Initial hemodynamic results were excellent; however, 25 percent failed during a 7-month follow-up, and were replaced successfully. They were weakened, thinned, stretched, and torn. Electron micrographs showed macrophage ingestion of portions of the otherwise acellular cusps. This correlated well with the late experimental results. Other methods of formalinization were therefore evaluated experimentally. Three separate heterograft cusps treated in different ways were reconstructed into a composite valve and placed in 60 dogs. Variations of formalin concentration (1/2, 4, 10%), pH (4.0, 5.6, 7.4), temperature (4°, 20°, 37°C), and storage time (2, 30, 60 days) produced no improvement in long-term function. We conclude that formalin is a weak, destructive, unreliable tanning agent for preservation of heterograft aortic valves.

28. Left Ventricular Akinesia: Experimental Production, Hemo-tlynamic Effects, and Results of Excision

P. C. Pairolero,* B. D. McCallister,* F. J.Hallermann,*

and F. H. Ellis, Jr., Rochester, Minn.

A technique of producing canine myocardial infarcts of predictable size has been developed which results in chronic survival and in left ventricular (LV) non-contractility as confirmed by cineangiocardiography. Infarcts were produced in 28 dogs and were excised either 3 to 5 days later (8 dogs) or 4 to 6 weeks later (20 dogs). Hemodynamics were measured before and after excision of the infarct at rest (R), and during infusion of acetylcholine (Ac), angiotensin II (Ag), and isoproterenol (I). These findings were compared with normal values and with those from 5 dogs in whom a segment (3 x 4cm.) of normal myocardium was excised. Excision of normal myocardium was poorly tolerated, 4 dogs dying of pulmonary edema. Small infarcts (1 x 2cm, 8 dogs) produced no change in hemo-dynamics either before or after excision. Large infarcts (3 x 4cm., 20 dogs) resulted in a significant increase (P .001) in LV end-diastolic pressure which remained elevated after excision in the 10 survivors. The response of cardiac output to Ac and I was also abnormal (P .001) but remained so after excision. Neither early nor late excision of experimentally produced LV akinesis resulted in improvement of LV function as measured by the parameters analyzed in this study.

29. Myocardial Metablism in Acute Regional Ischemia

Hendrick B. Earner,* George C. Kaiser, Max Jellinek,*

Akira Taira,* and Vallee L. Willman, St. Louis, Mo.

Regional myocardial ischemia was studied in ten anesthetized dogs using the right heart bypass preparation so that cardiac output, heart rate and aortic pressure could be independently controlled. A snare was placed on the left anterior descending coronary artery for occlusion. The coronary sinus was catheterized and arteriovenous levels of oxygen, lactate and pyruvate and glucose were measured every 15 seconds using an automated system during one, five and 15 minute periods of LAD occlusion. One minute of LAD occlusion resulted in a fall in total coronary flow (TCF) and a comparable fall in substrate utilization. Longer LAD occlusion was associated with slowly rising TGF, oxygen and pyruvate uptake and gradually diminishing lactate utilization. Release of the snare caused reactive hyperemia with increased TCF, oxygen and pyruvate uptake and washout of lactate from the ischemic myocardium. Consumption of lactate was rapidly restored while pyruvate utilization fell. Although lactate production is a well recognized sign of severe myocardial ischemia its detection may be extremely difficult during regional ischemia, even under relatively ideal experimental conditions. Absent lactate production does not exclude the presence of severe local ischmia.

30. Mapping of Epicardial and Intramural Activation of the Heart: A Technique for Localization and Extent of Chronic Infarction During Myocardial Revascularization

Thomas M. Daniel,* Jimmy L. Cox,* David C. Sabiston, Jr ,

and John P. Boineau,* Durham, N.C.

Areas of chronic infarction in coronary artery disease may be multiple and difficult to recognize by visual examination or palpation of the epicardium. In addition, coronary arteriograms do not define the site or degree of myocardial infarction. By the direct recording of unipolar and bipolar potentials from the epicardial surface at operation, the underlying areas of infarction can be delineated with accuracy. This information assists in the determination of sites for revascularization. Mapping of activation is regarded as a potential aid for other surgical procedures on the heart and as a technique for estimating the amount of intrinsic heart disease present and thereby increasing the predictability of postoperative results. Eight human subjects were studied at the time of revascularization procedures. Comparative epicardial data was also obtained from normal hearts during thoracotomy for pulmonary disease, and the normal variations in Q-wave duration were determined for the human epicardial surface. Similar variations in epicardial activation time were also determined. Abnormal prolongation of either Q duration or activation time, or both, were used to delineate areas of underlying chronic infarction. The significance of these changes was validated by detailed anatomic-electrophysiologic correlations in a canine model with chronic experimental myocardial infarction. The technic has been of considerable clinical usefulness at the time of operation.

31. Operative Assessment of Ventricular Aneurysm and Adynamic Myocardium

Ted A. Calinog,* V. S. Mehta,* S. Tjonneland,* Frank Begg,*

W. Cushing,* Edward Kent, and George J. Magovern,

Pittsburgh, Pa.

Preopcrative evaluation of the extent of damaged myocardium is difficult even with present-day techniques of cardioangiography and electrocardi-ography. The operative assessment of ventricular aneurysm and akinetic areas is a difficult task for the surgeon faced with preserving functioning myocardium vital to the hemodynamic workload of the ventricle. We have found two valuable intraoperative procedures which can easily be applied. (1) Creating an intraluminar negative pressure in the ventricle and (2) electrophysiologic technique utilizing epicardial electrogram with unipolar and bipolar electrodes. The patient is placed on cardiopulmonary bypass and a vent inserted in the left ventricle through the left atrial appendage. A negative pressure of 30 mm. of Hg. is applied. Gross collapse of the aneurysmal and adynamic areas can be appreciated with clearcut delineation of its margins. Epicardial electrogram with unipolar and bipolar electrode probes are applied at these margins. A precise line of resection can be shown, thus preserving viable functioning tissue. Techniques, experimental assessment, development, and clinical application will be presented. Seven patients to date have had successful resection based on this method. The use of the epicardial electrogram has further extended to selection of a vascular areas for myocardial revascularization. The technique and results, likewise, will be shown.

*By Invitation