Page 1

Original Communications

Heterotopic Heart Transplantation in Three Patients at the Texas Heart Institute 0. Howard Frazier, M.D., O.U. John Okereke, M.B., F.R.C.S., Denton A. Cooley, M.D., and Branislav Radovancevic, M.D., Linda B. Chandler, R.N., and Penny Powers, R.N. Seventy-three orthotopic and three heterotopic transplantations have been done in our institution, and in this report, we describe the procedure and outcome ofthose who underwent heterotopic transplantation. Three patients were in critical condition while awaiting donors for heart transplantation, and in each case, a suitable donor could not be found. Smaller donor hearts became available, and knowing that these patients would die without some kind ofimmediate action, we performed heterotopic heart transplantations. Patient Number 1 was a 53-year-old diabetic man who was in the last stages of heart disease when a small donor heart became available. Because of his rapidly deteriorating condition, we did a heterotopic transplantation. Thepatient is presently well andfunctioning normally. Patient Number 2 was a 26-year-old woman who received the heart of a 13-year-old donor after it became obvious that she could not wait for a suitable donor. We performed a heterotopic transplantation, after which the patient continues to function well. Patient Number 3 was a 53-year-old man who weighed 260 lbs. When a suitable donor could not be found, the heart of a 170-lb man became available and was used in a heterotopic transplantation. This patient also continues to be active and well. After considering the various advantages and disadvantages of heterotopic transplantation, we are convinced that there is a definite placefor this procedure in some patients with end-stage cardiacfailure, although we still believe that orthotopic transplantation should be offered to most recipients. CLINICAL CARDIAC transplantation has been performed at the Texas Heart Institute since 1968.1 Conventional immunosuppression with azathioprine (Imuran) and steroids were used in 19 patients who were transplanted in the early years of cardiac transplantation. In July of 1982, cardiac transplan-

tation was resumed with cyclosporine as the

major immunosuppressive drug.2 By July 1983, 76 patients had undergone cardiac transplantation, with three patients having been heterotopically transplanted. We have considered the usefulness of this operation siiice Novitzky,3 Barnard,4'5 and Losman6 provided

From the Division of Surgery and the Transplantation Unit, Texas Heart Institute and St. Luke's Episcopal Hospital, Houston, Texas. Address for reprints: 0. Howard Frazier, M.D., Texas Heart Institute P.O. Box 20345, Houston, Texas 77225. Texas Heart Institute Journal

221


more information on the procedure. We have also done experimental procedures on techniques, and have tested aspects of postoperative hemodynamics. Recently, a patient in terminal cardiac failure with high pulmonary pressure and resistance was referred to our institution for cardiac transplantation. After awaiting a donor for a long time, we finally located a suitable tissuematched donor who was not a suitable sizematch. Since we were not certain whether we could wean him off of cardiopulmonary bypass after orthotopic transplantation, we decided to do a heterotopic transplant. Surprisingly, he did well postoperatively, even with elevated pulmonary pressure. Since then, we have performed two additional heterotopic transplants in patients whose clinical conditions did not meet our criteria for transplantation, nor did the available donors meet our

specifications. We report the three cases performed in this institution, and describe some interesting findings during invasive and noninvasive assessment of the hearts in the immediate and late postoperative period.

CASE REPORTS Case 1 A 53-year-old diabetic man, controlled with oral hypoglycemic therapy, recently sustained a transmural, anterolateral myocardial infarction and was successfully managed in the coronary care unit. Cardiovascular investigations before the patient's discharge showed a left ventricular ejection fraction (LVEF) of 15%, biventricular hypokinesis of 50%, right coronary artery (RCA) occlusion, severe distal left anterior descending (LAD) disease, right ventricular pressure of 85/10, pulmonary artery wedge of 24, right atrial pressure of 24, and cardiac output of approximately 3 liters/ min. The patient was obese (308 lbs), and was put on a weight reduction program. His condition progressively worsened and, despite his diabetes mellitus, age, weight, and high pulmonary resistance, he was accepted into the heart transplantation program. After several weeks in the hospital, it became 222

obvious that he would die if a suitable donor could not be found. When a small-sized donor heart became available, we decided to perform a heterotopic transplantation. He tolerated the operation well and was discharged within 1 month post-transplantation. He experienced one episode of moderate allograft rejection, which was treated with steroid pulse. He is now well and able to function normally.

Case 2 A 26-year-old woman was well until approximately 1 year prior to admittance, when she experienced an episode of upper respiratory tract infection and probable viral infection with fever. Following this attack, she went into cardiac failure, and was in progressive heart failure at the time of her referral to our institution. She was given the intravenous inotropes Dopamine and Inocor, but her condition deteriorated, and she was intubated. Thrombophlebitis developed, with the possibility of blood-clot formation in the right atrium, for which she received Coumadin therapy. This led to massive gastrointestinal bleeding, subarachnoid bleeding, and seizures. Pneumonia developed, with positive sputum cultures for Klebsiella and Staphylococcus. She responded well to appropriate antibiotic therapy, and her seizures were controlled with Dilantin. While on Dopamine and Amrinone, the patient was found to have LVEF of 23%, biventricular enlargement, biventricular hypokinesis, and a cardiac output of 3.5 to 4.2 liters/min. Her cardiac index (CI) was 2.0 to 2.5; pulmonary pressure was 73/32; pulmonary artery wedge pressure was 20; and the pulmonary vascular resistance was calculated at 5 to 7 wood units. However, the patient's heart condition continued to deteriorate, even though she was on mechanical support, with an intraaortic balloon pump (IABP) in place. After 4 days with IABP support, a 13-year-old donor was located over 1000 miles away. Since her condition was worsening rapidly and she had multi-organ failure, we used the small donor heart. After a heterotopic transplantation was performed, the patient was discharged in good condition and continues to function well. Vol. 12, No. 3, September, 1985


Case 3 One year ago, a 53-year-old man with bronchitis developed congestive cardiac failure after an episode of influenza. His cardiac biopsy showed myocarditis, and he was treated with steroids and azathioprine (Imuran) in addition to inotropic agents. He improved initially on this regimen, but tachycardia persisted. Two months before transplantation, his condition began to deteriorate again. His bronchitis exacerbated, and a pulmonary infection, with mixed organisms, developed. Cardiac catheterization showed an ejection fraction of 16%; his pulmonary artery pressure was 30/20; his

pulmonary artery wedge pressure was 22; and his CI was approximately 2.1. The arteriogram showed large, normal coronary vessels with no significant valvular disease. He had benign prostatitis hypertrophy that had been symptomatic; however, surgery was postponed because of his heart condition. He was later subjected to transurethral resection, after which, his cardiac condition deteriorated rapidly. His weight of 260 lbs was also a problem. Finally, a donor who weighed about 170 lbs became available; and in view of the patient's terminal condition and because the donor heart was small for an orthotopic implant, we decided to perform a heterotopic

A. AOI

AZYGOUS V.

PULMONARY TRUNK' LT PULMONARY VV.-

,

VV.

INF. VENA CAVA

Fig. IA Donor Heart Preparation. The openings of the right superior and inferior pulmonary veins and the inferior have been closed carefully. The right atrial incision is extended high up in the superior vena cava. The left superior and inferior pulmonary vein openings are connected by incising the bridge of tissue separating them.

vena cava

Texas Heart Institute Journal

223


transplantation. The patient did well postoperatively and continues to function normally.

MATERIALS AND METHODS Donor Heart Procurement and Preparation The first heterotopically implanted donor heart was obtained from a hospital in Houston, whereas the two others were obtained from distant cities. The technique of donor heart excision was similar to orthotopic transplantation, except that the superior vena cava (SVC), pulmonary artery (PA), and the ascending aorta were transected as high as possible. As described previously, all donor hearts were cross-clamped and arrested with cardioplegia before removal.2 They were then put into a sterile plastic bag containing normal saline at

40 C, which was subsequently put into a cooler containing ice chips, and transported to Houston. The final preparation of the donor heart was done in the operating room to ensure careful incisions in the SVC and pulmonary veins, as well as to save time. The method used throughout the operation was that described by Novitzky et al,3 but with minor modifications. A bowl was half-filled with normal saline at 4째 C. The donor heart was then taken out of the plastic bag and prepared in the bowl. The inferior vena cava (IVC) and the right superior and inferior pulmonary veins were closed with 5-0 prolene sutures. An incision was made into the bridge of tissue joining the left superior and inferior pulmonary veins to form a common opening into the left atrium. A longitudinal incision was then made in the posterior aspect of the SVC and right atrium (Fig. 1 A).

1B Anastomosis of the Left Atria. The opening in the donor left atrium may be extended to achieve a wider connection. 224

Vol. 12, No. 3, September, 1985


Fig. IC and D Anastomosis of the Right Atria. (C) The anastomosis is started by suturing the inferior angle of the incision into the donor right atrium to the midpoint of the posterior edge in the native atrium. (D) Completed right atrial anastomosis.

Recipient Preparation A median sternotomy was performed, and some blood was removed for preclotting of the Dacron graft to be used in the pulmonary artery anastomosis. The size of the graft was approximately the same diameter as the donor pulmonary artery. Full cardiopulmonary bypass (CPB) was then established as usual with SVC and IVC cannulae. A high aortic cannulation was done while the SVC cannula passed through the right atrial appendage. The IVC was cannulated as low as possible. As soon as CPB was established, cooling of the patient commenced. A right pleuropericardial flap was created to make space for the heterotopic heart. Adequate hemostasis of the edges of this flap was done, because it would Texas Heart Institute Journal

not be accessible after the operation. When the patient's temperature had reached 280 C, the aorta was cross-clamped and cardioplegic solution was administered through the aortic root to arrest and protect the native heart. Cold topical saline was also applied to the heart, and a left apical suction vent was inserted. The recipient's left atrium was then incised anterior to the right superior pulmonary vein, and the incision was carried downward to a short distance beyond the right inferior pulmonary vein. The common opening of the left superior and inferior pulmonary veins was then anastomosed to the left atrium with 4-0 prolene suture (Fig. I B). The anastomosis of the right atria was done with continuous 4-0 prolene suture. The incision from the SVC into 225


the right atrium of the donor heart was extended further into the right atrium to ensure a wide connection between both atria. The anastomosis was started by suturing the inferior angle of the incision in the donor atrium to the midpoint of the posterior edge of the incision in the native atrium (Fig. IC and D). A large hemoclip was placed around the upper limit of the anastomosis on the donor SVC to act as a reference point during endomyocardial biopsy. The donor aorta was then anastomosed to the ascending aorta end-to-side, using continuous 4-0 prolene suture (Fig. IE). Care was taken to ensure adequate length of the donor aorta and a wide anastomotic opening. Using the preclotted Dacron tube graft, the distal

anastomosis between the graft and the native pulmonary artery trunk was made with continuous 5-0 prolene suture. The proximal endto-end anastomosis between the graft and the pulmonary artery was then similarly completed (Fig. IF). Rewarming was usually started after the aortic anastomosis was completed. Thorough inspection of all suture lines was done. Air was completely removed from both hearts, and the aortic cross-clamp was removed. Occasionally, both hearts had to be defibrillated with electrical shock.

POSTOPERATIVE COURSE All three patients did well postoperatively. The immunosuppressive regimen was the

1E Anastomosis of the donor-heart aorta to the recipient ascending aorta. 226

Vol. 12, No. 3, September, 1985


1F Completed heterotopic transplantation with interposed Dacron tube graft between the donor and recipient pulmonary arteries.

same as for our orthotopic recipients. All patients received oral cyclosporine, 10 to 14 mg/kg body weight, 4 to 6 hours preoperatively, depending on the renal function. Intraoperatively, 500 mg Solu-Medrol was given. Cyclosporine was given orally or through the nasogastric tube in the immediate postoperative period to maintain the serum trough level between 20 and 400 ng/ml. Prednisone was also started, with 120 mg in divided doses daily, and tapered rapidly to a maintenance dose of 15 to 20 mg within 2 months. Steroid tapering was more rapid in the elderly recipients. Endomyocardial biopsies were done weekly and only moderate or severe rejection episodes were treated. Depending on the time of rejection postoperatively, the severity of rejection, and the age of the patient, such Texas Heart Institute Journal

episodes were treated with a steroid pulse consisting of 500 mg of intravenous SoluMedrol every 8 hours for 4 to 6 doses. Endomyocardial biopsies were repeated 3 to 5 days post-steroid pulse. Antithymocyte globulin was added duri ng steroid-resistant rejection episodes. Antithymocyte globulin was used when a severe rejection was encountered during the first week post-transplantation, especially if the cyclosporine trough levels were within the therapeutic range. Dipyridamole and aspirin were given to all heterotopic recipients postoperatively. CARDIOVASCULAR ASSESSMENT The performance of both hearts in the immediate postoperative period was assessed 227


d

r

d

r

dr

d

r

d

r

d

d

d

Fig. 2 Electrocardiograms from two heterotopic cardiac transplant recipients. D = Donor heart QRS complexes R = Recipient heart QRS complexes

so that deterioration of the hearts was detectable. There was concern over decreased function of the native heart after ischemic arrest during surgery, but, so far, we have had no serious problems. Electrocardiography Before closing the chest, temporary pacing wires were inserted into both hearts. It was possible to use these wires to monitor separate electrical activities in difficult situations. Ordinarily, it is easy to identify the QRS complexes of the native and donor hearts, whereby heart rates and identification of arrhythmias can be calculated. Arrhythmias were common in the native heart, provided the donor heart was not rejecting, or in some way affecting the overall condition of the patient. Generally, therefore, we did not treat the arrhythmias known to have originated in the native heart. The electrocardiographic changes during rejection episodes were not reliable even in our orthotopic recipients, but their presence in the donor heart prompted us to perform an endomyocardial biopsy. However, it should be noted that the heart rate on the monitor did not reflect the heart rate of either of the hearts, and was not a direct sum of both heart rates. Accurate rates of each heart were counted by using the electrocardiogram (Fig. 2).

Echocardiography We have used two-dimensional echocardiograms for all our patients in the immediate 228

postoperative period and subsequently during biopsies, especially when donor heart rejection was suspected. Analysis of two-dimensional echocardiograms in all patients and comparison with the postoperative records showed progressive biventricular enlargement and worsening contractility of the recipient heart. The donor heart was seen to improve in contractility, and when rejection started, the contractility diminished. The blood pressure of one of our patients fell suddenly on the second day postoperatively. The central venous pressure also rose, but there was no remarkable change on the heart rates or electrocardiographic pattern. When it was shown that the native heart was supporting the circulation most of the time, two-dimensional echocardiography was done at the bedside because acute donor heart rejection was thought to be present. However, an isoprenaline drip was started, and the repeat two-dimensional echocardiograms showed improved function and restoration of the blood pressure. Subsequent endomyocardial biopsy showed only moderate allograft rejection. In another patient, the arterial line tracings seemed to reflect the function of only one heart most of the time. There was also a suggestion of a clot in the left atrium of the recipient heart. This patient was then started on heparin. There was gradual improvement over the next few weeks, and this may have been similar to the

r

dr

.,_._____

_ ~

\r-/

Fig. 3 Arterial pulse-wave tracings in two heterotopic transplantation patients. Patient A shows good recipient and donor heart function. Patient B shows deteriorating native heart function one month after transplantation. d = donor heart pulse wave. r = recipient (native) heart pulse wave. Vol. 12, No. 3, September, 1985


improvement reported by Barnard et al.4 Since this event took place in the early postoperative period, it is possible that the native heart suffered minor ischemic injury in the period of crystalloid cardioplegic arrest during the transplant. We found two-dimensional echocardiography useful for following events in both the native and donor hearts; however, visualization of the donor right atrium was not always easy. Saline contrast echocardiography was used on one patient, with normal saline injected during screening, and it was easy to follow the echoes generated into the donor right atrium. Radionuclide Angiography We used multigated equilibrium nuclear blood pool scanning with technetium-99m to evaluate the ejection fraction of both left ventricles. On the whole, the ejection fraction of the donor heart increased steadily as it took over most of the work, whereas, that of the native heart failed. Although the ejection fraction of the donor heart fell during rejection episodes, it had no direct relationship on the severity of rejection. We have seen this in some of our recipients who underwent orthotopic transplantation. Their ejection fraction, blood pressure, and other cardiovascular parameters seemed to be normal in the face of severe allograft rejection, as indicated by an endomyocardial biopsy during this period. Arterial Pressure Monitoring We have found the pattern of the arterial pulse wave in the heterotopic cardiac transplant recipient helpful in following the performance of both hearts. It was usually easy to identify the arterial pulse wave generated by either heart. This became difficult when the activity of both hearts was about equal during allograft rejection, but a few maneuvers, such as mild exercise or pacing, solved the problem, along with careful assessment of the electrocardiogram. Usually, the donor heart produced the higher pulse wave, and sometimes a summated large pulse wave was seen (Fig. 3). During periods of acute severe rejection episodes, the native heart pulse wave increased, whereas that of the donor heart decreased. During a severe rejection episode, Texas Heart Institute Journal

the donor heart pulse wave still remained high. However, arterial pulse-wave monitoring was useful in the immediate postoperative period to indicate the events in each heart, and also during periods of known allograft rejection.

Cardiac Catheterization Catheterization of the right heart was done during endomyocardial biopsy - usually percutaneously through the jugular vein or the femoral vein. Due to the manner in which the right atrial anastomosis was done (rather than SVC to SVC as done elsewhere), there was no difficulty in entering the donor right atrium. Therefore, we did not find it necessary to use the left supraclavicular approach to the subclavian vein to gain direct access to the donor

The Evaluation of Cardiac Allograft Rejection By Endomyocardial Biopsy at the Texas Heart Institute (McAllister, H.A. 1985)

No evidence of rejection. Perivascular aggregates of mononuclear cells. 3 Perivascular aggregates of mononuclear cells with extension into the interstitium. 4-8 Interstitial mononuclear cells with cardiac myocyte degeneration of 0 1-2

increasing severity. 9-10

Extensive cardiac myocyte degeneration, interstitial mononuclear cells and polymorphonuclear leukocytes.

Comparison of THI and Stanford Grading of Cardiac Allograft Rejection

0 1

2

Mild

3

4

5

6

7

Moderate

8

9

10

Severe

l1 Fig. 4 The relationship between the new Texas Heart Institute (THI) grading system and the Stanford grading system. 229


right atrium. The pressures in the right atria and ventricles of both hearts were recorded, as were the pulmonary artery pressure and pulmonary wedge pressure. Endomyocardial biopsy specimens were taken from the right ventricular cavity and sent to pathology. The histopathological changes were scored according to a new system developed by our pathology department.7 (The relationship between this new scoring system and the Stanford grading system is shown in Figure 4.) Generally, only moderately severe to severe rejection episodes (5 to 10) were treated.

Radiography, Computerized Tomography and Bronchoscopy Portable chest radiographs (Fig. 5) were adequate initially to evaluate effusions, infiltrates, or atelectasis. In doubtful situations, chest radiographs were done in the radiology department, at times with fluoroscopic thoracentesis. Computerized tomography was useful in following the postoperative course of these patients, especially when there were pulmonary infiltrates. Frequently, because of the presence of the heterotopic heart on the right side, with consequent compression of the right middle lobe, it was not easy on a chest radiograph to delineate all the opacities seen. Computerized tomograms were useful in locating loculated fluid collections that were missed on previous attempts at drainage (Fig. 6). Bronchoscopies to clear the right middle lobe bronchus were performed about 2 to 3 times a week for the first 2 weeks. Thereafter, the patients seemed to tolerate the compressed lobe, and thus far have not required more bronchoscopies.

centers8 9 have done heterotopic cardiac transplantation under different circumstances when orthotopic transplantation would have resulted in disaster or produced very poor results at best. The ability to achieve good, long-term results in such situations has heightened interest in heterotopic transplantations. The major advantage proposed for the heterotopic procedure is that it can be done in the presence of a high pulmonary resistance, since the hypertrophied native right ventricle can still overcome the pulmonary resistance to deliver enough blood to the left heart. Other advantages include the native heart's functioning as an assist device during periods of reversible or irreversible loss, or reduction of donor heart function, such as during severe acute, or chronic rejection episodes. Heterotopic transplantation also allows a heart that is otherwise considered small for a particular recipient to be used, especially in urgent situations. Another advantage is that in cases of acute myocarditis, it is feasible that recovery of the recipient heart may take place with time. In actual fact, it provides psychological uplift to the transplant surgeon and the patient who know that the native heart is still in situ should problems occur with the donor heart. We are certain that the first and second patients would have died if we had waited for the ideal donors. We are also convinced that all three patients would probably have died or experienced very bad postoperative problems

DISCUSSION In many centers, orthotopic cardiac transplantation is the standard operation for endstage cardiac failure from any cause. When Barnard5 reported the advantages of heterotopic transplantation, many people were not convinced that the performance of this operation would be preferred at any time to orthotopic cardiac transplantation. Many 230

Fig. 5 Portable chest X ray of the heterotopic donor heart in the right thoracic cavity. There is also a significant right pleural effusion. Vol. 12, No. 3, September, 1985


Fig. 6 Computerized tomogram of the chest shows the heterotopic heart in the right chest. The loculated effusion in the right pleural cavity was completely emptied with fluoroscopic guidance.

if we had performed orthotopic instead of heterotopic transplantations. We now wonder if some of our patients who died while awaiting a suitable donor could have benefited from heterotopic transplantation. There is no difference between the immunosuppression and management of heterotopic and orthotopic transplantations. Attention is directed toward arterial pulsewave patterns on the monitor during the immediate postoperative period, since this assesses the performance of both hearts. It should be noted that in the resting state, even if the donor heart is not functioning well, the recipient heart may still maintain adequate circulation. The donor heart of our second patient fibrillated in the recovery room while the recipient heart maintained adequate circulation until normal sinus rhythm was restored in the donor heart. As pointed out by Barnard and Losman,j46 this may be a disadvantage, especially when the patient is discharged, because he may not seek help until rejection has progressed to an advanced stage. This is because of the recipient heart's support of the circulation. A treated rejection episode has occurred in only one of the three patients. It was diagnosed on routine biopsy, but there had been no previous clinical signs suggestive of rejection in this patient. Using a few parameters such as arterial pulse-wave patterns, intracardiac pressures and two-dimensional echocardiography, we noted definite evidence of deterioration in the ITxas Heart Institute Journal

function of the recipient heart in one of our patients. Her anticoagulation therapy is being carefully scrutinized, since she may develop blood clots as the recipient heart deteriorates further. The disadvantages of heterotopic transplantation include the risk of emboli, both systemic and pulmonary, from thrombus in the poorly contracting recipient heart chambers; persistent angina due to coronary artery disease; risk of infection due to a prosthesis in the recipient heart; and persistent hemodynamically significant arrhythmias in the recipient heart. To date, we have had clots in the atria that resolved after heparin therapy. The patients receive aspirin and dipyridamole at the present time, and we intend to introduce Coumadin if the recipient heart deteriorates further. Heterotopic transplantation has the same complications as orthotopic transplantation, especially those related to infections by opportunistic organisms. However, the transplant surgeon would feel more comfortable in reducing immunosuppression drastically in the face of a serious infection in a heterotopic recipient than in an orthotopic recipient. In conclusion, after considering the various advantages and disadvantages of heterotopic transplantation, we are convinced that there is a definite place for this procedure in some patients with end-stage cardiac failure. The bitter experience of seeing a potential recipient die for lack of a suitable donor could be avoided in some cases if heterotopic transplantation were performed. The knowledge that there is back-up for either heart is encouraging to the transplant surgeon. The three cases reported here emphasize the importance of this procedure as life-saving in urgent situations. However, we still believe that orthotopic transplantation should be offered to most recipients who require cardiac transplantation.

REFERENCES 1. Cooley DA, Bloodwell RD, Hallman GL, Nora JJ, Harrison GM, Leachman RD. Organ transplantation for advanced cardiopulmonary disease. Ann Thorac Surg 1969; 8:30. 2. Okereke OUJ, Frazier OH, Cooley DA, Waldenberger F, Radovancevic B. Cardiac transplantation: Current results at the Texas Heart Institute. Texas Heart Institute Journal 1984; 11:228-232.

231


3. Novitzky D, Cooper DKC, Barnard CN. The surgical technique of heterotopic heart transplantation. Ann Thorac Surg 1983; 4:476-482. 4. Barnard CN, Barnard MS, Cooper DKC, Curchio CA, Hassoulas J, Novitzky D, Wolpowitz A. The present status of heterotopic cardiac transplantation. J Thorac Cardiovasc Surg 1981; 81:433-439. 5. Barnard CN, Losman JG, Curcio CA, Sanchez HE, Wolpowitz A, Barnard MS. The advantage of heterotopic cardiac transplantation over orthotopic cardiac transplantation in the management of severe acute rejection. J Thorac Cardiovasc Surg 1977; 74:918-924. 6. Losman JG. Review of the Cape Town experience with heterotopic cardiac transplantation. Cardiovascular Diseases, Bulletin of the Texas Heart Institute 1977; 4(3):243-255.

232

7. McAllister HA Jr. A system for grading cardiac allograft rejection. Presented at the Texas Heart Institute's International Symposium on Cardiovascular Surgery, Houston, Texas, September 12-14, 1985. 8. Melvin KR, Pollick C, Hunt SA, McDougall R, Goris ML, Oyer P, Popp RL, Stinson EB. Cardiovascular physiology in a case of heterotopic cardiac transplantation. Am J Cardiol 1982; 49:1301-1307. 9. Emery RW, Copeland JG. Heart transplantation in Arizona. Heart Transplantation 1985; 4:203205.

Vol. 12, No. 3, September, 1985

heterotopic heart transplantation  

articolo trapianto eterotopico cuore

Advertisement