Myocardial fibrinolytic activity in allogenic cardiac rejection.

The relationship between alterations in myocardial fibrinolytic activity and the degree of graft tolerance or rejection was studied in 22 nonimmunosuppressed heterotopic cardiac transplants in chacma baboons. Fibrinolysis was evaluated on tissue sections and tissue extracts. Fibrinolytic activity was compared with electrocardiographic voltage alterations and multiple myocardial biopsies and terminal heart specimens were examined by light and electron microscopy. Histopathology and reduction in fibrinolytic activity proved superior to electrocardiographic voltage reductions in assessing early cardiac rejection. The two former modalities correlated well with one another. Myocardial histology showed rejection change earlier than fibrinolytic activity reduction.

Evaluation of endomyocardial biopsy in the diagnosis of cardiac rejection. A study using bioptome samples of formalin-fixed tissue.

The reliability of endomyocardial bioptome samples in detecting cardiac rejection was assessed in 26 formalin-fixed previously transplanted hearts. Thirteen human donor hearts (mean postoperative survival 128 days) and 13 baboon donor hearts (mean survival 16.5 days) were studied. Twenty samples were taken under direct vision from the endomyocardium of each heart with an Olympus bioptome catheter. A total of 397 tissue samples was examined "blindly" histologically (177 human and 220 baboon). The bioptome samples were assigned a histological rejection score and then compared with the score accorded multiple tissue sections from the same heart. Sample scores agreed with tissue section scores as follows: humans 86% (samples showed more severe alterations in 5% and less severe in 9%) and baboons 57% (samples more severe in 40% and less severe in 3%). Only 2 false-negative samples were encountered among 285 tissue samples from hearts showing rejection. Changes of rejection were equally distributed between the left and right ventricles. Endomyocardial sampling proved an accurate means of detecting the presence of rejection. In the baboon hearts the endomyocardium tended to show more severe changes than the rest of the myocardium.

Use of a double atrial-triggered standby pacemaker system for a patient with a biventricular bypass heterotopic cardiac homograft.

In a patient who had a biventricular bypass heterotopic cardiac homograft a double atrial-triggered standby pacemaker system was implanted to allow sequential atrial pacing of both hearts. The system design permitted either the recipient or the donor heart to dictate the rate of its fellow, depending on which heart had the faster spontaneous sinus rate at any time. Alternative methods for achieving sequential pacing are discussed.

Changes in indications for heart transplantation. An additional argument for the preservation of the recipient's own heart.

The 1 year survival rate after heart transplantation since 1967 from +/-30% to +/-70%, and the 5 year survival rate is now +/-50%. This improvement has brought renewed interest in this procedure, now done in about twenty centers in eight countries, and increased confidence has widened the indication to patients who are less than terminally ill, to restore quality of life. This trend is illustrated by the Cape Town series, which can be divided into two parts: 10 patients treated by orthotopic heart transplantation (OHT), from 1967 to 1973, and 40 patients treated by heterotopic heart transplantation (HHT), from 1974 to 1981. The HHT group was younger (mean 37 +/- 10 years versus 51 +/- 9 years, p less than 0.001), had been ill for a shorter length of time (mean 3.6 +/- 0.7 years versus 6.6 +/- 1.4 years, p less than 0.091), and were in a lower New York Heart Association (NYHA) class (mean 3.45 +/- 0.11 versus 3.9 +/- 1.0, p less than 0.006). The improved survival is linked to patient selection, progress in management, and switch to HHT, but not to progress in matching between donor and recipient. Since there is no means to predict tolerance of the donor heart, HHT limits the risks from unforseeable mismatch. The recipient's heart is a built-in assist device, maintaining life when the donor heart fails acutely at operation or during acute [three cases] or chronic [two cases] rejection. Had these patients undergone OHT they would have died. Comparing the 10 oldest HHT patients with the OHT series, no difference in pretransplant parameters was found. However, survival of HHT recipients was longer during the critical post-HHT period: at 3 months, p less than 0.011; at 6 months, p less than 0.05. Larger series will separate the effects of progress in management from the intrinsic advantages of HHT. Retaining the recipient's heart is logical and has brought few complications. Survival rate of 40 HHT patients was 73% at 6, 65% at 12, and 51% at 36 months; 85% of survivors are in NYHA Class I. In patients in less than desperate condition, but who refuse to remain cripples, HHT eliminates the growing ethical problem of removing a recipient's heart that may still support the patient.

The advantage of heterotopic cardiac transplantation over orthotopic cardiac transplantation in the management of severe acute rejection.

The major problems with organ transplantation are rejection of the allograft and the side effects of antirejection therapy. This report describes the successful treatment of a patient in whom rejection of the donor heart developed 10 months after implantation. The recipient's own heart had been left intact and was able to support the circulation during the period of rejection. Indications are that the "rest" period of 10 months was beneficial to the myopathic left ventricle of the recipient's heart.

Myocardial surgical revascularization after streptokinase treatment for acute myocardial infarction.

Eighty-six patients admitted with evolving myocardial infarction within 6 hours of symptom onset were treated with streptokinase. Thirty-nine received intracoronary streptokinase, and 47 received intravenous streptokinase. There were no streptokinase-related complications. Twenty-three patients treated with intracoronary streptokinase and 28 patients receiving intravenous streptokinase underwent coronary artery bypass grafting. On admission, 16 patients receiving intracoronary streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and seven had evidence of inferior evolving myocardial infarction. Time from first symptom to intracoronary streptokinase was 4.4 +/- 1.6 hours. In seven patients, intracoronary streptokinase failed to open the obstructed coronary. All developed severe left ventricular hypokinesia in the area supplied by that coronary artery. In spite of recanalization, nine of 14 patients developed severe hypokinesia in the supplied area, and one an apical aneurysm. Four patients developed mild to moderate hypokinesia, and one had no left ventricular damage. On admission, 14 patients receiving intravenous streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and four had evidence of inferior evolving myocardial infarction. Time from first symptom to intravenous streptokinase was 3.2 +/- 1.5 hours. In seven patients, intravenous streptokinase failed to open the coronary, and all developed severe hypokinesia of the supplied area, with formation of apical left ventricular aneurysm in three. In 21 patients, intravenous streptokinase opened the artery. Eighteen angiographies performed 9.6 +/- 7.9 days after therapy showed a normal left ventricle in eight patients, moderate hypokinesia in seven, and severe hypokinesia in three. Time from first symptom to therapy was shorter in the patients receiving intravenous therapy (p less than 0.01). Coronary artery bypass grafting and four resections after left ventricular aneurysm were performed without operative death. Two patients receiving intracoronary therapy died in the hospital, and one died 2 months later from arrhythmias. Freedom from angina and rehabilitation (New York Heart Association Class I) were achieved in 69.5% of patients receiving intracoronary streptokinase and in 75% of patients receiving intravenous streptokinase. Thus streptokinase-induced thrombolysis salvages myocardium, and the intravenous route seems as effective as the intracoronary. Advantages of the former are earlier administration that might increase myocardial salvage, no invasive procedure, and lesser cost.

Normal cardiac function with a hybrid heart.

A left ventricular bypass procedure using a cardiac allograft was performed in a patient with a long history of rheumatic heart disease and two aortic valve replacements. Normal cardiac function was reestablished, and the only problem following transplantation was that of serious arrhythmias involving the recipient heart. Eighteen months after left ventricular bypass bacterial endocarditis which was resistant to medical treatment developed on the aortic prosthesis. The patient underwent operation, the prosthesis was removed, and the recipient left ventricle was partially resected and excluded from the circulation. Since then the patient has been asymptomatic and, at the time of writing three years after cardiac allograft, he is our longest survivor.

Subvalvular left ventricular false aneurysm complicating mitral valve replacement.

Surgical replacement of the mitral valve by a prosthetic valve may lead to localized disruption of atrioventricular continuity resulting from direct surgical trauma or from delayed rupture of the weakened annulus. Such disruption leads to subepicardial hematoma formation that may remain localized if pericardial adhesions are present. Of two patients who suffered this complication, the first died of rupture of the epicardial hematoma. The hemorrhage in the second patient was contained by pericardial adhesions and had organized, thus resulting in a subannular left ventricular false aneurysm. The aneurysm was found incidentally at autopsy after the patient died of cerebral embolism from prosthetic valve thrombi.

Joint transplantation of the heart and lungs. Past experience and present potentials.

The history of experimental and clinical attempts at allogenic transplantation of the heart and lungs is reviewed and the physiological, technical and pathological implications of this procedure are illustrated by the unreported case of a 49 year-old male who underwent cardiopulmonary transplantation for terminal respiratory failure due to chronic obstructive airways disease and cor pulmonale. While there have been dramatic complications, the patient survived 23 days without major signs of cardiopulmonary dysfunction. The surgical technique, the post-operative management and the vicissitudes of this third human cardiopulmonary graft are described and the promises of this method discussed.

Cardiac surgical research and heart transplantation in Papio ursinus.

The use of non-human primates stems from the concern for employing an animal genetically closely related to man. During a 3 year period over 300 baboons were handled in the Cardiac Research Unit and more than 60 heterotopic cardiac transplantations were performed. The baboon presents multiple advantages if compared with the problems arising from the use of the dog or the pig in cardiac surgical experimentation. This experimental work illustrated these advantages and demonstrated that heterotopic cardiac transplantation is a valuable model for treatment of patients in end stage cardiac failure. The procedure has been performed successfully in 16 patients, 12 being presently alive, 1-36 months following transplant.

Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.

Cardiovascular disease is the chief cause of death in technologically advanced countries and accounts for more than 50% of all deaths in the USA. For a patient with end-stage cardiac failure the only treatment presently available is organ replacement, either by transplantation or by the use of a mechanical heart. Transplantation has demonstrated its value: survival of more than 8 years and restoration of a normal quality of life to patients who were in end-stage cardiac decompensation. However, the prospect of routine clinical application of an artificial heart remains distant. The development of a totally implantable artificial heart still presents a series of challenging engineering problems with regard to strict constraints of size, weight, blood-material compatibility, adaptability of output to demand, efficiency and reliability of the power supply, and safety if nuclear fuel is used. The totally artificial heart is presently not an alternative to the cardiac allograft, but could provide short-term support for patients awaiting cardiac transplantation.

Left ventricular bypass.

The removal of the patient's own diseased heart in order to perform a total cardiac transplantation has several disadvantages. A new technique for bypassing the patient's diseased left ventricle by using a cardiac allograft has been developed in our laboratory and applied clinically in 2 patients. This technique carried no direct surgical mortality, and no complications resulting from the patient's own heart being left in situ have been observed thus far. The presence of a second heart lying partly in the anterior mediastinum and partly in the right pleural space appeared to have no deleterious effects. Several advantages over the conventional transplant have been noted and are discussed.

Risk factors in surgical correction of congenital heart defects in early childhood.

The technique of surface-induced hypothermia, circulatory arrest and limited extracorporeal circulation was used in the surgical correction of congenital heart defects in 125 young children. Hospital mortality was 18% and no death could be attributed to the surgical technique. An analysis of risk factors demonstrated that successful corrective surgery was not significantly related to age, body weight or pulmonary vascular obstructive disease. In transposition of the great arteries, the presence of a ventricular septal defect was associated with an increased mortality. Emergency operations performed because of severe hypoxaemia carried a high mortality, especially in patients with tetralogy of Fallot.