J.P. Scott

HEART-LUNG TRANSPLANTATION FOR CYSTIC FIBROSIS

Abstract 13 patients with severe lung disease and cor pulmonale from cystic fibrosis were accepted for heart-lung transplantation (HLT). 6 have had the operation, of whom 5 are well, with normal lung function, 3-29 months after operation. 1 patient died from adult respiratory distress syndrome after reoperation to control persistent chest-wall bleeding: at necropsy, this patient proved to have cirrhosis. Respiratory tract infections and acute lung rejection after HLT for cystic fibrosis were no more common than in other HLT patients. Of the 7 patients for whom suitable donor organs were not found, 3 died within 3 months of assessment. Initial severity of disease had been similar to that in the transplant group. The cost of assessment, operation, and 1 years treatment after HLT is similar to that of medical treatment for such patients.

Primary pulmonary hypertension: diagnosis, medical and surgical treatment

Primary pulmonary hypertension continues to present both diagnostic and therapeutic challenges to the physician, reflecting the lack of understanding about the basic mechanism of the disease. The natural history of the condition has been described only recently, and this has allowed a reasonably accurate prognosis for the individual patient to be determined. New treatments have been found effective, including heart-lung transplantation, which can now offer improved survival. Long-term intravenous infusion of prostacyclin has a place in the treatment of severely affected patients awaiting heart-lung transplantation. However, the major impact of prostacyclin has been, perhaps, to concentrate research upon the role of the endothelial cell in the development of this disorder, in particular the potential role of an impairment of release of the recently described endothelium-derived relaxing factor in certain forms of pulmonary hypertension. We have attempted in this review to focus on the problems of diagnosis and treatment together with current developments in the understanding of primary pulmonary hypertension.

Diagnosis of Early Cardiac Transplant Rejection by Fall in Evoked T Wave Amplitude Measured Using an Externalized QT Driven Rate Responsive Pacemaker

Reliable diagnosis of cardiac ailograft rejection is at present only possible using endomyocardial biopsy. We have serially measured epicardial evoked T wave amplitude during ventricular pacing with an externalized QT driven rate responsive pacemaker telemetered to a TP2 analyzer in 13 patients (12 males) followed for 19 (14–26) days after transplantation. A total of 228 records were analyzed. Rejection was defined on endom‐yocardial biopsy. On 17 of the 31 occasions on which biopsy was performed during the study, specimens showed significant (moderate) rejection. In 11 patients the initial biopsy proven rejection episode was associated with a significant fall in the evoked T wave amplitude from 1.3 (0.7–2.3) mV to 0.6 (0.5–1.8) mV (P < 0.005), which began 2 (1–4) days earlier. One patient with uncontrolled diabetes mellitus had no change in evoked T wave amplitude during rejection. The evoked T wave amplitude did not fall in the absence of histologic rejection. These results suggest a noninvasive method for detecting cardiac rejection, which appears both sensitive (92%) and specific (100%) in the first rejection episodes.

Cardiac transplant waiting lists, donor shortage and retransplantation and implications for using donor hearts

Abstract Cardiac transplantation is established as the standard therapy for end-stage heart failure. 1 The shortage of donors is the limiting factor in heart transplantation. 2 Much emphasis has been placed on increasing donor referrals 3 and appropriate management of potential donors to widen the donor pool. 4 An alternative approach is to examine potential cardiac transplant recipients and identify patient subgroups with poor survival. We assessed the impact of donor shortage on the mortality of patients awaiting operation.

Effects of the immunosuppressant cyclosporine on the circulation of heart transplant recipients

The effect of cyclosporine on the systemic circulation and on heart rate is unknown for heart transplant recipients. Thirty-four heart transplant recipients were studied by right-sided cardiac catheterization after endomyocardial biopsy. A direct linear relation was found between systemic and pulmonary vascular resistance and cyclosporine trough blood levels, which were negatively related to heart rate. The effect of cyclosporine on pulmonary vascular resistance, however, was not statistically significant by multivariate analysis when patient age was considered. In contrast, renal function appeared unrelated to systemic vascular resistance or heart rate. It appears that cyclosporine trough blood levels may have a direct effect on systemic vascular resistance as well as an unexplained negative chronotropic effect on heart rate.

Transplantation of the lungs

Over the last eight years a completely new form of treatment has been introduced for end-stage pulmonary vascular disease and chronic lung disease, including cystic fibrosis. Lung transplantation and heart-lung transplantation have moved from an experimental and innovative stage to clinical treatments. The exclusion criteria for selecting potential recipients have become relaxed whilst preservation techniques have improved to allow ischaemic times of donor organs to be extended beyond 4 h. Monitoring of graft function with daily spirometry and use of transbronchial lung biopsy have enabled early diagnosis of lung rejection or infection and thus effective treatment. Lung transplantation and heart-lung transplantation, by their success, are providing new insight into lung disease and pulmonary physiology.

Cardiac and lung transplantation.

The lirst successful clinical cardiac transplant was performed by Christian Barnard in Cape Town, South Africa, in 1967. After a flurry of activity worldwide, poor Initial results limited the use of this technique. Several further developments were necessary before the procedure could be applied more widely. During the 197Os, further work, principally at Stanford Hospital in California, established improvements in patient management related to the detection and treatment of rejection. These included the use of repeated cardiac biopsy to detect cardiac allograft rejection and the use of anti-thymocyte globulin. In addition, the legal definition of brain death became accepted in several countries and methods for long-distance organ retrieval were successfully developed.

The Management of Cytomegalovirus Infection in Heart-Lung Transplant Recipients

In the 1980s heart-lung transplantation (HLT) [1, 2], evolved from an experimental and innovative stage to a clinical treatment. Despite improvements in survival and understanding of pathogenesis of the lung disease in HLT recipients, cytomegalovirus (CMV) infection remains an important cause of death and morbidity. Donor-acquired primary CMV disease may be effectively prevented by prospective donor and recipient matching. Considerable progress has been made in the diagnosis of CMV pneumonia by the use of trans-bronchial lung biopsy (TBB), and the antiviral drug ganciclovir provides effective treatment of reactivation or reinfection. However, the mechanisms and immunological response to CMV infection in this patient population remain poorly understood.

The Ethics of Domino Heart Transplantation

Domino transplantation provides a further source of hearts for transplantation (Dark 1990; Baumgartner 1989; Cavarrochi 1989). It is essential that neither donors nor recipients are disadvantaged as a result of this practice (Sutor 1988; Rhenman 1989). We have studied the first 28 donors and recipients of the domino procedure at our institute and compared them with comparable groups of heart-lung and heart transplant recipients not involved in the domino procedure. Comparison was made of ischaemic time of in-house and distant procurement hearts, of ischaemic time for donors and non-donors of domino hearts, time in hospital and early survival figures at 3 months after transplantation.

Cardiac Retransplantation: Is It an Ethical Use of Scarce Resource?

Cardiac transplantation is established as the standard therapy for end-stage heart failure.The acute shortage of donors is the limiting factor preventing its wider application at present (Wallwork 1989). Regular audit is necessary to ensure that the best potential is being realised from each organ. We assessed the impact of donor shortage on our cardiac transplant programme. We also noted that retransplanted patients had a particularly poor outcome and attempted to identify preventable risk factors.