Graft Coronary Disease Research Articles

Cardiac allografts from high-risk donors: Excellent clinical results

Rising waiting list mortality and increasing demand for donor organs have led to extension of traditionally accepted criteria for evaluation of cardiac grafts. From December 1985 to June 1992, 188 cardiac grafts were orthotopically transplanted into 178 recipients. Of these grafts, 38.3% ( 72 / 188 ) were defined as high-risk donors. Risk criteria included prolonged cardiopulmonary resuscitation, age greater than 40 years, high inotrope requirements, undersizing by more than 20% body weight, significant wall motion impairment by echocardiography, elevation of myocardial enzyme levels, and cold ischemia time greater than 4 hours. There were no recipient deaths attributable to primary graft failure in the perioperative period. Operative (30-day), 1-year and 5-year survival was 95.5%, 86.1%, and 77.3%, respectively, in the high-risk group compared with 93.7%, 86.0%, and 67.2%, respectively, in the low-risk donor cohort( p = 0.94). Comparison of duration of postoperative inotrope use, intensive care unit stay, total hospital stay, and in-hospital costs revealed no significant trends favoring either group in postoperative morbidity. Among long-term survivors, development of graft coronary disease was noted in 47.1% ( 24 / 51 ) of the high-risk donor group and only 17.4% ( 12 / 69 ) of the remaining group ( p = 0.0005). Left ventricular ejection fractions in the high risk donor group were 0.58 ± 0.01 at 2 years. Review of this series suggests that selective use of apparently compromised cardiac donors is compatible with excellent cardiac function and survival. Higher incidence of graft vasculopathy may cause significant morbidity during late follow-up.

LATE CYCLOSPORINE TREATMENT AMELIORATES ESTABLISHED CORONARY GRAFT DISEASE IN RAT ALLOGRAFTS

The development of post-transplantation coronary graft disease (CGD) is a major cause of late morbidity and mortality. Recent reports have suggested that CGD is a type of chronic vascular rejection, possibly enhanced by cofactors such as concurrent CMV infection and hyperlipidemia. It remains controversial whether established CGD can be improved by modifications in immunosuppressive therapy. The purpose of this study was to examine whether CsA could reverse or halt the progression of CGD after it was already established. Lewis to Fisher (F-344) heterotopic heart allografts develop CGD resembling human disease. Group 1 (n = 29) had no CsA therapy for chronic rat CMV (RCMV) infection in recipients for 8 weeks before transplant. Group 2 (n = 17) had chronic RCMV infection along with CsA therapy from days 15 to 28 post-transplant. Allografts were killed at 2 and 4 weeks and 90 days post-transplantation. In group 1, leukocyte adhesion to arterial endothelium and intimal hyperplasia were well established at 2 weeks and progressed to stenotic, proliferative arterial lesions at 4 weeks. In group 2, CsA therapy was effective in significantly reversing histologic parameters of vascular rejection such as leukocyte adhesion, intimal proliferation, and periarterial edema at 4 weeks. By 90 days, however, arterial pathology was as severe as in group 1. In conclusion, these results support the hypothesis that CGD is a form of chronic vascular rejection, and once established, can be significantly modified by CsA therapy. These effects are not permanent, and progressive CGD recurs after CsA therapy is discontinued.

Increase in Serum Lipid Peroxide Level and Development of Intimal Proliferation in Graft Coronary Artery after Heart Transplantation in Rats.

Change in serum lipid peroxide level was examined in rats undergoing acute or chronic rejection of heart transplants, in order to clarify the role of lipid peroxides in the development of graft coronary disease. In the rat heart transplantation model under acute rejection conditions, the serum lipid peroxide level of the recipients did not change. While, in the chronic rejection model the level of the recipients significantly increased on the 15th day after the transplantation as compared with that of sham-operated control rats. Light microscopic observations of an allograft on the 15th day after the operation revealed the presence of inflammatory lesions involving infiltration of lymphocytes into the myocardium, edema, and necrosis. On the 22nd day after the operation, intimal thickening in the coronary artery was observed, and it became more remarkable on the 50th day. These results suggest that the increase in serum lipid peroxide level could be one of the signs of graft coronary disease.

Propagation of infiltrating lymphocytes and graft coronary disease in cardiac transplant recipients

The pattern of lymphocyte growth from endomyocardial biopsies in 55 heart transplant recipients was shown to be correlated with the subsequent development of graft coronary disease. Persistent lymphocyte growth was observed in 39 patients, and 15 of these growers (or 41%) developed graft coronary disease. In contrast, only 1 of 15 patients (or 6%) with nongrower biopsies showed subsequent graft coronary disease. Thus, biopsy growth was associated with a higher incidence of subsequent GCD ( p=0.02). A comparison between the group of 15 growers with subsequent graft coronary disease and the 24 growers without subsequent graft coronary disease did not show any differences with respect to patient age, presence of coronary artery disease in the native heart, biopsy histology, donor alloreactivity of biopsy grown lymphocytes, and immunosuppressive drug regimen. On the other hand, the number of treated rejection episodes was significantly lower in the grower group with subsequent graft coronary disease ( p=0.04). These data support the concept that graft coronary disease may involve rejection and that more immunosuppression may lower its incidence. This concept is strengthened by findings showing that alloreactive T cells can be propagated from coronary arteries of cardiac allografts with graft coronary disease.