Inhibition of graft coronary arteriosclerosis after heart transplantation.

Graft coronary arteriosclerosis (GCA) is the leading cause of long-term mortality after heart transplantation (HTx). The goal of this study was to demonstrate that inhibition of immunemediated injury by cyclosporine (CsA) protects the allograft from GCA. ACI-to-Lewis rat allografts were disparate in major and nonmajor histocompatibility loci. Isografts (Lewis-Lewis) were controls. Treatment groups received either olive oil or CsA at 2.5, 5, 10, or 20 mg/kg/day for 3 months. Histology (elastin) and immunohistochemistry using monoclonal antibodies to CD4, CD8, CD45R, RT1B, CD11b/c, CD25, and alpha-actin was performed to examine the epicardial and intramyocardial coronary arteries. Computerized image morphometry was utilized to measure intimal and medial thickness and area. Rats receiving olive oil or CsA at 2.5 mg/kg/day had severe rejection and no graft survival. CsA at 5 mg/kg/day resulted in less severe rejection with significant intimal and medial proliferation (P < 0.001). CsA at 10-20 mg/kg/day paralleled Lewis-Lewis isograft outcomes and inhibited arteriosclerotic vascular changes in the allograft (P < 0.001). Perivascular T-helper cells and macrophages were a characteristic finding with low-dose CsA but rare with higher CsA doses. In this new model of accelerated GCA in rats, immune-mediated antigen-dependent vasculopathy as a result of inadequate immunosuppresion is fundamental in the development of GCA, which appeared equally in epicardial arteries and intramyocardial arterioles. CsA prevents GCA in a dose-dependent fashion in the rat allograft.

Heart transplantation with donors fifty years of age and older.

OBJECTIVE: Limited availability of donor organs has led to the progressive expansion of the criteria for donor selection, particularly a higher age limit of potential donors. We retrospectively reviewed the outcomes of patients who underwent heart transplantation using cardiac allografts 50 years of age and older and compared them with patients who had donor organs younger than 50 years. METHOD: Between September 1989 and May 2000, 20 patients underwent orthotopic heart transplantation using donor hearts 50 years of age and older (range 50-56 years, mean 52.7 +/- 1.8 years) and were compared with 267 patients who received donor organs less than 50 years of age (range 9-49.9 years, mean 27.2 +/- 8.6 years). Patient and donor criteria were identical in both groups. Follow-up was 4 to 128 months with a mean of 37.4 +/- 2.8 months in the older donor group and 52.6 +/- 2.4 months in the younger donor group. RESULTS: There were no differences between these 2 cohorts of patients regarding age, sex, cardiomyopathy, preoperative cytomegalovirus status, New York Heart Association class, and transplant status at transplantation. Donor characteristics, including sex, left ventricular ejection fraction, diabetes, cytomegalovirus status, and allograft ischemic times, were also similar in the 2 groups. Donor/recipient cytomegalovirus matching showed no differences as well. Thirty-day or to discharge operative mortality was similar in the older and younger donor groups (5% +/- 4.8% vs 3.5% +/- 1.1%; P =.84). Actuarial survival at 1 and 5 years was also similar in both groups (89.7% +/- 6.9% vs 91% +/- 1.8% and 53.1% +/- 14.7% vs 71.0% +/- 3.1%, respectively; P =.59). No patient in the older donor group required coronary artery bypass grafting or retransplantation during the follow-up period, whereas 2 patients in the younger donor group required coronary artery bypass, and 5 patients underwent retransplantation (P > or =.50). Two patients in the older donor group died of nonspecific allograft failure, whereas 3 patients in the younger donor group experienced similar posttransplant complication (P > or =.50). CONCLUSIONS: Carefully selected donor hearts 50 years of age and older can be used for heart transplantation with long-term survival and related outcomes similar to those of younger donor organs. This use of selective cardiac allografts maximizes donor organ usage and expands the donor pool effectively without an adverse impact on long-term results.