Comparison of coronary endothelial dysfunction in the working and nonworking graft in porcine heterotopic heart transplantation

Abstract

Background. The nonworking heterotopic heart transplantation model has been used extensively for the study of rejection and coronary endothelial function in different species. The effect of left ventricular loading in a working heart transplantation model, which may be associated with different coronary flow patterns and local nitric oxide release, on the development of coronary endothelial dysfunction and intimal hyperplasia, is unknown. Methods. Porcine retroperitoneal "nonworking" heterotopic transplantations (n=10) and "working" heart (with left ventricular filling) transplantations (n=7) were performed. The left ventricular pressure was 0±0 mm Hg and 91±11 mm Hg in the nonworking and working groups, respectively. In the latter, the left ventricle to systemic arterial pressure ratio was 0.76±0.08. Results. Sixty days after transplantation, epicardial coronary arteries from working and nonworking allografts developed a comparable selective endothelial dysfunction of Gi-protein mediated relaxations. There were no statistically significant differences in the prevalence of intimal hyperplasia, but the severity of intimal hyperplasia was significantly greater in allograft coronary arteries from the working hearts. Conclusion. Working heterotopic allografts develop an endothelial dysfunction comparable with that of nonworking allografts, which validates the use of the simpler nonworking graft for the study of endothelial function. The similar prevalence of intimal hyperplasia with the development of more severe coronary lesions in working hearts may be due to differences in local nitric oxide release in these two models.