Features of Cardiac Allograft Coronary Endothelial Dysfunction

Abstract

The aim of the study was to evaluate the features and mechanism of cardiac allograft coronary endothelial dysfunction. Coronary blood flow and epicardial coronary artery diameter response to intracoronary acetylcholine and N(G)-monomethyl-l-arginine were assessed in 19 cyclosporine-treated heart transplant recipients with normal coronary angiograms (3.8 +/- 2.3 years after transplantation) and compared with 19 age-, gender-, and cardiovascular risk factor-matched nontransplantation control patients with normal coronary angiograms. Heart transplant recipients had more epicardial vasoconstriction in response to intracoronary acetylcholine (mean -16 +/- 19% [SD] vs 4 +/- 10%; p = 0.036). Microvascular endothelial function was similar between groups. Coronary flow reserve in response to adenosine was higher in the transplant group (3.6 +/- 0.8 vs 3.1 +/- 0.7; p = 0.04). The effect of N(G)-monomethyl-l-arginine (64 micromol/min) on coronary blood flow (-16 +/- 21% vs -37 +/- 19%; p = 0.018), coronary artery diameter (-10 +/- 13% vs -21 +/- 11%; p = 0.04), and coronary vascular resistance (34 +/- 40% vs 73 +/- 63%; p = 0.047) was significantly attenuated in the transplant group compared with controls. In conclusion, cardiac allograft epicardial coronary endothelial function was abnormal and may be related to an impaired endogenous NO synthetase pathway and reduced endothelial nitric oxide production in transplant recipients.