Injury of the coronary endothelium at implantation increases endothelial dysfunction and intimal hyperplasia after heart transplantation

Abstract

Background Coronary endothelial dysfunction occurs early after heart transplantation and predicts the development of intimal thickening characteristic of cardiac allograft vasculopathy. Objectives To assess the effects of removal of the endothelium by balloon injury of coronary arteries of allografts without rupture of the internal elastic lamina at the time of implantation and on coronary endothelial dysfunction, and to assess the development of accelerated atherosclerosis after heart transplantation. Methods A porcine model of heterotopic heart transplantation with preoperative immunologic typing, enabling progressive rejection without immunosuppression, was used to study the effect of endothelial removal on these 2 end points. Endothelium-dependent relaxations of epicardial coronary arteries from allografts submitted to endothelial denudation after harvest, arteries from allografts not undergoing denudation, and native coronary arteries were compared 30 days after graft implantation by using standard organ chamber experiments. Intimal thickening was measured by light microscopy with a semiquantitative scale (0 to 4+ grading). Results Relaxations to serotonin and to bradykinin were significantly decreased in denuded arteries compared with nondenuded allograft arteries. There was a significant increase in the incidence of severe intimal hyperplasia in denuded arteries compared with nondenuded arteries, which were both significantly increased compared to native coronary arteries. Conclusions Endothelial injury at implantation worsens the endothelial dysfunction as a result of rejection after heart transplantation and compounds the intimal thickening leading to cardic allograft vasculopathy. All efforts should be deployed to maintain a morphologically intact and functional endothelium at the time of graft implantation.