DISCORDANT EPICARDIAL AND MICROVASCULAR ENDOTHELIAL RESPONSES IN HEART-TRANSPLANT RECIPIENTS EARLY AFTER TRANSPLANTATION

Background: Cardiac allograft vasculopathy represents the leading caus e of death in heart transplant recipients who survive more than 1 year . Functional endothelial abnormalities are sensitive measures of the e arly development of cardiac allograft vasculopathy, but the relative i mportance of large and small coronary vessel abnormalities has not bee n evaluated. The purpose of the study was to distinguish between large and small coronary endothelial dysfunction in patients early after he art transplantation and to test the hypothesis that microvascular endo thelial responses can be preserved in the presence of epicardial endot helial dysfunction. Methods: Changes in epicardial lumen area and coro nary artery blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneous ly by use of an intravascular ultrasound catheter positioned over a Do ppler flow wire in the left anterior descending coronary artery. The c ombination of these techniques allowed distinction between large and s mall coronary vascular responses. In 19 patients studied early after t ransplantation, adenosine (16 and 32 mu g), acetylcholine (5.4 and 54 mu g), and nitroglycerin (200 mu g) were infused, with continuous intr avascular ultrasound imaging and Doppler velocity measurements. Result s: Acetylcholine induced paradoxical epicardial vasoconstriction in 12 of 19 patients (73% +/- 6% of baseline); vasodilation occurred in 7 ( 108% +/- 3%). In spite of this constriction, coronary artery flow incr eased in all 19 patients, to the same extent in patients with constric tion and those with dilation (239 +/- 26 vs 193 +/- 20, p = 0.38). Ade nosine and nitroglycerin increased area (107% +/- 1% and 112% +/- 3%) and flow (258% +/- 17% and 197% +/- 11%) in all patients. None of the area or flow responses correlated with the degree of intimal thickenin g. Conclusions: Acetylcholine increased coronary artery flow early aft er transplantation, indicating preserved microvascular responses in sp ite of epicardial vasoconstriction. Simultaneous measurement of area a nd velocity responses, by permitting evaluation of the relative contri bution of epicardial and microvascular vessels, may offer unique insig hts into coronary endothelial function.