Discordant epicardial and microvascular endothelial responses in heart transplant recipients early after transplantation

Abstract

Background: Cardiac allograft vasculopathy represents the leading cause of death in heart transplant recipients who survive more than 1 year. Functional endothelial abnormalities are sensitive measures of the early development of cardiac allograft vasculopathy, but the relative importance of large and small coronary vessel abnormalities has not been evaluated. The purpose of the study was to distinguish between large and small coronary endothelial dysfunction in patients early after heart transplantation and to test the hypothesis that microvascular endothelial responses can be preserved in the presence of epicardial endothelial dysfunction.

Methods: Changes in epicardial lumen area and coronary artery blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneously by use of an intravascular ultrasound catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these techniques allowed distinction between large and small coronary vascular responses. In 19 patients studied early after transplantation, adenosine (16 and 32 microg), acetylcholine (5.4 and 54 microg), and nitroglycerin (200 microg) were infused, with continuous intravascular ultrasound imaging and Doppler velocity measurements.

Results: 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 increased in all 19 patients, to the same extent in patients with constriction and those with dilation (239 +/- 26 vs 193 +/- 20, p = 0.38). Adenosine 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 thickening.

Conclusions: Acetylcholine increased coronary artery flow early after transplantation, indicating preserved microvascular responses in spite of epicardial vasoconstriction. Simultaneous measurement of area and velocity responses, by permitting evaluation of the relative contribution of epicardial and microvascular vessels, may offer unique insights into coronary endothelial function.