Simultaneous intracoronary ultrasound and Doppler flow studies distinguishflow-mediated from receptor-mediated endothelial responses

Abnormalities in vascular endothelial function, which occur early In athero sclerosis, may play an etiologic role in the development of the disease or represent a marker for the extent of atherosclerosis. Endothelial dysfuncti on, usually characterized by demonstration of decreased endothelium-depende nt vasorelaxation, may be a sensitive and specific method to detect vascula r disease in its earliest stages. In this context, separation of abnormalit ies in receptor-mediated and flow-mediated endothelium-dependent vasodilato ry responses may allow for the most accurate characterization of endothelia l dysfunction. In 35 patients undergoing routine annual cardiac catheteriza tion after heart transplantation, changes in epicardial lumen area and coro nary blood flow in response to intracoronary administration of adenosine, a cetylcholine, and nitroglycerin were measured simultaneously using an intra vascular ultrasound (IVUS) catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these tech niques allowed for distinction between receptor-mediated and flow-mediated endothelium-dependent vascular responses. Peak flow with the endothelium-in dependent resistance vessel dilator adenosine occurred at 18 +/- 2 sec; the maximal lumen area response occurred later, at 43 +/- fl sec (P < 0.001). Acetylcholine, an endothellum-dependent small- and large-vessel vasodilator , caused an immediate increase in both flow and lumen area, but a second pe ak of dilation was observed, and maximal area occurred 46 sec after maximal flow (54 +/- 14 vs. 100 +/- 26 sec, P < 0.001). Simultaneous IVUS and Dopp ler flow measurements after infusion of vasoactive agents allows for distin ction between and evaluation of the relative contribution of agonist-mediat ed and flow-mediated responses, which may offer important and unique insigh ts into coronary endothelial function. (C) 1999 Wiley-Liss, Inc.