PHARMACOLOGICAL ACTIVATION OF THE HUMAN CORONARY MICROCIRCULATION IN-VITRO - ENDOTHELIUM-DEPENDENT DILATION AND DIFFERENTIAL RESPONSES TO ACETYLCHOLINE

Objectives: In vivo studies of the human coronary resistance circulati on cannot control for indirect effects of myocardial metabolism, compr ession, and neurohumoral influences. This study directly examined the vasodilator responses of the human coronary microcirculation to both r eceptor-dependent and -independent agonists. Methods: Atrial arteriole s were dissected from human right atrial appendage (103 +/- 2 mu m dia meter, n = 185 vessels from 145 patients) obtained at the time of card iopulmonary bypass and left ventricular vessels from explanted human h earts (148 +/- 10 mu m diameter, n = 57 vessels from 18 patients). Aft er dissection, vessels were mounted onto pipettes in Kreb's buffer und er conditions of zero flow and at a constant distending pressure of 60 mmHg. Drugs were applied extraluminally and steady state changes in d iameter measured with videomicroscopy. Results: After contraction by e ndothelin or spontaneous tone, increasing concentrations of adenosine diphosphate (ADP) produced a similar dose-dependent dilation in vessel s from atria (maximum 89 +/- 4%, n = 76) and ventricles (maximum 74 +/ - 9%, n = 10). The dilation to ADP was abolished by mechanical removal of the endothelium. Similar dilator responses were found to bradykini n, substance P, arachidonic acid, and the calcium ionophore A23187 in both atria and ventricle. In contrast, acetylcholine (ACh) constricted all atrial vessels (-58 +/- 3%, n = 63) regardless of patient age or underlying disease. This constriction was attenuated by denudation, bu t not affected by inhibition of nitric oxide synthase or cyclo-oxygena se. Microvessels isolated from human ventricle exhibited a heterogeneo us response to ACh with dilation being the predominant response. Concl usions: We conclude that isolated human coronary arterioles demonstrat e endothelium-dependent dilation. However, the response to acetylcholi ne is unique with vasoconstriction in atrial vessels and dilation in v entricular arterioles. (C) 1998 Elsevier Science B.V. All rights reser ved.