ENDOTHELIAL DYSFUNCTION IN HUMAN INTRAMYOCARDIAL SMALL ARTERIES IN ATHEROSCLEROSIS AND HYPERCHOLESTEROLEMIA

Vascular responses of human intramyocardial small arteries were examin ed in vitro to assess the influence of atherosclerosis and risk factor s for coronary artery disease on endothelium-dependent relaxation. Rec ipient hearts were obtained from patients with ischemic (n = 14) and n onischemic (n = 13) cardiomyopathy undergoing heart transplantation. S mall intramyocardial coronary arteries (mean internal diameter 313 +/- 11 mu m) were mounted on a wire myograph for measurement of morpholog y and isometric tension. Vasodilation was examined after preconstricti on with U-46619, a thromboxane A(2) analog. Endothelium-dependent rela xation to acetylcholine and bradykinin was impaired in patients with i schemic compared with nonischemic cardiomyopathy (P < 0.01 and P < 0.0 01, respectively). Endothelium-independent relaxation to sodium nitrop russide was preserved. Incubation with L-arginine (3 mmol/l) did not i mprove endothelium-dependent relaxation to acetylcholine or bradykinin . With the use of stepwise multivariate analysis, hypercholesterolemia , but no other risk factor for atherosclerosis, was independently asso ciated with impaired endothelium-dependent relaxation to acetylcholine (r = -0.50, P = 0.05) but not to bradykinin. Endothelial dysfunction in intramyocardial small arteries may predispose patients with nonobst ructive epicardial atherosclerosis and hypercholesterolemia to myocard ial ischemia.