Large coronary arteries in humans are responsive to changing blood flow: An endothelium-dependent mechanism that fails in patients with atherosclerosis

Abstract

Changes in blood flow can alter vasomotion of conduit arteries. This study examined vasomotor responses to incremental blood flow induced by papaverine in the epicardial arteries of 10 patients with angiographically normal coronary arteries (group 1) and in 14 patients with arterial irregularities (group 2) using quantitative angiography and Doppler ultrasound flow velocity measurements. An increase in coronary blood flow of 384.3 ± 32.8% (p < 0.001) in group 1 patients was associated with dilation of the proximal coronary artery segment and a 23.2 ± 4.6% increase in cross-sectional area (p < 0.001). In contrast, in group 2 patients a similar increase in coronary blood flow of 339.3 ± 18.7% (p < 0.001) was associated with mixed responses and a Modest net constriction in cross-sectional area of -7.4 ± 2.8% (p < 0.05). The dilation response to nitroglycerin was intact in group 1 (31.7 ± 4.2%, p < 0.001) and in group 2 (26.4 ± 3.2%, p < 0.001).In five patients from group 1 acetylcholine, an endothelium-dependent dilator, produced an increase in cross-sectional area of 20.7 ± 4.6% (p < 0.05) that paralleled the response to an increase in flow in the same segment (a 24.3 ± 6.1% increase in cross-sectional area, p < 0.05). Five group 21 patients demonstrated a vasoconstrictor response to acetylcholine (a − 22.8 ± 3.4% decrease in cross-sectional area, p < 0.05) together with an impaired dilation response to incremental flow (a − 6.4 ± 3.2% decrease in cross-sectional area). Thus, the normal flow-mediated dilation of coronary arteries is lost in atherosclerosis and this impairment may be due to endothelial cell vasodilator dysfunction.