Experimental hyperhomocysteinemia impairs coronary flow velocity reserve

Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. One mechanism is considered to be deteriorated endothelial function that is recovered by vitamin C. However, its direct action on coronary circulation has yet to be examined. This study was designed to test the hypothesis that experimental acute hyperhomocysteinemia would impair coronary flow velocity reserve (CFR) by increasing oxidative stress. Eleven healthy male volunteers (aged 23.3±0.9 years) were enrolled. CFR induced by intravenous 5′-adenosine triphosphate infusion was measured by transthoracic-Doppler echocardiography. Measurements were taken before and 4 h after administration of a placebo, oral methionine (L-methionine 0.1 g/kg) or oral methionine plus vitamin C (2 g) on 3 separate days. The baseline average diastolic peak velocity (APV) was similar in all 3 groups. In the methionine group, plasma homocysteine increased (12.9±7.0 to 32.1±9.4 nmol/ml, p