Yamashita Kazuhito, Tasaki Hiromi, Nagai Yoshitaka, Suzuka Hiroshi, Nihei Shun-ichi, Kobayashi Kengo, Horiuchi Masataka, Nakashima Yasuhide, Adachi Tetsuo
The 2nd Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitayushu 807-8555, Japan.
Int J Cardiol. 2005 Sep 30;104(2):163-9. doi: 10.1016/j.ijcard.2004.10.026.
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<0.0001), while APV under hyperemic conditions (APV-hyp) and CFR significantly decreased (87.2+/-11.4 cm/sec and 4.02+/-0.70 to 73.2+/-10.2 cm/sec and 3.35+/-0.52, p=0.0022 and 0.0030, respectively). Moreover, there was a significant inverse correlation between the plasma homocysteine and CFR (r=-0.620, p=0.0021). However, upon simultaneous administration of vitamin C, APV-hyp and CVR did not decrease despite an elevation in plasma homocysteine.
Experimentally induced acute hyperhomocysteinemia significantly decreased CFR, and this decrease was significantly reversed by vitamin C administration. Oxidative stress is suggested to play a major role in the deleterious effects of homocysteine on the coronary microcirculation.
高同型半胱氨酸血症已被确认为冠状动脉疾病的一个独立危险因素。一种机制被认为是内皮功能恶化，而维生素C可使其恢复。然而，其对冠状动脉循环的直接作用尚未得到研究。本研究旨在验证实验性急性高同型半胱氨酸血症会通过增加氧化应激损害冠状动脉血流速度储备（CFR）这一假说。
招募了11名健康男性志愿者（年龄23.3±0.9岁）。通过经胸多普勒超声心动图测量静脉注射三磷酸腺苷诱导的CFR。在3个不同日期分别于服用安慰剂、口服蛋氨酸（L-蛋氨酸0.1 g/kg）或口服蛋氨酸加维生素C（2 g）之前和之后4小时进行测量。
所有3组的基线平均舒张期峰值速度（APV）相似。在蛋氨酸组中，血浆同型半胱氨酸升高（12.9±7.0至32.1±9.4 nmol/ml，p<0.0001），而充血状态下的APV（APV-hyp）和CFR显著降低（87.2±11.4 cm/秒和4.02±0.70至73.2±10.2 cm/秒和3.35±0.52，p分别为0.0022和0.0030）。此外，血浆同型半胱氨酸与CFR之间存在显著的负相关（r=-0.620，p=0.0021）。然而，同时服用维生素C时，尽管血浆同型半胱氨酸升高，APV-hyp和CVR并未降低。
实验性诱导的急性高同型半胱氨酸血症显著降低了CFR，而维生素C给药可显著逆转这种降低。氧化应激被认为在同型半胱氨酸对冠状动脉微循环的有害作用中起主要作用。
