Aikawa Kazuhiko, Saitoh Shu-Ichi, Muto Mitsuru, Osugi Taku, Matsumoto Ken, Onogi Futoshi, Maehara Kazuhira, Yaoita Hiroyuki, Maruyama Yukio
First Department of Internal Medicine, Fukushima Medical University, Japan.
Coron Artery Dis. 2004 Feb;15(1):21-30. doi: 10.1097/00019501-200402000-00004.
The effect of oxidative stress on coronary microvascular disease is unknown. We investigated whether chronic administration of ascorbic acid (ASC) or glutathione (GSH) prevents microvascular dysfunction and remodeling induced by upstream repeated coronary artery endothelial injury.
Balloon endothelial injury was repeated at the left anterior descending coronary artery (LAD), just distal to an implanted flow meter, every 2 weeks for 6 weeks in pigs. Changes in LAD blood flow induced by acetylcholine (ACh) and 5-hydroxytryptamine were assessed before each endothelial injury and at 8 weeks after the first endothelial injury in pigs without treatment (endothelial injury group, n = 12) and in pigs treated with oral ASC (3 g/day) (ASC group, n = 12) and ASC (3 g/day) plus GSH (1 g/day) (ASC + GSH group, n = 12).
In the endothelial injury group, reduced blood flow in response to ACh was augmented from a decrease of 18 +/- 17% to a decrease of 100% (that is, zero flow, 8 weeks, P < 0.01), accompanied by an increase of ascorbyl free radicals (AFRs) in coronary sinus blood. In contrast, in the ASC + GSH group, blood flow response to ACh was altered to a decrease of 45 +/- 17% (8 weeks, P < 0.01 compared with the endothelial injury group), coronary sinus blood AFRs did not change (8 weeks, 21.4 +/- 12.5 signal intensities, P < 0.01 compared with the endothelial injury group) and the rate of platelet aggregation induced by adenosine diphosphate was small (8 weeks, 56 +/- 17%, P < 0.01 compared with the endothelial injury group).
Chronic administration of antioxidants suppressed microvascular hypercontraction, suggesting that it may be a promising therapeutic strategy for treating coronary microvessel disorders, including microvascular angina.
氧化应激对冠状动脉微血管疾病的影响尚不清楚。我们研究了长期给予抗坏血酸（ASC）或谷胱甘肽（GSH）是否能预防上游反复冠状动脉内皮损伤所致的微血管功能障碍和重塑。
在猪的左前降支冠状动脉（LAD），于植入流量计的远端每2周重复进行一次球囊内皮损伤，共持续6周。在未治疗的猪（内皮损伤组，n = 12）、口服ASC（3 g/天）的猪（ASC组，n = 12）以及口服ASC（3 g/天）加GSH（1 g/天）的猪（ASC + GSH组，n = 12）中，在每次内皮损伤前及首次内皮损伤后8周评估乙酰胆碱（ACh）和5 - 羟色胺诱导的LAD血流变化。
在内皮损伤组，对ACh反应的血流减少从18±17%增加至100%（即零血流，8周，P < 0.01），同时冠状窦血中抗坏血酸自由基（AFRs）增加。相比之下，在ASC + GSH组，对ACh的血流反应变为减少45±17%（8周，与内皮损伤组相比P < 0.01），冠状窦血AFRs未改变（8周，21.4±12.5信号强度，与内皮损伤组相比P < 0.01），且二磷酸腺苷诱导的血小板聚集率较小（8周，56±17%，与内皮损伤组相比P < 0.01）。
长期给予抗氧化剂可抑制微血管过度收缩，提示这可能是治疗包括微血管性心绞痛在内的冠状动脉微血管疾病的一种有前景的治疗策略。
