Saitoh S, Onogi F, Aikawa K, Muto M, Saito T, Maehara K, Maruyama Y
Fukushima Medical University, Japan.
J Am Coll Cardiol. 2001 Jan;37(1):308-15. doi: 10.1016/s0735-1097(00)01081-0.
The study was undertaken to develop a coronary microvascular spasm model in pigs by repeated epicardial coronary artery endothelial injury.
The pathophysiologic mechanisms responsible for coronary microvascular spasm remain unclear, in large part because a suitable animal model has yet to be found.
Balloon endothelial denudation was done just distal to the site of an implanted Doppler flowmeter in the left anterior descending coronary artery (LAD) every two weeks for a total of four times. Changes in LAD blood flow by intracoronary administration of vasoactive agents were assessed before each denudation.
In the epicardial LAD endothelial denudation pigs, decreases in LAD blood flow caused by acetylcholine were augmented. Before denudation, it was - 15 +/- 4%, and at week 8 (i.e., two weeks after the fourth denudation) it was -100% (i.e., zero flow [p < 0.01]). The LAD flow changes in response to 5-hydroxytryptamine (5-HT) changed from an increase to a decrease, accompanied by medial thickening of microvessels in the LAD perfusion area. These flow responses were observed without significant changes in LAD diameter. In contrast, the LAD blood flow responses to acetylcholine and 5-HT did not change throughout the experiment in pigs given aspirin and a thromboxane A2 (TXA2) synthase inhibitor orally.
This microvascular spasm model indicates that hypersensitivity to vasoactive substances in the microvascular beds as well as microvascular remodeling are brought about partly through TXA2. This model should be useful for examining the pathophysiology and treatment of microvascular angina.
通过反复进行心外膜冠状动脉内皮损伤，建立猪冠状动脉微血管痉挛模型。
冠状动脉微血管痉挛的病理生理机制尚不清楚，很大程度上是因为尚未找到合适的动物模型。
每两周在左前降支冠状动脉（LAD）植入多普勒流量计的部位远端进行一次球囊内皮剥脱术，共进行四次。在每次剥脱术前，评估冠状动脉内给予血管活性药物后LAD血流的变化。
在心外膜LAD内皮剥脱的猪中，乙酰胆碱引起的LAD血流减少增强。剥脱术前，减少率为-15±4%，在第8周（即第四次剥脱术后两周）时为-100%（即血流为零[p<0.01]）。LAD对5-羟色胺（5-HT）的血流变化从增加变为减少，同时LAD灌注区域微血管中层增厚。这些血流反应在LAD直径无明显变化的情况下观察到。相比之下，口服阿司匹林和血栓素A2（TXA2）合酶抑制剂的猪在整个实验过程中，LAD对乙酰胆碱和5-HT的血流反应没有变化。
该微血管痉挛模型表明，微血管床对血管活性物质的超敏反应以及微血管重塑部分是通过TXA2实现的。该模型对于研究微血管性心绞痛的病理生理学和治疗应该是有用的。
