Multiple endothelial injury in epicardial coronary artery induces downstream microvascular spasm as well as remodeling partly via thromboxane A(2)

OBJECTIVES The study was undertaken to develop a coronary microvascular spa sm model in pigs by repeated epicardial coronary artery endothelial injury. BACKGROUND The pathophysiologic mechanisms responsible for coronary microva scular spasm remain unclear, in large part because a suitable animal model has yet to be found. METHODS Balloon endothelial denudation was done just distal to the site of an implanted Doppler flowmeter in the left anterior descending coronary art ery (LAD) every two weeks for a total of four times. Changes in LAD blood f low by intracoronary administration of vasoactive agents were assessed befo re each denudation. RESULTS In the epicardial LAD endothelial denudation pigs, decreases in LAD blood flow caused by acetylcholine were augmented. Before denudation, it w as -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 respons e to 5-hydroxytryptamine (5-HT) changed from an increase to a decrease, acc ompanied by medial thickening of microvessels in the LAD perfusion area. Th ese flow responses were observed without significant changes in LAD diamete r. In contrast, the LAD blood flow responses to acetylcholine and 5-HT did not change throughout the experiment in pigs given aspirin and a thromboxan e A(2) (TXA(2)) synthase inhibitor orally. CONCLUSIONS This microvascular spasm model indicates that hypersensitivity to vasoactive substances in the microvascular beds as well as microvascular remodeling are brought about partly through TXA(2). This model should be u seful for examining the pathophysiology and treatment of microvascular angi na. (J Am Cell Cardiol 2001;37:308-15) (C) 2001 by the American College of Cardiology.