S. Saitoh et al., Multiple endothelial injury in epicardial coronary artery induces downstream microvascular spasm as well as remodeling partly via thromboxane A(2), J AM COL C, 37(1), 2001, pp. 308-315
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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