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EXPERIMENTAL STUDY

Multiple endothelial injury in epicardial coronary artery induces downstream microvascular spasm as well as remodeling partly via thromboxane A₂

^a Fukushima Medical University, Fukushima, Japan

Manuscript received May 2, 2000; revised manuscript received August 15, 2000, accepted September 28, 2000.

Reprint requests and correspondence: Dr. Yukio Maruyama, First Department of Internal Medicine, Fukushima Medical University, 1-Hikari-ga-oka, Fukushima, 960-1295, Japan
maruyama{at}fmu.ac.jp

OBJECTIVES

The study was undertaken to develop a coronary microvascular spasm model in pigs by repeated epicardial coronary artery endothelial injury.

BACKGROUND

The pathophysiologic mechanisms responsible for coronary microvascular 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 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.

RESULTS

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.

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 TXA₂. This model should be useful for examining the pathophysiology and treatment of microvascular angina.

Abbreviations and Acronyms   ADP = adenosine diphosphate   ECG = electrocardiogram   ED group = repeated LAD endothelial denudation group   5-HT = 5-hydroxytryptamine   ISDN = isosorbide dinitrate   LAD = left anterior descending coronary artery   LCA = left coronary artery   L-NAME = N-nitro-L-arginine methyl ester   PRP = platelet-rich plasma   TXA2 = thromboxane A2   TXB2 = thromboxane B2

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