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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

View larger version (121K): [in a new window]   Figure 1 Photomicrographs of week 8 coronary arteries stained with hematoxylin-eosin. Large epicardial coronary arteries (top) and downstream microvascular arterioles (middle; 50 µm lumen diameter <150 µm; bottom; lumen diameter <50 µm). Left panel is from the Control group, center panel from the ED group and right panel from the Drug group. In the ED group, thickening of the media and increased perivascular fibrosis are shown. Epicardial coronary arteries in the center and right upper panels show the denuded portions. Scale bars indicate 100 µm.

View larger version (14K): [in a new window]   Figure 2 Scatterplots showing the relation between the averaged values of external elastic membrane (EEM) cross-sectional area (CSA)-to-lumen CSA ratios, and the averaged values of vessel diameter in the Control group (a), the ED group (b) and the Drug group (c). Each point in the plot represents the average of vessels in a 10 µm range of diameters in an individual pig. In the Control and Drug groups, the ratios are relatively constant in coronary arteries of various diameters from 10 to 200 µm, and there was no significant correlation between the averaged values of EEM CSA-to-lumen CSA ratios and the vessel diameters. In the ED group, a significant correlation existed between the EEM CSA-to-lumen CSA ratios and the vessel diameters (y = –0.0001x2 + 0.0230x + 1.6921, r2 = 0.208, p = 0.006).

View larger version (56K): [in a new window]   Figure 3 Representative tracings and coronary angiograms from a pig in the ED group at (a) week 0 (before endothelial denudation) and (b) week 8 (2 weeks after four denudations). Coronary blood flow at week 8 initially decreased to zero flow, and subsequent reactive hyperemia appeared with ECG ST depression in limb lead III after intracoronary administration of 0.05 µg/kg acetylcholine (ACh) without showing epicardial coronary artery vasoconstriction. BP = aortic blood pressure; CBF = coronary blood flow in LAD; ECG = electrocardiogram.

View larger version (27K): [in a new window]   Figure 4 Time-related percent changes in LAD blood flow from the baseline state in response to various vasoactive agents: (a) acetylcholine, 0.05 µg/kg; (b) 5-HT, 1 µg/kg; (c) ISDN, 10 µg/kg; (d) adenosine, 10 µg/kg. Control group (x); ED group (open circle); and Drug group (closed circle) (n = 12, each). Values are means ± SEM. ¥p < 0.01 by two-way ANOVA. p < 0.01 vs. 0 week at the same portion in the same condition. p < 0.01 vs. two weeks at the same portion in the same condition. @p < 0.01 vs. the Control group in the same experimental period. ¶p < 0.01 vs. the Drug group in the same experimental period.