Mitsuru Muto

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

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.

Effects of antioxidants on coronary microvascular spasm induced by epicardial coronary artery endothelial injury in pigs.

ObjectivesThe effect of oxidative stress on coronary microvascular disease is unknown. We investigated whether chronic administration of ascorbic acid (ASC) or glutathione (GSH) prevents microvascular dysfunction and remodeling induced by upstream repeated coronary artery endothelial injury. MethodsBalloon endothelial injury was repeated at the left anterior descending coronary artery (LAD), just distal to an implanted flow meter, every 2 weeks for 6 weeks in pigs. Changes in LAD blood flow induced by acetylcholine (ACh) and 5-hydroxytryptamine were assessed before each endothelial injury and at 8 weeks after the first endothelial injury in pigs without treatment (endothelial injury group, n=12) and in pigs treated with oral ASC (3 g/day) (ASC group, n=12) and ASC (3 g/day) plus GSH (1 g/day) (ASC+GSH group, n=12). ResultsIn the endothelial injury group, reduced blood flow in response to ACh was augmented from a decrease of 18±17% to a decrease of 100% (that is, zero flow, 8 weeks, P<0.01), accompanied by an increase of ascorbyl free radicals (AFRs) in coronary sinus blood. In contrast, in the ASC+GSH group, blood flow response to ACh was altered to a decrease of 45±17% (8 weeks, P<0.01 compared with the endothelial injury group), coronary sinus blood AFRs did not change (8 weeks, 21.4±12.5 signal intensities, P<0.01 compared with the endothelial injury group) and the rate of platelet aggregation induced by adenosine diphosphate was small (8 weeks, 56±17%, P<0.01 compared with the endothelial injury group). ConclusionsChronic administration of antioxidants suppressed microvascular hypercontraction, suggesting that it may be a promising therapeutic strategy for treating coronary microvessel disorders, including microvascular angina.

Syncope at sleep onset in a patient with nasopharyngeal carcinoma

SummaryA patient with nasopharyngeal carcinoma developed atypical parapharyngeal-lesion syncope syndrome associated with stereotypical cycles of heart rate variation, which occurred only when he was drowsy before falling asleep. Vagal tone fluctuation is implicated.