Inhibitory effects of a novel antiplatelet aggregating agent, E-5510, on cyclic flow variations in electrically stimulated coronary arteries of the pig.
We examined the inhibitory effects of a novel antiplatelet aggregating agent, E-5510, on cyclic flow variations (CFVs) of coronary blood flow (CBF) in anesthetized open-chest pigs. These CFVs, which are characterized by progressive declines in CBF followed by sudden restoration of flow, were initiated by electrical stimulation of the intimal surface of the left circumflex coronary artery (LCX). A reduction in CBF to zero during CFVs was accompanied by ischemic changes in the surface electrocardiogram and regional segment shortening of the left ventricular wall. Occlusive thrombi were detected postmortem in the coronary arteries of the animals in which CFVs had occurred. After CFVs had been observed for 1 h, E-5510 (0.01 or 0.1 mg/kg) or saline was administered intravenously. Once CFVs were initiated, both the frequency and the severity (the mean of the three lowest nadirs of CBF) were unchanged by the administration of saline. E-5510 at 0.01 mg/kg decreased the frequency of CFVs from 7.7 +/- 0.9 to 4.6 +/- 1.1 CFV s/h (n = 7, p less than 0.05), and increased the mean lowest nadir from 13.5 +/- 5.2% of the CBF level before electrical stimulation to 54.3 +/- 11.1% (n = 7, p less than 0.01). E-5510 at 0.1 mg/kg further decreased the frequency from 8.9 +/- 0.7 to 2.4 +/- 0.5 CFVs/h (n = 9, p less than 0.01), and increased the mean lowest nadir from 14.3 +/- 3.2% to 53.6 +/- 10.8% (n = 9, p less than 0.01). E-5510, however, showed no ameliorative effect on ischemia-induced myocardial dysfunction, as expressed by the decrease in regional myocardial shortening.(ABSTRACT TRUNCATED AT 250 WORDS)
Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
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Adachi
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Fujimori
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Shoji
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003328:Coronary Thrombosis / Q000188:drug therapy; D004558:Electric Stimulation; D004562:Electrocardiography; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013552:Swine
D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D005996:Nitroglycerin; C054678:Satigrel