Effects of the novel thromboxane antagonist Bay U 3405 on experimental coronary artery disease.
Bay U 3405 is a novel thromboxane receptor blocker. The present investigations describe its effects on experimental canine and porcine cardiac damage. In anesthetized dogs, a coronary artery was occluded for 6 hours and reperfused for 30 minutes. Bay U 3405 was administered intravenously 15 minutes after occlusion (1 mg/kg) followed by infusion of 10 mg/kg/hr from 30 minutes after ligature. In a second study, the effects of Bay U 3405 on endoperoxide analogue U-46619-induced coronary constriction were studied in anesthetized, open-chest pigs. Bay U 3405 reduced myocardial infarct expansion by 65% (p less than 0.01) assessed with biochemical staining. Hemodynamics and collateral blood flow were unaffected. However, reperfusion arrhythmias were suppressed. In porcine experiments, 1 mg/kg Bay U 3405, given intravenously or intraduodenally, antagonized U-46619-induced coronary vasoconstriction over 5 hours. The studies demonstrate anti-ischemic and antivasoconstrictor properties of Bay U 3405 probably due to binding to platelet and smooth muscle thromboxane receptors. This may have clinical relevance in angina pectoris and myocardial infarction.
Fiedler
V B
VB
Department of Pharmacology, Bayer AG, Wuppertal, FRG.
Seuter
F
F
Perzborn
E
E
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013552:Swine; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects
D002227:Carbazoles; D011450:Prostaglandin Endoperoxides, Synthetic; D013449:Sulfonamides; D013931:Thromboxanes; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C063119:ramatroban