Effects of a thromboxane synthetase inhibitor, Y-20811, on infarct size, neutrophil accumulation, and arrhythmias after coronary artery occlusion and reperfusion in dogs.
To examine effects of a new thromboxane synthetase inhibitor, Y-20811, on infarct size, neutrophil accumulation, and arrhythmias, coronary artery was occluded for 90 min and reperfused for 6 h in anesthetized dogs. Y-20811 administered intravenously (i.v.) 30 min before occlusion decreased serum thromboxane B2 (TBX2) formation by 98% 30 min later and by 79% at 6 h after reperfusion. Ventricular fibrillation (VF) developed in 1 of 15 control and 3 of 10 treated dogs during occlusion (p = NS), whereas after reperfusion it occurred in 7 of 14 control and none of seven treated dogs (p < 0.05). The number of arrhythmias during the first hour of reperfusion was significantly reduced in treated dogs (134 +/- 74 beats/min in control vs. 14 +/- 4 beats/min in treated dogs, p < 0.05). Hemodynamics, area at risk, and collateral flow to the ischemic region were similar for the two groups. The extent of myocardial necrosis was 28.0 +/- 10.0% (n = 7) of the area at risk in control dogs and 27.6 +/- 6.2% (n = 7) in treated dogs (p = NS). The relation between the ratio of myocardial necrosis to area at risk and collateral flow was similar. The degree of neutrophil accumulation did not differ but correlated with infarct size (r = 0.85). Thus, Y-20811 reduced reperfusion arrhythmias but failed to limit infarct size and neutrophil accumulation after coronary artery occlusion/reperfusion in dogs.
Sato
N
N
First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Endo
T
T
Kiuchi
K
K
Hayakawa
H
H
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009504:Neutrophils / Q000187:drug effects*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; C049966:Y 20811; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase