Myocardial salvage by a novel thromboxane A2 synthetase inhibitor in a canine coronary occlusion-reperfusion model.
The effects of the new thromboxane A2 (TXA2) synthetase inhibitor sodium 6-(2-[1-(1H)-imidazolyl]methyl-4,5-dihydrobenzo[b]thiophene)carboxylate (RS-5186), 10 mg/kg i.v., on infarct size, polymorphonuclear leukocytes (PMNs) infiltration, gross myocardial hemorrhage and ventricular arrhythmias were studied using a canine coronary occlusion (2 h)-reperfusion (5 h) model. Infarct size (IS) and risk area (RA) were determined by a dual staining technique. 60 min before coronary occlusion dogs were randomly assigned to either the RS-5186 treated group (n = 11) or the control group (n = 15). RS-5186 reduced infarct size (RS-5186: 26.3 +/- 2.4% of RA (mean +/- SEM) vs control: 50.7 +/- 5.9%, p less than 0.01), and also reduced the area of gross myocardial hemorrhage (RS-5186: 3.9 +/- 2.6% of IS vs control: 22.4 +/- 4.0%, p less than 0.01). The drug also decreased the intensity of PMNs infiltration into the infarcted area (p less than 0.05). However, RS-5186 had no significant influence on the incidence of ventricular arrhythmias. These results suggest that the new thromboxane A2 synthetase inhibitor RS-5186 might be useful in salvaging ischemic myocardium.
Toki
Y
Y
2nd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hieda
N
N
Okumura
K
K
Hashimoto
H
H
Ito
T
T
Ogawa
K
K
Satake
T
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D012307:Risk Factors; D013876:Thiophenes / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D013876:Thiophenes; C055806:RS 5186; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase