Beneficial effects of a new 5-lipoxygenase inhibitor on occlusion- and occlusion-reperfusion-induced myocardial injury.
Effects of a new 5-lipoxygenase inhibitor TZI-41127 (2-(4-hydroxy-3,5-dimethylphenyl)-5-methoxy-3-methylindole) on occlusion- and occlusion-reperfusion-induced myocardial injury were examined in rats and dogs. The occlusion-reperfusion-induced myocardial injury was produced by the occlusion of the left anterior descending (LAD) coronary artery for 90 min following 22 h reperfusion in Beagle dogs. The drug was orally administered twice in a dose of 30 mg/kg. The first administration was 2 h before the occlusion and the second one was 1 h after the start of the occlusion. Eighteen dogs were divided into two groups. Nine were for control which were administered the vehicle, and the other were for the drug treatment. One animal of each group died because of ventricular fibrillation. The risk area and the infarct area were measured 22 h after reperfusion. The risk area as percent of total ventricle was not different between the two groups. However, the infarct area as percent of the risk area was significantly less in the drug-treated group. Although the ventricular arrhythmias immediately after the reperfusion were not prevented by the drug treatment, the ventricular arrhythmias 22 h after the reperfusion were significantly less in the drug-treated group. The arterial blood pressure, the heart rate and the double product were not significantly different between the two groups. The infarct size induced by LAD occlusion in rats was also reduced by the pretreatment with TZI-41127. Thus, TZI-41127 has beneficial effects on occlusion- and occlusion-reperfusion-induced myocardial injury.
Hashimoto
H
H
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Miyazawa
K
K
Hagiwara
M
M
Miyasaka
K
K
Nakashima
M
M
D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D051381:Rats
D007211:Indoles; D016859:Lipoxygenase Inhibitors; C063918:2-(4-hydroxy-3,5-dimethylphenyl)-5-methoxy-3-methylindole; D001091:Arachidonate Lipoxygenases