Hashimoto H, Miyazawa K, Hagiwara M, Miyasaka K, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Arzneimittelforschung. 1990 Feb;40(2 Pt 1):126-9.
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.
在大鼠和犬中研究了新型5-脂氧合酶抑制剂TZI-41127（2-(4-羟基-3,5-二甲基苯基)-5-甲氧基-3-甲基吲哚）对闭塞和闭塞再灌注诱导的心肌损伤的影响。在比格犬中，通过闭塞左冠状动脉前降支（LAD）90分钟，随后再灌注22小时来诱导闭塞再灌注诱导的心肌损伤。该药物以30mg/kg的剂量口服给药两次。第一次给药在闭塞前2小时，第二次给药在闭塞开始后1小时。18只犬被分为两组。9只为对照组，给予赋形剂，另一组为药物治疗组。每组各有1只动物因室颤死亡。在再灌注22小时后测量危险区和梗死区。两组之间危险区占全心室的百分比没有差异。然而，药物治疗组中梗死区占危险区的百分比显著更低。虽然药物治疗不能预防再灌注后立即出现的室性心律失常，但药物治疗组再灌注22小时后的室性心律失常明显更少。两组之间动脉血压、心率和双乘积没有显著差异。用TZI-41127预处理也可减少大鼠中由LAD闭塞诱导的梗死面积。因此，TZI-41127对闭塞和闭塞再灌注诱导的心肌损伤具有有益作用。
