Kanzik I, Cakici I, Ersoy S, Ark M, Abacioglu N, Zengil H
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey.
Pharmacol Res. 1992 Oct-Nov;26(3):305-16. doi: 10.1016/1043-6618(92)90219-2.
Effects of cyclooxygenase and lipoxygenase inhibitors of digoxin-induced arrhythmias and haemodynamics were studied in guinea-pigs. ECG, mean arterial blood pressure heart rate, pressure rate index and arrhythmias were recorded, starting 15 min before digoxin administration and continuing for 30 min afterwards. The cyclooxygenase inhibitor aspirin (50 mg kg-1) and the dual cyclooxygenase/lipoxygenase inhibitor BW 755C (0.25-10.0 mg kg-1) were found to produce a significant protection against the arrhythmias, whereas aspirin (100 mg kg-1) and CGS 8515 were found to be ineffective. SK&F 104 353, a potent and selective peptidoleukotriene receptor antagonist significantly attenuated the arrhythmias and mortality in a dose-dependent manner. It is concluded that production of both cyclooxygenase and lipoxygenase metabolites could favour the occurrence and/or the maintenance of digoxin-induced cardiac toxicity.
在豚鼠中研究了环氧化酶和脂氧化酶抑制剂对地高辛诱导的心律失常和血流动力学的影响。记录心电图、平均动脉血压、心率、压力速率指数和心律失常，从给予地高辛前15分钟开始，持续至给药后30分钟。发现环氧化酶抑制剂阿司匹林（50毫克/千克）和双环氧化酶/脂氧化酶抑制剂BW 755C（0.25 - 10.0毫克/千克）对心律失常有显著的保护作用，而阿司匹林（100毫克/千克）和CGS 8515则无效。强效选择性肽白三烯受体拮抗剂SK&F 104 353以剂量依赖方式显著减轻心律失常和死亡率。结论是，环氧化酶和脂氧化酶代谢产物的产生可能有利于地高辛诱导的心脏毒性的发生和/或维持。
