Rybak L P, Whitworth C, Scott V
Department of Surgery, Southern Illinois University School of Medicine, Springfield 62794-9230.
Hear Res. 1990 Jun;46(1-2):95-9. doi: 10.1016/0378-5955(90)90142-c.
Previous studies have shown a reduction of the ototoxicity of furosemide in chinchillas pretreated with organic acid transport inhibitors. The current studies were designed to investigate whether such a protective effect could be observed in chinchillas receiving ethacrynic acid. Chinchillas weighing 400-600 g were injected with saline followed by ethacrynic acid 12.5 mg/kg i.v. (controls) or one of three organic acids (probenecid, penicillin G and or sodium salicylate) 50 mg/kg i.v., thirty minutes prior to ethacrynic acid injection (experimentals). Endocochlear potential (EP) and compound action potential of the eighth nerve (CAP) elicited by click stimuli were simultaneously monitored before and after injection in both groups. The mean change in EP and CAP findings are consistent with observations by other investigators of the actions of these loop diuretics in the isolated loop of Henle. In the latter tissues, the 'furosemide-like loop diuretics' appear to have a different mechanism of action than does ethacrynic acid. It appears from the findings of the present study that the actions of furosemide and ethacrynic acid on the cochlea are by different mechanisms as well.
先前的研究表明,用有机酸转运抑制剂预处理的龙猫中,速尿的耳毒性降低。当前的研究旨在调查在接受依他尼酸的龙猫中是否能观察到这种保护作用。体重400 - 600克的龙猫静脉注射生理盐水,随后静脉注射12.5毫克/千克依他尼酸(对照组),或在注射依他尼酸前30分钟静脉注射三种有机酸(丙磺舒、青霉素G和水杨酸钠)中的一种,剂量为50毫克/千克(实验组)。两组在注射前后均同时监测由点击刺激诱发的蜗内电位(EP)和第八神经复合动作电位(CAP)。EP和CAP结果的平均变化与其他研究者对这些袢利尿剂在离体亨氏袢中的作用观察结果一致。在后者的组织中,“速尿样袢利尿剂”似乎具有与依他尼酸不同的作用机制。从本研究结果来看,速尿和依他尼酸对耳蜗的作用似乎也通过不同的机制。