EFFECTS OF INTRA-COCHLEAR PERFUSION OF SALICYLATES ON COCHLEAR MICROPHONIC AND OTHER AUDITORY RESPONSES IN THE GUINEA-PIG
EFFECTS OF INTRA-COCHLEAR PERFUSION OF SALICYLATES ON COCHLEAR MICROPHONIC AND OTHER AUDITORY RESPONSES IN THE GUINEA-PIG
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DOI：
10.1016/0378-5955(93)90242-s
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发表时间：
1993-05-01
期刊：
影响因子：
2.8
通讯作者：
JOHNSTONE, BM
中科院分区：
文献类型：
--
作者：
FITZGERALD, JJ;ROBERTSON, D;JOHNSTONE, BM
通过鼓阶灌注水杨酸盐和溴水杨酸盐，在豚鼠中研究了水杨酸盐的耳毒性作用。结果定性地证实了在猫中使用静脉注射给药的实验（Stypulkowski，1990），结果显示复合动作电位（CAP）阈值呈剂量依赖性升高、耳蜗颤音（CM）增加以及2f1-f2声失真产物的水平依赖性降低。耳蜗内电位没有受到显着影响，并且将水杨酸盐离子电渗注入阶梯介质中对 CAP 阈值没有可测量的影响，这与对毛细胞基底侧壁的作用一致。吲哚美辛灌注产生与水杨酸盐相似的效果，但采用非生理剂量。加上 5-溴水杨酸盐的巨大功效，这表明水杨酸盐不会通过抑制前列腺素合成来发挥作用。结果在质量上与水杨酸盐作用于外毛细胞的基底侧壁的命题一致。然而，CM 的幅度增加，特别是在高药物浓度下，并且水杨酸盐减少但没有消除橄榄耳蜗传出刺激对 CM 幅度的影响这一事实表明，仅基于外毛细胞膜电导增加对水杨酸盐效应的简单解释可能是不够的。
The ototoxic action of salicylate was investigated in the guinea pig by perfusion of both salicylate and bromosalicylate through scala tympani. The results qualitatively confirmed experiments using intravenous administration in cats (Stypulkowski, 1990), showing dose-dependent elevations in compound action potential (CAP) thresholds, increases in cochlear microphonics (CM) and level-dependent reductions in 2f1-f2 acoustic distortion products. The endocochlear potential was not significantly affected and iontophoretic injection of salicylate into scala media had no measurable effect on CAP thresholds, consistent with an action on the basolateral walls of the hair cells. Perfusion with indomethacin produced effects similar to those of the salicylates, but at non-physiological doses. Together with the great effectiveness of 5-bromosalicylate, this suggests that salicylate does not act by inhibiting prostaglandin synthesis. The results are qualitatively consistent with the proposition that salicylates act on the basolateral walls of the outer hair cells. However, the magnitude of the CM increases, particularly at high drug concentrations, and the fact that salicylate reduced, but did not eliminate the effects of olivocochlear efferent stimulation on CM amplitude indicate that a simple explanation for salicylate effects based solely on a conductance increase in the outer hair cell membranes may be inadequate.