OTOTOXICITY OF CHEMICAL ASPHYXIANTS AND NOISE

准确预测可能产生特定 听觉系统的损伤需要了解 耳毒性机制、耳蜗的正常生理适应 内耳的压力和基本代谢需求。 我们一直 研究了锡化合物的耳毒性，并证明了一个很长的 持续但部分可逆的听力损失模式， 化学性耳中毒 我们建议确定TMT 产生高频听力损失，特别注意其 对能量代谢可能造成的干扰。 我们也一直 研究内耳对缺氧暴露的脆弱性， 一氧化碳（CO）在噪声暴露和安静的条件下。 我们 已经注意到耳蜗血流的大量增加，这是由于CO 暴露，并可用于维持正常的耳蜗氧分压。 然而，在高碳氧血红蛋白水平下，我们注意到一种短暂的， 高频听力损失 同时存在CO缺氧 在噪声暴露期间产生更深刻和更持久的听力 比噪音更可怕。 此外，共同暴露于噪音和CO变化 对比噪音更高的频率听觉损失最大的区域 一个人 我们会继续研究噪音和缺氧 同时产生协同效应。 我们研究 氧化代谢作为听觉功能障碍的一般机制， 采用基于反射修正测听法的听力测量，以及 耳蜗功能的电生理学测量，沿着测量 氧气输送和耳蜗血液流动。 直接测量 氧化磷酸化，锡积累和结合在耳蜗和 随后的组织病理学研究使用两种表面制备的 Corti器和塑料包埋厚切片用于光学显微镜 将提供必要的生化和组织病理学数据， 确定耳毒性的机制。

Accurate prediction of environmental agents likely to produce specific injury to the auditory system requires an understanding of general mechanisms of ototoxicity, normal physiological adaptation of the cochlea to stress and basic metabolic requirements of the inner ear. We have been studying the ototoxicity of tin compounds and have demonstrated a very long lasting, but partially reversible patterns of hearing loss which is unusual for chemical ototoxics. We propose to determine the mechanism by which TMT produces high frequency hearing loss with particular attention paid to its possible disrupting effects on energy metabolism. We have also been studying the vulnerability of the inner ear to hypoxic exposure produced by carbon monoxide (CO) under conditions of noise exposure and in quiet. We have noted a large increase in cochlear bloodflow which results from CO exposure and may serve to maintain normal cochlear oxygen tension. However, at high carboxyhemoglobin levels we have noted a transient and specific high frequency hearing loss. CO hypoxia present concurrently during noise exposure produces a more profound and longer lasting hearing loss than does noise alone. Further, co-exposure to noise and CO shifts the region of greatest auditory loss toward higher frequencies than noise alone. We will continue to address the reason that noise and hypoxia presented simultaneously produce synergistic effects. Our study of oxidative metabolism as a general mechanism of auditory dysfunction will employ measures of hearing based on reflex modification audiometry, and electrophysiological measures of cochlear function, along with measurement of oxygen delivery and cochlear blood flow. Direct measurement of oxidative phosphorylation, tin accumulation and binding in the cochlea and subsequent histopathological studies using both surface preparation of the organ of Corti and plastic embedded thick sections for light microscopy will provide biochemical and histopathological data essential to determining mechanisms of ototoxicity.