OTOTOXICITY OF CHEMICAL ASPHYXIANTS AND NOISE

准确预测可能产生特定影响的环境因子 对听觉系统的损伤需要了解一般情况 耳毒性的机制、耳蜗的正常生理适应 应激和内耳的基本新陈代谢要求。我们一直在 研究锡化合物的耳毒性已经证明了很长一段时间 持续的，但部分可逆的听力损失模式，这是不寻常的 用于化学耳毒性药物。我们建议确定TMT的机制 产生高频听力损失，并特别注意其 可能对能量代谢产生干扰作用。我们也一直在 研究内耳对低氧暴露的易感性 噪声暴露和安静条件下的一氧化碳(CO)。我们 注意到由一氧化碳引起的耳蜗血流量的大幅增加 暴露可能有助于维持正常的耳蜗氧分压。 然而，在高碳氧血红蛋白水平下，我们注意到一过性和 特定的高频听力损失。一氧化碳缺氧症同时存在 暴露在噪音中会产生更深刻和更持久的听力 损失要比只有噪音强。此外，共同暴露于噪声和一氧化碳漂移 听力损失最大的区域朝向比噪声更高的频率 独自一人。我们将继续解决噪音和缺氧的原因 呈现同时产生协同效应。我们的研究 氧化代谢作为听觉功能障碍的一般机制将 采用基于反射修正测听的听力测量方法，以及 耳蜗功能的电生理测量与测量 氧气输送和耳蜗血流量。直接测量 氧化磷酸化、锡在耳蜗内的积累和结合 随后的组织病理学研究使用两种表面准备的 用于光学显微镜的科尔蒂器和塑料包埋厚切片 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.