Didier A, Miller J M, Nuttall A L
Laboratoire de Neurophysiologie Sensorielle, Universite Claude Bernard, Villeurbaune, France.
Hear Res. 1993 Sep;69(1-2):199-206. doi: 10.1016/0378-5955(93)90108-d.
Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (> or = 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosecretory function a decreased blood flow contributes to the ototoxicity of salicylates.
水杨酸盐类药物（阿司匹林样药物）具有可逆性耳毒性。电生理和超微结构证据表明，水杨酸盐治疗后耳蜗的感觉毛细胞会受损。此外，由于这些药物会引起血管收缩，水杨酸盐的耳毒性可能还涉及内耳血液循环受损。然而，水杨酸盐毒性的血管假说并未受到太多关注。在本研究中，我们同时测量了耳蜗血流量（通过激光多普勒血流仪）和圆窗的声诱发电位。肌肉注射低剂量水杨酸钠（100mg/kg）后30分钟内，水杨酸钠导致耳蜗血流量下降。该水杨酸钠剂量未引起听觉敏感性变化。对于更高剂量（200mg/kg和300mg/kg），耳蜗血流量和听觉敏感性均受到影响。300mg/kg剂量使血流量降低约25%，高频（≥8kHz）复合动作电位阈值升高10至25dB。进一步的实验表明，当血管舒张药物肼屈嗪增加耳蜗血流量时（抵消水杨酸盐引起的血流量减少），水杨酸盐诱导的中频率阈值变化显著降低。这些数据表明，除了全身给药的水杨酸盐对神经分泌功能的直接作用外，血流量减少也导致了水杨酸盐的耳毒性。
