Heoring Research, 36 (1988) 89-96 Elsevier 89 HRR 01126 Acute effects of noradrenalin related vasoactive agents on the ototoxicity of aspirin: An experimental study in the guinea pig Y. Cazals, X.Q. Li, C. Aurousseau and A. Didier Luhoratoire d’Audiologie expb-imentale, INSERM unitP 229, UniuersitP Bordeaux II. Bordeaux, France (Received 22 February 1988; accepted 25 June 1988) Aspirin is known to be ototoxic when administered at high doses. Its mode of action is unknown but an alteration of the vascular function has been suspected. To further document this hypothesis, acute effects of some vasoactive agents on the ototoxicity of aspirin were tested in experiments on the guinea pig using sensor&neural electrophysiological responses and morphometry of the vessels of the stria and the spiral lamina. Electrophysiological measures showed no modification of sensory responses but neural responses revealed clear changes after administration of noradrenalin related agents, limited modifications after a drug acting partly as a serotonin antagonist. and no change after a dopaminergic agent. Morphometric studies showed no modification of the strial but some effect on the spiral vessels. The results are compatible with the hypothesis of a vascular involvement in the ototoxicity of aspirin and they point toward an interaction with the noradrenergic sympathetic cochlear system in the spiral lamina. Cochlea; Aspirin; Vascularization; Guinea pig zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Introduction Since the beginning of the century aspirin has been known to produce auditory impairments, starting with tinnitus and followed by a deafness affecting all frequencies (Myers and Bernstein, 1965; McCabe and Dey, 1965; Bernstein and Weiss, 1967; Evans et al., 1981; McFadden and Plattsmier 1983; Cazals et al., 1984; Jastreboff and Sasaki, 1986). The hearing loss for pure tones ranges from lo-45 dB and is entirely reversible within 24-72 h. The extent of the loss is related to the level of aspirin in the plasma and duration of treatment, but there are large individual dif- ferences (Myers and Bernstein, 1965; Bernstein and Weiss, 1967; Gold and Wilpizeski, 1967; Mc- Correspondence to: Y. Cazals, Laboratoire d’Audiologie experi- mentale. INSERM unit.4 229, Universite Bordeaux II, Bordeaux. France. * These experiments were performed while Xing Qi Li was on leave from the Institute of ENT at the PLA Postgraduate Medical College, 28 Fu-Xing road, Beijing, China. Fadden and Plattsmier, 1983: McFadden et al.. 1984). Clinical and animal studies suggested that the effective sites of this drug is in the cochlea (Myers and Bernstein, 1965; McCabe and Dey. 1965; Gold and Wilpizeski, 1966; Silverstein et al., 1967) a vascular involvement being particularly suspected after observations on the cochlear lateral wall (Ishii et al., 1967; Perez De Moura, 1968; Hawkins, 1976; Escoubet et al., 1986). This study aimed at further assessing a vascular alteration by examining the effects of some well known vasoac- tive drugs on the ototoxicity of aspirin in experi- ments on the guinea pig. Three vasodilators of potential cochlea-vestibular effectiveness were chosen: a sympathetic adrenolytic, a sympathetic antagonist of serotonin, and a dopaminergic agent; a very potent sympathomimetic vasoconstrictor was also chosen. This study investigated only acute effects of a single dose of the drugs on the ototoxicity induced by a single dose of aspirin. Electrophysiological measures of sensory poten- tials (cochlear microphonic CM and summating potential SP), and neural responses (compound action potential CAP) were taken from an elec- 037%5955/88/$03.50 0 1988 Elsevier Science Publishers B.V. (Biomedical Division)