Cochlear microphonic potential response of the dog to diuretic compounds

Abstract

Studies have been carried out to determine the ototoxic effects of diuretics in the dog. After baseline levels had been determined at peak frequencies for each animal, cochlear microphonic potentials (CMP) were followed for 4- to 6-hr periods following single or cumulative iv administration of the drugs. Studies assessing the ototoxicity of single and cumulative iv doses of ethacrynic acid in the dog demonstrated that a dose of 40 mg/kg produced a 100% reduction of the CMP within 15 min. This depression was followed by a slow recovery to 57% of predrug values within 3 hr without any additional appreciable recovery observed at 4 hr. The minimum effective diuretic dose in dogs is 0.05 mg/kg. Lower doses of ethacrynic acid produced correspondingly lower reductions in the CMP at a slower rate with supracompensatory recovery to levels 21% greater than predrug values occurring at 10 mg/kg. A 40 mg/kg iv dose of furosemide yielded approximately a 50% reduction of the CMP. This reduction of the CMP was still present after 4–6 hr. The minimum effective diuretic dose of furosemide in dogs is 0.5 mg/kg. The duration of the initial CMP reduction and recovery was quite rapid, occurring within 10–30 min. However, when recovery proceeded to values from 30% to 80% of the initial CMP, a secondary but variable reduction of the CMP occurred. Chlorothiazide, sorbitol and acetazolamide had no effect on CMP, while mannitol and ammonium chloride depressed the CMP to diuretics in dogs. This report is the result of such studies.