Ototoxicity of furosemide during development.

The rat is an altricial animal which serves as a useful model for human auditory development. The purpose of the present study was to investigate the effects of furosemide on cochlear function and the stria vascularis ultrastructure at various postnatal ages. Rat pups anesthetized with ketamine hydrochloride/xylazine hydrochloride received furosemide 35 mg/kg intravenously (IV), and the endocochlear potential and compound action potential of the eighth nerve were recorded. The stria vascularis was removed and prepared for transmission electron microscopy. Rat pups 9 to 28 days of age had a much greater reduction of endocochlear potential and elevation of the compound action potential threshold than animals older than 30 days. These physiologic changes were accompanied by edema of the stria on transmission electron microscopy only in animals at susceptible ages. These findings support the concept of a critical period of susceptibility to ototoxic drugs during development and could have important clinical implications in premature infants.