FUROSEMIDE OTOTOXICITY IS ENHANCED IN ANALBUMINEMIC RATS

Objective.-The purpose of this study was to investigate the effect of furosemide on the endocochlear potential (EP) of Sprague-Dawley rats a nd rats that lack albumin in their serum (Nagase analbuminemic rats [N AR]). Design.-Group comparisons between analbuminemic rats and normal Sprague-Dawley rats was carried out, with statistical evaluation using the Student's t test.Setting.-Experiments were carried out in a sound -attenuated booth in a research laboratory. Subjects.-Young adult Spra gue-Dawley and analbuminemic rats (NAR) 50 to 80 days of age were used as experimental animals. Interventions.-Subjects were anesthetized wi th ketamine and xylazine. Furosemide, 35 mg/kg, was injected intraveno usly in each of three groups: NAR rats, NAR rats pretreated with album in and normal Sprague-Dawley rats. Main Outcome Measures.-Endocochlear potential was measured via the round window membrane approach. Urine samples were collected with a metabolic cage, and volumes were recorde d. Results.-Sprague-Dawley rats had a very slight EP reduction followi ng furosemide. The NAR rats, however, were found to have an extremely large and rapid reduction of the EP one order of magnitude greater. Th e NAR rats pretreated with albumin had a significantly smaller reducti on of EP than NAR rats not receiving albumin. However, NAR rats pretre ated with albumin had a significantly greater urine output than contro l NAR rats. Conclusions.-These findings support the hypothesis that th e access of furosemide to its site of ototoxic action in the cochlea d epends on the quantity of unbound furosemide in the serum.