Furosemide ototoxicity is enhanced in analbuminemic rats

L. P. Rybak, C. Whitworth and V. Scott
Department of Surgery, Southern Illinois University School of Medicine, Springfield 62794-9230.

OBJECTIVE--The purpose of this study was to investigate the effect of furosemide on the endocochlear potential (EP) of Sprague-Dawley rats and rats that lack albumin in their serum (Nagase analbuminemic rats [NAR]). 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 Sprague-Dawley and analbuminemic rats (NAR) 50 to 80 days of age were used as experimental animals. INTERVENTIONS--Subjects were anesthetized with ketamine and xylazine. Furosemide, 35 mg/kg, was injected intravenously in each of three groups: NAR rats, NAR rats pretreated with albumin 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 recorded. RESULTS--Sprague-Dawley rats had a very slight EP reduction following furosemide. The NAR rats, however, were found to have an extremely large and rapid reduction of the EP one order of magnitude greater. The NAR rats pretreated with albumin had a significantly smaller reduction of EP than NAR rats not receiving albumin. However, NAR rats pretreated with albumin had a significantly greater urine output than control NAR rats. CONCLUSIONS--These findings support the hypothesis that the access of furosemide to its site of ototoxic action in the cochlea depends on the quantity of unbound furosemide in the serum.