STRAIN DIFFERENCES IN METABOLISM AND SUSCEPTIBILITY TO THE NEPHROTOXIC EFFECTS OF METHOXYFLURANE IN RATS

¹ Departments of Anesthesia and Pathology, Stanford University School of Medicine, Stanford, California; Veterans Administration Hospital, Palo Alto, California

Renal insufficiency due to metabolism of methoxyflurane to inorganic fluoride has been reported in man; however, an animal model has not been available. Therefore, the metabolism of methoxyflurane to inorganic fluoride and the renal effects of this metabolite were studied in adult male Fischer 344, Buffalo, Wistar, Sprague-Dawley and Long-Evans rats anesthetized with 0.5% methoxyflurane for three hours. Fischer 344 and Buffalo rats metabolized methoxyflurane to a greater extent than the other three strains, as evidenced by higher serum and urine inorganic fluoride activity. However, only Fischer 344 rats developed biochemical and pathological evidence of a renal lesion. Injection of identical doses of inorganic fluoride (NaF) produced a much greater degree of renal insufficiency in Fischer 344 rats than in Buffalo rats. It is concluded that there is variation in the rate of metabolism of methoxyflurane to inorganic fluoride and in its nephrotoxic effects among various rat strains. A high rate of methoxyflurane metabolism and increased susceptibility to the nephrotoxic effects of inorganic fluoride result in polyuric renal insufficiency in Fischer 344 rats.