INFLUENCE OF CISPLATIN ON THE SENSITIVITY OF THE RAT SCIATIC-NERVE TOLOCAL HYPERTHERMIA

The influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated Rats received 1.7 mg/kg cispla tin i.p., twice a week for 6 weeks, up to a cumulative dose of 20.4 mg /kg. After termination of cisplatin treatment, a 5 mm segment of the n erve was locally heated ata temperature of 45-degrees-C (5-30 min). Lo ss of motor function was assessed by means of the toe-spreading test, 24 h post heating. The calculated ED50 for control nerves was signific antly (p < 0.01) larger than the ED50 for cisplatin treated rats; 16.3 +/- 1.1 min vs. 10.9 +/- 1.1 min. This indicates that nerves from cis platin treated rats were more sensitive to heat than nerves from contr ol rats (dose modifying factor = 1.5 +/- 0.2). Histopathological inves tigation of nerves after heat alone or after heat preceded by cisplati n confirmed these differences and showed that edema, vascular damage a nd axonal degenerative changes of axons and myelin sheaths occurred at lower heat doses when compared to control nerves. Recovery studies sh owed that cisplatin treatment before hyperthermia caused a delay in re covery from motor function loss of about 6 days. Cisplatin treatment a fter hyperthermia had no influence on recovery from motor function los s. (C) 1993 Intox Press, Inc.