Effect of pentobarbital on normal brain protection and on the response of 9L rat brain tumor to radiation therapy

The authors attempted to confirm published reports that pentobarbital protects against radiation-induced damage to normal rat brain, as well as enhances radiotherapeutic efficacy in a rat brain tumor model. They evaluated animal survival in 9L gliosarcoma-burdened rats that received whole-brain radiation therapy (16, 24, 32, or 40 Gy) while under intraperitoneal pentobarbital (60 mg/kg) or intramuscular ketamine (60 mg/kg) sedation. The animals were examined at autopsy to attribute death to either intracranial tumor growth or normal brain toxicity in the absence of discernible tumor. There was no difference between the two anesthesia groups regarding the survival of unirradiated animals. Radiation therapy produced a significant dose-dependent prolongation in animal survival, which was limited by the development of normal tissue toxicity at the higher doses. When compared to ketamine anesthesia, pentobarbital anesthesia appeared to offer some protection (not statistically significant) against early (but not late) toxicity at selected radiation doses. A reduction in the number of deaths from tissue toxicity suggested an increased antitumor effect, but again this was not statistically significant. Only in one case was there even a marginal significant difference (p = 0.045) between overall therapeutic efficacy in rats sedated with pentobarbital versus ketamine. While there may be a radioprotective effect of pentobarbital in rat brains without intracranial tumor, there is no conclusive evidence for either radioprotection or significant improvement of radiotherapeutic efficacy in this 9L rat brain tumor model.