Repeated exposure to hyperbaric oxygen sensitizes rats to oxygen-induced seizures

Abstract

Repeated exposure to increased partial pressure of oxygen (Po 2) is the standard of care for several medical conditions. The side-effects of repeated exposure to hyperbaric oxygen (HBO), however, are not well defined. Previous studies have demonstrated that acute exposure of rats to HBO causes hypothermia that precedes convulsions. In the present studies, rats that were repeatedly exposed to 100% oxygen at 4 atmospheres absolute (ATA) pressure developed convulsions earlier than naive controls. There was also a trend toward less hypothermia in the rats repeatedly exposed to oxygen. The purpose of this study was to test the hypothesis that repeated exposure to HBO increases sensitivity to convulsions induced by HBO and to determine if the time to onset of convulsions is affected by the hypothermia caused by exposure to HBO. Rats were repeatedly exposed to 2 ATA oxygen for a total of 10 days. After 72 h, these rats were challenged by exposure to 100% oxygen at 4 ATA pressure. Rats repeatedly exposed to HBO had convulsions significantly earlier than the naive controls (84±8min compared to 147±11min), and they developed significantly less hypothermia. Control studies suggested that the decrease in the degree of hypothermia was caused by both repeated exposure to oxygen and adaptation to the mild restraint used during oxygen re-exposures. Adaptation to restraint eliminated the hypothermia induced by oxygen but did not change the time to onset of convulsions. Increased sensitivity to convulsions was present after five exposures to 2 ATA oxygen and persisted for 10 days after the last 2 ATA oxygen re-exposure. Kindling is an animal model of epilepsy which is caused by repeated exposure to subthreshold doses of convulsant stimuli. This repeated dosing causes an increase in the sensitivity of the animal to the convulsant stimuli that can persist for weeks. The increased sensitivity of rats to convulsions during subsequent HBO challenge that is induced by repeated exposures to subconvulsant ‘doses’ of HBO (2 ATA) is similar to kindling. At present the mechanism that causes either kindling or the increased sensitivity to seizures induced by HBO are unknown, and therefore may not be the same.