New "rest period" protocol for inducing tolerance to high O2 exposure in adult rats

We report a new protocol for inducing marked tolerance to prolonged exposure to hyperoxia in adult rats that entails the use of a single "rest period" between exposures to a usually lethal concentration of O2. Exposure of adult rats to greater than 95% O2 for 48 h followed by a rest in air, or a rest even in 50-75% O2, consistently resulted in 100% survival with evidence of only slight pulmonary edema during continuation of exposure to greater than 95% O2 for 3-7 more days (7-day survival for rats rested in room air for 24 h = 23/23; for rats rested in 50-75% O2 for 24 h = 27/27; for continuously O2-exposed control rats = 0/11). Induction of tolerance to hyperoxia was associated with significant increases in the lungs' antioxidant enzyme activities during the reexposure to greater than 95% O2 following the rest period. The molecular means by which the events in this protocol lead to increased lung antioxidant enzyme activity is only partially known, but because of the marked tolerance produced, the elucidation of the mechanisms must be important to our understanding of tolerance to hyperoxia.