Optimization of oxygen tolerance extension in rats by intermittent exposure

Optimization of oxygen tolerance extension by intermittent exposure was studied in groups of 20 rats exposed to systematically varied patterns of alternating oxygen and normoxic breathing periods at 4.0, 2.0, and 1.5 ATA. Oxygen periods of 20, 60, and 120 min were alternated with normoxic intervals that provided oxygen-to-normoxia ratios of 4:1, 2:1, 1:1, and 1:3. In general, median survival times had nearly linear relationships to increasing normoxic intervals with oxygen period held constant. Exceptions occurred at 4.0 and 2.0 ATA where a 5-min normoxic interval was too short for adequate recovery even with a 20-min oxygen period, and an oxygen period of 120 min was too long even with a normoxic interval of 30 min. These exceptions did not occur at 1.5 ATA. Survival time for many intermittent exposure patterns was equivalent to that for continuous exposure to an oxygen pressure definable as a time-weighted average of the alternating oxygen and normoxia periods. However, this predictive method underestimated the degree of protection achieved by several of the intermittent exposure patterns, especially those performed at 4.0 ATA. Results provided guidance for selection of intermittent exposure patterns for direct evaluation in humans breathing oxygen at 2.0 ATA. Definition of intermittent exposure patterns and conditions that produced prominent gains in oxygen tolerance can also facilitate the performance of future experiments designed to study potential mechanisms for oxygen tolerance extension by intermittent exposure. Heat shock and oxidation-specific stress proteins that are induced by exposure to oxidant injury are suggested for emphasis in such investigations.