Submitted on January 14, 2005
Accepted on November 16, 2005
Optimization of Oxygen Tolerance Extension in Rats by Intermittent Exposure
J. M. Clark1*, C. J. Lambertsen1, R. Gelfand1, and A. B. Troxel1
1 Environmental Biomedical Stress Data Center, Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA; Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
* To whom correspondence should be addressed. E-mail: jmclark{at}mail.med.upenn.edu.
Optimization of O2 tolerance extension by intermittent exposure was studied in groups of 20 rats exposed to systematically varied patterns of alternating O2 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: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 O2 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 O2 period, and an O2 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 O2 pressure definable as a time-weighted average of the alternating O2 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 O2 at 2.0 ATA. Definition of intermittent exposure patterns and conditions that produced prominent gains in O2 tolerance can also facilitate the performance of future experiments designed to study potential mechanisms for O2 tolerance extension by intermittent exposure. Heat shock and oxidation-specific stress proteins which are induced by exposure to oxidant injury are suggested for emphasis in such investigations.
