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Strain differences in response to acute hypoxia: CD-1 versus C57BL/6J mice

¹Department of Biology, Dickinson College, Carlisle, Pennsylvania; ²College of Literature, Science, and The Arts, University of Michigan, Ann Arbor; ³Department of Molecular and Integrative Physiology and ⁴Department of Surgery (Vascular), University of Michigan Medical School, Ann Arbor; and ⁵William Beaumont Hospital, Department of Surgery, Royal Oak, Michigan

Submitted 12 May 2006 ; accepted in final form 9 August 2006

Some mammals respond to hypoxia by lowering metabolic demand for oxygen and others by maximizing efficiency of oxygen usage: the former strategy is generally held to be the more effective. We describe within the same species one outbred strain (CD-1) that lowers demand and another inbred strain (C57BL/6J) that maximizes oxygen efficiency to markedly extend hypoxic tolerance. Unanesthetized adult male mice (Mus musculus, CD-1 and C57BL/6J) between 20 and 35 g were used. Sham-conditioned (SC) C57BL/6J mice survived severe hypoxia (4.5% O₂, balance N₂) roughly twice as long as SC CD-1 mice (median 211 and 93.5 s, respectively; P < 0.0001). Following acute hypoxic conditioning (HC), C57BL/6J mice survived subsequent hypoxia 10 times longer than HC CD-1 mice (median 2,198 and 238 s respectively; P < 0.0001). Therefore, C57BL/6J mice are both naturally more tolerant to hypoxia and show a greater increase in hypoxic tolerance in response to hypoxic conditioning. Indirect calorimetry indicates that CD-1 mice lower mass-specific oxygen consumption ('O₂ in ml O₂·kg^–1·min^–1) and carbon dioxide production ('CO₂ in ml CO₂·kg^–1·min^–1) in response to HC (P = 0.002 and P < 0.0001, respectively), but C57BL/6J mice maintain 'O₂ and 'CO₂ after HC. Respiratory exchange ratio and fluorometric assay of plasma ketones suggest that C57BL/6J mice rapidly switch to ketone metabolism, a more efficient substrate, while CD-1 mice reduce overall metabolic activity. We conclude that under severe hypoxia in mice, switching fuel, possibly to ketones, while maintaining 'O₂, may confer a greater survival advantage than simply lowering demand.

hypoxic survival time; hypoxic conditioning; indirect calorimetry; respiratory exchange ratio; D--hydroxybutyrate

This article has been cited by other articles:

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