Strain differences in response to acute hypoxia: CD-1 versus C57BL/6J mice.
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% O(2), balance N(2)) 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 (V'o(2) in ml O(2).kg(-1).min(-1)) and carbon dioxide production (V'co(2) in ml CO(2).kg(-1).min(-1)) in response to HC (P = 0.002 and P < 0.0001, respectively), but C57BL/6J mice maintain V'o(2) and V'co(2) 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 V'o(2), may confer a greater survival advantage than simply lowering demand.
Zwemer
Charles F
CF
Department of Biology, Dickinson College, Carlisle, Pennsylvania, USA.
Song
Michael Y
MY
Carello
Katari A
KA
D'Alecy
Louis G
LG
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D006885:Hydroxybutyrates / Q000097:blood; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007659:Ketones / Q000378:metabolism; D008297:Male; D008433:Mathematics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology*; D016019:Survival Analysis
D006885:Hydroxybutyrates; D007659:Ketones; D002245:Carbon Dioxide; D010100:Oxygen