Author:
Zwemer Charles F.,Song Michael Y.,Carello Katari A.,D'Alecy Louis G.
Abstract
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 (V̇′o2 in ml O2·kg−1·min−1) and carbon dioxide production (V̇′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 V̇′o2 and V̇′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 V̇′o2, may confer a greater survival advantage than simply lowering demand.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
29 articles.
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