Physiological Differences Between Torpor and Forced Hypothermia in Mice

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Clinical advantages of forced hypothermia (FH) are mitigated by homeostatic mechanisms invoked to prevent core cooling. Torpor, a physiological state used by mice as a survival strategy, lowers body temperature (Tb) without eliciting such mechanisms. It was hypothesized that torpor is different from FH at multiple levels, including autonomic balance, aerobic/anaerobic metabolism, and hypoxia related gene expression in heart and liver. To test this hypothesis, female C57Bl/6 mice were implanted with ECG/ Tb telemeters and subjected to both conditions‐ FH and naturally induced torpor‐ in a random crossover design. During cooling and at a Tb of 30°C, mice showed a heart rate (HR) of 185 ± 18 bpm during torpor, and a HR of 484 ± 20 bpm during forced hypothermia. Analysis of hysteresis curves of Tb vs HR showed parasympathetic influence during entrance and maintenance of torpor, which shifted to sympathetic influence during recovery. Mice undergoing FH showed consistent and maximal sympathetic activity. ECG tracings showed evidence of substantial shivering during rewarming from both states, but showed vigorous shivering during cooling only in FH. Circulating lactate levels were significantly elevated in FH relative to torpor, (3.9 ± 0.9 vs 0.6 ± 0.2 mM, respectively), suggesting an increased reliance on anaerobic metabolism during forced hypothermia. Steady state mRNA levels in the heart and liver from torpid mice, as assessed by qRTPCR arrays (80 different genes), showed a unique pattern of expression compared to euthermic and forced hypothermic mice. In conclusion, data in this study support the hypothesis that forced and natural hypothermia only have low Tb in common, and have vastly different sympathetic, shivering, anaerobic, and hepatic/cardiac gene expression profiles.