Regulation of blood oxygen transport in hibernating mammals

Along with the periodic reductions in O₂ requirements of mammalian hibernators during winter, the O₂ affinity of the blood of mammalian hibernators is seasonally regulated to help match O₂ supply to consumption, contributing to limit tissue oxidative stress, particularly at arousals. Specifically, mammalian hibernators consistently show an overall increase in the blood-O₂ affinity, which causes a decreased O₂ unloading to tissues, while having similar or lower tissue O₂ tensions during hibernation. This overview explores how the decreased body temperature and concentration of red blood cell 2,3-diphosphoglycerate (DPG) that occur in hibernation contribute separately or in combination to the concurrent increase in the O₂ affinity of the hemoglobin, the O₂ carrier protein of the blood. Most mammalian hemoglobins are responsive to changes in DPG concentrations, including that of the hibernating brown bear, although the smaller hibernators, such as golden-mantled ground squirrel, chipmunks, and dormice, have hemoglobins with low sensitivity to DPG. While the effect of DPG on oxygenation may vary, the decrease in body temperature invariably increases hemoglobin's O₂ affinity in all hibernating species. However, the temperature sensitivity of hemoglobin oxygenation is low in hibernators compared to human, apparently due in part to endothermic allosteric quaternary transition in ground squirrels and dissociation of chloride ions in brown bears. A low heat of blood oxygenation in temporal heterotherms, like hibernators, may thus contribute to reduce heat loss, as found in regional heterotherms, like polar mammals, although the significance would be low in winter hibernation.