Ventilatory acclimatization to hypoxia in mice: Methodological considerations

We examined ventilatory acclimatization to hypoxia (VAH) in CD1 mice, and contrasted results obtained using the barometric method on unrestrained mice with pneumotachography and pulse oximetry on restrained mice. Responses to progressive step reductions in O₂ fraction (21%-8%) were assessed in mice acclimated to normoxia and hypobaric hypoxia (barometric pressure of 60kPa for 6-8 weeks). Hypoxia acclimation increased the hypoxic ventilatory response (primarily by increasing breathing frequency rather than tidal volume), arterial O₂ saturation (Sa_O2) and heart rate in deep hypoxia, hypoxic chemosensitivity (ventilatory O₂/CO₂ equivalents versus Sa_O2), and respiratory water loss, and it blunted the hypoxic depression of metabolism and body temperature. Although some effects of hypoxia acclimation were qualitatively similar between methods, the effects were often greater in magnitude when assessed using pneumotachography. Furthermore, whereas hypoxia acclimation reduced ventilatory O₂ equivalent and increased pulmonary O₂ extraction in barometric experiments, it had the opposite effects in pneumotachography experiments. Our findings highlight the importance of considering the impact of how breathing is measured on the apparent responses to hypoxia.