Mechanisms of thermoregulation in combined hypoxic-cold environments

This thesis provides several novel findings on the autonomic thermoregulatory response of humans to the cold and the modulation of parameters by hypoxia. Informing methodological considerations, the reliability and validity of four independent metrics in the quantification of shivering thermogenesis were first assessed, as well as two analytical methods used to determine the inflection point at which humans start shivering. The extent to which shivering thermogenesis can be voluntarily suppressed in response to whole-body cooling, and the resultant impact on body temperature was also examined. Building on the literature reviewed, this thesis subsequently investigated the mechanisms through which cold and hypoxia interact on thermoregulation, focusing on the underpinning role of nitric oxide. First, using dietary nitrate ingestion as a medium through which to increase nitic oxide bioavailability, the impact of independent and combined normobaric hypoxia and acute dietary nitrate ingestion on cold-induced thermoeffectors was assessed. Data showed a hypoxia-induced decrease in the onset time of shivering thermogenesis, however, despite significantly increased plasma nitrite concentrations following nitrate ingestion, no interactions were observed between nitrate and hypoxia. As such, the nitric oxide production pathway through which hypoxia acts on cutaneous vascular tone remains unclear. The subsequent chapter was therefore approached from a different perspective; this time intradermally inhibiting nitric oxide synthase (NOS; via L-NAME) and the nitrite reductase, xanthine oxidase (via allopurinol), two primary sources of nitric oxide production. Focusing on microvascular function, the nitric oxide dependence of independent and combined hypoxic cold exposure on cutaneous vascular conductance was assessed. It is hoped that the findings of these investigations will aid in the development and understanding of interventions and countermeasures for use in clinical and occupational settings; for example, improving the use and mechanistic understanding of cold stress as a clinical tool to protect against severe hypoxemia during critical care and surgery. The translation of research findings obtained from healthy individuals at their physiological limit to those who are critically ill, provides an important rationale for work in environmental physiology.