Is alkalosis the dominant factor in hypoxia‐induced cognitive dysfunction?

Exposure to high altitude poses risks for human function and survival. Humans acclimatize to hypoxia by way of highly orchestrated integrative responses acting to defend whole-body homeostasis. An immediate increase in ventilatory drive improves pulmonary gas exchange, serving to limit hypoxaemia. However, hypoxia-induced hyperventilation causes hypocapnia and respiratory alkalosis owing to excessive elimination of carbon dioxide. During acute exposure to hypoxia, cerebral vessels dilate, increasing cerebral blood flow and combating the reduction in arterial oxygen content in hypoxia, thereby maintaining cerebral oxygen delivery. In contrast, hypocapnia mediates constriction of the cerebrovasculature, acting to decrease brain blood flow. The counteractive effect of these opposing stimuli during exposure to hypoxia is an important net determinant of oxygen delivery to the brain, critical for neuronal performance and behaviour. Although it is widely recognized that cognitive function is impaired during exposure to hypoxia, the relative influence of hypoxia and hypocapnia per se is not fully established. In this issue of Experimental Physiology, Friend, Balanos, and Lucas (2019) explore the independent effects of acute normobaric hypoxia and hypocapnia on cerebrovascular haemodynamics and cognitive function. Healthy, young, male participants were exposed to 60 min of poikilocapnic hypoxia (allowing carbon dioxide to decline freely during hypoxic hyperventilation) and, on a separate day, to 60 min of isocapnic hypoxia (with dynamic end-tidal forcing used to clamp carbon dioxide to baseline levels). A subset of participants also performed a 60 min voluntary hyperventilation task during an additional experimental session toestablish euoxic hypocapnia.Middle cerebral artery velocity was measured as an index of ‘global’ cerebral blood flowusing transcranial Doppler ultrasound. Cognitive testswere performed before and after gas manipulations. Indices of prefrontal