Ventilatory and cerebrovascular regulation and integration at high-altitude

Ascent to high-altitude elicits compensatory physiological adaptations in order to improve oxygenation throughout the body. The brain is particularly vulnerable to the hypoxemia of terrestrial altitude exposure. Herein we review the ventilatory and cerebrovascular changes at altitude and how they are both implicated in the maintenance of oxygen delivery to the brain. Further, the interdependence of ventilation and cerebral blood flow at altitude is discussed. Following the acute hypoxic ventilatory response, acclimatization leads to progressive increases in ventilation, and a partial mitigation of hypoxemia. Simultaneously, cerebral blood flow increases during initial exposure to altitude when hypoxemia is the greatest. Following ventilatory acclimatization to altitude, and an increase in hemoglobin concentration—which both underscore improvements in arterial oxygen content over time at altitude—cerebral blood flow progressively decreases back to sea-level values. The complimentary nature of these responses (ventilatory, hematological and cerebral) lead to a tightly maintained cerebral oxygen delivery while at altitude. Despite this general maintenance of global cerebral oxygen delivery, the manner in which this occurs reflects integration of these physiological responses. Indeed, ventilation directly influences cerebral blood flow by determining the prevailing blood gas and acid/base stimuli at altitude, but cerebral blood flow may also influence ventilation by altering central chemoreceptor stimulation via central CO₂ washout. The causes and consequences of the integration of ventilatory and cerebral blood flow regulation at high altitude are outlined.