Breathe, Breathe in the Air

Abstract

See related article, pp 106–113 Blood flow to the brain is highly regulated through an array of interacting cells and molecular signals, all impinging on the vasculature. Although many mechanisms influence cerebrovascular resistance and, thus, cerebral blood flow,1 2 of the most powerful regulators are molecular oxygen and carbon dioxide.1,2 The impact of sustained hypoxia (decreases in arterial Po2) and hypercapnia (increases in arterial Pco2) on cerebral blood flow has been studied widely in animal models and in people.2 Both hypoxia and hypercapnia can occur as a result of environmental factors but also occur under some pathophysiological conditions. For example, periodic hypoxia and hypercapnia are both key elements of sleep-disordered breathing, a group of abnormalities that include obstructive sleep apnea.3 Obstructive sleep apnea is an increasingly prevalent condition with a complex pathophysiology that encompasses activation of the sympathetic nervous system and vascular abnormalities, as well as disturbed sleep patterns.3 Obstructive sleep apnea is often associated with hypertension and is known to increase the risk for cerebrovascular disease, stroke, and cognitive decline.4,5 Because intermittent hypoxia is one element of obstructive sleep apnea and is relatively easy to produce experimentally, many investigators have studied effects of this type of hypoxia using animal models. Although intermittent hypoxia does not mimic the entire array of changes that occur, there is evidence that brief repetitive periods of hypoxia contribute to the overall pathophysiology of obstructive sleep apnea.6 Previous studies of the effects of intermittent hypoxia have described diverse vascular effects that include activation of oxidant- and immune-related pathways, endothelial dysfunction, vascular hypertrophy, and the progression of atherosclerosis.3,6 Although obstructive sleep apnea is a risk factor for stroke and cognitive decline,4, …