RESPONSE TO ACUTE HYPOXIA: A Challenge to Mimic Disease
Because hypoxia affects human physiology at multiple levels ranging from reflex mechanisms, such as the peripheral chemoreflex, to specific cellular pathways regulated through oxygen, experimental hypoxia could have utility in clinical research in various settings. Tonic chemoreceptor hyperactivity with subsequent sympathetic nervous system activation has been implicated in the pathogenesis of arterial hypertension [56]. Thus, peripheral chemoreceptor modulation could have therapeutic utility in this condition, particularly in patients not responding sufficiently to established therapies [57]. Recent studies demonstrated that acute hypoxia during high-resolution functional magnetic resonance imaging (fMRI) can be used to trace peripheral chemoreceptor responses in human beings [58]. Because changes in CO2 confound the response to hypoxic peripheral chemoreceptor stimulation, isocapnic hypoxia protocols have been proven useful in clinical research [59].
Acute hypoxia can also be used to test the tolerance in patients or those in occupational settings such as in fighter pilots. Moreover, hypoxia may produce a phenotype resembling a clinical condition, which could then be utilized to probe new therapies. However, hypoxia may also regulate a disease-relevant signaling pathway. Indeed, hypoxia plays a major role in a multitude of human diseases, either as a result of the disease, like in the case of pulmonary dysfunction, or by modifying the disease process as seen in some forms of cancer, where local hypoxia may affect differentiation of the tumor to more aggressive phenotypes [60].
PULMONARY ARTERIAL HYPERTENSION