Therapeutic hypoxia to protect and revive ischemic heart and brain

Although hypoxia plays a central role in the pathobiology of cardiovascular and cerebrovascular diseases, controlled hypoxic stimuli, such as intermittent hypoxia conditioning (IHC), can trigger beneficial adaptations that counteract those diseases. IHC has been studied as a readily administered, non-pharmacological intervention for almost a century, it has not yet been widely adopted in clinical practice. Growing evidence demonstrates the beneficial preventive and therapeutic effects of IHC on the cardiovascular system, and although less conclusively established, on the brain. Moreover, IHC is highly feasible and raises few safety concerns. A notable limitation, similar to that of remote ischemic conditioning, is the lack of refined IHC protocols for personalized, disease-specific applications in the individual patient. Significant progress has been achieved in addressing this limitation. For example, increasingly sophisticated modern hypoxia equipment permits customization of IHC parameters according to each individual's responses to and tolerance of hypoxia. Still to be evaluated are the persistence of IHC's effects and the capacity of IHC booster protocols to renew its benefits. Comparative analyses of the mechanisms and efficacy of IHC and remote ischemic conditioning could aid in defining their respective applications and possible synergistic effects. This perspective article summarizes the historical development of IHC, presents a selection of preclinical and clinical studies exemplifying recent research progress, and discusses strategies to address the lingering concerns limiting clinical IHC applications.