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Exp Physiol. 2018 Dec 31. doi: 10.1113/EP087122. [Epub ahead of print]

Ischemic and hypoxic conditioning: Potential for protection of vital organs.

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Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, 30307.
Department of Physiology & Anatomy, University of North Texas Health Science Center, Fort Worth, TX, 76107.
Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, 48201, USA.



What is the topic of this review? Paradoxically, ischemic and hypoxic conditioning paradigms protect vital organs from ischemic and hypoxic injury. In this Symposium Report, we focus on remote ischemic preconditioning (RIPC) and hypoxic preconditioning as novel therapeutic approaches for cardiac- and neuro-protection. What advances does it highlight? Growing interest in ischemic and hypoxic preconditioning has facilitated improved understanding of associated mechanisms and signaling pathways, and identified potential pitfalls with application of these therapies to clinical trials. Novel adaptations of preconditioning paradigms have also been developed, including intermittent hypoxia training, RIPC training, and RIPC-exercise, extending their utility to chronic settings.


Myocardial infarction and stroke remain leading causes of death worldwide, despite extensive resources directed towards developing effective treatments. In this Symposium Report we highlight the potential applications of intermittent ischemic and hypoxic conditioning protocols to combat the deleterious consequences of heart and brain ischemia. Insights into mechanisms underlying the protective effects of intermittent hypoxia training (IHT) are discussed, including the activation of hypoxia-inducible factor-1 and Nrf2 transcription factors, synthesis of antioxidant and ATP-generating enzymes, and a shift in microglia from pro- to anti-inflammatory phenotypes. Although there is little argument regarding the efficacy of remote ischemic preconditioning (RIPC) in pre-clinical models, this strategy has not consistently translated into the clinical arena. This lack of translation may be related to the patient populations targeted thus far, and the anesthetic regimen used in two of the major RIPC clinical trials. Additionally, we do not fully understand the mechanism through which RIPC protects the vital organs, and co-morbidities (e.g., hypercholesterolemia, diabetes) may interfere with its efficacy. Finally, novel adaptations have been made to extend RIPC to more chronic settings. One adaptation is RIPC-exercise (RIPC-X), an innovative paradigm that applies cyclical RIPC to blood flow restriction exercise (BFRE). Recent findings suggest that this novel exercise modality attenuates the exaggerated hemodynamic responses that may limit the use of conventional BFRE in some clinical settings. Collectively, intermittent ischemic and hypoxic conditioning paradigms remain an exciting frontier for the protection against ischemic injuries. This article is protected by copyright. All rights reserved.


blood flow restriction exercise; cardioprotection; cerebroprotection; intermittent hypoxia; remote ischemic preconditioning


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