Ischaemic and hypoxic conditioning: potential for protection of vital organs

• Authors: Justin D Sprick, Emory University; Robert T Mallet, University of North Texas; Karin Przyklenk, Wayne State University; Caroline A Rickards, University of North Texas
• Journal Title: EXPERIMENTAL PHYSIOLOGY
• Volume: Volume 104, Number 3
• Publisher: WILEY | 2019-03-01, Pages 278-294
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1113/EP087122
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Physiology; blood flow restriction exercise; cardioprotection; cerebroprotection; intermittent hypoxia; remote ischaemic preconditioning; BLOOD-FLOW RESTRICTION; CHRONIC INTERMITTENT HYPOXIA; EXERCISE PRESSOR REFLEX; AMERICAN-HEART-ASSOCIATION; CENTRAL-NERVOUS-SYSTEM; INJURY SALVAGE KINASE; BYPASS GRAFT-SURGERY; NITRIC-OXIDE; REPERFUSION INJURY; HYPOBARIC HYPOXIA

Abstract

New Findings: What is the topic of this review? Remote ischaemic preconditioning (RIPC) and hypoxic preconditioning as novel therapeutic approaches for cardiac and neuroprotection. What advances does it highlight? There is improved understanding of mechanisms and signalling pathways associated with ischaemic and hypoxic preconditioning, and potential pitfalls with application of these therapies to clinical trials have been identified. Novel adaptations of preconditioning paradigms have also been developed, including intermittent hypoxia training, RIPC training and RIPC–exercise, extending their utility to chronic settings. Abstract: 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 ischaemic and hypoxic conditioning protocols to combat the deleterious consequences of heart and brain ischaemia. Insights into mechanisms underlying the protective effects of intermittent hypoxia training 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 ischaemic 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 anaesthetic 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 haemodynamic responses that may limit the use of conventional BFRE in some clinical settings. Collectively, intermittent ischaemic and hypoxic conditioning paradigms remain an exciting frontier for the protection against ischaemic injuries.