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      An overview of protective strategies against ischemia/reperfusion injury: The role of hyperbaric oxygen preconditioning

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          Abstract

          Introduction

          Ischemia/reperfusion (I/R) injury, such as myocardial infarction, stroke, and peripheral vascular disease, has been recognized as the most frequent causes of devastating disorders and death currently. Protective effect of various preconditioning stimuli, including hyperbaric oxygen (HBO), has been proposed in the management of I/R.

          Methods

          In this study, we searched and reviewed up‐to‐date published papers to explore the pathophysiology of I/R injury and to understand the mechanisms underlying the protective effect of HBO as conditioning strategy.

          Results

          Animal study and clinic observation support the notion that HBO therapy and conditioning provide beneficial effect against the deleterious effects of postischemic reperfusion. Several explanations have been proposed. The first likely mechanism may be that HBO counteracts hypoxia and reduces I/R injury by improving oxygen delivery to an area with diminished blood flow. Secondly, by reducing hypoxia–ischemia, HBO reduces all the pathological events as a consequence of hypoxia, including tissue edema, increased affective area permeability, postischemia derangement of tissue metabolism, and inflammation. Thirdly, HBO may directly affect cell apoptosis, signal transduction, and gene expression in those that are sensitive to oxygen or hypoxia. HBO provides a reservoir of oxygen at cellular level not only carried by blood, but also by diffusion from the interstitial tissue where it reaches high concentration that may last for several hours, improves endothelial function and rheology, and decreases local inflammation and edema.

          Conclusion

          Evidence suggests the benefits of HBO when used as a preconditioning stimulus in the setting of I/R injury. Translating the beneficial effects of HBO into current practice requires, as for the “conditioning strategies”, a thorough consideration of risk factors, comorbidities, and comedications that could interfere with HBO‐related protection.

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          Most cited references120

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          Hypoxia-inducible factor 1: master regulator of O2 homeostasis.

          Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates essential homeostatic responses to reduced O2 availability in mammals. Recent studies have provided insights into the O2-dependent regulation of HIF-1 expression, target genes regulated by HIF-1, and the effects of HIF-1 deficiency on cellular physiology and embryonic development.
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            Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy.

            Since the initial description of the phenomenon by Jennings et al 50 years ago, our understanding of the underlying mechanisms of reperfusion injury has grown significantly. Its pathogenesis reflects the confluence of multiple pathways, including ion channels, reactive oxygen species, inflammation, and endothelial dysfunction. The purposes of this review are to examine the current state of understanding of ischemia-reperfusion injury, as well as to highlight recent interventions aimed at this heretofore elusive target. In conclusion, despite its complexity our ongoing efforts to mitigate this form of injury should not be deterred, because nearly 2 million patients annually undergo either spontaneous (in the form of acute myocardial infarction) or iatrogenic (in the context of cardioplegic arrest) ischemia-reperfusion. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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              Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore.

              Environmental stresses converge on the mitochondria that can trigger or inhibit cell death. Excitable, postmitotic cells, in response to sublethal noxious stress, engage mechanisms that afford protection from subsequent insults. We show that reoxygenation after prolonged hypoxia reduces the reactive oxygen species (ROS) threshold for the mitochondrial permeability transition (MPT) in cardiomyocytes and that cell survival is steeply negatively correlated with the fraction of depolarized mitochondria. Cell protection that exhibits a memory (preconditioning) results from triggered mitochondrial swelling that causes enhanced substrate oxidation and ROS production, leading to redox activation of PKC, which inhibits glycogen synthase kinase-3beta (GSK-3beta). Alternatively, receptor tyrosine kinase or certain G protein-coupled receptor activation elicits cell protection (without mitochondrial swelling or durable memory) by inhibiting GSK-3beta, via protein kinase B/Akt and mTOR/p70(s6k) pathways, PKC pathways, or protein kinase A pathways. The convergence of these pathways via inhibition of GSK-3beta on the end effector, the permeability transition pore complex, to limit MPT induction is the general mechanism of cardiomyocyte protection.
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                Author and article information

                Contributors
                yangz@upstate.edu
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                30 March 2018
                May 2018
                : 8
                : 5 ( doiID: 10.1002/brb3.2018.8.issue-5 )
                : e00959
                Affiliations
                [ 1 ] Master II level in Hyperbaric Medicine Department of Biomedical Sciences University of Padova Padova Italy
                [ 2 ] Faculty of Medicine “Victor Babeș” University of Medicine and Pharmacy Timișoara Romania
                [ 3 ] TEAMHealth Research Institute TGH Tampa FL USA
                [ 4 ] The Institute for Human Performance SUNY Upstate Medical University Syracuse NY USA
                [ 5 ] Center for Translational Research and Systems Medicine “Victor Babeș” University of Medicine and Pharmacy Timișoara Romania
                Author notes
                [*] [* ] Correspondence

                Zhongjin Yang, Department of Anesthesiology, Upstate Medical University, Syracuse, NY, USA.

                Email: yangz@ 123456upstate.edu

                Author information
                http://orcid.org/0000-0001-6044-7849
                Article
                BRB3959
                10.1002/brb3.959
                5943756
                29761012
                e2d4af47-eab4-458b-9b81-ff6f0e24b7a4
                © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 June 2017
                : 12 February 2018
                : 18 February 2018
                Page count
                Figures: 2, Tables: 1, Pages: 14, Words: 12993
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                brb3959
                May 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.7.2 mode:remove_FC converted:10.05.2018

                Neurosciences
                hyperbaric oxygenation,ischemia–reperfusion injury,preconditioning
                Neurosciences
                hyperbaric oxygenation, ischemia–reperfusion injury, preconditioning

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