Ischaemic and hypoxic conditioning

potential for protection of vital organs

Justin D. Sprick, Robert T. Mallet, Karin Przyklenk, Caroline Alice Rickards

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)278-294
Number of pages17
JournalExperimental Physiology
Volume104
Issue number3
DOIs
StatePublished - 1 Mar 2019

Fingerprint

Ischemic Preconditioning
Exercise
Clinical Trials
Hypoxia-Inducible Factor 1
Microglia
Hypercholesterolemia
Brain Ischemia
Anesthetics
Cause of Death
Anti-Inflammatory Agents
Transcription Factors
Therapeutics
Antioxidants
Adenosine Triphosphate
Hemodynamics
Stroke
Myocardial Infarction
Morbidity
Phenotype
Wounds and Injuries

Keywords

  • blood flow restriction exercise
  • cardioprotection
  • cerebroprotection
  • intermittent hypoxia
  • remote ischaemic preconditioning

Cite this

@article{c291d3b4dc764fe5aa8dee3a6d590106,
title = "Ischaemic and hypoxic conditioning: potential for protection of vital organs",
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.",
keywords = "blood flow restriction exercise, cardioprotection, cerebroprotection, intermittent hypoxia, remote ischaemic preconditioning",
author = "Sprick, {Justin D.} and Mallet, {Robert T.} and Karin Przyklenk and Rickards, {Caroline Alice}",
year = "2019",
month = "3",
day = "1",
doi = "10.1113/EP087122",
language = "English",
volume = "104",
pages = "278--294",
journal = "Experimental Physiology",
issn = "0958-0670",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",

}

Ischaemic and hypoxic conditioning : potential for protection of vital organs. / Sprick, Justin D.; Mallet, Robert T.; Przyklenk, Karin; Rickards, Caroline Alice.

In: Experimental Physiology, Vol. 104, No. 3, 01.03.2019, p. 278-294.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Ischaemic and hypoxic conditioning

T2 - potential for protection of vital organs

AU - Sprick, Justin D.

AU - Mallet, Robert T.

AU - Przyklenk, Karin

AU - Rickards, Caroline Alice

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

KW - blood flow restriction exercise

KW - cardioprotection

KW - cerebroprotection

KW - intermittent hypoxia

KW - remote ischaemic preconditioning

UR - http://www.scopus.com/inward/record.url?scp=85060637277&partnerID=8YFLogxK

U2 - 10.1113/EP087122

DO - 10.1113/EP087122

M3 - Article

VL - 104

SP - 278

EP - 294

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 3

ER -