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  • Review Article
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Ischaemic conditioning and reperfusion injury

Key Points

  • Currently, no treatment has been proven to be effective for preventing 'myocardial reperfusion injury' — the death of cardiomyocytes that paradoxically occurs when reperfusing ischaemic myocardium

  • One or more brief cycles of ischaemia and reperfusion can protect the heart from acute myocardial infarction and myocardial reperfusion injury — a phenomenon termed 'ischaemic conditioning'

  • Ischaemic conditioning can be applied either directly to the heart or from afar; that is, to a remote organ or tissue (such as an arm or a leg)

  • Investigation of signalling pathways underlying ischaemic conditioning has identified molecular targets for pharmacological manipulation — a therapeutic strategy termed 'pharmacological cardioprotection'

  • Proof-of-concept clinical studies have shown mixed results of ischaemic conditioning in cardiac surgery and percutaneous coronary intervention; more consistently positive results have been observed in acute myocardial infarction

  • The results of large, multicentre, randomized, controlled clinical trials of ischaemic conditioning on clinical outcomes after cardiac surgery have highlighted the challenges in translating cardioprotection into clinical practice

Abstract

The 30-year anniversary of the discovery of 'ischaemic preconditioning' is in 2016. This endogenous phenomenon can paradoxically protect the heart from acute myocardial infarction by subjecting it to one or more brief cycles of ischaemia and reperfusion. Apart from complete reperfusion, this method is the most powerful intervention known for reducing infarct size. The concept of ischaemic preconditioning has evolved into 'ischaemic conditioning', a term that encompasses a number of related endogenous cardioprotective strategies, applied either directly to the heart (ischaemic preconditioning or postconditioning) or from afar, for example a limb (remote ischaemic preconditioning, perconditioning, or postconditioning). Investigations of signalling pathways underlying ischaemic conditioning have identified a number of therapeutic targets for pharmacological manipulation. Over the past 3 decades, a number of ischaemic and pharmacological cardioprotection strategies, discovered in experimental studies, have been examined in the clinical setting of acute myocardial infarction and CABG surgery. The results from many of the studies have been disappointing, and no effective cardioprotective therapy is currently used in clinical practice. Several large, multicentre, randomized, controlled clinical trials on cardioprotection have highlighted the challenges of translating ischaemic conditioning and pharmacological cardioprotection strategies into patient benefit. However, a number of cardioprotective therapies have shown promising results in reducing infarct size and improving clinical outcomes in patients with ischaemic heart disease.

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Figure 1: Ischaemic conditioning.
Figure 2: Signalling pathways of ischaemic conditioning.

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Acknowledgements

We thank the British Heart Foundation (FS/10/039/28270) and the Rosetrees Trust for continued support. This work was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre funding scheme, of which D.M.Y. is a senior investigator.

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Hausenloy, D., Yellon, D. Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol 13, 193–209 (2016). https://doi.org/10.1038/nrcardio.2016.5

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