Remote ischaemic preconditioning: closer to the mechanism?

Jonathan Gleadle, Annette Mazzone

    Research output: Contribution to journalArticle

    8 Citations (Scopus)
    3 Downloads (Pure)

    Abstract

    Brief periods of ischaemia followed by reperfusion of one tissue such as skeletal muscle can confer subsequent protection against ischaemia-induced injury in other organs such as the heart. Substantial evidence of this effect has been accrued in experimental animal models. However, the translation of this phenomenon to its use as a therapy in ischaemic disease has been largely disappointing without clear evidence of benefit in humans. Recently, innovative experimental observations have suggested that remote ischaemic preconditioning (RIPC) may be largely mediated through hypoxic inhibition of the oxygen-sensing enzyme PHD2, leading to enhanced levels of alpha-ketoglutarate and subsequent increases in circulating kynurenic acid (KYNA). These observations provide vital insights into the likely mechanisms of RIPC and a route to manipulating this mechanism towards therapeutic benefit by direct alteration of KYNA, alpha-ketoglutarate levels, PHD inhibition, or pharmacological targeting of the incompletely understood cardioprotective mechanism activated by KYNA.

    Original languageEnglish
    Article number2846
    Number of pages8
    JournalF1000Research
    Volume5
    DOIs
    Publication statusPublished - 13 Dec 2016

    Keywords

    • ischaemia
    • reperfusion
    • remote ischaemic preconditioning
    • cardioprotection

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