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Current Modalities and Mechanisms Underlying Cardioprotection by Ischemic Conditioning

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Abstract

Ischemic preconditioning is a process which serves to mitigate reperfusion injury. Preconditioning of the heart can be achieved through natural, pharmacological, and mechanical means. Mechanical preconditioning appears to have the greatest chance of good outcomes while methods employing pharmacologic preconditioning have been largely unsuccessful. Remote ischemic preconditioning achieves a cardioprotective effect by applying cycles of ischemia and reperfusion in a distal limb, stimulating the release of a neurohumoral cardioprotective factor incited by stimulation of afferent neurons. The cardioprotective factor stimulates the reperfusion injury salvage kinase (RISK) and survivor activator factor enhancement (SAFE) signaling cascades in cardiomyocytes which promote cell survival by the expression of anti-apoptotic genes and inhibition of the opening of mitochondrial permeability transition pores. Clinical application of ischemic preconditioning involving targets in the RISK and SAFE signaling appears promising in the treatment of acute myocardial infarction; however, clinical trials have yet to demonstrate additional benefit to current therapy.

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Funding

This work was supported by research grants R01 HL112597, R01 HL116042, and R01 HL120659 to DK Agrawal from the National Heart, Lung and Blood Institute, National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Clinical & Translational Science, The Peekie Nash Carpenter Endowed Chair in Medicine, Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE, 68178, USA

    John H. Rosenberg, John H. Werner & Devendra K. Agrawal

  2. Department of Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, NE, USA

    Michael J. Moulton

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  1. John H. Rosenberg
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  2. John H. Werner
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  3. Michael J. Moulton
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  4. Devendra K. Agrawal
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Correspondence to Devendra K. Agrawal.

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This article does not contain any studies with human participants or animals performed by any of the authors. Findings were gathered from the published articles in the literature.

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The contributing editor for this article was Junjie Xiao.

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Rosenberg, J.H., Werner, J.H., Moulton, M.J. et al. Current Modalities and Mechanisms Underlying Cardioprotection by Ischemic Conditioning. J. of Cardiovasc. Trans. Res. 11, 292–307 (2018). https://doi.org/10.1007/s12265-018-9813-1

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  • DOI: https://doi.org/10.1007/s12265-018-9813-1

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