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  • Review Article
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New and revisited approaches to preserving the reperfused myocardium

Nature Reviews Cardiology volume 14, pages 679–693 (2017)Cite this article

Subjects

Key Points

  • Mortality after acute ST-segment elevation myocardial infarction (STEMI) has plateaued in the past decade, after a period of continual decline

  • Beyond early reperfusion, a variety of adjunctive agents to reduce myocardial infarction after reperfusion have been tested in clinical settings, and have yielded largely disappointing results

  • Before clinical testing, candidate cardioprotective agents should be tested in animal models with comorbidities similar to that in patients, and in combination with P2Y12 inhibitors

  • Approaches for improving cardiac function following STEMI that have been promising in preclinical studies include those that target mitochondrial bioenergetics, pyroptosis, autophagy, and no-reflow and anaesthetic preconditioning

Abstract

Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.

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Figure 1: New and updated approaches to treat the reperfused myocardium.
Figure 2: Sites of reactive oxygen species (ROS) production within the mitochondria.
Figure 3: The interplay between Toll-like receptor 9 (TLR9) and the NLRP3 inflammasome.

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Acknowledgements

D.A.B. has received funding from the NIH (NHLBI R01-123647). R.A.G. is supported by NIH (P01 HL112730, R01 HL132075).

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Authors and Affiliations

  1. Cardiovascular Research Institute, Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, 91101, California, USA

    Robert A. Kloner, Marie Csete, Wangde Dai, Sharon L. Hale & Jianru Shi

  2. Division of Cardiovascular Medicine and Department of Medicine, Keck School of Medicine, University of Southern California, 1975 Zonal Avenue, Los Angeles, 90033, California, USA

    Robert A. Kloner, Wangde Dai & Jianru Shi

  3. Department of Human Nutrition, Foods, and Exercise, 1981 Kraft Drive, Blacksburg, 24060, Virginia, USA

    David A. Brown

  4. Virginia Tech Center for Drug Discovery, Virginia Tech, 1981 Kraft Drive, Blacksburg, 24060, Virginia, USA

    David A. Brown

  5. Virginia Tech Metabolic Phenotyping Core, Virginia Tech, 1981 Kraft Drive, Blacksburg, 24060, Virginia, USA

    David A. Brown

  6. Department of Anesthesiology, Keck School of Medicine, University of Southern California, Los Angeles, 90017, California, USA

    Marie Csete

  7. Department of Physiology and Cell Biology, University of South Alabama, 5851 USA Drive North, Mobile, 36688, Alabama, USA

    James M. Downey

  8. Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai, Cedars-Sinai Medical Center, 127 South San Vicente Boulevard, Los Angeles, 90048, California, USA

    Roberta A. Gottlieb

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Contributions

R.A.K., D.A.B., M.C., W.D., J.M.D., R.G., and J.S. researched data for the article. R.A.K., D.A.B., M.C., J.M.D., and R.G. wrote the article and substantially contributed to the discussion of its content. R.A.K., D.A.B., M.C., J.M.D., R.G., S.L.H., and J.S. reviewed/edited the manuscript before submission.

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Correspondence to Robert A. Kloner.

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Competing interests

R.A.K. has received grant funding from Faraday Pharmaceuticals and Laboratoires Servier. D.A.B. has received funding from Catabasis Pharmaceuticals and Stealth BioTherapeutics, and has received consulting income from Stealth BioTherapeutics. The other authors declare no competing interests.

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Kloner, R., Brown, D., Csete, M. et al. New and revisited approaches to preserving the reperfused myocardium. Nat Rev Cardiol 14, 679–693 (2017). https://doi.org/10.1038/nrcardio.2017.102

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