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Effects of intracoronary melatonin on ischemia–reperfusion injury in ST-elevation myocardial infarction

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Abstract

Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia–reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia–reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8 % (16.1; 24.8) vs. placebo 20.2 % (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8 % (2.7; 7.1) vs. placebo 3.7 % (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32 % in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

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Acknowledgments

A special thanks to the Department of Diagnostic Imaging, the Laboratory of Biomedical Science and the staff at the Department of Cardiology, Aalborg University Hospital, Denmark. This work was supported by grants from the Lundbeck Foundation, the Aase and Ejnar Danielsens Foundation, the A. P. Møller Foundation for the Advancement of Medical Science, the Axel Muusfeldts Foundation, the Arvid Nilssons Foundation and the Snedkermester Sophus Jacobsens Foundation. These funders have had no influence on the study design, data collection, analysis and interpretation of data, or writing of the manuscript.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgery, Herlev Hospital, Centre for Perioperative Optimization, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark

    Sarah V. Ekeløf, Natalie L. Halladin, Jacob Rosenberg & Ismail Gögenur

  2. Department of Cardiology, Aalborg University Hospital, Hobrovej 18, 9000, Aalborg, Denmark

    Svend E. Jensen, Tomas Zaremba & Jens Aarøe

  3. Department of Cardiothoracic Surgery, Aalborg University Hospital, Hobrovej 18, 9000, Aalborg, Denmark

    Benedict Kjærgaard

  4. Department of Diagnostic Imaging, Aalborg University Hospital, Hobrovej 18, 9000, Aalborg, Denmark

    Carsten W. Simonsen

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  1. Sarah V. Ekeløf
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Correspondence to Sarah V. Ekeløf.

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Ekeløf, S.V., Halladin, N.L., Jensen, S.E. et al. Effects of intracoronary melatonin on ischemia–reperfusion injury in ST-elevation myocardial infarction. Heart Vessels 31, 88–95 (2016). https://doi.org/10.1007/s00380-014-0589-1

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