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Effect of Intracoronary and Intravenous Melatonin on Myocardial Salvage Index in Patients with ST-Elevation Myocardial Infarction: a Randomized Placebo Controlled Trial

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Abstract

Melatonin has attenuated myocardial ischemia reperfusion injury in experimental studies. We hypothesized that the administration of melatonin during acute myocardial reperfusion improves myocardial salvage index in patients with ST-elevation myocardial infarction. Patients (n = 48) were randomized in a 1:1 ratio to intracoronary and intravenous melatonin (total 50 mg) or placebo. The myocardial salvage index assessed by cardiac magnetic resonance imaging at day 4 (± 1 day) after primary percutaneous coronary intervention was similar in the melatonin group (n = 22) at 55.3% (95% CI 47.0–63.6) and the placebo group (n = 19) at 61.5% (95% CI 57.5–65.5), p = 0.21. The levels of high-sensitive troponin T, creatinine kinase myocardial band, and oxidative biomarkers (advanced oxidation protein products, malondialdehyde, myeloperoxidase) were similar in the groups. The frequency of clinical events at 90 days did not differ between the groups. In conclusion, melatonin did not improve the myocardial salvage index after primary percutaneous coronary intervention in patients with ST elevation myocardial infarction compared with placebo.

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Abbreviations

AAR:

Area at risk

AUC:

Area under the curve

AOPP:

Advanced oxidation protein products

STEMI:

ST-elevation myocardial infarction

CKMB:

Creatinine kinase myocardial band

CMR:

Cardiac magnetic resonance imaging

hs-TnT:

High-sensitive troponin T

iqr:

Interquartile range

LGE:

Late gadolinium enhancement images

MDA:

Malondialdehyde

MPO:

Myeloperoxidase

MSI:

Myocardial salvage index

NFE2L2:

Nuclear factor erythroid 2-like 2

pPCI:

Primary percutaneous coronary intervention

SSFP:

Steady-state free procession

TIMI:

Thrombosis in myocardial infarction

T2-STIR imaging:

Short-axis tau inversion recovery T2-weighted imaging

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Acknowledgements

We would like to thank the project nurses Kasper Villefrance and Charlotte Schmidt Skov, the PCI operators, and the staff in the catheterization laboratory at the Aalborg University Hospital.

Funding

This work was supported by grants from the University of Copenhagen, the Aase and Ejnar Danielsen’s Foundation, the Arvid Nilssons Foundation, the A P Møller Foundation for the Advancement of Medical Science, the Beckett Foundation, the Hede Nielsen Family Foundation, the Jens Anker Andersen Foundation, the Edith and Olfert Dines Hansen Foundation, the Axel Muusfeldts Foundation, the snedkermester Sophus Jacobsen and wife Astrid Jacobsen Foundation, and the Holger and Ruth Hesse Memorial Scholarship. None of the funders has had any influence on the study design, data collection, data analysis, interpretation, or writing of the manuscript. This study received no financial support from the industry.

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Authors and Affiliations

  1. Center for Surgical Science, Department of Surgery, Zealand University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark

    Sarah Ekeloef & Ismail Gögenur

  2. Center for Perioperative Optimization, Department of Surgery, Herlev University Hospital, Herlev Ringvej 75, 2730, Herlev, Denmark

    Natalie Halladin, Siv Fonnes & Jacob Rosenberg

  3. Department of Cardiology, Aalborg University Hospital, Hobrovej 18-22, 9100, Aalborg, Denmark

    Svend Eggert Jensen, Tomas Zaremba & Jens Aarøe

  4. Department of Medical Biochemistry, Stavanger University Hospital, PB 8100, 4068, Stavanger, Norway

    Grete Jonsson

  5. Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark

    Lærke Smidt Gasbjerg & Mette Marie Rosenkilde

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  1. Sarah Ekeloef
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  2. Natalie Halladin
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  3. Siv Fonnes
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Correspondence to Sarah Ekeloef.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors

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Ekeloef, S., Halladin, N., Fonnes, S. et al. Effect of Intracoronary and Intravenous Melatonin on Myocardial Salvage Index in Patients with ST-Elevation Myocardial Infarction: a Randomized Placebo Controlled Trial. J. of Cardiovasc. Trans. Res. 10, 470–479 (2017). https://doi.org/10.1007/s12265-017-9768-7

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