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Journal of Cardiovascular Translational Research
Published in: Journal of Cardiovascular Translational Research 5-6/2017

01-12-2017 | Original Article

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

Authors: Sarah Ekeloef, Natalie Halladin, Siv Fonnes, Svend Eggert Jensen, Tomas Zaremba, Jacob Rosenberg, Grete Jonsson, Jens Aarøe, Lærke Smidt Gasbjerg, Mette Marie Rosenkilde, Ismail Gögenur

Published in: Journal of Cardiovascular Translational Research | Issue 5-6/2017

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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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Literature
1.
Goldberg, R. J., Currie, K., White, K., Brieger, D., Steg, P. G., Goodman, S. G., et al. (2004). Six-month outcomes in a multinational registry of patients hospitalized with an acute coronary syndrome (the Global Registry of Acute Coronary Events [GRACE]). The American Journal of Cardiology, 93(3), 288–293.CrossRef
2.
Larose, E., Rodes-Cabau, J., Pibarot, P., Rinfret, S., Proulx, G., Nguyen, C. M., et al. (2010). Predicting late myocardial recovery and outcomes in the early hours of ST-segment elevation myocardial infarction traditional measures compared with microvascular obstruction, salvaged myocardium, and necrosis characteristics by cardiovascular magnetic resonance. Journal of the American College of Cardiology, 55(22), 2459–2469.CrossRef
3.
Lonborg, J., Vejlstrup, N., Kelbaek, H., Holmvang, L., Jorgensen, E., Helqvist, S., et al. (2013). Final infarct size measured by cardiovascular magnetic resonance in patients with ST elevation myocardial infarction predicts long-term clinical outcome: an observational study. European Heart Journal. Cardiovascular Imaging, 14(4), 387–395.CrossRef
4.
Burns, R. J., Gibbons, R. J., Yi, Q., Roberts, R. S., Miller, T. D., Schaer, G. L., et al. (2002). The relationships of left ventricular ejection fraction, end-systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction treated by thrombolysis. Journal of the American College of Cardiology, 39(1), 30–36.CrossRef
5.
Yellon, D. M., & Hausenloy, D. J. (2007). Myocardial reperfusion injury. NEJM, 357(11), 1121–1135.CrossRef
6.
Frohlich, G. M., Meier, P., White, S. K., Yellon, D. M., & Hausenloy, D. J. (2013). Myocardial reperfusion injury: looking beyond primary PCI. European Heart Journal, 34(23), 1714–1722.CrossRef
7.
Reiter, R. J., Mayo, J. C., Tan, D. X., Sainz, R. M., Alatorre-Jimenez, M., & Qin, L. (2016). Melatonin as an antioxidant: under promises but over delivers. Journal of Pineal Research, 61(3), 253–278.CrossRef
8.
Reiter, R. J., Tan, D. X., Paredes, S. D., & Fuentes-Broto, L. (2010). Beneficial effects of melatonin in cardiovascular disease. Annals of Medicine, 42(4), 276–285.CrossRef
9.
Lochner, A., Genade, S., Davids, A., Ytrehus, K., & Moolman, J. A. (2006). Short- and long-term effects of melatonin on myocardial post-ischemic recovery. Journal of Pineal Research, 40(1), 56–63.CrossRef
10.
Genade, S., Genis, A., Ytrehus, K., Huisamen, B., & Lochner, A. (2008). Melatonin receptor-mediated protection against myocardial ischaemia/reperfusion injury: role of its anti-adrenergic actions. Journal of Pineal Research, 45(4), 449–458.CrossRef
11.
Dobsak, P., Siegelova, J., Eicher, J. C., Jancik, J., Svacinova, H., Vasku, J., et al. (2003). Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart. Pathophysiology, 9(3), 179–187.CrossRef
12.
Petrosillo, G., Colantuono, G., Moro, N., Ruggiero, F. M., Tiravanti, E., Di Venosa, N., et al. (2009). Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening. American Journal of Physiology. Heart and Circulatory Physiology, 297(4), H1487–H1493.CrossRef
13.
Paradies, G., Petrosillo, G., Paradies, V., Reiter, R. J., & Ruggiero, F. M. (2010). Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease. Journal of Pineal Research, 48(4), 297–310.CrossRef
14.
Halladin, N. L., Busch, S. E., Jensen, S. E., Hansen, H. S., Zaremba, T., Aaroe, J., et al. (2014). Intracoronary and systemic melatonin to patients with acute myocardial infarction: protocol for the IMPACT trial. Danish Medical Journal, 61(2), A4773.PubMed
15.
Schulz, K. F., Altman, D. G., & Moher, D. (2011). CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. International Journal of Surgery, 9(8), 672–677.CrossRef
16.
Rosenkilde, M. M., McLean, K. A., Holst, P. J., & Schwartz, T. W. (2004). The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G12/13 proteins but constitutive signaling only through Gi and G12/13 proteins. The Journal of Biological Chemistry, 279(31), 32524–32533.CrossRef
17.
Heydorn, A., Ward, R. J., Jorgensen, R., Rosenkilde, M. M., Frimurer, T. M., Milligan, G., et al. (2004). Identification of a novel site within G protein alpha subunits important for specificity of receptor-G protein interaction. Molecular Pharmacology, 66(2), 250–259.CrossRef
18.
Benned-Jensen, T., & Rosenkilde, M. M. (2008). Structural motifs of importance for the constitutive activity of the orphan 7TM receptor EBI2: analysis of receptor activation in the absence of an agonist. Molecular Pharmacology, 74(4), 1008–1021.CrossRef
19.
Hanasand, M., Omdal, R., Norheim, K. B., Goransson, L. G., Brede, C., & Jonsson, G. (2012). Improved detection of advanced oxidation protein products in plasma. Clinica Chimica Acta, 413(9–10), 901–906.CrossRef
20.
Yagi, K. (1998). Simple assay for the level of total lipid peroxides in serum or plasma. Methods in Molecular Biology, 108, 101–106.PubMed
21.
Lykkesfeldt, J. (2001). Determination of malondialdehyde as dithiobarbituric acid adduct in biological samples by HPLC with fluorescence detection: comparison with ultraviolet-visible spectrophotometry. Clinical Chemistry, 47(9), 1725–1727.PubMed
22.
Seljeskog, E., Hervig, T., & Mansoor, M. A. (2006). A novel HPLC method for the measurement of thiobarbituric acid reactive substances (TBARS). A comparison with a commercially available kit. Clinical Biochemistry, 39(9), 947–954.CrossRef
23.
Lonborg, J., Vejlstrup, N., Kelbaek, H., Botker, H. E., Kim, W. Y., Mathiasen, A. B., et al. (2012). Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. European Heart Journal, 33(12), 1491–1499.CrossRef
24.
Tan, D. X., Manchester, L. C., Reiter, R. J., Qi, W., Kim, S. J., & El-Sokkary, G. H. (1998). Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: prevention by melatonin. Journal of Pineal Research, 25(3), 184–191.CrossRef
25.
Liu, L. F., Qin, Q., Qian, Z. H., Shi, M., Deng, Q. C., Zhu, W. P., et al. (2014). Protective effects of melatonin on ischemia-reperfusion induced myocardial damage and hemodynamic recovery in rats. European Review for Medical and Pharmacological Sciences, 18(23), 3681–3686.PubMed
26.
Giacomo, C. G., & Antonio, M. (2007). Melatonin in cardiac ischemia/reperfusion-induced mitochondrial adaptive changes. Cardiovasc Hematol Dis Drug. Targets, 7(3), 163–169.
27.
Petrosillo, G., Di Venosa, N., Pistolese, M., Casanova, G., Tiravanti, E., Colantuono, G., et al. (2006). Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia-reperfusion: role of cardiolipin. The FASEB Journal, 20(2), 269–276.CrossRef
28.
Diez, E. R., Renna, N. F., Prado, N. J., Lembo, C., Ponce Zumino, A. Z., Vazquez-Prieto, M., et al. (2013). Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats. Journal of Pineal Research, 55(2), 166–173.CrossRef
29.
Ekeløf, S. V., Halladin, N. L., Jensen, S. E., Zaremba, T., Aaroe, J., Kjaergaard, B., et al. (2016). Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction. Heart and Vessels, 31(1), 88–95.CrossRef
30.
Gogenur, I., Kucukakin, B., Panduro Jensen, L., Reiter, R. J., & Rosenberg, J. (2014). Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair: a randomized, placebo-controlled, clinical trial. Journal of Pineal Research, 57(3), 10–15.CrossRef
31.
Dwaich, K. H., Al-Amran, F. G., Al-Sheibani, B. I., & Al-Aubaidy, H. A. (2016). Melatonin effects on myocardial ischemia-reperfusion injury: Impact on the outcome in patients undergoing coronary artery bypass grafting surgery. International Journal of Cardiology, 221, 977–986.CrossRef
32.
Dominguez-Rodriguez, A., Abreu-Gonzalez, P., de la Torre-Hernandez, JM., Gonzalez-Gonzalez, J., Garcia-Camarero, T., Consuegra-Sanchez, L., et al. (2017). Effect of intravenous and intracoronary melatonin as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: results of the melatonin adjunct in the acute myocardial infarction treated with angioplasty trial. Journal of Pineal Research, 62(1). https://​doi.​org/​10.​1111/​jpi.​12374.CrossRef
33.
Galley, H. F., Lowes, D. A., Allen, L., Cameron, G., Aucott, L. S., & Webster, N. R. (2014). Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis. Journal of Pineal Research, 56(4), 427–438.CrossRef
34.
Sahna, E., Parlakpinar, H., Turkoz, Y., & Acet, A. (2005). Protective effects of melatonin on myocardial ischemia/reperfusion induced infarct size and oxidative changes. Physiological Research, 54(5), 491–495.PubMed
35.
Sahna, E., Acet, A., Ozer, M. K., & Olmez, E. (2002). Myocardial ischemia-reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin. Journal of Pineal Research, 33(4), 234–238.CrossRef
36.
Andrabi, S. A., Sayeed, I., Siemen, D., Wolf, G., & Horn, T. F. (2004). Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. The FASEB Journal, 18(7), 869–871.CrossRef
37.
Engblom, H., Heiberg, E., Erlinge, D., Jensen, S. E., Nordrehaug, J. E., Dubois-Rande, J. L., et al. (2016). Sample size in clinical cardioprotection trials using myocardial salvage index, infarct size, or biochemical markers as endpoint. Journal of the American Heart Association, 5(3), e002708.CrossRef
38.
Carrick, D., Haig, C., Ahmed, N., Rauhalammi, S., Clerfond, G., Carberry, J., et al. (2016). Temporal evolution of myocardial hemorrhage and edema in patients after acute ST-segment elevation myocardial infarction: pathophysiological insights and clinical implications. Journal of the American Heart Association, 5(2).
39.
Fernandez-Jimenez, R., Sanchez-Gonzalez, J., Aguero, J., Garcia-Prieto, J., Lopez-Martin, G. J., Garcia-Ruiz, J. M., et al. (2015). Myocardial edema after ischemia/reperfusion is not stable and follows a bimodal pattern: imaging and histological tissue characterization. Journal of the American College of Cardiology, 65(4), 315–323.CrossRef
40.
Andersen, L. P., Gogenur, I., Rosenberg, J., & Reiter, R. J. (2016). Pharmacokinetics of melatonin: the missing link in clinical efficacy? Clinical Pharmacokinetics, 55(9), 1027–1030.CrossRef
41.
Serdar, Z., Serdar, A., Altin, A., Eryilmaz, U., & Albayrak, S. (2007). The relation between oxidant and antioxidant parameters and severity of acute coronary syndromes. Acta Cardiologica, 62(4), 373–380.CrossRef
42.
Lotfollahi, H., Mohammadi, M., Ghaffari, S., Badalzadeh, R., Sohrabi, B., Aslanabadi, N., et al. (2016). Effect of remote ischemic post-conditioning on oxidative stress in blood of STEMI patients treated with primary angioplasty. J Cardiovasc Thoracic Res, 8(3), 113–118.CrossRef
43.
Brennan, M. L., Penn, M. S., Van Lente, F., Nambi, V., Shishehbor, M. H., Aviles, R. J., et al. (2003). Prognostic value of myeloperoxidase in patients with chest pain. NEJM, 349(17), 1595–1604.CrossRef
44.
Vriend, J., & Reiter, R. J. (2015). The Keap1-Nrf2-antioxidant response element pathway: a review of its regulation by melatonin and the proteasome. Molecular and Cellular Endocrinology, 401, 213–220.CrossRef
45.
Guo, P., Pi, H., Xu, S., Zhang, L., Li, Y., Li, M., et al. (2014). Melatonin improves mitochondrial function by promoting MT1/SIRT1/PGC-1 alpha-dependent mitochondrial biogenesis in cadmium-induced hepatotoxicity in vitro. Toxicological Sciences, 142(1), 182–195.CrossRef
Metadata
Title
Effect of Intracoronary and Intravenous Melatonin on Myocardial Salvage Index in Patients with ST-Elevation Myocardial Infarction: a Randomized Placebo Controlled Trial
Authors
Sarah Ekeloef
Natalie Halladin
Siv Fonnes
Svend Eggert Jensen
Tomas Zaremba
Jacob Rosenberg
Grete Jonsson
Jens Aarøe
Lærke Smidt Gasbjerg
Mette Marie Rosenkilde
Ismail Gögenur
Publication date
01-12-2017
Publisher
Springer US
Published in
Journal of Cardiovascular Translational Research / Issue 5-6/2017
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI
https://doi.org/10.1007/s12265-017-9768-7

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