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

Sarah V Ekeløf, Natalie L Halladin, Svend E Jensen, Tomas Zaremba, Jens Aarøe, Benedict Kjærgaard, Carsten W Simonsen, Jacob Rosenberg, Ismail Gögenur

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

11 Citationer (Scopus)

Resumé

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.

OriginalsprogEngelsk
TidsskriftHeart and Vessels
Vol/bind31
Udgave nummer1
Sider (fra-til)88-95
Antal sider8
ISSN0910-8327
DOI
StatusUdgivet - 2016

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Melatonin
Reperfusion Injury
Placebos
Area Under Curve
Myocardial Reperfusion Injury
Troponin T
Swine
ST Elevation Myocardial Infarction
Coronary Occlusion
Percutaneous Coronary Intervention
Infarction
Myocardial Ischemia
Oxidative Stress
Thorax
Antioxidants
Magnetic Resonance Imaging
Hormones
Wounds and Injuries

Citer dette

Ekeløf, Sarah V ; Halladin, Natalie L ; Jensen, Svend E ; Zaremba, Tomas ; Aarøe, Jens ; Kjærgaard, Benedict ; Simonsen, Carsten W ; Rosenberg, Jacob ; Gögenur, Ismail. / Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction. I: Heart and Vessels. 2016 ; Bind 31, Nr. 1. s. 88-95.
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title = "Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction",
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.",
author = "Ekel{\o}f, {Sarah V} and Halladin, {Natalie L} and Jensen, {Svend E} and Tomas Zaremba and Jens Aar{\o}e and Benedict Kj{\ae}rgaard and Simonsen, {Carsten W} and Jacob Rosenberg and Ismail G{\"o}genur",
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doi = "10.1007/s00380-014-0589-1",
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Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction. / Ekeløf, Sarah V; Halladin, Natalie L; Jensen, Svend E; Zaremba, Tomas; Aarøe, Jens; Kjærgaard, Benedict; Simonsen, Carsten W; Rosenberg, Jacob; Gögenur, Ismail.

I: Heart and Vessels, Bind 31, Nr. 1, 2016, s. 88-95.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction

AU - Ekeløf, Sarah V

AU - Halladin, Natalie L

AU - Jensen, Svend E

AU - Zaremba, Tomas

AU - Aarøe, Jens

AU - Kjærgaard, Benedict

AU - Simonsen, Carsten W

AU - Rosenberg, Jacob

AU - Gögenur, Ismail

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1007/s00380-014-0589-1

DO - 10.1007/s00380-014-0589-1

M3 - Journal article

VL - 31

SP - 88

EP - 95

JO - Heart and Vessels

JF - Heart and Vessels

SN - 0910-8327

IS - 1

ER -