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.

Melatonin in Heart Failure: A Promising Therapeutic Strategy?

“…Despite multiple cardiovascular benefits of melatonin supplementation, it is worth mentioning that due to various reasons few studies do not demonstrate the protective effect of melatonin in HF, such as in a rat model of isoproterenol-induced left ventricular hypertrophy [ 133 ] and a rabbit model of myocardial infarction [ 134 ]. This observation is consistent with the recent clinical studies conducted in the context of myocardial ischemia/reperfusion injury where the effect of melatonin administration is neutral [ 135 , 136 ] with unexpected detrimental effect favoring ventricular remodeling [ 135 ]. Most of the unexpected findings are due to methodological issues including, mainly, the severity of cardiac damage, dosages, time and mode of administration of the treatment, the type of animal models, age and comorbidities [ 137 ].…”

Cardiovascular Benefits of Dietary Melatonin: A Myth or a Reality?

“…In view of the above benefits in animal studies, melatonin supplementation is highly regarded as an effective therapy in cardiac diseases (Yang et al, 2014 ; Opie and Lecour, 2016 ; Sun et al, 2016 ). Unfortunately, very few clinical trials have investigated the effects of exogenous melatonin in cardiac diseases (Dominguez-Rodriguez et al, 2007 ; Gogenur et al, 2014 ; Ekelof et al, 2016 ) (Table 2 ). In patients undergoing surgery for abdominal aortic aneurisms, an infusion of 50 mg melatonin over a 2 h period followed by oral administration of 10 mg melatonin for the first three nights after surgery, protects the heart against reperfusion injury by reducing cardiac morbidity as well as the occurrence of myocardial ischemia after abdominal aortic aneurism repair (Gogenur et al, 2014 ).…”

“…A lack of beneficial effects of melatonin is also reported in other clinical study (Ekeloef et al, 2017 ). Interestingly, preclinical testing showed that melatonin fails to protect the heart in a closed-chest porcine model of acute myocardial infarction (Halladin et al, 2014 ; Ekelof et al, 2016 ) and in a rabbit model of myocardial I/R injury (Dave et al, 1998 ). It is possible that the intracoronary and intravenous administrations, as opposed to the preferred oral administration, may contribute to the neutral outcomes as suggested by other studies (Dwaich et al, 2016 ).…”

Effects of melatonin on cardiovascular diseases: progress in the past year

“…Ghaeli et al [ 19 ] reported that in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, administration of melatonin plus standard treatment significantly reduced the level of creatine kinase-MB compared with the control group, receiving only standard therapy. However, in a porcine closed-chest reperfusion infarct model, intracoronary or intravenous melatonin administration did not reduce myocardial reperfusion injury [ 20 ]. The lack of effect may be because of the ineffective dose and route of administration.…”