Melatonin and the cardiovascular system in animals: systematic review and meta-analysis

Abstract

Melatonin, a hormone released by the pineal gland, demonstrates several effects on the cardiovascular system. Herein, we performed a systematic review and meta-analysis to verify the effects of melatonin in an experimental model of myocardial infarction. We performed a systematic review according to PRISMA recommendations and reviewed MEDLINE, Embase, and Cochrane databases. Only articles in English were considered. A systematic review of the literature published between November 2008 and June 2019 was performed. The meta-analysis was conducted using the RevMan 5.3 program provided by the Cochrane Collaboration. In total, 858 articles were identified, of which 13 were included in this review. The main results of this study revealed that melatonin benefits the cardiovascular system by reducing infarct size, improving cardiac function according to echocardiographic and hemodynamic analyses, affords antioxidant effects, improves the rate of apoptosis, decreases lactate dehydrogenase activity, enhances biometric analyses, and improves protein levels, as analyzed by western blotting and quantitative PCR. In the meta-analysis, we observed a statistically significant decrease in infarct size (mean difference [MD], -20.37 [-23.56, -17.18]), no statistical difference in systolic pressure (MD, -1.75 [-5.47, 1.97]), a statistically significant decrease in lactate dehydrogenase in animals in the melatonin group (MD, -4.61 [-6.83, -2.40]), and a statistically significant improvement in the cardiac ejection fraction (MD, -8.12 [-9.56, -6.69]). On analyzing potential bias, we observed that most studies presented a low risk of bias; two parameters were not included in the analysis, and one parameter had a high risk of bias. Melatonin exerts several effects on the cardiovascular system and could be a useful therapeutic target to combat various cardiovascular diseases.

Figure 1. Flow chart of experimental design.

Figure 2. Representation of the SYRCLE’s risk of bias tool for animal studies. Hooijmans et al. (43).

Figure 3a. Metanalysis of infarct size measurement by echocardiography (% left ventricular).

Figure 3b. Metanalysis of systolic blood pressure (mmHg).

Figure 3c. Metanalysis of lactate dehydrogenase (U/L).

Figure 3d. Metanalysis of ejection fraction measured by echocardiography (% left ventricular).

Figure 4. Risk of bias graph: review of authors’ judgment regarding each risk of bias item presented as percentages across all included studies.

Figure 5. Risk of bias summary: review of authors’ judgment regarding each risk of bias item for each included study.