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Aims   Myocardial reperfusion damage after severe ischemia was an important issue during a clinical practice. However, the exacted pathogenesis involved remained unclear and also lacks effective interventions. Melatonin was identified to exert protective effects for alleviating the myocardial I/R injury. This meta-analysis was determined to evaluate the efficacy of melatonin treatment against reperfusion insult and further summarize potential molecular and cellular mechanisms.Methods and Results   15 eligible studies with 211 animals (108 received melatonin and 103 received vehicle) were included after searching the databases of PubMed, MEDLINE, Embase, and Cochrane. Pretreatment with melatonin was associated with a significant lower infarct size in comparison with vehicle in myocardial I/R damage (WMD: -20.45, 95% CI: -25.43 to -15.47,  p  < 0.001;  I  2  = 91.4%,  p  < 0.001). Evidence from subgroup analyses and sensitivity analysis indicated the robust and consistent cardioprotective effect of melatonin, while the metaregression also did not unmask any significant interactions between the pooled estimates and covariates (i.e., sample size, state, species, study type, route of administration, and duration of reperfusion, along with timing regimen of pretreatment). Accordingly, melatonin evidently increased EF (WMD: 17.19, 95% CI: 11.08 to 23.29,  p  < 0.001;  I  2  = 77.0%,  p  < 0.001) and FS (WMD: 14.18, 95% CI: 11.22 to 17.15,  p  < 0.001;  I  2  = 3.5%,  p  = 0.387) in the setting of reperfusion damage.Conclusions   Melatonin preadministration conferred a profound cardioprotection against myocardial I/R injury in preclinical studies.

Melatonin against Myocardial Ischemia-Reperfusion Injury: A Meta-analysis and Mechanism Insight from Animal Studies