Evaluation of Melatonin Therapy in Patients with Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis.

Tingting Lv,Yunwei Lou,Hangyuan Guo,Junwei Yan,Hui Lin,Jian Zhang,Zeying Zhang,Jiedong Zhou,Zheng Liu,Mengfei Ye,Chenchen Bi,Fangyi Luo,Daniel Lopez Malo

doi:10.1155/2022/4610522

Abstract

Objectives We conducted a meta-analysis to quantitatively evaluate the effect of melatonin therapy on patients with myocardial ischemia-reperfusion injury (MIRI) and explore the influencing factors. Background Although preclinical studies have shown that melatonin can alleviate MIRI, its protective effect on MIRI in patients remains controversial. Methods We searched PubMed, the Cochrane Library, and Embase. The primary outcome was cardiac function (left ventricular ejection fraction [LVEF], left ventricular end-diastolic volume [LVEDV], and left ventricular end-systolic volume [LVESV]) and myocardial infarct parameters (total left ventricular mass and infarct size). Results We included nine randomized controlled clinical trials with 631 subjects. Our results showed that melatonin had no significant effects on the primary outcome, but subgroup analyses indicated that when melatonin was administered by intravenous and intracoronary injection at the early stage of myocardial ischemia, LVEF was improved (<3.5 h; standardized mean difference [SMD]:0.50; 95% CI: 0.06 to 0.94; P = 0.03) and the infarct size was reduced (<2.5 h, SMD: −0.86; 95% CI: −1.51 to −0.22; P = 0.01), whereas when melatonin was injected at the late stage of myocardial ischemia (≥3.5 h or 2.5 h), the results were the opposite. Furthermore, melatonin intervention reduced the level of cardiac injury markers, inflammatory cytokines, oxidation factors, and increased the level of antioxidant factors (P < 0.001). Conclusions The results indicated that the cardioprotective function of melatonin for MIRI was influenced by the route and timing regimen of melatonin administration; the mechanism of which may be associated with the production of inflammatory cytokines, the balance of oxidation, and antioxidant factors.

Highlights

Acute myocardial infarction (AMI) is a leading cause of disability and mortality worldwide and is responsible for a third of all deaths in developed countries annually [1]
The remaining 122 studies were accessed by reviewing the full text, after which 113 articles were excluded as they had inappropriate experimental design, inappropriate study subjects or outcome measures, or lacked full text or adequate data
The results showed that LVEF was enhanced when melatonin was intravenous and intracoronary injection in the early stage of myocardial ischemia (

Summary

Introduction

Acute myocardial infarction (AMI) is a leading cause of disability and mortality worldwide and is responsible for a third of all deaths in developed countries annually [1]. Rapid restoration of coronary blood flow is the key to salvage the endangered myocardium [2, 3]. The most effective and prompt methods of revascularization are thrombolysis, primary percutaneous coronary intervention (pPCI), and coronary artery bypass graft (CABG), all of which have been proven to reduce infarct size and mortality. Subsequent myocardial reperfusion itself can lead to further myocardial damage, which accounts for up to 50% of the final myocardial injury [4–9]. Fast restoration of myocardial blood flow may induce myocardial injury (impaired myocardial contractility), ventricular arrhythmias, and microvascular dysfunction; this phenomenon is called myocardial ischemia-reperfusion injury (MIRI), which is strongly associated with adverse prognosis [5, 10–12].

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Discussion

Conclusion