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

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.

Melatonin Improves Ischemia-Induced Circulation Recovery Impairment in Mice with Streptozotocin-Induced Diabetes by Improving the Endothelial Progenitor Cells Functioning

“…The doses of 10 mg/kg in mice imply equivalent doses of 0.81 mg/kg (around 50 mg/60 kg) in humans [ 38 ]. A recent review study for human myocardial ischemia-reperfusion injury found that intravenous route (with doses of 12–49 mg) of administration and early timing regimen benefit the cardioprotective effects of melatonin [ 39 ]. Melatonin is commonly administered orally in relatively small doses (1–10 mg) to humans but has a poor and variable bioavailability [ 40 ].…”

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure

“…The high levels of melatonin in these organelles are an evolutionary feature resulting from eukaryotes engulfing melatonin-synthesizing bacteria, along with their subsequent transformation into mitochondria (Figures 2 and 4) [58]. Considering the seriousness of ischemic/reperfusion lesions, it is not surprising that melatonin has been extensively experimentally and clini-cally tested to overcome the damaging actions of oxygen/glucose deprivation at the level of cardiomyocytes [59][60][61].…”

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

“…Moving to cardiac effects, in a small scale, placebo-controlled double-blinded randomized clinical trial of 92 patients with HF and a reduced ejection fraction, nighttime MT at a dose of 10 mg decreased the concentration of natriuretic peptides and improved the quality of life of the patients, compared to placebo [ 147 ]. Moreover, in recently reported systematic reviews and meta-analyses, MT conferred cardiac protection and improved cardiac function [ 148 , 149 ]. At the same time, it reduced the level of cardiac injury markers, inflammatory cytokines, and oxidative markers while it increased the concentration of antioxidant factors [ 148 ].…”