Protective Effect of Remote Ischemic Preconditioning against Myocardial Ischemia-Reperfusion Injury in Rats and Mice: A Systematic Review and Meta-Analysis

Background: Remote ischemic preconditioning (RIPC) has cardioprotective effects. This study was designed to evaluate the effectiveness and potential influencing factors of RIPC for myocardial ischemia-reperfusion injury (MIRI) in rats and mice. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to identify animal model studies that explored the effect of RIPC on MIRI. The primary outcome was myocardial infarct size, and secondary outcomes included serum cardiac markers, vital signs, hemodynamic parameters, and TUNEL-positive cells. Quality was assessed using SYRCLE’s Risk of Bias Tool. Results: This systematic review and meta-analysis included 713 male animals from 37 studies. RIPC significantly protected against MIRI in small animal models by reducing infarct size, decreasing serum myocardial marker levels and cell death, and improving cardiac function. Subgroup analysis indicated that RIPC duration and sites influence the protective effect of RIPC on MIRI. Meta-regression suggested that study type and staining method might be sources of heterogeneity. The funnel plot, Egger’s test, and Begg’s test suggested the existence of publication bias, but results of the sensitivity analysis and nonparametric trim-and-fill method showed that the overall effect of RIPC on MIRI infarct size was robust. Conclusions: RIPC significantly protected against MIRI in small animal models by reducing infarct size, decreasing serum myocardial markers and limiting cell death, and improving cardiac function. RIPC duration and site influence the protective effect of RIPC on MIRI, which contributes in reducing confounding factors and determines the best approach for human studies.