Abstract
Aims Myocardial ischemia/reperfusion (I/R) injury is a leading cause of cardiomyocyte loss and subsequent ventricular dysfunction after restoring the coronary blood flow and contributes to considerable increase in morbidity and mortality. Resveratrol has been declared to confer cardioprotection against in vivo and ex vivo myocardial I/R injury. Here, we have sought to investigate the effects of preconditioning with resveratrol on myocardial I/R damage across the small animal studies. Methods and Results The MEDLINE, Google Scholar, PubMed, and Cochrane databases were searched for preclinical studies investigating resveratrol vs. vehicle published from the inception to July 2018. Eventually, 10 in vivo and 7 ex vivo studies with 261 animals (130 for resveratrol; 131 for vehicle) were included for meta-analysis. Pooled estimates for primary outcomes demonstrated that pretreatment with resveratrol significantly reduced the infarct size after myocardial I/R injury irrespective of in vivo (weighted mean difference (WMD): -13.42, 95% CI: -16.63 to -10.21, P ≤ 0.001) or ex vivo (WMD: -15.05, 95% CI: -18.23 to -11.86, P ≤ 0.001) studies. Consistently, stratified analysis according to the reperfusion duration, route of administration, or timing regimen of pretreatment all showed the infarct-sparing benefit of resveratrol. Metaregression did not indicate any difference in infarct size based on species, sample size, state, route of administration, reperfusion duration, and timing regimen of pretreatment. Meanwhile, sensitivity analysis also identified the cardioprotection of resveratrol with robust results in spite of significant heterogeneity. Conclusions Preconditioning with resveratrol appears to prevent the heart from I/R injury in comparison with vehicle, as evidenced by limited infarct size in a preclinical setting. Studies with large animals or randomized controlled trials will add more evidence and provide the rationale for clinical use.
Highlights
Acute myocardial infarction is the leading cause of disability and mortality worldwide [1]
Pooled estimates for primary outcomes demonstrated that pretreatment with resveratrol significantly reduced the infarct size after myocardial I/R injury irrespective of in vivo (weighted mean difference (WMD): -13.42, 95% CI: -16.63 to -10.21, P ≤ 0 001) or ex vivo (WMD: -15.05, 95% CI: -18.23 to -11.86, P ≤ 0 001) studies
For ex vivo studies, only TTC staining was used for evaluating the infarct size after reperfusion; (2) resveratrol vs. vehicle treatment; (3) nonhuman setting; (4) all the procedures and animal care were confirmed to the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (NIH publication No 85-23, revised 1996), and the animals were anesthetized before sacrifice, and the heart was excised for further analysis; and (5) no additional anti-inflammatory drugs were used
Summary
Acute myocardial infarction is the leading cause of disability and mortality worldwide [1]. It has been currently reported to confer a promising cardioprotective effect against ischemic heart disease in vivo, especially myocardial I/R injury, by modulating angiogenesis, oxidative stress, inflammatory, cardiomyocyte apoptosis, and mitochondrial function, along with energy metabolism [10,11,12,13,14,15,16]. It prevents the heart from fibrotic remodeling and hypertrophy. We conduct a comprehensive systematic review and meta-analysis to assess the critical role of resveratrol on myocardial I/R injury across the in vivo and ex vivo small animal studies
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