Pre- and postconditioning the heart with hydrogen sulfide (H ₂S) against ischemia/reperfusion injury in vivo: a systematic review and meta-analysis

Abstract

Conditioning-like infarct limitation by enhanced level of hydrogen sulfide (H ₂S) has been demonstrated in many animal models of myocardial ischemia/reperfusion injury (MIRI) in vivo. We sought to evaluate the effect of H ₂S on myocardial infarction across in vivo pre-clinical studies of MIRI using a comprehensive systematic review followed by meta-analysis. Embase, Pubmed and Web of Science were searched for pre-clinical investigation of the effect of H ₂S on MIRI in vivo. Retained records (6031) were subjected to our pre-defined inclusion criteria then were objectively critiqued. Thirty-two reports were considered eligible to be included in this study and were grouped, based on the time of H ₂S application, into preconditioning and postconditioning groups. Data were pooled using random effect meta-analysis. We also investigated the possible impact of different experimental variables and the risk of bias on the observed effect size. Preconditioning with H ₂S ( n = 23) caused a significant infarct limitation of − 20.25% (95% CI − 25.02, − 15.47). Similarly, postconditioning with H ₂S ( n = 40) also limited infarct size by − 21.61% (95% CI − 24.17, − 19.05). This cardioprotection was also robust and consistent following sensitivity analyses where none of the pre-defined experimental variables had a significant effect on the observed infarct limitation. H ₂S shows a significant infarct limitation across in vivo pre-clinical studies of MIRI which include data from 825 animals. This infarct-sparing effect is robust and consistent when H ₂S is applied before ischemia or at reperfusion, independently on animal size or sulfide source. Validating this infarct limitation using large animals from standard medical therapy background and with co-morbidities should be the way forward.

Electronic supplementary material

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