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

Conditioning-like infarct limitation by enhanced level of hydrogen sulfide (H(2)S) has been demonstrated in many animal models of myocardial ischemia/reperfusion injury (MIRI) in vivo. We sought to evaluate the effect of H(2)S 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(2)S 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(2)S 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(2)S (n = 23) caused a significant infarct limitation of − 20.25% (95% CI − 25.02, − 15.47). Similarly, postconditioning with H(2)S (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(2)S 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(2)S 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: The online version of this article (10.1007/s00395-017-0664-8) contains supplementary material, which is available to authorized users.