Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia–reperfusion injuryEvidence for a role of KATP channels

Hydrogen sulfide (H2S) is a gaseous mediator, produced by the metabolic pathways that regulate tissue concentrations of sulfur–containing amino acids. Recent studies indicate that endogenous or exogenous H2S exerts physiological effects in the cardiovascular system of vertebrates, possibly through modulation of KATP channel opening. The present study was undertaken to examine the hypothesis that H2S is cytoprotective against myocardial ischemia–reperfusion injury and that this protective action is mediated by KATP opening. Rat isolated hearts were Langendorff–perfused and underwent 30 min left main coronary artery occlusion and 120 min reperfusion. The resulting injury was assessed as infarct size, determined by tetrazolium staining. Treatment of hearts with the H2S–donor, NaHS, commencing 10 min prior to the onset of coronary occlusion and maintained until 10 min reperfusion, resulted in a concentration–dependent limitation of infarct size (control, 41.0 ± 2.6% of risk zone; NaHS 0.1 μM, 33.9 ± 2.1%, [0.05 > P < 0.1]; NaHS 1 μM, 20.2 ± 2.1% [P < 0.01]). Pretreatment with the KATP channel blockers glibenclamide 10 μM or sodium 5–hydroxydecanoate (5HD) 100 μM led to abrogation of the infarct–limiting effect of NaHS 1 μM (glibenclamide + NaHS 42.5 ± 3.6%; 5HD + NaHS 44.7 ± 2.2%). No statistically significant effects of NaHS treatment on coronary flow, heart rate or left ventricular developed pressure were observed in this experimental preparation. These data provide the first evidence that exogenous H2S protects against irreversible ischemia–reperfusion injury in myocardium and support the involvement of KATP opening in the mechanism of action. Further work is required to elucidate the potential role of endogenous H2S as a cytoprotective mediator against myocardial ischemia–reperfusion injury, the mechanisms regulating its generation, and the nature of its interaction with protein targets such as the KATP channel.