All in the timing: A comparison between the cardioprotection induced by H2S preconditioning and post-infarction treatment

Abstract

In the current study, we investigated the delayed cardioprotection induced by H2S preconditioning in an in vivo rat model of myocardial infarction. Assessment of infarct size revealed that a single bolus of NaHS (a donor of H2S, at 0.1-10 μmol/kg body weight) administered 1 day before myocardial infarction produced a strong infarct-limiting effect. A time course study demonstrated that the protection lasted at least 3 days after the preconditioning stimulus. We further compared the effect of H2S preconditioning with post-infarction treatment. Although injection of NaHS (1 μmol/kg once daily) for 3 days after myocardial infarction also significantly decreased infarct size, the protective effect was significantly lower than that afforded by H2S preconditioning. A combination of both preconditioning and post-treatment did not produce a stronger protection compared with H2S preconditioning alone. Pretreatment with chelerythrine chloride (5 mg/kg, i.p.), a protein kinase C (PKC) inhibitor, 15 min before NaHS administration blocked the infarct-sparing effect of H2S preconditioning. In conclusion, the current study provided the first evidence that H2S preconditioning produces strong late cardioprotection through a PKC-dependent mechanism. Such protection could not be reproduced by H2S treatment after the infarction occurred. A combination of both preconditioning and post-treatment does not provide additional benefit and hence is not necessary when the access to preconditioning has been secured. © 2009 Elsevier B.V.