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

In the current study, we investigated the delayed cardioprotection induced by H(2)S preconditioning in an in vivo rat model of myocardial infarction. Assessment of infarct size revealed that a single bolus of NaHS (a donor of H(2)S, at 0.1-10 micromol/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 H(2)S preconditioning with post-infarction treatment. Although injection of NaHS (1 micromol/kg once daily) for 3 days after myocardial infarction also significantly decreased infarct size, the protective effect was significantly lower than that afforded by H(2)S preconditioning. A combination of both preconditioning and post-treatment did not produce a stronger protection compared with H(2)S 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 H(2)S preconditioning. In conclusion, the current study provided the first evidence that H(2)S preconditioning produces strong late cardioprotection through a PKC-dependent mechanism. Such protection could not be reproduced by H(2)S 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.