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.