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.
Pan
Ting-Ting
TT
Department of Pharmacology, National University of Singapore, Singapore.
Chen
Yong Qian
YQ
Bian
Jin-Song
JS
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D006862:Hydrogen Sulfide