| Abstract
| - Abstract. Objective: We tested the hypotheses that low concentration of H2O2 attenuates the Ca2+ paradox (Ca2+ PD) injury, and that activation of protein kinase C (PKC) and/or ATP-sensitive potassium channel (KATP) are involved in the protective effects of H2O2. Methods: Langendorff-perfused rat hearts were subjected to the Ca2+PD (10 min of Ca2+ depletion followed by 10 min of Ca2+ repletion). Functional and biochemical effects of H2O2 and other interventions on the cell injury induced by the Ca2+ PD were assessed. Results: In the Ca2+ PD hearts pretreated with 20 μmol/l H2O2, left ventricular end-diastolic pressure and coronary flow were significantly preserved. Furthermore, peak lactate dehydrogenase release was significantly decreased and ATP contents were more preserved, compared with non-treated Ca2+ PD hearts. H2O2-treated hearts also showed remarkable preservation of cell structure. Addition of a specific PKC inhibitor, chelerythrine during H2O2 treatment completely abolished the beneficial effects of H2O2 on the Ca2+ PD. Similarly, an activator of PKC, Phorbol 12-myristate 13 acetate mimicked the protection by H2O2. Furthermore, pretreatment with a KATP opener, cromakalim also provided protection similar to H2O2 against the Ca2+ PD injury. However, a specific KATP inhibitor, glibenclamide was not able to completely block the effects of H2O2. Conclusions: These findings suggest that pretreatment with low concentration of H2O2 provides significant protection against the lethal injury of Ca2+ PD in rat hearts. PKC-mediated signaling pathways appear to play a crucial role in the protection against the Ca2+ PD injury.
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