Zusammenfassung
Background Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase. Methods Pentobarbital-anaesthetized male ...
Zusammenfassung
Background Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase. Methods Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10 mu g/g intraperitoneally) or its vehicle dimethy sulfoxide (10 mu l/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18?min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-BadSer112 and B-cell lymphoma 2 was determined using Western immunoblotting analysis. Results Infarct size in control animals (CON) was 46 +/- 3%. Dimethylsulfoxide (47 +/- 3%) and Pim-1 kinase inhibitor II (44 +/- 5%) did not significantly reduce infarct size. Desflurane (16 +/- 2%*; *P?<?0.05 vs. CON) and IPOST (21 +/- 2%*) significantly reduced infarct size compared with CON. Inhibition of Pim-1 kinase abolished desflurane-induced postconditioning (46 +/- 4%) and IPOST (44 +/- 5%). Western blot analysis revealed that only desflurane enhances phosphorylation of Bad at serine 112 that was abrogated by Pim-1 kinase inhibitor II. Conclusion These data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.
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