• Acta Anaesthesiol Scand · Aug 2012

    Desflurane-induced and ischaemic postconditioning against myocardial infarction are mediated by Pim-1 kinase.

    • J Stumpner, T M Smul, A Redel, T Hilz, T Tischer-Zeitz, H Eisenbarth, M A Schick, F Kehl, N Roewer, and M Lange.
    • Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany. stumpner_j@klinik.uni-wuerzburg.de
    • Acta Anaesthesiol Scand. 2012 Aug 1;56(7):904-13.

    BackgroundAnaesthetic-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.MethodsPentobarbital-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 μg/g intraperitoneally) or its vehicle dimethy sulfoxide (10 μl/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-Bad(Ser112) and B-cell lymphoma 2 was determined using Western immunoblotting analysis.ResultsInfarct 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.ConclusionThese data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

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