Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by P im‐1 kinase

Background Anaesthetic‐induced ( APOST ) and ischaemic postconditioning ( IPOST ) against myocardial infarction are mediated via phosphatidylinositol‐3‐kinase/ A kt. P im‐1 kinase is acting downstream of A kt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by P im‐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 P im‐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 P im‐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 P im‐1 kinase inhibitor II . Infarct size was determined with triphenyltetrazolium chloride and area at risk with E vans blue. Protein expression of P im‐1 kinase, B ad, phospho‐ B ad Ser112 and B‐cell lymphoma 2 was determined using W estern immunoblotting analysis. Results Infarct size in control animals ( CON ) was 46 ± 3%. Dimethylsulfoxide (47 ± 3%) and P im‐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 P im‐1 kinase abolished desflurane‐induced postconditioning (46 ± 4%) and IPOST (44 ± 5%). W estern blot analysis revealed that only desflurane enhances phosphorylation of B ad at serine 112 that was abrogated by P im‐1 kinase inhibitor II . Conclusion These data suggest that P im‐1 kinase mediates both desflurane‐induced postconditioning and IPOST in mice.