Differential Role of Pim-1 Kinase in Anesthetic-induced and Ischemic Preconditioning against Myocardial Infarction

Background: Ischemic preconditioning (IPC) and anesthetic-induced preconditioning; against myocardial infarction are mediated via protein kinase B. Pim-1 kinase acts downstream of protein kinase B and was recently shown to regulate cardiomyocyte survival. The authors tested the hypothesis that IPC and anesthetic-induced preconditioning are mediated by Pim-1 kinase. Methods: Pentobarbital-anesthetized male C57Black/6 mice were subjected to 45 min of coronary artery occlusion and 3 h of reperfusion. Animals received no intervention, Pim-1 kinase inhibitor II (10 mu g/g intraperitoneally), its vehicle dimethyl sulfoxide (10 mu l/g intraperitoneally), or 1.0 minimum alveolar concentration desflurane alone or in combination with Pim-1 kinase inhibitor II (10 mu g/g intraperitoneally). IPC was induced by three cycles of 5 min ischemia-reperfusion each, and animals received IPC either alone or in combination with Pim-1 kinase inhibitor II (10 mu g/g; intraperitoneally). Infarct size was determined with triphenyltetrazolium chloride, and area at risk was determined with Evans blue (Sigma-Aldrich, Taufkirchen, Germany). Protein expression of Pim-1 kinase, Bad, phospho-Bad(Ser112), and cytosolic content of cytochrome c were measured using Western immunoblotting. Results: Infarct size in the control group was 47 +/- 2%. Pim-1 kinase inhibitor II (44 +/- 20%) had no effect on infarct size. Desflurane (17 +/- 3%) and IPC (19 +/- 2%) significantly reduced infarct size compared with control (both P < 0.05 vs. control). Blockade of Pim-1 kinase completely abrogated desflurane-induced preconditioning (43 +/- 3%), whereas IPC (35 +/- 3%) was blocked partially. Desflurane tended to reduce cytosolic content of cytochrome c, which was abrogated by Pim-1 kinase inhibitor II, Conclusion: These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice.