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

• Published in: Anesthesiology (Philadelphia) 2009-12, Vol.111 (6), p.1257-1264
• Main Authors: STUMPNER, Jan, REDEL, Andreas, KELLERMANN, Anna, LOTZ, Christopher A, BLOMEYER, Christoph A, SMUL, Thorsten M, KEHL, Franz, ROEWER, Norbert, LANGE, Markus
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Inhalation - pharmacology; Animals; bcl-Associated Death Protein - metabolism; Biological and medical sciences; Blood Pressure - drug effects; Blotting, Western; Cytochromes c - metabolism; Data Interpretation, Statistical; Enzyme Activation - drug effects; Heart Rate - drug effects; Ischemic Preconditioning, Myocardial; Isoflurane - analogs & derivatives; Isoflurane - pharmacology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Myocardial Infarction - enzymology; Myocardial Infarction - prevention & control; Myocardium - pathology; Proto-Oncogene Proteins c-pim-1 - antagonists & inhibitors; Proto-Oncogene Proteins c-pim-1 - physiology; Reperfusion Injury - pathology; Signal Transduction - drug effects
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0b013e3181bdf9f4

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. 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 microg/g intraperitoneally), its vehicle dimethyl sulfoxide (10 microl/g intraperitoneally), or 1.0 minimum alveolar concentration desflurane alone or in combination with Pim-1 kinase inhibitor II (10 microg/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 microg/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, and cytosolic content of cytochrome c were measured using Western immunoblotting. Infarct size in the control group was 47 + or - 2%. Pim-1 kinase inhibitor II (44 + or - 2%) had no effect on infarct size. Desflurane (17 + or - 3%) and IPC (19 + or - 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 + or - 3%), whereas IPC (35 + or - 3%) was blocked partially. Desflurane tended to reduce cytosolic content of cytochrome c, which was abrogated by Pim-1 kinase inhibitor II. These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice.