title: Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats.
abstract: This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.
authors.affiliation: Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, China.
authors.forename: S M
authors.initials: SM
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou, China.
authors.forename: S G
authors.initials: SG
authors.lastname: Qiao
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Davis, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, China.
authors.forename: C F
authors.initials: CF
authors.lastname: Liu
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D015153:Blotting, Western; D053181:Caspase 8 / Q000032:analysis; D003652:Decanoic Acids / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D007511:Ischemia / Q000517:prevention & control; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015221:Potassium Channels / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D000077149:Sevoflurane; D013997:Time Factors; D019210:Troponin I / Q000032:analysis
chemical_list: D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008738:Methyl Ethers; D010975:Platelet Aggregation Inhibitors; D015221:Potassium Channels; D020011:Protective Agents; D019210:Troponin I; C117780:mitochondrial K(ATP) channel; D000077149:Sevoflurane; C052853:5-hydroxydecanoic acid; D011493:Protein Kinase C; D053181:Caspase 8
references.citation: Brain Res. 1990 Sep 24;528(1):21-4
references.pmid: 2245337
references.citation: Anesthesiology. 2004 Nov;101(5):1160-6
references.pmid: 15505452
references.citation: Anesthesiology. 1997 Aug;87(2):361-70
references.pmid: 9286901
references.citation: Adv Biochem Eng Biotechnol. 1998;62:107-28
references.pmid: 9755642
references.citation: Mol Pharmacol. 1999 Jun;55(6):1000-5
references.pmid: 10347240
references.citation: Cardiovasc Drug Rev. 2005 Spring;23(1):71-98
references.pmid: 15867949
references.citation: Prog Cardiovasc Dis. 2005 Jan-Feb;47(4):240-57
references.pmid: 15991153
references.citation: Anesth Analg. 2006 Apr;102(4):984-90
references.pmid: 16551886
references.citation: Eur J Pharmacol. 2006 Jun 6;539(1-2):1-9
references.pmid: 16716295
references.citation: Neuroscience. 2007 Mar 30;145(3):1097-107
references.pmid: 17291693
references.citation: Am J Physiol. 1999 Dec;277(6 Pt 2):H2425-34
references.pmid: 10600865
references.citation: Br J Anaesth. 1999 Sep;83(3):415-21
references.pmid: 10655912
references.citation: Pharmacol Ther. 2000 Jan;85(1):39-53
references.pmid: 10674713
references.citation: J Thorac Cardiovasc Surg. 2000 Aug;120(2):387-92
references.pmid: 10917958
references.citation: Am J Physiol Heart Circ Physiol. 2001 Jan;280(1):H246-55
references.pmid: 11123239
references.citation: Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1249-55
references.pmid: 11179070
references.citation: Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1346-53
references.pmid: 11179083
references.citation: Basic Res Cardiol. 2001 Apr;96(2):136-42
references.pmid: 11327331
references.citation: Circulation. 2001 Jul 3;104(1):85-90
references.pmid: 11435343
references.citation: Anesthesiology. 2002 Jan;96(1):125-33
references.pmid: 11753012
references.citation: Nat Cell Biol. 2002 Feb;4(2):95-105
references.pmid: 11788820
references.citation: Neurosci Lett. 2002 Jul 26;327(3):208-12
references.pmid: 12113913
references.citation: Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2322-30
references.pmid: 12388234
references.citation: Anesth Analg. 2003 Jan;96(1):233-7, table of contents
references.pmid: 12505958
references.citation: Horm Metab Res. 2007 Sep;39(9):672-6
references.pmid: 17846975
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H345-53
references.pmid: 17951366
references.citation: Shock. 2008 Feb;29(2):300-8
references.pmid: 17693941
references.citation: Am J Physiol Heart Circ Physiol. 2009 May;296(5):H1296-304
references.pmid: 19304943
references.citation: Eur J Anaesthesiol. 2009 Jun;26(6):496-503
references.pmid: 19445059
references.citation: Int J Exp Pathol. 2009 Jun;90(3):338-46
references.pmid: 19563616
references.citation: J Cardiovasc Pharmacol. 2010 Sep;56(3):268-74
references.pmid: 20571431
references.citation: J Anesth. 2013 Apr;27(2):251-60
references.pmid: 23143013
references.citation: Anesth Analg. 2005 Jun;100(6):1584-93
references.pmid: 15920178
references.citation: Anesthesiology. 2003 Aug;99(2):421-8
references.pmid: 12883415
references.citation: Biochim Biophys Acta. 2003 Sep 30;1606(1-3):1-21
references.pmid: 14507424
references.citation: J Mol Cell Cardiol. 1997 Mar;29(3):1055-60
references.pmid: 9152866