Sevoflurane Postconditioning Inhibits Pulmonary Apoptosis via PI3K/AKT in Dog Cardiopulmonary Bypass Model
Keywords:cardiopulmonary bypass, Ischemia-reperfusion, lung apoptosis, PI3K/Akt pathway, Sevoflurane postconditioning
Aims: The study aimed to investigate the protective effects and regulatory mechanism of sevoflurane postconditioning (SPC) in pulmonary apoptosis induced by cardiopulmonary bypass (CPB).
Methods: Twenty-four healthy dogs were divided into a control (C group), ischemia/reperfusion (I/R group), sevoflurane postconditioning (S group), and wortmannin group (S+W group). At 10 min after the establishment of CPB, the left pulmonary artery was blocked. When the pulmonary artery was reopened, 2% sevoflurane was administered. Wortmannin was delivered 10 min before the pulmonary artery was open. Before thoracotomy was implemented (T1), when the artery was reopened (T2) and 2 h after CPB (T3), blood and the inferior lobe of the left lung were isolated and subjected to gas analysis, pathological examination, western blot, and TUNEL staining.
Results: No obvious changes were observed in the C group throughout the experiment. The conditions of all treated groups progressively deteriorated, and no difference could be found except in the number of apoptotic cells of T3 between the S+W and I/R groups. At T2, the treated groups showed similar conditions. At T3, the lung function and structure of the S group were improved in I/R and S+W groups. The S group showed the highest p-Akt expression, the lowest cleaved-caspase 3 expression, and apoptotic cell percentage.
Conclusions: Ischemia-reperfusion of the lung during CPB reduces lung function and injures the pulmonary structure via inducing lung apoptosis. Sevoflurane postconditioning preserves lung function and structure by alleviating apoptosis via activation of PI3K/Akt.
Denault AY, Deschamps A, Couture P. 2010. Intraoperative hemodynamic instability during and after separation from cardiopulmonary bypass. Semin Cardiothorac Vasc Anesth. 14(3):165-82.
Fischer S, Cassivi SD, Xavier AM, Cardella JA, Cutz E, Xavier AM, et al. 2000. Cell death in human lung transplantation: Apoptosis induction in human lungs during ischemia and after transplantation. Ann Surg. 231:424–431.
Inamura Y, Miyamae M, Sugioka S, Domae N, Kotani J. 2010. Sevoflurane postconditioning prevents activation of caspase 3 and 9 through antiapoptotic signaling after myocardial ischemia-reperfusion. J Anesth. 24(2):215-24.
Jeon YT, Hwang JW, Lim YJ, Kim AN, Park HP. 2013. A combination of sevoflurane postconditioning and albumin increases Bcl-2 expression after transient global cerebral ischemia compared with either sevoflurane postconditioning or albumin alone. J Neurosurg Anesthesiol. 25(1):43-50.
Kiessling AH, Guo FW, Gökdemir Y, Thudt M, Reyher C, Scherer M, et al. 2014. The influence of selective pulmonary perfusion on the inflammatory response and clinical outcome of patients with chronic obstructive pulmonary disease undergoing cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 18(6):732-9.
Klass O, Fischer UM, Antonyan A, Bosse M, Fischer JH, et al. 2007. Pneumocyte apoptosis induction during cardiopulmonary bypass: effective prevention by radical scavenging using N-acetylcysteine. J Invest Surg. 20: 349–356.
Lee H, Park YH, Jeon YT, Hwang JW, Lim YJ, Kim E, et al. 2015. Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia. Br J Anaesth. 114(2):307-18.
Li D, Huang B, Liu J, Li L, Li X. 2013. Decreased brain K(ATP) channel contributes to exacerbating ischemic brain injury and the failure of neuroprotection by sevoflurane post-conditioning in diabetic rats. PLoS One. 26;8(8):e73334.
Li J, Zhou J, Zhang D, Song D, She J, Bai C. 2015. Bone marrow-derived mesenchymal stem cells enhance autophagy via PI3K/AKT signalling to reduce the severity of ischaemia/reperfusion-induced lung injury. J Cell Mol Med. 19(10):2341-51.
Li R, Xu X, Chen C, Yu X, Edin ML, Degraff LM, et al. 2012. Cytochrome P450 2J2 is protective against global cerebral ischemia in transgenic mice. Prostaglandins Other Lipid Mediat. 2012, 99(3-4):68-78.
Li X, Luo P, Wang F, Yang Q, Li Y, Zhao M, et al. 2014. Inhibition of N-myc downstream-regulated gene-2 is involed in an astrocyte-specific neuroproction induced by sevoflurane preconditioning. Anesthesiology. 121(3):549-62.
Liu C, Shen Z, Liu Y, Peng J, Miao L, Zeng W, Li Y. 2015. Sevoflurane protects against intestinal ischemia-reperfusion injury partly by phosphatidylinositol 3 kinases/Akt pathway in rats. Surgery. 157(5):924-33.
Meybohm P, Gruenewald M, Albrecht M, Müller C, Zitta K, Foesel N, et al. 2011. Pharmacological postconditioning with sevoflurane after cardiopulmonary resuscitation reduces myocardial dysfunction. Crit Care. 15(5): R241.
Ren XP, Wu J, Wang X, Sartor MA, Qian J, Jones K, et al. 2009. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation. 119(17):2357-66.
Rodríguez A, Taurà P, García Domingo MI, Herrero E, Camps J, Forcada P, et al. 2015. Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion: a randomized clinical trial. Surgery. 157(2):249-59.
Slottosch I, Liakopoulos O, Kuhn E, Deppe A, Lopez-Pastorini A, Schwarz D, et al. 2014. Controlled lung reperfusion to reduce pulmonary ischaemia/reperfusion injury after cardiopulmonary bypass in a porcine model.Interact Cardiovasc Thorac Surg. 19(6):962-70.
Steurer M, Schläpfer M, Steurer M, Z'graggen BR, Booy C, Reyes L, et al. 2009. The volatile anaesthetic sevoflurane attenuates lipopolysaccharide-induced injury in alveolar macrophages. Clin Exp Immunol.155(2):224-30.
Tsai HJ, Huang SS, Tsou MT, Wang HT, Chiu JH. 2015. Role of Opioid Receptors Signaling in Remote Electrostimulation - Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts. PLoS One. 10(10):e0138108.
Van Putte BP, Kesecioglu J, Hendriks JM, Persy VP, van Marck E, van Schil P, et al. 2005. Cellular infiltrates and injury evaluation in a rat model of warm pulmonary ischemia-reperfusion. Crit Care. 9: R1–R8.
Wang C, Xie H, Liu X, Qin Q, Wu X, Liu H, et al. 2010. Role of nuclear factor-κB in volatile anaesthetic preconditioning with sevoflurane during myocardial ischaemia/reperfusion. Eur J Anaesthesiol. 27(8):747-56.
Wang H, Shi H, Yu Q, Chen J, Zhang F, Gao Y. 2016. Sevoflurane Preconditioning Confers Neuroprotection via Anti-apoptosis Effects. Acta Neurochir Suppl. 121:55-61.
Wei K, Liu L, Xie F, Hao X, Luo J, Min S. 2015. Nerve growth factor protects the ischemic heart via attenuation of the endoplasmic reticulum stress induced apoptosis by activation of phosphatidylinositol 3-kinase. Int J Med Sci. 12(1):83-91.
White LE, Cui Y, Shelak CM, Lie ML, Hassoun HT. 2012. Lung endothelial cell apoptosis during ischemic acute kidney injury. Shock. 38(3):320-7.
Yang K, Gao B, Wei W, Li Z, Pan L, Zhang J, et al. 2015. Changed profile of microRNAs in acute lung injury induced by cardio-pulmonary bypass and its mechanism involved with SIRT1. Int J Clin Exp Pathol. 8(2):1104-15.
Yao H, Han X, Han X. 2014. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway. Am J Cardiovasc Drugs. 14(6):433-42.
Ye Z, Xia P, Cheng ZG, Guo Q. 2015. Neuroprotection induced by sevoflurane-delayed post-conditioning is attributable to increased phosphorylation of mitochondrial GSK-3β through the PI3K/Akt survival pathway. J Neurol Sci. 348(1-2):216-25.
Yu Y, Gao M, Li H, Zhang F, Gu C. 2013. Pulmonary artery perfusion with anti-tumor necrosis factor alpha antibody reduces cardiopulmonary bypass-induced inflammatory lung injury in a rabbit model. PLoS One. 8(12): e83236.
Zhang J, Wang C, Yu S, Luo Z, Chen Y, Liu Q. 2014. Sevoflurane Postconditioning Protects Rat Hearts against Ischemia-Reperfusion Injury via the Activation of PI3K/AKT/mTOR Signaling. Sci Rep. 4:7317.
Zhang L, Zhao X, Jiang X. 2015. Sevoflurane Post-conditioning Protects Primary Rat Cortical Neurons Against Oxygen-Glucose Deprivation/Resuscitation: Roles of Extracellular Signal-Regulated Kinase 1/2 and Bid, Bim, Puma. Neurochem Res. 40(8):1609-19.
Zhang LM, Zhao XC, Sun WB, Li R, Jiang XJ. 2015. Sevoflurane post-conditioning protects primary rat cortical neurons against oxygen-glucose deprivation/resuscitation via down-regulation in mitochondrial apoptosis axis of Bid, Bim, Puma-Bax and Bak mediated by Erk1/2. J Neurol Sci. 357(1-2):80-7.
Zhang Y, Tian SY, Li YW, Zhang L, Yu JB, Li J, et al. 2015. Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model viaPI3K/Akt signaling pathway. Gene. 569(1):60-5.
Zhao S, Wu J, Zhang L, Ai Y. 2014. Postconditioning with sevoflurane induces heme oxygenase-1 expression via the PI3K/Akt pathway in lipopolysaccharide-induced acute lung injury. Mol Med Rep. Jun;9(6):2435-40.
Zhou L, Zhao D, An H, Zhang H, Jiang C, Yang B. 2015. Melatonin prevents lung injury induced by hepatic ischemia-reperfusion through anti-inflammatory and anti-apoptosis effects. Int Immunopharmacol. pii: S1567-5769(15)30146-6.
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