PMID- 23178815 OWN - NLM STAT- MEDLINE DCOM- 20140305 LR - 20130517 IS - 1873-734X (Electronic) IS - 1010-7940 (Linking) VI - 43 IP - 6 DP - 2013 Jun TI - Ischaemic preconditioning prevents the liver inflammatory response to lung ischaemia/reperfusion in a swine lung autotransplant model. PG - 1194-201 LID - 10.1093/ejcts/ezs599 [doi] AB - OBJECTIVES: Lung ischaemia/reperfusion (IR) induces a systemic inflammatory response that causes damage to remote organs. The liver is particularly sensitive to circulating inflammatory mediators that occur after IR of remote organs. Recently, remote ischaemic preconditioning has been proposed as a surgical tool to protect several organs from IR. The present study was designed to investigate a possible protective effect of lung ischaemic preconditioning (IP) against the liver inflammatory response to lung IR. METHODS: Two groups [IP and control (CON)] of 10 Large White pigs underwent lung autotransplants (left pneumonectomy, ex situ cranial lobectomy and caudal lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two 5-min cycles of left pulmonary arterial occlusion and a 5-min interval of reperfusion between the two occlusions. Five animals underwent sham surgery. Liver biopsies were obtained during surgery at (i) prepneumonectomy, (ii) prereperfusion, (iii) 10 min after reperfusion of the implanted lobe and (iv) 30 min after reperfusion. The expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-10 and inducible form of nitric oxide synthase (iNOS) was analysed by western blotting. The expression of mRNA for TNF-alpha, IL1, IL-10, monocyte chemoattractant protein-1 (MCP-1), nuclear factor kappa beta and iNOS was analysed by reverse transcription-polymerase chain reaction. Caspase-3 activity was determined by enzyme-linked immunosorbent assay. Non-parametric tests were used to compare differences between and within groups. RESULTS: Lung IR markedly increased expression of TNF-alpha (P = 0.0051) and IL-1 (P = 0.0051) and caspase-3 activity (P = 0.0043) in the CON group compared with the prepneumonectomy levels. A decrease of IL-10 mRNA expression was observed in the CON group after lung reperfusion. In the IP group, TNF-alpha (P = 0.0011) and IL-1 (P = 0.0001) expression and caspase-3 activity (P < 0.0009) were lower after reperfusion than in the CON group. IP caused reversion of the observed decrease of IL-10 mRNA expression (P = 0.016) induced in liver tissue by lung IR. Lung IR markedly increased the expression of mRNA MCP-1 after 10 min (P = 0.0051) and 30 min (P = 0.0051) of reperfusion. These increases were not observed in the IP or sham groups. CONCLUSIONS: IP prevented liver injury induced by lung IR through the reduction of proinflammatory cytokines and hepatocyte apoptosis. FAU - Huerta, Luis AU - Huerta L AD - Department of Thoracic Surgery, Gregorio Maranon University General Hospital, Madrid, Spain. luishuema@hotmail.com FAU - Rancan, Lisa AU - Rancan L FAU - Simon, Carlos AU - Simon C FAU - Isea, Jesus AU - Isea J FAU - Vidaurre, Eduardo AU - Vidaurre E FAU - Vara, Elena AU - Vara E FAU - Garutti, Ignacio AU - Garutti I FAU - Gonzalez-Aragoneses, Federico AU - Gonzalez-Aragoneses F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121123 PL - Germany TA - Eur J Cardiothorac Surg JT - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JID - 8804069 RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Caspase 3/metabolism MH - Chemokine CCL2/genetics/metabolism MH - Cytokines/genetics/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Inflammation/*metabolism MH - Ischemic Preconditioning/*methods MH - Liver Diseases/*etiology/metabolism MH - Lung Transplantation/*methods MH - Nitric Oxide Synthase Type II/genetics/metabolism MH - Pneumonectomy MH - Random Allocation MH - Reperfusion Injury/*metabolism/*prevention & control MH - Statistics, Nonparametric MH - Swine OTO - NOTNLM OT - Ischaemia/reperfusion injury OT - Ischaemic preconditioning OT - Liver OT - Lung EDAT- 2012/11/28 06:00 MHDA- 2014/03/07 06:00 CRDT- 2012/11/27 06:00 PHST- 2012/11/27 06:00 [entrez] PHST- 2012/11/28 06:00 [pubmed] PHST- 2014/03/07 06:00 [medline] AID - ezs599 [pii] AID - 10.1093/ejcts/ezs599 [doi] PST - ppublish SO - Eur J Cardiothorac Surg. 2013 Jun;43(6):1194-201. doi: 10.1093/ejcts/ezs599. Epub 2012 Nov 23.