title: Ischaemic preconditioning prevents the liver inflammatory response to lung ischaemia/reperfusion in a swine lung autotransplant model.
abstract: OBJECTIVE
  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-α (TNF-α), interleukin (IL)-1, IL-10 and inducible form of nitric oxide synthase (iNOS) was analysed by western blotting. The expression of mRNA for TNF-α, 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-α (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-α (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.
authors.affiliation: Department of Thoracic Surgery, Gregorio Marañón University General Hospital, Madrid, Spain. luishuema@hotmail.com
authors.forename: Luis
authors.initials: L
authors.lastname: Huerta
authors.forename: Lisa
authors.initials: L
authors.lastname: Rancan
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.forename: Jesús
authors.initials: J
authors.lastname: Isea
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vidaurre
authors.forename: Elena
authors.initials: E
authors.lastname: Vara
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garutti
authors.forename: Federico
authors.initials: F
authors.lastname: González-Aragoneses
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism; D016040:Lung Transplantation / Q000379:methods*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011013:Pneumonectomy; D011897:Random Allocation; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D013552:Swine
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3