title: Hypothermic preservation of lung allograft inhibits cytokine-induced chemoattractant-1, endothelial leucocyte adhesion molecule, vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 expression.
abstract: Organ dysfunction is a major clinical problem after lung transplantation. Prolonged cold ischaemia and reperfusion injury are believed to play a central role in this complication. The influence of cold preservation on subsequent warm reperfusion was studied in an isolated, ventilated and perfused rat lung. Rat lungs were flushed with cold Perfadex-solution and stored at 4 degrees C for different time periods. Thereafter lungs were perfused and ventilated for up to 3 h. Physiological parameters, production of inflammatory mediators and leucocyte infiltration were measured before and after perfusion. Lungs subjected to a cold ischaemia time of up to 6 h showed stable physiological conditions when perfused for 3 h. However, cold-ischaemia time beyond 6 h resulted in profound tissue oedema, thereby impairing ventilation and perfusion. Warm reperfusion and ventilation per se induced a strong inflammatory response, as demonstrated by a significant up-regulation of chemokines and adhesion molecules (cytokine-induced chemoattractant-1, intracellular adhesion molecule and endothelial leucocyte adhesion molecule), accompanied by enhanced leucocyte infiltration. Although the up-regulation of inflammatory mediators was blunted in lungs that were subjected to cold ischaemia, this did not influence leucocyte infiltration. In fact, cold ischaemia time correlated with leucocyte sequestration. Although cold preservation inhibits the expression of inflammatory mediators it does not affect leucocyte sequestration during warm reperfusion. Cold preservation might cause impairment of the endothelial barrier function, as evidenced by tissue oedema and profound leucocyte infiltration.
authors.affiliation: Clinic of Anaesthesiology and Critical Care, University-Hospital Mannheim, University of Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hanusch
authors.forename: K
authors.initials: K
authors.lastname: Nowak
authors.forename: I S
authors.initials: IS
authors.lastname: Gill
authors.forename: P
authors.initials: P
authors.lastname: Törlitz
authors.forename: N
authors.initials: N
authors.lastname: Rafat
authors.forename: A M
authors.initials: AM
authors.lastname: Mueller
authors.forename: K C
authors.initials: KC
authors.lastname: Van Ackern
authors.forename: B
authors.initials: B
authors.lastname: Yard
authors.forename: G C
authors.initials: GC
authors.lastname: Beck
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D019040:E-Selectin / Q000096:biosynthesis; D007036:Hypothermia, Induced / Q000379:methods*; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008168:Lung / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D016040:Lung Transplantation; D011651:Pulmonary Artery / Q000503:physiopathology; D011654:Pulmonary Edema / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D014021:Tissue Preservation / Q000379:methods*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D019040:E-Selectin; D018836:Inflammation Mediators; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1