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

• Published in: Clinical and experimental immunology Vol. 149; no. 2; pp. 364 - 371
• Main Authors: Hanusch, C, Nowak, K, Gill, I.S, Törlitz, P, Rafat, N, Mueller, A.M, Van Ackern, K.C, Yard, B, Beck, G.C
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-08-2007; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Basic Immunology; Biological and medical sciences; Blood Pressure; Cell Adhesion Molecules - biosynthesis; Chemokine CCL2 - biosynthesis; cold preservation; cytokines; E-Selectin - biosynthesis; Fundamental and applied biological sciences. Psychology; Hypothermia, Induced - methods; Inflammation Mediators - metabolism; Intercellular Adhesion Molecule-1 - biosynthesis; ischaemia/reperfusion; leucocytes; leukocytes; Leukocytes, Mononuclear - physiology; lung; Lung - blood supply; Lung - metabolism; Lung - physiopathology; Lung Transplantation; Molecular biophysics; Pulmonary Artery - physiopathology; Pulmonary Edema - metabolism; Pulmonary Edema - physiopathology; Rats; Rats, Wistar; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Tissue Preservation - methods; Vascular Cell Adhesion Molecule-1 - biosynthesis; Temperature; Endothelial cell; Vascular cell adhesion molecule 1; Leukocyte; Lung; Conservation; Homograft; Environmental factor; Biochemistry; cold preservation; ischaemia/reperfusion; Respiratory system; Graft; cytokines; Cold; Intercellular adhesion molecule 1; Preservation; Ischemia reperfusion; Cytokine; Cell adhesion molecule; leucocytes; Chemotaxis; Animal; Inhibitor; Molecular biology
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2007.03417.x

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°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.