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

SummaryOrgan 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.

Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats

“…Accumulating evidence demonstrates that leukocyte-endothelial adhesion is mediated by cell adhesion molecules on vascular endothelial cells and counterpart ligands on leukocytes, especially in IR [30,31] . ICAM-1 and VCAM-1 expressed on these cells are central for the adherence of neutrophils and monocytes to the endothelium [32] .…”

Effects of whole-body cryotherapy on serum mediators of inflammation and serum muscle enzymes in athletes

“…It could be argued that long-term cold exposure, especially when associated with psychological discomfort and mood modifications, depresses immunoglobulin production and release, whereas very short cold exposure does not affect Ig levels. Moreover, cold inhibits the expression of inflammatory mediators; hypothermia inhibits activation of neutrophils and expression of intercellular adhesion molecule-1 (ICAM-1), the adhesion and activation of neutrophils during inflammation (Hanusch et al, 2007). Therefore hypothermia induced expression of the anti-inflammatory cytokines IL-10 (Scumpia et al, 2004); hypothermia attenuates the inflammatory response during WBC, thus contributing to its beneficial role in organ protection (Hofstetter et al, 2007).…”

Pre-ischaemic conditioning of the pulmonary endothelium by immunotargeting of catalase via angiotensin-converting-enzyme antibodies☆☆☆

“…Lungs not subjected to CP were used for comparison (no CP). The Kaplan-Meyer analysis was performed using delta (D) weight increase of more than 4 g, and PIP and PAP increases of more than 21 mmHg as endpoints [10]. Isolated lung perfusion was stopped when all of these endpoints were reached, shown in Fig.…”

“…They were ventilated with a small animal respirator using 95% O 2 /5% CO 2 gas, a tidal volume of 2 ml and a rate of 60 breaths/min with 2 cm H 2 O of positive end-expiratory pressure. Median sternotomy and thymectomy were performed to expose the heart-lung block for preparation of isolated lung perfusion and ventilation, as described previously [10].…”

“…The animals were anaesthetised as described previously [10]. In all the animals a 14-gauge angiocatheter was inserted into the trachea by cervical tracheotomy.…”