Effects of ischemic postconditioning on NF-κB and ICAM-1 expression during lung ischemia-reperfusion injury in a dog model of CPB

Abstract

Objective To evaluate the effects of ischemic postconditioning on nuclear factor kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) expression during lung ischemia-reperfusion (I/R) injury in a dog model of cardiopulmonary bypass (CPB), and further investigate the pulmonary protection induced by ischemic postconditioning and the underlying mechanism. Methods Twelve adult mongrel dogs of both sexes, weighing 12-15 kg, were randomly divided into either CPB group or ischemic postconditioning group (IPO group) using a random number table, with 6 dogs in each group.CPB was established after the chest was opened in dogs anesthetized with pentobarbital sodium.Ischemic postconditioning was induced by 2 cycles of 5 min reperfusion followed by 5 min ischemia immediately after occlusion of the left pulmonary artery was released in group IPO.Before CPB (T1), before occlusion of the artery was released (T2), and at 2 h after termination of CPB, lung specimens were obtained for examination of pathological changes which were scored (with light microscope) and for determination of the expression of NF-κB and ICAM-1 (using Western blot) and wet/dry lung weight ratio (W/D ratio) in left lung tissues.Blood samples were collected from femoral arteries at T1 and T3 for blood gas analysis, and oxygenation index (OI), respiration index (RI) and dynamic lung compliance (Cdyn) were calculated. Results OI and Cdyn were significantly decreased, and RI was increased at T3, and W/D ratio, pathological scores, and expression of NF-κB and ICAM-1 were increased at T2, 3 than at T1 in the two groups.W/D ratio, pathological scores, and expression of NF-κB and ICAM-1 were significantly higher at T3 than at T2 in the two groups.Compared with group CPB, OI and Cdyn were significantly increased, and RI, W/D ratio, pathological scores, and expression of NF-κB and ICAM-1 were decreased at T3 in group IPO. Conclusion Ischemic postconditioning up-regulates the expression of ICAM-1 through inhibiting NF-κB activity, thus reducing lung I/R injury induced by CPB and improving the lung function in dogs. Key words: Cardiopulmonary bypass; Lung; Reperfusion injury; NF-kappa B; Intercellular adhesion molecule-1; Ischemic postconditioning