Attenuation of lung reperfusion injury after transplantation using an inhibitor of nuclear factor-κB

A central role for nuclear factor-kappa B (NF-kappa B) in the induction of lung inflammatory injury is emerging. We hypothesized that NF-kappa B is a critical early regulator of the inflammatory response in lung ischemia-reperfusion injury, and inhibition of NF-kappa B activation reduces this injury and improves pulmonary graft function. With use of a porcine transplantation model, left lungs were harvested and stored in cold Euro-Collins preservation solution for 6 h before transplantation. Activation of NF-kappa B occurred 30 min and 1 h after transplant and declined to near baseline levels after 4 h. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappa B, given to the lung graft during organ preservation (40 mmol/l) effectively inhibited NF-kappa B activation and significantly improved lung function. Compared with control lungs 4 h after transplant, PDTC-treated lungs displayed significantly higher oxygenation, lower PCO2, reduced mean pulmonary arterial pressure, and reduced edema and cellular infiltration. These results demonstrate that NF-kappa B is rapidly activated and is associated with poor pulmonary graft function in transplant reperfusion injury, and targeting of NF-kappa B may be a promising therapy to reduce this injury and improve lung function.