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

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-repe rfusion injury, and inhibition of NF-kappa B activation reduces this injury and improves pulmonary graft function. With use of a porcine transplantati on model, left lungs were harvested and stored in cold Euro-Collins preserv ation solution for 6 h before transplantation. Activation of NF-kappa B occ urred 30 min and 1 h after transplant and declined to near baseline levels after 4 h. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kap pa B, given to the lung graft during organ preservation (40 mmol/l) effecti vely inhibited NF-kappa B activation and significantly improved lung functi on. Compared with control lungs 4 h after transplant, PDTC-treated lungs di splayed significantly higher oxygenation, lower PCO2, reduced mean pulmonar y arterial pressure, and reduced edema and cellular infiltration. These res ults demonstrate that NF-kappa B is rapidly activated and is associated wit h poor pulmonary graft function in transplant reperfusion injury, and targe ting of NF-kappa B may be a promising therapy to reduce this injury and imp rove lung function.