Protective effects of NF-κB inhibitor and continuous perfusion of pulmonary arteries on pulmonary injury in piglet models of deep hypothermia low flow

Abstract

Deep hypothermia with low flow perfusion (DHLF) is a common cardiopulmonary bypass (CPB) technique. The associated lung ischemia/reperfusion injury is a major cause of postoperative morbidity and mortality in patients undergoing DHLP; we aimed to investigate the effects of nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) with continuous perfusion of pulmonary arteries (CPP) on DHLF-induced lung injury and the related molecular mechanisms. Twenty-four piglets were randomly divided into the DHLF (control), CPP (with DHLF), or CPP+PDTC (intravenous PDTC before CPP with DHLF) groups. Lung injury was evaluated by respiratory function measurement, lung immunohistochemistry, and serum levels of TNF, IL-8, IL-6, and NF-κB before CPB, at CPB completion, and at 1 h post-CPB. Western blot was used to detect NF-κB protein expression in lung tissues. After CPB, decreased parcial pressure of oxygen (PaO2) and increased parcial pressure of carbon dioxide (PaCO2) and serum levels of TNF, IL-8, IL-6, and NF-κB were observed in the DHLF group. Both CPP and CPP+PDTC groups showed better indices of lung function, decreased levels of TNF, IL-8, and IL-6, and less severe pulmonary edemas and injuries. PDTC with CPP further improved pulmonary function and mitigated pulmonary injury than did CPP alone. PDTC with CPP better attenuates DHLF-induced lung injury than does CPP alone.