Pancreatitis-associated pulmonary injury - effects of Lexipafant, a PAF-antagonist

Objective. Pulmonary injury is an important determinant of outcome in severe acute pancreatitis. The aim of this experimental study was to investigate the potential effect of lexipafant, a platelet-activating factor (PAF) antagonist, on pancreatitis-associated pulmonary injury in experimental acute pancreatitis. Material and methods. Acute pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats that were given the PAF antagonist lexipafant either before (pretreatment) or after (treatment) induction of pancreatitis. Pulmonary endothelial barrier permeability, oedema, protease inhibitor levels, pulmonary ultrastructure and membrane system integrity and levels of interleukin-1 and -6 were evaluated. Results. Pulmonary injury was characterized by increased pulmonary endothelial barrier permeability, alveolar oedema and hypoxaemia, which were noted 12 h after the induction of pancreatitis. Pretreatment with lexipafant counteracted the increase in endothelial permeability and partially prevented derangements of protease inhibitor levels. Treatment with lexipafant reduced the severity of pulmonary endothelial barrier dysfunction and diminished the pancreatitis-induced increase in cytokines. Conclusions. PAF seems to play a major role in experimental pancreatitis-associated pulmonary injury and protease inhibitor imbalance. Treatment with a PAF inhibitor may ameliorate pancreatitis-associated pulmonary injury.