Respiratory complications are major factors contributing to death in
acute pancreatitis. However, the mechanisms of these pulmonary complications are not completely elucidated. We studied the effects of pretreatment with purified
crotapotin (a
phospholipase A2 inhibitor),
N-acetylcysteine (a
reactive oxygen species inhibitor), and a combination of both on the pulmonary mechanical and morphometric changes secondary to severe acute necrohemorrhagic
pancreatitis in Wistar rats. A total of 69 male Wistar rats were studied.
Pancreatitis was induced by infusion of 0.5 mL of a 4%
solution of
sodium taurocholate into the biliopancreatic duct.
Crotapotin,
N-acetylcysteine, or a combination of both was given intraperitoneally 30 min before inducing
pancreatitis. Data were compared with data from
sham-operated animals with or without those pretreatments. The severity of pancreatic and
pulmonary injuries was evaluated 4 h after inducing
pancreatitis by morphometric and pulmonary mechanical studies.
N-acetylcysteine prevented the development of alveolar
edema, alveolar distention, and collapse.
Crotapotin prevented alveolar distention and collapse, and pulmonary dynamic elastance increase. When used in combination,
crotapotin and
N-acetylcysteine prevented both pulmonary morphological and mechanical changes induced by
acute pancreatitis, suggesting an increase in protective effect when these drugs are used together compared with individual effects. However, the severity of
pancreatic necrosis and the increase in polymorphonuclear cells in alveolar septa induced by
pancreatitis were not reduced by previous administration of
crotapotin,
N-acetylcysteine, or both. These results suggest that the protective effects of these drugs are probably due to an extra-pancreatic action in the circulation, or even directly in the lung.