LUNG INJURY IN THE MICROEMBOLIC MODEL OF ACUTE-PANCREATITIS AND AMELIORATION BY LEXIPAFANT (BB-882), A PLATELET-ACTIVATING-FACTOR ANTAGONIST

Acute pancreatitis is associated with the development of pulmonary dys function in a number of patients. The aim of this study was to determi ne whether acute lung injury was a feature of the microembolic model o f pancreatitis in rats and to assess the therapeutic effect of lexipaf ant (BB-882), a potent platelet-activating factor antagonist, on the l ung injury. Acute pancreatitis was induced by microembolisation of the pancreas with 20-mu m polystyrene microspheres, After 12 h tissue cap illary permeability was assessed by an Evans blue dye (EBD) extravasat ion technique and compared with that in control animals. A further gro up of animals received an intraperitoneal injection of BB-882 (5 mg/kg ) 30 min after the induction of pancreatitis. There was a significantl y increased tissue content of EBD in the pancreas and lungs of the gro up of animals with acute pancreatitis (p < 0.05). BB-882 ameliorated t he pulmonary changes when administered after the induction of pancreat itis, as demonstrated by a significant reduction in the EBD content of the lungs (p < 0.01). Increased pulmonary vascular permeability is an early feature of the microembolic model of acute pancreatitis and the se changes appear to be modified by the administration of BB-882, prov iding further evidence for the potential role of platelet-activating f actor antagonists in the treatment of acute pancreatitis and its compl ications.