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 dysfunction in a number of patients. The aim of this study was to determine whether Acute Lung Injury was a feature of the microembolic model of Pancreatitis in rats and to assess the therapeutic effect of lexipafant (BB-882), a potent platelet-activating factor antagonist, on the lung injury. Acute Pancreatitis was induced by microembolisation of the Pancreas with 20-microns polystyrene microspheres. After 12 h tissue capillary permeability was assessed by an Evans blue dye (EBD) extravasation technique and compared with that in control Animals. A further group of Animals received an intraperitoneal injection of BB-882 (5 mg/kg) 30 min after the induction of Pancreatitis. There was a significantly increased tissue content of EBD in the Pancreas and Lungs of the group of Animals with acute Pancreatitis (p < 0.05). BB-882 ameliorated the pulmonary changes when administered after the induction of Pancreatitis, 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 these changes appear to be modified by the administration of BB-882, providing further evidence for the potential role of platelet-activating factor antagonists in the treatment of acute Pancreatitis and its complications.