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.
Galloway
S W
SW
Department of Surgery, University of Liverpool, England.
Kingsnorth
A N
AN
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability; D004396:Coloring Agents; D005070:Evans Blue; D007668:Kidney / Q000098:blood supply; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D010195:Pancreatitis / Q000150:complications*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
C094498:BB 882; D004396:Coloring Agents; D010972:Platelet Activating Factor; D005070:Evans Blue; D007930:Leucine