Effect of a platelet-activating factor antagonist on pancreas perfusion after 24 h of ischemia.
Platelet-activating factor (PAF) is a strong mediator of inflammation that is present in many mammalian tissues and cell types. In the pancreas, PAF can be synthesized in acinar cells after stimulation with secretagogues. The present study uses a perfused porcine pancreas model to investigate the role of PAF in pancreatic ischemia and the effect of the PAF antagonist bepafant on pancreas preservation. Pancreata were preserved with or without bepafant, stored for 24 h at 4 degrees C, and then reperfused at 37 degrees C in a perfusion chamber. Reperfusions were significantly improved by the addition of bepafant. This was indicated by a significantly increased arteriovenous volume flow (16.54 +/- 1.88 ml/min versus controls 8.54 +/- 1.31 ml/min; p = 0.0068; bepafant, n = 7; controls, n = 12) and a reduced vascular resistance (p = 0.0068; bepafant, 1.95 +/- 0.22 mm Hg * min/ml versus controls 4.08 +/- 0.56 mm Hg * min/ml). Radioimmunological quantification of PAF in pancreatic tissue revealed that PAF levels remain unchanged during storage in a cold protective solution at 4 degrees C but increase significantly during surgical pancreas preparation under general anesthesia (from 142.1 +/- 21.2 to 368.8 +/- 52.5 pg/g; n = 15; p = 0.0007). The present study shows that bepafant improves pancreas preservation after cold ischemia. The beneficial effect might be explained by antagonizing inflammatory and vasoconstrictory responses to PAF synthesized during surgical pancreas preparation.
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D003080:Cold Temperature; D007511:Ischemia / Q000503:physiopathology; D010179:Pancreas / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D015424:Reperfusion; D013552:Swine; D014021:Tissue Preservation; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C063964:bepafant