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 pancr eas, PAF can be synthesized in acinar cells after stimulation with sec retagogues. The present study uses a perfused porcine pancreas model t o 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, an d then reperfused at 37 degrees C in a perfusion chamber. Reperfusions were significantly improved by the addition of bepafant. This was ind icated 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 = 0.006 8; 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 c old protective solution at 4 degrees C but increase significantly duri ng 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 sh ows 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 panc reas preparation.