Effect of FR167653 on pancreatic ischemia-reperfusion injury in dogs

Background. The role of inflammatory cytokines is still unclear in ischemia -reperfusion injury of the pancreas. We investigated the effect of FR167G53 (FR), a newly developed compound that is a potent suppressor of interleuki n (IL)-1 beta and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the isolated pancreatic tail in dogs. Methods. The tail of the pancreas was subjected to ischemia for 90 minutes. During occlusion of the vascular inflow the head of the pancreas was remov ed. A control group (n = 14) and an FR treatment group (n = II) were evalua ted for survival rate, tissue bloodflow, arterial oxygen pressure (PaO2), s erum amylase and lipase levels, glucose and insulin, liver enzymes, creatin ine, IL-1 beta mRNA in the peripheral blood, and histopathology. Results. Six of the 14 control animals and 2 of the II FR-treated animals d ied. The FR treatment group showed lower amylase (P = .037) and lipase (P = .030) levels, lower IL-1 beta mRNA expression (P = 033), and less pancreat ic tissue damage (P = .041) than did the control group, but there was no re markable change in endocrine function (P = .422). PaO2 during the acute pha se in the FR treatment group was maintained (P= .009), but pulmonary tissue was damaged. Results of biochemical and histologic examinations of the liv er and Kidneys were unremarkable. Conclusions. FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the production of inflammatory cytokines that may! contribute to s econdary damage to distant organs.