Raised plasma thromboxane B2 levels in experimental acute necrotizing pancreatitis in rats. The effects of flunarizine, dazoxiben, and indomethacin.

The possible role of thromboxane A2 (TXA2) in acute necrotizing pancreatitis (ANP) was investigated in rats. After ANP was induced by injecting sodium taurocholate (5% w/v) into the pancreatic duct, the thromboxane B2 (TXB2) levels in plasma increased significantly. The effects of indomethacin, a general blocker of prostaglandin synthesis, on survival time and on plasma TXB2 levels were compared with those of dazoxiben, a more specific blocker of TXA2 synthesis, and Flunarizine, a calcium entry blocker known to inhibit the effects of TXA2. In a test group without any treatment, all animals died within 30 h of ANP induction. Although TXB2 levels were lowered by the administration of indomethacin, dazoxiben, and Flunarizine, survival times were not significantly altered. Indomethacin pretreatment had no beneficial effect, whereas 30% and 40% of the animals survived for 36 h after treatment with Flunarizine and dazoxiben, respectively. The results of the present study indicate that inhibition of TXA2 synthesis alone does not dramatically alter survival time. However, a potential role for other arachidonate metabolites in ANP cannot be ruled out by this study.