Raised Plasma Thromboxane B₂ Levels in Experimental Acute Necrotizing Pancreatitis in Rats: The Effects of Flunarizine, Dazoxiben, and Indomethacin

Abstract

van Ooijen B, Ouwendijk RJT, Kort WJ, Zijlstra FJ, Vincent JE, Wilson JHP, Westbroek DL. Raised plasma thromboxane B₂ levels in experimental acute necrotizing pancreatitis in rats. The effects of flunarizine, dazoxiben, and indomethacin. Scand J Gastroenterol 1988, 23, 188–192

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 prosta-glandin synthesis, on survival time and on plasma TXB₂ levels were compared with those of dazoxiben, a more specific blocker of TXA, 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 TXB, 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 TXA, 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.

Key Words:

• Acute necrotizing pancreatitis
• survival time
• thromboxane A₂
• thromboxane A₂ blockers