Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2levels were not. The significance of these alterations was investigated. Pancreatitis was induced by injecting 5 sodium taurocholate into the pancreatic duct. Iloprost (ZK 36374, a stable analog of prostaglandin I2, 25 ng/kg body weight) decreased the mortality rate from 100 to 50. When treatment with iloprost was combined with simultaneous administration of either Sibelium (flunarizine R 14 950, 0.2 mg/kg body weight) or dazmegrel (UK 38 485, 50 mg/kg body weight) an additional decrease in the mortality rate was recorded. Dazmegrel is a selective thromboxane A2synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2levels. With flunarizine and iloprost the mortality rate was 40 (P<0.05); with dazmegrel and iloprost it was 10 (P<0.01). The results of the present study suggest that thromboxane A2and prostaglandin I2play a role in the course of acute necrotizing pancreatitis.
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