Significance of thromboxane A2 and prostaglandin I2 in acute necrotizing pancreatitis in rats.
Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2 levels 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 A2 synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2 levels. With flunarizine and iloprost the mortality rate was 40% (P less than 0.05); with dazmegrel and iloprost it was 10% (P less than 0.01). The results of the present study suggest that thromboxane A2 and prostaglandin I2 play a role in the course of acute necrotizing pancreatitis.
Department of Experimental Surgery, Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands.
B
B
van Ooijen
W J
WJ
Kort
C J
CJ
Tinga
J H
JH
Wilson
D000208:Acute Disease; D000818:Animals; D011464:Epoprostenol / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use*; D005444:Flunarizine / Q000627:therapeutic use; D016285:Iloprost; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000097:blood / Q000502:physiology*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D007093:Imidazoles; D014665:Vasodilator Agents; C039242:dazmegrel; D013928:Thromboxane A2; D011464:Epoprostenol; D016285:Iloprost; D005444:Flunarizine