The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia-reperfusion injury of the dog pancreas.
The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia-reperfusion injury of the pancreas were evaluated using an isolated in-vivo-perfused dog pancreas model. Pancreatic endocrine and exocrine function were stimulated with cholecystokinin octapeptide (10(-12) mol). This dose significantly increased endogenous prostaglandin I2 and thromboxane A2 production by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a decrease of insulin release (P < 0.01). There was also a decrease of pancreatic juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting damage to the acinar, ductular, and beta cells. Intravenous administration of ONO 3708 (200 micrograms/kg/min) throughout the experiment prevented these abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the peroxidation of cell membrane lipids and by decreasing the thromboxane A2/prostaglandin I2 ratio, which is a predictor of cellular injury.
Kuroda
T
T
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Shiohara
E
E
Haba
Y
Y
Hanazaki
K
K
D000681:Amylases / Q000097:blood; D000818:Animals; D004285:Dogs; D011464:Epoprostenol / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012844:Sincalide / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D007328:Insulin; D008054:Lipid Peroxides; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; C049855:ONO 3708; D005934:Glucagon; D011464:Epoprostenol; D000681:Amylases; D012844:Sincalide