THE EFFECT OF A THROMBOXANE A(2) RECEPTOR ANTAGONIST (ONO-3708) ON ISCHEMIA-REPERFUSION INJURY OF THE DOG PANCREAS

The effects of a thromboxane A(2) 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 I-2 and thromboxane A(2) 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 mu g/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 I-2 level (P<0.01) without changing thromboxane A(2) levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the perioxidation of cell membrane lipids and by decreasing the thromboxane A(2)/prostaglandin I-2 ratio, which is a predictor of cellular injury.