VASOACTIVE MEDIATORS AND THE PROGRESSION FROM EDEMATOUS TO NECROTIZING EXPERIMENTAL ACUTE-PANCREATITIS

Little is known about the pathophysiological factors that determine th e clinical severity of acute pancreatitis. Because impairment of pancr eatic circulation and oxygenation is associated with greater disease s everity and morphological damage in experimental pancreatitis it has b een suggested that various vasoactive mediators might participate in t he progression from the oedematous to the necrotising variety of the d isease. This study used an animal model of acute pancreatitis induced by intravenous caeruleint (10 mu g/kg/h for up to six hours), which do es not entail either haemorrhage or significant necrosis of the pancre as. This study considered whether the administration or the inhibition of either nitric oxide, bradykinin, or adrenergic mediators can conve rt this mild variety into haemorrhagic and necrotising pancreatitis. N either nitric oxide nor catecholamines were involved in the progressio n from oedematous to haemorrhagic pancreatitis. Their substitution, ac tivation, and inhibition all failed to change the severity of the dise ase process. Bradykinin alone seemed to be critically involved in the pathogenesis of pancreatic haemorrhage and necrosis. However, the inhi bition of bradykinin and not its activation or substitution increased the severity of the disease.