ET-1 induces pancreatitis-like microvascular deterioration and acinar cellinjury

Using in vivo microscopy red blood cell (RBC) velocities, functional capill ary density (FCD) and capillary diameters were estimated after inducing acu te pancreatitis by intraductal infusion of sodium taurocholate (0.8 mi; 4%) or after topical superfusion of the pancreas with ET-1 (100 pmol). Sodium taurocholate mediated a significant decrease in RBC velocities between 50 a nd 70%, transient decrease in capillary diameters by 10%, and a sustained d ecrease in FCD between 60 and 70% paralleled by a dramatic heterogeneity in blood flow. Topical superfusion of the exteriorized pancreas with ET-1 cau sed a significant decrease in RBC velocities between 65 and 75%, a sustaine d decrease in capillary diameters by 10%, and a decrease in FCD by 45% acco mpanied by an increase in flow heterogeneity. Following sodium taurocholate infusion pancreas histology revealed a severe edema and sublobular acinar cell necrosis, while topical ET-1 application displayed a severe edema of t he pancreas with focal acinar cell necrosis. Thus, ET-1 mediated a deterior ation of the pancreatic microcirculation, which is similar to the microcirc ulatory failure found in sodium taurocholate-induced experimental pancreati tis and was associated with focal acinar cell necrosis. We are thus incline d to hypothesize that endothelin released by injured endothelial cells duri ng acute biliary pancreatitis promotes microcirculatory failure and ischemi a in acute pancreatitis, eventually leading to acinar cell necrosis. (C) 19 99 Academic Press.