With use of in vivo microscopy, pancreatic duct permeability, red blood cell (RBC) velocities, functional capillary density (FCD), and overall changes in capillary blood flow (perfusion index) were estimated after intraductal infusion of sodium taurocholate (0.8 ml, 4%) alone or in combination with systemic administration of cholecystokinin (CCK, 0.3 microg/100 g body wt) or secretin (Sec, 10 microg/100 g body wt). Sodium taurocholate mediated a significant increase in pancreatic duct and capillary permeability within 105 +/- 26 s followed by a transient decrease in RBC velocities and a sustained decrease in FCD, which were paralleled by dramatic flow heterogeneity. Therefore, a significant reduction in overall capillary blood flow was calculated. CCK stimulation aggravated the microcirculatory failure due to a decrease in RBC velocities, which was accompanied by an increase in acinar cellular necrosis. Sec stimulation attenuated microcirculatory failure due to a more moderate reduction of FCD. The enhanced pancreatic duct and capillary permeability, which enables free diffusion of pancreatic digestive enzymes into the parenchyma, is the initiating event in acute biliary pancreatitis, causing microcirculatory failure and tissue damage. The microcirculatory changes are secondary and a propagating factor for the development of acini necrosis. Stimulation with CCK worsened the course of acute biliary pancreatitis.
Dehydrocholic Acid Ameliorates Sodium Taurocholate-Induced Acute Biliary Pancreatitis in Mice
