BACKGROUND/AIMS: The reticuloendothelial system and in particular the Kupffer cells in the liver are important for eliminating antigens and toxic substances in many diseases including acute pancreatitis. Optimal Kupffer cell function is believed to depend on numerous factors including intact hepatic blood supply and microcirculation. The aim of the study was to evaluate whether hepatic microcirculation and Kupffer cell function are impaired in acute pancreatitis and whether enhancement of hepatic capillary blood flow leads to improved reticuloendothelial system function. METHODOLOGY: Acute pancreatitis was induced in rats by intraductal infusion of bile salt followed by i.v. cerulein hyperstimulation. Animals were randomized to receive either a selective endothelin-A receptor antagonist (ET-RA; LU-135252; 50 mg/kg) or saline. Sham-operated animals (intraductal and i.v. saline infusion) treated according to the same protocol served as controls. Liver phagocytic function was evaluated in 6 animals per group 6 and 24 hrs after acute pancreatitis induction and treatment using 99mTc-labeled Nanocoll and a scintillation camera technique. Another 6 animals of each group were used for intravital microscopic determination of hepatic capillary blood flow using fluorescein-labeled erythrocytes. RESULTS: Six hours after acute pancreatitis induction, hepatic capillary blood flow and nanocoll clearance were significantly decreased in saline-treated animals (compared to saline-treated healthy controls). Endothelin-A receptor antagonist significantly improved hepatic capillary blood flow and nanocoll clearance. This beneficial effect was no longer seen after 24 hrs when these parameters had spontaneously returned to values not significantly different from normal. CONCLUSIONS: Reticuloendothelial system function and hepatic capillary blood flow are impaired (only) in the early stage of this acute pancreatitis model. Endothelin-A receptor antagonist improves hepatic capillary blood flow at this stage. Enhancement of hepatic capillary blood flow is accompanied by normalization of nanocoll clearance, suggesting that hepatic microcirculation influences phagocytic Kupffer cell function early in acute pancreatitis.
BACKGROUND/AIMS: The reticuloendothelial system and in particular the Kupffer cells in the liver are important for eliminating antigens and toxic substances in many diseases including acute pancreatitis. Optimal Kupffer cell function is believed to depend on numerous factors including intact hepatic blood supply and microcirculation. The aim of the study was to evaluate whether hepatic microcirculation and Kupffer cell function are impaired in acute pancreatitis and whether enhancement of hepatic capillary blood flow leads to improved reticuloendothelial system function. METHODOLOGY:Acute pancreatitis was induced in rats by intraductal infusion of bile salt followed by i.v. cerulein hyperstimulation. Animals were randomized to receive either a selective endothelin-A receptor antagonist (ET-RA; LU-135252; 50 mg/kg) or saline. Sham-operated animals (intraductal and i.v. saline infusion) treated according to the same protocol served as controls. Liver phagocytic function was evaluated in 6 animals per group 6 and 24 hrs after acute pancreatitis induction and treatment using 99mTc-labeled Nanocoll and a scintillation camera technique. Another 6 animals of each group were used for intravital microscopic determination of hepatic capillary blood flow using fluorescein-labeled erythrocytes. RESULTS: Six hours after acute pancreatitis induction, hepatic capillary blood flow and nanocoll clearance were significantly decreased in saline-treated animals (compared to saline-treated healthy controls). Endothelin-A receptor antagonist significantly improved hepatic capillary blood flow and nanocoll clearance. This beneficial effect was no longer seen after 24 hrs when these parameters had spontaneously returned to values not significantly different from normal. CONCLUSIONS: Reticuloendothelial system function and hepatic capillary blood flow are impaired (only) in the early stage of this acute pancreatitis model. Endothelin-A receptor antagonist improves hepatic capillary blood flow at this stage. Enhancement of hepatic capillary blood flow is accompanied by normalization of nanocoll clearance, suggesting that hepatic microcirculation influences phagocytic Kupffer cell function early in acute pancreatitis.