IMPROVEMENT OF PANCREATIC CAPILLARY BLOOD-FLOW DOES NOT AUGMENT THE PANCREATIC TISSUE CONCENTRATION OF IMIPENEM IN ACUTE EXPERIMENTAL PANCREATITIS

Background: Acute necrotizing pancreatitis (ANP) is characterized by d ecreased capillary pancreatic blood flow. Thus, antibiotics may not re ach pancreatic necrosis in therapeutic concentrations and consequently fail to prevent bacterial infection of the pancreas which today is th e major cause of morbidity and mortality in ANP. Objective: To evaluat e whether improvement of impaired pancreatic microcirculation by isovo lemic hemodilution with dextran leads to an increase in the pancreatic tissue concentration of imipenem (IMI), an antibiotic widely used in clinical ANP. Method: After induction of ANP rats were randomized for either standard fluid therapy with Ringer's lactate (RL) or isovolemic hemodilution with dextran 70,000 (IHD/DEX). Thereafter the animals re ceived an intravenous injection of IMI, and 15 min later they were sac rificed for determination of IMI in serum and tissue. Capillary pancre atic blood flow (CPBF) at the time of antibiotic therapy was assessed by intravital microscopy in an additional set of animals. Results: The re was no significant difference in the pancreatic tissue concentratio n of IMI in animals pretreated with either RL (11.7 +/- 0.6 mu g/g) or IHD/DEX (11.4 +/- 1.4 mu g/g), although CPBF was significantly increa sed in the latter group (1.3 +/- 0.05 vs. 0.8 +/- 0.04 nl/min/capillar y). Conclusion: (1) IMI is concentrated by the pancreas in experimenta l ANP despite impaired CPBF. (2) Enhancement of pancreatic capillary b lood flow by IHD/DEX does not increase the pancreatic tissue concentra tion of IMI. This suggests that CPBF is not a decisive factor influenc ing the accumulation of this antibiotic in the pancreas, which may be one reason for the high efficacy of IMI in clinical ANP.