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 decreased capillary pancreatic blood flow. Thus, antibiotics may not reach pancreatic necrosis in therapeutic concentrations and consequently fail to prevent bacterial infection of the pancreas which today is the major cause of morbidity and mortality in ANP.


OBJECTIVE
To evaluate whether improvement of impaired pancreatic microcirculation by isovolemic hemodilution with dextran leads to an increase in the pancreatic tissue concentration of imipenem (IMI), an antibiotic widely used in clinical ANP.


METHODS
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 received an intravenous injection of IMI, and 15 min later they were sacrificed for determination of IMI in serum and tissue. Capillary pancreatic blood flow (CPBF) at the time of antibiotic therapy was assessed by intravital microscopy in an additional set of animals.


RESULTS
There was no significant difference in the pancreatic tissue concentration of IMI in animals pretreated with either RL (11.7 +/- 0.6 micrograms/g) or IHD/DEX (11.4 +/- 1.4 micrograms/g), although CPBF was significantly increased in the latter group (1.3 +/- 0.05 vs. 0.8 +/- 0.04 nl/min/capillary).


CONCLUSIONS
(1) IMI is concentrated by the pancreas in experimental ANP despite impaired CPBF. (2) Enhancement of pancreatic capillary blood flow by IHD/DEX does not increase the pancreatic tissue concentration of IMI. This suggests that CPBF is not a decisive factor influencing the accumulation of this antibiotic in the pancreas, which may be one reason for the high efficacy of IMI in clinical ANP.
Foitzik
T
T
Department of Surgery, Free University of Berlin, Germany.
Hotz
H G
HG
Kinzig
M
M
Sörgel
F
F
Klar
E
E
Warshaw
A L
AL
Buhr
H J
HJ
D000208:Acute Disease; D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D003911:Dextrans / Q000494:pharmacology; D015378:Imipenem / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000098:blood supply* / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013845:Thienamycins / Q000493:pharmacokinetics*
D003911:Dextrans; D013845:Thienamycins; D015378:Imipenem