Effects of dopexamine on the intestinal microvascular blood flow and leukocyte  activation in a sepsis model in rats.
BACKGROUND
The administration of dopexamine may constitute a therapeutical option to improve hepatosplanchnic perfusion in sepsis. In order to verify this hypothesis, we administered dopexamine in an experimental sepsis model in rats.


METHODS
This prospective, randomized, controlled laboratory study was conducted in 42 Wistar rats. The animals were divided into 3 groups. Group 1 (CON group) served as control group. The Animals of groups 2 (LPS Group) and 3 received an endotoxin infusion (20 mg/kgfor 15 min). In addition, in group 3 (DPX group) dopexamine was administered 0.5 microg/kg/minover 4 hours. One half of the animals of each group underwent studies of intestinal microvascular blood flow (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic evaluation of the leukocyte endothelium cell interaction in the intestinal microcirculation was performed. Functional capillary denstity (FCD) in the intestinal mucosaand the circular as well as the longitudinal muscle layer was estimated.


RESULTS
One hour after endotoxin challenge IMBF decreased significantly in the untreated LPS group to 51% compared to baseline (p<0.05). In DPX treated endotoxin animals we found significantly higher values at the level of CON group. The after endotoxin challenge impaired FCD was improved by dopexamine in the longitudinal (DPX + 33% vs. LPS; p <0.05) and in the circular muscle layer (DPX + 48% vs. LPS; p < 0.05) as a result of dopexamine administration. The administration of dopexamine reduced the count of firmly adherent leukocytes when compared to the untreated LPS group (-31%, p<0.05). TNF-alpha plasma levels were reduced by dopexamine infusion (LPS group 3637 +/- 553 pg/mL; DPXgroup 1933 +/- 201 pg/mL) one hour after endotoxin challenge.


CONCLUSIONS
The administration of dopexamine improved IMBF and FCD as parameters of intestinal microcirculation and reduced leukocyte activation as a parameter of inflammation in experimental sepsis.
Birnbaum
Jurgen
J
Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte, Charité-University Medicine, Berlin, Germany. juergen.birnbaum@charite.de
Klotz
Edda
E
Spies
Claudia D
CD
Lorenz
Bjorn
B
Stuebs
Patrick
P
Hein
Ortrud Vargas
OV
Grundling
Matthias
M
Pavlovic
Dragan
D
Usichenko
Taras
T
Wendt
Michael
M
Kox
Wolfgang J
WJ
Lehmann
Christian
C
D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
C046318:dopexamine; D004298:Dopamine