Metronidazole improves intestinal microcirculation in septic rats independently of bacterial burden.
To explore the effects of metronidazole (Me) on intestinal microcirculation in septic rats, intravital microscopy (IVM) following 16 hours of colon ascendens stent peritonitis (CASP model) was used. Four groups of animals were studied: control group (sham operation) and CASP group, each with and without Me treatment (10 mg/kg i.v.). In order to investigate the substance-specific effects of Me independently of the antibacterial effects within a pathologically altered microcirculation, a second experimental series with lipopolysaccharide challenge (LPS model) was carried out. The LPS model consisted of the four groups (control animals and LPS animals (15 mg/kg i.v. LPS from E. coli) with and without Me). IVM in the LPS experiments was performed following a two hour observation period. Me treated CASP or LPS animals, as compared with untreated, demonstrated significant improvement of functional capillary density (FCD) of the intestinal wall. The increase in the number of leukocytes firmly adhered to the endothelium (leukocyte sticking) in the untreated CASP or LPS animals within the V1 venules of the intestinal submucosal layer, was significantly reduced in the Me treated animals. In conclusion, Me exerts beneficial anti-bacterial and anti-inflammatory effects within the septic microcirculation.
Lehmann
Ch
Ch
Klinik für Anästhesiologie und Intensivmedizin, Ernst-Moritz-Arndt-Universität Greifswald, Germany. christian.lehmann@uni-greifswald.de
Bac
V H
VH
Pavlovic
D
D
Lustig
M
M
Maier
S
S
Feyerherd
F
F
Usichenko
T-I
TI
Meissner
K
K
Haase
H
H
Jünger
M
M
Wendt
M
M
Heidecke
C-D
CD
Gründling
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001421:Bacteria, Anaerobic / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy; D007422:Intestines / Q000098:blood supply*; D008297:Male; D008642:Mesenteric Veins / Q000502:physiology; D008795:Metronidazole / Q000627:therapeutic use*; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D008856:Microscopy, Fluorescence / Q000379:methods; D010538:Peritonitis / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D014741:Video Recording
D000890:Anti-Infective Agents; D016207:Cytokines; D008795:Metronidazole