Intravenous free and dipeptide-bound glutamine maintains intestinal microcirculation in experimental endotoxemia.
OBJECTIVE
The administration of glutamine (Gln), which is depleted in critical illness, is associated with an improvement of gut metabolism, structure, and function. The aim of the present study was to evaluate the effects of intravenous Gln and its galenic formulation, l-alanyl-l-glutamine dipeptide (AlaGln), on the intestinal microcirculation during experimental endotoxemia using intravital fluorescence microscopy. Gln or AlaGln administration was performed as pretreatment or post-treatment, respectively. To identify further the underlying mechanisms, amino acid levels were studied.


METHODS
Sixty male Lewis rats were randomly divided into six groups (n = 10/group): control, LPS (lipopolysaccharide 5 mg/kg intravenously), Gln/LPS (LPS animals pretreated with Gln 0.75 g/kg Gln intravenously), AlaGln/LPS (LPS animals pretreated with AlaGln intravenously, 0.75 g/kg Gln content), LPS/Gln (LPS animals post-treated with Gln 0.75 g/kg intravenously), and LPS/AlaGln (LPS animals post-treated with AlaGln intravenously, 0.75 g/kg Gln content). Two hours after the endotoxin challenge, the microcirculation of the terminal ileum was studied using intravital fluorescence microscopy. Blood samples were drawn at the beginning, during, and the end of the experiment to determine the amino acid levels.


RESULTS
The Gln and AlaGln pre- and post-treatment, respectively, prevented the LPS-induced decrease in the functional capillary density of the intestinal muscular and mucosal layers (P < 0.05). The number of adherent leukocytes in the submucosal venules was significantly attenuated after the Gln and AlaGln pre- and post-treatment (P < 0.05).


CONCLUSIONS
The Gln and AlaGln administrations improved the intestinal microcirculation by increasing the functional capillary density of the intestinal wall and decreasing the submucosal leukocyte activation.
Department of Anesthesia, Ernst-Moritz-Arndt-Universität, Greifswald, Germany. chlehmann@dal.ca
Christian
C
Lehmann
Dragan
D
Pavlovic
Juan
J
Zhou
Ulrich
U
Wuttke
Daniela
D
Saeger
Alexander
A
Spassov
Orlando
O
Hung
Vladimir
V
Cerny
Tobias
T
Witter
Sara
S
Whynot
Ulrich
U
Suchner
Birgit
B
Alteheld
Peter
P
Stehle
Matthias
M
Gründling
D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004151:Dipeptides / Q000494:pharmacology*; D019446:Endotoxemia / Q000188:drug therapy*; D005973:Glutamine / Q000494:pharmacology*; D007082:Ileum / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew
D004151:Dipeptides; D008070:Lipopolysaccharides; D005973:Glutamine; C054122:alanylglutamine