Ileal mucosal oxygen consumption is decreased in endotoxemic rats but is restored toward normal by treatment with aminoguanidine.
OBJECTIVE
We sought to test the hypothesis that ileal mucosal oxygen consumption is impaired in endotoxemic rats.


METHODS
Male Sprague-Dawley rats were injected intravenously with either Escherichia coli lipopolysaccharide (5 mg/kg) or a similar volume of vehicle. A segment of ileum was excised 8 hrs later, and the serosal and muscular layers of the bowel were stripped away from the mucosa. A strip of mucosa was mounted in a polarographic chamber containing air-saturated Krebs-Henseleit buffer plus 20 mM glucose, PO2 being monitored during a 10-min period. Some rats were injected intraperitoneally with the inducible nitric oxide synthase inhibitor, aminoguanidine (30 mg/kg per dose), or a similar volume of vehicle, at 1, 3 and 6 hrs after injection of lipopolysaccharide.


RESULTS
In an initial experiment, the rate of oxygen consumption was significantly lower for mucosal samples from endotoxemic rats as compared with control rats (0.76+/-0.11 ng-atoms vs. 1.42+/-0.22 ng-atoms of 0/min per microg dry weight, respectively; n = 8 per group; p<.05). The rate of mucosal oxygen consumption was higher in aminoguanidine-treated as compared with vehicle-treated endotoxemic rats (1.25+/-0.11 ng-atoms and 0.73+/-0.07 ng-atoms of 0/min per microg, respectively; n = 7 and n = 6, respectively; p<.05).


CONCLUSIONS
Endotoxemia is associated with diminished intestinal mucosal oxygen utilization due to an intrinsic acquired derangement in cellular respiration that is caused, at least in part, by an aminoguanidine-inhibitable mechanism.
King
C J
CJ
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Tytgat
S
S
Delude
R L
RL
Fink
M P
MP
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D010100:Oxygen; C004479:pimagedine