Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits.
OBJECTIVE
Recent evidence demonstrated that hypercapnic acidosis due to lung protective strategy was not only permissive but also even therapeutic for injured lung. Since the effects of hypercapnic acidosis on extra-pulmonary organs remain to be clarified, we tested the hypothesis that hypercapnic acidosis protects gut mucosal barrier function by modulating inflammation in a rabbit model of endotoxemia.


METHODS
Prospective randomized animal study.


METHODS
University research laboratory.


METHODS
Male New Zealand white rabbits.


METHODS
Thirty-two animals were randomly allocated into two groups: normocapnia (n = 17) and hypercapnia (n = 15). The latter group received F(I)CO(2) 5% under mechanical ventilation to achieve hypercapnia throughout the study periods, whereas the former with F(I)CO(2) 0%.


RESULTS
Arterial blood gas, intramucosal pH (pHi) and portal blood flow were assessed at baseline, 2-h and 4-h infusion of lipopolysaccharide. At 4 h, ileal myeloperoxidase (MPO) activity and intestinal permeability were measured. The animals in the hypercapnia group showed apparent hypercapnic acidosis and progressive intramucosal acidosis at 4 h, accompanied by significantly lower intestinal permeability versus normocapnia group. Ileal MPO activity was comparable between the study groups.


CONCLUSIONS
Hypercapnic acidosis attenuates endotoxin-induced gut barrier dysfunction possibly through neutrophil-independent mechanisms.
Morisaki
Hiroshi
H
Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. morisaki@z8.keio.jp
Yajima
Satoshi
S
Watanabe
Yoko
Y
Suzuki
Takeshi
T
Yamamoto
Michiko
M
Katori
Nobuyuki
N
Hashiguchi
Saori
S
Takeda
Junzo
J
D000142:Acidosis, Respiratory / Q000503:physiopathology*; D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D019446:Endotoxemia / Q000503:physiopathology / Q000517:prevention & control*; D006935:Hypercapnia / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000502:physiology*; D008297:Male; D009195:Peroxidase / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D013152:Splanchnic Circulation / Q000502:physiology
D009195:Peroxidase