Endotoxin-induced ileal mucosal hyperpermeability in pigs: Role of tissue acidosis

A. L. Salzman, H. Wang, P. S. Wollert, T. J. Vandermeer, C. C. Compton, A. G. Denenberg, M. P. Fink

Research output: Contribution to journalArticle

Abstract

Administration of lipopolysaccharide (LPS) to experimental animals leads to diminished mesenteric perfusion, increased ileal mucosal [H+], and increased gut epithelial permeability to hydrophilic solutes. We sought to determine whether these phenomena are causally related. Experiments were performed in anesthetized pigs. Permeability was assessed by measuring the plasma-to-lumen clearance of fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion (Q(muc)) and [H+] were estimated using laser-Doppler flowmetry and tonometry, respectively. In an initial series of experiments, we showed that mucosal permeability was linearly correlated with mucosal [H+] in animals subjected to graded degrees of mechanically induced mesenteric ischemia (n = 14, R2 = 0.58, P <0.002) or injected with graded doses of LPS (n = 11, R2 = 0.93, P <0.0001). In a second series of experiments, we induced mucosal acidosis in normal pigs by mechanical ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture. In both groups, ileal mucosal permeability to FD-4 increased significantly (P <0.05), although transmesenteric release of lactate increased significantly only in the hypoxic group. Q(muc) was unchanged in both groups. These data suggest that mucosal acidosis, even in the absence of tissue ischemia or hypoxia, increases intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis may be an important factor contributing to LPS-induced gut mucosal hyperpermeability.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume266
Issue number4 29-4
StatePublished - 1994
Externally publishedYes

Fingerprint

Acidosis
Endotoxins
Permeability
Swine
Lipopolysaccharides
Perfusion
Laser-Doppler Flowmetry
Manometry
Ileum
Artificial Respiration
Lactic Acid
Ischemia
Gases

Keywords

  • acidosis
  • epithelium
  • lipopolysaccharide
  • sepsis

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Salzman, A. L., Wang, H., Wollert, P. S., Vandermeer, T. J., Compton, C. C., Denenberg, A. G., & Fink, M. P. (1994). Endotoxin-induced ileal mucosal hyperpermeability in pigs: Role of tissue acidosis. American Journal of Physiology - Gastrointestinal and Liver Physiology, 266(4 29-4).

Endotoxin-induced ileal mucosal hyperpermeability in pigs : Role of tissue acidosis. / Salzman, A. L.; Wang, H.; Wollert, P. S.; Vandermeer, T. J.; Compton, C. C.; Denenberg, A. G.; Fink, M. P.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 266, No. 4 29-4, 1994.

Research output: Contribution to journalArticle

Salzman, AL, Wang, H, Wollert, PS, Vandermeer, TJ, Compton, CC, Denenberg, AG & Fink, MP 1994, 'Endotoxin-induced ileal mucosal hyperpermeability in pigs: Role of tissue acidosis', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 266, no. 4 29-4.
Salzman, A. L. ; Wang, H. ; Wollert, P. S. ; Vandermeer, T. J. ; Compton, C. C. ; Denenberg, A. G. ; Fink, M. P. / Endotoxin-induced ileal mucosal hyperpermeability in pigs : Role of tissue acidosis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1994 ; Vol. 266, No. 4 29-4.
@article{1a4b6b5e890b4cd99065654ec37730ac,
title = "Endotoxin-induced ileal mucosal hyperpermeability in pigs: Role of tissue acidosis",
abstract = "Administration of lipopolysaccharide (LPS) to experimental animals leads to diminished mesenteric perfusion, increased ileal mucosal [H+], and increased gut epithelial permeability to hydrophilic solutes. We sought to determine whether these phenomena are causally related. Experiments were performed in anesthetized pigs. Permeability was assessed by measuring the plasma-to-lumen clearance of fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion (Q(muc)) and [H+] were estimated using laser-Doppler flowmetry and tonometry, respectively. In an initial series of experiments, we showed that mucosal permeability was linearly correlated with mucosal [H+] in animals subjected to graded degrees of mechanically induced mesenteric ischemia (n = 14, R2 = 0.58, P <0.002) or injected with graded doses of LPS (n = 11, R2 = 0.93, P <0.0001). In a second series of experiments, we induced mucosal acidosis in normal pigs by mechanical ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture. In both groups, ileal mucosal permeability to FD-4 increased significantly (P <0.05), although transmesenteric release of lactate increased significantly only in the hypoxic group. Q(muc) was unchanged in both groups. These data suggest that mucosal acidosis, even in the absence of tissue ischemia or hypoxia, increases intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis may be an important factor contributing to LPS-induced gut mucosal hyperpermeability.",
keywords = "acidosis, epithelium, lipopolysaccharide, sepsis",
author = "Salzman, {A. L.} and H. Wang and Wollert, {P. S.} and Vandermeer, {T. J.} and Compton, {C. C.} and Denenberg, {A. G.} and Fink, {M. P.}",
year = "1994",
language = "English (US)",
volume = "266",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 29-4",

}

TY - JOUR

T1 - Endotoxin-induced ileal mucosal hyperpermeability in pigs

T2 - Role of tissue acidosis

AU - Salzman, A. L.

AU - Wang, H.

AU - Wollert, P. S.

AU - Vandermeer, T. J.

AU - Compton, C. C.

AU - Denenberg, A. G.

AU - Fink, M. P.

PY - 1994

Y1 - 1994

N2 - Administration of lipopolysaccharide (LPS) to experimental animals leads to diminished mesenteric perfusion, increased ileal mucosal [H+], and increased gut epithelial permeability to hydrophilic solutes. We sought to determine whether these phenomena are causally related. Experiments were performed in anesthetized pigs. Permeability was assessed by measuring the plasma-to-lumen clearance of fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion (Q(muc)) and [H+] were estimated using laser-Doppler flowmetry and tonometry, respectively. In an initial series of experiments, we showed that mucosal permeability was linearly correlated with mucosal [H+] in animals subjected to graded degrees of mechanically induced mesenteric ischemia (n = 14, R2 = 0.58, P <0.002) or injected with graded doses of LPS (n = 11, R2 = 0.93, P <0.0001). In a second series of experiments, we induced mucosal acidosis in normal pigs by mechanical ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture. In both groups, ileal mucosal permeability to FD-4 increased significantly (P <0.05), although transmesenteric release of lactate increased significantly only in the hypoxic group. Q(muc) was unchanged in both groups. These data suggest that mucosal acidosis, even in the absence of tissue ischemia or hypoxia, increases intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis may be an important factor contributing to LPS-induced gut mucosal hyperpermeability.

AB - Administration of lipopolysaccharide (LPS) to experimental animals leads to diminished mesenteric perfusion, increased ileal mucosal [H+], and increased gut epithelial permeability to hydrophilic solutes. We sought to determine whether these phenomena are causally related. Experiments were performed in anesthetized pigs. Permeability was assessed by measuring the plasma-to-lumen clearance of fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion (Q(muc)) and [H+] were estimated using laser-Doppler flowmetry and tonometry, respectively. In an initial series of experiments, we showed that mucosal permeability was linearly correlated with mucosal [H+] in animals subjected to graded degrees of mechanically induced mesenteric ischemia (n = 14, R2 = 0.58, P <0.002) or injected with graded doses of LPS (n = 11, R2 = 0.93, P <0.0001). In a second series of experiments, we induced mucosal acidosis in normal pigs by mechanical ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture. In both groups, ileal mucosal permeability to FD-4 increased significantly (P <0.05), although transmesenteric release of lactate increased significantly only in the hypoxic group. Q(muc) was unchanged in both groups. These data suggest that mucosal acidosis, even in the absence of tissue ischemia or hypoxia, increases intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis may be an important factor contributing to LPS-induced gut mucosal hyperpermeability.

KW - acidosis

KW - epithelium

KW - lipopolysaccharide

KW - sepsis

UR - http://www.scopus.com/inward/record.url?scp=0028357004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028357004&partnerID=8YFLogxK

M3 - Article

C2 - 7513959

AN - SCOPUS:0028357004

VL - 266

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 4 29-4

ER -