ENDOTOXIN-INDUCED ILEAL MUCOSAL HYPERPERMEABILITY IN PIGS - ROLE OF TISSUE ACIDOSIS

Administration of lipopolysaccharide (LPS) to experimental animals lea ds to diminished mesenteric perfusion, increased ileal mucosal [H+], a nd increased gut epithelial permeability to hydrophilic solutes. We so ught to determine whether these phenomena are causally related. Experi ments were performed in anesthetized pigs. Permeability was assessed b y measuring the plasma-to-lumen clearance of fluorescein isothiocyanat e dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion (Q(mue)) and [H+] were estimated u sing laser Doppler flowmetry and tonometry, respectively. In an initia l series of experiments, we showed that mucosal permeability was linea rly correlated with mucosal [H+] in animals subjected to graded degree s of mechanically induced mesenteric ischemia (n = 14, R(2) = 0.58, P < 0.002) or injected with graded doses of LPS (n = 11, R(2) = 0.93, P < 0.0001). In a second series of experiments, we induced mucosal acido sis in normal pigs by mechanical ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture. In both groups, ileal mucos al permeability to FD-4 increased significantly (P < 0.05), although t ransmesenteric release of lactate increased significantly only in the hypoxic group. Q(mue) was unchanged in both groups. These data suggest that mucosal acidosis, even in the absence of tissue ischemia or hypo xia, increases intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis may be an important factor contributing to LP S-induced gut mucosal hyperpermeability.