Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock

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Abstract
To evaluate the hypothesis that splanchnic ischemia and mucosal hypoxia are responsible for lipopolysaccharide-induced intramucosal acidosis in pigs. Prospective, randomized, unblinded study. Surgical research laboratory at a large, university-affiliated medical center. Anesthetized, mechanically ventilated swine. Pigs were infused with lactated Ringer's solution (12 mL/kg/hr) and, starting at 30 mins, 25-mL boluses of dextran-70 (maximum 15 mL/kg/hr) to maintain cardiac output at 90% to 110% of the baseline value for each pig. Ileal mucosal hydrogen ion concentration was measured tonometrically. A segment of distal ileum was exteriorized, opened, and placed on a platform to permit measurement of mucosal PO2, using an array of Clark-type microelectrodes and a computerized data acquisition and analysis system. Mucosal perfusion was measured using laser-Doppler flowmetry. The control group (n = 4) received no further interventions. Pigs in the lipopolysaccharide group (n = 6) were infused with 150 micrograms/kg of Escherichia coli lipopolysaccharide over 60 mins. To assess the effect of mucosal acidosis on mucosal PO2 in nonendotoxemic animals, intramucosal hydrogen ion concentration, mucosal PO2, and mucosal perfusion were measured in pigs rendered hypercarbic through deliberate hypoventilation (hypercarbia group; n = 4). Infusion of lipopolysaccharide resulted in a significant increase in intramucosal hydrogen ion concentration. However, in the lipopolysaccharide group, mucosal perfusion did not change significantly and mucosal PO2 increased significantly. In the hypercarbia group, hypercarbia was associated with significant increases in both intramucosal hydrogen ion concentration and mucosal PO2. Mucosal hypoxia is not responsible for lipopolysaccharide-induced mucosal acidosis in this normodynamic pig model of septic shock. A rightward shift of the oxyhemoglobin dissociation curve (the Bohr effect) can explain the increase in mucosal oxygenation observed in endotoxemic pigs.