ENDOTOXEMIA CAUSES ILEAL MUCOSAL ACIDOSIS IN THE ABSENCE OF MUCOSAL HYPOXIA IN A NORMODYNAMIC PORCINE MODEL OF SEPTIC SHOCK

Objective: To evaluate the hypothesis that splanchnic ischemia and muc osal hypoxia are responsible for lipopolysaccharide-induced intramucos al acidosis in pigs. Design: Prospective, randomized, unblinded study. Setting: Surgical research laboratory at a large, university-affiliat ed medical center. Subjects: Anesthetized, mechanically ventilated swi ne. Interventions: Pigs were infused with lactated Ringer's solution ( 12 mL/kg/hr) and, starting at 30 mins, 25-mL boluses of dextran-70 (ma ximum 15 mL/kg/hr) to maintain cardiac output at 90% to 110% of the ba seline value for each pig. Ileal mucosal hydrogen ion concentration wa s measured tonometrically. A segment of distal ileum was exteriorized, opened, and placed on a platform to permit measurement of mucosal Po- 2, using an array of Clark-type microelectrodes and a computerized dat a acquisition and analysis system. Mucosal perfusion was measured usin g laser-Doppler flowmetry. The control group (n = 4) received no furth er interventions. Pigs in the lipopolysaccharide group (n = 6) were in fused with 150 mu g/kg of Escherichia coli lipopolysaccharide over 60 mins. To assess the effect of mucosal acidosis on mucosal Po-2 in none ndotoxemic animals, intramucosal hydrogen ion concentration, mucosal P o-2, and mucosal perfusion were measured in pigs rendered hypercarbic through deliberate hypoventilation (hypercarbia group; n = 4). Measure ments and Main Results: Infusion of lipopolysaccharide resulted in a s ignificant increase in intramucosal hydrogen ion concentration. Howeve r, in the lipopolysaccharide group, mucosal perfusion did not change s ignificantly and mucosal Po-2 increased significantly. In the hypercar bia group, hypercarbia was associated with significant increases in bo th intramucosal hydrogen ion concentration and mucosal Po-2. Conclusio ns: Mucosal hypoxia is not responsible for lipopolysaccharide-induced mucosal acidosis in this normodynamic pig model of septic shock. A rig htward shift of the oxyhemoglobin dissociation curve (the Bohr effect) can explain the increase in mucosal oxygenation observed in endotoxem ic pigs.