Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia.

When systemic delivery of oxygen (QO2 = blood flow X arterial O2 content) is reduced, the systemic O2 extraction ratio [(CaO2 - CVO2)/CaO2; where CaO2 is arterial O2 content and CVO2 is venous O2 content] increases until a critical limit is reached below which O2 uptake (VO2) becomes limited by delivery. Patients with adult respiratory distress syndrome and sepsis exhibit supply dependence of VO2 even at high levels of QO2, which suggests that a peripheral O2 extraction defect may be present. We tested the hypothesis that endotoxemia might produce a similar defect in the efficacy of tissue O2 extraction by determining the whole-body critical systemic QO2 (QO2 c) and critical extraction ratio in a control group of dogs and a group receiving a 5-mg/kg dose of Escherichia coli endotoxin. QO2 c was determined in each group by measuring VO2 as QO2 was gradually reduced by bleeding. The VO2 and QO2 of an isolated segment of small intestine were also measured to determine whether O2 extraction was impaired within a local region of tissue. The dogs were anesthetized, paralyzed, and ventilated with room air. Systemic QO2 was reduced in stages by hemorrhage as hematocrit was maintained. The systemic and intestinal critical points were determined from a plot of VO2 vs. QO2. The mean systemic QO2 c and critical O2 extraction ratio of the endotoxemic group (12.8 +/- 2.0 and 0.54 +/- 0.11 ml.min-1.kg-1) were significantly different from control (6.8 +/- 1.2 and 0.78 +/- 0.04) (P less than 0.001), indicating that endotoxin administration impaired systemic extraction of O2. Endotoxin also increased base-line systemic VO2 [6.1 +/- 0.7 (before) to 7.4 +/- 0.1 (after)] (P less than 0.001). The critical and maximal intestinal O2 extraction ratios of the endotoxemic group (0.47 +/- 0.10 and 0.71 +/- 0.04) were significantly less than control (0.69 +/- 0.06 and 0.83 +/- 0.05) (P less than 0.001). In addition, intestinal reactive hyperemia disappeared in six of seven endotoxemic dogs, whereas it remained intact in all control dogs. Thus endotoxin reduced the ability of tissues to extract O2 from a limited supply at the whole body level as well as within a 40- to 50-g segment of small intestine. These results could be explained by a defect in microvascular regulation of blood flow that interfered with the optimal distribution of a limited QO2 in accordance with tissue O2 needs.