Effect of endotoxin on systemic and skeletal muscle O₂ extraction

Patients with the adult respiratory distress syndrome (ARDS) show a pathological dependence of O₂ consumption (V̇O₂) on O₂ delivery (Q̇O₂, blood flow x arterial O₂ content). In these patients, a defect in tissues' ability to extract O₂ from blood can leave tissue O₂ needs unmet, even at a normal Q̇O₂. Endotoxin administration produces a similar state in dogs, and we used this model to study mechanisms that may contribute to human pathology. We measured systemic and hindlimb V̇O₂ and Q̇O₂ while reducing cardiac output by blood withdrawal. At the onset of supply dependence, the systemic Q̇O₂ was 11.4 ± 2.7 ml · kg^-1 · min^-1 in the endotoxin group vs. 8.0 ± 0.7 in controls (P < 0.05). At this point, the endotoxin-treated animals extracted only 61 ± 11% of the arterial O₂, whereas control animals extracted 70 ± 7% (P < 0.05). Systemic V̇O₂ rose by 15% after endotoxin (P < 0.05) but did not change in controls. Despite this poorer systemic ability to extract O₂ by the endotoxin-treated dogs, isolated hindlimb O₂ extraction at the onset of supply dependence was the same in endotoxin-treated and control dogs. At normal levels of Q̇O₂ hindlimb V̇O₂ in endotoxin-treated dogs was 23% higher than in controls (P < 0.05). Fractional blood flow to skeletal muscle did not differ between control and endotoxin-treated dogs. Thus skeletal muscle was not overperfused in endotoxemia and did not contribute to a systemic extraction defect by stealing blood flow from other tissues. Skeletal muscle in endotoxin-treated dogs demonstrated an increase in V̇O₂ but no defect in O₂ extraction, differing in both respects from the intestine.