Normally, supply-dependency of oxygen uptake (VO2) is not demonstrable unless oxygen delivery (DO2) is less than a critical value (DO2crit) below which VO2 is linearly dependent upon DO2. Because recent evidence suggests that VO2 is pathologically supply-dependent in endotoxic or septic animals and humans, we sought to determine whether 1) pathological systemic and/or mesenteric oxygen extraction (O2EXT) defects occur in a porcine model of endotoxicosis and 2) arterial lactate and ileal intramucosal pH (pHI) serve as useful markers of supply-dependency of VO2 in endotoxic animals. Normal (group I, n = 11) and endotoxic (group II, n = 8) anesthetized pigs were subjected to graded hemorrhage. Endotoxicosis was induced by infusing Escherichia coli lipopolysaccharide (150 micrograms/kg bolus at t = 0 min and 20 micrograms/kg-hr at t = 60 min). From t = 0-60 min, pigs in group II were resuscitated with hetastarch and blood (12 ml/kg each). Hemorrhage was initiated at t = 0 min or t = 70 min in groups I and II, respectively. DO2crit was determined by a modified "dual-line" regression method. Systemic DO2crit was 12.9 +/- 0.9 ml/kg-min in group I and 16.9 +/- 1.3 ml/kg-min in group II (P less than .05). Systemic O2EXT at DO2crit was similar in both groups. Arterial lactate concentration at DO2crit was significantly higher in endotoxic pigs (group I, 2.64 +/- 0.29 mM; vs. group II, 3.88 +/- 0.45 mM; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)