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

Our aim was to assess whether endotoxemia impairs the ability of the diaphragm to extract O2 and whether this defect leads to a greater dependence of O2 uptake on O2 delivery. In two groups of anesthetized mechanically ventilated dogs, the left hemidiaphragm was vascularly isolated. Diaphragmatic blood flow and cardiac output (CO) were measured simultaneously in all animals. Saline (S group) or Escherichia coli endotoxin (100 mg; E group) was infused intravenously over 60 min. In both groups, CO was reduced in stages by controlled hemorrhage, and systemic and diaphragmatic O2 deliveries and consumptions were measured at each stage to construct the O2 delivery-O2 consumption relationships. In the S group, the average systemic O2 delivery below which O2 uptake became supply dependent was 7.2 ml.kg-1.min-1. At this O2 delivery, systemic O2 extraction ratio (ER) averaged 67.9%, whereas the maximum O2 ER was 91.3%. Critical diaphragmatic O2 delivery and critical and maximum diaphragmatic O2 ER, by comparison, averaged 9.0 ml.kg-1.min-1, 65%, and 81.9%, respectively. Endotoxin infusion raised critical systemic O2 delivery to 16.7 ml.kg-1.min-1 (P < 0.05) and reduced critical and maximum systemic O2 ER to 55.5 and 77% (P < 0.05), respectively. Similarly, critical diaphragmatic O2 delivery in the E group increased to 14.8 ml.kg-1.min-1 (P < 0.05), whereas critical and maximum O2 ER declined to 51.8 and 72.8%, respectively (P < 0.05). Thus, endotoxemia impairs diaphragmatic O2 extraction. This, in turn, leads to a greater dependence of diaphragmatic O2 uptake on O2 delivery.