Ileal Vo(2)-Do(2) alterations induced by endotoxin correlate with severityof mitochondrial injury

Sepsis is usually associated with altered O-2 metabolism in systemic organs . Until recently, inadequate O-2 delivery was thought to be the putative me chanism underlying these metabolic alterations. However, current investigat ions suggest that impaired O-2 consumption due to disrupted O-2 use by mito chondria may be the culprit. Therefore, we hypothesized that endotoxin (LPS )-induced (V) over dot o(2)-(D) over dot o(2) alterations would correlate w ith the severity of mitochondrial injury in a systemic organ (i.e., the ile um). Using an in situ autoperfused feline ileum preparation, we assessed (V ) over dot o(2)-(D) over dot o(2) relationships and mitochondrial ultrastru cture after 2 h in LPS-treated (3 mg/kg, intravenous; n = 11) and time-matc hed control (n = 5) animals, Mitochondrial injury was graded in a blinded f ashion on the basis of characteristics associated with established stages o f cell injury. LPS-treated animals developed severe mitochondrial injury in the ileal mucosa despite unchanged regional tissue perfusion and ileal oxy hemoglobin levels compared with controls. Worsening of mitochondrial injury correlated with increases in the critical O-2 delivery (r = 0.85; p < 0.00 2) and decreases in the maximum O-2 extraction (r = -0.61; p < 0.02) in the ileum. These results suggest that mitochondrial injury, leading to impaire d O-2 utilization, may be primarily responsible for altered (V) over dot o( 2)-(D) over dot o(2) relationships in systemic organs during sepsis.