Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1347-1353

Ileal O₂-O₂ Alterations Induced by Endotoxin Correlate with Severity of Mitochondrial Injury

ELLIOTT D. CROUSER, MARK W. JULIAN, and PAUL M. DORINSKY

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ohio State University Medical Center, Columbus, Ohio

Sepsis is usually associated with altered O₂ metabolism in systemic organs. Until recently, inadequate O₂ delivery was thought to be the putative mechanism underlying these metabolic alterations. However, current investigations suggest that impaired O₂ consumption due to disrupted O₂ use by mitochondria may be the culprit. Therefore, we hypothesized that endotoxin (LPS)-induced O₂- O₂ alterations would correlate with the severity of mitochondrial injury in a systemic organ (i.e., the ileum). Using an in situ autoperfused feline ileum preparation, we assessed O₂- O₂ relationships and mitochondrial ultrastructure after 2 h in LPS-treated (3 mg/kg, intravenous; n = 11) and time-matched control (n = 5) animals. Mitochondrial injury was graded in a blinded fashion on the basis of characteristics associated with established stages of cell injury. LPS-treated animals developed severe mitochondrial injury in the ileal mucosa despite unchanged regional tissue perfusion and ileal oxyhemoglobin levels compared with controls. Worsening of mitochondrial injury correlated with increases in the critical O₂ delivery (r = 0.85; p < 0.002) and decreases in the maximum O₂ extraction (r = 0.61; p < 0.02) in the ileum. These results suggest that mitochondrial injury, leading to impaired O₂ utilization, may be primarily responsible for altered O₂- O₂ relationships in systemic organs during sepsis.

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