title: Ileal VO(2)-O(2) alterations induced by endotoxin correlate with severity of mitochondrial injury.
abstract: Sepsis is usually associated with altered O(2) metabolism in systemic organs. Until recently, inadequate O(2) delivery was thought to be the putative mechanism underlying these metabolic alterations. However, current investigations suggest that impaired O(2) consumption due to disrupted O(2) use by mitochondria may be the culprit. Therefore, we hypothesized that endotoxin (LPS)-induced V O(2)- O(2) 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 V O(2)- O(2) 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 O(2) delivery (r = 0.85; p < 0.002) 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 impaired O(2) utilization, may be primarily responsible for altered V O(2)- O(2) relationships in systemic organs during sepsis.
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Ohio State University Medical Center, Columbus, Ohio, USA. Crouser-1@medctr.osu.edu
authors.forename: E D
authors.initials: ED
authors.lastname: Crouser
authors.forename: M W
authors.initials: MW
authors.lastname: Julian
authors.forename: P M
authors.initials: PM
authors.lastname: Dorinsky
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002415:Cats; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D007082:Ileum / Q000098:blood supply / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D010108:Oxyhemoglobins / Q000032:analysis; D014655:Vascular Resistance
chemical_list: D004731:Endotoxins; D010108:Oxyhemoglobins; D010100:Oxygen