Ed. Crouser et al., Ileal Vo(2)-Do(2) alterations induced by endotoxin correlate with severityof mitochondrial injury, AM J R CRIT, 160(4), 1999, pp. 1347-1353
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.