Rapid reduction of intestinal cytochrome a,a3 during lethal endotoxemia.
In vivo near-infrared spectrophotometry was used to determine whether lethal endotoxemia impairs small intestinal oxidative phosphorylation as reflected by the redox state of mitochondrial cytochrome a,a3 (AA3). Adult male Sprague-Dawley rats were anesthetized with 2.1% isoflurane in 30% O2:70% N2O, and the small intestine was partially exteriorized for spectrophotometric monitoring (OMNI-3). By 5 min after an iv bolus of Escherichia coli endotoxin (40 mg/kg, LD90, n = 7) a significant shift toward reduction in intestinal AA3 had occurred in association with hypotension and a marked fall in both superior mesenteric artery blood flow (SMAF) and cardiac output. In a separate group (n = 7) SMAF was kept at the baseline level by periodic infusions of donor rat plasma begun 1 min after endotoxin injection, and the reduction in AA3 was again found despite the fluid loading intervention which successfully maintained not only organ blood flow, but also cardiac output and mean arterial pressure in their normal ranges. Further experiments (n = 34) measuring SM vascular bed oxygen consumption indicated that intestinal VO2 remained unchanged during early endotoxemia. These findings suggest a rapid impairment of oxidative phosphorylation by endotoxin which seems to occur through direct (and/or indirect) toxic cellular effects rather than through impaired tissue perfusion.
Schaefer
C F
CF
Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Biber
B
B
Lerner
M R
MR
Jöbsis-VanderVliet
F F
FF
Fagraeus
L
L
D000818:Animals; D003576:Electron Transport Complex IV / Q000032:analysis*; D004731:Endotoxins / Q000097:blood* / Q000633:toxicity; D006439:Hemodynamics / Q000187:drug effects; D007422:Intestines / Q000201:enzymology* / Q000473:pathology; D008297:Male; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000201:enzymology
D004731:Endotoxins; D010108:Oxyhemoglobins; D003576:Electron Transport Complex IV