Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole.
Underlying cellular hypoxia, which may be difficult to detect, has been postulated to be a major cause of morbidity and mortality in sepsis. We employed the novel hypoxic marker [18F]fluoromisonidazole to determine whether cellular hypoxia was present in a peritonitis model of sepsis in the rat. A second group of septic and control rats had organ blood flow measurements determined by the radiolabeled microsphere technique to relate possible ischemia to decreased organ perfusion. No evidence of cellular hypoxia was detected in skeletal muscle, brain, liver, heart, or diaphragm in the septic rats. Ligation of the femoral artery caused a greater reduction in flow (55% decrease vs. 20% decrease, P less than 0.05) and an increased retention of [18F]fluoromisonidazole in skeletal muscle of the septic rats. We conclude that sepsis does not invariably result in systemic, i.e., multiorgan, cellular hypoxia and that underlying cellular hypoxia is not the major pathophysiological abnormality in sepsis. The greater reduction in muscle blood flow and the increased retention of [18F]fluoromisonidazole in the ischemic muscle of septic rats implies that they may be more vulnerable to hypoxia.
Hotchkiss
R S
RS
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Rust
R S
RS
Dence
C S
CS
Wasserman
T H
TH
Song
S K
SK
Hwang
D R
DR
Karl
I E
IE
Welch
M J
MJ
D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes; D005740:Gases / Q000097:blood; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007239:Infections / Q000209:etiology*; D008920:Misonidazole / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013997:Time Factors
D005462:Fluorine Radioisotopes; D005740:Gases; C031843:fluoromisonidazole; D008920:Misonidazole