AJP - Regulatory, Integrative and Comparative Physiology, Vol 261, Issue 4 965-R972, Copyright © 1991 by American Physiological Society
Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole
R. S. Hotchkiss, R. S. Rust, C. S. Dence, T. H. Wasserman, S. K. Song, D. R. Hwang, I. E. Karl and M. J. Welch
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110.
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.
