Formation of free radicals and nitric oxide derivative of hemoglobin in rats during shock syndrome.
Free radicals have been postulated to play an important role as mediators in the pathogenesis of shock syndrome and multiple-organ failure. We attempted to directly detect the increased formation of radicals by Electron Spin Resonance (ESR) in animal models of shock, namely the endotoxin (ETX) shock or the hemorrhagic shock of the rat. In freeze-clamped lung tissue, a small but significant increase of a free radical signal was detected after ETX application. In the blood of rats under ETX shock, a significant ESR signal with a triplet hyperfine structure was observed. The latter ESR signal evolved within several hours after the application of ETX and was localized in the red blood cells. This signal was assigned to a nitric oxide (NO) adduct of hemoglobin with the tentative structure [alpha 2+ NO)beta 3+)2. The amount of hemoglobin-NO formed, up to 0.8% of total hemoglobin, indicated that under ETX shock a considerable amount of NO was produced in the vascular system. This NO production was strongly inhibited by the arginine analog NG-monomethyl-arginine (NMMA). The ESR signal of Hb-NO was also observed after severe hemorrhagic shock. There are three questions, namely (i) the type of vascular cells and the regulation of the process forming such a large amount of NO during ETX shock, (ii) the pathophysiological implications of the formed NO, effects which have been described as cytotoxic mediator, endothelium-derived relaxing factor (EDRF) or inhibitor of platelet aggregation, and (iii) the possible use of Hb-NO for monitoring phases of shock syndrome.
Westenberger
U
U
Department of Biomedical Engineering, Frauhofer Institute, St. Ingbert, Fed. Rep. of Germany.
Thanner
S
S
Ruf
H H
HH
Gersonde
K
K
Sutter
G
G
Trentz
O
O
D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006454:Hemoglobins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D009102:Multiple Organ Failure / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood*; D051381:Rats; D011917:Rats, Inbred Lew; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism
D005609:Free Radicals; D006454:Hemoglobins; D009569:Nitric Oxide