A novel nitric oxide scavenger decreases liver injury and improves survival after hemorrhagic shock.
We tested the ability of a nitric oxide (NO) scavenger to reduce tissue injury in a rodent model of hemorrhagic shock. Rats were hemorrhaged to a mean arterial blood pressure (MAP) of 40 mmHg and then resuscitated when either 30% of their shed blood had been returned (group 1) or after 100 min of continuous shock (group 2). Selected animals were treated with the NO scavenger NOX (30 mg. kg(-1). h(-1)) infused over 4 h. Hemorrhaged rats had a lower MAP after resuscitation compared with sham-shock control rats. NOX treatment significantly increased MAP after resuscitation from hemorrhage. Hemorrhagic shock also increased liver injury as reflected by elevated ornithine carbamoyltransferase (OCT) plasma levels, and NOX treatment significantly reduced OCT release. In addition, NOX was associated with significantly decreased hepatic neutrophil infiltration and improved 24-h survival (n = 8 of 9) compared with saline-treated shock animals (n = 3 of 9). These data suggest that excess NO mediates shock-induced tissue injury and that suppression of NO availability with NO scavengers may reduce the pathophysiological sequelae of severe hemorrhage.
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
J
J
Menezes
C
C
Hierholzer
S C
SC
Watkins
V
V
Lyons
A B
AB
Peitzman
T R
TR
Billiar
D J
DJ
Tweardy
B G
BG
Harbrecht
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009954:Ornithine Carbamoyltransferase / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000401:mortality* / Q000473:pathology* / Q000503:physiopathology; D013859:Thiocarbamates / Q000494:pharmacology*
D016207:Cytokines; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D013859:Thiocarbamates; D009569:Nitric Oxide; D009195:Peroxidase; D009954:Ornithine Carbamoyltransferase