The role of oxygen free radicals and nitric oxide in organ injury following hemorrhagic shock and reinfusion.
BACKGROUND
Vital organ injury due to tissue hypoperfusion is a major complication of hemorrhagic shock. Nitric oxide (NO) has been implicated in the pathophysiology of hemorrhagic shock.


OBJECTIVE
To determine the effects of L-arginine on the central organ injury due to severe hemorrhagic shock and reinfusion and the relationship among endogenous antioxidants, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in dogs.


METHODS
After induction of anesthesia, twenty six mongrel dogs were hemorrhaged to a mean arterial pressure (MAP) of 35 +/- 3.3 mmHg where they were held for 1 hr. Five minutes prior to the end of the shock period, either saline (5 mL/kg), L-arginine (250 mg/kg), or NG-nitro-L-arginine-methyl-ester (L-NAME) (25 mg/kg) was administered i.v., being followed by reinfusion of shed blood. MAP was monitored. Blood samples were taken for the measurement of blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), intraerythrocytic SOD, CAT, GSH-Px, and serum nitrite and nitrate levels. Tissue samples from liver, kidney and small intestines were taken for histological studies and liver samples were also taken for the mesurement of SOD, CAT, GSH-Px tissue levels.


RESULTS
L-arginine treatment reduced MAP. In contrast, L-NAME treatment significantly increased MAP. L-arginine treatment increased BUN and creatinine. L-NAME treatment significantly increased the activity of hepatic enzymes. L-arginine decreased the reinfusion injury in the liver and the small intestine histopathologically. In addition, L-arginine caused significant decreases in the intraerythrocytic and the liver SOD, CAT and GSH-Px levels from the shock levels.


CONCLUSIONS
L-arginine has a preventive role in liver and intestine following hemorrhagic shock and reinfusion. Inhibition of NO synthesis aggravates reinfusion injury.
Bedirli
A
A
Department of Surgery, School of Medicine, University of Erciyes, 38039 Kayseri, Turkey. bedirli@kaynet.com.tr
Sözüer
E M
EM
Muhtaroğlu
S
S
Alper
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004285:Dogs; D005979:Glutathione Peroxidase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000378:metabolism
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001120:Arginine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester