Abstract | BACKGROUND:
Hemorrhagic shock (HS) is associated with the generation of reactive oxygen species, which may contribute to delayed multiple organ system failure and death. Previous studies have shown that the antioxidant Tempol improved physiologic variables, although not necessarily outcome, in septic shock and HS. We hypothesized that the combination of free Tempol with polynitroxylated albumin (PNA)-bound Tempol (which prolongs half-life and decreases toxicity) improves outcome after HS in rats. METHODS: In study 1, HS was induced by blood withdrawal of 3 mL/100 g over 15 minutes. Mean arterial pressure was maintained at 40 mm Hg with either infusion of normal saline or withdrawal of blood from 20 to 90 minutes. Resuscitation (90-270 minutes) was with infusion of shed blood. Observation was to 72 hours. At HS 45 min, albumin (ALB) (n = 10) or PNA + Tempol (n = 10) was infused slowly (1 mL/100 g/h) until 120 minutes. Study 2 was the same as study 1 (n = 6 per group), but terminated at 150 minutes. Study 3 was the same as study 1, but started with ALB or PNA + Tempol (n = 7 per group) at 20 minutes. The primary outcome variable in studies 1 and 3 was survival, whereas the primary outcome variables in study 2 were antioxidant reserve (ability of the serum or tissue homogenate to scavenge peroxyl radicals produced by 2,2'-azobis [2-aminodipropane]-dihydrochloride) in serum and small intestine, and low-molecular-weight thiols in tissues (liver, small intestine, and kidney). RESULTS: In study 1, 72-hour survival was 1 of 10 (ALB group) versus 2 of 10 (PNA + Tempol group). At 90 minutes, pH was lower in the ALB group versus the PNA + Tempol group (p = 0.02) and remained low. Arterial lactate increased to 8.9 +/- 3.2 (mean +/- SD) versus 6.5 +/- 1.8 mmol/L (p = 0.04) and base excess was -9.6 +/- 4.3 versus -5.2 +/- 3.2 mmol/L (p = 0.01) (ALB vs. PNA + Tempol groups, respectively). In study 2, antioxidant reserve in serum was lower in the ALB group versus the PNA + Tempol group (p = 0.002). There were no differences between groups in antioxidant reserve in the small intestine or low-molecular-weight thiols in liver, kidney, and small intestine. In study 3, 72-hour survival was zero of seven (ALB group) versus five of seven (PNA + Tempol group) (p = 0.02). Heart rate and systolic blood pressure during late HS were higher in the ALB group in studies 1 and 3 (p < 0.05). CONCLUSION:
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Authors | Rainer Kentner, Peter Safar, Wilhelm Behringer, Xianren Wu, Valerian E Kagan, Yulia Y Tyurina, Jeremy Henchir, Li Ma, Carleton J C Hsia, Samuel A Tisherman |
Journal | The Journal of trauma
(J Trauma)
Vol. 53
Issue 5
Pg. 968-77
(Nov 2002)
ISSN: 0022-5282 [Print] United States |
PMID | 12435951
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Albumins
- Antioxidants
- Cyclic N-Oxides
- Nitrogen Oxides
- Spin Labels
- Sulfhydryl Compounds
- polynitroxyl-albumin
- tempol
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Topics |
- Acid-Base Equilibrium
(drug effects)
- Albumins
(pharmacology)
- Analysis of Variance
- Animals
- Antioxidants
(pharmacology)
- Blood Gas Analysis
- Cyclic N-Oxides
(pharmacology)
- Disease Models, Animal
- Half-Life
- Hemodynamics
- Male
- Nitrogen Oxides
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Shock, Hemorrhagic
(drug therapy, physiopathology)
- Spin Labels
- Statistics, Nonparametric
- Sulfhydryl Compounds
(metabolism)
- Survival Rate
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