Prophylactic and curative effects of recombinant human superoxide dismutase in lethal rat endotoxemia.
The continuous infusion of E. coli lipopolysaccharide (100 mg/kg in 4 h) caused a 100%-mortality in pentobarbital-anesthetized rats within 6 h. Recombinant human superoxide dismutase (r-HSOD) infused concomitantly with the E. coli endotoxin dose-dependently (0.1-1.0 mg/kg per min) increased survival rate up to 90%. Significant improvement of survival rate was also obtained when r-HSOD-infusion (0.464 mg/kg per min) was only started up to 3 h after beginning of the endotoxin application. Also, two single bolus injections of r-HSOD (20 mg/kg each) during endotoxemia significantly increased survival rate. Decrease of heart rate was prevented and decline of arterial blood pressure was diminished by r-HSOD (0.464 mg/kg per min) as compared to vehicle-treated endotoxemic rats. Lactic acidosis occurred with no significant statistical difference between r-HSOD- and vehicle-treated groups. Increase of hematocrit in endotoxemic control rats was balanced by fluid uptake. In contrast, in the groups treated with endotoxin plus r-HSOD or saline alone hematocrit decreased identically. Decrease of whole blood leukocytes (to 30.2 +/- 9.5% of baseline in endotoxemic controls) was less pronounced in the r-HSOD group (fall to 49.2 +/- 6.5% of baseline), but this difference did not reach statistical significance. Marked thrombocytopenia (to 12.9 +/- 3.2% of baseline) and consumption of plasma fibrinogen (to 39.5 +/- 10.3% of baseline) were significantly attenuated in r-HSOD-treated rats, where thrombocytes only decreased to 28.1 +/- 3.6% and plasma fibrinogen to 76.6 +/- 5.0% of baseline values at the end of endotoxin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Schneider
J
J
Department of Pharmacology, Grünenthal GmbH, Aachen, Fed. Rep. of Germany.
D000818:Animals; D001794:Blood Pressure; D004927:Escherichia coli Infections / Q000139:chemically induced / Q000188:drug therapy*; D006339:Heart Rate; D006400:Hematocrit; D007773:Lactates / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D011135:Polysaccharides, Bacterial; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000097:blood / Q000494:pharmacology*
D007773:Lactates; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D013482:Superoxide Dismutase