Effects of recombinant human superoxide dismutase on increased lung vascular permeability and respiratory disorder in endotoxemic rats.
A 4 hr intravenous infusion of Escherichia coli endotoxin in a total dose of 100 mg/kg produced significant morphological and functional pulmonary alterations in pentobarbitone anesthetized rats. Lung vascular permeability index was increased from 2.11 +/- 0.34 in normal rats to 4.82 +/- 0.65 in untreated endotoxemic rats. Treatment of endotoxemic rats with recombinant human superoxide dismutase (r-HSOD) in doses of 0.1, 0.215, and 0.464 mg/kg.min i.v., infused concomitantly with endotoxin, dose-dependently reduced the permeability index to 3.28 +/- 0.96, 2.83 +/- 0.55 (P less than 0.05), and 2.16 +/- 0.65 (P less than 0.05). The wet lung weight was 523 +/- 15 and 664 +/- 46 mg/100 g bwt in normal and in untreated endotoxemic rats, respectively. r-HSOD dose-dependently inhibited the endotoxin-induced increase in wet lung weight to 617 +/- 40, 577 +/- 31, and 559 +/- 39 (P less than 0.05) mg/100 g bwt. r-HSOD (0.464 mg/kg.min) did not affect permeability index and wet lung weight in normal, nonintoxicated rats. Endotoxin infusion produced a significant increase in respiratory rate (max. +69%) and blood gas alterations, indicating a hyperventilatory hypocapnia in endotoxemic control rats. Infusion of r-HSOD (0.464 mg/kg.min) significantly inhibited the endotoxin-induced tachypnoe (max. +13%) and blunted the alterations in arterial hydrogen carbonate content and carbon dioxide tension. In conclusion, infusion of r-HSOD dose-dependently and significantly inhibited pulmonary edema formation and hyperventilatory dyspnoe in endotoxemic rats.
Schneider
J
J
Grünenthal GmbH, Center of Research, Aachen, West Germany.
Friderichs
E
E
Heintze
K
K
Flohé
L
L
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004417:Dyspnea / Q000517:prevention & control; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D006801:Humans; D008168:Lung / Q000098:blood supply*; D008297:Male; D009929:Organ Size; D011654:Pulmonary Edema / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012129:Respiratory Function Tests; D013482:Superoxide Dismutase / Q000494:pharmacology*
D004731:Endotoxins; D011994:Recombinant Proteins; D013482:Superoxide Dismutase