Effect of polyethylene glycol-superoxide dismutase and catalase on endotoxemia in pigs.
We hypothesized that superoxide anion (O2-.) and hydrogen peroxide (H2O2) might be important mediators of endotoxin-induced acute respiratory failure (ARF) in pigs. As specific scavengers of O2-. and H2O2, we infused polyethylene glycol-superoxide dismutase (PEG-SOD; 2,000 IU/kg) and PEG-catalase (CAT; 15,000 IU/kg), respectively. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3.5 h. During phase 1 (i.e., 0-2 h) and 2 (i.e., 2-4.5 h), endotoxin decreased cardiac index (CI) and lung dynamic compliance, and increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), total peripheral resistance (TPR), alveolar-arterial O2 gradient, and hematocrit. Endotoxemia also caused granulocytopenia and increased the postmortem bronchoalveolar lavage fluid (BALF) albumin concentration and wet-to-dry ratio of bloodless lung. During endotoxemia, PEG-SOD failed to significantly alter any measured or calculated parameter. On the other hand, PEG-CAT attenuated the early (i.e., 0-1 h) endotoxin-induced decrease in CI and increases in Ppa, PVR, and TPR, but failed to modify these parameters during phase 2. PEG-CAT also attenuated the endotoxin-induced granulocytopenia and the increased BALF albumin concentration. In the presence of inactivated PEG-CAT, these protective effects were reversed. We conclude that O2-. does not directly contribute to endotoxin-induced lung injury and that H2O2 (or a subsequent metabolite) contributes to the early endotoxin-induced hemodynamic changes, granulocytopenia, and increased permeability of the alveolar-capillary membrane.
Olson
N C
NC
Department of Anatomy, Physiological Sciences, and Radiology, School of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Grizzle
M K
MK
Anderson
D L
DL
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D004731:Endotoxins / Q000097:blood*; D004800:Enzymes, Immobilized / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000502:physiology; D011092:Polyethylene Glycols; D012131:Respiratory Insufficiency / Q000209:etiology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013481:Superoxides / Q000502:physiology; D013552:Swine
D004731:Endotoxins; D004800:Enzymes, Immobilized; D005609:Free Radicals; D013481:Superoxides; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase