Potentiation of lung vascular response to endotoxin by superoxide dismutase.
We studied the effects of superoxide dismutase (SOD), an enzyme that converts superoxide into peroxide, on the cardiopulmonary response to endotoxin in sheep. Sheep (n = 18) were prepared for chronic measurement of cardiopulmonary variables, including lung lymph flow, by surgically implanting catheters under halothane anesthesia. Nine of the animals were studied before and after the administration of endotoxin (0.75 microgram/kg) with and without SOD. An additional nine animals received SOD without the lipopolysaccharide. Endotoxin produced an increase in lung lymph flow that was initially associated with a marked pulmonary arterial (PA) hypertension and reduced lymph-to-plasma protein ratio (L/P). The lymph flow remained elevated later in the response, but there was only a mild increase in PA pressure, and the L/P was normal. There was also a fall in blood neutrophils and in cardiac index. SOD increased this secondary elevation in lung lymph flow, and the corresponding L/P was greater than the preendotoxin value. The fall in neutrophil count, cardiac output, and the elevation in PA pressure seen with endotoxin were not affected by SOD. When administered in the absence of endotoxin, SOD produced no perceptible change in the cardiopulmonary and lymph values. We conclude that peroxide, hydroxyl ion, and/or other free radicals formed by the action of SOD must be responsible for a portion of the endotoxin response rather than superoxide itself.
D000818:Animals; D001794:Blood Pressure; D001798:Blood Proteins / Q000032:analysis; D002302:Cardiac Output; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology*; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D008196:Lymph / Q000032:analysis / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013997:Time Factors
D001798:Blood Proteins; D004731:Endotoxins; D013482:Superoxide Dismutase