Effect of intravenous catalase on the pulmonary vascular response to endotoxemia in goats.
Neutrophils have been implicated in the pathogenesis of acute lung injury associated with clinical and experimental sepsis. Data from in vitro systems and experimental animals have suggested that neutrophil-derived oxidants, particularly H2O2, may be primarily responsible for endothelial damage, vasoconstriction, and lung edema. With the use of endotoxin infusion as an in vivo model of sepsis we tested the hypothesis that pretreatment with catalase, a peroxide scavenger, would ameliorate the resultant changes in pulmonary vasoconstriction and lung fluid balance. Paired experiments were performed in 16 goats with chronic lung lymph fistulas. One group of animals (n = 7) received endotoxin first alone and then again, several days later, after pretreatment with Ficoll-linked catalase. As a control, identical experiments were performed in a separate group (n = 6) with Ficoll-linked albumin substituted for Ficoll-catalase. A third group (n = 3) was given endotoxin alone and then again during a continuous infusion of catalase. Plasma and lymph levels of catalase were comparable to or exceeded those previously shown to be completely protective in isolated perfused lung preparations and in vitro systems. Endotoxin caused neutropenia, pulmonary arterial hypertension, decreased cardiac output, and increases in lymph flow to approximately three times base line, with a return of all variables toward control values by 6 h. Catalase pretreatment produced no significant differences in any of these variables. These experiments do not support a role for H2O2 as a mediator of acute lung injury due to endotoxemia.
Maunder
R J
RJ
Department of Medicine, Harborview Medical Center, University of Washington.
Winn
R K
RK
Gleisner
J M
JM
Hildebrandt
J
J
Harlan
J M
JM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000097:blood / Q000494:pharmacology*; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D006041:Goats; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008196:Lymph / Q000502:physiology*; D011651:Pulmonary Artery / Q000503:physiopathology; D013929:Thromboxane B2 / Q000097:blood
D004731:Endotoxins; D013929:Thromboxane B2; D002374:Catalase