Studies of an antiendotoxin antibody in preventing the physiologic changes of endotoxemia in awake sheep.
In sheep, endotoxin (LPS) causes pulmonary hypertension, hypoxemia, leukopenia, exudation of protein-rich lung lymph, reduced dynamic compliance (Cdyn), and increased resistance to airflow (RL), changes similar to those seen in human sepsis and sepsis-induced ARDS. We used well-described methods in the awake sheep-endotoxin model to evaluate the effectiveness of a commercially manufactured antibody to prevent the physiologic changes of endotoxemia. In awake sheep with chronic lung lymph fistulas, we used a whole-body plethysmograph to measure Cdyn, RL, and FRC. Pulmonary artery, left atrial, and systemic arterial pressures were recorded continuously. Arterial blood gases (for calculating AaPO2), leukocyte counts, and lymph samples were collected every 30 min. Animals received a 30-min (2 mg/kg) infusion of antiendotoxin antibody 4 h before LPS (0.75 micrograms/kg) challenge (n = 4), or were given a mixture of LPS (0.75 micrograms/kg) and antibody (2 mg/kg) that had been incubated in vitro at 37 degrees C for 30 min before infusion (n = 6). A control group given only 2 mg/kg of antibody (n = 4) showed no change in any measured parameter, whereas control animals receiving LPS alone (n = 6) exhibited a typical endotoxin response. In all animals receiving endotoxin, Cdyn declined by approximately 50% within 30 to 60 min, and RL increased approximately sixfold over a similar time course. Accompanying the abnormalities in lung mechanics were pulmonary hypertension, leukopenia, and widening of the AaPO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Wheeler
A P
AP
Department of Medicine, Vanderbilt University, Nashville, Tennessee.
Hardie
W D
WD
Bernard
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D004731:Endotoxins / Q000097:blood* / Q000276:immunology; D004926:Escherichia coli; D006439:Hemodynamics; D007958:Leukocyte Count; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology; D008168:Lung / Q000503:physiopathology; D008196:Lymph / Q000502:physiology; D011659:Pulmonary Gas Exchange; D015656:Respiratory Mechanics; D012756:Sheep
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli