Diethylcarbamazine on pulmonary vascular response to endotoxin in awake sheep.
Diethylcarbamazine (DEC) is an inhibitor of lipoxygenase, with protective effects in several experimental models of anaphylaxis and lung dysfunction. The hypothesis of this study was that DEC would alter the pulmonary response to endotoxin infusion, especially the prolonged pulmonary hypertension, leukopenia, hypoxemia, and high flow of protein-rich lung lymph. We prepared sheep for chronic measurements of hemodynamics and collection of lung lymph. In paired studies we gave six sheep endotoxin (0.5 micrograms/kg iv) either with or without DEC. DEC was given (80-100 mg/kg iv) over 30 min followed by a continuous infusion at 1 mg X kg-1 X min-1. Endotoxin was given after the loading infusion of DEC, and variables were monitored for 4 h. The response to endotoxin was characterized by pulmonary hypertension, leukopenia, hypoxemia, and elevations of thromboxane B2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha). Lymph flow and protein content reflected hemodynamic and permeability changes in the pulmonary circulation. DEC did not significantly modify the response to endotoxin by any measured variable, including pulmonary arterial and left atrial pressures, cardiac output, lymph flow and protein content, alveolar-to-arterial PO2 difference, blood leukocyte count, and lymph thromboxane B2 and 6-keto-PGF1 alpha. We could not find evidence of release of leukotriene C4/D4 by radioimmunoassay in lung lymph after endotoxin infusion with or without DEC treatment. We conclude that lipoxygenase products of arachidonic acid may not be a major component of the pulmonary vascular response to endotoxin.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D004049:Diethylcarbamazine / Q000494:pharmacology*; D004731:Endotoxins / Q000633:toxicity*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D000860:Hypoxia / Q000139:chemically induced; D007970:Leukopenia / Q000139:chemically induced; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008196:Lymph / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D013189:SRS-A / Q000378:metabolism; D012756:Sheep; D013929:Thromboxane B2 / Q000378:metabolism
D004731:Endotoxins; D013189:SRS-A; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D004049:Diethylcarbamazine