Mechanisms of late hemodynamic and airway dynamic responses to endotoxin in awake sheep.
The mechanism of sustained alterations in pulmonary hemodynamics and lung mechanics after endotoxin infusion in sheep remains unclear. We examined the effects of metaproterenol, propranolol, atropine, and ibuprofen on pulmonary artery pressure (Ppa), dynamic compliance (Cdyn), resistance to airflow across the lungs (RL), specific airway conductance (SGaw), and alveolar-arterial oxygen difference (delta AaPO2) (room air) given 2.5 h after endotoxemia (except for propranolol, which was given 1 h after metaproterenol) in awake sheep. Atropine infusion had no effect on any of the variables measured. Ibuprofen infusion immediately reduced mean Ppa from 31 +/- 2 (mean +/- SEM) to 24 +/- 2 cm H2O (p less than 0.05). Metaproterenol and ibuprofen immediately increased Cdyn and SGaw and decreased RL to near baseline (p less than 0.05). No intervention affected delta AaPO2 (p greater than 0.05). In sheep treated with metaproterenol, propranolol immediately returned lung mechanics (p less than 0.05) to premetaproterenol levels without affecting delta AaPO2 (p greater than 0.05). Ibuprofen reduced lung lymph thromboxane-B2 towards baseline levels (p less than 0.05). We conclude that endotoxemia causes prolonged bronchoconstriction and pulmonary hypertension in sheep, which is largely mediated by constrictor prostanoids rather than by cholinergic mechanisms and is reversible with ibuprofen given 2.5 h after endotoxin.
Department of Medicine, Vanderbilt University, Nashville, Tennessee.
P E
PE
Wright
G R
GR
Bernard
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007052:Ibuprofen / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008170:Lung Compliance / Q000187:drug effects; D009921:Metaproterenol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects*; D012756:Sheep; D013929:Thromboxane B2 / Q000378:metabolism
D004731:Endotoxins; D009921:Metaproterenol; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C044101:endotoxin, Escherichia coli; D001285:Atropine; D011433:Propranolol; D007052:Ibuprofen