title: Synergistic hemodynamic effects of low-dose endotoxin and acute lung injury.
abstract: We evaluated the effects of low-dose endotoxin (15 microg/kg) on the pulmonary and systemic responses to oleic acid (OA)-induced acute lung injury in dogs. Animals given endotoxin alone (n = 5) showed a modest decrease in arterial blood pressure, but no effects on pulmonary hemodynamics, blood gases, cardiac output, or lung water accumulation. Animals (n = 6) given only OA (0.08 ml/kg) showed the expected development of mild-moderate pulmonary hypertension, a comparable reduction in arterial blood pressure, hypoxemia, increased lung water concentration, and an altered intrapulmonary perfusion pattern, as assessed by positron emission tomography. Animals (n = 7) given the same dose of endotoxin, followed 30 min later by the same dose of OA, developed a similar increase in lung water concentration as the group given OA alone, but failed to develop pulmonary hypertension or to redistribute pulmonary blood flow away from the edematous lung regions. In addition, arterial blood pressure fell significantly more than in the other groups. These responses were associated with a 30-fold increase in circulating prostacyclin (assayed as 6-keto prostaglandin F1 alpha [PGF1alpha]). The effects on systemic blood pressure, intrapulmonary blood flow redistribution, and eicosanoid production were eliminated by pretreating (n = 5) animals with meclofenamate (2 mg/kg). The results are consistent with a "priming" effect of low-dose endotoxin on the pulmonary endothelium, with exaggerated prostacyclin production in response to a subsequent lung injury. This interaction leads to altered intrapulmonary hemodynamics that exacerbate the development of hypoxemia, and to significant decreases in systemic blood pressure. To the extent that the lung is the most likely source of the increased prostacyclin production, the synergistic effects of low-dose endotoxin and lung injury may produce a kind of "lung shock."
authors.affiliation: Pulmonary and Critical Care Division, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gust
authors.forename: J
authors.initials: J
authors.lastname: Kozlowski
authors.forename: A H
authors.initials: AH
authors.lastname: Stephenson
authors.forename: D P
authors.initials: DP
authors.lastname: Schuster
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004731:Endotoxins / Q000008:administration & dosage* / Q000494:pharmacology; D015633:Extravascular Lung Water; D006439:Hemodynamics; D008168:Lung / Q000000981:diagnostic imaging; D008469:Meclofenamic Acid / Q000494:pharmacology; D019301:Oleic Acid; D011652:Pulmonary Circulation; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000097:blood; D014055:Tomography, Emission-Computed
chemical_list: D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D019301:Oleic Acid; D008469:Meclofenamic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha