title: Prior exposure to endotoxin exacerbates lipopolysaccharide-induced hypoxemia and alveolitis in anesthetized swine.
abstract: We sought to determine whether a standardized "priming" event, namely a small dose of LPS, would alter physiological responses to a subsequent larger "challenge" dose of endotoxin. Accordingly, four groups of pigs (N = 5-6) were studied. One group received neither priming nor challenge doses of LPS. A second group were not primed but were infused with a challenge dose (250 micrograms/kg) of LPS. A third group were pretreated 18 h before being studied with a priming dose of LPS (20 micrograms/kg), but were not infused with a second dose of LPS. A fourth group received both priming and challenge doses of LPS. Priming with LPS exacerbated endotoxin-induced arterial hypoxemia, and decreased animal-to-animal variability in the degree of hypoxemia induced by a challenge dose of endotoxin. Priming blunted the early phase (30 min) and exacerbated the delayed phase (120-210 min) of LPS-induced pulmonary hypertension. Priming blunted LPS-induced release of prostacyclin and thromboxane A2. The use of a priming dose of LPS increases the severity and reproducibility of LPS-induced acute lung injury in swine.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Wollert
authors.forename: M J
authors.initials: MJ
authors.lastname: Menconi
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: B P
authors.initials: BP
authors.lastname: O'Sullivan
authors.forename: V
authors.initials: V
authors.lastname: Larkin
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: M P
authors.initials: MP
authors.lastname: Fink
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid; D002302:Cardiac Output; D004334:Drug Administration Schedule; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D000860:Hypoxia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011292:Premedication; D011658:Pulmonary Fibrosis / Q000097:blood / Q000503:physiopathology*; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014655:Vascular Resistance
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010100:Oxygen