Effects of high dose E. coli lipopolysaccharide on rabbit lung function, and of subsequent addition of chemotactic granulocyte activators to their isolated, blood-perfused lungs.
E. coli LPS was infused (1 microgram/kg to 5 mg/kg over 30 min) to spontaneously breathing rabbits, and their arterial blood pressure (ABP), blood leukocyte count and blood gases were observed for 2.5-3.5 h. Pulmonary vascular and airway function were subsequently evaluated in vitro by comparing weight changes, fluid filtration rates, pulmonary vascular resistance (PVR) and airway pressures in their isolated, blood-perfused lungs with those in lungs from untreated rabbits. Lung preparations from both groups of animals were then exposed to autologous zymosan-activated plasma (ZAP) or n-formyl-methionyl-leucyl-phenylalanine (FMLP) and perfused for 2 more hours. LPS addition to isolated rabbit leukocytes increased cell aggregation; cell chemiluminescence after activation with FMLP was also enhanced. Infusion of 1-5 mg/kg LPS decreased the count of all types of leukocytes and caused a metabolic acidosis (BE < -8 mmol), but no decrease in ABP. PAO2-Pao2 increased by about 2.0 kPa. No vascular permeability increase was detected in the lungs of these animals during subsequent in vitro perfusion. Addition of ZAP or FMLP during perfusion markedly increased the PVR in lungs from LPS animals, but did not induce major microvascular leakage. No significant differences in edema between lungs from LPS-treated and control animals were found by microscopy.
Opdahl
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Department of Physiology, University of Oslo, Norway.
Mollnes
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TE
Naess
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O
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement; D002630:Chemotactic Factors / Q000494:pharmacology*; D015938:Complement Membrane Attack Complex / Q000032:analysis; D004926:Escherichia coli; D005260:Female; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008163:Luminescent Measurements; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D011650:Pulmonary Alveoli / Q000473:pathology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology
D002630:Chemotactic Factors; D015938:Complement Membrane Attack Complex; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D010100:Oxygen