Partial liquid ventilation reduces release of leukotriene B4 and interleukin-6 in bronchoalveolar lavage in surfactant-depleted newborn pigs.
Perfluorocarbons have been shown to reduce the inflammatory process generated by alveolar macrophages in vitro. The aim of this study was to evaluate the impact of different ventilator modalities such as partial liquid ventilation (PLV), conventional ventilation (CV), and high-frequency oscillatory ventilation (HFOV) on the release of inflammatory mediators in vivo. Acute lung injury was induced in 30 male piglets by repeated saline lavage (arterial oxygen tension, <60 mm Hg; fraction of inspired oxygen, 1.0). Thereafter, animals were randomly assigned to one of five groups of six animals each: 1) 24 h of CV; 2) 24 h of CV plus surfactant therapy (S+CV); 3) 24 h of HFOV plus surfactant therapy (S+HFOV); 4) 1 h of PLV followed by 23 h of CV (PLV); and 5) 24 h of CV without previous lung injury (control group). Piglets randomized to S+CV or S+HFOV received natural surfactant (100 mg/kg). PLV with FC-77 was started in an initial dose of 30 mL/kg over 30 min followed by 0.5 mL x kg(-1) x min(-1) for another 30 min. After 1 h of PLV the animals were conventionally ventilated for 23 h. Before acute lung injury and after 24 h the number of inflammatory cells and the levels of IL-6, leukotriene B4, and tumor necrosis factor-alpha were measured in the bronchoalveolar lavage fluid. Additionally, the oxygenation index and the histopathologic damage were evaluated. Before acute lung injury, the number of inflammatory cells and the levels of mediators in bronchoalveolar lavage fluid were not different among the groups. After 24 h, the number of granulocytes in the PLV group was as low as in the control group. leukotriene B4 and IL-6 levels were found to be elevated in all groups except the control group (p < 0.01). The release of leukotriene B4 and IL-6 was lowest in the PLV group when compared with S+HFOV, S+CV, or CV (p < 0.05). No differences among the groups were detected for tumor necrosis factor-alpha. Although the concentrations of leukotriene B4 and IL-6 after PLV were lowest in the PLV group, histopathologic evidence of damage and the oxygenation index in the PLV group did not differ from that found in the S+CV or S+HFOV groups. In conclusion, PLV with perfluorocarbons may protect the lung from acute pulmonary inflammation more effectively than CV or HFOV does.
Merz
Ulrich
U
Children's Hospital, Neonatal Intensive Care, Aachen University of Technology, 52057 Aachen, Germany. umerz@post.klinikum.rwth-aachen.de
Klosterhalfen
Bernd
B
Häusler
Martin
M
Kellinghaus
Melanie
M
Peschgens
Thomas
T
Hörnchen
Helmut
H
D000818:Animals; D000831:Animals, Newborn; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D005466:Fluorocarbons / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism*; D021061:Liquid Ventilation; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D055370:Lung Injury; D008297:Male; D011663:Pulmonary Surfactants / Q000008:administration & dosage; D011897:Random Allocation; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005466:Fluorocarbons; D015850:Interleukin-6; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; C429307:fluorocarbon 77; D007975:Leukotriene B4