title: High frequency oscillatory ventilation suppresses inflammatory response in lung tissue and microdissected alveolar macrophages in surfactant depleted piglets.
abstract: The impact of high frequency oscillatory ventilation (HFOV) compared with intermittent mandatory ventilation (IMV) on oxygenation and pulmonary inflammatory response was studied in a surfactant depleted piglet model. After establishment of lung injury by bronchoalveolar lavage, piglets either received HFOV (n =5) or IMV (control; n = 5) for eight hours. PaO(2) was higher and mean pulmonary arterial pressure (MPAP) was lower with HFOV (HFOV versus control, mean +/- SEM; endpoint PaO(2): 252 +/- 73 versus 68 +/- 8.4 mm Hg; p < 0.001; MPAP: 22 +/- 2.3 versus 34 +/- 2.5 mm Hg; p < 0.01). mRNA expression of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, TGF-beta 1, Endothelin-1, and adhesion molecules (E-selectin, P-selectin, ICAM-1) in lung tissue was quantified by real time PCR normalized to beta-actin and hypoxanthine-guanine-phosphoribosyl-transferase (HPRT). mRNA expression of all cytokines and adhesion molecules/HPRT was higher in controls (e.g.: HFOV versus control, mean +/- SEM; IL-1 beta/HPRT: 1.6 +/- 0.3 versus 23.1 +/- 8.6 relative units (RU), p < 0.001; IL-8/HPRT: 8.5 +/- 2.0 versus 63.5 +/- 15.2 RU, p < 0.001). IL-8/HPRT gene expression was quantified in microdissected single cells. With HFOV, IL-8 gene expression was highly reduced in alveolar macrophages: 10 +/- 3.4 copies IL-8 mRNA/copy HPRT mRNA versus 356 +/- 142; p < 0.05 (bronchiolar epithelial cells: 33 +/- 16 versus 208 +/- 108; alveolar septum: 2.1 +/- 1.3 versus 26 +/- 11; bronchiolar smooth muscle cells: 1.3 +/- 0.3 versus 2.8 +/- 1.0; vascular smooth muscle cells: 0.7 +/- 0.3 versus 1.1 +/- 0.4). In conclusion, HFOV improved oxygenation, reduced pulmonary arterial pressure and attenuated pulmonary inflammatory response.
authors.affiliation: Universitätsklinik für Kinder und Jugendliche, Loschgestr. 15, D-91054 Erlangen, Germany. k.vonderhardt@web.de
authors.forename: Katharina
authors.initials: K
authors.lastname: von der Hardt
authors.forename: Michael Andreas
authors.initials: MA
authors.lastname: Kandler
authors.forename: Ludger
authors.initials: L
authors.lastname: Fink
authors.forename: Ellen
authors.initials: E
authors.lastname: Schoof
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
authors.forename: Olga
authors.initials: O
authors.lastname: Brandenstein
authors.forename: Rainer Maria
authors.initials: RM
authors.lastname: Bohle
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000276:immunology; D006612:High-Frequency Ventilation; D006863:Hydrogen-Ion Concentration; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011014:Pneumonia / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D011652:Pulmonary Circulation / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000502:physiology; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine
chemical_list: D007375:Interleukin-1; D016209:Interleukin-8; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D016753:Interleukin-10; D007041:Hypoxanthine Phosphoribosyltransferase