High frequency oscillatory ventilation suppresses inflammatory response in lung tissue and microdissected alveolar macrophages in surfactant depleted piglets.
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.
von der Hardt
Katharina
K
Universitätsklinik für Kinder und Jugendliche, Loschgestr. 15, D-91054 Erlangen, Germany. k.vonderhardt@web.de
Kandler
Michael Andreas
MA
Fink
Ludger
L
Schoof
Ellen
E
Dötsch
Jörg
J
Brandenstein
Olga
O
Bohle
Rainer Maria
RM
Rascher
Wolfgang
W
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
D007375:Interleukin-1; D016209:Interleukin-8; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D016753:Interleukin-10; D007041:Hypoxanthine Phosphoribosyltransferase