title: Proteoglycan fragmentation and respiratory mechanics in mechanically ventilated healthy rats.
abstract: This research investigated whether stretching of lung tissue due to increased positive alveolar pressure swings during mechanical ventilation (MV) at various tidal volumes (V(T)) might affect the composition and/or structure of the glycosaminoglycan (GAG) components of pulmonary extracellular proteoglycans. Experiments were performed in 30 healthy rats: 1) anesthetized and immediately killed (controls, C-0); 2) anesthetized and spontaneously breathing for 4 h (C-4h); and 3) anesthetized, paralyzed, and mechanically ventilated for 4 h with air at 0-cmH(2)O end-expiratory pressure and V(T) of 8 ml/kg (MV-1), 16 ml/kg (MV-2), 24 ml/kg (MV-3), or 32 ml/kg (MV-4), adjusting respiratory rates at a minute ventilation of 270 ml/min. Compared with C-0 and C-4h, a significant reduction of dynamic and static compliance of the respiratory system and of the lung was observed only in MV-4, while extravascular lung water significantly increased in MV-3 and MV-4, but not in MV-1 and MV-2. However, even in MV-1, MV induced a significant fragmentation of pulmonary GAGs. Extraction of covalently bound GAGs and wash out of loosely bound or fragmented GAGs progressively increased with increasing V(T) and was associated with increased expression of local (matrix metalloproteinase-2) and systemic (matrix metalloproteinase-9) activated metalloproteases. We conclude that 1) MV, even at "physiological" low V(T), severely affects the pulmonary extracellular architecture, exposing the lung parenchyma to development of ventilator-induced lung injury; and 2) respiratory mechanics is not a reliable clinical tool for early detection of lung injury.
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, Via J.H. Dunant 5, 21100 Varese, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Moriondo
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Alberto
authors.initials: A
authors.lastname: Passi
authors.forename: Manuela
authors.initials: M
authors.lastname: Viola
authors.forename: Cristiana
authors.initials: C
authors.lastname: Marcozzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Severgnini
authors.forename: Vittoria
authors.initials: V
authors.lastname: Ottani
authors.forename: Marilisa
authors.initials: M
authors.lastname: Quaranta
authors.forename: Daniela
authors.initials: D
authors.lastname: Negrini
mesh_terms: D000399:Air Pressure; D000818:Animals; D006025:Glycosaminoglycans / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects*; D015656:Respiratory Mechanics / Q000502:physiology*; D013990:Tidal Volume / Q000502:physiology
chemical_list: D006025:Glycosaminoglycans; D015850:Interleukin-6; D011509:Proteoglycans; D045726:Metalloproteases