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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 103/3/747    most recent 00056.2007v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Moriondo, A. Articles by Negrini, D. Search for Related Content PubMed PubMed Citation Articles by Moriondo, A. Articles by Negrini, D.

Proteoglycan fragmentation and respiratory mechanics in mechanically ventilated healthy rats

¹Dipartimento di Scienze Biomediche Sperimentali e Cliniche and ²Dipartimento Ambiente, Salute e Sicurezza, Università degli Studi dell'Insubria, Varese; and ³Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Università degli Studi di Bologna, Bologna, Italy

Submitted 12 January 2007 ; accepted in final form 14 June 2007

This research investigated whether stretching of lung tissue due to increased positive alveolar pressure swings during mechanical ventilation (MV) at various tidal volumes (VT) 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-cmH₂O end-expiratory pressure and VT 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 VT 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 VT, 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.

ventilator-induced lung injury; pulmonary extracellular matrix; respiratory mechanics; lung proteoglycans; metalloproteases