title: Regional lung tissue changes with mechanical ventilation and fluid load.
abstract: OBJECTIVE
  To investigate the regional gravity-dependent impact of mechanical ventilation and fluid overload on lung extracellular matrix (ECM) in healthy lungs.
  
  
  METHODS
  The glycosaminoglycans (GAGs) composition of the ventral and dorsal lung parenchyma was determined in anesthetized supine healthy rats mechanically ventilated for 4 hours in air: (a) at low (∼7.5 mL/kg) or high (∼ 23 mL /kg) tidal volume (V(T)) and 0 cmH2O positive end-expiratory pressure (PEEP); (b) at low or high V(T) at 5 cmH2O PEEP and (c) with or without 7 mL /(kg·h) intravenous saline infusion.
  
  
  RESULTS
  Mechanical ventilation degraded lung ECM, with alveolar septa thinning and structural GAGs disorganization. Low V(T) ventilation was associated with significant tissue structure changes in both ventral and dorsal lung regions, while high VT mainly affected the dependent ones. PEEP decreased ECM injury mainly in the ventral lung regions, although it did not prevent matrix fragmentation and washout at high V(T). Intravascular fluid load increased lung damage prevalently in the ventral lung regions.
  
  
  CONCLUSIONS
  Mechanical ventilation and fluid load may cause additive injuries in healthy lungs, mainly in ventral regions.
authors.affiliation: 1Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Marcozzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Moriondo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Solari
authors.forename: Marcella
authors.initials: M
authors.lastname: Reguzzoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Severgnini
authors.forename: Marina
authors.initials: M
authors.lastname: Protasoni
authors.forename: Alberto
authors.initials: A
authors.lastname: Passi
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Daniela
authors.initials: D
authors.lastname: Negrini
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D005440:Fluid Therapy / Q000009:adverse effects* / Q000379:methods; D006025:Glycosaminoglycans / Q000378:metabolism; D007262:Infusions, Intravenous; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D017208:Rats, Wistar; D012307:Risk Factors; D012965:Sodium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D013314:Stress, Mechanical; D016683:Supine Position; D013990:Tidal Volume; D013997:Time Factors; D055397:Ventilator-Induced Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D006025:Glycosaminoglycans; D012965:Sodium Chloride
keywords: hydrodynamic tissue stress; lung extracellular matrix; mechanical tissue stress; pulmonary interstitium; regional lung injury