title: Maintaining end-expiratory transpulmonary pressure prevents worsening of ventilator-induced lung injury caused by chest wall constriction in surfactant-depleted rats.
abstract: OBJECTIVE
  To see whether in acute lung injury 1) compression of the lungs caused by thoracoabdominal constriction degrades lung function and worsens ventilator-induced lung injury; and 2) maintaining end-expiratory transpulmonary pressure by increasing positive end-expiratory pressure reduces the deleterious effects of chest wall constriction.
  
  
  METHODS
  Experimental study in rats.
  
  
  METHODS
  Physiology laboratory.
  
  
  METHODS
  Acute lung injury was induced in three groups of nine rats by saline lavage. Nine animals immediately killed served as a control group. Group L had lavage only, group LC had the chest wall constricted with an elastic binder, and group LCP had the same chest constriction but with positive end-expiratory pressure raised to maintain end-expiratory transpulmonary pressure. After lavage, all groups were ventilated with the same pattern for 1½ hrs.
  
  
  RESULTS
  Transpulmonary pressure, measured with an esophageal balloon catheter, lung volume changes, arterial blood gasses, and pH were assessed during mechanical ventilation. Lung wet-to-dry ratio, albumin, tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and macrophage inflammatory protein-2 in serum and bronchoalveolar lavage fluid and serum E-selectin and von Willebrand Factor were measured at the end of mechanical ventilation. Lavage caused hypoxemia and acidemia, increased lung resistance and elastance, and decreased end-expiratory lung volume. With prolonged mechanical ventilation, lung mechanics, hypoxemia, and wet-to-dry ratio were significantly worse in group LC. Proinflammatory cytokines except E-selectin were elevated in serum and bronchoalveolar lavage fluid in all groups with significantly greater levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in group LC, which also exhibited significantly worse bronchiolar injury and greater heterogeneity of airspace expansion at a fixed transpulmonary pressure than other groups.
  
  
  CONCLUSIONS
  Chest wall constriction in acute lung injury reduces lung volume, worsens hypoxemia, and increases pulmonary edema, mechanical abnormalities, proinflammatory mediator release, and histologic signs of ventilator-induced lung injury. Maintaining end-expiratory transpulmonary pressure at preconstriction levels by adding positive end-expiratory pressure prevents these deleterious effects.
authors.affiliation: Dipartimento di Fisiologia Umana, Università degli Studi di Milano, and Servizio di Coagulazione, IRCCS Ospedale San Raffaele, Milan, Italy. sloring@bidmc.harvard.edu
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Loring
authors.forename: Matteo
authors.initials: M
authors.lastname: Pecchiari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Della Valle
authors.forename: Ario
authors.initials: A
authors.lastname: Monaco
authors.forename: Guendalina
authors.initials: G
authors.lastname: Gentile
authors.forename: Edgardo
authors.initials: E
authors.lastname: D'Angelo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D018450:Disease Progression; D008297:Male; D011175:Positive-Pressure Respiration / Q000379:methods*; D011322:Primary Prevention / Q000379:methods; D011659:Pulmonary Gas Exchange; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D012016:Reference Values; D015656:Respiratory Mechanics; D018709:Statistics, Nonparametric; D035441:Thoracic Wall; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D011663:Pulmonary Surfactants