title: Effects of vascular flow and PEEP in a multiple hit model of lung injury in isolated perfused rabbit lungs.
abstract: BACKGROUND
  High vascular flow aggravates lung damage in animal models of ventilator-induced lung injury. Positive end-expiratory pressure (PEEP) can attenuate ventilator-induced lung injury, but its continued effectiveness in the setting of antecedent lung injury is unclear. The objective of the present study was to evaluate whether the application of PEEP diminishes lung injury induced by concurrent high vascular flow and high alveolar pressures in normal lungs and in a preinjury lung model.
  
  
  METHODS
  Two series of experiments were performed. Fifteen sets of isolated rabbit lungs were randomized into three groups (n = 5): low vascular flow/low PEEP; high vascular flow/low PEEP, and high vascular flow/high PEEP. Subsequently, the same protocol was applied in an additional 15 sets of isolated rabbit lungs in which oleic acid was added to the vascular perfusate to produce mild to moderate lung injury. All lungs were ventilated with peak airway pressure of 30 cm H2O for 30 minutes. Outcome measures included frequency of gross structural failure, pulmonary hemorrhage, edema formation, changes in static compliance, pulmonary vascular resistance, and pulmonary ultrafiltration coefficient.
  
  
  RESULTS
  In the context of high vascular flow, application of a moderate level of PEEP reduced pulmonary rupture, edema formation, and lung hemorrhage. The protective effects of PEEP were not observed in lungs concurrently injured with oleic acid.
  
  
  CONCLUSIONS
  Under these experimental conditions, PEEP attenuates lung injury in the setting of high vascular flow. The protective effect of PEEP is lost in a two-hit model of lung injury.
authors.affiliation: Critical Care Center, Hospital de Sabadell, CIBER de Enfermedades Respiratorias (CIBERES), Institut Universitari Parc Taulí, Esfera Universitat Autònoma de Barcelona, Sabadell, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Piacentini
authors.forename: Josefina
authors.initials: J
authors.lastname: López-Aguilar
authors.forename: Carolina
authors.initials: C
authors.lastname: García-Martín
authors.forename: Ana
authors.initials: A
authors.lastname: Villagrá
authors.forename: Alicia
authors.initials: A
authors.lastname: Saenz-Valiente
authors.forename: Gastón
authors.initials: G
authors.lastname: Murias
authors.forename: Pilar
authors.initials: P
authors.lastname: Fernández-Segoviano
authors.forename: John R
authors.initials: JR
authors.lastname: Hotchkiss
authors.forename: Lluis
authors.initials: L
authors.lastname: Blanch
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019301:Oleic Acid; D011175:Positive-Pressure Respiration / Q000009:adverse effects / Q000379:methods*; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011669:Pulmonary Wedge Pressure; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014692:Ventilation-Perfusion Ratio
chemical_list: D019301:Oleic Acid