title: Effects of mean airway pressure and tidal excursion on lung injury induced by mechanical ventilation in an isolated perfused rabbit lung model.
abstract: OBJECTIVE
  To study the relative contributions of mean airway pressure (mPaw) and tidal excursion (V(T)) to ventilator-induced lung injury under constant perfusion conditions.
  
  
  METHODS
  Prospective, randomized study.
  
  
  METHODS
  Experimental animal laboratory.
  
  
  METHODS
  Fifteen sets of isolated rabbit lungs.
  
  
  METHODS
  Rabbit lungs were perfused (constant flow, 500 mL/min; capillary pressure, 10 mm Hg) and randomized to be ventilated at identical peak transpulmonary pressure (pressure control ventilation [30 cm H2O and frequency of 20/min]) with three different ventilatory patterns that differed from each other by either mPaw or V(T): group A (low mPaw [13.4+/-0.2 cm H2O]/large V(T) [55+/-8 mL], n = 5); group B (high mPaw [21.2+/-0.2 cm H2O]/small V(T) [18+/-1 mL], n = 5); and group C (high mPaw [21.8+/-0.5 cm H2O]/large V(T) [53+/-5 mL], n = 5).
  
  
  RESULTS
  Continuous weight gain (edema formation), change in ultrafiltration coefficient (deltaKf, vascular permeability index), and histology (lung hemorrhage) were examined. In group A, deltaKf (0.08+/-0.08 g/min/cm H2O/100 g) was less than in group B (0.28+/-0.19 g/min/cm H2O/100 g) or group C (0.41+/-0.29 g/min/cm H2O/100 g) (p = .05). Group A experienced significantly less hemorrhage (histologic score, 5.4+/-2.2) than groups B (10.3+/-2.1) and C (11.1+/-3.0) (p < .05). A similar trend was observed for weight gain. In contrast to tidal excursion, mPaw was found to be a significant factor for lung hemorrhage and increased Kf (two-way analysis of variance; p < .05). Weight gain (r2 = .54, p = .04) and lung hemorrhage (r2 = .65, p = .01) correlated with the mean pulmonary artery pressure changes that resulted from the implementation of the ventilatory strategies. The difference between the changes in mPaw and mean pulmonary artery pressure linearly predicted deltaKf (p = .005 and .05, respectively, r2 = 0.73).
  
  
  CONCLUSIONS
  Under these experimental conditions, mPaw contributes more than tidal excursion to lung hemorrhage and permeability alterations induced by mechanical ventilation.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Minnesota, Minneapolis, USA. Alain.Broccard@chuv.hospvd.ch
authors.forename: A F
authors.initials: AF
authors.lastname: Broccard
authors.forename: J R
authors.initials: JR
authors.lastname: Hotchkiss
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: D
authors.initials: D
authors.lastname: Olson
authors.forename: J J
authors.initials: JJ
authors.lastname: Marini
mesh_terms: D000403:Airway Resistance; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics; D066298:In Vitro Techniques; D016014:Linear Models; D009929:Organ Size; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D015203:Reproducibility of Results; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D013990:Tidal Volume