title: Effect of Airway Pressure Release Ventilation on Dynamic Alveolar Heterogeneity.
abstract: OBJECTIVE
  Ventilator-induced lung injury may arise from heterogeneous lung microanatomy, whereby some alveoli remain collapsed throughout the breath cycle while their more compliant or surfactant-replete neighbors become overdistended, and this is called dynamic alveolar heterogeneity.
  
  
  OBJECTIVE
  To determine how dynamic alveolar heterogeneity is influenced by 2 modes of mechanical ventilation: low tidal-volume ventilation (LTVV) and airway pressure release ventilation (APRV), using in vivo microscopy to directly measure alveolar size distributions.
  
  
  METHODS
  In a randomized, nonblinded laboratory animal study conducted between January 2013 and December 2014, 14 rats (450-500 g in size) were randomized to a control group with uninjured lungs (n = 4) and 2 experimental groups with surfactant deactivation induced by polysorbate lavage: the LTVV group (n = 5) and the APRV group (n = 5). For all groups, a thoracotomy and in vivo microscopy were performed. Following lung injury induced by polysorbate lavage, the LTVV group was ventilated with a tidal volume of 6 mL/kg and progressively higher positive end-expiratory pressure (PEEP) (5, 10, 16, 20, and 24 cm H2O). Following lung injury induced by polysorbate lavage, the APRV group was ventilated with a progressively shorter time at low pressure, which increased the ratio of the end-expiratory flow rate (EEFR) to the peak expiratory flow rate (PEFR; from 10% to 25% to 50% to 75%).
  
  
  METHODS
  Alveolar areas were quantified (using PEEP and EEFR to PEFR ratio) to determine dynamic heterogeneity.
  
  
  RESULTS
  Following lung injury induced by polysorbate lavage, a higher PEEP (20-24 cm H2O) with LTVV resulted in alveolar occupancy (reported as percentage of total frame area) at inspiration (39.9%-42.2%) and expiration (35.9%-38.7%) similar to that in the control group (inspiration 53.3%; expiration 50.3%; P > .01). Likewise, APRV with an increased EEFR to PEFR ratio (50%-75%) resulted in alveolar occupancy at inspiration (46.7%-47.9%) and expiration (40.2%-46.6%) similar to that in the control group (P > .01). At inspiration, the distribution of the alveolar area of the control group was similar to that of the APRV group (P > .01) (but not to that of the LTVV group [P < .01]). A lower PEEP (5-10 cm H2O) and a decreased EEFR to PEFR ratio (≤50%) demonstrated dynamic heterogeneity between inspiration and expiration (P < .01 for both) with a greater percentage of large alveoli at expiration. Dynamic alveolar homogeneity between inspiration and expiration occurred with higher PEEP (16-24 cm H2O) (P > .01) and an increased EEFR to PEFR ratio (75%) (P > .01).
  
  
  CONCLUSIONS
  Increasing PEEP during LTVV increased alveolar recruitment and dynamic homogeneity but had a significantly different alveolar size distribution compared with the control group. By comparison, reducing the time at low pressure (EEFR to PEFR ratio of 75%) in the APRV group provided dynamic homogeneity and a closer approximation of the dynamics observed in the control group.
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kollisch-Singule
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Trauma Critical Care Medicine, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore.
authors.forename: Penny
authors.initials: P
authors.lastname: Andrews
authors.affiliation: Department of Medicine, University of Vermont, Burlington.
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of Vermont, Burlington.
authors.forename: Katharine L
authors.initials: KL
authors.lastname: Hamlington-Smith
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Shreyas
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: David
authors.initials: D
authors.lastname: DiStefano
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Emily
authors.initials: E
authors.lastname: Nuss
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Josh
authors.initials: J
authors.lastname: Satalin
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse4Syracuse Veterans Affairs Medical Center, Syracuse, New York.
authors.forename: William
authors.initials: W
authors.lastname: Marx
authors.affiliation: Department of Medicine, University of Vermont, Burlington.
authors.forename: Jason H T
authors.initials: JH
authors.lastname: Bates
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse5Department of Biological Sciences, State University of New York at Cortland, Cortland.
authors.forename: Louis A
authors.initials: LA
authors.lastname: Gatto
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Nieman
authors.affiliation: Department of Trauma Critical Care Medicine, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore.
authors.forename: Nader M
authors.initials: NM
authors.lastname: Habashi
mesh_terms: D000818:Animals; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D005540:Forced Expiratory Flow Rates; D008853:Microscopy; D023421:Models, Animal; D011175:Positive-Pressure Respiration / Q000379:methods*; D011650:Pulmonary Alveoli / Q000473:pathology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013908:Thoracotomy; D055397:Ventilator-Induced Lung Injury / Q000473:pathology*