title: High tidal volume ventilation is not deleterious in infant rats exposed to severe hemorrhage.
abstract: BACKGROUND
  Both high tidal volume (V(T)) ventilation and hemorrhage induce acute lung injury in adult rodents. It is not known whether injurious ventilation augments lung injury in infant rats exposed to severe hemorrhage.
  
  
  METHODS
  Two-week-old rats were allocated for ventilation with VT 7 mL/kg and positive end-expiratory pressure (PEEP) 5 cm H₂O (low V(T)) or V(T) 21 mL/kg and PEEP 1 (high V(T)) for 4 hours. Additional rats were subjected to volume-controlled hemorrhage and delayed saline resuscitation, followed by low V(T) or high V(T) ventilation for 4 hours. Nonventilated control groups were also included. Airway resistance and the coefficient of tissue elastance were derived from respiratory input impedance measurements using the low-frequency forced oscillation technique. Pressure-volume curves were obtained at baseline and at the end of the study. Interleukin-6, macrophage inflammatory protein-2, and tumor necrosis factor alpha were determined in bronchoalveolar lavage fluid (BALF) and serum.
  
  
  RESULTS
  In both healthy and hemorrhage-exposed animals, high V(T) resulted in reduced elastance (better lung compliance) and increased transcutaneous oxygen saturation. Interleukin-6 in BALF was greater in ventilated animals when compared with nonventilated controls, but not different among ventilated groups. No significant differences were found for all other inflammatory mediators, total protein concentration in BALF, and histology.
  
  
  CONCLUSIONS
  High V(T) ventilation with low PEEP improves respiratory system mechanics without causing additional damage to healthy and hemorrhage-exposed infant rats after 4 hours of ventilation. This study highlights the tolerance to high V(T) ventilation in infant rats and underscores the need for age-specific animal models.
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, Centre for Child Health Research, the University of Western Australia, Perth, Australia. vincenzo.cannizzaro@kispi.uzh.ch
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cannizzaro
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Berry
authors.forename: Philip K
authors.initials: PK
authors.lastname: Nicholls
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Hantos
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
mesh_terms: D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054426:Chemokine CXCL2 / Q000378:metabolism; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D008170:Lung Compliance / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D011175:Positive-Pressure Respiration / Q000379:methods*; D051381:Rats; D015656:Respiratory Mechanics / Q000502:physiology*; D013990:Tidal Volume / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen