title: Effects of respiratory rate on ventilator-induced lung injury at a constant PaCO2 in a mouse model of normal lung.
abstract: OBJECTIVE
  The aim of this study was to evaluate the effects of respiratory rate (RR) at a constant PaCO2 and conventional tidal volume (VT) on the development of ventilator-induced lung injury in normal lungs.
  
  
  METHODS
  Prospective, randomized, experimental study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Adult male C57BL/6 mice.
  
  
  METHODS
  Four groups of anesthetized mice were exposed to mechanical ventilation with different RRs and VTs. Three groups were assigned to one of three RRs (80, 120, and 160 breaths/min), and VT was set to 12, 10, and 8 mL/kg, respectively (RR80 VT12, RR120 VT10, and RR160 VT8), to achieve normal PaCO2. A fourth group was ventilated at 160 breaths/min and VT of 10 mL/kg (RR160 VT10) with adjustment of dead space. All animals were ventilated for 120 mins with a positive end-expiratory pressure of 1.5 cm H2O and FiO2 of 1. Nonventilated animals were also studied.
  
  
  RESULTS
  Arterial blood gases and static pressure-volume curves were not different among groups at the end of the experiment. Independent of ventilator settings, mechanical ventilation was associated with increased bronchoalveolar lavage protein and increased bronchoalveolar lavage and serum interleukin-6. Total bronchoalveolar lavage protein and interleukin-6 were significantly lower in RR80 VT12 and RR160 VT8 compared with RR120 VT10 and RR160 VT10. In all experimental conditions, mechanical ventilation was associated with activation of AKT and ERK1/2 kinases, known to be activated on stretch. Phosphorylation both of AKT and ERK1/2 was lower in RR80 VT12 compared with other groups of ventilated animals. Histologic injury did not differ among nonventilated, RR80 VT12, and RR160 VT8 animals; however, it increased significantly and progressively in RR120 VT10 and RR160 VT10 animals.
  
  
  CONCLUSIONS
  Mechanical ventilation with conventional VT induces lung injury in normal lungs, even without alteration in lung mechanics. Reduction of RR and VT ameliorates lung inflammation and injury.
authors: Department of Intensive Care Medicine, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete, Greece.
authors: Katerina
authors: K
authors: Vaporidi
authors: Giorgos
authors: G
authors: Voloudakis
authors: George
authors: G
authors: Priniannakis
authors: Eumorfia
authors: E
authors: Kondili
authors: Anastasis
authors: A
authors: Koutsopoulos
authors: Christos
authors: C
authors: Tsatsanis
authors: Dimitris
authors: D
authors: Georgopoulos
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012119:Respiration; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013990:Tidal Volume