title: Injurious mechanical ventilation affects neuronal activation in ventilated rats.
abstract: BACKGROUND
  Survivors of critical illness often have significant long-term brain dysfunction, and routine clinical procedures like mechanical ventilation (MV) may affect long-term brain outcome. We aimed to investigate the effect of the increase of tidal volume (Vt) on brain activation in a rat model.
  
  
  METHODS
  Male Sprague Dawley rats were randomized to three groups: 1) Basal: anesthetized unventilated animals, 2) low Vt (LVt): MV for three hours with Vt 8 ml/kg and zero positive end-expiratory pressure (ZEEP), and 3) high Vt (HVt) MV for three hours with Vt 30 ml/kg and ZEEP. We measured lung mechanics, mean arterial pressure (MAP), arterial blood gases, and plasma and lung levels of cytokines. We used immunohistochemistry to examine c-fos as a marker of neuronal activation. An additional group of spontaneously breathing rats was added to discriminate the effect of surgical procedure and anesthesia in the brain.
  
  
  RESULTS
  After three hours on LVt, PaO2 decreased and PaCO2 increased significantly. MAP and compliance remained stable in MV groups. Systemic and pulmonary inflammation was higher in MV rats than in unventilated rats. Plasma TNFα was significantly higher in HVt than in LVt. Immunopositive cells to c-fos in the retrosplenial cortex and thalamus increased significantly in HVt rats but not in LVt or unventilated rats.
  
  
  CONCLUSIONS
  MV promoted brain activation. The intensity of the response was higher in HVt animals, suggesting an iatrogenic effect of MV on the brain. These findings suggest that this novel cross-talking mechanism between the lung and the brain should be explored in patients undergoing MV.
authors.affiliation: CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, C/ Sinesio Delgado 6, Madrid; Critical Care Center, Corporaciò Sanitaria Parc Taulí, Institut Universitari, Esfera UAB, Parc Taulí sn. Sabadell 08208; Universitat Autònoma de Barcelona, Campus de la UAB, Bellaterra 08193, Spain.
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Quilez
authors.forename: Gemma
authors.initials: G
authors.lastname: Fuster
authors.forename: Jesús
authors.initials: J
authors.lastname: Villar
authors.forename: Carlos
authors.initials: C
authors.lastname: Flores
authors.forename: Octavi
authors.initials: O
authors.lastname: Martí-Sistac
authors.forename: Lluís
authors.initials: L
authors.lastname: Blanch
authors.forename: Josefina
authors.initials: J
authors.lastname: López-Aguilar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000502:physiology*; D001930:Brain Injuries / Q000503:physiopathology*; D004195:Disease Models, Animal; D008168:Lung / Q000502:physiology; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D013990:Tidal Volume / Q000502:physiology*
chemical_list: D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos