title: GABA receptor ameliorates ventilator-induced lung injury in rats by improving alveolar fluid clearance.
abstract: BACKGROUND
  Mechanical ventilators are increasingly used in critical care units. However, they can cause lung injury, including pulmonary edema. Our previous studies indicated that γ-aminobutyric acid (GABA) receptors are involved in alveolar-fluid homeostasis. The present study investigated the role of GABA receptors in ventilator-induced lung injury.
  
  
  METHODS
  Adult female Sprague-Dawley rats were subjected to high-tidal-volume ventilation of 40 ml/kg body weight for 1 hour, and lung injuries were assessed.
  
  
  RESULTS
  High-tidal-volume ventilation resulted in lung injury, as indicated by an increase in total protein in bronchoalveolar fluid, wet-to-dry ratio (indication of pulmonary edema), and Evans Blue dye extravasation (indication of vascular damage). Intratracheal administration of GABA before ventilation significantly reduced the wet-to-dry ratio. Further, histopathologic analysis indicated that GABA reduced ventilator-induced lung injury and apoptosis. GABA-mediated reduction was effectively blocked by the GABAA-receptor antagonist, bicuculline. The GABA-mediated effect was not due to the vascular damage, because no differences in Evans Blue dye extravasation were noted. However, the decrease in alveolar fluid clearance by high-tidal-volume ventilation was partly prevented by GABA, which was blocked by bicuculline.
  
  
  CONCLUSIONS
  These results suggest that GABA reduces pulmonary edema induced by high-tidal-volume ventilation via its effects on alveolar fluid clearance and apoptosis.
authors.affiliation: Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078, USA.
authors.forename: Narendranath Reddy
authors.initials: NR
authors.lastname: Chintagari
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001640:Bicuculline / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D020287:In Situ Nick-End Labeling; D011654:Pulmonary Edema / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism*; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D018079:Receptors, GABA; D005070:Evans Blue; D001640:Bicuculline