title: Metformin attenuates ventilator-induced lung injury.
abstract: BACKGROUND
  Diabetic patients may develop acute lung injury less often than non-diabetics; a fact that could be partially ascribed to the usage of antidiabetic drugs, including metformin. Metformin exhibits pleiotropic properties which make it potentially beneficial against lung injury. We hypothesized that pretreatment with metformin preserves alveolar capillary permeability and, thus, prevents ventilator-induced lung injury.
  
  
  METHODS
  Twenty-four rabbits were randomly assigned to pretreatment with metformin (250 mg/Kg body weight/day per os) or no medication for two days. Explanted lungs were perfused at constant flow rate (300 mL/min) and ventilated with injurious (peak airway pressure 23 cmH₂O, tidal volume ≈17 mL/Kg) or protective (peak airway pressure 11 cmH₂O, tidal volume ≈7 mL/Kg) settings for 1 hour. Alveolar capillary permeability was assessed by ultrafiltration coefficient, total protein concentration in bronchoalveolar lavage fluid (BALF) and angiotensin-converting enzyme (ACE) activity in BALF.
  
  
  RESULTS
  High-pressure ventilation of the ex-vivo lung preparation resulted in increased microvascular permeability, edema formation and microhemorrhage compared to protective ventilation. Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation. In contrast, no differences regarding pulmonary artery pressure and BALF total cell number were noted. Administration of metformin did not impact on outcomes of lungs subjected to protective ventilation.
  
  
  CONCLUSIONS
  Pretreatment with metformin preserves alveolar capillary permeability and, thus, decreases the severity of ventilator-induced lung injury in this model.
authors: George
authors: G
authors: Tsaknis
authors: Ilias I
authors: II
authors: Siempos
authors: Petros
authors: P
authors: Kopterides
authors: Nikolaos A
authors: NA
authors: Maniatis
authors: Christina
authors: C
authors: Magkou
authors: Matina
authors: M
authors: Kardara
authors: Stefania
authors: S
authors: Panoutsou
authors: Anastasia
authors: A
authors: Kotanidou
authors: Charis
authors: C
authors: Roussos
authors: Apostolos
authors: A
authors: Armaganidis
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000517:prevention & control; D011817:Rabbits; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000517:prevention & control*
chemical_list: D008687:Metformin