Περίληψη:
Introduction: 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 cmH(2)O, tidal
volume approximate to 17 mL/Kg) or protective (peak airway pressure 11
cmH(2)O, tidal volume approximate to 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.
Συγγραφείς:
Tsaknis, George
Siempos, Ilias I.
Kopterides, Petros and
Maniatis, Nikolaos A.
Magkou, Christina
Kardara, Matina and
Panoutsou, Stefania
Kotanidou, Anastasia
Roussos, Charis and
Armaganidis, Apostolos
