Prolonged mechanical ventilation causes excessive worsening in gas exchange in a model of type two diabetes

Abstract

Introduction: Prolonged mechanical ventilation may lead to the onset of ventilator-induced lung injury (VILI). While type two diabetes (T2DM) reduces airway patency and facilitates atelectasis development, exaggeration of VILI can be anticipated. Thus, we aimed at characterizing whether T2DM modulates VILI, and we also characterized how T2DM therapy affects adverse pulmonary changes.

Methods: Rats were randomly assigned into three groups: a model of untreated T2DM received a low dose of streptozotocin with high-fat diet (T2DM, n=8); a model of T2DM where this treatment was supplemented by metformin therapy (MET, n=8); and a control group (CTRL, n=8). VILI in each animal was induced by ventilating the rats with high tidal volume (VT=23 ml/kg) for four hours. Blood samples were analyzed to measure the arterial oxygen tension (PaO₂), oxygen saturation (SaO₂) and the intrapulmonary shunt fraction (Qs/Qt) in every two hours. Airway and respiratory tissue mechanics were assessed by forced oscillations. The level of injury and the oxidative stress were determined by lung histology.

Results: Significant worsening of VILI was observed in PaO₂, SaO₂ and Qs/Qt in T2DM group, without differences in the respiratory mechanics. These functional defects were also reflected in the lung injury score. Animals in the MET group showed no difference to rats in the CTRL group.

Conclusion: Impairment of the gas exchange without significant mechanical changes suggests that untreated diabetes exaggerates VILI via destructing the alveolar-capillary barrier. Metformin therapy reduces the manifestations of respiratory defects in diabetes during prolonged mechanical ventilation. Supported by UNKP-20-3