INTRODUCTION Mechanical ventilation is known to activate oxidative stress and proteolytic pathways in the diaphragm. Trauma by inducing inflammation and activating proteolytic pathways may potentiate the effects of mechanical ventilation on the diaphragm. In a blunt chest trauma with concomitant injuries we tested the hypothesis that trauma via inflammation further activates the proteolytic pathways and worsens atrophy in the diaphragm. MATERIAL AND METHODS Piglets were separated into 2 groups and underwent 72hrs of mechanical ventilation. One group received a polytrauma (PT) by unilateral femur fracture, blunt chest trauma with lung contusion, laparotomy with standardized liver incision and a predefined haemorrhagic shock. The second mechanically ventilated group (MV) did not receive any trauma. A non-ventilated group (Con) served as control.Diaphragmatic fibre dimensions, Western Blot analyses of proteolytic pathways and lipid peroxidation and mRNA levels of cytokines and NFkB subunit p65 were measured. RESULTS Active Caspase-3 was significantly increased in MV (p = 0.019), and in PT (p = 0.02) compared to Con. NFkB subunit p65, was up-regulated in PT (p = 0.010) compared to Con. IL-6 mRNA increased significantly in PT compared to Con (p = 0.0024) but did not differ between Con and MV. CONCLUSION Trauma and mechanical ventilation induced proteolysis and atrophy in the diaphragm, but only polytrauma induced an inflammatory response in the diaphragm. The additional traumatic inflammatory stimulus did not increase the levels of the pre-mentioned variables. These data underline that inflammation is not a major contributor to VIDD. TRIAL REGISTRY NUMBER AZ 84-02.04.2014.A265 (Landesamt für Natur-, Umwelt- und Verbraucherschutz, LANUV NRW, Germany).
Effect of Long-Term Polytrauma on Ventilator-Induced Diaphragmatic Dysfunction in a Piglet Model.