Diaphragm Neurostimulation Mitigates Ventilation-Associated Brain Injury in a Preclinical Acute Respiratory Distress Syndrome Model

Abstract

CONTEXT:. In a porcine healthy lung model, temporary transvenous diaphragm neurostimulation (TTDN) for 50 hours mitigated hippocampal apoptosis and inflammation associated with mechanical ventilation (MV). HYPOTHESIS:. Explore whether TTDN in combination with MV for 12 hours mitigates hippocampal apoptosis and inflammation in an acute respiratory distress syndrome (ARDS) preclinical model. METHODS AND MODELS:. Compare hippocampal apoptosis, inflammatory markers, and serum markers of neurologic injury between never ventilated subjects and three groups of mechanically ventilated subjects with injured lungs: MV only (LI-MV), MV plus TTDN every other breath, and MV plus TTDN every breath. MV settings in volume control were tidal volume 8 mL/kg and positive end-expiratory pressure 5 cm H2O. Lung injury, equivalent to moderate ARDS, was achieved by infusing oleic acid into the pulmonary artery. RESULTS:. Hippocampal apoptosis, microglia, and reactive-astrocyte percentages were similar between the TTDN-every-breath and never ventilated groups. The LI-MV group had a higher percentage of these measures than all other groups (p < 0.05). Transpulmonary driving pressure at study end was lower in the TTDN-every-breath group than in the LI-MV group; systemic inflammation and lung injury scores were not significantly different. The TTDN-every-breath group had considerably lower serum concentration of homovanillic acid (cerebral dopamine production surrogate) at study end than the LI-MV group (p < 0.05). Heart rate variability declined in the LI-MV group and increased in both TTDN groups (p < 0.05). INTERPRETATIONS AND CONCLUSIONS:. In a moderate-ARDS porcine model, MV is associated with hippocampal apoptosis and inflammation, and TTDN mitigates that hippocampal apoptosis and inflammation.