Transvenous Diaphragm Neurostimulation Mitigates Ventilation-associated Brain Injury.

Abstract

RATIONALE\nMechanical ventilation (MV) is associated with hippocampal apoptosis and inflammation, and it is important to study strategies to mitigate them.\n\n\nOBJECTIVES\nExplore whether temporary transvenous diaphragm neurostimulation (TTDN) in association with MV mitigates hippocampal apoptosis and inflammation after 50 hours of MV.\n\n\nMETHODS\nNormal-lung porcine study comparing apoptotic index, inflammatory markers, and neurological-damage serum markers between never-ventilated subjects, subjects undergoing 50 hours of MV plus either TTDN every other breath or every breath, and subjects undergoing 50 hours of MV (MV group). MV settings in volume control were tidal volume of 8 ml/kg, and positive end-expiratory pressure of 5 cmH2O.\n\n\nMEASUREMENTS AND MAIN RESULTS\nApoptotic indices, microglia percentages, and reactive astrocyte percentages were greater in the MV group in comparison to the other groups (p<0.05). Transpulmonary pressure at baseline and at study end were both lower in the group receiving TTDN every breath, but lung injury scores and systemic inflammatory markers were not different between the groups. Serum concentrations of four neurological-damage markers were lower in the group receiving TTDN every breath than in the MV group (p<0.05). Heart rate variability declined significantly in the MV group and increased significantly in both TTDN groups over the course of the experiments.\n\n\nCONCLUSION\nOur study found that mechanical ventilation is associated with hippocampal apoptosis and inflammation, independent of lung injury and systemic inflammation. Also, in a porcine model, TTDN results in neuroprotection after 50 hours, and the degree of neuroprotection increases with greater exposure to TTDN. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).