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

Thiago G Bassi; Elizabeth C Rohrs; Mr Karl C Fernandez; Ms Marlena Ornowska; Ms Michelle Nicholas; Ms Jessica Wittmann; Mr Matt Gani; Mr Doug Evans; Steven C Reynolds

doi:10.1097/CCE.0000000000000820

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

Crit Care Explor. 2022 Dec 22;4(12):e0820. doi: 10.1097/CCE.0000000000000820. eCollection 2022 Dec.

Authors

Thiago G Bassi¹, Elizabeth C Rohrs^{2

3}, Mr Karl C Fernandez^{2

3}, Ms Marlena Ornowska³, Ms Michelle Nicholas^{2

3}, Ms Jessica Wittmann², Mr Matt Gani¹, Mr Doug Evans¹, Steven C Reynolds^{2

3}

Affiliations

¹ Lungpacer Medical Inc., Vancouver, BC, Canada.
² Fraser Health Authority, Royal Columbian Hospital, New Westminster, BC, Canada.
³ Simon Fraser University, Burnaby, BC, Canada.

Abstract

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.

Keywords: acute respiratory distress syndrome; diaphragm neurostimulation; mechanical ventilators; neuroinflammation; ventilation-induced.