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Abstract
Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury. It is induced by sepsis, aspiration, and pneumonia, including that caused by SARS coronavirus and human influenza viruses. The main pathophysiological mechanism of ARDS is a systemic inflammatory response. Vagus nerve stimulation (VNS) can limit cytokine production in the spleen and thereby dampen any systemic inflammation and inflammation-induced tissue damage in the lungs and other organs. However, the effects of increased parasympathetic outflow to the lungs when non-selective VNS is applied may result in bronchoconstriction, increased mucus secretion and enhance local pulmonary inflammatory activity; this may outweigh the beneficial systemic anti-inflammatory action of VNS. Organ/function-specific therapy can be achieved by imaging of localized fascicle activity within the vagus nerve and selective stimulation of identified organ-specific fascicles. This may be able to provide selective neuromodulation of different pathways within the vagus nerve and offer a novel means to improve outcome in ARDS. This has motivated this review in which we discuss the mechanisms of anti-inflammatory effects of VNS, progress in selective VNS techniques, and a possible application for ARDS.
Highlights
Acute respiratory distress syndrome (ARDS) is a fulminant condition which may result in a mortality rate of more than 40% (Diamond et al, 2020)
Analysis of the lung immune microenvironment using bronchoalveolar lavage fluid from severe and moderate COVID-19 patients showed that highly inflammatory monocyte-derived splenic macrophages prevail in the excessive inflammatory response in the lungs from patients with ARDS (Liao et al, 2020)
In our group at University College London, we have developed a method to image localized fascicle compound action potential activity with Electrical Impedance Tomography (EIT) using a silicone rubber cuff with 14 circumferential electrodes (Figure 2A; Ravagli et al, 2019, 2020)
Summary
Acute respiratory distress syndrome (ARDS) is a fulminant condition which may result in a mortality rate of more than 40% (Diamond et al, 2020). Vagus nerve stimulation (VNS) has indirect inhibitory effects on the cytokine production in the spleen even though there is no evidence for direct cholinergic (vagal) innervation of the spleen in humans (Verlinden et al, 2019).
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