MP-453088-5 THE EFFECT OF LOW–LEVEL TRANSCUTANEOUS VAGUS NERVE STIMULATION ON AUTONOMIC REMODELING OF GANGLIONATED PLEXI (GP) IN HUMANS

Abstract

The intrinsic cardiac autonomic nervous system (CANS), which is formed by interconnected clusters of autonomic ganglia called ganglionated plexi (GP), has been found to play a key role in the onset and maintenance of atrial fibrillation (AF). The ability of GP neurons to change parasympathetic activity suggests that synaptic plasticity occurs at synapses generated on and by GP neurons. Such changes could be a source of maladaptive plasticity and fine-tuning autonomic innervation of the heart during AF Low-level tragus stimulation (LLTS), which has antiarrhythmic and anti-inflammatory properties, has been shown to benefit patients with paroxysmal AF. The purpose of this study was to determine the effect of LLTS on the synaptic plasticity of GP in patients undergoing open heart surgery by examining changes in protein levels of neural markers. Furthermore, the effect of LLTS on inflammatory markers in GP has been determined. Patients undergoing cardiac surgery (including patients with paroxysmal AF, persistent AF, or no history of AF) were randomized to active LLTS (20Hz, 30mA) for 1 hour or no stimulation. A 2-3 mm biopsy of the GP tissue was taken immediately after stimulation, and immunohistochemistry was used to stain for neural (choline acetyltransferase (ChAT), synaptophysin, S100B, PGP9.5, nNOS, and GFAP) and inflammatory markers (CD3, CD68). Twenty five patients were included. Patients' clinical and echocardiographic characteristics were distributed evenly across groups (LLTS, n=12, 75% male, age 65±9 years vs. sham, n=13, 92% male, age 63±11 years). In comparison to sham, LLTS significantly decreased the protein expression level of S100B, nNOS, GFAP, PGP9.5, and choline acetyltransferase (ChAT) in GP tissue (Figure 1). The expression of synaptophysin in both groups was not significantly different. Following stimulation, the expression of the inflammatory marker CD3 was significantly reduced. There was no statistically significant difference in CD68 expression between the LLTS and sham groups. Significant changes in neural markers within the GP occurred following LLTS, consistent with acute autonomic remodeling. Further studies are warranted to understand the clinical significance of this finding.