Abstract 19251: Cardiac Afferent Denervation Abolishes Ganglionated Plexi and Sympathetic Responses to Apnea. Implications for Atrial Fibrillation

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Abstract

Introduction: Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF), mediated by the extrinsic and intrinsic cardiac autonomic system. Resiniferatoxin (RTX) activates TRPV1 receptors in afferent neurons leading to cell death and afferent denervation.

Hypothesis: RTX leads to cardiac afferent denervation in the intrinsic cardiac ganglia and can disrupt the autonomic response to apnea and apnea-induced AF.

Methods: Sixteen dogs were anesthetized and mechanically ventilated. Apnea was induced by switching off the ventilator and maintained as long as needed to reach oxygen saturations of 80%. In 9 dogs, left atrial (LA) single extrastimulation were performed in 3 sites before and after apnea, before and after epicardial RTX administration via subxiphoid puncture. In 7 dogs, nerve activity from the left and right cervical vagus nerves, anterior right ganglionated plexi (GP) and left stellate ganglion (SG), was obtained before and during apnea, before and after RTX via local GP injection. Apnea post-RTX was induced, along with repeat LA extrastimulation and nerve recordings. Immunohistochemical staining from TRPV1 was performed in the GPs.

Results: Apnea led to increased blood pressure, and increased vagal, SG and GP firings, and was associated with decreases in effective refractory period (ERP) and AF induction. RTX led to decreased GP and SG firing but did not alter vagal firings during apnea. After RTX, ERP during apnea significantly increased (from 107.6±23.9 to 126.7±26.9; p=0.0001) and AF was no longer induced with single extrastimulation. Immunohistochemical studies confirmed the presence of TRPV1-postive neurons in the GP.

Conclusion: RTX abolishes the electrophysiological response to apnea, including ERP shortening and AF induction. Local RTX administration decreases GP and SG activity.

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