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

ABSTRACT: Background The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.

SUBMITTER: Tavares L

PROVIDER: S-EPMC6553493 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Project description:The aim of our study was to investigate, whether enhancement of left atrial cryoablation by ablation of the autonomic nervous system of left atrium leads to influencing the outcomes of surgical treatment of atrial fibrillation in patients with structural heart disease undergoing open-heart surgery.The observed patient file consisted of 100 patients, who have undergone a combined open-heart surgery at our department between July 2012 and December 2014. The patients were indicated for the surgical procedure due to structural heart disease, and suffered from paroxysmal, persistent, or long-standing persistent atrial fibrillation. In all cases, left atrial cryoablation was performed in the extent of isolation of pulmonary veins, box lesion, connecting lesion with mitral annulus, amputation of the left atrial appendage and connecting lesion of the appendage base with left pulmonary veins. Furthermore, 35 of the patients underwent mapping and radiofrequency ablation of ganglionated plexi, together with discision and ablation of the ligament of Marshall (Group GP). A control group was consisted of 65 patients without ganglionated plexi intervention (Group LA). The main primary outcome was establishment and duration of sinus rhythm in the course of one-year follow-up.Evaluation of the number of patients with a normal sinus rhythm in per cent has shown comparable values in both groups (Group GP - 93.75%, Group LA - 86.67%, p = 0.485); comparable results were also observed in patients with normal sinus rhythm without anti-arrhythmic treatment in the 12th month (Group GP - 50%, Group LA - 47%, p = 0.306). We have not observed any relation between the recurrence of atrial fibrillation and the presence of a mitral valve surgery, or between the presence of a mitral and tricuspid valves surgery and between the left atrial diameter > 50 mm.Enhancement of left atrial cryoablation by gangionated plexi ablation did not influence the outcomes of surgical ablation due to atrial fibrillation in our population in the course of 12-month follow-up.The study was approved retrospectively by the Ethics Committee of the University Hospital Ostrava ( reference number 867/2016).

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

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