Neural Mechanisms of Paroxysmal Atrial Fibrillation and Paroxysmal Atrial Tachycardia in Ambulatory Canines

Abstract

Background-The relationship between autonomic activation and the mechanisms of paroxysmal atrial fibrillation remains unclear. Methods and Results-We implanted a pacemaker and a radio transmitter in 7 dogs (group 1). After baseline recording, we paced the left atrium at 20 Hz for 1 week and then monitored left stellate ganglion nerve activity, left vagal nerve activity, and left atrial electrogram without pacing for 24 hours. This protocol repeated itself until sustained atrial fibrillation (Ͼ48 hours) was induced in 3Ϯ1 weeks. In another 6 dogs (group 2), we cryoablated left and right stellate ganglia and the cardiac branch of the left vagal nerve during the first surgery and then repeated the same pacing protocol until sustained atrial fibrillation was induced in 7Ϯ4 weeks (Pϭ0.01). There were 4Ϯ2 episodes of paroxysmal atrial fibrillation per day and 10Ϯ3 episodes of paroxysmal atrial tachycardia per day in group 1. Simultaneous sympathovagal discharges were observed to immediately precede the onset of atrial arrhythmias in 73% of episodes. In comparison, group 2 dogs had no paroxysmal atrial fibrillation (Pϭ0.046) or paroxysmal atrial tachycardia (PϽ0.001) episodes. Nerve sprouting, sympathetic hyperinnervation, and a massive elevation of transcardiac norepinephrine levels occurred in both groups. Conclusions-Intermittent rapid left atrial pacing results in sympathetic hyperinnervation, paroxysmal atrial fibrillation, and paroxysmal atrial tachycardia. Simultaneous sympathovagal discharges are common triggers of these arrhythmias. Cryoablation of extrinsic sympathovagal nerves eliminated paroxysmal atrial fibrillation and paroxysmal atrial tachycardia, which suggests that simultaneous sympathovagal discharges and these arrhythmias are causally related. Because cryoablation only delayed but did not prevent sustained atrial fibrillation, autonomic nerve activity is not the only factor that determines atrial fibrillation maintenance. (Circulation. 2008; 118:916-925.)

Renal Sympathetic Denervation Suppresses Postapneic Blood Pressure Rises and Atrial Fibrillation in a Model for Sleep Apnea

“…8,18,19 Interestingly, studies in lone AF patients and in animal models of both intermittent rapid atrial pacing and congestive heart failure have indicated that AF onset is associated with simultaneous sympathovagal activation rather than with an increase in vagal or sympathetic drive alone. [20][21][22][23] Previously we have shown increased AF susceptibility and AF duration caused by pronounced AERP shortening in a pig model for OSA.…”

Non- Isolation Treatment of Atrial Fibrillation: Does Autonomic Nerve Modulation Really Act?

“…A 12-month follow-up showed that the 34.4% who appeared the vagal response had a 99% freedom from atrial fibrillation recurrence whereas the other group had an 85% success rate, that is, freedom from recurrence. Scherlag stated that ablation of only the ganglionated plexi in the cadiac fat pads may result in higher success rates and may reduce damage incurred to healthy myocardium.Tan (Tan et al, 2008) further demonstrated that cryoablation of extrinsic sympatho-vagal nerves eliminated paroxysmal atrial fibrillation. These results indicate that rapid ANS modulation does act in the treatment of AF.…”

Modulação eletrofisiológica das aurículas e veias pulmonares: interação da estimulação simpática e parassimpática na inducibilidade de fibrilhação aguda auricular num modelo experimental in vivo

“…Apesar de resultados controversos na aná-lise da variabilidade da frequência cardíaca no período que precede o início espontâneo de FA, os episódios paroxísti-cos recorrentes parecem estar relacionados com flutuações dinâmicas do tónus autonómico, possivelmente dependendo do sinergismo entre o influxo adrenérgico e a modulação da atividade vagal 5,18,36,37 . São necessários estudos futuros para elucidar o impacto da inervação e da interação da atividade reflexa simpático-vagal na dinâmica complexa do substrato funcional da arritmogénese auricular.…”

“…Foi também demonstrado que a estimulação dos plexus ganglionares cardíacos, que modulam a inervação autonómica, provoca libertação local de neurotransmissores do simpático e parassimpático que podem aumentar o automatismo e encurtar a duração do potencial de ação e refratariedade locais 15 . Recentemente, no modelo do cão, num trabalho com registo direto da atividade autonómica eferente, demonstrou-se que as descargas simultâneas simpático-vagais são frequentemente o fator iniciador de taquicardia auricular paroxística e de FA após um período de pacing auricular esquerdo de alta-frequência 18 . Embora se reconheça que o SNA possa desempenhar um papel importante na fisiopatologia da FA, permanece por esclarecer qual o impacto (isolado ou em combinação) da atividade simpática e/ou vagal na arritmogénese das aurículas e sua implicação na génese, manutenção e interrupção da FA.…”