Clinical observations strongly suggest that ANS activity is important in the initiation of AF. Recent advances from many investigators have provided further insights into the development of paroxysmal AF. Figure 1 summarizes a possible sequence of events leading to the generation and maintenance of paroxysmal AF. Our preliminary results demonstrated that simultaneous sympathovagal discharges were the immediate autonomic triggers of spontaneous paroxysmal AF in ambulatory dogs. At the site of focal discharge, there was juxtapositioning of rich autonomic innervation and periodic acid-Schiff-positive (Purkinje) cells. Simultaneous sympathovagal discharge might lead to tachycardia and Cai accumulation in the presence of significantly shortened APD. High diastolic Cai then activates the sodium/calcium exchanger, causing triggered activity and rapid heart rate that further increases Cai accumulation and promotes triggered activity in other parts of the atria or thoracic veins. Shortened APD also predisposes to the development of wavebreak and reentry, which in turn contributes to rapid rates that maintain Cai accumulation and triggered activity. These findings have important therapeutic implications. In addition to the known efficacy of ANS denervation in controlling AF, these findings suggest that an antiarrhythmic drug that blocks ion channels, beta receptors, as well as IKAch would be more effective than beta-blockers or ion channel blockers alone in controlling AF. Compatible with this hypothesis, amiodarone, which, unlike most other antiarrhythmic drugs, blocks all these channels including IKAch,50 is one of the most effective drugs for AF control.51 Although the exact mechanism by which ANS activation triggers AF is still under investigation, recent progress in this area has provided us with new insights into the mechanisms of AF and might lead to new therapeutic strategies that one day can be used to successfully control this arrhythmia.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)