Focal atrial fibrillation: Experimental evidence for a pathophysiologic role of the autonomic nervous system

Focal AF and Autonomic Nerves. Introduction: Focal paroxysmal atrial fibril lation (AF) was shown recently to originate in the pulmonary veins (PVs) an d superior vena cava (SVC), Tn the present study, we describe an animal mod el in which local high-frequency electrical stimulation produces focal atri al activation and AF/AT (atrial tachycardia) with electrogram characteristi cs consistent with clinical reports. Methods and Results: In 21 mongrel dogs, local high-frequency electrical st imulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. At rial premature depolarizations (APDs), AT, and AF occurred with increasing high-frequency electrical stimulation voltage. APD/AT/AF originated adjacen t to the site of high-frequency electrical stimulation and were inducible i n 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13 +/- 8 V and AT/AF at 15 +/- 9 V (P < 0.01; n = 25) . In the SVC, APDs were elicited at 19 +/- 6 V and AT/AF at 26 +/- 6 V (P < 0.01; n 12), High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical st imulation was blunted or prevented after beta-receptor blockade and abolish ed by atropine. In vitro, high-frequency electrical stimulation induced a h eterogeneous response, with shortening of the action potential in some cell s (from 89 +/- 35 msec to 60 +/- 22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolarizations that triggered APD/AT in other cells, Action potential shortening was abolished by atropine. Conclusion: High-frequency electrical stimulation evokes rapid ectopic beat s from the PV/SVC, which show variable degrees of conduction block to the a tria and induce AF, resembling findings in patients with focal idiopathic p aroxysmal AF, The occurrence of the arrhythmia in this animal model was lik ely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the obser ved effects of high-frequency electrical stimulation were caused by autonom ic nerve stimulation.