Abstract 15707: Inhibition of Atrial Fibrillation Inducibility by Low Level Vagus Nerve Stimulation: the Role of Nitric Oxide Signaling Pathway
Background: Low level vagus nerve stimulation (LLVNS, 50% below that which slows the sinus rate) inhibits atrial fibrillation (AF) inducibility but the exact mechanism is unclear. We examined the role of the phosphatidylinositol-3 kinase (PI3K)/nitric oxide (NO) signaling pathway in LLVNS-mediated inhibition of AF inducibility.
Methods: In 17 pentobarbital anesthetized dogs bilateral thoracotomies allowed the attachment of electrode catheters to superior and inferior pulmonary veins (PVs) and atrial appendages (AA). Programmed stimulation, at 10x diastolic threshold, was used to determine effective refractory period (ERP) at all tested sites and the width of the window of vulnerability (WOV), a measure of AF inducibility. AF was induced by rapid atrial pacing (RAP) for 6 hours. During the last 3 hours, RAP was overlapped with right LLVNS. Each hour, RAP was temporarily stopped and ERP and WOV were measured during sinus rhythm. In groups 2 (n=6) and 3 (n=4), at the end of the 3rd hour, the NO synthase inhibitor L-NAME and the PI3K inhibitor wortmannin, respectively, were injected in the anterior right (AR) GP and inferior right GP. Acetylcholine, 100mM, was applied on the right AA at baseline and at 6 hours to induce AF and measure AF duration. Voltage-sinus rate response curves (a surrogate for GP function) were constructed by applying high frequency stimulation to the ARGP with increasing voltage until AF was induced. The maximal change in sinus rate was also determined.
Results: Both L-NAME and wortmannin abrogated the LLVNS-induced decrease in acetylcholine-induced AF duration (9.1±2.7 vs. 1.3±0.7 min, p<0.001). The cumulative WOV (the sum of the individual WOVs) increased significantly during the first 3 hours of RAP (p<0.001) and decreased towards baseline with LLVNS (p<0.001). L-NAME and wortmannin failed to inhibit this effect during the 4th hour (p>0.05), but blunted this effect during the 5th (L-NAME only; p<0.05) and 6th hour (L-NAME and wortmannin; p<0.05). LLVNS suppressed the ability of ARGP stimulation to slow the sinus rate (38±9 vs. 13±6%, p=0.001), whereas L-NAME (48±19 vs. 40±20%, p=0.75) and wortmannin (63±14 vs. 57±8%, p=0.89) abolished this effect.
Conclusion: The effects of LLVNS may be mediated by the PI3K/NO signaling pathway.
- © 2011 by American Heart Association, Inc.