[Effect of α7nAChR mediated cholinergic anti-inflammatory pathway on inhibition of atrial fibrillation by low-level vagus nerve stimulation].

ABSTRACT

Objective: To investigate the effect of α7nAChR mediated cholinergic anti-inflammatory pathway on inhibition of atrial fibrillation by low-level vagus nerve stimulation(LL-VNS). Methods: Eighteen beagles were randomized into control group (n=6), LL-VNS group (n=6) and methyllycaconitine (MLA) + LL-VNS group (n=6). All the beagles were subjected to rapid atrial pacing at 800 beats/min for 6 hours.And the effective refractory period (ERP) of atriums and pulmonary veins and induced atrial fibrillation (AF) were measured hourly during non-pacing.After cessation of pacing for 3 hours, the beagles in control group were injected with saline into four ganglionated plexis (GPs), the beagles in LL-VNS group were given LL-VNS and saline injected into four GPs, and the beagles in MLA+ LL-VNS group were injected with MLA into four GPs combined with LL-VNS.And the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and acetylcholine (ACh) in the plasma at baseline condition, 3 h and 6 h were measured.At the end of this experiment, atrial tissues were collected to examine the levels of TNF-α, IL-6, ACh, NF-κBp65 and STAT3 proteins. Results: During the right atrium pacing for the first 3 hours, the ERPs were gradually decreased while AF inducibility were gradually increased in all groups. At the end of this experiment, compared with the control group and MLA+ LL-VNS group, the ERPs in LL-VNS group were increased, and the induced times and duration of AF were significantly decreased. The levels of TNF-α and IL-6 in plasma were all significantly decreased in LL-VNS group and MLA+ LL-VNS group when compared with the control group(pg/ml) [IL-6 (101±6) vs (119±7), P<0.05; (102±5) vs (119±7), P<0.05; TNF-α (17.8±1.7) vs (22.1±2.0), P<0.05; (17.9±2.2) vs (22.1±2.0), P<0.05]. And the levels of ACh were higher than in the control group(µg/ml)[(151±13) vs (123±10), P<0.05; (145±5) vs (123±10), P<0.05]. After cessation of pacing for 6 hours, compared with the control groupand MLA+ LL-VNS group, the tissue levels of TNF-α and IL-6 were significantly decreased in LL-VNS group (P<0.05). The concentrations of NF-κBp65 proteins in atrial tissues were lower in the LL-VNS group (P<0.05), and the levels of STAT3 proteins in those tissues were higher in the LL-VNS group than in thein the two other groups (P<0.05). Conclusion: LL-VNS could inhibit the atrial electrical remodeling and atrial fibrillation induction; cholinergic anti-inflammatory pathway mediated by α7nAChR may be the important mechanism in vagal nerve regulated AF.