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Effects of low-intensity autonomic nerve stimulation on atrial electrophysiology.

Cho Y, Cha MJ, Choi EK, Oh IY, Oh S - Korean Circ J (2014)

Bottom Line: Neither WOV for AF nor AF inducibility changed significantly during 3 hours RAP with simultaneous LI-ANS.There was no significant difference between the control and LI-ANS group in nerve density and sprouting evaluated by anti-tyrosine hydroxylase and anti-growth associated protein-43 staining.Among the various sites for LI-ANS, the ARGP-stimulation group showed marginally lower ΔWOV (p=0.077) and lower nerve sprouting (p=0.065) compared to the RVN-stimulation group.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

ABSTRACT

Background and objectives: The cardiac autonomic nervous system is an emerging target for therapeutic control of atrial fibrillation (AF). We evaluated the effects of low-intensity autonomic nerve stimulation (LI-ANS) on atrial electrophysiology, AF vulnerability, and neural remodeling.

Subjects and methods: Fourteen dogs were subjected to 3 hours rapid atrial pacing (RAP, 5 Hz) and concomitant high frequency LI-ANS (20 Hz, at voltages 40% below the threshold) as follows: no autonomic stimulation (control, n=3); or right cervical vagus nerve (RVN, n=6), anterior right ganglionated plexi (ARGP, n=3), and superior left ganglionated plexi (SLGP, n=2) stimulation. Programmed and burst atrial pacing were performed at baseline and at the end of each hour to determine atrial effective refractory period (ERP), window of vulnerability (WOV), and inducibility of sustained AF.

Results: Atrial ERP was significantly shortened by 3 hours RAP (in control group, ΔERP=-47.9±8.9%, p=0.032), and RAP-induced ERP shortening was attenuated by LI-ANS (in LI-ANS group, ΔERP=-15.4±5.9%, p=0.019; vs. control, p=0.035). Neither WOV for AF nor AF inducibility changed significantly during 3 hours RAP with simultaneous LI-ANS. There was no significant difference between the control and LI-ANS group in nerve density and sprouting evaluated by anti-tyrosine hydroxylase and anti-growth associated protein-43 staining. Among the various sites for LI-ANS, the ARGP-stimulation group showed marginally lower ΔWOV (p=0.077) and lower nerve sprouting (p=0.065) compared to the RVN-stimulation group.

Conclusion: Low-intensity autonomic nerve stimulation significantly attenuated the shortening of atrial ERP caused by RAP. ARGP may be a better target for LI-ANS than RVN for the purpose of suppressing atrial remodeling in AF.

No MeSH data available.


Related in: MedlinePlus

Study protocol. Diagram of the study protocol. Electrophysiologic study (EPS) was performed at baseline and at the end of each hour of rapid atrial pacing with concomitant low-intensity autonomic stimulation. RVN: right cervical vagus nerve, ARGP: anterior right ganglionated plexi, SLGP: superior left ganglionated plexi.
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Figure 1: Study protocol. Diagram of the study protocol. Electrophysiologic study (EPS) was performed at baseline and at the end of each hour of rapid atrial pacing with concomitant low-intensity autonomic stimulation. RVN: right cervical vagus nerve, ARGP: anterior right ganglionated plexi, SLGP: superior left ganglionated plexi.

Mentions: The overall study scheme is presented as Fig. 1. To induce acute atrial remodeling, the lateral wall of the left atrium was rapidly paced at 300 beats/min. According to the assigned experimental group, the designated site of autonomic nervous system was simultaneously stimulated by high-frequency electrical stimulation (20 Hz, 0.2 ms duration, square waves) using a S88 dual channel stimulator (Grass Instrument Co., MA, USA). First, ANS threshold was determined as the lowest voltage inducing any reduction in heart rate at each site {3.1±0.6 V for RVN stimulation, 7.8±3.1 V for ganglionated plexi (GP) stimulation}. Then, autonomic nerves were stimulated at a voltage 40% lower than the threshold during the 3 hours experimental protocol for LI-ANS. After each hour rapid atrial pacing (RAP) was temporarily stopped for 5 to 10 minutes to perform electrophysiological evaluation. The effective refractory period (ERP), window of vulnerability (WOV) for AF, and AF inducibility were measured at the lateral free wall of both left and right atria. ERP was determined by programmed stimulation consisting of 8 consecutive stimuli (S1-S1=400 ms) followed by a premature stimulus (S1-S2). WOV for AF was defined as the difference between the longest and shortest S1-S2 interval at which AF of >3 seconds was induced. AF inducibility was tested by counting the episodes of induced sustained AF (>30 seconds) after 5 burst atrial pacings (10 seconds, 600 beats/min).


Effects of low-intensity autonomic nerve stimulation on atrial electrophysiology.

Cho Y, Cha MJ, Choi EK, Oh IY, Oh S - Korean Circ J (2014)

Study protocol. Diagram of the study protocol. Electrophysiologic study (EPS) was performed at baseline and at the end of each hour of rapid atrial pacing with concomitant low-intensity autonomic stimulation. RVN: right cervical vagus nerve, ARGP: anterior right ganglionated plexi, SLGP: superior left ganglionated plexi.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4117845&req=5

Figure 1: Study protocol. Diagram of the study protocol. Electrophysiologic study (EPS) was performed at baseline and at the end of each hour of rapid atrial pacing with concomitant low-intensity autonomic stimulation. RVN: right cervical vagus nerve, ARGP: anterior right ganglionated plexi, SLGP: superior left ganglionated plexi.
Mentions: The overall study scheme is presented as Fig. 1. To induce acute atrial remodeling, the lateral wall of the left atrium was rapidly paced at 300 beats/min. According to the assigned experimental group, the designated site of autonomic nervous system was simultaneously stimulated by high-frequency electrical stimulation (20 Hz, 0.2 ms duration, square waves) using a S88 dual channel stimulator (Grass Instrument Co., MA, USA). First, ANS threshold was determined as the lowest voltage inducing any reduction in heart rate at each site {3.1±0.6 V for RVN stimulation, 7.8±3.1 V for ganglionated plexi (GP) stimulation}. Then, autonomic nerves were stimulated at a voltage 40% lower than the threshold during the 3 hours experimental protocol for LI-ANS. After each hour rapid atrial pacing (RAP) was temporarily stopped for 5 to 10 minutes to perform electrophysiological evaluation. The effective refractory period (ERP), window of vulnerability (WOV) for AF, and AF inducibility were measured at the lateral free wall of both left and right atria. ERP was determined by programmed stimulation consisting of 8 consecutive stimuli (S1-S1=400 ms) followed by a premature stimulus (S1-S2). WOV for AF was defined as the difference between the longest and shortest S1-S2 interval at which AF of >3 seconds was induced. AF inducibility was tested by counting the episodes of induced sustained AF (>30 seconds) after 5 burst atrial pacings (10 seconds, 600 beats/min).

Bottom Line: Neither WOV for AF nor AF inducibility changed significantly during 3 hours RAP with simultaneous LI-ANS.There was no significant difference between the control and LI-ANS group in nerve density and sprouting evaluated by anti-tyrosine hydroxylase and anti-growth associated protein-43 staining.Among the various sites for LI-ANS, the ARGP-stimulation group showed marginally lower ΔWOV (p=0.077) and lower nerve sprouting (p=0.065) compared to the RVN-stimulation group.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

ABSTRACT

Background and objectives: The cardiac autonomic nervous system is an emerging target for therapeutic control of atrial fibrillation (AF). We evaluated the effects of low-intensity autonomic nerve stimulation (LI-ANS) on atrial electrophysiology, AF vulnerability, and neural remodeling.

Subjects and methods: Fourteen dogs were subjected to 3 hours rapid atrial pacing (RAP, 5 Hz) and concomitant high frequency LI-ANS (20 Hz, at voltages 40% below the threshold) as follows: no autonomic stimulation (control, n=3); or right cervical vagus nerve (RVN, n=6), anterior right ganglionated plexi (ARGP, n=3), and superior left ganglionated plexi (SLGP, n=2) stimulation. Programmed and burst atrial pacing were performed at baseline and at the end of each hour to determine atrial effective refractory period (ERP), window of vulnerability (WOV), and inducibility of sustained AF.

Results: Atrial ERP was significantly shortened by 3 hours RAP (in control group, ΔERP=-47.9±8.9%, p=0.032), and RAP-induced ERP shortening was attenuated by LI-ANS (in LI-ANS group, ΔERP=-15.4±5.9%, p=0.019; vs. control, p=0.035). Neither WOV for AF nor AF inducibility changed significantly during 3 hours RAP with simultaneous LI-ANS. There was no significant difference between the control and LI-ANS group in nerve density and sprouting evaluated by anti-tyrosine hydroxylase and anti-growth associated protein-43 staining. Among the various sites for LI-ANS, the ARGP-stimulation group showed marginally lower ΔWOV (p=0.077) and lower nerve sprouting (p=0.065) compared to the RVN-stimulation group.

Conclusion: Low-intensity autonomic nerve stimulation significantly attenuated the shortening of atrial ERP caused by RAP. ARGP may be a better target for LI-ANS than RVN for the purpose of suppressing atrial remodeling in AF.

No MeSH data available.


Related in: MedlinePlus