Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Respirol. Jul 28, 2013; 3(2): 11-19
Published online Jul 28, 2013. doi: 10.5320/wjr.v3.i2.11
High-frequency electrical stimulation of cervical vagi reduces airway response to methacholine
Jianguo Zhuang, Daniel Bailet, Robert Curtis, Fadi Xu
Jianguo Zhuang, Fadi Xu, Lovelace Respiratory Research Institute, Pathophysiology Program, Albuquerque, NM 87108, United States
Daniel Bailet, Robert Curtis, NeuroStimulation Technologies, Inc., Albuquerque, NM 87108, United States
Author contributions: Zhuang J and Xu F performed the majority of experiments, data analysis and statistics, manuscript preparation and revision; Bailet D, Curtis R, and Xu F involved in the study design and endeavored to obtain financial support.
Supported by RO1 HL107462 from the National Heart, Lung, and Blood Institute, Bethesda, MD, and NeuroStimulation Techologies, Inc. Albuquerque, NM
Correspondence to: Dr. Fadi Xu, Lovelace Respiratory Research Institute, Pathophysiology Program, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, United States. fxu@lrri.org
Telephone: +1-505-3489565 Fax: +1-505-3488567
Received: February 20, 2013
Revised: May 31, 2013
Accepted: June 18, 2013
Published online: July 28, 2013
Abstract

AIM: To test whether high-frequency electrical stimulation (HES) of the bilateral cervical vagus nerves reduces the airway responses to methacholine (MCh).

METHODS: Guinea pigs were pretreated with saline (Sal, n = 9) or ovalbumin (Ova, n = 10) aerosol for two weeks (5 min/d, 5 d/wk) and subsequently anesthetized, paralyzed, tracheotomized and artificially ventilated. Both total lung resistance (RL) and dynamic pulmonary compliance (Cdyn) were recorded. In addition, the effects of vagal low-frequency electrical stimulation (LES, monophasic, 50 Hz) and HES (monophasic and biphasic, 1 and 2.5 kHz) for about 10 s or 2 min on the responses of RL and Cdyn to MCh aerosol-induced bronchoconstriction were compared in both groups of guinea pigs. In a few guinea pigs, the impact of bivagotomy on the RL responses to MCh was assessed.

RESULTS: Before MCh challenge, LES, but not HES, significantly increased RL by about 30% (P < 0.01) and decreased Cdyn by about 20% (P < 0.01) similarly in both groups. MCh aerosol for 2 min elevated RL and diminished Cdyn more in Ova- than Sal-treated animals (RL: 313% ± 52% vs 113% ± 17%, P < 0.01; Cdyn: -56% ± 7% vs -21% ± 3%, P < 0.01). During MCh-induced airway constriction, LES further enhanced, but HES decreased RL and this decrease was greater in Ova- (about 45%) than Sal-treated animals (about 34%, P < 0.01) with little change in cardiovascular activity. On the other hand, LES further reduced whereas HES increased Cdyn more in Ova- (about 20%) than Sal-treated animals (about 13%, P < 0.01). In addition, bivagotomy almost eliminated the RL and Cdyn responses to MCh.

CONCLUSION: We conclude that vagal HES is able to alleviate the bronchoconstriction induced by MCh in anesthetized guinea pigs, likely via reversible inhibition/blockade of vagal conduction.

Keywords: Bronchodilation, Acetylcholine, Airway hyperreactivity, Ovalbumin, Asthma

Core tip: In summary, our study revealed that vagal high-frequency electrical stimulation (HES) significantly suppressed the airway response to methacholine (MCh) more greatly in the ovalbumin- than saline-treated animals, while vagal low-frequency electrical stimulation always increased airway resistance. Importantly, the HES-evoked bronchodilation during MCh challenge is concomitant with the on-and-off electrical stimulation and with no effect on cardiovascular activity. These, along with the greatly blunted airway resistance response to MCh after bivagotomy, suggest that vagal HES may be a potentially useful approach in alleviating asthmatic bronchoconstriction (likely via reversible inhibition or blockade of the vagal nerve conduction).