Chronic vagal nerve stimulation exerts additional beneficial effects on the beta-blocker-treated failing heart
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Vagal nerve stimulation (VNS) induces bradycardia in chronic heart failure (CHF). We hypothesized that beta-blocker would cover the beneficial effects of VNS on CHF if the anti-beta-adrenergic effect was the main VNS effect. This study investigated the effects of VNS on cardiac remodeling in rats with CHF treated with metoprolol. Two weeks after myocardial infarction, surviving rats were randomly assigned to groups of sham stimulation (SS), sham stimulation with metoprolol (SSM), or VNS with metoprolol (VSM). Compared to the SS group, heart rate was significantly reduced in the SSM and VSM groups. Hemodynamic assessments showed that VSM rats maintained better cardiac pump function and presented higher cardiac index and lower heart weight than SSM rats. VSM was also associated with lower plasma brain natriuretic peptide and norepinephrine levels than SSM. VSM but not SSM improved the 50-day survival rate compared with the SS group. The results suggest that VNS may exert its beneficial effects on the failing heart independently of its anti-beta-adrenergic mechanism.
KeywordsVagal nerve stimulation Beta-blocker Myocardial infarction Cardiac remodeling Chronic heart failure
This study was partly supported by JSPS KAKENHI (Grant Number: C—26461099, 17K09544).
ML, CZ, and MS designed the study. ML and CZ performed the measurements and statistical analysis, and drafted the manuscript. KT, MI, and KU joined in interpreting the data. All authors have read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The author(s) declare that they have no competing interests.
Research involving animals
The care of animals and all animal experiments were performed in strict accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996), and the Guiding Principles for the Care and Use of Animals in the Field of Physiological Sciences, which have been approved by the Physiological Society of Japan. All protocols were reviewed and approved by the Animal Subject Committee in the National Cerebral and Cardiovascular Center.
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