Stochastic vagus nerve stimulation affects acute heart rate dynamics in rats

Steven W. Lee, Kanchan Kulkarni, Elizabeth M. Annoni, Imad Libbus, Bruce H. KenKnight, Elena G. Tolkacheva

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Vagus nerve stimulation (VNS) is an approved therapy for treatment of epilepsy and depression. While also shown to be promising in several preclinical and clinical studies to treat cardiovascular diseases, optimal therapeutic stimulation paradigms are still under investigation. Traditionally, parameters such as frequency, current, and duty cycle are used to adjust the efficacy of VNS therapy. This study explored the effect of novel stochastic VNS (S-VNS) on acute heart rate (HR) dynamics. The effect of S-VNS was evaluated in Sprague Dawley rats by comparing the acute HR and HR variability (HRV) responses to standard, periodic VNS (P-VNS) across different frequencies (FREQs, 10–30 Hz). Our results demonstrate that both S-VNS and P-VNS produced negative chronotropic effects in a FREQ-dependent manner with S-VNS inducing a significantly smaller drop in HR at 10 Hz and 20 Hz compared to P-VNS (p<0.05). S-VNS demonstrated a FREQ-dependent drop in the SD1/SD2 ratio, a measure of HRV, which was absent in P-VNS, suggesting that S-VNS may acutely modulate the nonlinear relationship between short- and long-term HRV. In conclusion, S-VNS is a novel stimulation procedure that may provide different physiological outcomes from standard P-VNS, as indicated by our analysis of HR dynamics. Our study provides a rationale for further detailed investigations into the therapeutic potential of S-VNS as a novel neuromodulation technique.

Original languageEnglish (US)
Article numbere0194910
JournalPloS one
Volume13
Issue number3
DOIs
StatePublished - Mar 2018

Bibliographical note

Funding Information:
Funding: This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health F31HL129544 (to SWL), R21HL128790 (to EGT), and by National Science Foundation CAREER PHY-125541 (to EGT), DCSD 1662250 (to EGT), as well as support from LivaNova, PLC (Cyberonics, Inc). The funder LivaNova, PLC provided support in the form of salaries for authors (to IL, BHK, and EGT) and research materials (vagus nerve electrodes), but did not have any additional role in the study design, data collection and analysis, and decision to publish. The specific roles of these authors are articulated in the ‘Author Contributions’ section.

Funding Information:
Funding: This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health F31HL129544 (to SWL), R21HL128790 (to EGT), and by National Science Foundation CAREER PHY-125541 (to EGT), DCSD 1662250 (to EGT), as well as support from LivaNova, PLC (Cyberonics, Inc). The funder LivaNova, PLC provided support in the form of salaries for authors (to IL, BHK, and EGT) and research materials (vagus nerve electrodes), but did not have any additional role in the study design, data collection and analysis, and decision to publish. The specific roles of these authors are articulated in the ?Author Contributions? section.

Publisher Copyright:
© 2018 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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