Differential hemodynamic and respiratory responses to right and left cervical vagal nerve stimulation in rats.

Harald M Stauss

doi:10.14814/phy2.13244

Abstract

Neuromodulation through vagal nerve stimulation (VNS) is currently explored for a variety of clinical conditions. However, there are no established VNS parameters for animal models of human diseases, such as hypertension. Therefore, the aim of this study was to assess hemodynamic and respiratory responses to right‐ or left‐sided cervical VNS in a hypertensive rat model. Anesthetized stroke‐prone spontaneously hypertensive rats were instrumented for arterial blood pressure and heart rate monitoring and left‐ or right‐sided VNS. Cervical VNS was applied through bipolar coil electrodes. Stimulation parameters tested were 3 V and 6 V, 2 Hz to 20 Hz stimulation frequency, and 50 μsec to 20 msec pulse duration. Each combination of stimulation parameters was applied twice with altered polarity, that is, anode and cathode in the cranial and caudal position. Respiration rate was derived from systolic blood pressure fluctuations. In general, cervical VNS caused bradycardia, hypotension, and tachypnea. These responses were more pronounced with left‐sided than with right‐sided VNS and depended on the stimulation voltage, stimulation frequency, and pulse duration, but not on the polarity of stimulation. Furthermore, the results suggest that at low stimulation frequencies (<5 Hz) and short pulse durations (<0.5 msec) primarily larger A‐fibers are activated, while at longer pulse durations (>0.5 msec) smaller B‐fibers are also recruited. In conclusion, in rats left‐sided cervical VNS causes greater cardio‐respiratory responses than right‐sided VNS and at lower stimulation frequencies (e.g., 5 Hz), longer pulse durations (>0.5 msec) seem to be required to consistently recruit B‐fibers in addition to A‐fibers.

Highlights

IntroductionSince the discovery of the anti-inflammatory action of the parasympathetic nervous system (Tracey 2002), neuromodulation of vagal activity is increasingly explored as a potential treatment option for a variety of conditions associated with chronic inflammation, such as obesity (Pardo et al 2007; Bodenlos et al 2014), diabetes (Meyers et al 2016), heart failure (Premchand et al 2014; Zannad et al 2015; Gold et al 2016), hypertension (Chapleau et al 2016), or diseases with an autoimmune component, such as lupus or rheumatoid arthritis (Das 2011)
The pulse duration of the charge-balanced rectangular impulses used for vagal nerve stimulation had a significant impact on the heart rate response, but not on the responses of mean blood pressure or respiration rate
Tachypneic effects than right-sided vagal nerve stimulation (Table 3). The magnitude of these responses to vagal nerve stimulation depended on the stimulation voltage (Table 3), pulse duration (Fig. 2), and stimulation frequency (Fig. 3)

Summary

Introduction

Since the discovery of the anti-inflammatory action of the parasympathetic nervous system (Tracey 2002), neuromodulation of vagal activity is increasingly explored as a potential treatment option for a variety of conditions associated with chronic inflammation, such as obesity (Pardo et al 2007; Bodenlos et al 2014), diabetes (Meyers et al 2016), heart failure (Premchand et al 2014; Zannad et al 2015; Gold et al 2016), hypertension (Chapleau et al 2016), or diseases with an autoimmune component, such as lupus or rheumatoid arthritis (Das 2011). One important problem in the interpretation of such studies is that different investigators utilize different sites of vagal nerve stimulation (e.g., right vs left cervical vagus nerve) and different stimulation parameters (e.g., voltage, frequency, pulse duration, polarity). Stimulating different branches of the vagus nerve (e.g., right- vs leftsided, cervical vs subdiaphragmatic, etc.) may affect different target organs and different stimulation parameters may result in recruitment of different fiber types within the vagus nerve. The aim of this study was to explore the impact of different stimulation parameters, including voltage Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society

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