Chronic vagal nerve stimulation has no effect on tachycardia-induced heart failure progression or excitation-contraction couplingCitation formats

  • External authors:
  • Emma Radcliffe
  • Amy Watkins
  • Michael Lawless
  • Graeme Kirkwood

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Chronic vagal nerve stimulation has no effect on tachycardia-induced heart failure progression or excitation-contraction coupling. / Radcliffe, Emma; Pearman, Charles; Watkins, Amy; Lawless, Michael; Kirkwood, Graeme; Saxton, Sophie; Eisner, David; Trafford, Andrew (Corresponding).

In: Physiological Reports, Vol. 8, No. 2, e14321, 20.01.2020.

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@article{d7ad4a0cb3f24b67b6884f46e1f30c67,
title = "Chronic vagal nerve stimulation has no effect on tachycardia-induced heart failure progression or excitation-contraction coupling",
abstract = "Autonomic dysregulation plays a key role in the development and progression of heart failure (HF). Vagal nerve stimulation (VNS) may be a promising therapeutic approach. However, the outcomes from clinical trials evaluating VNS in HF have been mixed, and the mechanisms underlying this treatment remain poorly understood. Intermittent high-frequency VNS (pulse width 300 µs, 30 Hz stimulation, 30 secs on and 300 secs off) was used in healthy sheep and sheep in which established HF had been induced by 4 weeks rapid ventricular pacing to assess 1) the effects of VNS on intrinsic cardiac vagal tone, 2) whether VNS delays the progression of established HF, and 3) whether high-frequency VNS affects the regulation of cardiomyocyte calcium handling in health and disease.VNS had no effect on resting heart rate or intrinsic vagal tone in the healthy heart. Although fewer VNS-treated animals showed subjective signs of heart failure at 6 weeks, overall VNS did not slow the progression of clinical or echocardiographic signs of HF. Chronic VNS did not affect left ventricular cardiomyocyte calcium handling in healthy sheep. Rapid ventricular pacing decreased the L-type calcium current and calcium transient amplitude, but chronic VNS did not rescue dysfunctional calcium handling.Overall, high frequency VNS did not prevent progression of established HF or influence cellular excitation-contraction coupling. However, a different model of HF or selection of different stimulation parameters may have yielded different results. These results highlight the need for greater insight into VNS dosing and parameter selection and a deeper understanding of its physiological effects.",
author = "Emma Radcliffe and Charles Pearman and Amy Watkins and Michael Lawless and Graeme Kirkwood and Sophie Saxton and David Eisner and Andrew Trafford",
year = "2020",
month = jan,
day = "20",
doi = "10.14814/phy2.14321",
language = "English",
volume = "8",
journal = "Physiological Reports",
publisher = "John Wiley & Sons Ltd",
number = "2",

}

RIS

TY - JOUR

T1 - Chronic vagal nerve stimulation has no effect on tachycardia-induced heart failure progression or excitation-contraction coupling

AU - Radcliffe, Emma

AU - Pearman, Charles

AU - Watkins, Amy

AU - Lawless, Michael

AU - Kirkwood, Graeme

AU - Saxton, Sophie

AU - Eisner, David

A2 - Trafford, Andrew

PY - 2020/1/20

Y1 - 2020/1/20

N2 - Autonomic dysregulation plays a key role in the development and progression of heart failure (HF). Vagal nerve stimulation (VNS) may be a promising therapeutic approach. However, the outcomes from clinical trials evaluating VNS in HF have been mixed, and the mechanisms underlying this treatment remain poorly understood. Intermittent high-frequency VNS (pulse width 300 µs, 30 Hz stimulation, 30 secs on and 300 secs off) was used in healthy sheep and sheep in which established HF had been induced by 4 weeks rapid ventricular pacing to assess 1) the effects of VNS on intrinsic cardiac vagal tone, 2) whether VNS delays the progression of established HF, and 3) whether high-frequency VNS affects the regulation of cardiomyocyte calcium handling in health and disease.VNS had no effect on resting heart rate or intrinsic vagal tone in the healthy heart. Although fewer VNS-treated animals showed subjective signs of heart failure at 6 weeks, overall VNS did not slow the progression of clinical or echocardiographic signs of HF. Chronic VNS did not affect left ventricular cardiomyocyte calcium handling in healthy sheep. Rapid ventricular pacing decreased the L-type calcium current and calcium transient amplitude, but chronic VNS did not rescue dysfunctional calcium handling.Overall, high frequency VNS did not prevent progression of established HF or influence cellular excitation-contraction coupling. However, a different model of HF or selection of different stimulation parameters may have yielded different results. These results highlight the need for greater insight into VNS dosing and parameter selection and a deeper understanding of its physiological effects.

AB - Autonomic dysregulation plays a key role in the development and progression of heart failure (HF). Vagal nerve stimulation (VNS) may be a promising therapeutic approach. However, the outcomes from clinical trials evaluating VNS in HF have been mixed, and the mechanisms underlying this treatment remain poorly understood. Intermittent high-frequency VNS (pulse width 300 µs, 30 Hz stimulation, 30 secs on and 300 secs off) was used in healthy sheep and sheep in which established HF had been induced by 4 weeks rapid ventricular pacing to assess 1) the effects of VNS on intrinsic cardiac vagal tone, 2) whether VNS delays the progression of established HF, and 3) whether high-frequency VNS affects the regulation of cardiomyocyte calcium handling in health and disease.VNS had no effect on resting heart rate or intrinsic vagal tone in the healthy heart. Although fewer VNS-treated animals showed subjective signs of heart failure at 6 weeks, overall VNS did not slow the progression of clinical or echocardiographic signs of HF. Chronic VNS did not affect left ventricular cardiomyocyte calcium handling in healthy sheep. Rapid ventricular pacing decreased the L-type calcium current and calcium transient amplitude, but chronic VNS did not rescue dysfunctional calcium handling.Overall, high frequency VNS did not prevent progression of established HF or influence cellular excitation-contraction coupling. However, a different model of HF or selection of different stimulation parameters may have yielded different results. These results highlight the need for greater insight into VNS dosing and parameter selection and a deeper understanding of its physiological effects.

U2 - 10.14814/phy2.14321

DO - 10.14814/phy2.14321

M3 - Article

VL - 8

JO - Physiological Reports

JF - Physiological Reports

IS - 2

M1 - e14321

ER -