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December 27, 2022AJP Regulatory Integrative and Comparative Physiology5 citations

Dynamic accentuated antagonism of heart rate control during different levels of vagal nerve stimulation intensity in rats

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TKToru KawadaAYAimi YokoiANAkitsugu Nishiura

Key Result

Concomitant sympathetic nerve stimulation increased the asymptotic low-frequency gain of the vagal heart rate transfer function during high-intensity vagal stimulation (7.39 vs 4.77 beats/min/Hz; P=0.011).

Key Points

  • This research investigates the dynamic effects of vagal nerve stimulation intensity on heart rate modulation in the presence of sympathetic tone.
  • Performed vagal nerve stimulation on anesthetized rats (n=8) under different stimulation rates (low, moderate, high).
  • Measured heart rate responses with and without sympathetic nerve stimulation at 5 Hz.
  • Analyzed transfer function dynamics and gain ratios during the experiments.
  • Asymptotic low-frequency heart rate gain increased with sympathetic stimulation across all vagal stimulation levels, with significant differences (P=0.021, P=0.018, P=0.011).
  • Sympathetic nerve stimulation enhanced the high-frequency to low-frequency gain ratio.
  • Effects of sympathetic background tone were neutralized by ivabradine in another rat group (n=6).

Structured PICO

Does concomitant sympathetic nerve stimulation augment the dynamic gain of the vagal heart rate transfer function during different levels of vagal nerve stimulation in anesthetized rats?

P
Population
14 anesthetized rats undergoing vagal nerve stimulation with and without concomitant sympathetic nerve stimulation.
I
Intervention
Vagal nerve stimulation (VNS) at three different stimulation rates (low-intensity: 0-10 Hz, moderate-intensity: 0-20 Hz, high-intensity: 0-40 Hz) with concomitant tonic sympathetic nerve stimulation (SNS) at 5 Hz
C
Comparator
Vagal nerve stimulation (VNS) without concomitant tonic sympathetic nerve stimulation (SNS)
O
Outcome
Transfer function from VNS to heart rate (asymptotic low-frequency gain and high-frequency gain)surrogate

Background sympathetic tone enables finer heart rate control by increasing the dynamic gain of the vagal heart rate transfer function regardless of vagal nerve stimulation intensity.

Main Result

Absolute Event Rate: 7.39% vs 4.77%

p-value: p=0.011

Abstract

Accentuated antagonism refers to a phenomenon in which the vagal effect on heart rate (HR) is augmented by background sympathetic tone. The dynamic aspect of accentuated antagonism remains to be elucidated during different levels of vagal nerve stimulation (VNS) intensity. We performed VNS on anesthetized rats ( n = 8) according to a binary white noise signal with a switching interval of 500 ms at three different stimulation rates (low-intensity: 0–10 Hz, moderate-intensity: 0–20 Hz, and high-intensity: 0–40 Hz). The transfer function from VNS to HR was estimated with and without concomitant tonic sympathetic nerve stimulation (SNS) at 5 Hz. The asymptotic low-frequency (LF) gain (in beats/min/Hz) of the transfer function increased with SNS regardless of the VNS rate low-intensity: 3.93 ± 0.70 vs. 5.82 ± 0.65 ( P = 0.021), moderate-intensity: 3.87 ± 0.62 vs. 5.36 ± 0.53 ( P = 0.018), high-intensity: 4.77 ± 0.85 vs. 7.39 ± 1.36 ( P = 0.011). Moreover, SNS slightly increased the ratio of high-frequency (HF) gain to the LF gain. These effects of SNS were canceled by the pretreatment of ivabradine, an inhibitor of hyperpolarization-activated cyclic nucleotide-gated channels, in another group of rats ( n = 6). Although background sympathetic tone antagonizes the vagal effect on mean HR, it enables finer HR control by increasing the dynamic gain of the vagal HR transfer function regardless of VNS intensity. When interpreting the HF component of HR variability, the augmenting effect from background sympathetic tone needs to be considered.

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Cite This Study

Kawada et al. (2022) studied this question. Concomitant tonic sympathetic nerve stimulation (SNS) vs. Without concomitant tonic sympathetic nerve stimulation was evaluated on Asymptotic low-frequency (LF) gain of the transfer function from VNS to HR (p=0.011). Concomitant sympathetic nerve stimulation increased the asymptotic low-frequency gain of the vagal heart rate transfer function during high-intensity vagal stimulation (7.39 vs 4.77 beats/min/Hz; P=0.011).

synapsesocial.com/papers/6a22843affccceb004b73a43https://doi.org/10.1152/ajpregu.00229.2022
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