High‐frequency dominant depression of peripheral vagal control of heart rate in rats with chronic heart failure

Kawada, Toru; Li, M.; Shimizu, Shuji; Kamiya, Atsunori; Uemura, Kazunori; Turner, Michael J.; Mizuno, Masaki; Sugimachi, Masaru

doi:10.1111/apha.12055

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…All these measurements estimate high‐frequency variations and thus are highly correlated with parasympathetic activity (Kawada et al . ). Indeed, it is well established that the high‐frequency component of R‐R interval variability primarily reflects the vagal modulation of the respiratory sinus arrhythmia (RSA) (Malik ).…”

Section: Discussionmentioning

confidence: 97%

Ventricular remodelling in rabbits with sustained high‐fat diet

et al. 2013

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Section: Discussionmentioning

confidence: 97%

Ventricular remodelling in rabbits with sustained high‐fat diet

et al. 2013

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“…The HF gain ratio is positively correlated with the VNS rate in normal control rats, as evidenced by the CNT data in Figure 4d . However, the correlation is lost in rats with chronic heart failure after myocardial infarction (Kawada et al, 2013 ). In failing human hearts, atrial myocytes exhibited a less negative resting membrane potential with I K,ACh dysfunction (Koumi et al, 1994 ).…”

Section: Discussionmentioning

confidence: 99%

“…The following mathematical model (Equation ) was used to describe the estimated transfer function from VNS to HR according to previous studies (Kawada et al, 2013, 2021; Kawada, Yamamoto, et al, 2019):

H_{Model} (f) = ‐ K (\frac{1 ‐ R}{1 + \frac{f}{f_{C}} j} + R) \exp (‐ 2 π f L j),

where j , imaginary unit; f , frequency (Hz); K , steady‐state gain (bpm/Hz), referred to as “asymptotic LF gain”; f C , corner frequency (Hz); R , fraction of the HF gain to K , referred to as “HF gain ratio”; and L , dead time (s).…”

Section: Methodsmentioning

confidence: 99%

Ivabradine increases the high frequency gain ratio in the vagal heart rate transfer function via an interaction with muscarinic potassium channels

et al. 2021

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Muscarinic potassium channels (IK,ACh) are thought to contribute to the high frequency (HF) dynamic heart rate (HR) response to vagal nerve stimulation (VNS) because they act faster than the pathway mediated by hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels. However, the interactions between the two pathways have not yet been fully elucidated. We previously demonstrated that HCN channel blockade by ivabradine (IVA) increased the HF gain ratio of the transfer function from VNS to HR. To test the hypothesis that IVA increases the HF gain ratio via an interaction with IK,ACh, we examined the dynamic HR response to VNS under conditions of control (CNT), IK,ACh blockade by tertiapin‐Q (TQ, 50 nM/kg), and TQ plus IVA (2 mg/kg) (TQ + IVA) in anesthetized rats (n = 8). In each condition, the right vagal nerve was stimulated for 10 min with binary white noise signals between 0–10, 0–20, and 0–40 Hz. On multiple regression analysis, the HF gain ratio positively correlated with the VNS rate with a coefficient of 1.691 ± 0.151 (×0.01) (p < 0.001). TQ had a negative effect on the HF gain ratio with a coefficient of −1.170 ± 0.214 (×0.01) (p < 0.001). IVA did not significantly increase the HF gain ratio in the presence of TQ. The HF gain ratio remained low under the TQ + IVA condition compared to controls. These results affirm that the IVA‐induced increase in the HF gain ratio is dependent on the untethering of the hyperpolarizing effect of IK,ACh.

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“…In protocol 3, HVN¡HR was quantified using the following mathematical model according to our previous studies (14,18,19): 4) where j denotes the imaginary unit; K (in beats•min Ϫ1 •Hz Ϫ1 ) is the steady-state gain, which represents the asymptotic gain when the frequency tends to zero; f C (in Hz) is the corner frequency relating to low-pass characteristics; L (in seconds) is the pure dead time; and R (dimensionless) is the fraction of the frequency-independent gain relative to the steady-state gain. The dynamic gain of H VN¡HR approaches KR as the frequency approaches infinity.…”

Section: Modeling Of the Vagal Efferent Limbmentioning

confidence: 99%

Contrasting open-loop dynamic characteristics of sympathetic and vagal systems during baroreflex-mediated heart rate control in rats

Kawada

Yamamoto

Hayama

et al. 2019

American Journal of Physiology-Regulatory, Integrative and Comp

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Although heart rate (HR) is governed by the sympathetic and parasympathetic nervous systems, a head-to-head comparison of the open-loop dynamic characteristics of the total arc from a baroreceptor pressure input to the HR response has yet to be performed. We estimated the transfer function from carotid sinus pressure input to the HR response ( HCSP→HR) before and after bilateral vagotomy ( n = 7) as well as before and after the administration of a β-blocker propranolol ( n = 8) in anesthetized male Wistar-Kyoto rats. The carotid sinus pressure was perturbed according to a Gaussian white noise signal so that the input power spectra were relatively flat between 0.01 and 1 Hz. The gain plot of HCSP→HR was V-shaped. Vagotomy reduced the dynamic gain at 1 Hz (0.0598 ± 0.0065 to 0.0025 ± 0.0004 beats·min−1·mmHg−1, P < 0.001) but not at 0.01 or 0.1 Hz. β-Blockade reduced the dynamic gain at 0.01 Hz (0.247 ± 0.069 to 0.077 ± 0.017 beats·min−1·mmHg−1, P = 0.020) but not at 0.1 or 1 Hz. We also estimated the efferent limb transfer function from electrical vagal efferent stimulation to the HR response ( HVN→HR) under β-blockade conditions. We associated the model parameters of HVN→HR with the mean HR and the standard deviation of HR so that HVN→HR could be estimated based only on the HR data. We finally estimated the neural arc transfer function from a pressure input to efferent vagal nerve activity by dividing HCSP→HR by HVN→HR. The mathematically determined vagal neural arc showed derivative characteristics with its phase near zero radians at the lowest frequency.

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High‐frequency dominant depression of peripheral vagal control of heart rate in rats with chronic heart failure

Abstract: Changes in the dynamic characteristics of the peripheral vagal control of HR may contribute to the manifestation of decreased HF components of HR variability observed in CHF.

Cited by 8 publications

References 32 publications

Ventricular remodelling in rabbits with sustained high‐fat diet

Ventricular remodelling in rabbits with sustained high‐fat diet

Ivabradine increases the high frequency gain ratio in the vagal heart rate transfer function via an interaction with muscarinic potassium channels

Contrasting open-loop dynamic characteristics of sympathetic and vagal systems during baroreflex-mediated heart rate control in rats

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