Heart rate reduction after ivabradine might be associated with reverse electrical remodeling in patients with cardiomyopathy and left bundle branch block

Kučerová, Andrea; Doškář, Petr; Dujka, Libor; Lekešová, Veronika; Volf, Petr; Koščová, Katarína; Neužil, Petr; Málek, Filip

doi:10.1177/0300060518799566

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…Clinical study and fundamental research suggest that IVA reverses electrical and mechanical remodeling, adjusting the imbalance of the autonomic nervous system with sympathetic activation (Milliez et al, 2009; Kucerova et al, 2018). We show that IVA inhibited HCN channel expression and current density, these results are in consistent with previous reports (Suffredini et al, 2012; Li et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Hyperpolarization-Activated Cyclic Nucleotide-Gated Ion (HCN) Channels Regulate PC12 Cell Differentiation Toward Sympathetic Neuron

Zhong

Fan

Shi

et al. 2019

Front. Cell. Neurosci.

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Hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN channels) are widely expressed in the central and peripheral nervous systems and organs, while their functions are not well elucidated especially in the sympathetic nerve. The present study aimed to investigate the roles of HCN channel isoforms in the differentiation of sympathetic neurons using PC12 cell as a model. PC12 cells derived from rat pheochromocytoma were cultured and induced by nerve growth factor (NGF) (25 ng/ml) to differentiate to sympathetic neuron-like cells. Sympathetic directional differentiation of PC12 cells were evaluated by expressions of growth-associated protein 43 (GAP-43) (a growth cone marker), tyrosine hydroxylase (TH) (a sympathetic neuron marker) and neurite outgrowth. Results show that the HCN channel isoforms (HCN1-4) were all expressed in PC12 cells; blocking HCN channels with ivabradine suppressed NGF-induced GAP-43 expression and neurite outgrowth; silencing the expression of HCN2 and HCN4 using silenced using small interfering RNAs (siRNA), rather than HCN1 and HCN3, restrained GAP-43 expression and neurite outgrowth, while overexpression of HCN2 and HCN4 channels with gene transfer promoted GAP-43 expression and neurite outgrowth. Patch clamp experiments show that PC12 cells exhibited resting potentials (RP) of about −65 to −70 mV, and also presented inward HCN channel currents and outward (K+) currents, but no inward voltage-gated Na+ current was induced; NGF did not significantly affect the RP but promoted the establishment of excitability as indicated by the increased ability to depolarize and repolarize in the evoked suspicious action potentials (AP). We conclude that HCN2 and HCN4 channel isoforms, but not HCN1 and HCN3, promote the differentiation of PC12 cells toward sympathetic neurons. NGF potentiates the establishment of excitability during PC12 cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Hyperpolarization-Activated Cyclic Nucleotide-Gated Ion (HCN) Channels Regulate PC12 Cell Differentiation Toward Sympathetic Neuron

Zhong

Fan

Shi

et al. 2019

Front. Cell. Neurosci.

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“…Therefore, it would be interesting to know if medical treatment that results in reverse remodelling of the left ventricle such as sacubitril/valsartan is also accompanied by reduction of conduction delay. This has only been reported in small case series (e.g 5 …”

Section: Figurementioning

confidence: 96%

“…This has only been reported in small case series (e.g. 5 ) but not investigated systematically. Still, the treatment with sacubitril/valsartan was reported to result in electromechanical remodelling in animals 6 and is also accompanied by a reduced risk of clinically significant arrhythmias.…”

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confidence: 95%

The importance of electrocardiographic follow‐up in heart failure

Vernooy

Rocca

2020

European J of Heart Fail

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Pharmacology of Ivabradine and the Effect on Chronic Heart Failure

Zhou

Wang

Meng

et al. 2019

CTMC

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Chronic Heart Failure (CHF) is a complex clinical syndrome with a high incidence worldwide. Although various types of pharmacological and device therapies are available for CHF, the prognosis is not ideal, for which, the control of increased Heart Rate (HR) is critical. Recently, a bradycardic agent, ivabradine, is found to reduce HR by inhibiting the funny current (If). The underlying mechanism states that ivabradine can enter the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and bind to the intracellular side, subsequently inhibiting the If. This phenomenon can prolong the slow spontaneous phase in the diastolic depolarization, and thus, reduce HR. The clinical trials demonstrated the significant effects of the drug on reducing HR and improving the symptoms of CHF with fewer adverse effects. This review primarily introduces the chemical features and pharmacological characteristics of ivabradine and the mechanism of treating CHF. Also, some expected therapeutic effects on different diseases were also concluded. However, ivabradine, as a typical If channel inhibitor, necessitates additional research to verify its pharmacological functions.

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Heart rate reduction after ivabradine might be associated with reverse electrical remodeling in patients with cardiomyopathy and left bundle branch block

Cited by 3 publications

References 7 publications

Hyperpolarization-Activated Cyclic Nucleotide-Gated Ion (HCN) Channels Regulate PC12 Cell Differentiation Toward Sympathetic Neuron

Hyperpolarization-Activated Cyclic Nucleotide-Gated Ion (HCN) Channels Regulate PC12 Cell Differentiation Toward Sympathetic Neuron

The importance of electrocardiographic follow‐up in heart failure

Pharmacology of Ivabradine and the Effect on Chronic Heart Failure

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