Sinus node revisited

Lau, Dennis H.; Roberts‐Thomson, Kurt C.; Sanders, Prashanthan

doi:10.1097/hco.0b013e32834138f4

Cited by 16 publications

(9 citation statements)

References 54 publications

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“…7 In addition, many patients with AF have evidence of sinus node remodeling in which the increased incidence of bradycardia may further reduce cerebral perfusion. 8 The results of the present study add further strength to the existing evidence base regarding oral anticoagulation and the risk of dementia. Anticoagulation with warfarin or direct oral anticoagulants (DOACs) was associated with lower dementia risk in the largest reported study from the Swedish registry of 444,106 individuals with newly diagnosed AF with the absence of anticoagulation associated with a greater than 2-fold increase in dementia risk.…”

supporting

confidence: 59%

Reducing Risk of Dementia in AF—Is Oral Anticoagulation the Key?

Gallagher

Lau

Sanders

2018

Mayo Clinic Proceedings

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supporting

confidence: 59%

Reducing Risk of Dementia in AF—Is Oral Anticoagulation the Key?

Gallagher

Lau

Sanders

2018

Mayo Clinic Proceedings

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“…; Lau et al . ). Therefore, it is possible that β‐adrenergic/PKA regulation of Cav3.1 participates in the positive chronotropic effects of β‐adrenergic agonists by enhancing both phase 4 diastolic depolarization current (‘membrane clock’) and SANC Ca 2+ handling (‘calcium clock’).…”

Section: Discussionmentioning

confidence: 97%

“…; Lau et al . ). To adapt to the needs of the body, the HR of animals and human beings is constantly regulated (Lau et al .…”

Section: Introductionmentioning

confidence: 97%

“…To adapt to the needs of the body, the HR of animals and human beings is constantly regulated (Lau et al . ). HR regulation occurs by a change in the automaticity of the SAN cells and the conduction rate, especially via the atrioventricular node (AVN) in response to changes in autonomic nerve activity (Lakatta et al .…”

Section: Introductionmentioning

confidence: 97%

“…Abnormal SAN automaticity and its regulation contribute to sinus node disease, a type of arrhythmia often requiring pacemaker implantation (Lau et al . ), whereas modulating SAN automaticity is an effective way of treating heart failure (Borer et al . ).…”

Section: Introductionmentioning

confidence: 99%

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Increasing T‐type calcium channel activity by β‐adrenergic stimulation contributes to β‐adrenergic regulation of heart rates

Zhang

et al. 2018

The Journal of Physiology

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Cav3.1 T-type Ca channel current (I ) contributes to heart rate genesis but is not known to contribute to heart rate regulation by the sympathetic/β-adrenergic system (SAS). We show that the loss of Cav3.1 makes the beating rates of the heart in vivo and perfused hearts ex vivo, as well as sinoatrial node cells, less sensitive to β-adrenergic stimulation; it also renders less conduction acceleration through the atrioventricular node by β-adrenergic stimulation. Increasing Cav3.1 in cardiomyocytes has the opposite effects. I in sinoatrial nodal cells can be upregulated by β-adrenergic stimulation. The results of the present study add a new contribution to heart rate regulation by the SAS system and provide potential new mechanisms for the dysregulation of heart rate and conduction by the SAS in the heart. T-type Ca channel can be a target for heart disease treatments that aim to slow down the heart rate ABSTRACT: Cav3.1 (α ) T-type Ca channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular (AV) nodal cells and contributes to heart rate (HR) genesis and AV conduction. However, its role in HR regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear. In the present study, L- (I ) and T-type (I ) Ca currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice. I was absent in KO SANCs but enhanced in TG SANCs. In anaesthetized animals, different doses of isoproterenol (ISO) were infused via the jugular vein and the HR was recorded. The EC of the HR response to ISO was lower in TG mice but higher in KO mice, and the maximal percentage of HR increase by ISO was greater in TG mice but less in KO mice. In Langendorff-perfused hearts, ISO increased HR and shortened PR intervals to a greater extent in TG but to a less extent in KO hearts. KO SANCs had significantly slower spontaneous beating rates than control SANCs before and after ISO; TG SANCs had similar basal beating rates as control SANCs probably as a result of decreased I but a greater response to ISO than control SANCs. I in SANCs was significantly increased by ISO. I upregulation by β-adrenergic stimulation contributes to HR and conduction regulation by the SAS. TTCC can be a target for slowing the HR.

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Atrial fibrillation and conduction system disease: the roles of catheter ablation and permanent pacing

Thiyagarajah

Lau

Sanders

2018

J Interv Card Electrophysiol

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Atrial fibrillation (AF) and diseases of the cardiac conduction system frequently co-exist, and interactions between these rhythm disturbances can adversely impact patient outcomes. Concurrent AF and sinus node disease often manifests as the tachy-brady syndrome wherein the underlying sinus node dysfunction can pose a challenge to AF management. Similarly, the combination of AF and left bundle branch block increases mortality in individuals with co-existent heart failure and hampers effective delivery of cardiac resynchronization therapy. A thorough understanding of the therapeutic interventions available for these conditions, including the role of catheter ablation and permanent pacemaker programming, is crucial for optimal management in affected patients.

show abstract

Sinus node revisited

Abstract: Ongoing research with improved technology and techniques continues to unravel new understandings and challenges to the century old discovery of the anatomical sinus node.

Cited by 16 publications

References 54 publications

Reducing Risk of Dementia in AF—Is Oral Anticoagulation the Key?

Reducing Risk of Dementia in AF—Is Oral Anticoagulation the Key?

Increasing T‐type calcium channel activity by β‐adrenergic stimulation contributes to β‐adrenergic regulation of heart rates

Atrial fibrillation and conduction system disease: the roles of catheter ablation and permanent pacing

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