Electrophysiology of normal sinus node with and without autonomic blockade.

Alboni, Paoló; Malcarne, C; Pedroni, P.; Masoni, A; Narula, Onkar S.

doi:10.1161/01.cir.65.6.1236

Cited by 84 publications

(12 citation statements)

References 31 publications

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“…Altered activity of A 1 AR could contribute to the differences in intrinsic heart rate recorded in vivo in the presence of atropine and ␤-adrenoreceptor blockers (1,15,16). Further studies may determine whether these findings in a mouse model with high-level overexpression of A 1 AR can be reproduced in conditions that are closer to human physiology.…”

Section: Discussionmentioning

confidence: 99%

Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A₁ adenosine receptor

Kirchhof

Fabritz²,

Fortmüller³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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. Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A1 adenosine receptor. Am J Physiol Heart Circ Physiol 285: H145-H153, 2003. First published March 13, 2003 10.1152/ ajpheart.01036.2002To investigate whether altered function of adenosine receptors could contribute to sinus node or atrioventricular (AV) nodal dysfunction in conscious mammals, we studied transgenic (TG) mice with cardiac-specific overexpression of the A 1 adenosine receptor (A1AR). A Holter ECG was recorded in seven freely moving littermate pairs of mice during normal activity, exercise (5 min of swimming), and 1 h after exercise. TG mice had lower maximal heart rates (HR) than wild-type (WT) mice (normal activity: 437 Ϯ 18 vs. 522 Ϯ 24 beats/min, P Ͻ 0.05; exercise: 650 Ϯ 13 vs. 765 Ϯ 28 beats/min, P Ͻ 0.05; 1 h after exercise: 588 Ϯ 18 vs. 720 Ϯ 12 beats/min, P Ͻ 0.05; all values are means Ϯ SE). Mean HR was lower during exercise (589 Ϯ 16 vs. 698 Ϯ 34 beats/min, P Ͻ 0.05) and after exercise (495 Ϯ 16 vs. 592 Ϯ 27 beats/min, P Ͻ 0.05). Minimal HR was not different between genotypes. HR variability (SD of RR intervals) was reduced by 30% (P Ͻ 0.05) in TG compared with WT mice. Pertussis toxin (n ϭ 4 pairs, 150 g/kg ip) reversed bradycardia after 48 h. TG mice showed first-degree AV nodal block (PQ interval: 42 Ϯ 2 vs. 37 Ϯ 2 ms, P Ͻ 0.05), which was diminished but not abolished by pertussis toxin. Isolated Langendorffperfused TG hearts developed spontaneous atrial arrhythmias (3 of 6 TG mice vs. 0 of 9 WT mice, P Ͻ 0.05). In conclusion, A 1AR regulate sinus nodal and AV nodal function in the mammalian heart in vivo. Enhanced expression of A 1AR causes sinus nodal and AV nodal dysfunction and supraventricular arrhythmias. heart rate regulation; autonomous nervous system; heart rate variability; sinus node dysfunction; atrioventricular block; atrial fibrillation

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Section: Discussionmentioning

confidence: 99%

Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A₁ adenosine receptor

Kirchhof

Fabritz²,

Fortmüller³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…The sensitivity of IHRp is very low for diagnosing sinus node dysfunction. Initially the same dosages were used for distinguishing between intrinsic and extrinsic sinus node dysfunction when assessing sinus node recovery time [164,165] , and later modified to 75% by Tonkin et al [166] . From a diagnostic point of view it seems sufficient to use propranolol 0·1 mg .…”

Section: Task Force Report 1273mentioning

confidence: 99%

Guidelines on management (diagnosis and treatment) of syncope

Brignole¹,

Alboni²,

Benditt

et al. 2001

European Heart Journal

680

432

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“…40 cSNRT is defined as the interval between the last paced beat and the next spontaneous beat, minus the spontaneous cycle length. 41 A longer cSNRT indicates an increased tendency for suppression by ectopic activity from outside the SAN.…”

Section: Diseases Of the Sinoatrial Nodementioning

confidence: 99%

Biology of the Sinus Node and its Disease

Choudhury

Boyett

Morris

2015

Arrhythmia &Amp; Electrophysiology Review

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The sinoatrial or sinus node (SAN) is the heart's natural pacemaker.Located in the superior right atrium, it automatically produces cyclical electrical activity to initiate each heartbeat in normal sinus rhythm. SAN dysfunction (SND) in humans, also known as 'sick sinus syndrome', can manifest as pathological bradycardia and asystolic pauses. As a result, SND can lead to symptoms of reduced cerebral perfusion such as dizziness and syncope.However, early SND may be latent and individuals may remain asymptomatic. Implantable electronic pacemakers are currently the only effective treatment. SND is the most common reason to have a pacemaker implanted, the indication for 27.5 % of all pacemakers implanted in the UK. 1 The prevalence of SND in the UK is around 0.03 % affecting all ages, but it is much more common in the elderly population. The aetiology of SND can be intrinsic, extrinsic or often a mixture of the two. One retrospective study of 277 patients presenting to the emergency department with compromising bradycardia showed that 51 % of cases were attributable to a treatable extrinsic cause such as an adverse drug reaction, electrolyte imbalance or acute myocardial infarction. The other 49 % were assumed to be intrinsic or 'idiopathic'. The pathophysiology of 'idiopathic' SND is still not clearly understood.Historically it is attributed to fibrosis and cell senescence and this is often still quoted today. 4,5 However, contemporary evidence suggests that electrical remodelling of molecular pacemaking mechanisms such as membrane ion channels and intracellular Ca 2+ cycling are important factors in SND. 6 In this article we summarise the mechanisms of SAN function and review the current evidence surrounding the pathophysiology of SND. Development of the Sinoatrial NodeThe SAN is the uppermost part of the cardiac conduction system (CCS), a chain of specialised tissue that directs electrical impulses through the heart and thus co-ordinates the way it contracts. The CCS is defined by a specific pattern of gene expression, differing to the surrounding 'working myocardium'. During early embryogenesis as the heart tube forms, mesodermal cells quickly multiply and differentiate into working cardiomyocytes capable of contraction and fast conduction.7 However, the CCS is derived from primary myocardium that is instead led down a different lineage directed by specific transcription factors (Figure 1). 7Tbx3 is a T-box transcription factor found selectively within the CCS.Transgenic mice have been used to demonstrate its role in repressing working myocardial development and promoting a pacemaker programme of genes.8 These include key pacemaker genes, such as those encoding the low conductance gap junction connexin (Cx)45 and the hyperpolarisation-activated cyclic nucleotide-gated (HCN) membrane ion channel. 8,9 The function of HCN channels within the SAN is discussed below.The SAN is derived from an area of the developing CCS called the sinus venosus. The sinus venosus expresses a homeobox regulatory gene named Shox2.10 Sho...

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Electrophysiology of normal sinus node with and without autonomic blockade.

Abstract: The purpose of the present study was to determine the normal intrinsic SN function in the absence of autonomic influences. Therefore, in addition to the in-

Cited by 84 publications

References 31 publications

Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A₁ adenosine receptor

Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A₁ adenosine receptor

Guidelines on management (diagnosis and treatment) of syncope

Biology of the Sinus Node and its Disease

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