Sinus Node Dysfunction

Benditt, David G.; Sakaguchi, Scott; Lurie, Keith G.; Lü, Fei

doi:10.1007/978-1-84628-715-2_93

Cited by 4 publications

(9 citation statements)

References 104 publications

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“…This form of arrhythmia or dysrhythmia is due to an abnormal delay in the firing of the SA node and manifests as blocked p-waves and alternating runs of bradycardia followed by tachycardia; this can increase the risk of escape beats and cardiac insufficiency in humans. Interestingly, some of the causes behind this phenomenon include an increase in vagal tone and airway irritation which leads to dyspneic breathing and airway spasm, both of which were observed in our animals (Benditt et al 2007; Haqqani and Kalman 2007).…”

Section: Discussionmentioning

confidence: 64%

Comparative Cardiopulmonary Effects of Particulate Matter- And Ozone-Enhanced Smog Atmospheres in Mice

Hazari

Stratford

Krantz

et al. 2018

Environ. Sci. Technol.

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This study was conducted to compare the cardiac effects of particulate matter (PM)- (SA-PM) and ozone(O)-enhanced (SA-O) smog atmospheres in mice. Based on our previous findings of filtered diesel exhaust we hypothesized that SA-O would cause greater cardiac dysfunction than SA-PM. Radiotelemetered mice were exposed to either SA-PM, SA-O, or filtered air (FA) for 4 h. Heart rate (HR) and electrocardiogram were recorded continuously before, during and after exposure. Both SA-PM and SA-O increased heart rate variability (HRV) but only SA-PM increased HR. Normalization of responses to total hydrocarbons, gas-only hydrocarbons and PM concentration were performed to assess the relative contribution of each phase given the compositional variability. Normalization to PM concentration revealed that SA-O was more potent in increasing HRV, arrhythmogenesis, and causing ventilatory changes. However, there were no differences when the responses were normalized to total or gas-phase only hydrocarbons. Thus, this study demonstrates that a single exposure to smog causes cardiac effects in mice. Although the responses of SA-PM and SA-O are similar, the latter is more potent in causing electrical disturbances and breathing changes potentially due to the effects of irritant gases, which should therefore be accounted for more rigorously in health assessments.

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Section: Discussionmentioning

confidence: 64%

Comparative Cardiopulmonary Effects of Particulate Matter- And Ozone-Enhanced Smog Atmospheres in Mice

Hazari

Stratford

Krantz

et al. 2018

Environ. Sci. Technol.

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“…La evolución de los pacientes con DNS es variable e impredecible. Los pacientes con antecedentes de síncope pueden presentar síncopes recurrentes (10) . La aparición de un bloqueo AV completo y de arritmias ventriculares malignas asociadas a los episodios de bradicardia es relativamente baja (2) .…”

Section: Figuraunclassified

“…La incidencia de muerte súbita parece ser baja también y el tratamiento con marcapasos no mejora la supervivencia total, aunque mejora notablemente los síntomas y la calidad de vida. Además, permite utilizar fármacos para el manejo de las taquiarritmias (2,7,10) .…”

Section: Figuraunclassified

“…Actualmente se denomina disfunción del nódulo sinusal (DNS) a esta entidad nosológica. Los pacientes con este trastorno son a menudo añosos (aunque algunas publicaciones describen una distribución bimodal) y en general presentan otras comorbilidades (6)(7)(8)(9)(10) .…”

Section: Introductionunclassified

“…Los pacientes a menudo buscan atención médica con síntomas de aturdimiento, presíncope, síncope y, en pacientes con periodos alternantes de bradicardia y taquicardia, palpitaciones u otros síntomas asociados con una frecuencia cardíaca rápida (3)(4)(5) . Debido a que los síntomas pueden ser de naturaleza variable, inespecíficos y frecuentemente transitorios, a veces puede ser difícil establecer esta relación síntomaalteración electrocardiográfica (8)(9)(10) . Los hallazgos electrocardiográficos típicos son uno o más episodios de bradicardia sinusal extrema (Rubenstein Tipo I), o pausas sinusales, paro y bloqueo de salida sinoatrial (Rubenstein Tipo II), o episodios de bradicardia y/o pausas alternantes con taquiarritmias auriculares (Rubenstein Tipo III) (2) .…”

Section: Introductionunclassified

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Conceptos actuales sobre la clasificación clínica y alteraciones electrofisiológicas en la disfunción del nódulo sinusal

Alderete

Centurión

2018

Mem. Inst. Investig. Cienc. Salud

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WITHDRAWN: Caveolar Compartmentalization is Required for Stable Rhythmicity of Sinus Nodal Cells and is Disrupted in Heart Failure

Lang,

Ni,

Medvedev

et al. 2024

Preprint

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Background: Heart rhythm relies on complex interactions between the electrogenic membrane proteins and intracellular Ca2+ signaling in sinoatrial node (SAN) myocytes; however, the mechanisms underlying the functional organization of the proteins involved in SAN pacemaking and its structural foundation remain elusive. Caveolae are nanoscale, plasma membrane pits that compartmentalize various ion channels and transporters, including those involved in SAN pacemaking, via binding with the caveolin-3 scaffolding protein, however the precise role of caveolae in cardiac pacemaker function is unknown. Our objective was to determine the role of caveolae in SAN pacemaking and dysfunction (SND). Methods: In vivo electrocardiogram monitoring, ex vivo optical mapping, in vitro confocal Ca2+ imaging, immunofluorescent and electron microscopy analysis were performed in wild type, cardiac-specific caveolin-3 knockout, and 8-weeks post-myocardial infarction heart failure (HF) mice. SAN tissue samples from donor human hearts were used for biochemical studies. We utilized a novel 3-dimensional single SAN cell mathematical model to determine the functional outcomes of protein nanodomain-specific localization and redistribution in SAN pacemaking. Results: In both mouse and human SANs, caveolae compartmentalized HCN4, Cav1.2, Cav1.3, Cav3.1 and NCX1 proteins within discrete pacemaker signalosomes via direct association with caveolin-3. This compartmentalization positioned electrogenic sarcolemmal proteins near the subsarcolemmal sarcoplasmic reticulum (SR) membrane and ensured fast and robust activation of NCX1 by subsarcolemmal local SR Ca2+ release events (LCRs), which diffuse across ~15-nm subsarcolemmal cleft. Disruption of caveolae led to the development of SND via suppression of pacemaker automaticity through a 50% decrease of the L-type Ca2+ current, a negative shift of the HCN current (If) activation curve, and 40% reduction of Na+/Ca2+-exchanger function. These changes significantly decreased the SAN depolarizing force, both during diastolic depolarization and upstroke phase, leading to bradycardia, sinus pauses, recurrent development of SAN quiescence, and significant increase in heart rate lability. Computational modeling, supported by biochemical studies, identified NCX1 redistribution to extra-caveolar membrane as the primary mechanism of SAN pauses and quiescence due to the impaired ability of NCX1 to be effectively activated by LCRs and trigger action potentials. HF remodeling mirrored caveolae disruption leading to NCX1-LCR uncoupling and SND. Conclusions: SAN pacemaking is driven by complex protein interactions within a nanoscale caveolar pacemaker signalosome. Disruption of caveolae leads to SND, potentially representing a new dimension of SAN remodeling and providing a newly recognized target for therapy.

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Sinus Node Dysfunction

Cited by 4 publications

References 104 publications

Comparative Cardiopulmonary Effects of Particulate Matter- And Ozone-Enhanced Smog Atmospheres in Mice

Comparative Cardiopulmonary Effects of Particulate Matter- And Ozone-Enhanced Smog Atmospheres in Mice

Conceptos actuales sobre la clasificación clínica y alteraciones electrofisiológicas en la disfunción del nódulo sinusal

WITHDRAWN: Caveolar Compartmentalization is Required for Stable Rhythmicity of Sinus Nodal Cells and is Disrupted in Heart Failure

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