Alterations in subsidiary pacemaker function after prolonged subsidiary pacemaker dominance in the canine right atrium

Rozanski, George J.; Lipsius, Stephen L.; Randall, Walter C.; Jones, Stephen B.

doi:10.1016/s0735-1097(84)80098-4

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…At 10 weeks and 6 months, the remapped 0 points were shifted slightly toward the vicinity of the edge of the lased area suggesting an origin from the caudal sinoatrial node. This differed from the findings of Rozanski et al 33 Under different experimental conditions, they found that atrial pacemakers emerging soon after removal of the sinoatrial node were the same that ultimately controlled the heart.…”

Section: Short-term Effects Of Lasingcontrasting

confidence: 99%

Modification of sinus node function by epicardial laser irradiation in dogs.

et al. 1990

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This study tested the feasibility of neodymium:YAG laser photocoagulation of selected sinus node areas to depress sinus rate responsiveness. In 14 open-chest dogs, origin of the sinus impulse (0 point) was electrically mapped from the epicardium before and during isoproterenol infusion. Epicardial laser photocoagulation was applied to the 0 point observed during isoproterenol infusion and stepwise to remapped new 0 points until a 30±5% decrease in heart rate occurred. Long-term effects were assessed by Holter monitoring and electropharmacologic testing preoperatively and up to 10 weeks or 6 months. Mean (± SEM) percent decreases were observed at 10 weeks in the following parameters: average 24-hour heart rate, 17.4+±5.0%; maximum heart rate on Holter, 30.5+±3.5%; heart rate during pharmacologic autonomic blockade, 32.7±3.5%; and maximum heart rate on isoproterenol, 23.1±4.6% (all p<0.01). Curves with pacemaker recovery time plotted against control cycle length remained unchanged. Holter monitoring did not show excessive bradycardic episodes even after administration of propranolol. In three control dogs (sham operation), sinus node function remained unchanged. Histologic study of the irradiated area showed replacement by inflammatory cells, fibrosis, and cartilage formation with surrounding normal cells and occasional cells resembling pacemakerlike cells at the caudal end of the sinoatrial node. This study suggests that 1) map-guided graded laser photocoagulation of sinus node regions showing earliest activation during catecholamine stimulation successfully limits maximum heart rates without causing significant bradycardia, 2) the effects are long lasting, and 3) the remaining pacemaker behaves like the sinus node. Laser modification of sinus node function could become a form of nonpharmacologic heart rate control in patients with coronary artery disease undergoing surgery and in the syndrome of inappropriate sinus tachycardia. (Circulation 1990;81:350-359) P harmacologic control of excessive sinus tachycardia in humans is occasionally limited by side effects inherent to the drugs used, patient intolerance, or treatment failure related to the nature of the disease.12 Therapeutic options for severe cases of drugresistant sinus tachycardia today include total surgical exclusion of the sinus node region or cryosurgical ablation.34 Both procedures usually result in atrial or Supported by grants from the Heineman Medical Research Center of Charlotte, NC, Inc, and HL-30558-06 from the National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, Maryland.Address for correspondence: Laszlo Littmann, MD, Laser and Applied Technologies Laboratory, Carolinas Heart Institute, PO Box 32861, Charlotte, NC 28232.Received April 11, 1989; revision accepted September 13, 1989. atrioventricular junctional escape rhythms and necessitate implantation of a permanent pacemaker. The functional anatomy of the sinus node region in humans and dogs is unique in that it shows widespread distribution and rate differ...

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Section: Short-term Effects Of Lasingcontrasting

confidence: 99%

Modification of sinus node function by epicardial laser irradiation in dogs.

et al. 1990

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“…In six experimental goats with successful ablation, five SAP tissues clustered along the caudal part of the CT adjacent to the IVC. These data would confirm previous similar findings in rat and dog, as well as being similar to the leading pacemaker site in humans with SND (Rozanski et al, 1984;Sanders et al, 2004;Morris et al, 2013).…”

Section: Subsidiary Pacemaker Regionssupporting

confidence: 92%

“…SAP tissue is functionally distinct from the SAN and it gives rise to a slower resting and exertional HR (Ardell et al, 1991). Over time, these differences subside and the SAP pacemaker becomes functionally more similar to the native SAN (Rozanski et al, 1984;Kalman et al, 1995).…”

Section: Subsidiary Pacemaker Regionsmentioning

confidence: 99%

Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease

et al. 2021

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BackgroundThe sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases.MethodsA goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques.ResultsWhen the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT).ConclusionsSAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker.

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“…Indeed, spontaneously beating cells can be isolated from the right atrium (408,427) and from the bundle branches of the mouse heart (Mangoni, unpublished observations). Automatic cells are also present around the tricuspid valve (11).…”

Section: Pacemaker Shift and Extranodal Supraventricular Automaticitymentioning

confidence: 99%

Genesis and Regulation of the Heart Automaticity

Mangoni

Nargeot²

2008

Physiological Reviews

508

565

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The heart automaticity is a fundamental physiological function in higher organisms. The spontaneous activity is initiated by specialized populations of cardiac cells generating periodical electrical oscillations. The exact cascade of steps initiating the pacemaker cycle in automatic cells has not yet been entirely elucidated. Nevertheless, ion channels and intracellular Ca(2+) signaling are necessary for the proper setting of the pacemaker mechanism. Here, we review the current knowledge on the cellular mechanisms underlying the generation and regulation of cardiac automaticity. We discuss evidence on the functional role of different families of ion channels in cardiac pacemaking and review recent results obtained on genetically engineered mouse strains displaying dysfunction in heart automaticity. Beside ion channels, intracellular Ca(2+) release has been indicated as an important mechanism for promoting automaticity at rest as well as for acceleration of the heart rate under sympathetic nerve input. The potential links between the activity of ion channels and Ca(2+) release will be discussed with the aim to propose an integrated framework of the mechanism of automaticity.

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Alterations in subsidiary pacemaker function after prolonged subsidiary pacemaker dominance in the canine right atrium

Cited by 11 publications

References 18 publications

Modification of sinus node function by epicardial laser irradiation in dogs.

Modification of sinus node function by epicardial laser irradiation in dogs.

Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease

Genesis and Regulation of the Heart Automaticity

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