[Sinus rhythm: mechanisms and function].

PubMed

Lerebours, Guy

2007-01-01

The normal cardiac rhythm originates in a specialized region of the heart, the sinus node that is part of the nodal tissue. The rhythmic, impulse initiation of sinus node pacemaker cells results from a spontaneous diastolic depolarization that is initiated immediately after repolarization of the preceding actions potential. This slow diastolic depolarisation is typical of automatic cells and essential to their function. Several currents are involved in this diastolic depolarisation: a hyperpolarization activated inward current, termed "pacemaker" I(f) current, two Ca2+ currents (a L type and a T type), a delayed K+ current and a Na/Ca exchange current. The frequency of the automatic discharge is the main determinant of heart rate. However the sinus node activity is regulated by adrenergic and cholinergic neurotransmitters. Acetylcholine provokes the hyperpolarization of pacemaker cells and decreases the speed of the spontaneous diastolic depolarisation, thus slowing the sinus rate. Catecholamines lead to sinus tachycardia by increasing the diastolic depolarisation speed. In normal conditions, the observed resting heart rate is lower than the intrinsic frequency of the sinus node due to a "predominance" of the vagal tone. Neural regulation of the heart rate aims at meeting the metabolic needs of the tissues through a varying blood flow. Differences between diurnal and nocturnal mean heart rates are accounted for by neural influences. During the night, the increased vagal tone results in decreased heart rate. The exercise-induced tachycardia results from the sympathetic stimulation. It allows more blood to reach skeletal muscles, and as a consequence an increased supply of oxygen and nutrients. Compared to the variety of clinical arrhythmias, sinus rhythm is the basis for optimal exercise capacity and quality of life.

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

PubMed Central

Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

2016-01-01

The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca2+-activated K+ channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity. PMID:26725737

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.

PubMed

Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

2016-01-01

The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

Clear cell hidradenocarcinoma developing in pacemaker pocket.

PubMed

Reyes, Cesar V

2008-11-01

An octagenerian woman developed clear cell hidradenocarcinoma, a rare neoplasm of eccrine sweat gland origin, 4 years following pacemaker implantation in her right lateral chest. The tumor immunohistochemically mimicked a metastatic lobular breast carcinoma, for example, strongly positive estrogen, weakly positive progesterone, and weakly reactive mammoglobin. A complete surgical excision of the tumor was complemented with ipsilateral dissection of involved adjacent axillary lymph nodes. Recommended irradiation was refused by the patient. Retrospective 3-year mammogram review, 2-year postsurgery follow-up, and complete postmortem evaluation failed to prove a primary breast malignancy or other metastatic lesion elsewhere.

[Temporary Pacemakers - Step by Step].

PubMed

Graf, Matthias; Stiller, Patrick; Karch, Martin

2018-06-01

Symptomatic bradycardia is usually caused by abnormalities of atrioventricular conduction or sinus node dysfunction. Reversible and irreversible causes must be considered.Temporary pacemakers are used in the emergency treatment in case of severe bradyarrhythmia.They help to bridge the acute phase until spontaneous restoration of atrioventricular or sinus node function or -if spontaneous restoration fails- until a permanent pacemaker system was implanted.In the following article we discuss the commonly used temporary pacemaker systems. We demonstrate their use and correct programming by an illustrated step by step explanation. For troubleshooting a flow chart was added. © Georg Thieme Verlag KG Stuttgart · New York.

Pheochromocytoma-Induced Atrial Tachycardia Leading to Cardiogenic Shock and Cardiac Arrest: Resolution with Atrioventricular Node Ablation and Pacemaker Placement

PubMed Central

Bajaj, Mandeep; Cunningham, Glenn R.

2014-01-01

Pheochromocytoma should be considered in young patients who have acute cardiac decompensation, even if they have no history of hypertension. Atrioventricular node ablation and pacemaker placement should be considered for stabilizing pheochromocytoma patients with cardiogenic shock due to atrial tachyarrhythmias. A 38-year-old black woman presented with cardiogenic shock (left ventricular ejection fraction, <0.15) that did not respond to the placement of an intra-aortic balloon pump. A TandemHeart® Percutaneous Ventricular Assist Device was inserted emergently. After atrioventricular node ablation and placement of a temporary pacemaker, the TandemHeart was removed. Computed tomography of the abdomen revealed a pheochromocytoma. After placement of a permanent pacemaker, the patient underwent a right adrenalectomy. This is, to our knowledge, the first reported case of pheochromocytoma-induced atrial tachyarrhythmia that led to cardiogenic shock and cardiac arrest unresolved by the placement of 2 different ventricular assist devices, but that was completely reversed by radiofrequency ablation of the atrioventricular node and the placement of a temporary pacemaker. We present the patient's clinical, laboratory, and imaging findings, and we review the relevant literature. PMID:25593537

Heterogeneous expression of Ca(2+) handling proteins in rabbit sinoatrial node.

PubMed

Musa, Hanny; Lei, Ming; Honjo, Hauro; Jones, Sandra A; Dobrzynski, Halina; Lancaster, Mathew K; Takagishi, Yoshiko; Henderson, Zaineb; Kodama, Itsuo; Boyett, Mark R

2002-03-01

We investigated the densities of the L-type Ca(2+) current, i(Ca,L), and various Ca(2+) handling proteins in rabbit sinoatrial (SA) node. The density of i(Ca,L), recorded with the whole-cell patch-clamp technique, varied widely in sinoatrial node cells. The density of i(Ca,L) was significantly (p<0.001) correlated with cell capacitance (measure of cell size) and the density was greater in larger cells (likely to be from the periphery of the SA node) than in smaller cells (likely to be from the center of the SA node). Immunocytochemical labeling of the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger, sarcoplasmic reticulum Ca(2+) release channel (RYR2), and sarcoplasmic reticulum Ca(2+) pump (SERCA2) also varied widely in SA node cells. In all cases there was significantly (p<0.05) denser labeling of cells from the periphery of the SA node than of cells from the center. In contrast, immunocytochemical labeling of the Na(+)-K(+) pump was similar in peripheral and central cells. We conclude that Ca(2+) handling proteins are sparse and poorly organized in the center of the SA node (normally the leading pacemaker site), whereas they are more abundant in the periphery (at the border of the SA node with the surrounding atrial muscle).

Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

PubMed Central

Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

2013-01-01

In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats. PMID:24250786

Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats.

PubMed

Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

2013-01-01

In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of "metabolic syndrome rats", compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats.

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice

PubMed Central

Froese, Alexander; Breher, Stephanie S.; Waldeyer, Christoph; Schindler, Roland F.R.; Nikolaev, Viacheslav O.; Rinné, Susanne; Wischmeyer, Erhard; Schlueter, Jan; Becher, Jan; Simrick, Subreena; Vauti, Franz; Kuhtz, Juliane; Meister, Patrick; Kreissl, Sonja; Torlopp, Angela; Liebig, Sonja K.; Laakmann, Sandra; Müller, Thomas D.; Neumann, Joachim; Stieber, Juliane; Ludwig, Andreas; Maier, Sebastian K.; Decher, Niels; Arnold, Hans-Henning; Kirchhof, Paulus; Fabritz, Larissa; Brand, Thomas

2012-01-01

Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention. PMID:22354168

Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells.

PubMed

Schweizer, Patrick A; Darche, Fabrice F; Ullrich, Nina D; Geschwill, Pascal; Greber, Boris; Rivinius, Rasmus; Seyler, Claudia; Müller-Decker, Karin; Draguhn, Andreas; Utikal, Jochen; Koenen, Michael; Katus, Hugo A; Thomas, Dierk

2017-10-16

Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium. Subsequent culturing in a specified fetal bovine serum (FBS)-enriched cell medium produced a pacemaker-type phenotype that was studied in detail using quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and patch-clamp electrophysiology. Further investigations comprised pharmacological stimulations and co-culturing with neonatal cardiomyocytes. hiPSC co-cultured in a serum-free medium with the visceral endoderm-like cell line END-2 produced spontaneously beating clusters after 10-12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18 were abundantly expressed at this early developmental stage, while levels of sarcomeric gene products remained low. We observed that working-type cardiomyogenic differentiation can be suppressed by transfer of early clusters into a FBS-enriched cell medium immediately after beating onset. After 6 weeks under these conditions, sinoatrial node (SAN) hallmark genes remained at high levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low. Clusters were characterized by regular activity and robust beating rates (70-90 beats/min) and were triggered by spontaneous Ca 2+ transients recapitulating calcium clock properties of genuine pacemaker cells. They were responsive to adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular myocytes in co-culture experiments. Action potential (AP) measurements of cells individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%) AP morphologies, while ventricular AP configurations were not observed. We provide a novel culture media-based, transgene-free approach for targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters and offer the potential for disease modeling, drug testing, and individualized cell-based replacement therapy of the SAN.

Sick Sinus Syndrome

MedlinePlus

... rhythm problems (arrhythmias) in which the heart's natural pacemaker (sinus node) doesn't work properly. The sinus ... people with sick sinus syndrome eventually need a pacemaker to keep the heart in a regular rhythm. ...

Sick sinus syndrome

MedlinePlus

... the heart (atria). This area is the heart's pacemaker. It may be called the sinoatrial node, sinus ... do so. You may need a permanent implanted pacemaker if your symptoms are related to bradycardia (slow ...

Acute desensitization of acetylcholine and endothelin-1 activated inward rectifier K+ current in myocytes from the cardiac atrioventricular node.

PubMed

Choisy, Stéphanie C M; James, Andrew F; Hancox, Jules C

2012-07-06

The atrioventricular node (AVN) is a vital component of the pacemaker-conduction system of the heart, co-ordinating conduction of electrical excitation from cardiac atria to ventricles and acting as a secondary pacemaker. The electrical behaviour of the AVN is modulated by vagal activity via activation of muscarinic potassium current, IKACh. However, it is not yet known if this response exhibits 'fade' or desensitization in the AVN, as established for the heart's primary pacemaker--the sinoatrial node. In this study, acute activation of IKACh in rabbit single AVN cells was investigated using whole-cell patch clamp at 37 °C. 0.1-1 μM acetylcholine (ACh) rapidly activated a robust IKACh in AVN myocytes during a descending voltage-ramp protocol. This response was inhibited by tertiapin-Q (TQ; 300 nM) and by the M2 muscarinic ACh receptor antagonist AFDX-116 (1 μM). During sustained ACh exposure the elicited IKACh exhibited bi-exponential fade (τf of 2.0 s and τs 76.9 s at -120 mV; 1 μM ACh). 10 nM ET-1 elicited a current similar to IKACh, which faded with a mono-exponential time-course (τ of 52.6 s at -120 mV). When ET-1 was applied following ACh, the ET-1 activated response was greatly attenuated, demonstrating that ACh could desensitize the response to ET-1. For neither ACh nor ET-1 was the rate of current fade dependent upon the initial response magnitude, which is inconsistent with K+ flux mediated changes in electrochemical driving force as the underlying mechanism. Collectively, these findings demonstrate that TQ sensitive inwardly rectifying K+ current in cardiac AVN cells, elicited by M2 muscarinic receptor or ET-1 receptor activation, exhibits fade due to rapid desensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

Remodeling of sinus node function after catheter ablation of right atrial flutter.

PubMed

Daoud, Emile G; Weiss, Raul; Augostini, Ralph S; Kalbfleisch, Steven J; Schroeder, Jason; Polsinelli, Georgia; Hummel, John D

2002-01-01

The purpose of this study was to investigate the effect of ablation of right atrial flutter upon sinus node function in humans. This study enrolled 35 patients. Twenty-four patients (16 men and 8 women; age 68 +/- 11 years) were referred for ablation of persistent atrial flutter (duration 8 +/- 11 months). After ablation, there was abnormal sinus node function defined as a corrected sinus node recovery time (CSNRT) > or = 550 msec. The control group consisted of 11 patients who were undergoing pacemaker implantation for sinus node disease but did not have a history of atrial dysrhythmias or ablation. Within 24 hours of ablation or pacemaker implantation, baseline maximal CSNRT was measured through a permanent pacemaker by AAI pacing at six cycle lengths: 600, 550, 500, 450, 400, and 350 msec. CSNRT then was measured in the same manner at 48 hours, 14 days, and 3 months after ablation/pacemaker implantation. P wave amplitude and duration, and percent atrial sensing also were assessed at the same intervals. For patients undergoing atrial flutter ablation, there was progressive temporal recovery of CSNRT (1,204 +/- 671 msec at baseline vs 834 +/- 380 msec at 3 months; P < 0.001) and a significant increase in the percent atrial sensing and P wave amplitude at 3 months compared with baseline (P < 0.001). In control subjects, there was no change in the CSNRT, percent atrial pacing, or P wave amplitude. After ablation of persistent atrial flutter, there is temporal recovery of CSNRT and increase in spontaneous atrial activity. These findings suggest that atrial flutter induces reversible changes in sinus node function.

Recovery of Ventriculo-Atrial Conduction after Adrenaline in Patients Implanted with Pacemakers.

PubMed

Cismaru, Gabriel; Gusetu, Gabriel; Muresan, Lucian; Rosu, Radu; Andronache, Marius; Matuz, Roxana; Puiu, Mihai; Mester, Petru; Miclaus, Maria; Pop, Dana; Mircea, Petru Adrian; Zdrenghea, Dumitru

2015-07-01

Ventriculo-atrial (VA) conduction can have negative consequences for patients with implanted pacemakers and defibrillators. There is concern whether impaired VA conduction could recover during stressful situations. Although the influence of isoproterenol and atropine are well established, the effect of adrenaline has not been studied systematically. The objective of this study was to determine if adrenaline can facilitate recovery of VA conduction in patients implanted with pacemakers. A prospective study was conducted on 61 consecutive patients during a 4-month period (April-July 2014). The presence of VA conduction was assessed during the pacemaker implantation procedure. In case of an impaired VA conduction, adrenaline infusio was used as a stress surrogate to test conduction recovery. The indications for pacemaker implantation were: sinus node dysfunction in 18 patients, atrioventricular (AV) block in 40 patients, binodal dysfunction (sinus node+ AV node) in two patients and other (carotid sinus syndrome) in one patient. In the basal state, 15/61 (24.6%) presented spontaneous VA conduction and 46/61 (75.4%) had no VA conduction. After administration of adrenaline, there was VA conduction recovery in 5/46 (10.9%) patients. Adrenaline infusion produced recovery of VA conduction in 10.9% of patients with absent VA conduction in a basal state. Recovery of VA conduction during physiological or pathological stresses could be responsible for the pacemaker syndrome, PMT episodes, or certain implantable cardiac defibrillator detection issues. © 2015 Wiley Periodicals, Inc.

Morpho-functional characterization of the systemic venous pole of the reptile heart.

PubMed

Jensen, Bjarke; Vesterskov, Signe; Boukens, Bastiaan J; Nielsen, Jan M; Moorman, Antoon F M; Christoffels, Vincent M; Wang, Tobias

2017-07-27

Mammals evolved from reptile-like ancestors, and while the mammalian heart is driven by a distinct sinus node, a sinus node is not apparent in reptiles. We characterized the myocardial systemic venous pole, the sinus venosus, in reptiles to identify the dominant pacemaker and to assess whether the sinus venosus remodels and adopts an atrium-like phenotype as observed in mammals. Anolis lizards had an extensive sinus venosus of myocardium expressing Tbx18. A small sub-population of cells encircling the sinuatrial junction expressed Isl1, Bmp2, Tbx3, and Hcn4, homologues of genes marking the mammalian sinus node. Electrical mapping showed that hearts of Anolis lizards and Python snakes were driven from the sinuatrial junction. The electrical impulse was delayed between the sinus venosus and the right atrium, allowing the sinus venosus to contract and aid right atrial filling. In proximity of the systemic veins, the Anolis sinus venosus expressed markers of the atrial phenotype Nkx2-5 and Gja5. In conclusion, the reptile heart is driven by a pacemaker region with an expression signature similar to that of the immature sinus node of mammals. Unlike mammals, reptiles maintain a sinuatrial delay of the impulse, allowing the partly atrialized sinus venosus to function as a chamber.

Mechanism underlying impaired cardiac pacemaking rhythm during ischemia: A simulation study

NASA Astrophysics Data System (ADS)

Bai, Xiangyun; Wang, Kuanquan; Yuan, Yongfeng; Li, Qince; Dobrzynski, Halina; Boyett, Mark R.; Hancox, Jules C.; Zhang, Henggui

2017-09-01

Ischemia in the heart impairs function of the cardiac pacemaker, the sinoatrial node (SAN). However, the ionic mechanisms underlying the ischemia-induced dysfunction of the SAN remain elusive. In order to investigate the ionic mechanisms by which ischemia causes SAN dysfunction, action potential models of rabbit SAN and atrial cells were modified to incorporate extant experimental data of ischemia-induced changes to membrane ion channels and intracellular ion homeostasis. The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-atrium. Using the multi-scale models, the functional impact of ischemia-induced electrical alterations on cardiac pacemaking action potentials (APs) and their conduction was investigated. The effects of vagal tone activity on the regulation of cardiac pacemaker activity in control and ischemic conditions were also investigated. The simulation results showed that at the cellular level ischemia slowed the SAN pacemaking rate, which was mainly attributable to the altered Na+-Ca2+ exchange current and the ATP-sensitive potassium current. In the 2D SAN-atrium tissue model, ischemia slowed down both the pacemaking rate and the conduction velocity of APs into the surrounding atrial tissue. Simulated vagal nerve activity, including the actions of acetylcholine in the model, amplified the effects of ischemia, leading to possible SAN arrest and/or conduction exit block, which are major features of the sick sinus syndrome. In conclusion, this study provides novel insights into understanding the mechanisms by which ischemia alters SAN function, identifying specific conductances as contributors to bradycardia and conduction block.

Morphological study of the innervation pattern of the rabbit sinoatrial node

NASA Technical Reports Server (NTRS)

Roberts, L. A.; Slocum, G. R.; Riley, D. A.

1989-01-01

The pattern of sinoatrial (SA) node innervations in rabbit was elucidated using a newly developed highly reproducible cholinesterase/silver impregnation staining procedure which made it possible to delineate large nerves, fine processes, and ganglion cells. The SA node and dominant pacemaker sites were identified by microelectrode recording. A generalized pattern of innnervation was recognized, which includes a large ganglionic complex inferior to the SA node; two or more moderately large nerves traversing the SA node parallel to the crista terminalis; nerves entering the intercaval region from the septum, the superior vena cava, and the inferior vena cava to impinge on the SA node; and a fine network of nerve processes, which was particularly dense in the SA node. From the location and distribution of the nerves and ganglionic branches, it can be inferred that the neural network in the intercaval region is capable of performing complex modulatory and integrative functions among the structures within this region.

Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart.

PubMed

Herrmann, Stefan; Layh, Beate; Ludwig, Andreas

2011-12-01

HCN pacemaker channels (I(f) channels) are believed to contribute to important functions in the heart; thus these channels became an attractive target for generating transgenic mouse mutants to elucidate their role in physiological and pathophysiological cardiac conditions. A full understanding of cardiac I(f) and the interpretation of studies using HCN mouse mutants require detailed information about the expression profile of the individual HCN subunits. Here we investigate the cardiac expression pattern of the HCN isoforms at the mRNA as well as at the protein level. The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals. We find a low, but highly differential HCN expression profile outside the cardiac conduction pathway including left and right atria and ventricles. Additionally HCN distribution was investigated in tissue slices of the sinoatrial node, the atrioventricular node, the bundle of His and the bundle branches. The conduction system was marked by acetylcholine esterase staining. HCN4 was confirmed as the predominant isoform of the primary pacemaker followed by a distinct expression of HCN1. In contrast HCN2 shows only a confined expression to individual pacemaker cells. Immunolabeling of the AV-node reveals also a pronounced specificity for HCN1 and HCN4. Compared to the SN and AVN we found a low but selective expression of HCN4 as the only isoform in the atrioventricular bundle. However in the bundle branches HCN1, HCN4 and also HCN2 show a prominent and selective expression pattern. Our results display a characteristic distribution of individual HCN isoforms in several cardiac compartments and reveal that beside HCN4, HCN1 represents the isoform which is selectively expressed in most parts of the conduction system suggesting a substantial contribution of HCN1 to pacemaking. 2011 Elsevier Ltd. All rights reserved.

Characterization of a right atrial subsidiary pacemaker and acceleration of the pacing rate by HCN over-expression.

PubMed

Morris, Gwilym M; D'Souza, Alicia; Dobrzynski, Halina; Lei, Ming; Choudhury, Moinuddin; Billeter, Rudi; Kryukova, Yelena; Robinson, Richard B; Kingston, Paul A; Boyett, Mark R

2013-10-01

Although the right atrium (RA contains subsidiary atrial pacemaker (SAP) tissue that can take over from the sinoatrial node (SAN) in sick sinus syndrome (SSS), SAP tissue is bradycardic. Little is known about SAP tissue and one aim of the study was to characterize ion channel expression to obtain insight into SAP pacemaker mechanisms. A second aim was to determine whether HCN over-expression (a 'biopacemaker'-like strategy) can accelerate the pacemaker rate producing a pacemaker that is similar in nature to the SAN. SAP tissue was isolated from the rat and the leading pacemaker site was characterized. Cell size at the leading pacemaker site in the SAP was smaller than in the RA and comparable to that in the SAN. mRNA levels showed the SAP to be similar to, but distinct from, the SAN. For example, in the SAN and SAP, expression of Tbx3 and HCN1 was higher and Nav1.5 and Cx43 lower than in the RA. Organ-cultured SAP tissue beat spontaneously, but at a slower rate than the SAN. Adenovirus-mediated gene transfer of HCN2 and the chimeric protein HCN212 significantly increased the pacemaker rate of the SAP close to that of the native SAN, but HCN4 was ineffective. SAP tissue near the inferior vena cava is bradycardic, but shares characteristics with the SAN. Pacing can be accelerated by the over-expression of HCN2 or HCN212. This provides proof of concept for the use of SAP tissue as a substrate for biopacemaking in the treatment of SSS.

Pacemaker Use Following Heart Transplantation

PubMed Central

Mallidi, Hari R.; Bates, Michael

2017-01-01

Background: The incidence of permanent pacemaker implantation after orthotopic heart transplantation has been reported to be 2%-24%. Transplanted hearts usually exhibit sinus rhythm in the operating room following reperfusion, and most patients do not exhibit significant arrhythmias during the postoperative period. However, among the patients who do exhibit abnormalities, pacemakers may be implanted for early sinus node dysfunction but are rarely used after 6 months. Permanent pacing is often required for atrioventricular block. A different cohort of transplant patients presents later with bradycardia requiring pacemaker implantation, reported to occur in approximately 1.5% of patients. The objectives of this study were to investigate the indications for pacemaker implantation, compare the need for pacemakers following bicaval vs biatrial anastomosis, and examine the long-term outcomes of heart transplant patients who received pacemakers. Methods: For this retrospective, case-cohort, single-institution study, patients were identified from clinical research and administrative transplant databases. Information was supplemented with review of the medical records. Standard statistical techniques were used, with chi-square testing for categorical variables and the 2-tailed t test for continuous variables. Survival was compared with the use of log-rank methods. Results: Between January 1968 and February 2008, 1,450 heart transplants were performed at Stanford University. Eighty-four patients (5.8%) were identified as having had a pacemaker implanted. Of these patients, 65.5% (55) had the device implanted within 30 days of transplantation, and 34.5% (29) had late implantation. The mean survival of patients who had an early pacemaker implant was 6.4 years compared to 7.7 years for those with a late pacemaker implant (P<0.05). Sinus node dysfunction and heart block were the most common indications for pacemaker implantation. Starting in 1997, a bicaval technique was used for implantation. The incidence of pacemaker implantation by technique was 2.0% for bicaval and 9.1% for biatrial (P=0.001). Significantly more rejection episodes occurred in the pacemaker group (2.67 ± 2.18) compared with the no-pacemaker group (2.01 ± 2.05) (P<0.05). Conclusion: Our results show a decreased pacemaker need after bicaval anastomosis and that more patients who needed a pacemaker after transplantation had a pretransplant diagnosis of ischemic cardiomyopathy. In our cohort, the need for a permanent pacemaker was also associated with older donor grafts and an increase in the number of treated rejection episodes. PMID:28331443

Tachycardia-bradycardia syndrome: Electrophysiological mechanisms and future therapeutic approaches (Review)

PubMed Central

Tse, Gary; Liu, Tong; Li, Ka Hou Christien; Laxton, Victoria; Wong, Andy On-Tik; Chan, Yin Wah Fiona; Keung, Wendy; Chan, Camie W.Y.; Li, Ronald A.

2017-01-01

Sick sinus syndrome (SSS) encompasses a group of disorders whereby the heart is unable to perform its pacemaker function, due to genetic and acquired causes. Tachycardia-bradycardia syndrome (TBS) is a complication of SSS characterized by alternating tachycardia and bradycardia. Techniques such as genetic screening and molecular diagnostics together with the use of pre-clinical models have elucidated the electrophysiological mechanisms of this condition. Dysfunction of ion channels responsible for initiation or conduction of cardiac action potentials may underlie both bradycardia and tachycardia; bradycardia can also increase the risk of tachycardia, and vice versa. The mainstay treatment option for SSS is pacemaker implantation, an effective approach, but has disadvantages such as infection, limited battery life, dislodgement of leads and catheters to be permanently implanted in situ. Alternatives to electronic pacemakers are gene-based bio-artificial sinoatrial node and cell-based bio-artificial pacemakers, which are promising techniques whose long-term safety and efficacy need to be established. The aim of this article is to review the different ion channels involved in TBS, examine the three-way relationship between ion channel dysfunction, tachycardia and bradycardia in TBS and to consider its current and future therapies. PMID:28204831

Development of the cardiac pacemaker

PubMed Central

Liang, Xingqun; Evans, Sylvia M.

2017-01-01

The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome and sudden death. A better understanding of genes and signaling pathways that regulate SAN development and function is essential to develop more effective treatment to sinus arrhythmia, including biological pacemakers. In this review, we briefly summarize the key processes of SAN morphogenesis during development, and focus on the transcriptional network that drives SAN development. PMID:27770149

Feasibility and safety of adenosine cardiovascular magnetic resonance in patients with MR conditional pacemaker systems at 1.5 Tesla.

PubMed

Klein-Wiele, Oliver; Garmer, Marietta; Urbien, Rhyan; Busch, Martin; Kara, Kaffer; Mateiescu, Serban; Grönemeyer, Dietrich; Schulte-Hermes, Michael; Garbrecht, Marc; Hailer, Birgit

2015-12-22

Cardiovascular Magnetic Resonance (CMR) with adenosine stress is a valuable diagnostic tool in coronary artery disease (CAD). However, despite the development of MR conditional pacemakers CMR is not yet established in clinical routine for pacemaker patients with known or suspected CAD. A possible reason is that adenosine stress perfusion for ischemia detection in CMR has not been studied in patients with cardiac conduction disease requiring pacemaker therapy. Other than under resting conditions it is unclear whether MR safe pacing modes (paused pacing or asynchronous mode) can be applied safely because the effect of adenosine on heart rate is not precisely known in this entity of patients. We investigate for the first time feasibility and safety of adenosine stress CMR in pacemaker patients in clinical routine and evaluate a pacing protocol that considers heart rate changes under adenosine. We retrospectively analyzed CMR scans of 24 consecutive patients with MR conditional pacemakers (mean age 72.1 ± 11.0 years) who underwent CMR in clinical routine for the evaluation of known or suspected CAD. MR protocol included cine imaging, adenosine stress perfusion and late gadolinium enhancement. Pacemaker indications were sinus node dysfunction (n = 18) and second or third degree AV block (n = 6). Under a pacing protocol intended to avoid competitive pacing on the one hand and bradycardia due to AV block on the other no arrhythmia occurred. Pacemaker stimulation was paused to prevent competitive pacing in sinus node dysfunction with resting heart rate >45 bpm. Sympatho-excitatory effect of adenosine led to a significant acceleration of heart rate by 12.3 ± 8.3 bpm (p < 0.001), no bradycardia occurred. On the contrary in AV block heart rate remained constant; asynchronous pacing above resting heart rate did not interfere with intrinsic rhythm. Adenosine stress CMR appears to be feasible and safe in patients with MR conditional pacemakers. Heart rate response to adenosine has to be considered for the choice of pacing modes during CMR.

Differentiation induction of mouse embryonic stem cells into sinus node-like cells by suramin

PubMed Central

Wiese, Cornelia; Nikolova, Teodora; Zahanich, Ihor; Sulzbacher, Sabine; Fuchs, Joerg; Yamanaka, Satoshi; Graf, Eva; Ravens, Ursula; Boheler, Kenneth R.; Wobus, Anna M.

2015-01-01

Background Embryonic stem (ES) cells differentiate into cardiac phenotypes representing early pacemaker-, atrial-, ventricular-, and sinus node-like cells, however, ES-derived specification into sinus nodal cells is not yet known. By using the naphthylamine derivative of urea, suramin, we were able to follow the process of cardiac specialization into sinus node-like cells. Methods Differentiating mouse ES cells were treated with suramin (500 μM) from day 5 to 7 of embryoid body formation, and cells were analysed for their differentiation potential via morphological analysis, flow cytometry, RT-PCR, immunohistochemistry and patch clamp analysis. Results Application of suramin resulted in an increased number of cardiac cells, but inhibition of neuronal, skeletal muscle and definitive endoderm differentiation. Immediately after suramin treatment, a decreased mesendoderm differentiation was found. Brachyury, FGF10, Wnt8 and Wnt3a transcript levels were significantly down-regulated, followed by a decrease in mesoderm- and cardiac progenitor-specific markers BMP2, GATA4/5, Wnt11, Isl1, Nkx2.5 and Tbx5 immediately after removal of the substance. With continued differentiation, a significant up-regulation of Brachyury, FGF10 and GATA5 transcript levels was observed, whereas Nkx2.5, Isl1, Tbx5, BMP2 and Wnt11 levels were normalized to control levels. At advanced differentiation stages, sinus node-specific HCN4, Tbx2 and Tbx3 transcript levels were significantly up-regulated. Immunofluorescence and patch-clamp analysis confirmed the increased number of sinus node-like cells, and electrophysiological analysis revealed a lower number of atrial- and ventricular-like cardiomyocytes following suramin treatment. Conclusion We conclude that the interference of suramin with the cardiac differentiation process modified mesoderm- and cardiac-specific gene expression resulting in enhanced formation of sinus node-like cells. PMID:19775764

Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1

PubMed Central

Glukhov, Alexey V.; Kalyanasundaram, Anuradha; Lou, Qing; Hage, Lori T.; Hansen, Brian J.; Belevych, Andriy E.; Mohler, Peter J.; Knollmann, Björn C.; Periasamy, Muthu; Györke, Sandor; Fedorov, Vadim V.

2015-01-01

Aims Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. Methods and results In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca2+ cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2−/−) mice. Casq2−/− mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca2+ cycling, including abnormal Ca2+ release, periods of significantly elevated diastolic Ca2+ levels leading to pauses and unstable pacemaker rate. Importantly, Ca2+ cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca2+ transient upstrokes throughout the atrial pacemaker complex. Conclusions Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca2+ release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients. PMID:24216388

Intracardiac Origin of Heart Rate Variability, Pacemaker Funny Current and their Possible Association with Critical Illness

PubMed Central

Papaioannou, Vasilios E; Verkerk, Arie O; Amin, Ahmed S; de Bakker, Jaques MT

2013-01-01

Heart rate variability (HRV) is an indirect estimator of autonomic modulation of heart rate and is considered a risk marker in critical illness, particularly in heart failure and severe sepsis. A reduced HRV has been found in critically ill patients and has been associated with neuro-autonomic uncoupling or decreased baroreflex sensitivity. However, results from human and animal experimental studies indicate that intracardiac mechanisms might also be responsible for interbeat fluctuations. These studies have demonstrated that different membrane channel proteins and especially the so-called ‘funny’ current (If), an hyperpolarization-activated, inward current that drives diastolic depolarization resulting in spontaneous activity in cardiac pacemaker cells, are altered during critical illness. Furthermore, membrane channels kinetics seem to have significant impact upon HRV, whose early decrease might reflect a cellular metabolic stress. In this review article we present research findings regarding intracardiac origin of HRV, at the cellular level and in both isolated sinoatrial node and whole ex vivo heart preparations. In addition, we will review results from various experimental studies that support the interrelation between If and HRV during endotoxemia. We suggest that reduced HRV during sepsis could also be associated with altered pacemaker cell membrane properties, due to ionic current remodeling. PMID:22920474

Excitation model of pacemaker cardiomyocytes of cardiac conduction system

NASA Astrophysics Data System (ADS)

Grigoriev, M.; Babich, L.

2015-11-01

Myocardium includes typical and atypical cardiomyocytes - pacemakers, which form the cardiac conduction system. Excitation from the atrioventricular node in normal conditions is possible only in one direction. Retrograde direction of pulses is impossible. The most important prerequisite for the work of cardiomyocytes is the anatomical integrity of the conduction system. Changes in contractile force of the cardiomyocytes, which appear periodically, are due to two mechanisms of self-regulation - heterometric and homeometric. Graphic course of the excitation pulse propagation along the heart muscle more accurately reveals the understanding of the arrhythmia mechanism. These models have the ability to visualize the essence of excitation dynamics. However, they do not have the proper forecasting function for result estimation. Integrative mathematical model enables further investigation of general laws of the myocardium active behavior, allows for determination of the violation mechanism of electrical and contractile function of cardiomyocytes. Currently, there is no full understanding of the topography of pacemakers and ionic mechanisms. There is a need for the development of direction of mathematical modeling and comparative studies of the electrophysiological arrangement of cells of atrioventricular connection and ventricular conduction system.

Electrophysiological effects of FK664, a new cardiotonic agent, on preparations from guinea pig ventricle and from rabbit sino-atrial node.

PubMed

Kodama, I; Anno, T; Sudo, Y; Satake, N; Shibata, S

1989-05-01

Effects of the cardiotonic agent FK664, 6-(3, 4-dimethoxy-phenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-dihydro-2 (1H)-pyrimidone, on isolated guinea pig ventricular muscles and rabbit sinus node pacemaker cells were studied using micro-electrode techniques. In ventricular muscles driven at 0.5-1.0 Hz, FK664 above 3 mumol.litre-1 caused an increase in contractile force and a shortening of time to peak tension. This positive inotropic effect of FK664 was accompanied by a slight elevation of the early plateau phase of the action potential, while other action potential variables were unaffected. The change in contractile force induced by FK664 was abolished in a low Ca2+ medium (0.12 mmol.litre-1) or by treatment with ryanodine (2 mumol.litre-1), whereas it was relatively well preserved in the preparations pretreated with nefedipine (1 mumol.litre-1). The slow action potentials induced by isoprenaline (0.3 mumol.litre-1) in high K+ medium (30 mmol.litre-1) and the slow inward current measured by single sucrose gap voltage clamp at a holding potential of -40 mV were unaffected by FK664. In sinus node pacemaker cells, FK664 (1-10 mumol.litre-1) caused a dose dependent acceleration of phase 4 depolarisation and a shortening of spontaneous firing cycle length. This positive chronotropic effect of FK664 was markedly inhibited in a low Ca2+ medium (0.3 mmol.litre-1). These findings suggest that FK664 has positive inotropic and chronotropic effects on the heart, due to an enhancement of transsarcolemmal calcium influx through the low threshold, dihydropyridine insensitive Ca2+ channel population.

Effect of Exogenous Extracellular Nicotinamide Adenine Dinucleotide (NAD⁺) on Bioelectric Activity of the Pacemaker and Conduction System of the Heart.

PubMed

Pustovit, K B; Kuz'min, V S; Sukhova, G S

2015-06-01

In rat sinoatrial node, NAD(+) (10 μM) reduced the rate of spontaneous action potentials, duration of action potentials, and the velocity of slow diastolic depolarization, but the rate of action potential front propagation increases. In passed rabbit Purkinje fibers, NAD(+) (10 μM) reduced the duration of action potentials. Under conditions of spontaneous activity of Purkinje fibers, NAD(+) reduced the fi ring rate and the rate of slow diastolic depolarization. The effects of extracellular NAD(+) on bioelectric activity of the pacemaker (sinoatrial node) and conduction system of the heart (Purkinje fibers) are probably related to activation of P1 and P2 purinoceptors.

Noise-induced effects on multicellular biopacemaker spontaneous activity: Differences between weak and strong pacemaker cells

NASA Astrophysics Data System (ADS)

Aghighi, Alireza; Comtois, Philippe

2017-09-01

Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes. However, the combined effect of pacemaker characteristics, density, and spatial distribution of the pacemaker cells on spontaneous activity is unknown. Using a simple stochastic pattern formation algorithm, we previously showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of pacemaker cells. In this study, we show that this behavior is dependent on the pacemaker cell characteristics, with weaker pacemaker cells requiring higher density and larger clusters to sustain multicellular activity. These multicellular structures also demonstrated an increased sensitivity to voltage noise that favored spontaneous activity at lower density while increasing temporal variation in the period of activity. This information will help researchers overcome the current limitations of biopacemakers.

Effects of Nicotinamide Adenine Dinucleotide (NAD(+)) and Diadenosine Tetraphosphate (Ap4A) on Electrical Activity of Working and Pacemaker Atrial Myocardium in Guinea Pigs.

PubMed

Pustovit, K B; Abramochkin, D V

2016-04-01

Effects of nucleotide polyphosphate compounds (nicotinamide adenine dinucleotide, NAD(+); diadenosine tetraphosphate, Ap4A) on the confi guration of action potentials were studied in isolated preparations of guinea pig sinoatrial node and right atrial appendage (auricle). In the working myocardium, NAD(+) and Ap4A in concentrations of 10(-5) and 10(-4) M had no effect on resting potential, but significantly reduced the duration of action potentials; the most pronounced decrease was found at 25% repolarization. In the primary pacemaker of the sinoatrial node, both concentrations of NAD(+) and Ap4A induced hyperpolarization and reduction in the rate of slow diastolic depolarization, but significant slowing of the sinus rhythm was produced by these substances only in the concentration of 10(-4) M. Moreover, AP shortening and marked acceleration of AP upstroke were observed in the pacemaker myocardium after application of polyphosphates. Comparative analysis of the effects of NAD(+) and Ap4A in the working and pacemaker myocardium drove us to a hypothesis on inhibitory effects of these substances on L-type calcium current accompanied by stimulation of one or several potassium currents, which induce enhancement of repolarization and hyperpolarization of membranes probably mediated by the activation of purine receptors.

Computer algorithms for automated detection and analysis of local Ca2+ releases in spontaneously beating cardiac pacemaker cells

PubMed Central

Kim, Mary S.; Tsutsui, Kenta; Stern, Michael D.; Lakatta, Edward G.; Maltsev, Victor A.

2017-01-01

Local Ca2+ Releases (LCRs) are crucial events involved in cardiac pacemaker cell function. However, specific algorithms for automatic LCR detection and analysis have not been developed in live, spontaneously beating pacemaker cells. In the present study we measured LCRs using a high-speed 2D-camera in spontaneously contracting sinoatrial (SA) node cells isolated from rabbit and guinea pig and developed a new algorithm capable of detecting and analyzing the LCRs spatially in two-dimensions, and in time. Our algorithm tracks points along the midline of the contracting cell. It uses these points as a coordinate system for affine transform, producing a transformed image series where the cell does not contract. Action potential-induced Ca2+ transients and LCRs were thereafter isolated from recording noise by applying a series of spatial filters. The LCR birth and death events were detected by a differential (frame-to-frame) sensitivity algorithm applied to each pixel (cell location). An LCR was detected when its signal changes sufficiently quickly within a sufficiently large area. The LCR is considered to have died when its amplitude decays substantially, or when it merges into the rising whole cell Ca2+ transient. Ultimately, our algorithm provides major LCR parameters such as period, signal mass, duration, and propagation path area. As the LCRs propagate within live cells, the algorithm identifies splitting and merging behaviors, indicating the importance of locally propagating Ca2+-induced-Ca2+-release for the fate of LCRs and for generating a powerful ensemble Ca2+ signal. Thus, our new computer algorithms eliminate motion artifacts and detect 2D local spatiotemporal events from recording noise and global signals. While the algorithms were developed to detect LCRs in sinoatrial nodal cells, they have the potential to be used in other applications in biophysics and cell physiology, for example, to detect Ca2+ wavelets (abortive waves), sparks and embers in muscle cells and Ca2+ puffs and syntillas in neurons. PMID:28683095

On the Evolution of the Cardiac Pacemaker

PubMed Central

Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

2017-01-01

The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. PMID:29367536

Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain.

PubMed

Singh, Anamika; Gebhart, Mathias; Fritsch, Reinhard; Sinnegger-Brauns, Martina J; Poggiani, Chiara; Hoda, Jean-Charles; Engel, Jutta; Romanin, Christoph; Striessnig, Jörg; Koschak, Alexandra

2008-07-25

Low voltage activation of Ca(V)1.3 L-type Ca(2+) channels controls excitability in sensory cells and central neurons as well as sinoatrial node pacemaking. Ca(V)1.3-mediated pacemaking determines neuronal vulnerability of dopaminergic striatal neurons affected in Parkinson disease. We have previously found that in Ca(V)1.4 L-type Ca(2+) channels, activation, voltage, and calcium-dependent inactivation are controlled by an intrinsic distal C-terminal modulator. Because alternative splicing in the Ca(V)1.3 alpha1 subunit C terminus gives rise to a long (Ca(V)1.3(42)) and a short form (Ca(V)1.3(42A)), we investigated if a C-terminal modulatory mechanism also controls Ca(V)1.3 gating. The biophysical properties of both splice variants were compared after heterologous expression together with beta3 and alpha2delta1 subunits in HEK-293 cells. Activation of calcium current through Ca(V)1.3(42A) channels was more pronounced at negative voltages, and inactivation was faster because of enhanced calcium-dependent inactivation. By investigating several Ca(V)1.3 channel truncations, we restricted the modulator activity to the last 116 amino acids of the C terminus. The resulting Ca(V)1.3(DeltaC116) channels showed gating properties similar to Ca(V)1.3(42A) that were reverted by co-expression of the corresponding C-terminal peptide C(116). Fluorescence resonance energy transfer experiments confirmed an intramolecular protein interaction in the C terminus of Ca(V)1.3 channels that also modulates calmodulin binding. These experiments revealed a novel mechanism of channel modulation enabling cells to tightly control Ca(V)1.3 channel activity by alternative splicing. The absence of the C-terminal modulator in short splice forms facilitates Ca(V)1.3 channel activation at lower voltages expected to favor Ca(V)1.3 activity at threshold voltages as required for modulation of neuronal firing behavior and sinoatrial node pacemaking.

Rescuing cardiac automaticity in L-type Cav1.3 channelopathies and beyond.

PubMed

Mesirca, Pietro; Bidaud, Isabelle; Mangoni, Matteo E

2016-10-15

Pacemaker activity of the sino-atrial node generates the heart rate. Disease of the sinus node and impairment of atrioventricular conduction induce an excessively low ventricular rate (bradycardia), which cannot meet the needs of the organism. Bradycardia accounts for about half of the total workload of clinical cardiologists. The 'sick sinus' syndrome (SSS) is characterized by sinus bradycardia and periods of intermittent atrial fibrillation. Several genetic or acquired risk factors or pathologies can lead to SSS. Implantation of an electronic pacemaker constitutes the only available therapy for SSS. The incidence of SSS is forecast to double over the next 50 years, with ageing of the general population thus urging the development of complementary or alternative therapeutic strategies. In recent years an increasing number of mutations affecting ion channels involved in sino-atrial automaticity have been reported to underlie inheritable SSS. L-type Ca v 1.3 channels play a major role in the generation and regulation of sino-atrial pacemaker activity and atrioventricular conduction. Mutation in the CACNA1D gene encoding Ca v 1.3 channels induces loss-of-function in channel activity and underlies the sino-atrial node dysfunction and deafness syndrome (SANDD). Mice lacking Ca v 1.3 channels (Ca v 1.3 -/- ) fairly recapitulate SSS and constitute a precious model to test new therapeutic approaches to handle this disease. Work in our laboratory shows that targeting G protein-gated K + (I KACh ) channels effectively rescues SSS of Ca v 1.3 -/- mice. This new concept of 'compensatory' ion channel targeting shines new light on the principles underlying the pacemaker mechanism and may open the way to new therapies for SSS. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Stem cells as biological heart pacemakers.

PubMed

Gepstein, Lior

2005-12-01

Abnormalities in the pacemaker function of the heart or in cardiac impulse conduction may result in the appearance of a slow heart rate, traditionally requiring the implantation of a permanent electronic pacemaker. In recent years, a number of experimental approaches have been developed in an attempt to generate biological alternatives to implantable electronic devices. These strategies include, initially, a number of gene therapy approaches (aiming to manipulate the expression of ionic currents or their modulators and thereby convert quiescent cardiomyocytes into pacemaking cells) and, more recently, the use of cell therapy and tissue engineering. The latter approach explored the possibility of grafting pacemaking cells, either derived directly during the differentiation of human embryonic stem cells or engineered from mesenchymal stem cells, into the myocardium. This review will describe each of these approaches, focusing mainly on the stem cell strategies, their possible advantages and shortcomings, as well as the avenues required to make biological pacemaking a clinical reality.

Oxidized CaMKII causes cardiac sinus node dysfunction in mice

PubMed Central

Swaminathan, Paari Dominic; Purohit, Anil; Soni, Siddarth; Voigt, Niels; Singh, Madhu V.; Glukhov, Alexey V.; Gao, Zhan; He, B. Julie; Luczak, Elizabeth D.; Joiner, Mei-ling A.; Kutschke, William; Yang, Jinying; Donahue, J. Kevin; Weiss, Robert M.; Grumbach, Isabella M.; Ogawa, Masahiro; Chen, Peng-Sheng; Efimov, Igor; Dobrev, Dobromir; Mohler, Peter J.; Hund, Thomas J.; Anderson, Mark E.

2011-01-01

Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47–/– mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII–triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients. PMID:21785215

Chest MRI

MedlinePlus

... heart valves Heart defibrillator or pacemaker Inner ear (cochlear) implants Kidney disease or are on dialysis (you ... Diagnose abnormal growths in the chest Evaluate blood flow Show lymph nodes and blood vessels Show the ...

Racing of the biological pacemaker.

PubMed

Yu, Han-Gang

2009-01-01

Over the past decade, rapid progress in the molecular studies of cardiac ion channels and stem cells biology has led to efforts to create a biological pacemaker to supplement the widely-used electronic pacemaker. We will review the main concepts of cardiac pacemaker activities in different heart regions and the approaches to design a working biological pacemaker. We will focus on how to use the gene- and cell-based approaches to meet the requirements of a working biological pacemaker. Possible future development and precautions for creation of an effective biological pacemaker superior to the electronic counterpart are also discussed along with recent patents.

Transvenous permanent pacemaker implantation in dextrocardia: technique, challenges, outcome, and a brief review of literature.

PubMed

Shenthar, Jayaprakash; Rai, Maneesh K; Walia, Rohit; Ghanta, Somasekhar; Sreekumar, Praveen; Reddy, Satish S

2014-09-01

Dextrocardia is a rare congenital anomaly. Pacemaker implantation in dextrocardia can be challenging because of the distorted anatomy and associated anomalies. The literature regarding implantation of pacemaker in dextrocardia is scarce. The study involved retrospective analysis of records of patients with dextrocardia who had undergone pacemaker implantation between January 2006 and July 2013 from a single centre. Six patients with dextrocardia (five males and one female) underwent permanent pacemaker implantation (PPI) between January 2006 and July 2013. Of them, three had situs solitus dextrocardia and three situs inversus dextrocardia. All three patients with situs solitus dextrocardia had associated corrected transposition of great arteries. The indication for pacemaker implantation was symptomatic complete atrioventricular (AV) block in four, high-grade AV block in one, and sinus node dysfunction in one patient. A favourable outcome was noted during a mean follow-up of 3.9 years (4 months to 7 years) with one patient needing a pulse generator replacement. Permanent pacemaker implantation in dextrocardia can be challenging because of the distorted anatomy. Use of a technique employing angiography to delineate chamber anatomy and relationship can assist the operator during such difficult PPIs. The medium- and long-term survival after a successful pacemaker implantation in dextrocardia is favourable. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Permanent pacemaker implantation in octogenarians with unexplained syncope and positive electrophysiologic testing.

PubMed

Giannopoulos, Georgios; Kossyvakis, Charalampos; Panagopoulou, Vasiliki; Tsiachris, Dimitrios; Doudoumis, Konstantinos; Mavri, Maria; Vrachatis, Dimitrios; Letsas, Konstantinos; Efremidis, Michael; Katsivas, Apostolos; Lekakis, John; Deftereos, Spyridon

2017-05-01

Syncope is a common problem in the elderly, and a permanent pacemaker is a therapeutic option when a bradycardic etiology is revealed. However, the benefit of pacing when no association of symptoms to bradycardia has been shown is not clear, especially in the elderly. The aim of this study was to evaluate the effect of pacing on syncope-free mortality in patients aged 80 years or older with unexplained syncope and "positive" invasive electrophysiologic testing (EPT). This was an observational study. A positive EPT for the purposes of this study was defined by at least 1 of the following: a corrected sinus node recovery time of >525 ms, a basic HV interval of >55 ms, detection of infra-Hisian block, or appearance of second-degree atrioventricular block on atrial decremental pacing at a paced cycle length of >400 ms. Among the 2435 screened patients, 228 eligible patients were identified, 145 of whom were implanted with a pacemaker. Kaplan-Meier analysis determined that time to event (syncope or death) was 50.1 months (95% confidence interval 45.4-54.8 months) with a pacemaker vs 37.8 months (95% confidence interval 31.3-44.4 months) without a pacemaker (log-rank test, P = .001). The 4-year time-dependent estimate of the rate of syncope was 12% vs 44% (P < .001) and that of any-cause death was 41% vs 56% (P = .023), respectively. The multivariable odds ratio was 0.25 (95% confidence interval 0.15-0.40) after adjustment for potential confounders. In patients with unexplained syncope and signs of sinus node dysfunction or impaired atrioventricular conduction on invasive EPT, pacemaker implantation was independently associated with longer syncope-free survival. Significant differences were also shown in the individual components of the primary outcome measure (syncope and death from any cause). Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Premature Ventricular Contractions (PVCs)

MedlinePlus

... This natural pacemaker produces the electrical impulses that trigger the normal heartbeat. From the sinus node, electrical ... occur? The reasons aren't always clear. Certain triggers, heart diseases or changes in the body can ...

Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction.

PubMed

Ozcan, Cevher; Jahangir, Arshad; Friedman, Paul A; Munger, Thomas M; Packer, Douglas L; Hodge, David O; Hayes, David L; Gersh, Bernard J; Hammill, Stephen C; Shen, Win-Kuang

2003-07-01

Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) < or =40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 +/- 10 years; 45 men), LVEF was 26% +/- 8% and 34% +/- 13% (p <0.001) before and after ablation, respectively. During follow-up (40 +/- 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (> or =45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.

Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age-associated alterations in heart rate variability in vivo.

PubMed

Yaniv, Yael; Ahmet, Ismayil; Tsutsui, Kenta; Behar, Joachim; Moen, Jack M; Okamoto, Yosuke; Guiriba, Toni-Rose; Liu, Jie; Bychkov, Rostislav; Lakatta, Edward G

2016-08-01

We aimed to determine how age-associated changes in mechanisms extrinsic and intrinsic to pacemaker cells relate to basal beating interval variability (BIV) reduction in vivo. Beating intervals (BIs) were measured in aged (23-25 months) and adult (3-4 months) C57BL/6 male mice (i) via ECG in vivo during light anesthesia in the basal state, or in the presence of 0.5 mg mL(-1) atropine + 1 mg mL(-1) propranolol (in vivo intrinsic conditions), and (ii) via a surface electrogram, in intact isolated pacemaker tissue. BIV was quantified in both time and frequency domains using linear and nonlinear indices. Although the average basal BI did not significantly change with age under intrinsic conditions in vivo and in the intact isolated pacemaker tissue, the average BI was prolonged in advanced age. In vivo basal BIV indices were found to be reduced with age, but this reduction diminished in the intrinsic state. However, in pacemaker tissue BIV indices increased in advanced age vs. adults. In the isolated pacemaker tissue, the sensitivity of the average BI and BIV in response to autonomic receptor stimulation or activation of mechanisms intrinsic to pacemaker cells by broad-spectrum phosphodiesterase inhibition declined in advanced age. Thus, changes in mechanisms intrinsic to pacemaker cells increase the average BIs and BIV in the mice of advanced age. Autonomic neural input to pacemaker tissue compensates for failure of molecular intrinsic mechanisms to preserve average BI. But this compensation reduces the BIV due to both the imbalance of autonomic neural input to the pacemaker cells and altered pacemaker cell responses to neural input. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Angiotensin II promotes differentiation of mouse c-kit-positive cardiac stem cells into pacemaker-like cells

PubMed Central

XUE, CHENG; ZHANG, JUN; LV, ZHAN; LIU, HUI; HUANG, CONGXIN; YANG, JING; WANG, TEN

2015-01-01

Cardiac stem cells (CSCs) can differentiate into cardiac muscle-like cells; however, it remains unknown whether CSCs may possess the ability to differentiate into pacemaker cells. The aim of the present study was to determine whether angiotensin II (Ang II) could promote the specialization of CSCs into pacemaker-like cells. Mouse CSCs were treated with Ang II from day 3–5, after cell sorting. The differentiation potential of the cells was then analyzed by morphological analysis, flow cytometry, reverse transcription-polymerase chain reaction, immunohistochemistry and patch clamp analysis. Treatment with Ang II resulted in an increased number of cardiac muscle-like cells (32.7±4.8% vs. 21.5±4.8%; P<0.05), and inhibition of smooth muscle-like cells (6.2±7.3% vs. 20.5±5.1%; P<0.05). Following treatment with Ang II, increased levels of the cardiac progenitor-specific markers GATA4 and Nkx2.5 were observed in the cells. Furthermore, the transcript levels of pacemaker function-related genes, including hyperpolarization-activated cyclic nucleotide-gated (HCN)2, HCN4, T-box (Tbx)2 and Tbx3, were significantly upregulated. Immunofluorescence analysis confirmed the increased number of pacemaker-like cells. The pacemaker current (If) was recorded in the cells derived from CSCs, treated with Ang II. In conclusion, treatment of CSCs with Ang II during the differentiation process modified cardiac-specific gene expression and resulted in the enhanced formation of pacemaker-like cells. PMID:25572000

Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation.

PubMed

Ozcan, C; Jahangir, A; Friedman, P A; Patel, P J; Munger, T M; Rea, R F; Lloyd, M A; Packer, D L; Hodge, D O; Gersh, B J; Hammill, S C; Shen, W K

2001-04-05

In patients with atrial fibrillation that is refractory to drug therapy, radio-frequency ablation of the atrioventricular node and implantation of a permanent pacemaker are an alternative therapeutic approach. The effect of this procedure on long-term survival is unknown. We studied all patients who underwent ablation of the atrioventricular node and implantation of a permanent pacemaker at the Mayo Clinic between 1990 and 1998. Observed survival was compared with the survival rates in two control populations: age- and sex-matched members of the Minnesota population between 1970 and 1990 and consecutive patients with atrial fibrillation who received drug therapy in 1993. A total of 350 patients (mean [+/-SD] age, 68+/-11 years) were studied. During a mean of 36+/-26 months of follow-up, 78 patients died. The observed survival rate was significantly lower than the expected survival rate based on the general Minnesota population (P<0.001). Previous myocardial infarction (P<0.001), a history of congestive heart failure (P=0.02), and treatment with cardiac drugs after ablation (P=0.03) were independent predictors of death. Observed survival among patients without these three risk factors was similar to expected survival (P=0.43). None of the 26 patients with lone atrial fibrillation died during follow-up (37+/-27 months). The observed survival rate among patients who underwent ablation was similar to that among 229 controls with atrial fibrillation (mean age, 67+/-12 years) who received drug therapy (P=0.44). In the absence of underlying heart disease, survival among patients with atrial fibrillation after ablation of the atrioventricular node is similar to expected survival in the general population. Long-term survival is similar for patients with atrial fibrillation, whether they receive ablation or drug therapy. Control of the ventricular rate by ablation of the atrioventricular node and permanent pacing does not adversely affect long-term survival.

Tachycardia | Fast Heart Rate

MedlinePlus

... sinoatrial (SA) node --- the heart's natural pacemaker. A series of early beats in the atria speeds up the heart rate. The rapid heartbeat does not allow enough time for the heart to fill before it contracts ...

A Single Center Study of 1,179 Heart Transplant Patients-Factors Affecting Pacemaker Implantation.

PubMed

Wellmann, Petra; Herrmann, Florian Ernst Martin; Hagl, Christian; Juchem, Gerd

2017-03-01

After around 10% of heart transplant patients require pacemaker implantation. The bradyarrhythmias causing pacemaker requirement include sinus node dysfunction (SND) and atrioventricular block (AVB). This study sought to define clinical predictors for pacemaker requirement as well as identify differences in the patient groups developing SND and AVB. Our operative database was used to collect retrospective recipient, donor, and operative data of all patients receiving orthotopic heart transplants between 1981 and 2016. In the 35-year period 1,179 transplants were performed (mean recipient age 45.5 ± 0.5 years, 20.4% female, 90.6% biatrial technique) with bradyarrhythmias requiring pacemaker implantation developing in 135 patients (11.5%). Independent risk factors were prolonged operative time 340 minutes versus 313 minutes (P = 0.027) and a biatrial anastomosis (P = 0.036). Ischemia time, cardiopulmonary bypass time, aortic cross clamp time, and reperfusion time all had no significant effect on pacemaker implantation rates. Similarly, whether the transplant was a reoperation, a retransplant, or performed after primary assist implantation had no effects on pacemaker implantation rates. There was no survival difference between the paced and nonpaced groups. The donor age was higher in the patients who developed AVB as the indication for pacemaker implantation (43 vs 34 years, P = 0.031). Patients with AVB had longer aortic cross clamp times and developed the arrhythmia later than those who developed SND. Use of the bicaval instead of the biatrial technique and shortened operative times should reduce pacemaker requirement after heart transplantation. Survival is not affected by this complication. © 2017 Wiley Periodicals, Inc.

Pacemaker Use in New Zealand - Data From the New Zealand Implanted Cardiac Device Registry (ANZACS-QI 15).

PubMed

Larsen, P D; Kerr, A J; Hood, M; Harding, S A; Hooks, D; Heaven, D; Lever, N A; Sinclair, S; Boddington, D; Tang, E W; Swampillai, J; Stiles, M K

2017-03-01

The New Zealand Cardiac Implanted Device Registry (Device) has recently been developed under the auspices of the New Zealand Branch of the Cardiac Society of Australia and New Zealand. This study describes the initial Device registry cohort of patients receiving a new pacemaker, their indications for pacing and their perioperative complications. The Device Registry was used to audit patients receiving a first pacemaker between 1 st January 2014 and 1 st June 2015. We examined 1611 patients undergoing first pacemaker implantation. Patients were predominantly male (59%), and had a median age of 70 years. The most common symptom for pacemaker implantation was syncope (39%), followed by dizziness (30%) and dyspnoea (12%). The most common aetiology for a pacemaker was a conduction tissue disorder (35%), followed by sinus node dysfunction (22%). Atrioventricular (AV) block was the most common ECG abnormality, present in 44%. Dual chamber pacemakers were most common (62%), followed by single chamber ventricular pacemakers (34%), and cardiac resynchronisation therapy - pacemakers (CRT-P) (2%). Complications within 24hours of the implant procedure were reported in 64 patients (3.9%), none of which were fatal. The most common complication was the need for reoperation to manipulate a lead, occurring in 23 patients (1.4%). This is the first description of data entered into the Device registry. Patients receiving a pacemaker were younger than in European registries, and there was a low use of CRT-P devices compared to international rates. Complications rates were low and compare favourably to available international data. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Carvedilol analog modulates both basal and stimulated sinoatrial node automaticity.

PubMed

Shinohara, Tetsuji; Kim, Daehyeok; Joung, Boyoung; Maruyama, Mitsunori; Vembaiyan, Kannan; Back, Thomas G; Wayne Chen, S R; Chen, Peng-Sheng; Lin, Shien-Fong

2014-05-01

The membrane voltage clock and calcium (Ca(2+)) clock jointly regulate sinoatrial node (SAN) automaticity. VK-II-36 is a novel carvedilol analog that suppresses sarcoplasmic reticulum (SR) Ca(2+) release but does not block the β-receptor. The effect of VK-II-36 on SAN function remains unclear. The purpose of this study was to evaluate whether VK-II-36 can influence SAN automaticity by inhibiting the Ca(2+) clock. We simultaneously mapped intracellular Ca(2+) and membrane potential in 24 isolated canine right atriums using previously described criteria of the timing of late diastolic intracellular Ca elevation (LDCAE) relative to the action potential upstroke to detect the Ca(2+) clock. Pharmacological interventions with isoproterenol (ISO), ryanodine, caffeine, and VK-II-36 were performed after baseline recordings. VK-II-36 caused sinus rate downregulation and reduced LDCAE in the pacemaking site under basal conditions (P < 0.01). ISO induced an upward shift of the pacemaking site in SAN and augmented LDCAE in the pacemaking site. ISO also significantly and dose-dependently increased the sinus rate. The treatment of VK-II-36 (30 μmol/l) abolished both the ISO-induced shift of the pacemaking site and augmentation of LDCAE (P < 0.01), and it suppressed the ISO-induced increase in sinus rate (P = 0.02). Our results suggest that the sinus rate may be partly controlled by the Ca(2+) clock via SR Ca(2+) release during β-adrenergic stimulation.

Carvedilol Analogue Modulates both Basal and Stimulated Sinoatrial Node Automaticity

PubMed Central

Shinohara, Tetsuji; Kim, Daehyeok; Joung, Boyoung; Maruyama, Mitsunori; Vembaiyan, Kannan; Back, Thomas G.; Chen, S.R. Wayne; Chen, Peng-Sheng; Lin, Shien-Fong

2013-01-01

Background The membrane voltage clock and calcium (Ca2+) clock jointly regulate sinoatrial node (SAN) automaticity. VK-II-36 is a novel carvedilol analog that suppress sarcoplasmic reticulum (SR) Ca2+ release but does not block β-receptor. The effect of VK-II-36 on SAN function remains unclear. The purpose of this study was to evaluate whether VK-II-36 can influence SAN automaticity through inhibiting the Ca2+ clock. Methods and Results We simultaneously mapped intracellular Ca2+ and membrane potential in 24 isolated canine right atriums, using previously described criteria of the timing of late diastolic intracellular Ca elevation (LDCAE) relative to the action potential upstroke to detect the Ca2+ clock. Pharmacological intervention with isoproterenol (ISO), ryanodine, caffeine, and VK-II-36 were performed after baseline recordings. VK-II-36 caused sinus rate downregulation and reduced LDCAE in the pacemaking site under basal condition (P<0.01). ISO induced an upward shift of the pacemaking site in SAN and augmented LDCAE in pacemaking site. ISO also significantly and dose-dependently increased the sinus rate. The treatment of VK-II-36 (30 μmol/L) abolished both the ISO-induced shift of pacemaking site and augmentation of LDCAE (P<0.01), and suppressed the ISO-induced increase in sinus rate (P=0.02). Conclusions Our results suggest that sinus rate may be partly controlled by Ca2+ clock via SR Ca2+ release during β-adrenergic stimulation. PMID:23836067

Clinically oriented device programming in bradycardia patients: part 1 (sinus node disease). Proposals from AIAC (Italian Association of Arrhythmology and Cardiac Pacing).

PubMed

Ziacchi, Matteo; Palmisano, Pietro; Biffi, Mauro; Ricci, Renato P; Landolina, Maurizio; Zoni-Berisso, Massimo; Occhetta, Eraldo; Maglia, Giampiero; Botto, Gianluca; Padeletti, Luigi; Boriani, Giuseppe

2018-04-01

: Modern pacemakers have an increasing number of programable parameters and specific algorithms designed to optimize pacing therapy in relation to the individual characteristics of patients. When choosing the most appropriate pacemaker type and programing, the following variables must be taken into account: the type of bradyarrhythmia at the time of pacemaker implantation; the cardiac chamber requiring pacing, and the percentage of pacing actually needed to correct the rhythm disorder; the possible association of multiple rhythm disturbances and conduction diseases; the evolution of conduction disorders during follow-up. The goals of device programing are to preserve or restore the heart rate response to metabolic and hemodynamic demands; to maintain physiological conduction; to maximize device longevity; to detect, prevent, and treat atrial arrhythmia. In patients with sinus node disease, the optimal pacing mode is DDDR. Based on all the available evidence, in this setting, we consider appropriate the activation of the following algorithms: rate responsive function in patients with chronotropic incompetence; algorithms to maximize intrinsic atrioventricular conduction in the absence of atrioventricular blocks; mode-switch algorithms; algorithms for autoadaptive management of the atrial pacing output; algorithms for the prevention and treatment of atrial tachyarrhythmias in the subgroup of patients with atrial tachyarrhythmias/atrial fibrillation. The purpose of this two-part consensus document is to provide specific suggestions (based on an extensive literature review) on appropriate pacemaker setting in relation to patients' clinical features.

Comparative Study of Electrical Stimulation of the Heart with VDD and DDD Pacemakers as to the Evolution to Atrial Fibrillation

PubMed Central

de Campos, Nelson Leonardo Kerdahi Leite; de Andrade, Rubens Ramos; Fellicio, Marcello Laneza; Martins, Antônio Sergio; Garzesi, André Monti; Garcia, Leonardo Rufino; Takeda, Tassya Bueno

2017-01-01

Introduction The pacemaker implantation VDD is considered simpler, faster, less expensive and causes fewer complications compared to DDD. However, the VDD pacemaker has not been widely used in many centers, perhaps for fear of dysfunction of the sinus node and the reduction of atrial sensitivity by the pacemaker during follow-up after implantation. Objective To compare patients with DDD and VDD pacemakers regarding the evolution of chronic atrial fibrillation (AF) and length of stay outside this postoperative arrhythmia. Methods It was included 158 patients with dual chamber pacemakers, 48 DDD and 110 VDD. Follow-up period: between January 1, 1999 and December 31, 2015. The mean follow-up of patients with DDD was 5.35 years and the VDD, 4.74 years. The percentage of each group (DDD and VDD) which evolved to AF during follow-up was assessed. Also, it was made an actuarial study with the respective curves indicating the time free from AF for each group. Patients were classified according to the diagnosis that led to pacemaker implantation and the degree of heart failure. Results The percentage of patients who developed AF was higher in DDD group (10.42%) than in VDD group (6.36%), but without statistical significance. Patients with DDD and VDD remained free of AF for similar period. Conclusion Considering the results, the VDD pacemaker continues to be a good option to the DDD for routine use in cases properly indicated. PMID:29211212

Comparative Study of Electrical Stimulation of the Heart with VDD and DDD Pacemakers as to the Evolution to Atrial Fibrillation.

PubMed

Campos, Nelson Leonardo Kerdahi Leite de; Andrade, Rubens Ramos de; Fellicio, Marcello Laneza; Martins, Antônio Sergio; Garzesi, André Monti; Garcia, Leonardo Rufino; Takeda, Tassya Bueno

2017-01-01

The pacemaker implantation VDD is considered simpler, faster, less expensive and causes fewer complications compared to DDD. However, the VDD pacemaker has not been widely used in many centers, perhaps for fear of dysfunction of the sinus node and the reduction of atrial sensitivity by the pacemaker during follow-up after implantation. To compare patients with DDD and VDD pacemakers regarding the evolution of chronic atrial fibrillation (AF) and length of stay outside this postoperative arrhythmia. It was included 158 patients with dual chamber pacemakers, 48 DDD and 110 VDD. Follow-up period: between January 1, 1999 and December 31, 2015. The mean follow-up of patients with DDD was 5.35 years and the VDD, 4.74 years. The percentage of each group (DDD and VDD) which evolved to AF during follow-up was assessed. Also, it was made an actuarial study with the respective curves indicating the time free from AF for each group. Patients were classified according to the diagnosis that led to pacemaker implantation and the degree of heart failure. The percentage of patients who developed AF was higher in DDD group (10.42%) than in VDD group (6.36%), but without statistical significance. Patients with DDD and VDD remained free of AF for similar period. Considering the results, the VDD pacemaker continues to be a good option to the DDD for routine use in cases properly indicated.

Cardiac cell: a biological laser?

PubMed

Chorvat, D; Chorvatova, A

2008-04-01

We present a new concept of cardiac cells based on an analogy with lasers, practical implementations of quantum resonators. In this concept, each cardiac cell comprises a network of independent nodes, characterised by a set of discrete energy levels and certain transition probabilities between them. Interaction between the nodes is given by threshold-limited energy transfer, leading to quantum-like behaviour of the whole network. We propose that in cardiomyocytes, during each excitation-contraction coupling cycle, stochastic calcium release and the unitary properties of ionic channels constitute an analogue to laser active medium prone to "population inversion" and "spontaneous emission" phenomena. This medium, when powered by an incoming threshold-reaching voltage discharge in the form of an action potential, responds to the calcium influx through L-type calcium channels by stimulated emission of Ca2+ ions in a coherent, synchronised and amplified release process known as calcium-induced calcium release. In parallel, phosphorylation-stimulated molecular amplification in protein cascades adds tuneable features to the cells. In this framework, the heart can be viewed as a coherent network of synchronously firing cardiomyocytes behaving as pulsed laser-like amplifiers, coupled to pulse-generating pacemaker master-oscillators. The concept brings a new viewpoint on cardiac diseases as possible alterations of "cell lasing" properties.

A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system--battery not included.

PubMed

Southcott, Mark; MacVittie, Kevin; Halámek, Jan; Halámková, Lenka; Jemison, William D; Lobel, Robert; Katz, Evgeny

2013-05-07

Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with serum solution mimicking the human blood circulatory system. The biofuel cell generated an open circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of 0.83 mA cm(-2)). The power generated by the implantable biofuel cell was used to activate a pacemaker connected to the cell via a charge pump and a DC-DC converter interface circuit to adjust the voltage produced by the biofuel cell to the value required by the pacemaker. The voltage-current dependencies were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of the interface circuit, or the power converter, and the pacemaker to study their operation. The correct pacemaker operation was confirmed using a medical device - an implantable loop recorder. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange

PubMed Central

Choisy, Stéphanie C; Cheng, Hongwei; Orchard, Clive H; James, Andrew F; Hancox, Jules C

2015-01-01

The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35–37°C. Hyperpolarizing voltage commands from −40 mV elicited a Ba2+-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from −40 mV L-type Ca2+ current, ICa,L, was elicited with a half maximal activation voltage (V0.5) of −7.6 ± 1.2 mV (n = 24). ICa,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IKr) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to −40 mV, with an activation V0.5 of −10.7 ± 4.7 mV (n = 8). The IKr magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (−40 mV). Spontaneous APs (5.2 ± 0.5 sec−1; n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca2+ release by 1 μmol/L ryanodine, implicating intracellular Ca2+ cycling in murine AVN cell electrogenesis. PMID:26607172

Involvement of mitochondrial Na+–Ca2+ exchange in intestinal pacemaking activity

PubMed Central

Kim, Byung Joo; Jun, Jae Yeoul; So, Insuk; Kim, Ki Whan

2006-01-01

AIM: Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We have aimed to investigate the involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity in cultured interstitial cells of Cajal. METHODS: Enzymatic digestions were used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane currents (voltage clamp) and potentials (current clamp) from cultured ICCs. RESULTS: Clonazepam and CGP37157 inhibited the pacemaking activity of ICCs in a dose-dependent manner. Clonazepam from 20 to 60 µmol/L and CGP37157 from 10 to 30 µmol/L effectively inhibited Ca2+ efflux from mitochondria in pacemaking activity of ICCs. The IC50s of clonazepam and CGP37157 were 37.1 and 18.2 µmol/L, respectively. The addition of 20 µmol/L NiCl2 to the internal solution caused a “wax and wane” phenomenon of pacemaking activity of ICCs. CONCLUSION: These results suggest that mitochondrial Na+-Ca2+ exchange has an important role in intestinal pacemaking activity. PMID:16521198

Lithium-cupric sulfide cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuesta, A.J.; Bump, D.D.

1980-01-01

Lithium cells have become the primary power source for cardiac pacemakers due to their reliability and longevity at low current drain rates. A lithium-cupric sulfide cell was developed which makes maximum use of the shape of a pacemaker's battery compartment. The cell has a stable voltage throughout 90% of its lifetime. It then drops to a second stable voltage before depletion. The voltage drop creates a small decrease in pacemaker rate, which alerts the physician to replace the pacemaker. No loss of capacity due to self-discharge as been seen to date, and cells have proven to be safe under extrememore » conditions. 2 refs.« less

Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell

PubMed Central

Maltsev, Victor A.; Yaniv, Yael; Maltsev, Anna V.; Stern, Michael D.; Lakatta, Edward G.

2015-01-01

Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent “coupled-clock” theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies, such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age. PMID:24748434

Rhabdomyosarcoma associated with the lead wire of a pacemaker generator implant.

PubMed

Thieman Mankin, Kelley M; Dunbar, Mark D; Toplon, David; Ginn, Pamela; Maisenbacher, Herbert W; Risselada, Marije

2014-06-01

An 11-year-old female spayed Labrador Retriever was presented for a draining, painful subcutaneous mass palpated over a previously implanted pacemaker generator. Infection was suspected and the mass was removed surgically. On cut surface, the mass was friable and mottled tan to brown with firm pale tan nodules, surrounding the pacemaker lead wire adjacent to the pacemaker generator. Cytologic interpretation of impression smears was consistent with a sarcoma, and suggestive of a rhabdomyosarcoma due to the presence of strap-like cells. On histopathologic examination, a highly invasive nodular mass surrounded the pacemaker lead, composed of pleomorphic round, spindle and strap cells, and multinucleated giant cells. The population exhibited microscopic invasion into the deep portion of the fibrous capsule surrounding the pacemaker generator. There were tumor emboli within small to medium subcutaneous veins adjacent to the mass. Immunohistochemically, the neoplastic cells stained positive for α-sarcomeric actin and vimentin, and negative for α-smooth muscle actin, consistent with a rhabdomyosarcoma arising at the site of the pacemaker generator. To our knowledge, this is the first report of a rhabdomyosarcoma associated with the lead wire of a pacemaker generator in a dog. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

Enrichment of cardiac pacemaker-like cells: neuregulin-1 and cyclic AMP increase I(f)-current density and connexin 40 mRNA levels in fetal cardiomyocytes.

PubMed

Ruhparwar, Arjang; Er, Fikret; Martin, Ulrich; Radke, Kristin; Gruh, Ina; Niehaus, Michael; Karck, Matthias; Haverich, Axel; Hoppe, Uta C

2007-02-01

Generation of a large number of cells belonging to the cardiac pacemaker system would constitute an important step towards their utilization as a biological cardiac pacemaker system. The aim of the present study was to identify factors, which might induce transformation of a heterogenous population of fetal cardiomyocytes into cells with a pacemaker-like phenotype. Neuregulin-1 (alpha- and beta-isoform) or the cAMP was added to fresh cell cultures of murine embryonic cardiomyocytes. Quantitative northern blot analysis and flowcytometry were performed to detect the expression of connexins 40, 43 and 45. Patch clamp recordings in the whole cell configuration were performed to determine current density of I (f), a characteristic ion current of pacemaker cells. Fetal cardiomyocytes without supplement of neuregulin or cAMP served as control group. Neuregulin and cAMP significantly increased mRNA levels of connexin 40 (Cx-40), a marker of the early differentiating conduction system in mice. On the protein level, flowcytometry revealed no significant differences between treated and untreated groups with regard to the expression of connexins 40, 43 and 45. Treatment with cAMP (11.2 +/- 2.24 pA/pF; P < 0.001) and neuregulin-1-beta (6.23 +/- 1.07 pA/pF; P < 0.001) significantly increased the pacemaker current density compared to control cardiomyocytes (1.76 +/- 0.49 pA/pF). Our results indicate that neuregulin-1 and cAMP possess the capacity to cause significant transformation of a mixed population of fetal cardiomyocytes into cardiac pacemaker-like cells as shown by electrophysiology and increase of Cx-40 mRNA. This method may allow the development of a biological cardiac pacemaker system when applied to adult or embryonic stem cells.

Inhibition of spontaneous activity of rabbit atrioventricular node cells by KB-R7943 and inhibitors of sarcoplasmic reticulum Ca2+ ATPase

PubMed Central

Cheng, Hongwei; Smith, Godfrey L.; Hancox, Jules C.; Orchard, Clive H.

2011-01-01

The atrioventricular node (AVN) can act as a subsidiary cardiac pacemaker if the sinoatrial node fails. In this study, we investigated the effects of the Na–Ca exchange (NCX) inhibitor KB-R7943, and inhibition of the sarcoplasmic reticulum calcium ATPase (SERCA), using thapsigargin or cyclopiazonic acid (CPA), on spontaneous action potentials (APs) and [Ca2+]i transients from cells isolated from the rabbit AVN. Spontaneous [Ca2+]i transients were monitored from undialysed AVN cells at 37 °C using Fluo-4. In separate experiments, spontaneous APs and ionic currents were recorded using the whole-cell patch clamp technique. Rapid application of 5 μM KB-R7943 slowed or stopped spontaneous APs and [Ca2+]i transients. However, in voltage clamp experiments in addition to blocking NCX current (INCX) KB-R7943 partially inhibited L-type calcium current (ICa,L). Rapid reduction of external [Na+] also abolished spontaneous activity. Inhibition of SERCA (using 2.5 μM thapsigargin or 30 μM CPA) also slowed or stopped spontaneous APs and [Ca2+]i transients. Our findings are consistent with the hypothesis that sarcoplasmic reticulum (SR) Ca2+ release influences spontaneous activity in AVN cells, and that this occurs via [Ca2+]i-activated INCX; however, the inhibitory action of KB-R7943 on ICa,L means that care is required in the interpretation of data obtained using this compound. PMID:21163524

Risk of pacemaker implantation after uneventful successful cavotricuspid isthmus radiofrequency ablation in patients with common atrial flutter.

PubMed

Rodríguez-Mañero, Moisés; González-Melchor, Layla; Ballesteros, Gabriel; Raposeiras-Roubín, Sergio; García-Seara, Javier; López, Xesús Alberte Fernández; Cambeiro, Cristina González; Alcalde, Oscar; García-Bolao, Ignacio; Martínez-Sande, Luis; González-Juanatey, José Ramón

2016-01-01

Little is known about the risk of pacemaker implantation after common atrial flutter ablation in the long-term. We retrospectively reviewed the electrophysiology laboratory database at two Spanish University Hospitals from 1998 to 2012 to identify patients who had undergone successful ablation for cavotricuspid dependent atrial flutter. Cox regression analysis was used to examine the risk of pacemaker implantation. A total of 298 patients were considered eligible for inclusion. The mean age of the enrolled patients was 65.7±11. During 57.7±42.8 months, 30 patients (10.1%) underwent pacemaker implantation. In the stepwise multivariate models only heart rate at the time of the ablation (OR: 0.96; 95% CI: 0.93-0.98; p<0.0001) and intraventricular conduction disturbances in the baseline ECG (OR: 3.87; 95% CI: 1.54-9.70; p=0.004) were independents predictors of the need of pacemaker implantation. A heart rate of ≤65 bpm was identified as the optimal cut-off value to predict the need of pacemaker implantation in the follow-up (sensitivity: 79%, specificity: 74%) by ROC curve analyses. This is the first study of an association between the slow conducting common atrial flutter and subsequent risk of pacemaker implantation. In light of these findings, assessing it prior to ablation can be helpful for the risk stratification of sinus node disease or atrioventricular conduction disease requiring a pacemaker implantation in patients with persistent atrial flutter. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Long-Term Outcome of Single-Chamber Atrial Pacing Compared with Dual-Chamber Pacing in Patients with Sinus-Node Dysfunction and Intact Atrioventricular Node Conduction

PubMed Central

Kim, Won Ho; Joung, Boyoung; Shim, Jaemin; Park, Jong Sung; Hwang, Eui-Seock; Pak, Hui-Nam; Kim, Sungsoon

2010-01-01

Purpose The optimal pacing mode with either single chamber atrial pacemaker (AAI or AAIR) or dual chamber pacemaker (DDD or DDDR) is still not clear in sinus-node dysfunction (SND) and intact atrioventricular (AV) conduction. Materials and Methods Patients who were implanted with permanent pacemaker using AAI(R) (n = 73) or DDD(R) (n = 113) were compared. Results The baseline characteristics were comparable between the two groups, with a mean follow-up duration of 69 months. The incidence of death did not show statistical difference. However, the incidence of hospitalization for congestive heart failure (CHF) was significantly lower in the AAI(R) group (0%) than the DDD(R) group (8.8%, p = 0.03). Also, atrial fibrillation (AF) was found in 2.8% in the AAI(R) group, which was statistically different from 15.2% of patients in the DDD(R) group (p = 0.01). Four patients (5.5%) with AAI(R) developed AV block, and subsequently switched to DDD(R) pacing. The risk of AF was lower in the patients implanted with AAI(R) than those with DDD(R) [hazard ratio (HR), 0.84; 95% confidence interval, 0.72 to 0.97, p = 0.02]. Conclusion In patients with SND and intact AV conduction, AAI(R) pacing can achieve a better clinical outcome in terms of occurrence of CHF and AF than DDD(R) pacing. These findings support AAI(R) pacing as the preferred pacing mode in patients with SND and intact AV conduction. PMID:20879047

Hemodynamic instability after pulmonary veins isolation in a patient with dual chamber pacemaker

PubMed Central

Kiuchi, Márcio Galindo; Lobato, Guilherme Miglioli; Chen, Shaojie

2017-01-01

Abstract Introduction: The standard treatment of sinus node dysfunction (SND) is the pacemaker implantation, and the ideal methodology for the management of atrial fibrillation (AF) is rhythm control, but this is sometimes very hard to accomplish. For such actions, complete isolation of all pulmonary veins (PVI) is currently widely accepted as the best endpoint. Case Presentation: In this case, we report a female patient, 81 years old, with controlled hypertension, without coronary artery disease, bearer of bilateral knee replacement, and dual chamber pacemaker implanted 1.5 years ago owing to sinus node disease, presenting the following symptoms: presyncope episodes associated with sustained irregular palpitation tachycardia. The evaluation of the pacemaker-recorded episodes of atrial fibrillation, the echocardiogram-presented normal systolic function and measurements, as well as the resting myocardial scintigraphy and with drug use did not demonstrate ischemia and/or fibrosis. The patient was in use of valsartan 320 mg daily, amlodipine 10 mg daily, sotalol hydrochloride 120 mg 2 times daily, and dabigatran 110 mg 2 times daily. At the end of the PVI, the patient presented hemodynamic instability, with a decrease in heart rate to 30 bpm and invasive arterial blood pressure to 60/30 mmHg. The pericardial puncture was quickly carried out with the possibility of cardiac tamponade as the first hypothesis, but no pericardial effusion was found. Next, we detected acute capture loss from the ventricular pacemaker lead, unvarying with high voltage and pulse width, even with stable impedance, sense and keeping the same position visualized by fluoroscopy. And there was soon afterwards induction of sustained ventricular tachycardia degenerating to spontaneous ventricular fibrillation. Electrical cardioversion-defibrillation was performed with 200J, and the sinus rhythm was reestablished, but there was a dead short, and the pacemaker generator was burned and disabled. Conclusions: So, we can speculate that application of atrial radiofrequency for PVI diffused through the tissues, affecting in some way the tip of the ventricular electrode, causing a microlesion in this structure and making it impossible to capture the right ventricle by the pacemaker. As we cannot see it, we can call it of phantom injury of the ventricular lead. PMID:28562571

Hemodynamic instability after pulmonary veins isolation in a patient with dual chamber pacemaker: The phantom injury of the ventricular lead.

PubMed

Kiuchi, Márcio Galindo; Lobato, Guilherme Miglioli; Chen, Shaojie

2017-06-01

The standard treatment of sinus node dysfunction (SND) is the pacemaker implantation, and the ideal methodology for the management of atrial fibrillation (AF) is rhythm control, but this is sometimes very hard to accomplish. For such actions, complete isolation of all pulmonary veins (PVI) is currently widely accepted as the best endpoint. In this case, we report a female patient, 81 years old, with controlled hypertension, without coronary artery disease, bearer of bilateral knee replacement, and dual chamber pacemaker implanted 1.5 years ago owing to sinus node disease, presenting the following symptoms: presyncope episodes associated with sustained irregular palpitation tachycardia. The evaluation of the pacemaker-recorded episodes of atrial fibrillation, the echocardiogram-presented normal systolic function and measurements, as well as the resting myocardial scintigraphy and with drug use did not demonstrate ischemia and/or fibrosis. The patient was in use of valsartan 320 mg daily, amlodipine 10 mg daily, sotalol hydrochloride 120 mg 2 times daily, and dabigatran 110 mg 2 times daily. At the end of the PVI, the patient presented hemodynamic instability, with a decrease in heart rate to 30 bpm and invasive arterial blood pressure to 60/30 mmHg. The pericardial puncture was quickly carried out with the possibility of cardiac tamponade as the first hypothesis, but no pericardial effusion was found. Next, we detected acute capture loss from the ventricular pacemaker lead, unvarying with high voltage and pulse width, even with stable impedance, sense and keeping the same position visualized by fluoroscopy. And there was soon afterwards induction of sustained ventricular tachycardia degenerating to spontaneous ventricular fibrillation. Electrical cardioversion-defibrillation was performed with 200J, and the sinus rhythm was reestablished, but there was a dead short, and the pacemaker generator was burned and disabled. So, we can speculate that application of atrial radiofrequency for PVI diffused through the tissues, affecting in some way the tip of the ventricular electrode, causing a microlesion in this structure and making it impossible to capture the right ventricle by the pacemaker. As we cannot see it, we can call it of phantom injury of the ventricular lead.

Splinter haemorrhages, Osler's nodes, Janeway lesions and Roth spots: the peripheral stigmata of endocarditis.

PubMed

Sethi, Karishma; Buckley, Jim; de Wolff, Jacob

2013-09-01

Infective endocarditis is a serious endo-vascular infection, potentially affecting not only native heart valves, but also intra-vascularly implanted foreign materials such as valvular prostheses and pacemaker electrodes (Westphal et al, 2009).

Pacemaker implantation after catheter ablation for atrial fibrillation.

PubMed

Deshmukh, Abhishek J; Yao, Xiaoxi; Schilz, Stephanie; Van Houten, Holly; Sangaralingham, Lindsey R; Asirvatham, Samuel J; Friedman, Paul A; Packer, Douglas L; Noseworthy, Peter A

2016-01-01

Sinus node dysfunction requiring pacemaker implantation is commonly associated with atrial fibrillation (AF), but may not be clinically apparent until restoration of sinus rhythm with ablation or cardioversion. We sought to determine frequency, time course, and predictors for pacemaker implantation after catheter ablation, and to compare the overall rates to a matched cardioversion cohort. We conducted a retrospective analysis using a large US commercial insurance database and identified 12,158 AF patients who underwent catheter ablation between January 1, 2005 and December 31, 2012. Over an average of 2.4 years of follow-up, 5.6 % of the patients underwent pacemaker implantation. Using the Cox proportional hazards models, we found that risk of risks of pacemaker implantation was associated with older age (50-64 and ≥65 versus <50 years), female gender, higher CHADS2 score (≥2 and 1 versus 0), higher Charlson index (≥2 versus 0-1), certain baseline comorbidities (conduction disorder, coronary atherosclerosis, and congestive heart failure), and the year of ablation. There was no significant difference in the risk of pacemaker implantation between ablation patients and propensity score (PS)-matched cardioversion groups (3.5 versus. 4.1 % at 1 year and 8.8 versus 8.3 % at 5 years). Overall, pacemaker implantation occurs in about 1/28 patients within 1 year of catheter ablation. The overall implantation rate decreased between 2005 and 2012. Furthermore, the risk after ablation is similar to cardioversion, suggesting that patients require pacing due to a common underlying electrophysiologic substrate, rather than the ablation itself.

The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila.

PubMed

Duvall, Laura B; Taghert, Paul H

2012-01-01

The neuropeptide Pigment Dispersing Factor (PDF) is essential for normal circadian function in Drosophila. It synchronizes the phases of M pacemakers, while in E pacemakers it decelerates their cycling and supports their amplitude. The PDF receptor (PDF-R) is present in both M and subsets of E cells. Activation of PDF-R stimulates cAMP increases in vitro and in M cells in vivo. The present study asks: What is the identity of downstream signaling components that are associated with PDF receptor in specific circadian pacemaker neurons? Using live imaging of intact fly brains and transgenic RNAi, we show that adenylate cyclase AC3 underlies PDF signaling in M cells. Genetic disruptions of AC3 specifically disrupt PDF responses: they do not affect other Gs-coupled GPCR signaling in M cells, they can be rescued, and they do not represent developmental alterations. Knockdown of the Drosophila AKAP-like scaffolding protein Nervy also reduces PDF responses. Flies with AC3 alterations show behavioral syndromes consistent with known roles of M pacemakers as mediated by PDF. Surprisingly, disruption of AC3 does not alter PDF responses in E cells--the PDF-R(+) LNd. Within M pacemakers, PDF-R couples preferentially to a single AC, but PDF-R association with a different AC(s) is needed to explain PDF signaling in the E pacemakers. Thus critical pathways of circadian synchronization are mediated by highly specific second messenger components. These findings support a hypothesis that PDF signaling components within target cells are sequestered into "circadian signalosomes," whose compositions differ between E and M pacemaker cell types.

The Circadian Neuropeptide PDF Signals Preferentially through a Specific Adenylate Cyclase Isoform AC3 in M Pacemakers of Drosophila

PubMed Central

Duvall, Laura B.; Taghert, Paul H.

2012-01-01

The neuropeptide Pigment Dispersing Factor (PDF) is essential for normal circadian function in Drosophila. It synchronizes the phases of M pacemakers, while in E pacemakers it decelerates their cycling and supports their amplitude. The PDF receptor (PDF-R) is present in both M and subsets of E cells. Activation of PDF-R stimulates cAMP increases in vitro and in M cells in vivo. The present study asks: What is the identity of downstream signaling components that are associated with PDF receptor in specific circadian pacemaker neurons? Using live imaging of intact fly brains and transgenic RNAi, we show that adenylate cyclase AC3 underlies PDF signaling in M cells. Genetic disruptions of AC3 specifically disrupt PDF responses: they do not affect other Gs-coupled GPCR signaling in M cells, they can be rescued, and they do not represent developmental alterations. Knockdown of the Drosophila AKAP-like scaffolding protein Nervy also reduces PDF responses. Flies with AC3 alterations show behavioral syndromes consistent with known roles of M pacemakers as mediated by PDF. Surprisingly, disruption of AC3 does not alter PDF responses in E cells—the PDF-R(+) LNd. Within M pacemakers, PDF-R couples preferentially to a single AC, but PDF-R association with a different AC(s) is needed to explain PDF signaling in the E pacemakers. Thus critical pathways of circadian synchronization are mediated by highly specific second messenger components. These findings support a hypothesis that PDF signaling components within target cells are sequestered into “circadian signalosomes,” whose compositions differ between E and M pacemaker cell types. PMID:22679392

Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

PubMed Central

Masoli, Stefano; Solinas, Sergio; D'Angelo, Egidio

2015-01-01

The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN. PMID:25759640

Primary prevention of atrial fibrillation: does the atrial lead position influence the incidence of atrial arrhythmias in patients with sinus node dysfunction? Results from the PASTA Trial.

PubMed

Spitzer, Stefan G; Wacker, Petra; Gazarek, Steffen; Malinowski, Klaus; Schibgilla, Volker

2009-12-01

PASTA (pacing of the atria in sinus node disease) is a prospective and randomized trial, assessing the effect of different atrial lead positions on the atrial fibrillation (AF) incidence in patients with sinus node disease (SND). The atrial lead position is randomized to: (a) free right atrial wall, (b) right atrial appendage (RAA), (c) coronary sinus ostium (CS-Os), or (d) dual site right atrial pacing (CS-Os + RAA). The pacemakers (Vitatron Selection 9000 or Prevent AF, Vitatron B.V., Arnhem, The Netherlands) are programmed in DDDR 70 mode and the total follow-up duration is 24 months. To describe the atrial rhythm state, pacemaker-derived data (arrhythmia counter) were assessed for AF episodes. AF was considered as evident, if the AF burden (time in AF related to follow-up interval) was >1% (i.e., 15 min/d). Follow-up data after 24 months were evaluated. The analysis evaluates 142 patients (77 male, 74.5 +/- 7.8 years). There was no statistical significant difference with respect to the occurrence of AF between the four groups after 24 months (A: 36%; B: 38%, C: 32%, D: 48%). The percentage of atrial/ventricular pacing was in A: 78/76%, in B: 84/81%, in C: 70/65%, and in D: 79/69%. These differences were not significant. The evaluation of the AF burden >1% and the total AF burden after 24 months did not show differences in the incidence of AF in patients with dual chamber pacemaker therapy for SND. We were not able to demonstrate a significant influence of right atrial lead position on the incidence of AF recurrence.

Safety and feasibility of leadless pacemaker in patients undergoing atrioventricular node ablation for atrial fibrillation.

PubMed

Yarlagadda, Bharath; Turagam, Mohit K; Dar, Tawseef; Jangam, Pragna; Veerapaneni, Vaishnavi; Atkins, Donita; Bommana, Sudharani; Friedman, Paul; Deshmukh, Abhishek J; Doshi, Rahul; Reddy, Vivek Y; Dukkipati, Srinivas R; Natale, Andrea; Lakkireddy, Dhanunjaya

2018-03-01

Atrioventricular node (AVN) ablation and permanent pacing is an established strategy for rate control in the management of symptomatic atrial fibrillation (AF). Leadless pacemakers (LPs) can overcome some of the short-term and long-term limitations of conventional transvenous pacemakers (CTPs). The purpose of this study was to compare the feasibility and safety of LP with those of single-chamber CTP in patients with AF undergoing AVN ablation. We conducted a multicenter observational study of patients undergoing AVN ablation and pacemaker implantation (LP vs single-chamber CTP) between February 2014 and November 2016. The primary efficacy end points were acceptable sensing (R wave ≥5.0 mV) and pacing thresholds (≤2.0 V at 0.4 ms) at follow-up. Safety end points included device-related major and minor (early ≤1 month, late >1 month) adverse events. A total of 127 patients with LP (n = 60) and CTP (n = 67) were studied. The median follow-up was 12 months (interquartile range 12-18 months). Ninety-five percent of the LP group and 97% of the CTP group met the primary efficacy end point at follow-up (57 of 60 vs 65 of 67; P = .66). There was 1 major adverse event (loss of pacing and sensing) in the LP group and 2 (lead dislodgement) in the CTP group (1 of 60 vs 2 of 67; P = 1.00). There were 6 minor adverse events (5 early and 1 late) in the LP group and 3 (early) in the CTP group (6 of 60 vs 3 of 67; P = .30). Our results demonstrate the feasibility and safety of LP compared with CTP in patients undergoing AVN ablation for AF. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange.

PubMed

Choisy, Stéphanie C; Cheng, Hongwei; Orchard, Clive H; James, Andrew F; Hancox, Jules C

2015-11-01

The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35-37°C. Hyperpolarizing voltage commands from -40 mV elicited a Ba(2+)-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from -40 mV L-type Ca(2+) current, IC a,L, was elicited with a half maximal activation voltage (V0.5) of -7.6 ± 1.2 mV (n = 24). IC a,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IK r) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to -40 mV, with an activation V0.5 of -10.7 ± 4.7 mV (n = 8). The IK r magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (-40 mV). Spontaneous APs (5.2 ± 0.5 sec(-1); n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca(2+) release by 1 μmol/L ryanodine, implicating intracellular Ca(2+) cycling in murine AVN cell electrogenesis. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Carbachol regulates pacemaker activities in cultured interstitial cells of Cajal from the mouse small intestine.

PubMed

So, Keum Young; Kim, Sang Hun; Sohn, Hong Moon; Choi, Soo Jin; Parajuli, Shankar Prasad; Choi, Seok; Yeum, Cheol Ho; Yoon, Pyung Jin; Jun, Jae Yeoul

2009-05-31

We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and Ca2+-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of-70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents. The effects of carbachol were blocked by 1-dimethyl-4-diphenylacetoxypiperidinium, a muscarinic M(3) receptor antagonist, but not by methotramine, a muscarinic M(2) receptor antagonist. Intracellular GDP-beta-S suppressed the carbachol-induced effects. Carbachol-induced effects were blocked by external Na+-free solution and by flufenamic acid, a non-selective cation channel blocker, and in the presence of thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum. However, carbachol still produced tonic inward pacemaker currents with the removal of external Ca2+. In recording of intracellular Ca2+ concentrations using fluo 3-AM dye, carbachol increased intracellular Ca2+ concentrations with increasing of Ca2+ oscillations. These results suggest that carbachol modulates the pacemaker activity of ICC through the activation of non-selective cation channels via muscarinic M(3) receptors by a G-protein dependent intracellular Ca2+ release mechanism.

Effects of pine needle extract on pacemaker currents in interstitial cells of Cajal from the murine small intestine.

PubMed

Cheong, Hyeonsook; Paudyal, Dilli Parasad; Jun, Jae Yeoul; Yeum, Cheol Ho; Yoon, Pyung Jin; Park, Chan Guk; Kim, Man Yoo; So, Insuk; Kim, Ki Whan; Choi, Seok

2005-10-31

Extracts of pine needles (Pinus densiflora Sieb. et Zucc.) have diverse physiological and pharmacological actions. In this study we show that pine needle extract alters pacemaker currents in interstitial cells of Cajal (ICC) by modulating ATP-sensitive K+ channels and that this effect is mediated by prostaglandins. In whole cell patches at 30 degrees , ICC generated spontaneous pacemaker potentials in the current clamp mode (I = 0), and inward currents (pacemaker currents) in the voltage clamp mode at a holding potential of -70 mV. Pine needle extract hyperpolarized the membrane potential, and in voltage clamp mode decreased both the frequency and amplitude of the pacemaker currents, and increased the resting currents in the outward direction. It also inhibited the pacemaker currents in a dose-dependent manner. Because the effects of pine needle extract on pacemaker currents were the same as those of pinacidil (an ATP-sensitive K+ channel opener) we tested the effect of glibenclamide (an ATP-sensitive K+ channels blocker) on ICC exposed to pine needle extract. The effects of pine needle extract on pacemaker currents were blocked by glibenclamide. To see whether production of prostaglandins (PGs) is involved in the inhibitory effect of pine needle extract on pacemaker currents, we tested the effects of naproxen, a non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, and AH6809, a prostaglandin EP1 and EP2 receptor antagonist. Naproxen and AH6809 blocked the inhibitory effects of pine needle extract on ICC. These results indicate that pine needle extract inhibits the pacemaker currents of ICC by activating ATP-sensitive K+ channels via the production of PGs.

Modulation of Pacemaker Potentials in Murine Small Intestinal Interstitial Cells of Cajal by Gamisoyo-San, a Traditional Chinese Herbal Medicine.

PubMed

Kim, Doeun; Kim, Jung Nam; Nam, Joo Hyun; Lee, Jong Rok; Kim, Sang Chan; Kim, Byung Joo

2018-04-19

The Gamisoyo-san (GSS) has been used for -improving the gastrointestinal (GI) symptoms. The purpose of this study was to investigate the effects of GSS, a traditional Chinese herbal medicine, on the pacemaker potentials of mouse small intestinal interstitial cells of Cajal (ICCs). ICCs from the small intestines were dissociated and cultured. Whole-cell patch-clamp configuration was used to record pacemaker potentials and membrane currents. GSS depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with 4-diphenylacetoxypiperidinium iodide completely inhibited GSS-induced pacemaker potential depolarizations. Intracellular GDP-β-S inhibited GSS-induced effects, and in the presence of U-73122, GSS-induced effects were inhibited. Also, GSS in the presence of a Ca2+-free solution or thapsigargin did not depolarize pacemaker potentials. However, in the presence of calphostin C, GSS slightly depolarized pacemaker potentials. Furthermore, GSS inhibited both transient receptor potential melastatin7 and Ca2+-activated Cl- channel (anoctamin1) currents. GSS depolarized pacemaker potentials of ICCs via G protein and muscarinic M3 receptor signaling pathways and through internal or external Ca2+-, phospholipase C-, and protein kinase C-dependent and transient receptor potential melastatin 7-, and anoctamin 1-independent pathways. The study shows that GSS may regulate GI tract motility, suggesting that GSS could be a basis for developing novel prokinetic agents for treating GI motility dysfunctions. © 2018 S. Karger AG, Basel.

The Mechanism of Action of Zingerone in the Pacemaker Potentials of Interstitial Cells of Cajal Isolated from Murine Small Intestine.

PubMed

Kim, Jung Nam; Kim, Hyun Jung; Kim, Iksung; Kim, Yun Tai; Kim, Byung Joo

2018-01-01

Zingerone, a major component found in ginger root, is clinically effective for the treatment of various diseases. Interstitial cells of Cajal (ICCs) are the pacemaker cells responsible for slow waves in the gastrointestinal (GI) tract. We investigated the effects of zingerone on the pacemaker potentials of ICCs to assess its mechanisms of action and its potential as a treatment for GI tract motility disorder. We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs. Under the current clamping mode, zingerone inhibited pacemaker potentials of ICCs concentration-dependently. These effects were blocked not by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, but by glibenclamide, a specific ATP-sensitive K+ channel blocker. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor), LY294002 (a phosphoinositide 3-kinase inhibitor), and calphostin C (a protein kinase C (PKC) inhibitor) did not block the effects of zingerone on the pacemaker potentials relative to treatment with zingerone alone. However, zingerone-induced pacemaker potential inhibition was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor), KT5823 (a protein kinase G (PKG) inhibitor), and L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor). In addition, zingerone stimulated cyclic guanosine monophosphate (cGMP) production in ICCs. Finally, pretreatment with PD98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and SP600125 (c-Jun N-terminal kinases (JNK)-specific inhibitor) blocked the zingerone-induced pacemaker potential inhibition. These results suggest that zingerone concentration-dependently inhibits pacemaker potentials of ICCs via NO/cGMP-dependent ATP-sensitive K+ channels through MAPK-dependent pathways. Taken together, this study shows that zingerone may have the potential for development as a GI regulation agent. © 2018 The Author(s). Published by S. Karger AG, Basel.

What Is a Pacemaker?

MedlinePlus

... your pacemaker. • If you work around industrial microwaves, electricity, cars or other large motors, ask your doctor about possible effects. Can I use a cell phone or microwave oven if I have a pacemaker? Microwave ovens, electric blankets, remote controls for TV and other common ...

Tachycardia-bradycardia syndrome: Electrophysiological mechanisms and future therapeutic approaches (Review).

PubMed

Tse, Gary; Liu, Tong; Li, Ka Hou Christien; Laxton, Victoria; Wong, Andy On-Tik; Chan, Yin Wah Fiona; Keung, Wendy; Chan, Camie W Y; Li, Ronald A

2017-03-01

Sick sinus syndrome (SSS) encompasses a group of disorders whereby the heart is unable to perform its pacemaker function, due to genetic and acquired causes. Tachycardia‑bradycardia syndrome (TBS) is a complication of SSS characterized by alternating tachycardia and bradycardia. Techniques such as genetic screening and molecular diagnostics together with the use of pre-clinical models have elucidated the electrophysiological mechanisms of this condition. Dysfunction of ion channels responsible for initiation or conduction of cardiac action potentials may underlie both bradycardia and tachycardia; bradycardia can also increase the risk of tachycardia, and vice versa. The mainstay treatment option for SSS is pacemaker implantation, an effective approach, but has disadvantages such as infection, limited battery life, dislodgement of leads and catheters to be permanently implanted in situ. Alternatives to electronic pacemakers are gene‑based bio‑artificial sinoatrial node and cell‑based bio‑artificial pacemakers, which are promising techniques whose long-term safety and efficacy need to be established. The aim of this article is to review the different ion channels involved in TBS, examine the three‑way relationship between ion channel dysfunction, tachycardia and bradycardia in TBS and to consider its current and future therapies.

Gene therapy to develop a genetically engineered cardiac pacemaker.

PubMed

Glenn, Christopher M; Pogwizd, Steven M

2003-01-01

While cardiac pacemakers are frequently used for the treatment of bradydysrhythmias (from diseases of the cardiac conduction system), their use is still limited by complications that can be life-threatening and expensive. Genetic engineering approaches offer an opportunity to modulate cellular automaticity in a manner that could have significant therapeutic potential. It is well known that ventricular myocytes exhibit a more negative diastolic potential than do pacemaker cells, in large part because of the inward rectifying potassium current/K1 (which pacemaker cells lack). Taking advantage of these intrinsic electrophysiological differences, a biological pacemaker has recently been developed by Miake et al (Nature 2002; 419:132-133) using adenoviral gene transfer approaches. By isolating the gene responsible for/K1 (the Kir2.1 gene), mutating it to make it a dysfunctional channel (a dominant-negative), inserting the mutated gene into an adenoviral vector, and delivering the virus to the hearts of guinea pigs, the investigators were able to successfully convert some ventricular myocytes to pacemaker cells. While issues of safety and long-term efficacy need to be further established, the results of these experiments provide proof of principle that gene transfer offers great promise for treatment of electrophysiological disorders including conduction system disease.

Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weinberger, Florian, E-mail: f.weinberger@uke.de; Mehrkens, Dennis, E-mail: dennis.mehrkens@uk-koeln.de; Starbatty, Jutta, E-mail: starbatty@uke.uni-hamburg.de

Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activitymore » and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.« less

Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon.

PubMed

Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok; Jun, Jae Yeoul

2014-08-01

Lubiprostone is a chloride (Cl(-)) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K(+)] channel blocker) and apamin (a calcium [Ca(2+)]-dependent K(+) channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K(+) channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K(+) channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K(+) channel through a prostanoid EP receptor-independent mechanism.

Effects of Lubiprostone on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Colon

PubMed Central

Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok

2014-01-01

Lubiprostone is a chloride (Cl-) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K+] channel blocker) and apamin (a calcium [Ca2+]-dependent K+ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K+ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K+ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K+ channel through a prostanoid EP receptor-independent mechanism. PMID:25177167

Spontaneous activity of isolated dopaminergic periglomerular cells of the main olfactory bulb.

PubMed

Puopolo, Michelino; Bean, Bruce P; Raviola, Elio

2005-11-01

We examined the electrophysiological properties of a population of identified dopaminergic periglomerular cells of the main olfactory bulb using transgenic mice in which catecholaminergic neurons expressed human placental alkaline phosphatase (PLAP) on the outer surface of the plasma membrane. After acute dissociation, living dopaminergic periglomerular cells were identified by a fluorescently labeled monoclonal antibody to PLAP. In current-clamp mode, dopaminergic periglomerular cells spontaneously generated action potentials in a rhythmic fashion with an average frequency of 8 Hz. The hyperpolarization-activated cation current (Ih) did not seem important for pacemaking because blocking the current with ZD 7288 or Cs+ had little effect on spontaneous firing. To investigate what ionic currents do drive pacemaking, we performed action-potential-clamp experiments using records of pacemaking as voltage command in voltage-clamp experiments. We found that substantial TTX-sensitive Na+ current flows during the interspike depolarization. In addition, substantial Ca2+ current flowed during the interspike interval, and blocking Ca2+ current hyperpolarized the neurons and stopped spontaneous firing. These results show that dopaminergic periglomerular cells have intrinsic pacemaking activity, supporting the possibility that they can maintain a tonic release of dopamine to modulate the sensitivity of the olfactory system during odor detection. Calcium entry into these neurons provides electrical drive for pacemaking as well as triggering transmitter release.

Zebrafish heart as a model to study the integrative autonomic control of pacemaker function

PubMed Central

Stoyek, Matthew R.; Quinn, T. Alexander; Croll, Roger P.

2016-01-01

The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons. PMID:27342878

The distribution of calcium in toad cardiac pacemaker cells during spontaneous firing.

PubMed

Ju, Y K; Allen, D G

2000-12-01

Isolated, spontaneously active pacemaker cells from the sinus venosus region of the toad heart were loaded with the calcium indicator fluo-3. The cells were examined with a confocal microscope to investigate the distribution of calcium during spontaneous activity. Three classes of calcium-related signals were present. First, intense, localised, time-invariant signals were detected from structures distributed across the cell interior. Based on the insensitivity to saponin and the distribution in the cell, these signals appear to arise from fluo-3 located in the sarcoplasmic reticulum and the nuclear envelope. Second, spatially uniform signals from the cytoplasm were present at rest and showed spontaneous increases in [Ca2+]i which propagated along the cell. These Ca2+ transients were uniform in intensity across the diameter of the cell and we could detect no significant delay in the middle of the cell compared to the edges. However, within the nucleus the Ca2+ transient showed a clear delay compared to the cytoplasm. Third, localised, transient increases in [Ca2+]i (Ca2+ sparks) which did not propagate were also detectable. These could be detected both near the surface membrane and in the interior of the cell and reduced in magnitude and increased in duration in the presence of ryanodine. The frequency of firing of Ca2+ sparks significantly increased in the 200-ms period preceding a spontaneous Ca2+ transient. These results suggest that pacemaker cells contain sarcoplasmic reticulum which is distributed across the cell. The Ca2+ transient is uniform across the cell indicating that near-synchronous release of Ca2+ from the sarcoplasmic reticulum is achieved. Ca2+ sparks occur in pacemaker cells though their role in pacemaker function remains to be elucidated.

Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart.

PubMed

Bunch, T Jared; Mahapatra, Srijoy; Bruce, G Keith; Johnson, Susan B; Miller, Dylan V; Horne, Benjamin D; Wang, Xiao-Li; Lee, Hon-Chi; Caplice, Noel M; Packer, Douglas L

2006-05-30

Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-beta1 (TGF-beta1), a stimulant of fibroblasts. Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1x10(6) cells/mL), 7 dogs received TGF-beta1 (5 microg), 4 dogs received fibroblasts and TGF-beta1 (1x10(6) cells/mL+5 microg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66+/-3 ms) and the average RR interval (331+/-17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23+/-4 versus 5+/-5 ms; P=0.05) and fibroblast plus TGF-beta1 (50+/-5 versus 5+/-5 ms; P<0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-beta1 injections. The AH interval was significantly longer after fibroblast plus TGF-beta1 injections than with either therapy (TGF-beta1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110+/-36 versus -41+/-34 ms) and to a greater extent with the addition of TGF-beta1 (294+/-108 versus -41+/-34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-beta1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.

PDF Receptor Expression Reveals Direct Interactions between Circadian Oscillators in Drosophila

PubMed Central

Im, Seol Hee; Taghert, Paul H.

2010-01-01

Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest the network is divisible into M and E oscillators which normally interact and synchronize. Sixteen oscillator neurons (the small and large LNvs) express a neuropeptide called pigment dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4-mediated rescue of pdfr phenotypes using a UAS-PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a ~70 kB PDF receptor (pdfr) transgene which does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non-pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF-expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non-neuronal cells that resides at the base of the eye. PMID:20394051

RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces bradycardia by disturbing the coupled clock pacemaker mechanism

PubMed Central

Wang, Yue Yi; Mesirca, Pietro; Marqués-Sulé, Elena; Villejoubert, Olivier; D’Ocon, Pilar; Ruiz, Cristina; Domingo, Diana; Zorio, Esther; Mangoni, Matteo E.; Benitah, Jean-Pierre; Gómez, Ana María

2017-01-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests syncope or sudden death in children and young adults under stress conditions. CPVT patients often present bradycardia and sino-atrial node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN function in two CPVT families and in a novel knock-in (KI) mouse model carrying the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate. Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was slower in KI mouse SAN preparations than in WT, without any significant alteration in the “funny” current (If ). The L-type Ca2+ current was reduced in KI SAN cells in a [Ca2+]i-dependent way, suggesting that bradycardia was due to disrupted crosstalk between the “voltage” and “Ca2+” clock, and the mechanisms of pacemaking was induced by aberrant spontaneous RyR2- dependent Ca2+ release. This finding was consistent with a higher Ca2+ leak during diastolic periods produced by long-lasting Ca2+ sparks in KI SAN cells. Our results uncover a mechanism for the CPVT-causing RyR2 N-terminal mutation R420Q, and they highlight the fact that enhancing the Ca2+ clock may slow the heart rhythm by disturbing the coupling between Ca2+ and voltage clocks. PMID:28422759

Clinical assessment of pacemaker power sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bilitch, M.; Parsonnet, V.; Furman, S.

1980-01-01

The development of power sources for cardiac pacemakers has progressed from a 15-year usage of mercury-zinc batteries to widely used and accepted lithium cells. At present, there are about 6 different types of lithium cells incorporated into commercially distributed pacemakers. The authors reviewed experience over a 5-year period with 1711 mercury-zinc, 130 nuclear (P238) and 1912 lithium powered pacemakers. The lithium units have included 698 lithium-iodide, 270 lithium-silver chromate, 135 lithium-thionyl chloride, 31 lithium-lead and 353 lithium-cupric sulfide batteries. 57 of the lithium units have failed (91.2% component failure and 5.3% battery failure). 459 mercury-zinc units failed (25% component failuremore » and 68% battery depletion). The data show that lithium powered pacemaker failures are primarily component, while mercury-zinc failures are primarily battery related. It is concluded that mercury-zinc powered pulse generators are obsolete and that lithium and nuclear (P238) power sources are highly reliable over the 5 years for which data are available. 3 refs.« less

A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms.

PubMed

Kozlov, Anatoly; Jaumouillé, Edouard; Machado Almeida, Pedro; Koch, Rafael; Rodriguez, Joseph; Abruzzi, Katharine C; Nagoshi, Emi

2017-07-12

Behavioral circadian rhythms are controlled by multioscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit fly Drosophila melanogaster are regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor unfulfilled ( unf ) represents a regulatory node that provides the small ventral lateral neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). We previously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene period ( per ) (Jaumouillé et al., 2015). To gain more insight into the mechanisms by which UNF contributes to the functioning of the circadian master pacemaker, we identified UNF target genes using chromatin immunoprecipitation. Our data demonstrate that a previously uncharacterized gene CG7837 , which we termed R and B ( Rnb ), acts downstream of UNF to regulate the function of the s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown of Rnb impair locomotor rhythms. RNB localizes to the nucleus, and its loss-of-function blunts the molecular rhythms and output rhythms of the s-LNvs, particularly the circadian rhythms in PDF accumulation and axonal arbor remodeling. These results establish a second pathway by which UNF interacts with the molecular clocks in the s-LNvs and highlight the mechanistic differences in the molecular clockwork within the pacemaker circuit. SIGNIFICANCE STATEMENT Circadian behavior is generated by a pacemaker circuit comprising diverse classes of pacemaker neurons, each of which contains a molecular clock. In addition to the anatomical and functional diversity, recent studies have shown the mechanistic differences in the molecular clockwork among the pacemaker neurons in Drosophila Here, we identified the molecular characteristics distinguishing the s-LNvs, the master pacemaker of the locomotor rhythms, from other clock neuron subtypes. We demonstrated that a newly identified gene Rnb is an s-LNv-specific regulator of the molecular clock and essential for the generation of circadian locomotor behavior. Our results provide additional evidence to the emerging view that the differential regulation of the molecular clocks underlies the functional differences among the pacemaker neuron subgroups. Copyright © 2017 the authors 0270-6474/17/376673-13$15.00/0.

HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia.

PubMed

Saito, Yukihiro; Nakamura, Kazufumi; Yoshida, Masashi; Sugiyama, Hiroki; Takano, Makoto; Nagase, Satoshi; Morita, Hiroshi; Kusano, Kengo F; Ito, Hiroshi

2018-05-30

A biological pacemaker is expected to solve the persisting problems of an artificial cardiac pacemaker including short battery life, lead breaks, infection, and electromagnetic interference. We previously reported HCN4 overexpression enhances pacemaking ability of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) in vitro. However, the effect of these cells on bradycardia in vivo has remained unclear. Therefore, we transplanted HCN4-overexpressing mESC-CMs into bradycardia model animals and investigated whether they could function as a biological pacemaker. The rabbit Hcn4 gene was transfected into mouse embryonic stem cells and induced HCN4-overexpressing mESC-CMs. Non-cardiomyocytes were removed under serum/glucose-free and lactate-supplemented conditions. Cardiac balls containing 5 × 10 3 mESC-CMs were made by using the hanging drop method. One hundred cardiac balls were injected into the left ventricular free wall of complete atrioventricular block (CAVB) model rats. Heart beats were evaluated using an implantable telemetry system 7 to 30 days after cell transplantation. The result showed that ectopic ventricular beats that were faster than the intrinsic escape rhythm were often observed in CAVB model rats transplanted with HCN4-overexpressing mESC-CMs. On the other hand, the rats transplanted with non-overexpressing mESC-CMs showed sporadic single premature ventricular contraction but not sustained ectopic ventricular rhythms. These results indicated that HCN4-overexpressing mESC-CMs produce rapid ectopic ventricular rhythms as a biological pacemaker.

PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila.

PubMed

Im, Seol Hee; Taghert, Paul H

2010-06-01

Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest that the network is divisible into M and E oscillators, which normally interact and synchronize. Sixteen oscillator neurons (the small and large lateral neurons [LNvs]) express a neuropeptide called pigment-dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4-mediated rescue of pdfr phenotypes using a UAS-PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a approximately 70-kB PDF receptor (pdfr) transgene that does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non-pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF-expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non-neuronal cells that resides at the base of the eye. (c) 2009 Wiley-Liss, Inc.

Signaling of Pigment-Dispersing Factor (PDF) in the Madeira Cockroach Rhyparobia maderae

PubMed Central

Funk, Nico W.; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca2+ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca2+ baseline concentration and frequency of oscillating Ca2+ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1–4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca2+ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K+ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K+ and Na+ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance. PMID:25269074

Small functional If current in sinoatrial pacemaker cells of the brown trout (Salmo trutta fario) heart despite strong expression of HCN channel transcripts.

PubMed

Hassinen, Minna; Haverinen, Jaakko; Vornanen, Matti

2017-12-01

Funny current ( I f ), formed by hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), is supposed to be crucial for the membrane clock regulating the cardiac pacemaker mechanism. We examined the presence and activity of HCN channels in the brown trout ( Salmo trutta fario ) sinoatrial (SA) pacemaker cells and their putative role in heart rate ( f H ) regulation. Six HCN transcripts (HCN1, HCN2a, HCN2ba, HCN2bb, HCN3, and HCN4) were expressed in the brown trout heart. The total HCN transcript abundance was 4.0 and 4.9 times higher in SA pacemaker tissue than in atrium and ventricle, respectively. In the SA pacemaker, HCN3 and HCN4 were the main isoforms representing 35.8 ± 2.7 and 25.0 ± 1.5%, respectively, of the total HCN transcripts. Only a small I f with a mean current density of -1.2 ± 0.37 pA/pF at -140 mV was found in 4 pacemaker cells out of 16 spontaneously beating cells examined, despite the optimization of recording conditions for I f activity. I f was not found in any of the 24 atrial myocytes and 21 ventricular myocytes examined. HCN4 coexpressed with the MinK-related peptide 1 (MiRP1) β-subunit in CHO cells generated large I f currents. In contrast, HCN3 (+MiRP1) failed to produce I f in the same expression system. Cs + (2 mM), which blocked 84 ± 12% of the native I f , reversibly reduced f H 19.2 ± 3.6% of the excised multicellular pacemaker tissue from 53 ± 5 to 44 ± 5 beats/min ( P < 0.05). However, this effect was probably due to the reduction of I Kr , which was also inhibited (63.5 ± 4.6%) by Cs + These results strongly suggest that f H regulation in the brown trout heart is largely independent on I f . Copyright © 2017 the American Physiological Society.

Lithium-iodine pacemaker cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneider, A.A.; Snyder, S.E.; DeVan, T.

1980-01-01

The lithium-iodine pacemaker cell is described as supplied by several manufacturers. The features of each design are discussed along with their effect on energy density, self-discharge and shape of the discharge curve. Differences in performance characteristics are related to morphology of the lithium iodine electrolyte and to the form of the cathode. A new, high-drain cell is mentioned which can supply 60 /mu/a/cm/sup 2/. 10 refs.

[Cellular mechanism of the generation of spontaneous activity in gastric muscle].

PubMed

Nakamura, Eri; Kito, Yoshihiko; Fukuta, Hiroyasu; Yanai, Yoshimasa; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

2004-03-01

In gastric smooth muscles, interstitial cells of Cajal (ICC) might be the pacemaker cells of spontaneous activities since ICC are rich in mitochondria and are connected with smooth muscle cells via gap junctions. Several types of ICC are distributed widely in the stomach wall. A group of ICC distributed in the myenteric layer (ICC-MY) were the pacemaker cells of gastrointestinal smooth muscles. Pacemaker potentials were generated in ICC-MY, and the potentials were conducted to circular smooth muscles to trigger slow waves and also conducted to longitudinal muscles to form follower potentials. In circular muscle preparations, interstitial cells distributed within muscle bundles (ICC-IM) produced unitary potentials, which were conducted to circular muscles to form slow potentials by summation. In mutant mice lacking inositol trisphosphate (IP(3)) receptor, slow waves were absent in gastric smooth muscles. The generation of spontaneous activity was impaired by the inhibition of Ca(2+)-release from internal stores through IP(3) receptors, inhibition of mitochondrial Ca(2+)-handling with proton pump inhibitors, and inhibition of ATP-sensitive K(+)-channels at the mitochondrial inner membrane. These results suggested that mitochondrial Ca(2+)-handling causes the generation of spontaneous activity in pacemaker cells. Possible involvement of protein kinase C (PKC) in the Ca(2+) signaling system was also suggested.

Mangalith: a new lithium pacemaker battery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerbier, G.; Lehmann, G.

1980-01-01

An original lithium battery system is being developed for pacemaker application. The material used, lithium-manganese dioxide, industrially available at the present time for a variety of electronic applications, has been modified and adapted for pacemaker power requirements. The utilization of a different modification of manganese dioxide offers performance advantages. The cell technology is described and performance comparisons between this new cathode material and the industrial counterpart are reported. 7 refs.

The neurochemical basis of photic entrainment of the circadian pacemaker

NASA Technical Reports Server (NTRS)

Rea, Michael A.; Buckley, Becky; Lutton, Lewis M.

1992-01-01

Circadian rhythmicity in mammals is controlled by the action of a light-entrainable hypothalamus, in association with two cell clusters known as the supra chiasmatic nuclei (SCN). In the absence of temporal environmental clues, this pacemaker continues to measure time by an endogenous mechanism (clock), driving biochemical, physiological, and behavioral rhythms that reflect the natural period of the pacemaker oscillation. This endogenous period usually differs slightly from 24 hours (i.e., circadian). When mammals are maintained under a 24 hour light-dark (LD) cycle, the pacemaker becomes entrained such that the period of the pacemaker oscillation matches that of the LD cycle. Potentially entraining photic information is conveyed to the SCN via a direct retinal projection, the retinohypothalamic tract (RHT). RHT neurotransmission is thought to be mediated by the release of excitatory amino acids (EAA) in the SCN. In support of this hypothesis, recent experiments using nocturnal rodents have shown that EAA antagonists block the effects of light on pacemaker-driven behavioral rhythms, and attenuate light induced gene expression in SCN cells. An understanding of the neurochemical basis of the photic entrainment process would facilitate the development of pharmacological strategies for maintaining synchrony among shift workers in environments, such as the Space Station, which provide unreliable or conflicting temporal photic clues.

Connectivity of Pacemaker Neurons in the Neonatal Rat Superficial Dorsal Horn

PubMed Central

Ford, Neil C.; Arbabi, Shahriar; Baccei, Mark L.

2014-01-01

Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations which are targeted by pacemaker axons have yet to be identified. The present study combines patch clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. While small pacemaker neurons possessed ramified axons which contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons which crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-PAG neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits as well as the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the CNS. PMID:25380417

Membrane currents underlying activity in frog sinus venosus

PubMed Central

Brown, Hilary F.; Giles, Wayne; Noble, Susan J.

1977-01-01

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential. 2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2·0 × 10-6 g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing. 3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca2+/Na+) current, Isi, of other cardiac tissues. The threshold for Isi is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization. 4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions. 5. Outward current decay is not a simple exponential, and Hodgkin—Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the `plateau' range of the sinus action potential. 6. These results are compared with other recently published voltage clamp data from the rabbit sino—atrial node. 7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, Isi. PMID:303699

Permanent epicardial pacing in pediatric patients: 12-year experience at a single center.

PubMed

Kwak, Jae Gun; Kim, Soo-Jin; Song, Jin Young; Choi, Eun Young; Lee, Sang Yoon; Shim, Woo Sup; Lee, Chang-Ha; Lee, Cheul; Park, Chun Soo

2012-02-01

Permanent cardiac pacing is not often done in children, and when done is usually accomplished through epicardial pacing. We reviewed a 12-year experience with the implantation of epicardial pacemakers by our clinical group. Fifty-three patients who underwent their first implantation of an epicardial pacemaker before the age of 18 years and between 1997 and 2009 were included in our study. The mean age of the patients at the time of first pacemaker implantation was 5.7±4.8 years. Indications for pacemaker implantation included postoperative or congenital atrioventricular block and sinus node dysfunction. The patients underwent 105 operations for the replacement of pacemaker pulse generators and 75 operations for the replacement of pacemaker leads. The most commonly used generator mode was the rate-responsive accelerometer-based (DDDR) mode, which was used in 40.9% of the patients. We used more non-steroid-eluting leads (70.1%) than steroid-eluting leads (29.1%). The overall duration of follow-up in the study was 8.0±4.5 years (range, 2.1 months to approximately 17.0 years). Freedom from the need for generator replacement was 98.0%, 60.7%, and 11.1% at 1, 5, and 8 years, respectively. A tendency toward early generator exhaustion was observed among younger patients (p=0.058). The generator mode used for pacing did not significantly affect generator longevity. Freedom from the need for lead replacement was 98.3%, 83.8%, and 63.6% at 1, 5, and 10 years, respectively. The mean longevity of the leads used in the study was 10.8±0.8 years. Neither patient age at the time of lead implantation nor type of lead significantly affected lead longevity. Lead longevity was sufficiently long and did not vary significantly according to type of lead. Generator longevity was not affected by lead type, generator mode, or patient age at the time of pacemaker implantation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Incidence and Time Course for Developing Heart Failure With High-Burden Right Ventricular Pacing.

PubMed

Merchant, Faisal M; Hoskins, Michael H; Musat, Dan L; Prillinger, Julie B; Roberts, Gregory J; Nabutovsky, Yelena; Mittal, Suneet

2017-06-01

Although right ventricular pacing can contribute to cardiomyopathy, the impact of complete atrioventricular block (cAVB) on heart failure (HF) development in pacemaker patients has not been well characterized. We evaluated the incidence and time course for developing HF after pacemaker implantation for cAVB. A MarketScan database identified patients undergoing dual-chamber pacemaker implantation from 2008 to 2014. Patients with cAVB were identified by an atrioventricular node ablation or diagnosis of third-degree AVB. Patients with ≥1 year of continuous MarketScan enrollment before and after implant and without a previous diagnosis of HF were dichotomized into those with cAVB and without AVB. The primary end point was new HF assessed over acute (0-6 months) and chronic (6 months to 4 years) phases post-pacemaker implantation. The cohort included 6994 cAVB patients and 14 208 patients without AVB, followed for 2.35 years (interquartile range, 1.62-3.39 years). After adjustment for baseline covariates, patients with cAVB experienced an increased risk of new-onset HF in the acute phase (hazard ratio, 1.62; 95% confidence interval, 1.48-1.79; P <0.001). Although the risk of HF remained elevated among those with cAVB in the chronic phase, the effect was attenuated (hazard ratio, 1.16; 95% confidence interval, 1.08-1.25; P <0.001). After pacemaker implantation, younger patients (≤55 years of age) and those with an antecedent history of atrial fibrillation experienced the highest risk of HF associated with cAVB. Patients with a diagnosis of cAVB, and thus presumed to have a higher burden of right ventricular pacing, experienced an increased risk of new-onset HF after pacemaker implantation compared with those without AVB. Better tools are needed to identify patients at high risk of developing HF in the setting of right ventricular pacing and to determine whether these patients benefit from upfront biventricular pacing. © 2017 American Heart Association, Inc.

From two competing oscillators to one coupled-clock pacemaker cell system

PubMed Central

Yaniv, Yael; Lakatta, Edward G.; Maltsev, Victor A.

2015-01-01

At the beginning of this century, debates regarding “what are the main control mechanisms that ignite the action potential (AP) in heart pacemaker cells” dominated the electrophysiology field. The original theory which prevailed for over 50 years had advocated that the ensemble of surface membrane ion channels (i.e., “M-clock”) is sufficient to ignite rhythmic APs. However, more recent experimental evidence in a variety of mammals has shown that the sarcoplasmic reticulum (SR) acts as a “Ca2+-clock” rhythmically discharges diastolic local Ca2+ releases (LCRs) beneath the cell surface membrane. LCRs activate an inward current (likely that of the Na+/Ca2+ exchanger) that prompts the surface membrane “M-clock” to ignite an AP. Theoretical and experimental evidence has mounted to indicate that this clock “crosstalk” operates on a beat-to-beat basis and determines both the AP firing rate and rhythm. Our review is focused on the evolution of experimental definition and numerical modeling of the coupled-clock concept, on how mechanisms intrinsic to pacemaker cell determine both the heart rate and rhythm, and on future directions to develop further the coupled-clock pacemaker cell concept. PMID:25741284

Maximum heart rate in brown trout (Salmo trutta fario) is not limited by firing rate of pacemaker cells.

PubMed

Haverinen, Jaakko; Abramochkin, Denis V; Kamkin, Andre; Vornanen, Matti

2017-02-01

Temperature-induced changes in cardiac output (Q̇) in fish are largely dependent on thermal modulation of heart rate (f H ), and at high temperatures Q̇ collapses due to heat-dependent depression of f H This study tests the hypothesis that firing rate of sinoatrial pacemaker cells sets the upper thermal limit of f H in vivo. To this end, temperature dependence of action potential (AP) frequency of enzymatically isolated pacemaker cells (pacemaker rate, f PM ), spontaneous beating rate of isolated sinoatrial preparations (f SA ), and in vivo f H of the cold-acclimated (4°C) brown trout (Salmo trutta fario) were compared under acute thermal challenges. With rising temperature, f PM steadily increased because of the acceleration of diastolic depolarization and shortening of AP duration up to the break point temperature (T BP ) of 24.0 ± 0.37°C, at which point the electrical activity abruptly ceased. The maximum f PM at T BP was much higher [193 ± 21.0 beats per minute (bpm)] than the peak f SA (94.3 ± 6.0 bpm at 24.1°C) or peak f H (76.7 ± 2.4 at 15.7 ± 0.82°C) (P < 0.05). These findings strongly suggest that the frequency generator of the sinoatrial pacemaker cells does not limit f H at high temperatures in the brown trout in vivo. Copyright © 2017 the American Physiological Society.

Signaling of pigment-dispersing factor (PDF) in the Madeira cockroach Rhyparobia maderae.

PubMed

Wei, Hongying; Yasar, Hanzey; Funk, Nico W; Giese, Maria; Baz, El-Sayed; Stengl, Monika

2014-01-01

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.

Prevalence of E/A wave fusion and A wave truncation in DDD pacemaker patients with complete AV block under nominal AV intervals.

PubMed

Poller, Wolfram C; Dreger, Henryk; Schwerg, Marius; Melzer, Christoph

2015-01-01

Optimization of the AV-interval (AVI) in DDD pacemakers improves cardiac hemodynamics and reduces pacemaker syndromes. Manual optimization is typically not performed in clinical routine. In the present study we analyze the prevalence of E/A wave fusion and A wave truncation under resting conditions in 160 patients with complete AV block (AVB) under the pre-programmed AVI. We manually optimized sub-optimal AVI. We analyzed 160 pacemaker patients with complete AVB, both in sinus rhythm (AV-sense; n = 129) and under atrial pacing (AV-pace; n = 31). Using Doppler analyses of the transmitral inflow we classified the nominal AVI as: a) normal, b) too long (E/A wave fusion) or c) too short (A wave truncation). In patients with a sub-optimal AVI, we performed manual optimization according to the recommendations of the American Society of Echocardiography. All AVB patients with atrial pacing exhibited a normal transmitral inflow under the nominal AV-pace intervals (100%). In contrast, 25 AVB patients in sinus rhythm showed E/A wave fusion under the pre-programmed AV-sense intervals (19.4%; 95% confidence interval (CI): 12.6-26.2%). A wave truncations were not observed in any patient. All patients with a complete E/A wave fusion achieved a normal transmitral inflow after AV-sense interval reduction (mean optimized AVI: 79.4 ± 13.6 ms). Given the rate of 19.4% (CI 12.6-26.2%) of patients with a too long nominal AV-sense interval, automatic algorithms may prove useful in improving cardiac hemodynamics, especially in the subgroup of atrially triggered pacemaker patients with AV node diseases.

Review of the If selective channel inhibitor ivabradine in the treatment of chronic stable angina.

PubMed

Prasad, Usha K; Gray, David; Purcell, Henry

2009-02-01

Coronary heart disease is the major cause of morbidity and mortality in industrialized countries, and its prevalence is predicted to grow as the population ages. Current drugs for chronic stable angina (such as beta-blockers, calcium-channel blockers, long- and short-acting nitrates, and potassium-channel activators) are often effective, either as monotherapy or in combination, but side effects and contraindications may limit their use. The "I(f)" (for "funny") channel, discovered in 1979, is expressed mainly in the membrane of pacemaker cells present in the sinus node, the atrioventricular node, the ventricular conduction pathways, and ventricular myocytes. By determining the slope of diastolic depolarization, which in turn controls action potential frequency, it is a key determinant of heart rate and so provides a new therapeutic target for controlling angina symptoms. A new antiangina drug, ivabradine, has been developed and licensed for clinical use. It exclusively reduces the heart rate by selectively blocking the I(f) channel of the sino-atrial node. As clinical trials have shown it to be remarkably well-tolerated, ivabradine offers an alternative for patients who cannot take, or are intolerant of, beta blockade. This review provides an insight into this new agent, its historical background, mechanism of action, and pathophysiologic basis, and provides up-to-date evidence-based information on its optimum use in stable angina.

Clinically oriented device programming in bradycardia patients: part 2 (atrioventricular blocks and neurally mediated syncope). Proposals from AIAC (Italian Association of Arrhythmology and Cardiac Pacing).

PubMed

Palmisano, Pietro; Ziacchi, Matteo; Biffi, Mauro; Ricci, Renato P; Landolina, Maurizio; Zoni-Berisso, Massimo; Occhetta, Eraldo; Maglia, Giampiero; Botto, Gianluca; Padeletti, Luigi; Boriani, Giuseppe

2018-04-01

: The purpose of this two-part consensus document is to provide specific suggestions (based on an extensive literature review) on appropriate pacemaker setting in relation to patients' clinical features. In part 2, criteria for pacemaker choice and programming in atrioventricular blocks and neurally mediate syncope are proposed. The atrioventricular blocks can be paroxysmal or persistent, isolated or associated with sinus node disease. Neurally mediated syncope can be related to carotid sinus syndrome or cardioinhibitory vasovagal syncope. In sinus rhythm, with persistent atrioventricular block, we considered appropriate the activation of mode-switch algorithms, and algorithms for auto-adaptive management of the ventricular pacing output. If the atrioventricular block is paroxysmal, in addition to algorithms mentioned above, algorithms to maximize intrinsic atrioventricular conduction should be activated. When sinus node disease is associated with atrioventricular block, the activation of rate-responsive function in patients with chronotropic incompetence is appropriate. In permanent atrial fibrillation with atrioventricular block, algorithms for auto-adaptive management of the ventricular pacing output should be activated. If the atrioventricular block is persistent, the activation of rate-responsive function is appropriate. In carotid sinus syndrome, adequate rate hysteresis should be programmed. In vasovagal syncope, specialized sensing and pacing algorithms designed for reflex syncope prevention should be activated.

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators.

PubMed

Wei, Ruihan; Parsons, Sean P; Huizinga, Jan D

2017-03-01

What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ICC network as a two-dimensional network of weakly coupled oscillators with a frequency gradient and showed changes over time in video and graphical formats. Model parameters were obtained from slow-wave-driven contraction patterns in the mouse intestine and pacemaker slow-wave activities from the cat intestine. Marked changes in propagating oscillation patterns (including changes from propagation to non-propagating) were observed by changing network parameters (coupling strength between oscillators, the frequency gradient and frequency noise), which affected synchronization, propagation velocity and occurrence of dislocations (termination of an oscillation). Complete uncoupling of a circumferential ring of oscillators caused the proximal and distal section to desynchronize, but complete synchronization was maintained with only a single oscillator connecting the sections with high enough coupling. The network of oscillators could withstand loss; even with 40% of oscillators lost randomly within the network, significant synchronization and anterograde propagation remained. A local increase in pacemaker frequency diminished anterograde propagation; the effects were strongly dependent on location, frequency gradient and coupling strength. In summary, the model puts forth the hypothesis that fundamental changes in oscillation patterns (ICC slow-wave activity or circular muscle contractions) can occur through physiological modulation of network properties. Strong evidence is provided to accept the ICC network as a system of coupled oscillators. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

A SERIES OF SUPPRESSIVE SIGNALS WITHIN THE DROSOPHILA CIRCADIAN NEURAL CIRCUIT GENERATES SEQUENTIAL DAILY OUTPUTS

PubMed Central

Liang, Xitong; Holy, Timothy E; Taghert, Paul H

2017-01-01

Summary We studied the Drosophila circadian neural circuit using whole brain imaging in vivo. Five major groups of pacemaker neurons display synchronized molecular clocks, yet each exhibits a distinct phase of daily Ca2+ activation. Light and neuropeptide PDF from morning cells (s-LNv) together delay the phase of the evening (LNd) group by ~12 h; PDF alone delays the phase of the DN3 group, by ~17 h. Neuropeptide sNPF, released from s-LNv and LNd pacemakers, produces latenight Ca2+ activation in the DN1 group. The circuit also features negative feedback by PDF to truncate the s-LNv Ca2+ wave and terminate PDF release. Both PDF and sNPF suppress basal Ca2+ levels in target pacemakers with long durations by cell autonomous actions. Thus, light and neuropeptides act dynamically at distinct hubs of the circuit to produce multiple suppressive events that create the proper tempo and sequence of circadian pacemaker neuronal activities. PMID:28552314

Biophysically based mathematical modeling of interstitial cells of Cajal slow wave activity generated from a discrete unitary potential basis.

PubMed

Faville, R A; Pullan, A J; Sanders, K M; Koh, S D; Lloyd, C M; Smith, N P

2009-06-17

Spontaneously rhythmic pacemaker activity produced by interstitial cells of Cajal (ICC) is the result of the entrainment of unitary potential depolarizations generated at intracellular sites termed pacemaker units. In this study, we present a mathematical modeling framework that quantitatively represents the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC operating over the physiological membrane potential range. The mathematical model presented here extends our recently developed biophysically based pacemaker unit modeling framework by including mechanisms necessary for coordinating unitary potential events, such as a T-Type Ca2+ current, Vm-dependent K+ currents, and global Ca2+ diffusion. Model simulations produce spontaneously rhythmic slow wave depolarizations with an amplitude of 65 mV at a frequency of 17.4 cpm. Our model predicts that activity at the spatial scale of the pacemaker unit is fundamental for ICC slow wave generation, and Ca2+ influx from activation of the T-Type Ca2+ current is required for unitary potential entrainment. These results suggest that intracellular Ca2+ levels, particularly in the region local to the mitochondria and endoplasmic reticulum, significantly influence pacing frequency and synchronization of pacemaker unit discharge. Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations.

High sensitivity of spontaneous spike frequency to sodium leak current in a Lymnaea pacemaker neuron.

PubMed

Lu, T Z; Kostelecki, W; Sun, C L F; Dong, N; Pérez Velázquez, J L; Feng, Z-P

2016-12-01

The spontaneous rhythmic firing of action potentials in pacemaker neurons depends on the biophysical properties of voltage-gated ion channels and background leak currents. The background leak current includes a large K + and a small Na + component. We previously reported that a Na + -leak current via U-type channels is required to generate spontaneous action potential firing in the identified respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea stagnalis. We further investigated the functional significance of the background Na + current in rhythmic spiking of RPeD1 neurons. Whole-cell patch-clamp recording and computational modeling approaches were carried out in isolated RPeD1 neurons. The whole-cell current of the major ion channel components in RPeD1 neurons were characterized, and a conductance-based computational model of the rhythmic pacemaker activity was simulated with the experimental measurements. We found that the spiking rate is more sensitive to changes in the Na + leak current as compared to the K + leak current, suggesting a robust function of Na + leak current in regulating spontaneous neuronal firing activity. Our study provides new insight into our current understanding of the role of Na + leak current in intrinsic properties of pacemaker neurons. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

I(f) inhibition in cardiovascular diseases.

PubMed

Thollon, Catherine; Vilaine, Jean-Paul

2010-01-01

Heart rate (HR) is determined by the pacemaker activity of cells from the sinoatrial node (SAN), located in the right atria. Spontaneous electrical activity of SAN cells results from a diastolic depolarization (DD). Despite controversy in the exact contribution of funny current (I(f)) in pacemaking, it is a major contributor of DD. I(f) is an inward Na(+)/K(+) current, activated upon hyperpolarization and directly modulated by cyclic adenosine monophosphate. The f-proteins are hyperpolarization-activated cyclic nucleotide-gated channels, HCN4 being the main isoform of SAN. Ivabradine (IVA) decreases DD and inhibits I(f) in a use-dependent manner. Under normal conditions IVA selectively reduces HR and limits exercise-induced tachycardia, in animals and young volunteers. Reduction in HR with IVA both decreases myocardial oxygen consumption and increases its supply due to prolongation of diastolic perfusion time. In animal models and in human with coronary artery disease (CAD), IVA has anti-anginal and anti-ischemic efficacy, equipotent to classical treatments, β-blockers, or calcium channel blockers. As expected from its selectivity for I(f), the drug is safe and well tolerated with minor visual side effects. As a consequence, IVA is the first inhibitor of I(f) approved for the treatment of stable angina. Available clinical data indicate that IVA could improve the management of stable angina in all patients including those treated with β-blockers. As chronic elevation of resting HR is an independent predictor of mortality, pure HR reduction by inhibition of I(f) could, beyond the control of anti-anginal symptoms, improve the prognosis of CAD and heart failure; this therapeutic potential is currently under evaluation with IVA. Copyright © 2010 Elsevier Inc. All rights reserved.

Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells.

PubMed

Sirenko, Syevda G; Yang, Dongmei; Maltseva, Larissa A; Kim, Mary S; Lakatta, Edward G; Maltsev, Victor A

2017-01-01

Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed "calcium clock"), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border.

Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells

PubMed Central

Sirenko, Syevda G.; Yang, Dongmei; Maltseva, Larissa A.; Kim, Mary S.; Lakatta, Edward G.

2017-01-01

Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed “calcium clock”), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border. PMID:28945810

Integrative Modeling of Electrical Properties of Pacemaker Cardiac Cells

NASA Astrophysics Data System (ADS)

Grigoriev, M.; Babich, L.

2016-06-01

This work represents modeling of electrical properties of pacemaker (sinus) cardiac cells. Special attention is paid to electrical potential arising from transmembrane current of Na+, K+ and Ca2+ ions. This potential is calculated using the NaCaX model. In this respect, molar concentration of ions in the intercellular space which is calculated on the basis of the GENTEX model is essential. Combined use of two different models allows referring this approach to integrative modeling.

Cell types and synaptic organization of the medullary electromotor nucleus in a constant frequency weakly electric fish, Sternarchus albifrons.

PubMed

Tokunaga, A; Akert, K; Sandri, C; Bennett, M V

1980-08-01

The medullary electromotor nucleus (EMN) of Sternarchus albifrons was studied at the light and electron microscopic levels. The EMN consists of a dense meshwork of myelinated axons and glial elements with interposed large neurons; it is provided with an abundant supply of capillaries. Two types of essentially adrendritic nerve cells were distinguished on the basis of size: giant neurons (approx. 70 micrometers in diameter) and large neurons (approx. 30 micrometers in diameter). Their population ratio is 1:4. Only giant cells are labelled following the injection of retrograde tracer into the spinal cord; they are therefore identified with the so-called "relay cells" of other gymnotids. Tracer experiments further suggest that the descending axons of these relay cells give off collateral branches throughout the elongated spinal electromotor nucleus. In contrast, the large cells remain unlabelled and therefore lack spinal projections; they most likely correspond to "pacemaker cells." The perikaryal surface, including axon hillock and proximal part of initial segment of both types of EMN cells, is contacted by clusters of synaptic terminals and astrocytic processes. Two main varieties of synaptic terminals occur: (1) large endings and (2) ordinary end feet with standard size (S-type) and variable size (Sv-type) clear, spherical vesicles. The junction between large endings and EMN cells is characterized by the combination of gap junctions and surrounding intermediate junctions whose freeze-fracture characteristics were morphometrically analyzed. The large endings were formed by nodes of Ranvier as well as by fiber terminations, and synchronization within the EMN may be achieved by presynaptic fibers. Some of the contacts occur directly on the initial segment, which could allow activity to bypass the soma. It is concluded that the elctromotor system of Sternarchus is comprised of a rapid conduction pathway where medullary pacemaker and relay cells as well as spinal electromotor neurons are coupled by synapses with gap junctions. In contrast to the spinal electromotor neurons, the medullary EMN cells receive synapses with morphological characteristics of chemical transmission, and the S-type and SV-type terminals may possibly correspond to Gray's Type I and Type II synapses, respectively. These synapses may be involved in modulation of the electric organ discharge frequency.

Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes—A model

NASA Astrophysics Data System (ADS)

Kanani, S.; Pumir, A.; Krinsky, V.

2008-01-01

One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler Reuter model, as well as with the elaborate dynamic Luo Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I channels is low enough. At too high an expression level of I channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I channels observed in ventricular myocytes, both in the Beeler Reuter and in the dynamic Luo Rudy models are too high to allow to observe oscillations. With expression levels below ˜1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

Diadenosine Polyphosphates Suppress the Effects of Sympathetic Nerve Stimulation in Rabbit Heart Pacemaker.

PubMed

Abramochkin, D V; Pustovit, K B; Kuz'min, V S

2017-09-01

The modulatory influence of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) on the effect of intramural autonomic nerve stimulation in isolated rabbit sinoatrial node were examined. Electrical activity of the sinoatrial node was recorded intracellularly. Against the background of blockade of adrenergic effects with propranolol (3×10 -6 M) or in preparations isolated 2 h after injection of reserpine (2 mg/kg), nerve stimulation induced short-term membrane hyperpolarization and diminished the sinus node firing rate. These phenomena were not affected by Ap4A or Ap5A (10 -5 M). Under the action of atropine (3×10 -6 M) that completely eliminated the cholinergic influences, nerve stimulation enhanced the sinus node firing rate by 17.30±3.45% from the initial rate. Both Ap4A and Ap5A moderated the stimulation-induced elevation of firing rate to 9.9±2.8 and 10.5±2.9%, respectively. The data suggest that diadenosine polyphosphates significantly modulate the sympathetic influences on the heart rhythm, but have no effect on the parasympathetic control over activity of sinoatrial node.

Biophysically Based Mathematical Modeling of Interstitial Cells of Cajal Slow Wave Activity Generated from a Discrete Unitary Potential Basis

PubMed Central

Faville, R.A.; Pullan, A.J.; Sanders, K.M.; Koh, S.D.; Lloyd, C.M.; Smith, N.P.

2009-01-01

Abstract Spontaneously rhythmic pacemaker activity produced by interstitial cells of Cajal (ICC) is the result of the entrainment of unitary potential depolarizations generated at intracellular sites termed pacemaker units. In this study, we present a mathematical modeling framework that quantitatively represents the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC operating over the physiological membrane potential range. The mathematical model presented here extends our recently developed biophysically based pacemaker unit modeling framework by including mechanisms necessary for coordinating unitary potential events, such as a T-Type Ca2+ current, Vm-dependent K+ currents, and global Ca2+ diffusion. Model simulations produce spontaneously rhythmic slow wave depolarizations with an amplitude of 65 mV at a frequency of 17.4 cpm. Our model predicts that activity at the spatial scale of the pacemaker unit is fundamental for ICC slow wave generation, and Ca2+ influx from activation of the T-Type Ca2+ current is required for unitary potential entrainment. These results suggest that intracellular Ca2+ levels, particularly in the region local to the mitochondria and endoplasmic reticulum, significantly influence pacing frequency and synchronization of pacemaker unit discharge. Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations. PMID:19527643

Design and Testing of a Percutaneously Implantable Fetal Pacemaker

PubMed Central

Loeb, Gerald E.; Zhou, Li; Zheng, Kaihui; Nicholson, Adriana; Peck, Raymond A.; Krishnan, Anjana; Silka, Michael; Pruetz, Jay; Chmait, Ramen; Bar-Cohen, Yaniv

2012-01-01

We are developing a cardiac pacemaker with a small, cylindrical shape that permits percutaneous implantation into a fetus to treat complete heart block and consequent hydrops fetalis, which can otherwise be fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. Acute tests in adult rabbits demonstrated the range of electrical parameters required for successful pacing and the feasibility of successfully implanting the device percutaneously under ultrasonic imaging guidance. The lithium cell can be recharged inductively as needed, as indicated by a small decline in the pulsing rate. PMID:22855119

Inward-rectifying potassium (Kir) channels regulate pacemaker activity in spinal nociceptive circuits during early life

PubMed Central

Li, Jie; Blankenship, Meredith L.; Baccei, Mark L.

2013-01-01

Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst-firing and are distinguished by a lower “leak” membrane conductance compared to adjacent, non-bursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (Kir) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and non-pacemakers indicate the presence of functionally distinct Kir currents in these two populations at room temperature. However, Kir currents in both groups showed high sensitivity to block by extracellular Ba2+ (IC50 ~ 10 µM), which suggests the presence of ‘classical’ Kir (Kir2.x) channels in the neonatal SDH. The reduced Kir conductance within pacemakers is unlikely to be explained by an absence of particular Kir2.x isoforms, as immunohistochemical analysis revealed the expression of Kir2.1, Kir2.2 and Kir2.3 within spontaneously bursting neurons. Importantly, Ba2+ application unmasked rhythmic burst-firing in ~42% of non-bursting lamina I neurons, suggesting that pacemaker activity is a latent property of a sizeable population of SDH cells during early life. In addition, the prevalence of spontaneous burst-firing within lamina I was enhanced in the presence of high internal concentrations of free Mg2+, consistent with its documented ability to block Kir channels from the intracellular side. Collectively, the results indicate that Kir channels are key modulators of pacemaker activity in newborn central pain networks. PMID:23426663

Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.

PubMed

Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

2014-03-11

Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.

Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations

PubMed Central

Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

2014-01-01

Summary Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks. PMID:24672755

Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

PubMed Central

Burkhard, Silja Barbara

2018-01-01

Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions. PMID:29400650

Induced Pluripotent Stem Cell–Derived Cardiomyocytes Provide In Vivo Biological Pacemaker Function

PubMed Central

Chauveau, Samuel; Anyukhovsky, Evgeny P.; Ben-Ari, Meital; Naor, Shulamit; Jiang, Ya-Ping; Danilo, Peter; Rahim, Tania; Burke, Stephanie; Qiu, Xiaoliang; Potapova, Irina A.; Doronin, Sergey V.; Brink, Peter R.; Binah, Ofer

2017-01-01

Background— Although multiple approaches have been used to create biological pacemakers in animal models, induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) have not been investigated for this purpose. We now report pacemaker function of iPSC-CMs in a canine model. Methods and Results— Embryoid bodies were derived from human keratinocytes, their action potential characteristics determined, and their gene expression profiles and markers of differentiation identified. Atrioventricular blocked dogs were immunosuppressed, instrumented with VVI pacemakers, and injected subepicardially into the anterobasal left ventricle with 40 to 75 rhythmically contracting embryoid bodies (totaling 1.3–2×106 cells). ECG and 24-hour Holter monitoring were performed biweekly. After 4 to 13 weeks, epinephrine (1 μg kg−1 min−1) was infused, and the heart removed for histological or electrophysiological study. iPSC-CMs largely lost the markers of pluripotency, became positive for cardiac-specific markers. and manifested If-dependent automaticity. Epicardial pacing of the injection site identified matching beats arising from that site by week 1 after implantation. By week 4, 20% of beats were electronically paced, 60% to 80% of beats were matching, and mean and maximal biological pacemaker rates were 45 and 75 beats per minute. Maximum night and day rates of matching beats were 53±6.9 and 69±10.4 beats per minute, respectively, at 4 weeks. Epinephrine increased rate of matching beats from 35±4.3 to 65±4.0 beats per minute. Incubation of embryoid bodies with the vital dye, Dil, revealed the persistence of injected cells at the site of administration. Conclusions— iPSC-CMs can integrate into host myocardium and create a biological pacemaker. Although this is a promising development, rate and rhythm of the iPSC-CMs pacemakers remain to be optimized. PMID:28500172

Pharmacological characterization of ionic currents that regulate high-frequency spontaneous activity of electromotor neurons in the weakly electric fish, Apteronotus leptorhynchus.

PubMed

Smith, G Troy

2006-01-01

The neural circuit that controls the electric organ discharge (EOD) of the brown ghost knifefish (Apteronotus leptorhynchus) contains two spontaneous oscillators. Both pacemaker neurons in the medulla and electromotor neurons (EMNs) in the spinal cord fire spontaneously at frequencies of 500-1,000 Hz to control the EOD. These neurons continue to fire in vitro at frequencies that are highly correlated with in vivo EOD frequency. Previous studies used channel blocking drugs to pharmacologically characterize ionic currents that control high-frequency firing in pacemaker neurons. The goal of the present study was to use similar techniques to investigate ionic currents in EMNs, the other type of spontaneously active neuron in the electromotor circuit. As in pacemaker neurons, high-frequency firing of EMNs was regulated primarily by tetrodotoxin-sensitive sodium currents and by potassium currents that were sensitive to 4-aminopyridine and kappaA-conotoxin SIVA, but resistant to tetraethylammonium. EMNs, however, differed from pacemaker neurons in their sensitivity to some channel blocking drugs. Alpha-dendrotoxin, which blocks a subset of Kv1 potassium channels, increased firing rates in EMNs, but not pacemaker neurons; and the sodium channel blocker muO-conotoxin MrVIA, which reduced firing rates of pacemaker neurons, had no effect on EMNs. These results suggest that similar, but not identical, ionic currents regulate high-frequency firing in EMNs and pacemaker neurons. The differences in the ionic currents expressed in pacemaker neurons and EMNs might be related to differences in the morphology, connectivity, or function of these two cell types.

Mitochondrial calcium handling within the interstitial cells of Cajal

PubMed Central

Cheng, Leo K.

2014-01-01

The interstitial cells of Cajal (ICC) drive rhythmic pacemaking contractions in the gastrointestinal system. The ICC generate pacemaking signals by membrane depolarizations associated with the release of intracellular calcium (Ca2+) in the endoplasmic reticulum (ER) through inositol-trisphosphate (IP3) receptors (IP3R) and uptake by mitochondria (MT). This Ca2+ dynamic is hypothesized to generate pacemaking signals by calibrating ER Ca2+ store depletions and membrane depolarization with ER store-operated Ca2+ entry mechanisms. Using a biophysically based spatio-temporal model of integrated Ca2+ transport in the ICC, we determined the feasibility of ER depletion timescale correspondence with experimentally observed pacemaking frequencies while considering the impact of IP3R Ca2+ release and MT uptake on bulk cytosolic Ca2+ levels because persistent elevations of free intracellular Ca2+ are toxic to the cell. MT densities and distributions are varied in the model geometry to observe MT influence on free cytosolic Ca2+ and the resulting frequencies of ER Ca2+ store depletions, as well as the sarco-endoplasmic reticulum Ca2+ ATP-ase (SERCA) and IP3 agonist concentrations. Our simulations show that high MT densities observed in the ICC are more relevant to ER establishing Ca2+ depletion frequencies than protection of the cytosol from elevated free Ca2+, whereas the SERCA pump is more relevant to containing cytosolic Ca2+ elevations. Our results further suggest that the level of IP3 agonist stimulating ER Ca2+ release, subsequent MT uptake, and eventual activation of ER store-operated Ca2+ entry may determine frequencies of rhythmic pacemaking exhibited by the ICC across species and tissue types. PMID:24789203

Early performance of a miniaturized leadless cardiac pacemaker: the Micra Transcatheter Pacing Study.

PubMed

Ritter, Philippe; Duray, Gabor Z; Steinwender, Clemens; Soejima, Kyoko; Omar, Razali; Mont, Lluís; Boersma, Lucas V A; Knops, Reinoud E; Chinitz, Larry; Zhang, Shu; Narasimhan, Calambur; Hummel, John; Lloyd, Michael; Simmers, Timothy Alexander; Voigt, Andrew; Laager, Verla; Stromberg, Kurt; Bonner, Matthew D; Sheldon, Todd J; Reynolds, Dwight

2015-10-01

Permanent cardiac pacing is the only effective treatment for symptomatic bradycardia, but complications associated with conventional transvenous pacing systems are commonly related to the pacing lead and pocket. We describe the early performance of a novel self-contained miniaturized pacemaker. Patients having Class I or II indication for VVI pacing underwent implantation of a Micra transcatheter pacing system, from the femoral vein and fixated in the right ventricle using four protractible nitinol tines. Prespecified objectives were >85% freedom from unanticipated serious adverse device events (safety) and <2 V 3-month mean pacing capture threshold at 0.24 ms pulse width (efficacy). Patients were implanted (n = 140) from 23 centres in 11 countries (61% male, age 77.0 ± 10.2 years) for atrioventricular block (66%) or sinus node dysfunction (29%) indications. During mean follow-up of 1.9 ± 1.8 months, the safety endpoint was met with no unanticipated serious adverse device events. Thirty adverse events related to the system or procedure occurred, mostly due to transient dysrhythmias or femoral access complications. One pericardial effusion without tamponade occurred after 18 device deployments. In 60 patients followed to 3 months, mean pacing threshold was 0.51 ± 0.22 V, and no threshold was ≥2 V, meeting the efficacy endpoint (P < 0.001). Average R-wave was 16.1 ± 5.2 mV and impedance was 650.7 ± 130 ohms. Early assessment shows the transcatheter pacemaker can safely and effectively be applied. Long-term safety and benefit of the pacemaker will further be evaluated in the trial. ClinicalTrials.gov ID NCT02004873. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Spanish Pacemaker Registry. Thirteenth Official Report of the Spanish Society of Cardiology Working Group on Cardiac Pacing (2015).

PubMed

Pombo Jiménez, Marta; Cano Pérez, Óscar; Fidalgo Andrés, María Luisa; Lorente Carreño, Diego; Coma Samartín, Raúl

2016-12-01

We describe the results of the analysis of the devices implanted and conveyed to the Spanish Pacemaker Registry in 2015. The report is based on the processing of information provided by the European Pacemaker Patient Identification Card. We received information from 111 hospitals, with a total of 12 555 cards, representing 32.1% of all the estimated activity. The use of conventional generators and resynchronization devices was 820 and 73 units per million population, respectively. The mean age of the patients receiving an implantation was 77.7 years, and more than 50% of the devices were implanted in patients over 80 years of age. Overall, 58.6% of the implants and 58.8% of the replacements were performed in men. All of the endocardial leads employed were bipolar, 81.5% had an active fixation system, and 16.5% were compatible with magnetic resonance. Although dual chamber sequential pacing continues to be more widespread, pacing with VVI/R mode is used because up to 23.8% of the patients with sinus node disease are in sinus rhythm, as are 24.1% of those with atrioventricular block. The total use of pacemaker generators in Spain has increased by about 5% with respect to 2014. The majority of the leads implanted are of active fixation, and less than 20% are protected from magnetic resonance. The factors directly related to the selection of pacing mode are age and sex. In around 20% of patients, the choice of the pacing mode could be improved. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Dexmedetomidine-related atrial standstill and loss of capture in a pediatric patient after congenital heart surgery.

PubMed

Shepard, Suzanne M; Tejman-Yarden, Shai; Khanna, Sandeep; Davis, Christopher K; Batra, Anjan S

2011-01-01

Dexmedetomidine (DEX; Precedex) is an alpha-2 adrenergic receptor agonist that produces anxiolysis and sleep-like sedation without narcosis or respiratory depression and has relatively few cardiovascular side effects. Given its favorable sedative properties combined with its limited effects on hemodynamic and respiratory function, it is widely used in pediatric intensive care and anesthesia settings. Case report. Pediatric intensive care unit. A three-yr-old girl was admitted after mitral valve replacement for persistent severe mitral insufficiency. Her prior history was significant for tetralogy of Fallot which was repaired at nine months of age. A year later the patient developed mitral and tricuspid valve insufficiency and subsequently underwent mitral and tricuspid valve repair, pulmonary valve replacement, and a maze procedure (the latter was performed for persistent atrial flutter). Following that operation she developed sinus node dysfunction and had a permanent epicardial dual-chamber pacemaker implanted. Due to remaining severe mitral insufficiency the patient had increasing pulmonary symptoms, necessitating the most recent surgery to replace her mitral valve. On postoperative day two the patient was hemodynamically stable and weaning off mechanical ventilation. Tracheal extubation was anticipated to occur within the next 24 hrs. A DEX infusion of 0.6 mcg/kg/hr was initiated. A pacemaker interrogation performed on postoperative day three, 21 hrs after the initiation of DEX, revealed unsuccessful atrial capture. Dexmedetomidine was subsequently discontinued and the patient's pacemaker was reinterrogated. The interrogation findings were similar to those seen prior to the initiation of DEX. As a result of these findings, caution is warranted in the administration of DEX to patients with predisposing conduction abnormalities and patients who are pacemaker-dependent.

Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease. An electrophysiological-pathological correlation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, S.I.; Bharati, S.; Glass, J.

1981-04-01

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis ofmore » the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.« less

Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease: an electrophysiological-pathological correlation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, S.I.; Bharati, S.; Glass, J.

1981-04-01

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis ofmore » the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.« less

Functional, Anatomical, and Molecular Investigation of the Cardiac Conduction System and Arrhythmogenic Atrioventricular Ring Tissue in the Rat Heart

PubMed Central

Atkinson, Andrew J.; Logantha, Sunil Jit R. J.; Hao, Guoliang; Yanni, Joseph; Fedorenko, Olga; Sinha, Aditi; Gilbert, Stephen H.; Benson, Alan P.; Buckley, David L.; Anderson, Robert H.; Boyett, Mark R.; Dobrzynski, Halina

2013-01-01

Background The cardiac conduction system consists of the sinus node, nodal extensions, atrioventricular (AV) node, penetrating bundle, bundle branches, and Purkinje fibers. Node‐like AV ring tissue also exists at the AV junctions, and the right and left rings unite at the retroaortic node. The study aims were to (1) construct a 3‐dimensional anatomical model of the AV rings and retroaortic node, (2) map electrical activation in the right ring and study its action potential characteristics, and (3) examine gene expression in the right ring and retroaortic node. Methods and Results Three‐dimensional reconstruction (based on magnetic resonance imaging, histology, and immunohistochemistry) showed the extent and organization of the specialized tissues (eg, how the AV rings form the right and left nodal extensions into the AV node). Multiextracellular electrode array and microelectrode mapping of isolated right ring preparations revealed robust spontaneous activity with characteristic diastolic depolarization. Using laser microdissection gene expression measured at the mRNA level (using quantitative PCR) and protein level (using immunohistochemistry and Western blotting) showed that the right ring and retroaortic node, like the sinus node and AV node but, unlike ventricular muscle, had statistically significant higher expression of key transcription factors (including Tbx3, Msx2, and Id2) and ion channels (including HCN4, Cav3.1, Cav3.2, Kv1.5, SK1, Kir3.1, and Kir3.4) and lower expression of other key ion channels (Nav1.5 and Kir2.1). Conclusions The AV rings and retroaortic node possess gene expression profiles similar to that of the AV node. Ion channel expression and electrophysiological recordings show the AV rings could act as ectopic pacemakers and a source of atrial tachycardia. PMID:24356527

Successful pacing using a batteryless sunlight-powered pacemaker.

PubMed

Haeberlin, Andreas; Zurbuchen, Adrian; Schaerer, Jakob; Wagner, Joerg; Walpen, Sébastien; Huber, Christoph; Haeberlin, Heinrich; Fuhrer, Juerg; Vogel, Rolf

2014-10-01

Today's cardiac pacemakers are powered by batteries with limited energy capacity. As the battery's lifetime ends, the pacemaker needs to be replaced. This surgical re-intervention is costly and bears the risk of complications. Thus, a pacemaker without primary batteries is desirable. The goal of this study was to test whether transcutaneous solar light could power a pacemaker. We used a three-step approach to investigate the feasibility of sunlight-powered cardiac pacing. First, the harvestable power was estimated. Theoretically, a subcutaneously implanted 1 cm(2) solar module may harvest ∼2500 µW from sunlight (3 mm implantation depth). Secondly, ex vivo measurements were performed with solar cells placed under pig skin flaps exposed to a solar simulator and real sunlight. Ex vivo measurements under real sunlight resulted in a median output power of 4941 µW/cm(2) [interquartile range (IQR) 3767-5598 µW/cm(2), median skin flap thickness 3.0 mm (IQR 2.7-3.3 mm)]. The output power strongly depended on implantation depth (ρSpearman = -0.86, P < 0.001). Finally, a batteryless single-chamber pacemaker powered by a 3.24 cm(2) solar module was implanted in vivo in a pig to measure output power and to pace. In vivo measurements showed a median output power of >3500 µW/cm(2) (skin flap thickness 2.8-3.84 mm). Successful batteryless VVI pacing using a subcutaneously implanted solar module was performed. Based on our results, we estimate that a few minutes of direct sunlight (irradiating an implanted solar module) allow powering a pacemaker for 24 h using a suitable energy storage. Thus, powering a pacemaker by sunlight is feasible and may be an alternative energy supply for tomorrow's pacemakers. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Gap junctions between accessory medulla neurons appear to synchronize circadian clock cells of the cockroach Leucophaea maderae.

PubMed

Schneider, Nils-Lasse; Stengl, Monika

2006-03-01

The temporal organization of physiological and behavioral states is controlled by circadian clocks in apparently all eukaryotic organisms. In the cockroach Leucophaea maderae lesion and transplantation studies located the circadian pacemaker in the accessory medulla (AMe). The AMe is densely innervated by gamma-aminobutyric acid (GABA)-immunoreactive and peptidergic neurons, among them the pigment-dispersing factor immunoreactive circadian pacemaker candidates. The large majority of cells of the cockroach AMe spike regularly and synchronously in the gamma frequency range of 25-70 Hz as a result of synaptic and nonsynaptic coupling. Although GABAergic coupling forms assemblies of phase-locked cells, in the absence of synaptic release the cells remain synchronized but fire now at a stable phase difference. To determine whether these coupling mechanisms of AMe neurons, which are independent of synaptic release, are based on electrical synapses between the circadian pacemaker cells the gap-junction blockers halothane, octanol, and carbenoxolone were used in the presence and absence of synaptic transmission. Here, we show that different populations of AMe neurons appear to be coupled by gap junctions to maintain synchrony at a stable phase difference. This synchronization by gap junctions is a prerequisite to phase-locked assembly formation by synaptic interactions and to synchronous gamma-type action potential oscillations within the circadian clock.

Percutaneously injectable fetal pacemaker: electrodes, mechanical design and implantation.

PubMed

Zhou, Li; Chmait, Ramen; Bar-Cohen, Yaniv; Peck, Raymond A; Loeb, Gerald E

2012-01-01

We are developing a self-contained cardiac pacemaker with a small, cylindrical shape (~3 × 20 mm) that permits it to be implanted percutaneously into a fetus to treat complete heart block and consequent hydrops fetalis, which is otherwise fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. The feasibility of implanting the device percutaneously under ultrasonic imaging guidance was demonstrated in acute adult rabbit experiments.

Frailty syndrome in patients with heart rhythm disorders.

PubMed

Mlynarska, Agnieszka; Mlynarski, Rafal; Golba, Krzysztof S

2017-09-01

To assess the prevalence of frailty syndrome in patients with heart rhythm disorders that qualified for pacemaker implantation. The study included 171 patients (83 women, aged 73.9 ± 6.7 years) who qualified for pacemaker implantation as a result of sinus node dysfunction (81 patients) or atrio-ventricular blocks (AVB; 90 patients). A total of 60 patients (25 women, aged 72.40 ± 7.09 years) without heart rhythm disorders were included in the control group. Frailty syndrome was diagnosed using the Canadian Study of Health and Aging Clinical Frailty Scale test. Frailty syndrome was diagnosed in 25.15% of the patients, and pre-frailty in 36.84% of the patients. Frailty syndrome was diagnosed in 10% of the control group, and the average value of frailty was 3.35 ± 0.92. Frailty occurred significantly more often among patients with AVB (33.34%) compared with patients who were diagnosed with sinus node dysfunction (16.05%); P = 0.0081. The average score of frailty for sinus node dysfunction was 3.71 ± 0.89, and for AVB it was 4.14 ± 0.93; P = 0.0152. In the case of AVB, the women had a statistically more intense level of frailty of 4.54 ± 0.90 as compared with the men 3.87 ± 0.85; P = 0.0294. In the multiple logistic analysis, the presence of any arrhythmia was strongly associated with frailty syndrome (OR 2.1286, 95% CI 1.4594 - 3.1049; P = 0.0001). Frailty syndrome was diagnosed in one-quarter of patients with cardiac arrhythmias, whereas a further 40% were at a higher risk of frailty syndrome, and its occurrence was significantly higher if compared with the control group. Frailty occurred significantly more often among patients with atrio-ventricular blocks, especially in women. The results of the present research showed that there is a statistical association between frailty and arrhythmias. Geriatr Gerontol Int 2017; 17: 1313-1318. © 2016 Japan Geriatrics Society.

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock.

PubMed

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-30

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit.

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock

PubMed Central

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-01

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit. PMID:28134281

Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation.

PubMed

Klose, Markus; Duvall, Laura; Li, Weihua; Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H

2016-05-18

The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness and does not require endogenous ligand (PDF) signaling or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additionally, cell-autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional PDF Signaling in the Drosophila Circadian Neural Circuit is Gated by Ral A-Dependent Modulation

PubMed Central

Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H.

2016-01-01

The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness, does not require endogenous ligand (PDF) signaling, or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additional, cell autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. PMID:27161526

Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

PubMed Central

Luo, Min; Guan, Xiaoqun; Luczak, Elizabeth D.; Lang, Di; Kutschke, William; Gao, Zhan; Yang, Jinying; Glynn, Patric; Sossalla, Samuel; Swaminathan, Paari D.; Weiss, Robert M.; Yang, Baoli; Rokita, Adam G.; Maier, Lars S.; Efimov, Igor R.; Hund, Thomas J.; Anderson, Mark E.

2013-01-01

Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction. Streptozotocin-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by myocardial infarction. We developed a knockin mouse model of oxidation-resistant CaMKIIδ (MM-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. Our findings suggest that activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after myocardial infarction. PMID:23426181

Developmental change in the contribution of voltage-gated Ca(2+) channels to the pacemaking of deep cerebellar nuclei neurons.

PubMed

Alviña, K; Tara, E; Khodakhah, K

2016-05-13

The activity of the deep cerebellar nuclei (DCN) neurons conveys the bulk of the output of the cerebellum. To generate these motor signals, DCN neurons integrate synaptic inputs with their own spontaneous activity. We have previously reported that N-type voltage-gated Ca(2+) channels modulate the spontaneous activity of the majority of juvenile DCN neurons in vitro. Specifically, pharmacologically blocking N-type Ca(2+) channels increases their firing rate causing DCN cells to burst. Adult DCN neurons however, behaved differently. To further investigate this change, we have studied here the effect of cadmium on the firing rate of DCN neurons in acute cerebellar slices obtained from adult (>2 months old) or juvenile (12-21 days old) rats and mice. Strikingly, and in contrast to juvenile DCN cells, cadmium did not affect the pacemaking of adult DCN cells. The activity of Purkinje cells (PCs) however was transformed into high-frequency bursting, regardless the age. Further, we questioned whether these findings could be due to an artifact associated with the added difficulty of preparing adult DCN slices. Hence we proceeded to examine the spontaneous activity of DCN neurons in anesthetized juvenile and adult rats and mice in vivo. When cadmium was injected into the DCN in vivo no significant change in firing rate was observed, conversely to most juvenile DCN neurons which showed high-frequency bursts after cadmium injection. In these same animals, PCs pacemaking showed no developmental difference. Thus our results demonstrate a remarkable age-dependent functional modification in the regulation of DCN neurons pacemaking. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

The Composition and Structure of Biofilms Developed by Propionibacterium acnes Isolated from Cardiac Pacemaker Devices.

PubMed

Okuda, Ken-Ichi; Nagahori, Ryuichi; Yamada, Satomi; Sugimoto, Shinya; Sato, Chikara; Sato, Mari; Iwase, Tadayuki; Hashimoto, Kazuhiro; Mizunoe, Yoshimitsu

2018-01-01

The present study aimed to understand the biofilm formation mechanism of Propionibacterium acnes by analyzing the components and structure of the biofilms. P. acnes strains were isolated from the surface of explanted cardiac pacemaker devices that exhibited no clinical signs of infection. Culture tests using a simple stamp culture method (pressing pacemakers against the surface of agar plates) revealed frequent P. acnes colonization on the surface of cardiac pacemaker devices. P . acnes was isolated from 7/31 devices, and the isolates were categorized by multilocus sequence typing into five different sequence types (STs): ST4 (JK18.2), ST53 (JK17.1), ST69 (JK12.2 and JK13.1), ST124 (JK5.3), ST125 (JK6.2), and unknown ST (JK19.3). An in vitro biofilm formation assay using microtiter plates demonstrated that 5/7 isolates formed biofilms. Inhibitory effects of DNase I and proteinase K on biofilm formation varied among isolates. In contrast, dispersin B showed no inhibitory activity against all isolates. Three-dimensional live/dead imaging of P. acnes biofilms with different biochemical properties using confocal laser microscopy demonstrated different distributions and proportions of living and dead cells. Additionally, it was suggested that extracellular DNA (eDNA) plays a role in the formation of biofilms containing living cells. Ultrastructural analysis of P. acnes biofilms using a transmission electron microscope and atmospheric scanning electron microscope revealed leakage of cytoplasmic components along with cell lysis and fibrous structures of eDNA connecting cells. In conclusion, the biochemical properties and structures of the biofilms differed among P. acnes isolates. These findings may provide clues for establishing countermeasures against biofilm-associated infection by P. acnes .

The Composition and Structure of Biofilms Developed by Propionibacterium acnes Isolated from Cardiac Pacemaker Devices

PubMed Central

Okuda, Ken-ichi; Nagahori, Ryuichi; Yamada, Satomi; Sugimoto, Shinya; Sato, Chikara; Sato, Mari; Iwase, Tadayuki; Hashimoto, Kazuhiro; Mizunoe, Yoshimitsu

2018-01-01

The present study aimed to understand the biofilm formation mechanism of Propionibacterium acnes by analyzing the components and structure of the biofilms. P. acnes strains were isolated from the surface of explanted cardiac pacemaker devices that exhibited no clinical signs of infection. Culture tests using a simple stamp culture method (pressing pacemakers against the surface of agar plates) revealed frequent P. acnes colonization on the surface of cardiac pacemaker devices. P. acnes was isolated from 7/31 devices, and the isolates were categorized by multilocus sequence typing into five different sequence types (STs): ST4 (JK18.2), ST53 (JK17.1), ST69 (JK12.2 and JK13.1), ST124 (JK5.3), ST125 (JK6.2), and unknown ST (JK19.3). An in vitro biofilm formation assay using microtiter plates demonstrated that 5/7 isolates formed biofilms. Inhibitory effects of DNase I and proteinase K on biofilm formation varied among isolates. In contrast, dispersin B showed no inhibitory activity against all isolates. Three-dimensional live/dead imaging of P. acnes biofilms with different biochemical properties using confocal laser microscopy demonstrated different distributions and proportions of living and dead cells. Additionally, it was suggested that extracellular DNA (eDNA) plays a role in the formation of biofilms containing living cells. Ultrastructural analysis of P. acnes biofilms using a transmission electron microscope and atmospheric scanning electron microscope revealed leakage of cytoplasmic components along with cell lysis and fibrous structures of eDNA connecting cells. In conclusion, the biochemical properties and structures of the biofilms differed among P. acnes isolates. These findings may provide clues for establishing countermeasures against biofilm-associated infection by P. acnes. PMID:29491850

Percutaneously Inject able Fetal Pacemaker: Electrodes, Mechanical Design and Implantation*

PubMed Central

Zhou, Li; Chmait, Ramen; Bar-Cohen, Yaniv; Peck, Raymond A.; Loeb, Gerald E.

2015-01-01

We are developing a self-contained cardiac pacemaker with a small, cylindrical shape (~3×20mm) that permits it to be implanted percutaneously into a fetus to treat complete heart block and consequent hydrops fetalis, which is otherwise fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. The feasibility of implanting the device percutaneously under ultrasonic imaging guidance was demonstrated in acute adult rabbit experiments. PMID:23367442

Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells

PubMed Central

Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

2014-01-01

Summary Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. PMID:24936448

(Re-)programming of subtype specific cardiomyocytes.

PubMed

Hausburg, Frauke; Jung, Julia Jeannine; Hoch, Matti; Wolfien, Markus; Yavari, Arash; Rimmbach, Christian; David, Robert

2017-10-01

Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential - a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing. Copyright © 2017 Elsevier B.V. All rights reserved.

Does calcium influx regulate melatonin production through the circadian pacemaker in chick pineal cells? Effects of nitrendipine, Bay K 8644, Co2+, Mn2+, and low external Ca2+.

PubMed

Zatz, M; Mullen, D A

1988-11-01

We have recently described a system, using dispersed chick pineal cells in static culture, which displays a persistent, photosensitive, circadian rhythm of melatonin production and release. Here, we describe the effects of nitrendipine (NTR) (a dihydropyridine 'antagonist' of L-type calcium channels), Bay K 8644 (BK) (a dihydropyridine calcium channel 'agonist'), cobalt and manganese ions (both inorganic calcium channel blockers), and low external calcium concentrations, on the melatonin rhythm. NTR inhibited and BK stimulated melatonin output; they were potent and effective. Co2+, Mn2+, and low external Ca2+ markedly inhibited melatonin output. These results support a role for calcium influx through voltage-dependent calcium channels (L-type) in the regulation of melatonin production. Four or 8 h pulses of white light or darkness, in otherwise constant red light, cause, in addition to acute effects, phase-dependent phase shifts of the melatonin rhythm in subsequent cycles. Such phase shifts indicate an effect on (proximal to) the pacemaker generating the rhythm. Four or 8 h pulses of NTR, BK, Co2+, or low Ca2+, however, did not appreciably alter the phase of subsequent melatonin cycles. Neither did BK interfere with phase shifts induced by light pulses. Mn2+ pulses did induce phase-dependent phase shifts, but, unlike those evoked by light or dark pulses, these were all delays. Such effects of Mn2+ in other systems have been attributed to, and are characteristic of, 'metabolic inhibitors'. On balance, the results fail to support a prominent role for calcium influx in regulating the pacemaker underlying the circadian rhythm in chick pineal cells. Rather, calcium influx appears to regulate melatonin production primarily by acting on the melatonin-synthesizing apparatus, distal to the pacemaker.

Clinical evaluation of pacemaker automatic capture management and atrioventricular interval extension algorithm.

PubMed

Chen, Ke-ping; Xu, Geng; Wu, Shulin; Tang, Baopeng; Wang, Li; Zhang, Shu

2013-03-01

The present study was to assess the accuracy of automatic atrial and ventricular capture management (ACM and VCM) in determining pacing threshold and the performance of a second-generation automatic atrioventricular (AV) interval extension algorithm for reducing unnecessary ventricular pacing. A total of 398 patients at 32 centres who received an EnPulse dual-chamber pacing/dual-chamber adaptive rate pacing pacemaker (Medtronic, Minneapolis, MN, USA) were enrolled. The last amplitude thresholds as measured by ACM and VCM prior to the 6-month follow-up were compared with manually measured thresholds. Device diagnostics were used to evaluate ACM and VCM and the percentage of ventricular pacing with and without the AV extension algorithm. Modelling was performed to assess longevity gains relating to the use of automaticity features. Atrial and ventricular capture management performed accurately and reliably provided complete capture management in 97% of studied patients. The AV interval extension algorithm reduced the median per cent of right ventricular pacing in patients with sinus node dysfunction from 99.7 to 1.5% at 6-month follow-up and in patients with intermittent AV block (excluding persistent 3° AV block) from 99.9 to 50.2%. On the basis of validated modelling, estimated device longevity could potentially be extended by 1.9 years through the use of the capture management and AV interval extension features. Both ACM and VCM features reliably measured thresholds in nearly all patients; the AV extension algorithm significantly reduced ventricular pacing; and the use of pacemaker automaticity features potentially extends device longevity.

Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling.

PubMed

Elvan, A; Wylie, K; Zipes, D P

1996-12-01

We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

[Late arrhythmias in the operated interatrial communication. Analysis of sinus node function and the conduction pathways by His bundle electrocardiography].

PubMed

Ramírez, A; Gil, M; Martínez Ríos, M A; Cárdenas, M; Pliego, J; Zamora, C; Mata, L A

1982-01-01

Four hundred patients with atrial septal defect treated surgically were reviewed. Thirty five (8.7%) developed arrhytmias post-surgery which persisted for over a year. Sinus bradycardia was found in 10 patients, nodal rhythm in 21, and atrial fibrilation and flutter in 4 patients. Thirty five per cent of the patients with late arrhythmias developed related symptomatology. In 14 patients the function of the sinus node was studied with electrical stimulation of the atrium and with His registry. The interatrial conduction time, AV node and His Purkinje were analized employing various stimulation frequencies. All the cases studied had normal intra-atrial conduction; the response of the atrio-ventricular node to increasing frequencies was normal, an the intraventricular conduction remained constant. In 8 patients (52%), alterations of the sinus node were found; these consisted of prolonged post-stimulation pauses, Wenckebach's type sinoatrial block and suppression of sinus automatism employing vagal procedures or through electrical stimulation. A patient with severe bradycardia detected by dynamic electrocardiography had to be treated with a permanent pacemaker. We confirm that these arrhytmias are not produced by lesions of the internodal tracts, and that an alteration of the sinus node is frequent without a concomitant lesion of the intraventricular pathway. The lesion to the nutrient artery could be due to trauma and/or surgically induced. The response to anticholinergic drugs was good. Prolonged observation of these patients could increase the morbility of these arrythmias and raise doubts of the surgical indications in cases with moderate hemodynamic repercussion.

Computer Three-Dimensional Reconstruction of the Atrioventricular Node

PubMed Central

Li, Jue; Greener, Ian D.; Inada, Shin; Nikolski, Vladimir P.; Yamamoto, Mitsuru; Hancox, Jules C.; Zhang, Henggui; Billeter, Rudi; Efimov, Igor R.; Dobrzynski, Halina; Boyett, Mark R.

2009-01-01

Because of its complexity, the atrioventricular node (AVN), remains 1 of the least understood regions of the heart. The aim of the study was to construct a detailed anatomic model of the AVN and relate it to AVN function. The electric activity of a rabbit AVN preparation was imaged using voltage-dependent dye. The preparation was then fixed and sectioned. Sixty-five sections at 60- to 340-μm intervals were stained for histology and immunolabeled for neurofilament (marker of nodal tissue) and connexin43 (gap junction protein). This revealed multiple structures within and around the AVN, including transitional tissue, inferior nodal extension, penetrating bundle, His bundle, atrial and ventricular muscle, central fibrous body, tendon of Todaro, and valves. A 3D anatomically detailed mathematical model (≈13 million element array) of the AVN and surrounding atrium and ventricle, incorporating all cell types, was constructed. Comparison of the model with electric activity recorded in experiments suggests that the inferior nodal extension forms the slow pathway, whereas the transitional tissue forms the fast pathway into the AVN. In addition, it suggests the pacemaker activity of the atrioventricular junction originates in the inferior nodal extension. Computer simulation of the propagation of the action potential through the anatomic model shows how, because of the complex structure of the AVN, reentry (slow-fast and fast-slow) can occur. In summary, a mathematical model of the anatomy of the AVN has been generated that allows AVN conduction to be explored. PMID:18309098

Combined application of extracorporeal membrane oxygenation and an artificial pacemaker in fulminant myocarditis in a child

PubMed Central

Ye, Sheng; Zhu, Lvchan; Ning, Botao; Zhang, Chenmei

2017-01-01

Fulminant myocarditis is severe and aggressive, but it is self-limited and usually has a favorable prognosis if the patients can survive the acute phase. When drug treatment is not effective, extracorporeal membrane oxygenation technology should be applied to support cardiopulmonary function. Extracorporeal membrane oxygenation can simultaneously support function of the left ventricle, right ventricle, and lungs, and provide stable blood circulation for patients with heart and respiratory failure, which allows sufficient time for the cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic function, as well as the function of autorhythmic cells and the conduction system. If severe bradycardia or atrioventricular block appears, a pacemaker needs to be installed. We report a child with fulminant myocarditis who was treated with extracorporeal membrane oxygenation combined with an artificial pacemaker. PMID:28747842

Combined application of extracorporeal membrane oxygenation and an artificial pacemaker in fulminant myocarditis in a child.

PubMed

Ye, Sheng; Zhu, Lvchan; Ning, Botao; Zhang, Chenmei

2017-06-01

Fulminant myocarditis is severe and aggressive, but it is self-limited and usually has a favorable prognosis if the patients can survive the acute phase. When drug treatment is not effective, extracorporeal membrane oxygenation technology should be applied to support cardiopulmonary function. Extracorporeal membrane oxygenation can simultaneously support function of the left ventricle, right ventricle, and lungs, and provide stable blood circulation for patients with heart and respiratory failure, which allows sufficient time for the cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic function, as well as the function of autorhythmic cells and the conduction system. If severe bradycardia or atrioventricular block appears, a pacemaker needs to be installed. We report a child with fulminant myocarditis who was treated with extracorporeal membrane oxygenation combined with an artificial pacemaker.

Measuring contraction propagation and localizing pacemaker cells using high speed video microscopy

PubMed Central

Akl, Tony J.; Nepiyushchikh, Zhanna V.; Gashev, Anatoliy A.; Zawieja, David C.; Coté, Gerard L.

2011-01-01

Previous studies have shown the ability of many lymphatic vessels to contract phasically to pump lymph. Every lymphangion can act like a heart with pacemaker sites that initiate the phasic contractions. The contractile wave propagates along the vessel to synchronize the contraction. However, determining the location of the pacemaker sites within these vessels has proven to be very difficult. A high speed video microscopy system with an automated algorithm to detect pacemaker location and calculate the propagation velocity, speed, duration, and frequency of the contractions is presented in this paper. Previous methods for determining the contractile wave propagation velocity manually were time consuming and subject to errors and potential bias. The presented algorithm is semiautomated giving objective results based on predefined criteria with the option of user intervention. The system was first tested on simulation images and then on images acquired from isolated microlymphatic mesenteric vessels. We recorded contraction propagation velocities around 10 mm∕s with a shortening speed of 20.4 to 27.1 μm∕s on average and a contraction frequency of 7.4 to 21.6 contractions∕min. The simulation results showed that the algorithm has no systematic error when compared to manual tracking. The system was used to determine the pacemaker location with a precision of 28 μm when using a frame rate of 300 frames per second. PMID:21361700

RGS6, but not RGS4, is the dominant regulator of G protein signaling (RGS) modulator of the parasympathetic regulation of mouse heart rate.

PubMed

Wydeven, Nicole; Posokhova, Ekaterina; Xia, Zhilian; Martemyanov, Kirill A; Wickman, Kevin

2014-01-24

Parasympathetic activity decreases heart rate (HR) by inhibiting pacemaker cells in the sinoatrial node (SAN). Dysregulation of parasympathetic influence has been linked to sinus node dysfunction and arrhythmia. RGS (regulator of G protein signaling) proteins are negative modulators of the parasympathetic regulation of HR and the prototypical M2 muscarinic receptor (M2R)-dependent signaling pathway in the SAN that involves the muscarinic-gated atrial K(+) channel IKACh. Both RGS4 and RGS6-Gβ5 have been implicated in these processes. Here, we used Rgs4(-/-), Rgs6(-/-), and Rgs4(-/-):Rgs6(-/-) mice to compare the relative influence of RGS4 and RGS6 on parasympathetic regulation of HR and M2R-IKACh-dependent signaling in the SAN. In retrogradely perfused hearts, ablation of RGS6, but not RGS4, correlated with decreased resting HR, increased heart rate variability, and enhanced sensitivity to the negative chronotropic effects of the muscarinic agonist carbachol. Similarly, loss of RGS6, but not RGS4, correlated with enhanced sensitivity of the M2R-IKACh signaling pathway in SAN cells to carbachol and a significant slowing of M2R-IKACh deactivation rate. Surprisingly, concurrent genetic ablation of RGS4 partially rescued some deficits observed in Rgs6(-/-) mice. These findings, together with those from an acute pharmacologic approach in SAN cells from Rgs6(-/-) and Gβ5(-/-) mice, suggest that the partial rescue of phenotypes in Rgs4(-/-):Rgs6(-/-) mice is attributable to another R7 RGS protein whose influence on M2R-IKACh signaling is masked by RGS4. Thus, RGS6-Gβ5, but not RGS4, is the primary RGS modulator of parasympathetic HR regulation and SAN M2R-IKACh signaling in mice.

Relevance of HCN2-expressing human mesenchymal stem cells for the generation of biological pacemakers.

PubMed

Bruzauskaite, Ieva; Bironaite, Daiva; Bagdonas, Edvardas; Skeberdis, Vytenis Arvydas; Denkovskij, Jaroslav; Tamulevicius, Tomas; Uvarovas, Valentinas; Bernotiene, Eiva

2016-04-30

The transfection of human mesenchymal stem cells (hMSCs) with the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2) gene has been demonstrated to provide biological pacing in dogs with complete heart block. The mechanism appears to be the generation of the ion current (If) by the HCN2-expressing hMSCs. However, it is not clear how the transfection process and/or the HCN2 gene affect the growth functions of the hMSCs. Therefore, we investigated survival, proliferation, cell cycle, and growth on a Kapton® scaffold of HCN2-expressing hMSCs. hMSCs were isolated from the bone marrow of healthy volunteers applying a selective cell adhesion procedure and were identified by their expression of specific surface markers. Cells from passages 2-3 were transfected by electroporation using commercial transfection kits and a pIRES2-EGFP vector carrying the pacemaker gene, mouse HCN2 (mHCN2). Transfection efficiency was confirmed by enhanced green fluorescent protein (EGFP) fluorescence, quantitative real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). After hMSCs were transfected, their viability, proliferation, If generation, apoptosis, cell cycle, and expression of transcription factors were measured and compared with non-transfected cells and cells transfected with pIRES2-EGFP vector alone. Intracellular mHCN2 expression after transfection increased from 22.14 to 62.66 ng/mg protein (p < 0.05). Transfection efficiency was 45 ± 5 %. The viability of mHCN2-transfected cells was 82 ± 5 %; they grew stably for more than 3 weeks and induced If current. mHCN2-transfected cells had low mitotic activity (10.4 ± 1.24 % in G2/M and 83.6 ± 2.5 % in G1 phases) as compared with non-transfected cells (52-53 % in G2/M and 31-35 % in G1 phases). Transfected cells showed increased activation of nine cell cycle-regulating transcription factors: the most prominent upregulation was of AMP-dependent transcription factor ATF3 (7.11-fold, p = 0.00056) which regulates the G1 phase. mHCN2-expressing hMSCs were attached and made anchorage-dependent connection with other cells without transmigration through a 12.7-μm thick Kapton® HN film with micromachined 1-3 μm diameter pores. mHCN2-expressing hMSCs preserved the major cell functions required for the generation of biological pacemakers: high viability, functional activity, but low proliferation rate through the arrest of cell cycle in the G1 phase. mHCN2-expressing hMSCs attached and grew on a Kapton® scaffold without transmigration, confirming the relevance of these cells for the generation of biological pacemakers.

Pacemaker syndrome with sub-acute left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker: consequence of lead switch at the header.

PubMed

Khurwolah, Mohammad Reeaze; Vezi, Brian Zwelethini

In the daily practice of pacemaker insertion, the occurrence of atrial and ventricular lead switch at the pacemaker box header is a rare and unintentional phenomenon, with less than five cases reported in the literature. The lead switch may have dire consequences, depending on the indication for the pacemaker. One of these consequences is pacemaker syndrome, in which the normal sequence of atrial and ventricular activation is impaired, leading to sub-optimal ventricular filling and cardiac output. It is important for the attending physician to recognise any worsening of symptoms in a patient who has recently had a permanent pacemaker inserted. In the case of a dual-chamber pacemaker, switching of the atrial and ventricular leads at the pacemaker box header should be strongly suspected. We present an unusual case of pacemaker syndrome and right ventricular-only pacinginduced left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker.

A case of atrial tachycardia treated with ivabradine as bridge to ablation.

PubMed

Meles, Ester; Carbone, Claudio; Maggiolini, Stefano; Moretti, Paolo; DE Carlini, Caterina C; Gentile, Gaetano; Gnecchi-Ruscone, Tomaso

2015-05-01

Ivabradine is indicated in cardiac failure and ischemia to reduce sinus rate by inhibition of the pacemaker I(f) current in sinoatrial node. We report a case of an 18-year-old woman with left atrial tachyarrhythmia resistant to several antiarrhythmic drugs and to electric cardioversion who responded only to ivabradine, which significantly reduced heart rate without abolishing the arrhythmia itself. An ectopic focus in the ostium of left pulmonary veins was found and the patient was successfully ablated. We suggest that ivabradine might be therefore useful in the treatment of supraventricular tachyarrhythmias due to an enhanced automaticity. © 2015 Wiley Periodicals, Inc.

Focal Atrial Tachycardia Arising from the Inferior Vena Cava

PubMed Central

Lim, Yeong-Min; Uhm, Jae-Sun

2017-01-01

The inferior vena cava (IVC) is a rare site of focal atrial tachycardia (AT). Here, we report a 20-year-old woman who underwent catheter ablation for anti-arrhythmic drug-resistant AT originating from the IVC. She had undergone open-heart surgery for patch closure of an atrial septal defect 17 years previously and permanent pacemaker implantation for sinus node dysfunction 6 years previously. The AT focus was at the anterolateral aspect of the IVC-right atrial junction, and it was successfully ablated under three-dimensional electroanatomical-mapping guidance. We suspect that the mechanism of this tachycardia was associated with previous IVC cannulation for open-heart surgery. PMID:28541006

[TRENDS OF PERMANENT PACEMAKER IMPLANTATION IN A SINGLE CENTER OVER A 20-YEAR PERIOD].

PubMed

Antonelli, Dante; Ilan, Limor Bushar; Freedberg, Nahum A; Feldman, Alexander; Turgeman, Yoav

2015-05-01

To review the changes in permanent pacemaker implantation indications, pacing modes and patients' demographics over a 20-year period. We retrospectively retrieved data on patients who underwent first implantation of the pacemaker between 1-1-1991 and 31-12-2010. One thousand and nine (1,009) patients underwent a first pacemaker implantation during that period; 535 were men (53%), their mean age was 74.6±19.5 years; the highest rate of implanted pacemaker was in patients ranging in age from 70-79 years, however there was an increasing number of patients aged over 80 years. The median survival time after initial pacemaker implantation was 8 years. Syncope was the most common symptom (62.5%) and atrioventricular block was the most common electrocardiographic indication (56.4%) leading to pacemaker implantation. There was increased utilization of dual chamber and rate responsive pacemakers over the years. There was no difference regarding mode selection between genders. Pacemaker implantation rates have increased over a 20-year period. Dual chamber replaced most of the single ventricular chamber pacemaker and rate responsive pacemakers became the norm. The data of a small volume center are similar to those reported in pacemaker surveys of high volume pacemaker implantation centers. They confirm adherence to the published guidelines for pacing.

Behavioral and molecular analyses suggest that circadian output is disrupted by disconnected mutants in D. melanogaster.

PubMed Central

Hardin, P E; Hall, J C; Rosbash, M

1992-01-01

Mutations in the disconnected (disco) gene act to disrupt neural cell patterning in the Drosophila visual system. These mutations also affect adult locomotor activity rhythms, as disco flies are arrhythmic under conditions of constant darkness (DD). To determine the state of the circadian pacemaker in disco mutants, we constructed with pers double mutants (a short period allele of the period gene) and assayed their behavioral rhythms in light-dark cycles (LD), and their biochemical rhythms of period gene expression under both LD and DD conditions. The results demonstrate that disco flies are rhythmic, indicating that they have an active circadian pacemaker that can be entrained by light. They also suggest that disco mutants block or interfere with elements of the circadian system located between the central pacemaker and its outputs that mediate overt rhythms. Images PMID:1740100

Noise effects on robust synchronization of a small pacemaker neuronal ensemble via nonlinear controller: electronic circuit design.

PubMed

Megam Ngouonkadi, Elie Bertrand; Fotsin, Hilaire Bertrand; Kabong Nono, Martial; Louodop Fotso, Patrick Herve

2016-10-01

In this paper, we report on the synchronization of a pacemaker neuronal ensemble constituted of an AB neuron electrically coupled to two PD neurons. By the virtue of this electrical coupling, they can fire synchronous bursts of action potential. An external master neuron is used to induce to the whole system the desired dynamics, via a nonlinear controller. Such controller is obtained by a combination of sliding mode and feedback control. The proposed controller is able to offset uncertainties in the synchronized systems. We show how noise affects the synchronization of the pacemaker neuronal ensemble, and briefly discuss its potential benefits in our synchronization scheme. An extended Hindmarsh-Rose neuronal model is used to represent a single cell dynamic of the network. Numerical simulations and Pspice implementation of the synchronization scheme are presented. We found that, the proposed controller reduces the stochastic resonance of the network when its gain increases.

Clinical use of isotope cardiac pacemakers (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, J.; Kreutzberg, B.

1973-01-01

Plutoninm-235 having a half-life of 86.4 yrs has proved suitable as a long-life energy source for a cardiac pacemaker. The radiation dose of this pacemaker is below the I. C. R. P.-recommended values. As the isotope pacemaker costs three times as much as a conventional pacemaker, the merits of implanting an isotope pacemaker vs. the conventional kind are discussed. A survey is given of the cases in which an isotope pacemaker has been used. (GE)

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

NASA Astrophysics Data System (ADS)

Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

2015-05-01

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network. Electronic supplementary information (ESI) available: Comparison of non-filtered and Savitzky-Golay filtered action potential recordings, electrical signals and corresponding optical signals. See DOI: 10.1039/c5nr01690h

Cell membrane temperature rate sensitivity predicted from the Nernst equation.

PubMed

Barnes, F S

1984-01-01

A hyperpolarized current is predicted from the Nernst equation for conditions of positive temperature derivatives with respect to time. This ion current, coupled with changes in membrane channel conductivities, is expected to contribute to a transient potential shift across the cell membrane for silent cells and to a change in firing rate for pacemaker cells.

Predicting spiral wave patterns from cell properties in a model of biological self-organization.

PubMed

Geberth, Daniel; Hütt, Marc-Thorsten

2008-09-01

In many biological systems, biological variability (i.e., systematic differences between the system components) can be expected to outrank statistical fluctuations in the shaping of self-organized patterns. In principle, the distribution of single-element properties should thus allow predicting features of such patterns. For a mathematical model of a paradigmatic and well-studied pattern formation process, spiral waves of cAMP signaling in colonies of the slime mold Dictyostelium discoideum, we explore this possibility and observe a pronounced anticorrelation between spiral waves and cell properties (namely, the firing rate) and particularly a clustering of spiral wave tips in regions devoid of spontaneously firing (pacemaker) cells. Furthermore, we observe local inhomogeneities in the distribution of spiral chiralities, again induced by the pacemaker distribution. We show that these findings can be explained by a simple geometrical model of spiral wave generation.

Hybrid automata models of cardiac ventricular electrophysiology for real-time computational applications.

PubMed

Andalam, Sidharta; Ramanna, Harshavardhan; Malik, Avinash; Roop, Parthasarathi; Patel, Nitish; Trew, Mark L

2016-08-01

Virtual heart models have been proposed for closed loop validation of safety-critical embedded medical devices, such as pacemakers. These models must react in real-time to off-the-shelf medical devices. Real-time performance can be obtained by implementing models in computer hardware, and methods of compiling classes of Hybrid Automata (HA) onto FPGA have been developed. Models of ventricular cardiac cell electrophysiology have been described using HA which capture the complex nonlinear behavior of biological systems. However, many models that have been used for closed-loop validation of pacemakers are highly abstract and do not capture important characteristics of the dynamic rate response. We developed a new HA model of cardiac cells which captures dynamic behavior and we implemented the model in hardware. This potentially enables modeling the heart with over 1 million dynamic cells, making the approach ideal for closed loop testing of medical devices.

Predicting spiral wave patterns from cell properties in a model of biological self-organization

NASA Astrophysics Data System (ADS)

Geberth, Daniel; Hütt, Marc-Thorsten

2008-09-01

In many biological systems, biological variability (i.e., systematic differences between the system components) can be expected to outrank statistical fluctuations in the shaping of self-organized patterns. In principle, the distribution of single-element properties should thus allow predicting features of such patterns. For a mathematical model of a paradigmatic and well-studied pattern formation process, spiral waves of cAMP signaling in colonies of the slime mold Dictyostelium discoideum, we explore this possibility and observe a pronounced anticorrelation between spiral waves and cell properties (namely, the firing rate) and particularly a clustering of spiral wave tips in regions devoid of spontaneously firing (pacemaker) cells. Furthermore, we observe local inhomogeneities in the distribution of spiral chiralities, again induced by the pacemaker distribution. We show that these findings can be explained by a simple geometrical model of spiral wave generation.

The pacemaker activity generating the intrinsic myogenic contraction of the dorsal vessel of Tenebrio molitor (Coleoptera).

PubMed

Markou, T; Theophilidis, G

2000-11-01

Combined intracellular and extracellular recordings from various parts of the isolated dorsal vessel of Tenebrio molitor revealed some of the following electrophysiological properties of the heart and the aorta. (i) The wave of depolarization causing forward pulsation of the dorsal vessel was always transmitted from posterior to anterior, with a conduction velocity of 0.014 m s(-1) in the heart and 0.001 m s(-1) in the aorta when the heart rate was 60 beats min(-1). (ii) There was no pacemaker activity in the aorta. (iii) The duration of the compound action potential in the aortic muscle depended on the duration of the pacemaker action potential generated in the heart. (iv) Isolated parts of the heart continued to contract rhythmically for hours, indicating powerful pacemaker activity in individual cardiac segments. (v) There was a direct relationship between action potential duration and the length of the preceding diastolic interval. (vi) The rhythmic wave of depolarization was dependent on the influx of Ca(2+). (vii) The recovery of the electrical properties of myocardial cells that had been disrupted by sectioning was rapid. (viii) In hearts sectioned into two halves, the rhythmic pacemaker action potentials recorded simultaneously from the two isolated halves eventually drifted out of phase, but they had the same intrinsic frequency. In the light of these data, we discuss two alternative models for the generation of spontaneous rhythmic pumping movements of the heart and aorta.

Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells.

PubMed

Midrio, P; Faussone-Pellegrini, M S; Vannucchi, M G; Flake, A W

2004-10-01

A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene--encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis. At 18.5 day's gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and transmission electron microscopy (TEM). In the controls, SMC were c-kit+ and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature. ICC and SMC differentiation is delayed in gastroschisis with the most damaged loops showing the most incomplete picture. These findings might help in understanding the delayed onset of peristalsis and the variable time-course of the recover seen in babies affected by gastroschisis.

DsRNA as a stimulator of cell pacemaker activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Airapetyan, S.N.; Zakharyan, R.A.; Rychkov, G.E.

1986-03-01

The authors study the action of double-stranded RNAs (dsRNA) on the characteristics of neuron pacemaker activity which permits prediction of the character of action of dsRNA on the pacemaker activity of cells and organs, and takes the investigators closer to an understanding of the membrane mechanisms underlying the action of dsRNA on the cell. The methods for isolating and fractionating dsRNA from yeasts and the intracellular recording of the electrical activity of the snail giant neuron have been described by the authors earlier. The authors determined the dependence of Ca/sup 2 +/ entry upon dsRNA concentration using the isotope /supmore » 45/Ca. Preweighed ganglia were incubated five each for an hour in 2 ml Ringer's solution containing dsRNA and 5 microliters /sup 45/CaCl/sub 2/ of 12.5 mCi activity. After incubation, the ganglia were rinsed three times for 8 min each time in normal Ringers solution. The washed ganglia were dissolved for one day in KOH. The amount of isotope entering was counted using Brav's scintillator and an RGT counter tuned to the /sup 45/Ca isotope. The physiological saline used for the isolated ganglion contained 85 mmole NaCl, 4 mmole KCl, 8 mmole CaCl/sub 2/, 10 mmole MgCl/sub 2/, 10 mmole Tris-HCl, and 5 mmole glucose.« less

Pacemaker Dependency after Cardiac Surgery: A Systematic Review of Current Evidence.

PubMed

Steyers, Curtis M; Khera, Rohan; Bhave, Prashant

2015-01-01

Severe postoperative conduction disturbances requiring permanent pacemaker implantation frequently occur following cardiac surgery. Little is known about the long-term pacing requirements and risk factors for pacemaker dependency in this population. We performed a systematic review of the literature addressing rates and predictors of pacemaker dependency in patients requiring permanent pacemaker implantation after cardiac surgery. Using a comprehensive search of the Medline, Web of Science and EMBASE databases, studies were selected for review based on predetermined inclusion and exclusion criteria. A total of 8 studies addressing the endpoint of pacemaker-dependency were identified, while 3 studies were found that addressed the recovery of atrioventricular (AV) conduction endpoint. There were 10 unique studies with a total of 780 patients. Mean follow-up ranged from 6-72 months. Pacemaker dependency rates ranged from 32%-91% and recovery of AV conduction ranged from 16%-42%. There was significant heterogeneity with respect to the definition of pacemaker dependency. Several patient and procedure-specific variables were found to be independently associated with pacemaker dependency, but these were not consistent between studies. Pacemaker dependency following cardiac surgery occurs with variable frequency. While individual studies have identified various perioperative risk factors for pacemaker dependency and non-resolution of AV conduction disease, results have been inconsistent. Well-conducted studies using a uniform definition of pacemaker dependency might identify patients who will benefit most from early permanent pacemaker implantation after cardiac surgery.

Procedure times, complication rates, and survival times associated with single-chamber versus dual-chamber pacemaker implantation in dogs with clinical signs of bradyarrhythmia: 54 cases (2004-2009).

PubMed

Genovese, David W; Estrada, Amara H; Maisenbacher, Herbert W; Heatwole, Bonnie A; Powell, Melanie A

2013-01-15

To compare procedure times and major and minor complication rates associated with single-chamber versus dual-chamber pacemaker implantation and with 1-lead, 2-lead, and 3-lead pacemaker implantation in dogs with clinical signs of bradyarrhythmia. Retrospective case series. 54 dogs that underwent pacemaker implantation because of clinical signs of bradyarrhythmia. Medical records of dogs that received pacemakers between July 2004 and December 2009 were reviewed for information regarding signalment, diagnosis, pacemaker implantation, pacemaker type, complications, and survival time. Analyses were performed to determine significant differences in anesthesia time, procedure time, and outcome for dogs on the basis of pacing mode and number of pacing leads. 28 of 54 (51.9%) dogs received single-chamber pacemakers and 26 (48.1%) received dual-chamber pacemakers. Mean ± SD procedural time was significantly longer for patients with dual-chamber pacemakers (133.5 ± 51.3 minutes) than for patients with single-chamber pacemakers (94.9 ± 37.0 minutes), and procedure time increased significantly as the number of leads increased (1 lead, 102.3 ± 51.1 minutes; 2 leads, 114.9 ± 24.8 minutes; 3 leads, 158.2 ± 8.5 minutes). Rates of major and minor complications were not significantly different between dogs that received single-chamber pacemakers and those that received dual-chamber pacemakers or among dogs grouped on the basis of the number of pacing leads placed. Although dual-chamber pacemaker implantation did result in increased procedural and anesthesia times, compared with single-chamber pacemaker implantation, this did not result in a higher complication rate.

Transcatheter leadless cardiac pacing: The new alternative solution.

PubMed

Da Costa, Antoine; Axiotis, Amandine; Romeyer-Bouchard, Cécile; Abdellaoui, Loucif; Afif, Zahi; Guichard, Jean Baptiste; Gerbay, Antoine; Isaaz, Karl

2017-01-15

A lack of information about the feasibility and safety of leadless pacemaker (LPMs) exists in a fragile population of patients with limited venous anatomy access or conventional pacemaker (PM) contraindication. Accordingly, the goal of this prospective observational study was to report our experience with this new leadless technology in a subset of patients with contraindication or limited venous access. Between May 2015 and July 2016, 14 patients were consecutively included. The indications for initial PM implantation were atrioventricular (AV) block in 10/14 patients (71%), bradyarrhythmia in one (7%), and uncontrolled atrial fibrillation (AFib) requiring AV-node ablation in three (21.5%). AFib was observed in 9 of the 14 patients (64.3%) and 3 were completely dependent with no escape rhythm (21.5%). Normal access pathways via the right or left subclavian veins were occluded due to previous PM implantations and revisions in 4 patients (28.6%) and total vena cava occlusion in 3 (21.4%). End-stage renal disease with hemodialysis was present in 8 (57%) with either local-device infections or presence of long-term implanted dialysis catheters. Evidence of previous bilaterally-infected pectoral tissue was present in 3 patients (21.5%). All procedures were successful (100%) and electrical parameters remained stable over time. No direct pacemaker-related adverse events were reported, including mechanical complications, except for one ventricular fibrillation one day post-implantation under very specific conditions. This series demonstrated very stable performance and reassuring safety results during mid-term follow-up in a very fragile population requiring a PM. The Micra LPM constitutes an excellent alternative to the epicardial surgical approach in this very fragile population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

Permanent Leadless Cardiac Pacemaker Therapy: A Comprehensive Review.

PubMed

Tjong, Fleur V Y; Reddy, Vivek Y

2017-04-11

A new technology, leadless pacemaker therapy, was recently introduced clinically to address lead- and pocket-related complications in conventional transvenous pacemaker therapy. These leadless devices are self-contained right ventricular single-chamber pacemakers implanted by using a femoral percutaneous approach. In this review of available clinical data on leadless pacemakers, early results with leadless devices are compared with historical results with conventional single-chamber pacing. Both presently manufactured leadless pacemakers show similar complications, which are mostly related to the implant procedure: cardiac perforation, device dislocation, and femoral vascular access site complications. In comparison with conventional transvenous single-chamber pacemakers, slightly higher short-term complication rates have been observed: 4.8% for leadless pacemakers versus 4.1% for conventional pacemakers. The complication rate of the leadless pacemakers is influenced by the implanter learning curve for this new procedure. No long-term outcome data are yet available for the leadless pacemakers. Larger leadless pacing trials, with long-term follow-up and direct randomized comparison with conventional pacing systems, will be required to define the proper clinical role of these leadless systems. Although current leadless pacemakers are limited to right ventricular pacing, future advanced, communicating, multicomponent systems are expected to expand the potential benefits of leadless therapy to a larger patient population. © 2017 American Heart Association, Inc.

21 CFR 870.3620 - Pacemaker lead adaptor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a pacemaker lead so that it...

21 CFR 870.3620 - Pacemaker lead adaptor.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a pacemaker lead so that it...

21 CFR 870.3620 - Pacemaker lead adaptor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a pacemaker lead so that it...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implantable pacemaker pulse generator. 870.3610... pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has... implantable pacemaker pulse generator device that was in commercial distribution before May 28, 1976, or that...

21 CFR 870.3620 - Pacemaker lead adaptor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a pacemaker lead so that it...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implantable pacemaker pulse generator. 870.3610... pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has... implantable pacemaker pulse generator device that was in commercial distribution before May 28, 1976, or that...

Pacemaker Dependency after Cardiac Surgery: A Systematic Review of Current Evidence

PubMed Central

2015-01-01

Background Severe postoperative conduction disturbances requiring permanent pacemaker implantation frequently occur following cardiac surgery. Little is known about the long-term pacing requirements and risk factors for pacemaker dependency in this population. Methods We performed a systematic review of the literature addressing rates and predictors of pacemaker dependency in patients requiring permanent pacemaker implantation after cardiac surgery. Using a comprehensive search of the Medline, Web of Science and EMBASE databases, studies were selected for review based on predetermined inclusion and exclusion criteria. Results A total of 8 studies addressing the endpoint of pacemaker-dependency were identified, while 3 studies were found that addressed the recovery of atrioventricular (AV) conduction endpoint. There were 10 unique studies with a total of 780 patients. Mean follow-up ranged from 6–72 months. Pacemaker dependency rates ranged from 32%-91% and recovery of AV conduction ranged from 16%-42%. There was significant heterogeneity with respect to the definition of pacemaker dependency. Several patient and procedure-specific variables were found to be independently associated with pacemaker dependency, but these were not consistent between studies. Conclusions Pacemaker dependency following cardiac surgery occurs with variable frequency. While individual studies have identified various perioperative risk factors for pacemaker dependency and non-resolution of AV conduction disease, results have been inconsistent. Well-conducted studies using a uniform definition of pacemaker dependency might identify patients who will benefit most from early permanent pacemaker implantation after cardiac surgery. PMID:26470027

Analysis of a five year experience of permanent pacemaker implantation at a Nigerian Teaching Hospital: need for a national database

PubMed Central

Falase, Bode; Sanusi, Michael; Johnson, Adeyemi; Akinrinlola, Fola; Ajayi, Reina; Oke, David

2013-01-01

Introduction Permanent pacemaker implantation is available in Nigeria. There is however no national registry or framework for pacemaker data collection. A pacemaker database has been developed in our institution and the results are analyzed in this study. Methods The study period was between January 2008 and December 2012. Patient data was extracted from a prospectively maintained database which was designed to include the fields of the European pacemaker patient identification code. Results Of the 51 pacemaker implants done, there were 29 males (56.9%) and 22 females (43.1%). Mean age was 68.2±12.7 years. Clinical indications were syncopal attacks in 25 patients (49%), dizzy spells in 15 patients (29.4%), bradycardia with no symptoms in 10 patients (17.7%) and dyspnoea in 2 patients (3.9%). The ECG diagnosis was complete heart block in 27 patients (53%), second degree heart block in 19 patients (37.2%) and sick sinus syndrome with bradycardia in 5 patients (9.8%). Pacemaker modes used were ventricular pacing in 29 patients (56.9%) and dual chamber pacing in 22 patients (43.1%). Files have been closed in 20 patients (39.2%) and 31 patients (60.8%) are still being followed up with median follow up of 26 months, median of 5 visits and 282 pacemaker checks done. Complications seen during follow up were 3 lead displacements (5.9%), 3 pacemaker infections (5.9%), 2 pacemaker pocket erosions (3.9%), and 1 pacemaker related death (2%). There were 5 non-pacemaker related deaths (9.8%). Conclusion Pacemaker data has been maintained for 5 years. We urge other implanting institutions in Nigeria to maintain similar databases and work towards establishment of a national pacemaker registry. PMID:24498465

Electrical interference in non-competitive pacemakers

PubMed Central

Sowton, E.; Gray, K.; Preston, T.

1970-01-01

Patients with 41 implanted non-competitive pacemakers were investigated. A variety of domestic electrical equipment, a motor-car, and a physiotherapy diathermy apparatus were each operated in turn at various ranges from the patient. Interference effects on pacemaker function were assessed on the electrocardiograph. Medtronic demand 5841 pacemakers were stopped by diathermy while Cordis Ectocor pacemakers developed a fast discharge rate. Cordis triggered pacemakers (both Atricor and Ectocor) were sensitive to interference from many items of domestic equipment and the motor car. The Elema EM153 ran at an increased rate when an electric razor was running close to the pacemaker. The Devices demand 2980 and the Medtronic demand 5841 were not affected by the domestic equipment tested. The significance of interference effects is discussed in relation to pacemaker design. Images PMID:5470044

Model for the respiratory modulation of the heart beat-to-beat time interval series

NASA Astrophysics Data System (ADS)

Capurro, Alberto; Diambra, Luis; Malta, C. P.

2005-09-01

In this study we present a model for the respiratory modulation of the heart beat-to-beat interval series. The model consists of a set of differential equations used to simulate the membrane potential of a single rabbit sinoatrial node cell, excited with a periodic input signal with added correlated noise. This signal, which simulates the input from the autonomous nervous system to the sinoatrial node, was included in the pacemaker equations as a modulation of the iNaK current pump and the potassium current iK. We focus at modeling the heart beat-to-beat time interval series from normal subjects during meditation of the Kundalini Yoga and Chi techniques. The analysis of the experimental data indicates that while the embedding of pre-meditation and control cases have a roughly circular shape, it acquires a polygonal shape during meditation, triangular for the Kundalini Yoga data and quadrangular in the case of Chi data. The model was used to assess the waveshape of the respiratory signals needed to reproduce the trajectory of the experimental data in the phase space. The embedding of the Chi data could be reproduced using a periodic signal obtained by smoothing a square wave. In the case of Kundalini Yoga data, the embedding was reproduced with a periodic signal obtained by smoothing a triangular wave having a rising branch of longer duration than the decreasing branch. Our study provides an estimation of the respiratory signal using only the heart beat-to-beat time interval series.

ParamAP: Standardized Parameterization of Sinoatrial Node Myocyte Action Potentials.

PubMed

Rickert, Christian; Proenza, Catherine

2017-08-22

Sinoatrial node myocytes act as cardiac pacemaker cells by generating spontaneous action potentials (APs). Much information is encoded in sinoatrial AP waveforms, but both the analysis and the comparison of AP parameters between studies is hindered by the lack of standardized parameter definitions and the absence of automated analysis tools. Here we introduce ParamAP, a standalone cross-platform computational tool that uses a template-free detection algorithm to automatically identify and parameterize APs from text input files. ParamAP employs a graphic user interface with automatic and user-customizable input modes, and it outputs data files in text and PDF formats. ParamAP returns a total of 16 AP waveform parameters including time intervals such as the AP duration, membrane potentials such as the maximum diastolic potential, and rates of change of the membrane potential such as the diastolic depolarization rate. ParamAP provides a robust AP detection algorithm in combination with a standardized AP parameter analysis over a wide range of AP waveforms and firing rates, owing in part to the use of an iterative algorithm for the determination of the threshold potential and the diastolic depolarization rate that is independent of the maximum upstroke velocity, a parameter that can vary significantly among sinoatrial APs. Because ParamAP is implemented in Python 3, it is also highly customizable and extensible. In conclusion, ParamAP is a powerful computational tool that facilitates quantitative analysis and enables comparison of sinoatrial APs by standardizing parameter definitions and providing an automated work flow. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Effects of 60-Heartz electric and magnetic fields on implanted cardiac pacemakers. Final report. [Hazards of power transmission line frequencies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bridges, J.E.; Frazier, M.J.

1979-09-01

The effects of 60-Hz electric and magnetic fields of exta-high voltage (EHV) transmission lines on the performance of implanted cardiac pacemakers were studied by: (1) in vitro bench tests of a total of thirteen cardiac pacemakers; (2) in vivo tests of six implanted cardiac pacemakers in baboons; and (3) non-hazardous skin measurement tests on four humans. Analytical methods were developed to predict the thresholds of body current and electric fields capable of affecting normal pacemaker operation in humans. The field strengths calculated to alter implanted pacemaker performance were compared with the range of maximum electric and magnetic field strengths amore » human would normally encounter under transmission lines of various voltages. Results indicate that the electric field or body current necessary to alter the normal operation of pacemakers is highly dependent on the type of pacemaker and the location of the implanted electrodes. However, cardiologists have not so far detected harmful effects of pacemaker reversion to the asynchronous mode in current types of pacemakers and with present methods of implantation. Such interferences can be eliminated by using advanced pacemakers less sensitive to 60-Hz voltages or by using implantation lead arrangements less sensitive to body current.« less

[Wide QRS tachycardia preceded by pacemaker spikes].

PubMed

Romero, M; Aranda, A; Gómez, F J; Jurado, A

2014-04-01

The differential diagnosis and therapeutic management of wide QRS tachycardia preceded by pacemaker spike is presented. The pacemaker-mediated tachycardia, tachycardia fibrillo-flutter in patients with pacemakers, and runaway pacemakers, have a similar surface electrocardiogram, but respond to different therapeutic measures. The tachycardia response to the application of a magnet over the pacemaker could help in the differential diagnosis, and in some cases will be therapeutic, as in the case of a tachycardia-mediated pacemaker. Although these conditions are diagnosed and treated in hospitals with catheterization laboratories using the application programmer over the pacemaker, patients presenting in primary care clinic and emergency forced us to make a diagnosis and treat the haemodynamically unstable patient prior to referral. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

A rhythmic modulatory gating system in the stomatogastric nervous system of Homarus gammarus. III. Rhythmic control of the pyloric CPG.

PubMed

Cardi, P; Nagy, F

1994-06-01

1. Two modulatory neurons, P and commissural pyloric (CP), known to be involved in the long-term maintenance of pyloric central pattern generator operation in the rock lobster Homarus gammarus, are members of the commissural pyloric oscillator (CPO), a higher-order oscillator influencing the pyloric network. 2. The CP neuron was endogenously oscillating in approximately 30% of the preparations in which its cell body was impaled. Rhythmic inhibitory feedback from the pyloric pacemaker anterior burster (AB) neuron stabilized the CP neuron's endogenous rhythm. 3. The organization of the CPO is described. Follower commissural neurons, the F cells, and the CP neuron receive a common excitatory postsynaptic potential from another commissural neuron, the large exciter (LE). When in oscillatory state, CP in turn excites the LE neuron. This positive feedback may maintain long episodes of CP oscillations. 4. The pyloric pacemaker neurons follow the CPO rhythm with variable coordination modes (i.e., 1:1, 1:2) and switch among these modes when their membrane potential is modified. The CPO inputs strongly constrain the pyloric period, which as a result may adopt only a few discrete values. This effect is based on mechanisms of entrainment between the CPO and the pyloric oscillator. 5. Pyloric constrictor neurons show differential sensitivity from the pyloric pacemaker neurons with respect to the CPO inputs. Consequently, their bursting period can be a shorter harmonic of the bursting period of the pyloric pacemakers neurons. 6. The CPO neurons seem to be the first example of modulatory gating neurons that also give timing cues to a rhythmic pattern generating network.

Dynamic, nonlinear feedback regulation of slow pacemaking by A-type potassium current in ventral tegmental area neurons.

PubMed

Khaliq, Zayd M; Bean, Bruce P

2008-10-22

We analyzed ionic currents that regulate pacemaking in dopaminergic neurons of the mouse ventral tegmental area by comparing voltage trajectories during spontaneous firing with ramp-evoked currents in voltage clamp. Most recordings were made in brain slice, with key experiments repeated using acutely dissociated neurons, which gave identical results. During spontaneous firing, net ionic current flowing between spikes was calculated from the time derivative of voltage multiplied by cell capacitance, signal-averaged over many firing cycles to enhance resolution. Net inward interspike current had a distinctive nonmonotonic shape, reaching a minimum (generally <1 pA) between -60 and -55 mV. Under voltage clamp, ramps over subthreshold voltages elicited a time- and voltage-dependent outward current that peaked near -55 mV. This current was undetectable with 5 mV/s ramps and increased steeply with depolarization rate over the range (10-50 mV/s) typical of natural pacemaking. Ramp-evoked subthreshold current was resistant to alpha-dendrotoxin, paxilline, apamin, and tetraethylammonium but sensitive to 4-aminopyridine and 0.5 mM Ba2+, consistent with A-type potassium current (I(A)). Same-cell comparison of currents elicited by various ramp speeds with natural spontaneous depolarization showed how the steep dependence of I(A) on depolarization rate results in small net inward currents during pacemaking. These results reveal a mechanism in which subthreshold I(A) is near zero at steady state, but is engaged at depolarization rates >10 mV/s to act as a powerful, supralinear feedback element. This feedback mechanism explains how net ionic current can be constrained to <1-2 pA but reliably inward, thus enabling slow, regular firing.

Radiation induced failures of complementary metal oxide semiconductor containing pacemakers: a potentially lethal complication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewin, A.A.; Serago, C.F.; Schwade, J.G.

1984-10-01

New multi-programmable pacemakers frequently employ complementary metal oxide semiconductors (CMOS). This circuitry appears more sensitive to the effects of ionizing radiation when compared to the semiconductor circuits used in older pacemakers. A case of radiation induced runaway pacemaker in a CMOS device is described. Because of this and other recent reports of radiation therapy-induced CMOS type pacemaker failure, these pacemakers should not be irradiated. If necessary, the pacemaker can be shielded or moved to a site which can be shielded before institution of radiation therapy. This is done to prevent damage to the CMOS circuit and the life threatening arrythmiasmore » which may result from such damage.« less

Sacral neuromodulation and cardiac pacemakers.

PubMed

Roth, Ted M

2010-08-01

Potential for cross-talk between cardiac pacemakers and sacral neuromodulation remains speculative. We present a case series of patients with cardiac pacemakers who underwent staged Interstim (Medtronic, Minneapolis, MN) implantation and patients who had pulse generator implantation who later required cardiac pacemakers. No cross-talk was demonstrated in either group. Sacral neuromodulation appears to be safe in the setting of cardiac pacemakers without cardioversion/defibrillation technology.

Dosimetric perturbations due to an implanted cardiac pacemaker in MammoSite{sup Registered-Sign} treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Wonmo; Kim, Siyong; Kim, Jung-in

2012-10-15

Purpose: To investigate dose perturbations for pacemaker-implanted patients in partial breast irradiation using high dose rate (HDR) balloon brachytherapy. Methods: Monte Carlo (MC) simulations were performed to calculate dose distributions involving a pacemaker in Ir-192 HDR balloon brachytherapy. Dose perturbations by varying balloon-to-pacemaker distances (BPD = 50 or 100 mm) and concentrations of iodine contrast medium (2.5%, 5.0%, 7.5%, and 10.0% by volume) in the balloon were investigated for separate parts of the pacemaker (i.e., battery and substrate). Relative measurements using an ion-chamber were also performed to confirm MC results. Results: The MC and measured results in homogeneous media withoutmore » a pacemaker agreed with published data within 2% from the balloon surface to 100 mm BPD. Further their dose distributions with a pacemaker were in a comparable agreement. The MC results showed that doses over the battery were increased by a factor of 3, compared to doses without a pacemaker. However, there was no significant dose perturbation in the middle of substrate but up to 70% dose increase in the substrate interface with the titanium capsule. The attenuation by iodine contrast medium lessened doses delivered to the pacemaker by up to 9%. Conclusions: Due to inhomogeneity of pacemaker and contrast medium as well as low-energy photons in Ir-192 HDR balloon brachytherapy, the actual dose received in a pacemaker is different from the homogeneous medium-based dose and the external beam-based dose. Therefore, the dose perturbations should be considered for pacemaker-implanted patients when evaluating a safe clinical distance between the balloon and pacemaker.« less

Impact of pacemaker mode in patients with atrioventricular conduction disturbance after trans-catheter aortic valve implantation.

PubMed

Takahashi, Masao; Badenco, Nicolas; Monteau, Jacques; Gandjbakhch, Estelle; Extramiana, Fabrice; Urena, Marina; Karam, Nicole; Marijon, Eloi; Algalarrondo, Vincent; Teiger, Emmanuel; Lellouche, Nicolas

2018-03-14

This study aimed to assess the impact of pacemaker mode programming on clinical outcomes in patients with high-degree atrioventricular conduction disturbance (AVCD) after transcatheter aortic valve implantation (TAVI). Although high-degree AVCD after TAVI can receive pacemaker, recovery of the AVCD is often observed. Specific pacemaker algorithms (AAI-DDD mode switch) are available which favor spontaneous atrioventricular conduction. Of 1,621 consecutive multi-center TAVI patients, 269 (16.4%) received pacemaker. We retrospectively included 91 patients with persistent high-degree AVCD at hospital discharge. Pacemaker dependency was defined as absence, inadequate intrinsic ventricular rhythm, or ventricular pacing time > 95% on pacemaker interrogation during follow-up. Comparison of heart failure hospitalization and death between conventional DDD (cDDD) and other modes was examined (AAI-DDD and VVI). During a mean follow-up duration of 13 months, the pacemaker dependency rate was 52.8%. Patients with cDDD mode (N = 36: 40.0%) had significantly more pacemaker dependency. Multivariate analysis showed that cDDD mode was independently associated with pacemaker dependency (odds ratio = 3.63, P = 0.03). Moreover, cDDD patients had a significant higher incidence of heart failure hospitalization (Hospitalization: cDDD vs. others = 45.4% vs. 18.2%, P = 0.03) and had a higher incidence of mortality (Death: cDDD vs. the others = 27.0% vs. 4.4%, P = 0.06). Up to half of patients implanted for high-degree AVCD after TAVI had conduction recovery. Patients with cDDD programming at hospital discharge had more pacemaker dependency and a worse cardiac prognosis. Thus, pacemaker mode should be systematically set to promote spontaneous atrioventricular conduction in patients with pacemaker implantation after TAVI. © 2018 Wiley Periodicals, Inc.

Spatial Noise in Coupling Strength and Natural Frequency within a Pacemaker Network; Consequences for Development of Intestinal Motor Patterns According to a Weakly Coupled Phase Oscillator Model

PubMed Central

Parsons, Sean P.; Huizinga, Jan D.

2016-01-01

Pacemaker activities generated by networks of interstitial cells of Cajal (ICC), in conjunction with the enteric nervous system, orchestrate most motor patterns in the gastrointestinal tract. It was our objective to understand the role of network features of ICC associated with the myenteric plexus (ICC-MP) in the shaping of motor patterns of the small intestine. To that end, a model of weakly coupled oscillators (oscillators influence each other's phase but not amplitude) was created with most parameters derived from experimental data. The ICC network is a uniform two dimensional network coupled by gap junctions. All ICC generate pacemaker (slow wave) activity with a frequency gradient in mice from 50/min at the proximal end of the intestine to 40/min at the distal end. Key features of motor patterns, directly related to the underlying pacemaker activity, are frequency steps and dislocations. These were accurately mimicked by reduction of coupling strength at a point in the chain of oscillators. When coupling strength was expressed as a product of gap junction density and conductance, and gap junction density was varied randomly along the chain (i.e., spatial noise) with a long-tailed distribution, plateau steps occurred at pointsof low density. As gap junction conductance was decreased, the number of plateaus increased, mimicking the effect of the gap junction inhibitor carbenoxolone. When spatial noise was added to the natural interval gradient, as gap junction conductance decreased, the number of plateaus increased as before but in addition the phase waves frequently changed direction of apparent propagation, again mimicking the effect of carbenoxolone. In summary, key features of the motor patterns that are governed by pacemaker activity may be a direct consequence of biological noise, specifically spatial noise in gap junction coupling and pacemaker frequency. PMID:26869875

Phasic Contractions of the Mouse Vagina and Cervix at Different Phases of the Estrus Cycle and during Late Pregnancy

PubMed Central

Gravina, Fernanda S.; van Helden, Dirk F.; Kerr, Karen P.; de Oliveira, Ramatis B.; Jobling, Phillip

2014-01-01

Background/Aims The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Methodology/Principal Findings Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Conclusions/Significance Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges. PMID:25337931

Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

PubMed

Gravina, Fernanda S; van Helden, Dirk F; Kerr, Karen P; de Oliveira, Ramatis B; Jobling, Phillip

2014-01-01

The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

Feasibility of dual-chamber (DDD) pacing via a single-pass (VDD) pacing lead employing a floating atrial ring (dipole): case series, future considerations, and refinements.

PubMed

Kassotis, John; Voigt, Louis; Mongwa, Mbu; Reddy, C V R

2005-01-01

The objective of this study was to assess the feasibility of DDD pacing from a standard single-pass VDD pacemaker system. Over the past 2 decades significant advances have been made in the development of single-pass VDD pacing systems. These have been shown in long-term prospective studies to effectively preserve atrioventricular (AV)synchrony in patients with AV block and normal sinus node function. What remains problematic is the development of a single-pass pacing system capable of DDD pacing. Such a lead configuration would be useful in those patients with peripheral venous anomalies and in younger patients with congenital anomalies, which may require lead revisions in the future. In addition, with the increased use of resynchronization (biventricular pacing) therapy, the availability of a reliable single-pass lead will minimize operative time, enhance patient safety, and minimize the amount of hardware within the heart. The feasibility of DDD pacing via a Medtronic Capsure VDD-2 (Model #5038) pacing lead was evaluated. Twenty patients who presented with AV block and normal sinus node function were recruited for this study. Atrial pacing thresholds and sensitivities were assessed intraoperatively in the supine position with various respiratory maneuvers. Five patients who agreed to participate in long-term follow-up received a dual-chamber generator and were evaluated periodically over a 12-month period. Mean atrial sensitivity was 2.35 +/- 0.83 mV at the time of implantation. Effective atrial stimulation was possible in all patients at the time of implantation (mean stimulation threshold 3.08 +/- 1.04 V at 0.5 ms [bipolar], 3.34 +/- 0.95 V at 0.5 ms [unipolar]). Five of the 20 patients received a Kappa KDR701 generator, and atrial electrical properties were followed up over a 1-year period. There was no significant change in atrial pacing threshold or incidence of phrenic nerve stimulation over the 1-year follow-up. A standard single-pass VDD pacing lead system was capable of DDD pacing intraoperatively and during long-term follow-up. Despite higher than usual thresholds via the atrial dipole, pacemaker telemetry revealed < 10% use of atrial pacing dipole over a 12-month period, which would minimally deplete the pacemaker's battery. In addition, the telemetry confirmed appropriate sensing and pacing of the atrial dipole throughout the study period. At this time such systems can serve as back-up DDD pacing systems with further refinements required to optimize atrial thresholds in all patients.

Pacemakers and implantable cardioverter defibrillators--general and anesthetic considerations.

PubMed

Rapsang, Amy G; Bhattacharyya, Prithwis

2014-01-01

A pacemaking system consists of an impulse generator and lead or leads to carry the electrical impulse to the patient's heart. Pacemaker and implantable cardioverter defibrillator codes were made to describe the type of pacemaker or implantable cardioverter defibrillator implanted. Indications for pacing and implantable cardioverter defibrillator implantation were given by the American College of Cardiologists. Certain pacemakers have magnet-operated reed switches incorporated; however, magnet application can have serious adverse effects; hence, devices should be considered programmable unless known otherwise. When a device patient undergoes any procedure (with or without anesthesia), special precautions have to be observed including a focused history/physical examination, interrogation of pacemaker before and after the procedure, emergency drugs/temporary pacing and defibrillation, reprogramming of pacemaker and disabling certain pacemaker functions if required, monitoring of electrolyte and metabolic disturbance and avoiding certain drugs and equipments that can interfere with pacemaker function. If unanticipated device interactions are found, consider discontinuation of the procedure until the source of interference can be eliminated or managed and all corrective measures should be taken to ensure proper pacemaker function should be done. Post procedure, the cardiac rate and rhythm should be monitored continuously and emergency drugs and equipments should be kept ready and consultation with a cardiologist or a pacemaker-implantable cardioverter defibrillator service may be necessary. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Pacemaker recycling: A notion whose time has come.

PubMed

Runge, Mason W; Baman, Timir S; Davis, Sheldon; Weatherwax, Kevin; Goldman, Ed; Eagle, Kim A; Crawford, Thomas C

2017-04-26

The purpose of this paper is to summarize the need, feasibility, safety, legality, and ethical perspectives of pacemaker reutilization in low- and middle-income countries (LMICs). It will also describe, in-depth, Project My Heart Your Heart (PMHYH) as a model for pacemaker reuse in LMICs. The primary source of the discussion points in this paper is a collection of 14 publications produced by the research team at the University of Michigan and its collaborative partners. The need for pacemaker reutilization in LMICs is evident. Numerous studies show that the concept of pacemaker reutilization in LMICs is feasible. Infection and device malfunction are the main concerns in regard to pacemaker reutilization, yet many studies have shown that pacemaker reuse is not associated with increased infection risk or higher mortality compared with new device implantation. Under the right circumstances, the ethical and legal bases for pacemaker reutilization are supported. PMHYH is a proof of concept pacemaker donation initiative that has allowed funeral home and crematory directors to send explanted devices to an academic center for evaluation and re-sterilization before donation to underserved patients in LMICs. The time is now to pursue large-scale studies and trials of pacemaker reuse for the betterment of society. PMHYH is leading the way in the effort and is poised to conduct a prospective randomized, non-inferiority, multicenter study to confirm the clinical efficacy and safety of pacemaker reuse, for clinical and legal support.

Pacemaker lead fracture associated with weightlifting: a report of two cases.

PubMed

Deering, J A; Pederson, D N

1993-12-01

Two cases of pacemaker lead fracture associated with weight-lifting are presented. This is a rare association which has only recently been described in the literature. In both cases, the pacemaker lead was fractured between the clavicle and the first rib, suggesting crush injury. The chest X-ray, pacemaker telemetry with measurement of lead impedance, and pacemaker reprogramming were all helpful in management.

Wireless power transfer for a pacemaker application.

PubMed

Vulfin, Vladimir; Sayfan-Altman, Shai; Ianconescu, Reuven

2017-05-01

An artificial pacemaker is a small medical device that uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate the beating of the heart. The pacemaker is implanted under the skin, and uses for many years regular non-rechargeable batteries. However, the demand for rechargeable batteries in pacemakers increased, and the aim of this work is to design an efficient charging system for pacemakers.

Roles of interleukin-9 in the growth and cholecystokinin-induced intracellular calcium signaling of cultured interstitial cells of Cajal.

PubMed

Gong, Yaoyao; Huang, Lei; Cheng, Wenfang; Li, Xueliang; Lu, Jia; Lin, Lin; Si, Xinmin

2014-01-01

Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract and loss of ICC is associated with many GI motility disorders. Previous studies have shown that ICC have the capacity to regenerate or restore, and several growth factors are critical to their growth, maintenance or regeneration. The present study aimed to investigate the roles of interleukin-9 (IL-9) in the growth, maintenance and pacemaker functions of cultured ICC. Here, we report that IL-9 promotes proliferation of ICC, and culturing ICC with IL-9 enhances cholecystokinin-8-induced Ca²⁺ transients, which is probably caused by facilitating maintenance of ICC functions under culture condition. We also show co-localizations of cholecystokinin-1 receptor and IL-9 receptor with c-kit by double-immunohistochemical labeling. In conclusion, IL-9 can promote ICC growth and help maintain ICC functions; IL-9 probably performs its functions via IL-9 receptors on ICC.

First percutaneous Micra leadless pacemaker implantation and tricuspid valve repair with MitraClip NT for lead-associated severe tricuspid regurgitation.

PubMed

Tang, Gilbert H L; Kaple, Ryan; Cohen, Martin; Dutta, Tanya; Undemir, Cenap; Ahmad, Hasan; Poniros, Angelica; Bennett, Joanne; Feng, Cheng; Lansman, Steven

2017-02-03

Pacemaker lead-associated severe tricuspid regurgitation (TR) can lead to right heart failure and poor prognosis. Surgery in these patients carries significant morbidities. We describe a successful treatment of symptomatic severe TR by leadless pacemaker implantation followed by tricuspid valve (TV) repair with the MitraClip NT. A 71-year-old frail female with poor functional status, chronic atrial fibrillation and permanent pacemaker implantation in 2012 presented with symptomatic moderate-severe mitral regurgitation (MR) and severe TR with the pacemaker lead as the culprit. She was deemed extreme risk for double valve surgery and, because of her pacemaker dependency, the decision was to stage her interventions first with transcatheter mitral repair, then laser lead extraction and leadless pacemaker implantation to free the TV from tethering, then TV repair. An obstructive LAD lesion was identified and treated during mitral repair with the MitraClip NT. The Micra leadless pacemaker implantation and subsequent TV repair with the MitraClip NT were successful and the patient's MR improved to mild and TR to moderate, respectively. We report here a first successful transcatheter strategy to treat lead-associated severe TR by leadless pacemaker and MitraClip. Removing the pacemaker lead relieved leaflet tethering and improved the reparability of the TV.

Pacemaker lead perforation of the right ventricle associated with Moraxella phenylpyruvica infection in a dog.

PubMed

Ciavarella, A; Nimmo, J; Hambrook, L

2016-04-01

A 13-year-old neutered male Border Collie was presented with acute onset syncope, weakness and anorexia 10 months after transvenous pacemaker implantation. The patient was laterally recumbent, bradycardic (36 beats/min) and febrile (40.7°C) on presentation. An electrocardiogram (ECG) revealed recurrence of third-degree atrioventricular block with a ventricular escape rhythm. Fluoroscopy identified migration of the pacemaker tip through the apex of the right ventricle. Echocardiography failed to reveal any evidence of pericardial effusion or cardiac tamponade. Full postmortem was performed after euthanasia. The pacemaker lead had perforated the apex of the right ventricle and lodged in the right pleural space. Culture of blood (taken antemortem), pericardial sac, right ventricular wall (surrounding pacemaker lead), pacemaker lead tip and pericardial fluid revealed a pure growth of Moraxella phenylpyruvica. Bacteraemia associated with M. phenylpyruvica has never been reported in the dog, but sporadic cases are reported in humans. Infection could have resulted from either pre-existing myocarditis or opportunistic infection and bacteraemia post pacemaker implantation. Evaluation of the pacemaker function at regular intervals would allow early detection of poor pacemaker-to-myocardium contact, which would prompt further investigation of pacemaker lead abnormalities such as perforation. © 2016 Australian Veterinary Association.

Pacemaker recycling: A notion whose time has come

PubMed Central

Runge, Mason W; Baman, Timir S; Davis, Sheldon; Weatherwax, Kevin; Goldman, Ed; Eagle, Kim A; Crawford, Thomas C

2017-01-01

The purpose of this paper is to summarize the need, feasibility, safety, legality, and ethical perspectives of pacemaker reutilization in low- and middle-income countries (LMICs). It will also describe, in-depth, Project My Heart Your Heart (PMHYH) as a model for pacemaker reuse in LMICs. The primary source of the discussion points in this paper is a collection of 14 publications produced by the research team at the University of Michigan and its collaborative partners. The need for pacemaker reutilization in LMICs is evident. Numerous studies show that the concept of pacemaker reutilization in LMICs is feasible. Infection and device malfunction are the main concerns in regard to pacemaker reutilization, yet many studies have shown that pacemaker reuse is not associated with increased infection risk or higher mortality compared with new device implantation. Under the right circumstances, the ethical and legal bases for pacemaker reutilization are supported. PMHYH is a proof of concept pacemaker donation initiative that has allowed funeral home and crematory directors to send explanted devices to an academic center for evaluation and re-sterilization before donation to underserved patients in LMICs. The time is now to pursue large-scale studies and trials of pacemaker reuse for the betterment of society. PMHYH is leading the way in the effort and is poised to conduct a prospective randomized, non-inferiority, multicenter study to confirm the clinical efficacy and safety of pacemaker reuse, for clinical and legal support. PMID:28515847

[The nature of pacemaker activity].

PubMed

Kabakov, A Iu

1991-01-01

A general equation of the membrane resting potential (RP) has been derived for closed cell membrane (CM) model. It is shown that Na,K-ATPase of cardiomyocytes is in the antielectrogenic phase. A hypothesis is proposed: a pacemaker cell is an excitable cell, which has RP corresponding to the given activity of Na,K-ATPase and non-activated cationic conductivities of CM higher than the activation threshold of Na-channels. The equation of the equipotential levels of the membrane RP on the surface of the cationic conductivities has been derived. It is shown that the substances (e. g. neuromediator) that change the membrane cation permeability are able to depolarize or to hyperpolarize CM. The direction of polarization is dependent on the state of the cell electrogenic system. The following factors promote the hyperpolarizing effect of the magnifying cation permeability substances: 1) high activity of Na,K-ATPase, 2) low background cation permeability of CM (among their number the integrity of CM) and 3) high ratio of the potassium permeability alteration in respect to that of sodium which is evoked by the substance (delta gK/delta gNa).

Pacemaker explosions in crematoria: problems and possible solutions

PubMed Central

Gale, Christopher P; Mulley, Graham P

2002-01-01

The number of artificial cardiac pacemakers is increasing, as is the number of bodies being cremated. Because of the explosive potential of pacemakers when heated, a statutory question on the cremation form asks whether the deceased has a pacemaker and if so whether it has been removed. We sent a questionnaire to all the crematoria in the UK enquiring about the frequency, consequences and prevention of pacemaker explosions. We found that about half of all crematoria in the UK experience pacemaker explosions, that pacemaker explosions may cause structural damage and injury and that most crematoria staff are unaware of the explosive potential of implantable cardiac defibrillators. Crematoria staff rely on the accurate completion of cremation forms, and doctors who sign cremation forms have a legal obligation to provide such information. PMID:12091510

Nanostructured cavity devices for extracellular stimulation of HL-1 cells.

PubMed

Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

2015-01-01

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.

21 CFR 870.3700 - Pacemaker programmers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker programmers. 870.3700 Section 870.3700...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used to change noninvasively one or more of...

21 CFR 870.3720 - Pacemaker electrode function tester.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker electrode function tester. 870.3720... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3720 Pacemaker electrode function tester. (a) Identification. A pacemaker electrode function tester is a device which is...

21 CFR 870.3730 - Pacemaker service tools.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker service tools. 870.3730 Section 870.3730...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as screwdrivers and Allen wrenches...

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External transcutaneous cardiac pacemaker... § 870.5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device used to supply a periodic electrical pulse intended to...

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false External transcutaneous cardiac pacemaker... § 870.5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device used to supply a periodic electrical pulse intended to...

21 CFR 870.3720 - Pacemaker electrode function tester.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker electrode function tester. 870.3720... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3720 Pacemaker electrode function tester. (a) Identification. A pacemaker electrode function tester is a device which is...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

21 CFR 870.3730 - Pacemaker service tools.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker service tools. 870.3730 Section 870.3730...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as screwdrivers and Allen wrenches...

21 CFR 870.3730 - Pacemaker service tools.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker service tools. 870.3730 Section 870.3730...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as screwdrivers and Allen wrenches...

21 CFR 870.3720 - Pacemaker electrode function tester.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker electrode function tester. 870.3720... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3720 Pacemaker electrode function tester. (a) Identification. A pacemaker electrode function tester is a device which is...

21 CFR 870.3700 - Pacemaker programmers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker programmers. 870.3700 Section 870.3700...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used to change noninvasively one or more of...

21 CFR 870.3730 - Pacemaker service tools.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker service tools. 870.3730 Section 870.3730...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as screwdrivers and Allen wrenches...

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false External transcutaneous cardiac pacemaker... § 870.5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device used to supply a periodic electrical pulse intended to...

21 CFR 870.3720 - Pacemaker electrode function tester.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker electrode function tester. 870.3720... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3720 Pacemaker electrode function tester. (a) Identification. A pacemaker electrode function tester is a device which is...

21 CFR 870.3700 - Pacemaker programmers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker programmers. 870.3700 Section 870.3700...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used to noninvasively change one or more of...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

21 CFR 870.3730 - Pacemaker service tools.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker service tools. 870.3730 Section 870.3730...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as screwdrivers and Allen wrenches...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false External transcutaneous cardiac pacemaker... § 870.5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device used to supply a periodic electrical pulse intended to...

21 CFR 870.3700 - Pacemaker programmers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker programmers. 870.3700 Section 870.3700...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used to noninvasively change one or more of...

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false External transcutaneous cardiac pacemaker... § 870.5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device used to supply a periodic electrical pulse intended to...

Evaluation of the effects of electric fields on implanted cardiac pacemakers. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moss, A.J.; Carstensen, E.

1985-02-01

The effects of extra high voltage (EHV) transmission line electric fields on pacemaker function were evaluated in 11 patients with seven different implanted pacemaker models from four manufacturers. Alteration in pacemaker function was demonstrated in five unipolar units (three different models) from two manufacturers during exposure to electric fields ranging from 2 to 9 kV/m, with total body currents from 47 to 175 ..mu..A. These electric fields and body currents are representative of values that can be encountered by individuals standing beneath EHV transmission lines. Transient alterations in pacemaker function observed in this study included inappropriate triggered activity, inhibition ofmore » impulse generation, reduction in rate, and reversion from demand to asynchronous mode. Electromagnetic interference from high voltage transmission lines can induce alterations in pacemaker function in certain designs of these devices. However, pacemaker manufacturers can incorporate appropriate circuits in the pacemaker design to eliminate this problem. 8 references.« less

Electromagnetic interference with pacemakers caused by portable media players.

PubMed

Thaker, Jay P; Patel, Mehul B; Jongnarangsin, Krit; Liepa, Valdis V; Thakur, Ranjan K

2008-04-01

Electromagnetic fields generated by electrical devices may cause interference with permanent pacemakers. Media players are becoming a common mode of portable entertainment. The most common media players used worldwide are iPods. These devices are often carried in a shirt chest pocket, which may place the devices close to an implanted pacemaker. The purpose of this study was to determine if iPods cause interference with pacemakers. In this prospective, single-blinded study, 100 patients who had cardiac pacemakers were tested with four types of iPods to assess for interference. Patients were monitored by a single-channel ECG monitor as well as the respective pacemaker programmer via the telemetry wand. iPods were tested by placing them 2 inches anterior to the pacemaker and wand for up to 10 seconds. To simulate actual use, standard-issue headphones were plugged into the iPods. To maintain consistency, the volume was turned up maximally, and the equalizer was turned off. A subset of 25 patients underwent testing on 2 separate days to assess for reproducibility of interference. Pacemaker interference was categorized as type I or type II telemetry interference. Type I interference was associated with atrial and/or ventricular high rates on rate histograms. Type II interference did not affect pacemaker rate counters. Electromagnetic emissions from the four iPods also were evaluated in a Faraday cage to determine the mechanism of the observed interference. One hundred patients (63 men and 37 women; mean age 77.1 +/- 7.6 years) with 11 single-chamber pacemakers and 89 dual-chamber pacemakers underwent 800 tests. The incidence of any type of interference was 51% of patients and 20% of tests. Type I interference was seen in 19% of patients and type II in 32% of patients. Reproducibility testing confirmed that interference occurred regardless of pacing configuration (unipolar or bipolar), pacing mode (AAI, VVI, or DDD), and from one day to the next. Electromagnetic emissions testing from the iPods demonstrated maximum emissions in the pacemaker carrier frequency range when the iPod was turned "on" with the headphones attached. iPods placed within 2 inches of implanted pacemakers monitored via the telemetry wand can cause interference with pacemakers.

21 CFR 870.1750 - External programmable pacemaker pulse generator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false External programmable pacemaker pulse generator. 870.1750 Section 870.1750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker...

21 CFR 870.1750 - External programmable pacemaker pulse generator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false External programmable pacemaker pulse generator. 870.1750 Section 870.1750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker...

21 CFR 870.1750 - External programmable pacemaker pulse generator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External programmable pacemaker pulse generator. 870.1750 Section 870.1750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker...

21 CFR 870.1750 - External programmable pacemaker pulse generator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false External programmable pacemaker pulse generator. 870.1750 Section 870.1750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker...

21 CFR 870.1750 - External programmable pacemaker pulse generator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false External programmable pacemaker pulse generator. 870.1750 Section 870.1750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker...

21 CFR 870.3710 - Pacemaker repair or replacement material.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

21 CFR 870.3670 - Pacemaker charger.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker charger. 870.3670 Section 870.3670 Food... DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used transcutaneously to recharge the batteries of a rechargeable...

21 CFR 870.3670 - Pacemaker charger.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker charger. 870.3670 Section 870.3670 Food... DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used transcutaneously to recharge the batteries of a rechargeable...

21 CFR 870.3710 - Pacemaker repair or replacement material.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

21 CFR 870.3670 - Pacemaker charger.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker charger. 870.3670 Section 870.3670 Food... DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used transcutaneously to recharge the batteries of a rechargeable...

21 CFR 870.3710 - Pacemaker repair or replacement material.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

21 CFR 870.3670 - Pacemaker charger.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker charger. 870.3670 Section 870.3670 Food... DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used transcutaneously to recharge the batteries of a rechargeable...

21 CFR 870.3710 - Pacemaker repair or replacement material.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

The mitochondrial uniporter controls fight or flight heart rate increases.

PubMed

Wu, Yuejin; Rasmussen, Tyler P; Koval, Olha M; Joiner, Mei-Ling A; Hall, Duane D; Chen, Biyi; Luczak, Elizabeth D; Wang, Qiongling; Rokita, Adam G; Wehrens, Xander H T; Song, Long-Sheng; Anderson, Mark E

2015-01-20

Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

Effect of electric and magnetic fields near an HVDC converter terminal on implanted cardiac pacemakers. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frazier, M.J.

1980-08-01

The electromagnetic fields associated with HVDC converters and transmission lines constitute a unique environment for persons with implanted cardiac pacemakers. A measurement program has been conducted to assess the potential interfering effects of these harmonically rich fields on implanted pacemakers. The experimental procedures that were employed take into account the combined effects of the electric and magnetic fields. The effect of the resulting body current on the response of six pacemakers was assessed in the laboratory, using a previously developed model to relate body current to pacemaker pickup voltage. The results show that R-wave pacemaker reversion can be expected atmore » some locations within the converter facility, but that a large safety margin for unperturbed pacemaker operation exists beneath the transmission lines.« less

21 CFR 870.3650 - Pacemaker polymeric mesh bag.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker polymeric mesh bag. 870.3650 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. (a) Identification. A pacemaker polymeric mesh bag is an implanted device used to hold a...

21 CFR 870.3650 - Pacemaker polymeric mesh bag.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker polymeric mesh bag. 870.3650 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. (a) Identification. A pacemaker polymeric mesh bag is an implanted device used to hold a...

21 CFR 870.3690 - Pacemaker test magnet.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker test magnet. 870.3690 Section 870.3690...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used to test an inhibited or triggered type...

21 CFR 870.3690 - Pacemaker test magnet.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker test magnet. 870.3690 Section 870.3690...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used to test an inhibited or triggered type...

21 CFR 870.3690 - Pacemaker test magnet.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker test magnet. 870.3690 Section 870.3690...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used to test an inhibited or triggered type...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implantable pacemaker pulse generator. 870.3610 Section 870.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has...

21 CFR 870.3650 - Pacemaker polymeric mesh bag.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker polymeric mesh bag. 870.3650 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. (a) Identification. A pacemaker polymeric mesh bag is an implanted device used to hold a...

21 CFR 870.3690 - Pacemaker test magnet.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker test magnet. 870.3690 Section 870.3690...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used to test an inhibited or triggered type...

21 CFR 870.3650 - Pacemaker polymeric mesh bag.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker polymeric mesh bag. 870.3650 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. (a) Identification. A pacemaker polymeric mesh bag is an implanted device used to hold a...

Radiation effect on implanted pacemakers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pourhamidi, A.H.

1983-10-01

It was previously thought that diagnostic or therapeutic ionizing radiation did not have an adverse effect on the function of cardiac pacemakers. Recently, however, some authors have reported damaging effect of therapeutic radiation on cardiac pulse generators. An analysis of a recently-extracted pacemaker documented the effect of radiation on the pacemaker pulse generator.

A Very Low Power MAC (VLPM) Protocol for Wireless Body Area Networks

PubMed Central

Ullah, Niamat; Khan, Pervez; Kwak, Kyung Sup

2011-01-01

Wireless Body Area Networks (WBANs) consist of a limited number of battery operated nodes that are used to monitor the vital signs of a patient over long periods of time without restricting the patient’s movements. They are an easy and fast way to diagnose the patient’s status and to consult the doctor. Device as well as network lifetime are among the most important factors in a WBAN. Prolonging the lifetime of the WBAN strongly depends on controlling the energy consumption of sensor nodes. To achieve energy efficiency, low duty cycle MAC protocols are used, but for medical applications, especially in the case of pacemakers where data have time-limited relevance, these protocols increase latency which is highly undesirable and leads to system instability. In this paper, we propose a low power MAC protocol (VLPM) based on existing wakeup radio approaches which reduce energy consumption as well as improving the response time of a node. We categorize the traffic into uplink and downlink traffic. The nodes are equipped with both a low power wake-up transmitter and receiver. The low power wake-up receiver monitors the activity on channel all the time with a very low power and keeps the MCU (Micro Controller Unit) along with main radio in sleep mode. When a node [BN or BNC (BAN Coordinator)] wants to communicate with another node, it uses the low-power radio to send a wakeup packet, which will prompt the receiver to power up its primary radio to listen for the message that follows shortly. The wake-up packet contains the desired node’s ID along with some other information to let the targeted node to wake-up and take part in communication and let all other nodes to go to sleep mode quickly. The VLPM protocol is proposed for applications having low traffic conditions. For high traffic rates, optimization is needed. Analytical results show that the proposed protocol outperforms both synchronized and unsynchronized MAC protocols like T-MAC, SCP-MAC, B-MAC and X-MAC in terms of energy consumption and response time. PMID:22163818

A two dimension model of the uterine electrical wave propagation.

PubMed

Rihana, S; Lefrançois, E; Marque, C

2007-01-01

The uterus, usually quiescent during pregnancy, exhibits forceful contractions at term leading to delivery. These contractions are caused by the synchronized propagation of electrical waves from the pacemaker cells to its neighbors inducing the whole coordinated contraction of the uterus wall leading to labor. In a previous work, we simulate the electrical activity of a single uterine cell by a set of ordinary differential equations. Then, this model has been used to simulate the electrical activity propagation. In the present work, the uterine cell tissue is assumed to have uniform and isotropic propagation, and constant electrical membrane properties. The stability of the numerical solution imposes the choice of a critical temporal step. A wave starts at a pacemaker cell; this electrical activity is initiated by the injection of an external stimulation current to the cell membrane. We observe synchronous wave propagation for axial resistance values around 0.5 GOmega or less and propoagation blocking for values greater than 0.7 GOmega. We compute the conduction velocity of the excitation, for different axial resistance values, and obtain a velocity about 10 cm/sec, approaching the one described by the literature for the rat at end of term.

Programmable Pacemaker

NASA Technical Reports Server (NTRS)

1980-01-01

St. Jude Medical's Cardiac Rhythm Management Division, formerly known as Pacesetter Systems, Inc., incorporated Apollo technology into the development of the programmable pacemaker system. This consists of the implantable pacemaker together with a physician's console containing the programmer and a data printer. Physician can communicate with patient's pacemaker by means of wireless telemetry signals transmitted through the communicating head held over the patient's chest. Where earlier pacemakers deliver a fixed type of stimulus once implanted, Programalith enables surgery free "fine tuning" of device to best suit the patient's changing needs.

Model for the heart beat-to-beat time series during meditation

NASA Astrophysics Data System (ADS)

Capurro, A.; Diambra, L.; Malta, C. P.

2003-09-01

We present a model for the respiratory modulation of the heart beat-to-beat interval series. The model consists of a pacemaker, that simulates the membrane potential of the sinoatrial node, modulated by a periodic input signal plus correlated noise that simulates the respiratory input. The model was used to assess the waveshape of the respiratory signals needed to reproduce in the phase space the trajectory of experimental heart beat-to-beat interval data. The data sets were recorded during meditation practices of the Chi and Kundalini Yoga techniques. Our study indicates that in the first case the respiratory signal has the shape of a smoothed square wave, and in the second case it has the shape of a smoothed triangular wave.

Redo surgery after permanent pacemaker implantation: performance indicator of surgical techniques and pacing technology.

PubMed

Bharat, Vijaya

2004-01-01

The incidence of permanent pacemaker-related complications is reducing due to advancement of technology and increasing operator experience. There are only few series from India reporting the annual complication rates from a single center over the years. This is a series of 782 pacemakers implanted over 20 years in a secondary healthcare set-up. Eighty-two patients underwent redo surgery, either for a procedure-related complication (n=34) or for replacement of a malfunctioning/end-of-life pacemaker (n=48). Through critical analysis and corrective measures, all the procedural complications were reduced to less than 4% of the annual implantations. The introduction of a pacemaker follow-up clinic contributed to reducing the rate of elective replacement for battery depletion from 19.17% of the implanted VVI pacemakers to 0.63%. Despite being a low-volume center, with less than 100 pacemakers implanted annually, the performance of our pacing practice has shown continuous improvement.

Wenckebach upper rate response in single chamber pacemaker.

PubMed

Barold, S S

2000-07-01

The Medtronic Minix pacemaker during normal function in the VVT mode was found to exhibit a Wenckenbach upper rate response similar to that of dual chamber devices. This behavior occurred only when the upper rate interval was longer than the pacemaker refractory period. In a single chamber device this response may simulate pacemaker malfunction.

Proton Beam Therapy Interference With Implanted Cardiac Pacemakers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oshiro, Yoshiko; Sugahara, Shinji; Noma, Mio

2008-11-01

Purpose: To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function. Methods and Materials: After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33-77 gray equivalents (GyE) in dose fractions of 2.2-6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation field. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined beforemore » and after PBT. Results: The phantom study showed no effect of neutron scatter on pacemaker generators. In the study, changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course. Conclusions: PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore, patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT.« less

Trends in Cardiac Pacemaker Batteries

PubMed Central

Mallela, Venkateswara Sarma; Ilankumaran, V; Rao, N.Srinivasa

2004-01-01

Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future. PMID:16943934

Short- and long-term need for permanent pacemaker after transcatheter implantation of the Edwards Sapien aortic valve prosthesis.

PubMed

Moreno, Raúl; Calvo, Luis; Sánchez-Recalde, Angel; Galeote, Guillermo; Jiménez-Valero, Santiago; López, Teresa; Plaza, Ignacio; González-Davia, Rosa; Ramírez, Ulises; Mesa, Jose Maria; Moreno-Gomez, Isidro; López-Sendón, José-Luis

2015-11-01

A permanent pacemaker is frequently needed after transcatheter aortic valve implantation, but the available data are mainly on the CoreValve system. To evaluate the need for new permanent pacemaker after implantation of the Edwards Sapien device, as well as related factors. We included the first 100 patients treated with the Edwards Sapien device at our institution. Of these, 12 had a permanent pacemaker before the procedure, and thus our study population was the remaining 88 patients. A permanent pacemaker was indicated in eight patients (9.1%) during hospitalization or at 30 days. After discharge, another four patients needed a pacemaker (at 42 days and three, 18, and 30 months). Two variables were associated with the need for pacemaker during hospitalization: previous dialysis (13% vs. 1%, p=0.042) and complete right bundle branch block before the procedure (25% vs. 5%, p=0.032). More than one month after the procedure, the characteristics associated with the need for pacemaker were plasma creatinine level (2.5±1.7 vs. 1.3±0.6 mg/dl, p=0.001) and previous myocardial infarction (50% vs. 10%, p=0.013). The rate of pacemaker implantation with the Edwards Sapien device was 9.1%. Right bundle branch block and dialysis were associated with this complication.

Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila.

PubMed

Liu, Tianxin; Mahesh, Guruswamy; Houl, Jerry H; Hardin, Paul E

2015-06-03

Circadian pacemaker neurons in the Drosophila brain control daily rhythms in locomotor activity. These pacemaker neurons can be subdivided into early or late groups depending on whether rhythms in period (per) and timeless (tim) expression are initiated at the first instar (L1) larval stage or during metamorphosis, respectively. Because CLOCK-CYCLE (CLK-CYC) heterodimers initiate circadian oscillator function by activating per and tim transcription, a Clk-GFP transgene was used to mark when late pacemaker neurons begin to develop. We were surprised to see that CLK-GFP was already expressed in four of five clusters of late pacemaker neurons during the third instar (L3) larval stage. CLK-GFP is only detected in postmitotic neurons from L3 larvae, suggesting that these four late pacemaker neuron clusters are formed before the L3 larval stage. A GFP-cyc transgene was used to show that CYC, like CLK, is also expressed exclusively in pacemaker neurons from L3 larval brains, demonstrating that CLK-CYC is not sufficient to activate per and tim in late pacemaker neurons at the L3 larval stage. These results suggest that most late pacemaker neurons develop days before novel factors activate circadian oscillator function during metamorphosis. Copyright © 2015 the authors 0270-6474/15/358662-10$15.00/0.

Third-generation mobile phones (UMTS) do not interfere with permanent implanted pacemakers.

PubMed

Ismail, Mohamed M; Badreldin, Akmal M A; Heldwein, Matthias; Hekmat, Khosro

2010-07-01

Third-generation mobile phones, UMTS (Universal Mobile Telecommunication System), were recently introduced in Europe. The safety of these devices with regard to their interference with implanted pacemakers is as yet unknown and is the point of interest in this study. The study comprised 100 patients with permanent pacemaker implantation between November 2004 and June 2005. Two UMTS cellular phones (T-Mobile, Vodafone) were tested in the standby, dialing, and operating mode with 23 single-chamber and 77 dual-chamber pacemakers. Continuous surface electrocardiograms (ECGs), intracardiac electrograms, and marker channels were recorded when calls were made by a stationary phone to cellular phone. All pacemakers were tested under a "worst-case scenario," which includes a programming of the pacemaker to unipolar sensing and pacing modes and inducing of a maximum sensitivity setting during continuous pacing of the patient. Patients had pacemaker implantation between June 1990 and April 2005. The mean age was 68.4 +/- 15.1 years. Regardless of atrial and ventricular sensitivity settings, both UMTS mobile phones (Nokia 6650 and Motorola A835) did not show any interference with all tested pacemakers. In addition, both cellular phones did not interfere with the marker channels and the intracardiac ECGs of the pacemakers. Third-generation mobile phones are safe for patients with permanent pacemakers. This is due to the high-frequency band for this system (1,800-2,200 MHz) and the low power output between 0.01 W and 0.25 W.

The nuclear pacemaker: Is renewed interest warranted

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parsonnet, V.; Berstein, A.D.; Perry, G.Y.

1990-10-01

From 1973 through 1987, 155 radioisotope-powered nuclear pacemakers were implanted in 132 patients at the Newark Beth Israel Medical Center. The longevity of the first 15 devices, all of which were fixed-rate (VOO) pacemakers, was significantly better than that of 15 lithium-chemistry demand (VVI) pacemakers used as control devices (p = 0.0002). Of the entire cohort of 155 nuclear pacemakers, 136 were VVI devices and 19 were VOO units. The patients with VOO pacemakers needed reoperations more often than did those with VVI pacemakers, chiefly for mode change (p less than 0.001). Power-source failure was observed in only 1 case,more » but 47 nuclear pacemakers were removed for other reasons, including component malfunction (15 units), mode change (12 units), high pacing thresholds (8 units) and lead or connector problems (5 units). The actuarial survival at 15 years was 99% for power sources and 82% for the entire pacing systems (pulse generators plus leads). The frequency of malignancy was similar to that of the population at large and primary tumor sites were randomly distributed. Deaths most commonly were due to cardiac causes (68%). Thus, nuclear pacemakers are safe and reliable and their greater initial cost appears to be offset by their longevity and the resulting decrease in the frequency of reoperations. It is reasonable to suggest that further use be made of long-lasting nuclear power sources for modern pacemakers and other implantable rhythm-management devices.« less

E AND M CIRCADIAN PACEMAKER NEURONS USE DIFFERENT PDF RECEPTOR SIGNALOSOME COMPONENTS IN DROSOPHILA

PubMed Central

Duvall, Laura B.

2014-01-01

We used real-time imaging to detect cAMP levels in neurons of intact fly brains to study mechanisms of circadian pacemaker synchronization by the neuropeptide PDF in Drosophila. PDF receptor (PDF-R) is expressed by both M (sLNv) and E (LNd) pacemaker sub-classes and is coupled to Gsα in both cases. We previously reported that PDF-R in M pacemakers elevates cAMP levels by activating the ortholog of mammalian Adenylate Cyclase 3 (AC3), but that AC3 disruptions had no effect on E pacemaker sensitivity to PDF. Here we show that PDF-R in E pacemakers activates a different AC isoform, AC78C, an ortholog of mammalian AC8. Knockdown of AC78C by transgenic RNAi substantially reduces, but does not completely abrogate, PDF responses in these E pacemakers. The knockdown effect is intact when restricted to mature stages, suggesting a physiological and not a development role for AC78C in E pacemakers. The AC78C phenotype is rescued by over-expression of AC78C, but not by over-expression of the rutabaga AC. AC78C over-expression does not disrupt PDF responses in these E pacemakers, and neither AC78C knockdown nor its over-expression disrupted locomotor rhythms. Finally, knockdown of two AKAPs, nervy and AKAP 200 partially reduces LNd PDF responses. These findings begin to identify the components of E pacemaker PDF-R signalosomes and indicate they are distinct from PDF-R signalosomes in M pacemakers: we propose they contain AC78C and at least one other AC. PMID:23929551

E and M circadian pacemaker neurons use different PDF receptor signalosome components in drosophila.

PubMed

Duvall, Laura B; Taghert, Paul H

2013-08-01

We used real-time imaging to detect cAMP levels in neurons of intact fly brains to study the mechanisms of circadian pacemaker synchronization by the neuropeptide pigment dispersing factor (PDF) in Drosophila. PDF receptor (PDF-R) is expressed by both M (sLNv) and E (LNd) pacemaker subclasses and is coupled to G(sα) in both cases. We previously reported that PDF-R in M pacemakers elevates cAMP levels by activating the ortholog of mammalian adenylate cyclase 3 (AC3) but that AC3 disruptions had no effect on E pacemaker sensitivity to PDF. Here, we show that PDF-R in E pacemakers activates a different AC isoform, AC78C, an ortholog of mammalian AC8. Knockdown of AC78C by transgenic RNAi substantially reduces, but does not completely abrogate, PDF responses in these E pacemakers. The knockdown effect is intact when restricted to mature stages, suggesting a physiological and not a development role for AC78C in E pacemakers. The AC78C phenotype is rescued by the overexpression of AC78C but not by overexpression of the rutabaga AC. AC78C overexpression does not disrupt PDF responses in these E pacemakers, and neither AC78C knockdown nor its overexpression disrupted locomotor rhythms. Finally, knockdown of 2 AKAPs, nervy and AKAP200, partially reduces LNd PDF responses. These findings begin to identify the components of E pacemaker PDF-R signalosomes and indicate that they are distinct from PDF-R signalosomes in M pacemakers: we propose they contain AC78C and at least 1 other AC.

The pacemaker-twiddler's syndrome: an infrequent cause of pacemaker failure.

PubMed

Salahuddin, Mohammad; Cader, Fathima Aaysha; Nasrin, Sahela; Chowdhury, Mashhud Zia

2016-01-20

The pacemaker-twiddler's syndrome is an uncommon cause of pacemaker malfunction. It occurs due to unintentional or deliberate manipulation of the pacemaker pulse generator within its skin pocket by the patient. This causes coiling of the lead and its dislodgement, resulting in failure of ventricular pacing. More commonly reported among elderly females with impaired cognition, the phenomenon usually occurs in the first year following pacemaker implantation. Treatment involves repositioning of the dislodged leads and suture fixation of the lead and pulse generator within its pocket. An 87 year old Bangladeshi lady who underwent a single chamber ventricular pacemaker (VVI mode: i.e. ventricle paced, ventricle sensed, inhibitory mode) implantation with the indication of complete heart block, and presented to us again 7 weeks later, with syncopal attacks. She admitted to repeatedly manipulating the pacemaker generator in her left pectoral region. Physical examination revealed a heart rate of 42 beats/minute, blood pressure 140/80 mmHg and bilateral crackles on lung auscultation. She had no cognitive deficit. An immediate electrocardiogram showed complete heart block with pacemaker spikes and failure to capture. Chest X-ray showed coiled and retracted right ventricular lead and rotated pulse generator. An emergent temporary pace maker was set at a rate of 60 beats per minute. Subsequently, she underwent successful lead repositioning with strong counselling to avoid further twiddling. Twiddler's syndrome should be considered as a cause of pacemaker failure in elderly patients presenting with bradyarrythmias following pacemaker implantation. Chest X-ray and electrocardiograms are simple and easily-available first line investigations for its diagnosis. Lead repositioning is required, however proper patient education and counselling against further manipulation is paramount to long-term management.

[Atrial fibrillation before and after pacemaker implantation (WI and DDD) in patients with complete atrioventricular block].

PubMed

Matusik, Paweł; Woznica, Natalia; Lelakowsk, Jacek

2010-05-01

Atrial fibrillation (AF) is a frequent problem of patients with pacemakers, and depends not only on disease but also on stimulation method. The aim of the study was to estimate the prevalence of AF before and after pacemaker implantation as well as to assess the influence of VVI and DDD cardiac pacing on onset of AF in patients with complete atrioventricularblock (AVB). We included 155 patients controlled between 2000 and 2008 in Pacemaker Clinic because of AVB III degree, treated with VVI or DDD pacemaker implantation. Information about the health status of the patients was gathered from medical documentation and analysis of clinical ambulatory electrocardiograms. The study group comprised of 68 women and 87 men, mean age 68.7 +/- 13.9 years during implantation. 69% of patients had VVI pacemaker. There were 72.3% of patients with sinus rhythm before pacemaker implantation. During follow-up 4 +/- 2.8 years in 19.6% cases onset of atrial fibrillation de novo was diagnosed (in 31.3% in VVI mode vs. 2.2% in DDD mode; p = 0.00014). Mean time to AF since implantation was approximately 2.5 years. In VVI group (21 persons) amounted 32.1 months, while in 1 patient with DDD pacemaker 18 months. Between group with AF after implantation and with sinus rhythm preserved there was no statistically significant difference in age or gender (p = 0.89512 and p = 0.1253, respectively). Prevalence of atrial fibrillation after pacemaker implantation increased to 40%. Atrial fibrillation is frequent in patients before and after pacemaker implantation, especially in patients stimulated in VVI mode. Major possibility of atrial fibrillation onset after pacemaker implantation should result in more attention during routine ECG examination.

The effect of single engine fixed wing air transport on rate-responsive pacemakers.

PubMed

De Rotte, A A; Van Der Kemp, P

1999-09-01

Insufficient information exists about the safety of patients with accelerometer-based rate-responsive pacemakers in air transport by general aviation aircraft. The response in pacing rate of two types of accelerometer-based rate-responsive pacemakers with data logging capabilities was studied during test flights with single engine fixed wing aircraft. Results were compared with the rate-response of these pacemakers during transportation by car and were also interpreted in respect to physiological heart rate response of aircrew during flights in single engine fixed wing aircraft. In addition, a continuous accelerometer readout was recorded during a turbulent phase of flight. This recording was used for a pacemaker-simulator experiment with maximal sensitive motion-sensor settings. Only a minor increase in pacing rate due to aircraft motion could be demonstrated during all phases of flight at all altitudes with the pacemakers programmed in the normal mode. This increase was of the same magnitude as induced during transport by car and would be of negligible influence on the performance of the individual pacemaker patient equipped with such a pacemaker. Moreover, simultaneous Holter monitoring of the pilots during these flights showed a similar rate-response in natural heart rate compared with the increase in pacing rate induced by aircraft motion in accelerometer-based rate-responsive pacemakers. No sensor-mediated pacemaker tachycardia was seen during any of these recordings. However, a 15% increase in pacing rate was induced by severe air turbulence. Programming the maximal sensitivity of the motion sensor into the pacemaker could, on the other hand, induce a significant increase in pacing rate as was demonstrated by the simulation experiments. These results seem to rule out potentially dangerous or adverse effects from motional or vibrational influences during transport in single engine fixed wing aircraft on accelerometer-based rate-responsive pacemakers with normal activity sensor settings.

Intermittent pacemaker dysfunction caused by digital mobile telephones.

PubMed

Naegeli, B; Osswald, S; Deola, M; Burkart, F

1996-05-01

This study was designed to evaluate possible interactions between digital mobile telephones and implanted pacemakers. Electromagnetic fields may interfere with normal pacemaker function. Development of bipolar sensing leads and modern noise filtering techniques have lessened this problem. However, it remains unclear whether these features also protect from high frequency noise arising from digital cellular phones. In 39 patients with an implanted pacemaker (14 dual-chamber [DDD], 8 atrial-synchronized ventricular-inhibited [VDD(R)] and 17 ventricular-inhibited [VVI(R)] pacemakers), four mobile phones with different levels of power output (2 and 8 W) were tested in the standby, dialing and operating mode. During continuous electrocardiographic monitoring, 672 tests were performed in each mode with the phones positioned over the pulse generator, the atrial and the ventricular electrode tip. The tests were carried out at different sensitivity settings and, where possible, in the unipolar and bipolar pacing modes as well. In 7 (18%) of 39 patients, a reproducible interference was induced during 26 (3.9%) of 672 tests with the operating phones in close proximity (<10 cm) to the pacemaker. In 22 dual-chamber (14 DDD, 8 VDD) pacemakers, atrial triggering occurred in 7 (2.8%) of 248 and ventricular inhibition in 5 (2.8%) of 176 tests. In 17 VVI(R) systems, pacemaker inhibition was induced in 14 (5.6%) of 248 tests. Interference was more likely to occur at higher power output of the phone and at maximal sensitivity of the pacemakers (maximal vs. nominal sensitivity, 6% vs. 1.8% positive test results, p = 0.009). When the bipolar and unipolar pacing modes were compared in the same patients, ventricular inhibition was induced only in the unipolar mode (12.5% positive test results, p = 0.0003). Digital mobile phones in close proximity to implanted pacemakers may cause intermittent pacemaker dysfunction with inappropriate ventricular tracking and potentially dangerous pacemaker inhibition.

The interference of electronic implants in low frequency electromagnetic fields.

PubMed

Silny, J

2003-04-01

Electronic implants such as cardiac pacemakers or nerve stimulators can be impaired in different ways by amplitude-modulated and even continuous electric or magnetic fields of strong field intensities. For the implant bearer, possible consequences of a temporary electromagnetic interference may range from a harmless impairment of his well-being to a perilous predicament. Electromagnetic interferences in all types of implants cannot be covered here due to their various locations in the body and their different sensing systems. Therefore, this presentation focuses exemplarily on the most frequently used implant, the cardiac pacemaker. In case of an electromagnetic interference the cardiac pacemaker reacts by switching to inhibition mode or to fast asynchronous pacing. At a higher disturbance voltage on the input of the pacemaker, a regular asynchronous pacing is likely to arise. In particular, the first-named interference could be highly dangerous for the pacemaker patient. The interference threshold of cardiac pacemakers depends in a complex way on a number of different factors such as: electromagnetic immunity and adjustment of the pacemaker, the composition of the applied low-frequency fields (only electric or magnetic fields or combinations of both), their frequencies and modulations, the type of pacemaker system (bipolar, unipolar) and its location in the body, as well as the body size and orientation in the field, and last but not least, certain physiological conditions of the patient (e.g. inhalation, exhalation). In extensive laboratory studies we have investigated the interference mechanisms in more than 100 cardiac pacemakers (older types as well as current models) and the resulting worst-case conditions for pacemaker patients in low-frequency electric and magnetic fields. The verification of these results in different practical everyday-life situations, e.g. in the fields of high-voltage overhead lines or those of electronic article surveillance systems is currently in progress. In case of the vertically-oriented electric 50 Hz fields preliminary results show that per 1 kV/m unimpaired electrical field strength (rms) an interference voltage of about 400 microVpp as worst-case could occur at the input of a unipolar ventricularly controlled, left-pectorally implanted cardiac pacemaker. Thus, already a field strength above ca. 5 kV/m could cause an interference with an implanted pacemaker. The magnetic fields induces an electric disturbance voltage at the input of the pacemaker. The body and the pacemaker system compose several induction loops, whose induced voltages rates add or subtract. The effective area of one representing inductive loop ranges from 100 to 221 cm2. For the unfavourable left-pectorally implantated and atrially-controlled pacemaker with a low interference threshold, the interference threshold ranges between 552 and 16 microT (rms) for magnetic fields at frequencies between 10 and 250 Hz. On this basis the occurrence of interferences with implanted pacemakers is possible in everyday-life situations. But experiments demonstrate a low probability of interference of cardiac pacemakers in practical situations. This apparent contradiction can be explained by a very small band of inhibition in most pacemakers and, in comparison with the worst-case, deviating conditions.

Pyloric obstruction secondary to epicardial pacemaker implantation: a case report.

PubMed

Bedoya Nader, G; Kellihan, H B; Bjorling, D E; McAnulty, J

2017-02-01

A 10-year old Lhasa Apso dog was presented for an acute history of exercise intolerance and hind limb weakness. High grade second degree atrioventricular block with an atrial rate of 200 beats per minute, ventricular rate of 40 beats per minute and an intermittent ventricular escape rhythm, was diagnosed on electrocardiograph. A transdiaphragmatic, unipolar, epicardial pacemaker was implanted without immediate surgical complications. Severe vomiting was noted 12 h post-operatively. Abdominal ultrasound and a barium study supported a diagnosis of pyloric outflow obstruction and exploratory abdominal surgery was performed. The pyloric outflow tract appeared normal and no other causes of an outflow obstruction were identified. The epicardial generator was repositioned from the right to the left abdominal wall. Pyloric cell pacing was presumed to be the cause for the pyloric obstruction and severe vomiting, and this was thought to be due to close proximity of the pacemaker generator to the pylorus situated in the right abdominal wall. Repositioning of the pulse generator to the left abdominal wall resulted in resolution of vomiting. Copyright © 2016 Elsevier B.V. All rights reserved.

Long-term clinical effects of ventricular pacing reduction with a changeover mode to minimize ventricular pacing in a general pacemaker population

PubMed Central

Stockburger, Martin; Boveda, Serge; Moreno, Javier; Da Costa, Antoine; Hatala, Robert; Brachmann, Johannes; Butter, Christian; Garcia Seara, Javier; Rolando, Mara; Defaye, Pascal

2015-01-01

Aim Right ventricular pacing (VP) has been hypothesized to increase the risk in heart failure (HF) and atrial fibrillation (AF). The ANSWER study evaluated, whether an AAI-DDD changeover mode to minimize VP (SafeR) improves outcome compared with DDD in a general dual-chamber pacemaker population. Methods and results ANSWER was a randomized controlled multicentre trial assessing SafeR vs. standard DDD in sinus node disease (SND) or AV block (AVB) patients. After a 1-month run-in period, they were randomized (1 : 1) and followed for 3 years. Pre-specified co-primary end-points were VP and the composite of hospitalization for HF, AF, or cardioversion. Pre-specified secondary end-points were cardiac death or HF hospitalizations and cardiovascular hospitalizations. ANSWER enrolled 650 patients (52.0% SND, 48% AVB) at 43 European centres and randomized in SafeR (n = 314) or DDD (n = 318). The SafeR mode showed a significant decrease in VP compared with DDD (11.5 vs. 93.6%, P < 0.0001 at 3 years). Deaths and syncope did not differ between randomization arms. No significant difference between groups [HR = 0.78; 95% CI (0.48–1.25); P = 0.30] was found in the time to event of the co-primary composite of hospitalization for HF, AF, or cardioversion, nor in the individual components. SafeR showed a 51% risk reduction (RR) in experiencing cardiac death or HF hospitalization [HR = 0.49; 95% CI (0.27–0.90); P = 0.02] and 30% RR in experiencing cardiovascular hospitalizations [HR = 0.70; 95% CI (0.49–1.00); P = 0.05]. Conclusion SafeR safely and significantly reduced VP in a general pacemaker population though had no effect on hospitalization for HF, AF, or cardioversion, when compared with DDD. PMID:25179761

Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine

PubMed Central

Kim, Hyungwoo; Kim, Hyun Jung; Yang, Dongki; Jung, Myeong Ho; Kim, Byung Joo

2017-01-01

Background: Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. Objective: The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. Materials and Methods: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C. Results: In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4 receptor antagonist) did. Methoctramine (a muscarinic M2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M3 receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca2+-free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore Ginseng radix and Zingiberis rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Conclusion: These results suggest that DKT depolarizes ICC PPs in an internal or external Ca2+-dependent manner by stimulating 5-HT4 and M3 receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of Ginseng radix and Zingiberis rhizomes. SUMMARY Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4 receptor antagonist) didMethoctramine (a muscarinic M2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-DAMP (a muscarinic M3 receptor antagonist) facilitated blockade of DKT-induced PP depolarizationGinseng radix and Zingiberis rhizomes depolarized PPswhereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Abbreviation used: DKT: Daikenchuto, GI: Gastrointestinal, ICCs: Interstitial cells of Cajal, PPs: Pacemaker Potentials. PMID:28216898

Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine.

PubMed

Kim, Hyungwoo; Kim, Hyun Jung; Yang, Dongki; Jung, Myeong Ho; Kim, Byung Joo

2017-01-01

Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C. In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT 3 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT 4 receptor antagonist) did. Methoctramine (a muscarinic M 2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M 3 receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca 2+ -free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore Ginseng radix and Zingiberis rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. These results suggest that DKT depolarizes ICC PPs in an internal or external Ca 2+ -dependent manner by stimulating 5-HT 4 and M 3 receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of Ginseng radix and Zingiberis rhizomes. Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT 3 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT 4 receptor antagonist) didMethoctramine (a muscarinic M 2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-DAMP (a muscarinic M 3 receptor antagonist) facilitated blockade of DKT-induced PP depolarizationGinseng radix and Zingiberis rhizomes depolarized PPswhereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Abbreviation used: DKT: Daikenchuto, GI: Gastrointestinal, ICCs: Interstitial cells of Cajal, PPs: Pacemaker Potentials.

Electromagnetic interference with cardiac pacemakers and implantable cardioverter-defibrillators from low-frequency electromagnetic fields in vivo.

PubMed

Tiikkaja, Maria; Aro, Aapo L; Alanko, Tommi; Lindholm, Harri; Sistonen, Heli; Hartikainen, Juha E K; Toivonen, Lauri; Juutilainen, Jukka; Hietanen, Maila

2013-03-01

Electromagnetic interference (EMI) can pose a danger to workers with pacemakers and implantable cardioverter-defibrillators (ICDs). At some workplaces electromagnetic fields are high enough to potentially inflict EMI. The purpose of this in vivo study was to evaluate the susceptibility of pacemakers and ICDs to external electromagnetic fields. Eleven volunteers with a pacemaker and 13 with an ICD were exposed to sine, pulse, ramp, and square waveform magnetic fields with frequencies of 2-200 Hz using Helmholtz coil. The magnetic field flux densities varied to 300 µT. We also tested the occurrence of EMI from an electronic article surveillance (EAS) gate, an induction cooktop, and a metal inert gas (MIG) welding machine. All pacemakers were tested with bipolar settings and three of them also with unipolar sensing configurations. None of the bipolar pacemakers or ICDs tested experienced interference in any of the exposure situations. The three pacemakers with unipolar settings were affected by the highest fields of the Helmholtz coil, and one of them also by the EAS gate and the welding cable. The induction cooktop did not interfere with any of the unipolarly programmed pacemakers. Magnetic fields with intensities as high as those used in this study are rare even in industrial working environments. In most cases, employees can return to work after implantation of a bipolar pacemaker or an ICD, after an appropriate risk assessment. Pacemakers programmed to unipolar configurations can cause danger to their users in environments with high electromagnetic fields, and should be avoided, if possible.

Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy initiation in a pacemaker practice.

PubMed

Yedlapati, Neeraja; Fisher, John D

2014-09-01

We aimed to determine the practical value of pacemaker diagnostics for atrial fibrillation (AF) in an unselected general pacemaker practice, specifically workflow and initiation of anticoagulation or antiarrhythmic drug (AAD) therapy. We prospectively followed consecutive pacemaker interrogations over a period of 1 year to identify patients with AF (burden from 1% to 99%). We contacted referring physicians with AF details, and then determined whether the information resulted in therapeutic changes. Of the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF diagnostic capability. AF was recorded in 73 (10%) but seven had limited information, leaving 66 patients; of these, 42 (63%) patients were already anticoagulated and in five (7%) patients, anticoagulation had been stopped because of complications. Initial diagnosis of AF was made by the pacemaker in 17 patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%) had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of 728) received new AADs. Of 728 patients with DDD pacemakers, only 17 were newly discovered to have AF, and six (0.8%) had changes in medications based on the pacemaker data. Adding pacemaker-derived data to existing clinical information had little therapeutic impact, due to a combination of cumbersome workflow, and because AF was usually known to practitioners. Developments in automated monitoring systems may provide more accessible and therapeutically useful information. ©2014 Wiley Periodicals, Inc.

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

PubMed

Al-Wakeel, Nadya; O h-Ici, Darach; Schmitt, Katharina R; Messroghli, Daniel R; Riesenkampff, Eugénie; Berger, Felix; Kuehne, Titus; Peters, Bjoern

2016-02-01

In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation

PubMed Central

Severi, Stefano; Fantini, Matteo; Charawi, Lara A; DiFrancesco, Dario

2012-01-01

The cellular basis of cardiac pacemaking is still debated. Reliable computational models of the sinoatrial node (SAN) action potential (AP) may help gain a deeper understanding of the phenomenon. Recently, novel models incorporating detailed Ca2+-handling dynamics have been proposed, but they fail to reproduce a number of experimental data, and more specifically effects of ‘funny’ (If) current modifications. We therefore developed a SAN AP model, based on available experimental data, in an attempt to reproduce physiological and pharmacological heart rate modulation. Cell compartmentalization and intracellular Ca2+-handling mechanisms were formulated as in the Maltsev–Lakatta model, focusing on Ca2+-cycling processes. Membrane current equations were revised on the basis of published experimental data. Modifications of the formulation of currents/pumps/exchangers to simulate If blockers, autonomic modulators and Ca2+-dependent mechanisms (ivabradine, caesium, acetylcholine, isoprenaline, BAPTA) were derived from experimental data. The model generates AP waveforms typical of rabbit SAN cells, whose parameters fall within the experimental ranges: 352 ms cycle length, 80 mV AP amplitude, −58 mV maximum diastolic potential (MDP), 108 ms APD50, and 7.1 V s−1 maximum upstroke velocity. Rate modulation by If-blocking drugs agrees with experimental findings: 20% and 22% caesium-induced (5 mm) and ivabradine-induced (3 μm) rate reductions, respectively, due to changes in diastolic depolarization (DD) slope, with no changes in either MDP or take-off potential (TOP). The model consistently reproduces the effects of autonomic modulation: 20% rate decrease with 10 nm acetylcholine and 28% increase with 1 μm isoprenaline, again entirely due to increase in the DD slope, with no changes in either MDP or TOP. Model testing of BAPTA effects showed slowing of rate, −26%, without cessation of beating. Our up-to-date model describes satisfactorily experimental data concerning autonomic stimulation, funny-channel blockade and inhibition of the Ca2+-related system by BAPTA, making it a useful tool for further investigation. Simulation results suggest that a detailed description of the intracellular Ca2+ fluxes is fully compatible with the observation that If is a major component of pacemaking and rate modulation. PMID:22711956

Cell proliferation in mammalian gastrulation: the ventral node and notochord are relatively quiescent.

PubMed

Bellomo, D; Lander, A; Harragan, I; Brown, N A

1996-04-01

During gastrulation, the node of the mammalian embryo appears to be an organising centre, homologous to Hensen's node in the chick and the dorsal lip of the amphibian blastopore. In addition, the node serves as a precursor population for the head process, notochord and foregut endoderm. We have studied node architecture and cell morphology by electron microscopy, and cell proliferation using bromodeoxyuridine incorporation and mitotic counts. The dorsal (ectodermal) and ventral (endodermal) components of the node are two distinct populations, separated by a basement membrane. The ventral node, contiguous with the head process, is characterised by a relatively low proliferation rate, with only approximately 10% of cells incorporating BrdU over 4 hr, compared to > 95% in surrounding mesodermal and ectodermal tissues. This is the case from the beginning of node formation, at the no-allantoic-bud stage, until the 7 somite stage, and is not compatible with the idea that the ventral node is a stem cell population. The dorsal node is highly proliferative, its rate of division being indistinguishable from the neurectoderm, with which it is contiguous. In the ventral node, two regions can be recognised: cells in the "pit" are columnar and all monociliated; around them lies a "crown" of cells arranged radially in a horseshoe shape and less often ciliated. Node derivatives share common features with the ventral node; the head process and the notochord are relatively quiescent; and some head process cells are also monociliated. Node and head process monocilia are immotile and appear to be associated with non-proliferation. We suggest that the ventral node contains all the properties of the organiser, while the dorsal node is indistinct from the surrounding epiblast. The cranial end of the foregut pouch, the thyroid diverticulum, and the promyocardium of early somite stage embryos are also areas of low cell division. All the described regions of relative quiescence are sites of expression of members of the TGF beta family, which may be involved in maintaining non-proliferation.

The retrospectroscope-the invention of the rechargeable cardiac pacemaker: vignette #9.

PubMed

Fischell, R E

1990-01-01

The idea for a rechargeable cardiac pacemaker came to the author in the late 1960s after reading an advertisement stating that a company's batteries were so good they would last two years in a heart pacemaker. This meant that pacemaker patients would have to undergo surgery for their replacement frequently. Having worked on the development of hermetically sealed, nickel-cadmium batteries that could function for a decade or longer in an orbiting spacecraft, the author constructed the first prototype of a rechargeable cardiac pacemaker around 1968 to show cardiologists at Johns Hopkins Hospital that a pacemaker of indefinitely long life and much smaller size and weight could be built readily. The subsequent development and marketing of the device, which came on the market in 1973, is recounted.

Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability

PubMed Central

Ambrosi, Christina M.; Boyle, Patrick M.; Chen, Kay; Trayanova, Natalia A.; Entcheva, Emilia

2015-01-01

Multiple cardiac pathologies are accompanied by loss of tissue excitability, which leads to a range of heart rhythm disorders (arrhythmias). In addition to electronic device therapy (i.e. implantable pacemakers and cardioverter/defibrillators), biological approaches have recently been explored to restore pacemaking ability and to correct conduction slowing in the heart by delivering excitatory ion channels or ion channel agonists. Using optogenetics as a tool to selectively interrogate only cells transduced to produce an exogenous excitatory ion current, we experimentally and computationally quantify the efficiency of such biological approaches in rescuing cardiac excitability as a function of the mode of application (viral gene delivery or cell delivery) and the geometry of the transduced region (focal or spatially-distributed). We demonstrate that for each configuration (delivery mode and spatial pattern), the optical energy needed to excite can be used to predict therapeutic efficiency of excitability restoration. Taken directly, these results can help guide optogenetic interventions for light-based control of cardiac excitation. More generally, our findings can help optimize gene therapy for restoration of cardiac excitability. PMID:26621212

Permanent pacemaker lead induced severe tricuspid regurgitation in patient undergoing multiple valve surgery.

PubMed

Lee, Jung Hee; Kim, Tae Ho; Kim, Wook Sung

2015-04-01

Severe and permanent tricuspid regurgitation induced by pacemaker leads is rarely reported in the literature. The mechanism of pacemaker-induced tricuspid regurgitation has been identified, but its management has not been well established. Furthermore, debate still exists regarding the proper surgical approach. We present the case of a patient with severe tricuspid regurgitation induced by a pacemaker lead, accompanied by triple valve disease. The patient underwent double valve replacement and tricuspid valve repair without removal of the pre-existing pacemaker lead. The operation was successful and the surgical procedure is discussed in detail.

The effects of nuclear magnetic resonance on patients with cardiac pacemakers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavlicek, W.; Geisinger, M.; Castle, L.

1983-04-01

The effect of nuclear magnetic resonance (NMR) imaging on six representative cardiac pacemakers was studied. The results indicate that the threshold for initiating the asynchronous mode of a pacemaker is 17 gauss. Radiofrequency levels are present in an NMR unit and may confuse or possibly inhibit demand pacemakers, although sensing circuitry is normally provided with electromagnetic interference discrimination. Time-varying magnetic fields can generate pulse amplitudes and frequencies to mimic cardiac activity. A serious limitation in the possibility of imaging a patient with a pacemaker would be the alteration of normal pulsing parameters due to time-varying magnetic fields.

The two nerve rings of the hypostomal nervous system of Hydra vulgaris-an immunohistochemical analysis.

PubMed

Hufnagel, L A; Kass-Simon, G

2016-11-01

In Hydra vulgaris, physiological and pharmacological evidence exists for a hypostomal circumferential neuro-effector pathway that initiates ectodermal pacemaker activity at tentacular-hypostomal loci coordinating body and tentacle contractions. Here, we describe an ectodermal nerve ring that runs below and between the tentacles, and an anti-GABA B receptor antibody-labeled ring coincident with it. The location of this ring is consistent with the physiology of the hypostomal pacemaker systems of hydra. We also describe a distally located, ectodermal ring of nerve fibers that is not associated with anti-GABA B receptor antibody labeling. The neurites and cell bodies of sensory cells contribute to both rings. The location of the distal ring and its sensory cell neurites suggests an involvement in the behavior of the mouth. Between the two rings is a network of anastomosing sensory and ganglion cell bodies and their neurites. Phase contrast, darkfield, and antibody-labeled images reveal that the mouth of hydra comprises five or six epithelial folds whose endoderm extensively labels with anti-GABA B receptor antibody, suggesting that endodermal metabotrobic GABA receptors are also involved in regulating mouth behavior.

21 CFR Appendix B to Subpart B of... - Scope of Product Coverage

Code of Federal Regulations, 2013 CFR

2013-04-01

... Portable air compressor 2 Cardiovascular Panel Cardiovascular Diagnostic 870.1425 Programmable diagnostic... Pacemaker & Accessories 870.1750 External programmable pacemaker pulse generator 2 870.3630 Pacemaker...

21 CFR Appendix B to Subpart B of... - Scope of Product Coverage

Code of Federal Regulations, 2014 CFR

2014-04-01

... Portable air compressor 2 Cardiovascular Panel Cardiovascular Diagnostic 870.1425 Programmable diagnostic... Pacemaker & Accessories 870.1750 External programmable pacemaker pulse generator 2 870.3630 Pacemaker...

21 CFR Appendix B to Subpart B of... - Scope of Product Coverage

Code of Federal Regulations, 2012 CFR

2012-04-01

... Portable air compressor 2 Cardiovascular Panel Cardiovascular Diagnostic 870.1425 Programmable diagnostic... Pacemaker & Accessories 870.1750 External programmable pacemaker pulse generator 2 870.3630 Pacemaker...

Devices for Arrhythmia

MedlinePlus

... with recurrent arrhythmias, medical devices such as a pacemaker and implantable cardioverter defibrillator (ICD) can help by ... with an ICD Questions to ask your doctor Pacemakers Learn what an artificial pacemaker is, how it ...

Heart pacemaker

MedlinePlus

... please enable JavaScript. A pacemaker is a small, battery-operated device. This device senses when your heart ... pacemakers have 2 parts: The generator contains the battery and the information to control the heartbeat. The ...

Pacemaker (image)

MedlinePlus

A pacemaker is a small, battery-operated electronic device which is inserted under the skin to help the heart beat regularly and at an appropriate rate. The pacemaker has leads that travel through a large vein ...

The usefulness of a stretch-polyester pouch to encase implanted pacemakers and defibrillators.

PubMed

Parsonnet, V; Bernstein, A D; Neglia, D; Omar, A

1994-12-01

This study was undertaken to assess the effects of enclosing permanent pacemaker and ICD pulse generators in a stretch-polyester pouch prior to implantation. Follow-up of 223 patients with oversized pacemakers and with ICDs and 344 with standard-sized pacemaker pulse generators showed that the pouch was effective in decreasing the frequency of pulse generator migration and extrusion.

Risk Factors For Bradycardia Requiring Pacemaker Implantation In Patients With Atrial Fibrillation

PubMed Central

Barrett, Tyler W.; Abraham, Robert L.; Jenkins, Cathy A.; Russ, Stephan; Storrow, Alan B.; Darbar, Dawood

2012-01-01

Symptomatic bradycardia may complicate atrial fibrillation (AF) and necessitate a permanent pacemaker. Identifying patients at increased risk for symptomatic bradycardia may reduce associated morbidities and healthcare costs. We investigated predictors for developing bradycardia requiring a permanent pacemaker among AF patients. We reviewed records of all patients treated for AF/flutter in an academic hospital’s emergency department from 8/1/2005 to 8/30/2008. We determined survival and presence of a pacemaker as of 11/1/2011. Cases were defined as patients with pacemakers placed for bradycardia after their AF diagnoses. Patients without a pacemaker who were followed at our hospital comprised the controls. We identified a priori variables for the logistic regression analysis. We fit a post-hoc model adjusting for AF type and atrioventricular nodal blocker (AVN) use. Of the 362 patients in our cohort, 119 cases had permanent pacemakers implanted for bradycardia subsequent to AF diagnosis and 243 controls were alive without a pacemaker. Median and interquartile range follow-up time was 4.5 (3.8 – 5.4) years. Odds ratios and 95% confidence intervals were determined for age at time of AF diagnosis (1.02 [1, 1.04]), female (1.58 [0.95, 2.63]), prior heart failure (2.72 [1.47, 5.01]), and African-American (0.33 [0.12, 0.94]). Post-hoc model identified permanent AF (2.99 [1.61, 5.57]) and AVN use (1.43 [0.85, 2.4]). In conclusion, among AF patients, heart failure and permanent AF each nearly triple the odds of developing bradycardia requiring a permanent pacemaker; while not statistically significant, our results suggest that women are more likely and African-Americans less likely to develop bradycardia requiring pacemaker implantation. PMID:22840846

Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

PubMed Central

Ma, Michelle W.; Medicherla, Ratna C.; Qian, Meng; de Miera, Eleazar Vega-Saenz; Friedman, Erica B.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Ott, Patrick A.; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod

2013-01-01

The sentinel lymph node is the initial site of metastasis. Down-regulation of anti-tumor immunity plays a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T-cells (Foxp3+) and dendritic cells (conventional: CD11c+, mature: CD86+) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunologic primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared to those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T-cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathologic variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Anti-tumor immunity was down-regulated in the positive sentinel lymph node with an increase in regulatory T-cells compared to the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared to the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T-cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions. PMID:22425909

Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

PubMed

Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

2016-09-26

As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling the emergence of circadian rhythms in a clock neuron network.

PubMed

Diambra, Luis; Malta, Coraci P

2012-01-01

Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping) of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i) the control of net entrance of PER into the nucleus and (ii) the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.

Retention of Ag-specific memory CD4+ T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

PubMed

Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

2017-05-01

Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4 + T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4 + T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4 + T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4 + T-cell populations are generated in peripheral lymph nodes following immunisation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reticulated telangiectatic erythema of the pacemaker.

PubMed

Martin, Lucy K; Wendschuh, Philip; Wendschuh, Peter

2008-05-01

Reticulated telangiectatic erythema is a rare entity; it has been reported to occur following the placement of implanted cardiac devices and drug delivery systems. Histologically, reticulated telangiectatic erythema of the pacemaker is characterized by slight spongiosis and increased dermal telangiectasias. We describe a patient that developed reticulated telangiectatic nonpruritic patches on the left chest after the placement of a pacemaker. The patient responded favorably to the removal of the pacemaker.

Retrieval of the Leadless Cardiac Pacemaker: A Multicenter Experience.

PubMed

Reddy, Vivek Y; Miller, Marc A; Knops, Reinoud E; Neuzil, Petr; Defaye, Pascal; Jung, Werner; Doshi, Rahul; Castellani, Mark; Strickberger, Adam; Mead, R Hardwin; Doppalapudi, Harish; Lakkireddy, Dhanunjaya; Bennett, Matthew; Sperzel, Johannes

2016-12-01

Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans. This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88-1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure. This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244. © 2016 American Heart Association, Inc.

Influence of digital and analogue cellular telephones on implanted pacemakers.

PubMed

Altamura, G; Toscano, S; Gentilucci, G; Ammirati, F; Castro, A; Pandozi, C; Santini, M

1997-10-01

The aim of this study was to find out whether digital and analogue cellular 'phones affect patients with pacemakers. The study comprised continuous ECG monitoring of 200 pacemaker patients. During the monitoring certain conditions caused by interference created by the telephone were looked for: temporary or prolonged pacemaker inhibition; a shift to asynchronous mode caused by electromagnetic interference; an increase in ventricular pacing in dual chamber pacemakers, up to the programmed upper rate. The Global System for Mobile Communications system interfered with pacing 97 times in 43 patients (21.5%). During tests on Total Access of Communication System telephones, there were 60 cases of pacing interference in 35 patients (17.5%). There were 131 interference episodes during ringing vs 26 during the on/off phase; (P < 0.0001); 106 at maximum sensitivity level vs 51 at the 'base' value; P < 0.0001). Prolonged pacing inhibition (> 4 s) was seen at the pacemaker 'base' sensing value in six patients using the Global system but in only one patient using Total Access. Cellular 'phones may be dangerous for pacemaker patients. However, they can be used safely if patients do not carry the 'phone close to the pacemaker, which is the only place where high risk interference has been observed.

Pacemaker therapy in low-birth-weight infants.

PubMed

Fuchigami, Tai; Nishioka, Masahiko; Akashige, Toru; Shimabukuro, Atsuya; Nagata, Nobuhiro

2018-02-01

Infants born with complete atrioventricular block (CAVB) and fetal bradycardia are frequently born with low birth weight. Three low-birth-weight CAVB infants underwent temporary pacemaker implantation, followed by permanent single-chamber pacemaker implantation at median body weights of 1.7 and 3.2 kg, respectively. All infants caught up with their growth curves and had >3 years of estimated residual battery life. This two-stage strategy was successful in facilitating permanent pacemaker implantation in low-birth-weight babies. Placement of single-chamber pacemaker on the apex of the left ventricle appears to be associated with longer battery lifespan. © 2018 Wiley Periodicals, Inc.

Effect on pacemakers of airport weapons detectors

PubMed Central

Johnson, David L.

1974-01-01

An investigation was carried out using a variety of pacemakers and all the types of weapons detectors in common use in Canada, to determine whether or not such detectors present a hazard to pacemaker bearers. The results indicate that only left-side implants of unipolar sensing pacemakers are likely to be affected, that ventricular fibrillation initiated by interference-induced competitive pacing is the only conceivable hazard, but that the probability of 10−9 for the occurrence of this event is so low that it may be completely disregarded. Physicians may therefore reassure pacemaker bearers of their safety in and around airport weapons detectors. ImagesFIG. 1 PMID:4825148

Advanced Pacemaker

NASA Technical Reports Server (NTRS)

1990-01-01

Synchrony, developed by St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.) is an advanced state-of-the-art implantable pacemaker that closely matches the natural rhythm of the heart. The companion element of the Synchrony Pacemaker System is the Programmer Analyzer APS-II which allows a doctor to reprogram and fine tune the pacemaker to each user's special requirements without surgery. The two-way communications capability that allows the physician to instruct and query the pacemaker is accomplished by bidirectional telemetry. APS-II features 28 pacing functions and thousands of programming combinations to accommodate diverse lifestyles. Microprocessor unit also records and stores pertinent patient data up to a year.

Space Derived Health Aids (Cardiac Pacemaker)

NASA Technical Reports Server (NTRS)

1981-01-01

St. Jude Medical's Cardiac Rhythm Management Division's (formerly known as Pacesetter Systems, Inc.) pacer is a rechargeable cardiac pacemaker that eliminates the recurring need for surgery to implant a new battery. The Programalith is an advanced cardiac pacing system which permits a physician to reprogram a patient's implanted pacemaker without surgery. System consists of a pacemaker, together with a physician's console containing the programmer and a data printer. Signals are transmitted by wireless telemetry. Two-way communications, originating from spacecraft electrical power systems technology, allows physician to interrogate the pacemaker as to the status of the heart, then to fine tune the device to best suit the patient's needs.

Isolation and characterization of node/notochord-like cells from mouse embryonic stem cells.

PubMed

Winzi, Maria K; Hyttel, Poul; Dale, Jacqueline Kim; Serup, Palle

2011-11-01

The homeobox gene Noto is expressed in the node and its derivative the notochord. Here we use a targeted Noto-GFP reporter to isolate and characterize node/notochord-like cells derived from mouse embryonic stem cells. We find very few Noto-expressing cells after spontaneous differentiation. However, the number of Noto-expressing cells was increased when using Activin A to induce a Foxa2- and Brachyury-expressing progenitor population, whose further differentiation into Noto-expressing cells was improved by simultaneous inhibition of BMP, Wnt, and retinoic acid signaling. Noto-GFP(+) cells expressed the node/notochord markers Noto, Foxa2, Shh, Noggin, Chordin, Foxj1, and Brachyury; showed a vacuolarization characteristic of notochord cells; and can integrate into midline structures when grafted into Hensen's node of gastrulating chicken embryos. The ability to generate node/notochord-like cells in vitro will aid the biochemical characterization of these developmentally important structures.

Isolation and Characterization of Node/Notochord-Like Cells from Mouse Embryonic Stem Cells

PubMed Central

Winzi, Maria K.; Hyttel, Poul; Dale, Jacqueline Kim; Serup, Palle

2014-01-01

The homeobox gene Noto is expressed in the node and its derivative the notochord. Here we use a targeted Noto-GFP reporter to isolate and characterize node/notochord-like cells derived from mouse embryonic stem cells. We find very few Noto-expressing cells after spontaneous differentiation. However, the number of Noto-expressing cells was increased when using Activin A to induce a Foxa2- and Brachyury-expressing progenitor population, whose further differentiation into Noto-expressing cells was improved by simultaneous inhibition of BMP, Wnt, and retinoic acid signaling. Noto-GFP+ cells expressed the node/notochord markers Noto, Foxa2, Shh, Noggin, Chordin, Foxj1, and Brachyury; showed a vacuolarization characteristic of notochord cells; and can integrate into midline structures when grafted into Hensen’s node of gastrulating chicken embryos. The ability to generate node/notochord-like cells in vitro will aid the biochemical characterization of these developmentally important structures. PMID:21351873

Pacemakers and Implantable Defibrillators - Multiple Languages

MedlinePlus

... Multiple Languages → All Health Topics → Pacemakers and Implantable Defibrillators URL of this page: https://medlineplus.gov/languages/ ... List of All Topics All Pacemakers and Implantable Defibrillators - Multiple Languages To use the sharing features on ...

Selective interference with pacemaker activity by electrical dental devices.

PubMed

Miller, C S; Leonelli, F M; Latham, E

1998-01-01

We sought to determine whether electromagnetic interference with cardiac pacemakers occurs during the operation of contemporary electrical dental equipment. Fourteen electrical dental devices were tested in vitro for their ability to interfere with the function of two Medtronics cardiac pacemakers (one a dual-chamber, bipolar Thera 7942 pacemaker, the other a single-chamber, unipolar Minix 8340 pacemaker). Atrial and ventricular pacemaker output and electrocardiographic activity were monitored by means of telemetry with the use of a Medtronics 9760/90 programmer. Atrial and ventricular pacing were inhibited by electromagnetic interference produced by the electrosurgical unit up to a distance of 10 cm, by the ultrasonic bath cleaner up to 30 cm, and by the magnetorestrictive ultrasonic scalers up to 37.5 cm. In contrast, operation of the amalgamator, electric pulp tester, composite curing light, dental handpieces, electric toothbrush, microwave oven, dental chair and light, ENAC ultrasonic instrument, radiography unit, and sonic scaler did not alter pacing rate or rhythm. These results suggest that certain electrosurgical and ultrasonic instruments may produce deleterious effects in medically fragile patients with cardiac pacemakers.

Prediction of significant conduction disease through noninvasive assessment of cardiac calcification.

PubMed

Mainigi, Sumeet K; Chebrolu, Lakshmi Hima Bindu; Romero-Corral, Abel; Mehta, Vinay; Machado, Rodolfo Rozindo; Konecny, Tomas; Pressman, Gregg S

2012-10-01

Cardiac calcification is associated with coronary artery disease, arrhythmias, conduction disease, and adverse cardiac events. Recently, we have described an echocardiographic-based global cardiac calcification scoring system. The objective of this study was to evaluate the severity of cardiac calcification in patients with permanent pacemakers as based on this scoring system. Patients with a pacemaker implanted within the 2-year study period with a previous echocardiogram were identified and underwent blinded global cardiac calcium scoring. These patients were compared to matched control patients without a pacemaker who also underwent calcium scoring. The study group consisted of 49 patients with pacemaker implantation who were compared to 100 matched control patients. The mean calcium score in the pacemaker group was 3.3 ± 2.9 versus 1.8 ± 2.0 (P = 0.006) in the control group. Univariate and multivariate analysis revealed glomerular filtration rate and calcium scoring to be significant predictors of the presence of a pacemaker. Echocardiographic-based calcium scoring correlates with the presence of severe conduction disease requiring a pacemaker. © 2012, Wiley Periodicals, Inc.

Stochastic resonance on a modular neuronal network of small-world subnetworks with a subthreshold pacemaker

NASA Astrophysics Data System (ADS)

Yu, Haitao; Wang, Jiang; Liu, Chen; Deng, Bin; Wei, Xile

2011-12-01

We study the phenomenon of stochastic resonance on a modular neuronal network consisting of several small-world subnetworks with a subthreshold periodic pacemaker. Numerical results show that the correlation between the pacemaker frequency and the dynamical response of the network is resonantly dependent on the intensity of additive spatiotemporal noise. This effect of pacemaker-driven stochastic resonance of the system depends extensively on the local and the global network structure, such as the intra- and inter-coupling strengths, rewiring probability of individual small-world subnetwork, the number of links between different subnetworks, and the number of subnetworks. All these parameters play a key role in determining the ability of the network to enhance the noise-induced outreach of the localized subthreshold pacemaker, and only they bounded to a rather sharp interval of values warrant the emergence of the pronounced stochastic resonance phenomenon. Considering the rather important role of pacemakers in real-life, the presented results could have important implications for many biological processes that rely on an effective pacemaker for their proper functioning.

Development of pacemaker properties and rhythmogenic mechanisms in the mouse embryonic respiratory network

PubMed Central

Chevalier, Marc; Toporikova, Natalia; Simmers, John; Thoby-Brisson, Muriel

2016-01-01

Breathing is a vital rhythmic behavior generated by hindbrain neuronal circuitry, including the preBötzinger complex network (preBötC) that controls inspiration. The emergence of preBötC network activity during prenatal development has been described, but little is known regarding inspiratory neurons expressing pacemaker properties at embryonic stages. Here, we combined calcium imaging and electrophysiological recordings in mouse embryo brainstem slices together with computational modeling to reveal the existence of heterogeneous pacemaker oscillatory properties relying on distinct combinations of burst-generating INaP and ICAN conductances. The respective proportion of the different inspiratory pacemaker subtypes changes during prenatal development. Concomitantly, network rhythmogenesis switches from a purely INaP/ICAN-dependent mechanism at E16.5 to a combined pacemaker/network-driven process at E18.5. Our results provide the first description of pacemaker bursting properties in embryonic preBötC neurons and indicate that network rhythmogenesis undergoes important changes during prenatal development through alterations in both circuit properties and the biophysical characteristics of pacemaker neurons. DOI: http://dx.doi.org/10.7554/eLife.16125.001 PMID:27434668

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

Energy-conserving programming of VVI pacemakers: a telemetry-supported, long-term, follow-up study.

PubMed

Klein, H H; Knake, W

1990-06-01

Thirty patients with VVI pacemakers (Quantum 253-09, 253-19, Intermedics Inc., Freeport, TX) were observed for a mean of 65 months. Within 12 months after implantation, optimized output programming was performed in 29 patients. This included a decrease in pulse amplitude (22 patients), pulse width (4 patients), and/or pacing rate (11 patients). After 65 months postimplantation, telemetered battery voltage and battery impedance were compared with the predicted values expected when the pulse generator constantly stimulates at nominal program conditions (heart rate 72.3 beats/min, pulse amplitude 5.4 V, pulse width 0.61 ms). Instead of an expected cell voltage of 2.6 V and a cell impedance of 10 k omega mean telemetered values amounted to 2.78 V and 1.4 k omega, respectively. These data correspond to a battery age of 12-15 months at nominal program conditions. This long-term follow-up study suggests that adequate programming will extend battery longevity and thus pulse generator survival in many patients.

1978 Pacemaker Newspaper Awards: What Makes a Pacemaker?

ERIC Educational Resources Information Center

Brasler, Wayne

1979-01-01

Lists the nine high school and college newspapers, and the one newsmagazine, that won Pacemaker Awards in 1978; discusses characteristics that make each of them outstanding, and provides reproductions of a front page from each publication. (GT)

Biofilm on artificial pacemaker: fiction or reality?

PubMed

Santos, Ana Paula Azevedo; Watanabe, Evandro; Andrade, Denise de

2011-11-01

Cardiac pacing through cardiac pacemaker is one of the most promising alternatives in the treatment of arrhythmias, but it can cause reactions natural or complex reactions, either early or late. This study aimed to describe the scientific evidence on the risk of infection and biofilm formation associated with cardiac pacemaker. This is a study of integrative literature review. It included 14 publications classified into three thematic categories: diagnosis (microbiological and/or clinical), complications and therapy of infections. Staphylococcus epidermidis and Staphylococcus aureus were the microorganisms most frequently isolated. It was not possible to determine the incidence of infection associated with pacemakers, since the studies were generally of prevalence. In terms of therapy, the complete removal of pacemakers stood out, especially in cases of suspected biofilm. Still controversial is the use of systemic antibiotic prophylaxis in reducing the incidence of infection associated with implantation of a pacemaker.

Case of pacemaker pocket infection caused by Finegoldia magna.

PubMed

Hosseini Dehkordi, Seyed Hamed; Osorio, Georgina

2017-10-01

Finegoldia magna (formerly called Peptostreptococcus magnus) is a Gram-positive anaerobic coccus which is increasingly recognized as an opportunistic pathogen. We present a case of F. magna associated non-valvular cardiovascular device-related infection in an 83 year-old male who received a permanent pacemaker for sick sinus syndrome seven weeks prior to his presentation. Five weeks after the implantation, the pacemaker and leads were explanted because of clinical evidence of pacemaker pocket infection. He was initially treated with sulfamethoxazole-trimethoprim based on the Gram stain results from the removed pacemaker. However, two weeks later, he was readmitted with sepsis and was successfully treated with ampicillin-sulbactam. Culture results from the pacemaker and pocket as well as blood cultures grew F. magna. Clinicians should be aware of the possibility of F. magna infection when initial gram stain results show "gram positive cocci". Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of high-intensity power-frequency electric fields on implanted modern multiprogrammable cardiac pacemakers.

PubMed

Butrous, G S; Meldrum, S J; Barton, D G; Male, J C; Bonnell, J A; Camm, A J

1982-05-01

The effect on an implanted, multiprogrammable pacemaker of power-frequency (50 Hz) electric fields up to an intensity (unperturbed value measured at 1.7 m) of 20 kV/m were assessed in ten paced patients. Radiotelemetric monitoring of the electrocardiogram allowed supervision of the electrocardiogram throughout exposure to the alternating electric field. Displacement body currents of up to 300μA were achieved depending on the position and height of the patient. None of the pacemakers was inhibited, triggered or reverted to fixed rate operation during the exposure. The programmable functions, programmability or output characteristics were not affected. Small changes in cardiac rate and rhythm elicited the correct pacemaker responses. Unlike earlier models of pacemaker, this modern implanted pacemaker, which represents `the state of the art', is not affected by 50 Hz electric fields likely to be encountered when standing underneath power lines.

Emergent global oscillations in heterogeneous excitable media: The example of pancreatic β cells

NASA Astrophysics Data System (ADS)

Cartwright, Julyan H. E.

2000-07-01

Using the standard van der Pol-FitzHugh-Nagumo excitable medium model, I demonstrate a generic mechanism, diversity, that provokes the emergence of global oscillations from individually quiescent elements in heterogeneous excitable media. This mechanism may be operating in the mammalian pancreas, where excitable β cells, quiescent when isolated, are found to oscillate when coupled, despite the absence of a pacemaker region.

A fully implantable pacemaker for the mouse: from battery to wireless power.

PubMed

Laughner, Jacob I; Marrus, Scott B; Zellmer, Erik R; Weinheimer, Carla J; MacEwan, Matthew R; Cui, Sophia X; Nerbonne, Jeanne M; Efimov, Igor R

2013-01-01

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice.

Frequency of pacemaker malfunction associated with monopolar electrosurgery during pulse generator replacement or upgrade surgery.

PubMed

Lin, Yun; Melby, Daniel P; Krishnan, Balaji; Adabag, Selcuk; Tholakanahalli, Venkatakrishna; Li, Jian-Ming

2017-08-01

The aim of this study is to investigate the frequency of electrosurgery-related pacemaker malfunction. A retrospective study was conducted to investigate electrosurgery-related pacemaker malfunction in consecutive patients undergoing pulse generator (PG) replacement or upgrade from two large hospitals in Minneapolis, MN between January 2011 and January 2014. The occurrence of this pacemaker malfunction was then studied by using MAUDE database for all four major device vendors. A total of 1398 consecutive patients from 2 large tertiary referral centers in Minneapolis, MN undergoing PG replacement or upgrade surgery were retrospectively studied. Four patients (0.3% of all patients), all with pacemakers from St Jude Medical (2.8%, 4 of 142) had output failure or inappropriately low pacing rate below 30 bpm during electrosurgery, despite being programmed in an asynchronous mode. During the same period, 1174 cases of pacemaker malfunctions were reported on the same models in MAUDE database, 37 of which (3.2%) were electrosurgery-related. Twenty-four cases (65%) had output failure or inappropriate low pacing rate. The distribution of adverse events was loss of pacing (59.5%), reversion to backup pacing (32.4%), inappropriate low pacing rate (5.4%), and ventricular fibrillation (2.7%). The majority of these (78.5%) occurred during PG replacement at ERI or upgrade surgery. No electrosurgery-related malfunction was found in MAUDE database on 862 pacemaker malfunction cases during the same period from other vendors. Electrosurgery during PG replacement or upgrade surgery can trigger output failure or inappropriate low pacing rate in certain models of modern pacemakers. Cautions should be taken for pacemaker-dependent patients.

The oral cavity is not a primary source for implantable pacemaker or cardioverter defibrillator infections

PubMed Central

2013-01-01

Background To test the hypothesis that the oral cavity is a potential source for implantable pacemaker and cardioverter defibrillators infections, the bacterial diversity on explanted rhythm heart management devices was investigated and compared to the oral microbiome. Methods A metagenomic approach was used to analyze the bacterial diversity on the surfaces of non-infected and infected pacemakers. The DNA from surfaces swaps of 24 non-infected and 23 infected pacemaker were isolated and subjected to bacterial-specific DNA amplification, single strand conformation polymorphism- (SSCP) and sequencing analysis. Species-specific primer sets were used to analyze for any correlation between bacterial diversity on pacemakers and in the oral cavity. Results DNA of bacterial origin was detected in 21 cases on infected pacemakers and assigned to the bacterial phylotypes Staphylococcus epidermidis, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus schleiferi and Stapyhlococcus. In 17 cases bacterial DNA was found on pacemakers with no clinical signs of infections. On the basis of the obtained sequence data, the phylotypes Propionibacterium acnes, Staphylococcus and an uncultured bacterium were identified. Propionibacterium acnes and Staphylococcus epidermidis were the only bacteria detected in pacemeaker (n = 25) and oral samples (n = 11). Conclusions The frequency of the coincidental detection of bacteria on infected devices and in the oral cavity is low and the detected bacteria are highly abundant colonizers of non-oral human niches. The transmission of oral bacteria to the lead or device of implantable pacemaker or cardioverter defibrillators is unlikely relevant for the pathogenesis of pacemaker or cardioverter defibrillators infections. PMID:23575037

Is pacemaker therapy the right key to patients with vasovagal syncope?

PubMed

Radovanović, Nikola N; Kirćanski, Bratislav; Raspopović, Srdjan; Pavlović, Siniša U; Jovanović, Velibor; Milašinović, Goran

2016-01-01

Vasovagal syncope is the most common type of reflex syncope. Efficacy of cardiac pacing in this indication has not been the subject of many studies and pacemaker therapy in patients with vasovagal syncope is still controversial. This study aimed to assess the efficacy and safety of pacing therapy in treatment of patients with vasovagal syncope, to determine contribution of new therapeutic models in increasing its success, and to identify risk factors associated with a higher rate of symptoms after pacemaker implantation. A retrospective study included 30 patients with pacemaker implanted due to vasovagal syncope in the Pacemaker Center, Clinical Center of Serbia, between November 2003 and June 2014. Head-up tilt test was performed to diagnose vasovagal syncope. Patients with cardioinhibitory and mixed type of disease were enrolled in the study. Mean age was 48.1 ± 11.1 years and 18 (60%) patients were men. Mean follow-up period was 5.9 ± 3.0 years. Primarily, implantable loop recorder was implanted in 10 (33.3%) patients. Twenty (66.7%) patients presented cardioinhibitory and 10 (33.3%) mixed type of vasovagal syncope. After pacemaker implantation, 11 (36.7%) patients had syncope. In multiple logistic regression analysis we showed that syncope is statistically more likely to occur after pacemaker implantation in patients with mixed type of vasovagal syncope (p = 0.018). There were two (6.7%) perioperative surgical complications. Pacemaker therapy is a safe treatment for patients with vasovagal syncope, whose efficacy can be improved by strict selection of patients. We showed that symptoms occur statistically more often in patients with mixed type of disease after pacemaker implantation.

Low pacemaker incidence with continuous-sutured valves: a retrospective analysis.

PubMed

Niclauss, Lars; Delay, Dominique; Pfister, Raymond; Colombier, Sebastien; Kirsch, Matthias; Prêtre, René

2017-06-01

Background Permanent pacemaker implantation after surgical aortic valve replacement depends on patient selection and risk factors for conduction disorders. We aimed to identify risk criteria and obtain a selected group comparable to patients assigned to transcatheter aortic valve implantation. Methods Isolated sutured aortic valve replacements in 994 patients treated from 2007 to 2015 were reviewed. Demographics, hospital stay, preexisting conduction disorders, surgical technique, and etiology in patients with and without permanent pacemaker implantation were compared. Reported outcomes after transcatheter aortic valve implantation were compared with those of a subgroup including only degenerative valve disease and first redo. Results The incidence of permanent pacemaker implantation was 2.9%. Longer hospital stay ( p = 0.01), preexisting rhythm disorders ( p < 0.001), complex prosthetic endocarditis ( p = 0.01), and complex redo ( p < 0.001) were associated with permanent pacemaker implantation. Although prostheses were sutured with continuous monofilament in the majority of cases (86%), interrupted pledgetted sutures were used more often in the pacemaker group ( p = 0.002). In the subgroup analysis, the incidence of permanent pacemaker implantation was 2%; preexisting rhythm disorders and the suture technique were still major risk factors. Conclusion Permanent pacemaker implantation depends on etiology, preexisting rhythm disorders, and suture technique, and the 2% incidence compares favorably with the reported 5- to 10-fold higher incidence after transcatheter aortic valve implantation. Cost analysis should take this into account. Often dismissed as minor complication, permanent pacemaker implantation increases the risks of endocarditis, impaired myocardial recovery, and higher mortality if associated with prosthesis regurgitation.

Magnetic Resonance Imaging in Nondependent Pacemaker Patients with Pacemakers and Defibrillators with a Nearly Depleted Battery.

PubMed

Okamura, Hideo; Padmanabhan, Deepak; Watson, Robert E; Dalzell, Connie; Acker, Nancy; Jondal, Mary; Romme, Abby L; Cha, Yong-Mei; Asirvatham, Samuel J; Felmlee, Joel P; Friedman, Paul A

2017-05-01

Magnetic resonance imaging (MRI) in patients with non-MRI-conditional cardiac implantable electronic devices (CIEDs) has been shown to be safe when performed under closely monitored protocols. However, the safety of MRI in patients with devices with a nearly depleted battery has not been reported. Prospective data were collected between January 2008 and May 2015 in patients with non-MRI-conditional CIEDs undergoing clinically indicated MRI under institutional protocol. Patients who were pacemaker dependent were excluded. Patients whose devices were at elective replacement indicator (ERI) at the time of MRI or close to ERI (ERI or replacement for battery depletion within 3 months of scan) were identified through database review and analyzed for clinical events. MRI scans (n = 569) were performed in 442 patients. Of these, we identified 13 scans performed with a nearly depleted battery in nine patients. All scans with implantable cardioverter defibrillators (ICDs, n = 9) were uneventful. However, two scans with pacemakers close to ERI resulted in a power-on-reset (PoR) event. One scan with a pacemaker close to ERI that was programmed to DOO mode reached ERI during MRI and automatically changed to VVI mode. Additionally, one scan with a pacemaker at ERI did not allow programming. All pacemakers with events were implanted before 2005. Patients with pacemakers and ICDs with a nearly depleted battery can safely undergo MRI when patients are not pacemaker dependent. Attention should be paid because old devices can result in PoR or ERI during MRI, which may lead to oversensing and inhibition of pacing. © 2017 Wiley Periodicals, Inc.

Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels

PubMed Central

Maltsev, Alexander V.; Maltsev, Victor A.; Stern, Michael D.

2017-01-01

Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (<100 nM) at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates. PMID:28792496

Cardiac rhythm and pacemaking abnormalities in patients affected by endemic pemphigus in Colombia may be the result of deposition of autoantibodies, complement, fibrinogen, and other molecules.

PubMed

Abreu Velez, Ana Maria; Howard, Michael S; Velazquez-Velez, Jorge Enrique

2018-05-01

We previously showed that one-third of patients affected by endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF), display autoreactivity to the heart. The purpose of this study was to investigate rhythm disturbances with the presence of autoantibodies and correlate them with ECG changes in these patients. We performed a study comparing 30 patients and 30 controls from the endemic area, matched by demographics, including age, sex, weight, work activities, and comorbidities. ECG as well as direct and indirect immunofluorescence, immunohistochemistry, and confocal microscopic studies focusing on cardiac node abnormalities were performed. Autopsies of 7 patients also were reviewed. The main ECG abnormalities seen in the El Bagre-EPF patients were sinus bradycardia (in one-half), followed by left bundle branch block, left posterior fascicular block, and left anterior fascicular block compared with the controls. One-third of the patients displayed polyclonal autoantibodies against the sinoatrial and/or AV nodes and the His bundle correlating with rhythm anomalies and delays in the cardiac conduction system (P <.01). The patient antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and myocardium-enriched zonula occludens-1-associated protein (MYZAP; Progen Biotechnik) (P <.01). One-third of the patients affected by El Bagre-EPF have rhythm abnormalities that slow the conduction of impulses in cardiac nodes and the cardiac conduction system. These abnormalities likely occur as a result of deposition of autoantibodies, complement, and other inflammatory molecules. We show for the first time that MYZAP is present in cardiac nodes. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Endometrial Stromal Cells and Immune Cell Populations Within Lymph Nodes in a Nonhuman Primate Model of Endometriosis

PubMed Central

Fazleabas, A. T.; Braundmeier, A. G.; Markham, R.; Fraser, I. S.; Berbic, M.

2011-01-01

Mounting evidence suggests that immunological responses may be altered in endometriosis. The baboon (Papio anubis) is generally considered the best model of endometriosis pathogenesis. The objective of the current study was to investigate for the first time immunological changes within uterine and peritoneal draining lymph nodes in a nonhuman primate baboon model of endometriosis. Paraffin-embedded femoral lymph nodes were obtained from 22 normally cycling female baboons (induced endometriosis n = 11; control n = 11). Immunohistochemical staining was performed with antibodies for endometrial stromal cells, T cells, immature and mature dendritic cells, and B cells. Lymph nodes were evaluated using an automated cellular imaging system. Endometrial stromal cells were significantly increased in lymph nodes from animals with induced endometriosis, compared to control animals (P = .033). In animals with induced endometriosis, some lymph node immune cell populations including T cells, dendritic cells and B cells were increased, suggesting an efficient early response or peritoneal drainage. PMID:21617251

Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells.

PubMed

Fletcher, Anne L; Malhotra, Deepali; Acton, Sophie E; Lukacs-Kornek, Veronika; Bellemare-Pelletier, Angelique; Curry, Mark; Armant, Myriam; Turley, Shannon J

2011-01-01

Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs) between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture.

Cardiac pacemaker dysfunction in children after thoracic drainage catheter manipulation.

PubMed

Lobdell, K W; Walters, H L; Hudson, C; Hakimi, M

1997-05-01

Two children underwent placement of permanent, epicardial-lead, dual-chamber, unipolar pacemaker systems for complete heart block. Postoperatively, both patients demonstrated subcutaneous emphysema-in the area of their pulse generators-temporally related to thoracic catheter manipulation. Acutely, each situation was managed with manual compression of the pulse generator, ascertaining appropriate pacemaker sensing and pacing. Maintenance of compression with pressure dressings, vigilant observation/monitoring, and education of the care givers resulted in satisfactory pacemaker function without invasive intervention.

Isolated perifacial lymph node metastasis in oral squamous cell carcinoma with clinically node-negative neck.

PubMed

Agarwal, Sangeet Kumar; Arora, Sowrabh Kumar; Kumar, Gopal; Sarin, Deepak

2016-10-01

The incidence of occult perifacial nodal disease in oral cavity squamous cell carcinoma is not well reported. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. The study will shed light on current controversies and will provide valuable clinical and pathological information in the practice of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. Prospective analysis. This study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of the metastatic rate to different lymph node levels in 231 patients of oral squamous cell cancer with a clinically node-negative neck. The current study demonstrated that 19 (8.22%) out of 231 patients showed ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial nodes did not differ significantly between the oral tongue (7.14%) and buccal mucosa (7.75%). Incidence was statistically significant in cases with lower age group (<45 years), advanced T stage, and higher depth of tumor invasion. Isolated perifacial node metastasis is high in oral squamous cell carcinoma with a clinically node-negative neck. The incidence of isolated perifacial involvement is high in cases of buccal mucosal and tongue cancers. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. 4 Laryngoscope, 126:2252-2256, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Influence of internal current and pacing current on pacemaker longevity.

PubMed

Schuchert, A; Kuck, K H

1994-01-01

The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8, 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/- 0.1 microA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.

Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study.

PubMed

Lin, Yu-Sheng; Chen, Tien-Hsing; Hung, Sheng-Ping; Chen, Dong Yi; Mao, Chun-Tai; Tsai, Ming-Lung; Chang, Shih-Tai; Wang, Chun-Chieh; Wen, Ming-Shien; Chen, Mien-Cheng

2015-01-01

Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications. Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07-0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08-0.83; P = 0.023). There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.

[Analysis of pacemaker ECGs].

PubMed

Israel, Carsten W; Ekosso-Ejangue, Lucy; Sheta, Mohamed-Karim

2015-09-01

The key to a successful analysis of a pacemaker electrocardiogram (ECG) is the application of the systematic approach used for any other ECG without a pacemaker: analysis of (1) basic rhythm and rate, (2) QRS axis, (3) PQ, QRS and QT intervals, (4) morphology of P waves, QRS, ST segments and T(U) waves and (5) the presence of arrhythmias. If only the most obvious abnormality of a pacemaker ECG is considered, wrong conclusions can easily be drawn. If a systematic approach is skipped it may be overlooked that e.g. atrial pacing is ineffective, the left ventricle is paced instead of the right ventricle, pacing competes with intrinsic conduction or that the atrioventricular (AV) conduction time is programmed too long. Apart from this analysis, a pacemaker ECG which is not clear should be checked for the presence of arrhythmias (e.g. atrial fibrillation, atrial flutter, junctional escape rhythm and endless loop tachycardia), pacemaker malfunction (e.g. atrial or ventricular undersensing or oversensing, atrial or ventricular loss of capture) and activity of specific pacing algorithms, such as automatic mode switching, rate adaptation, AV delay modifying algorithms, reaction to premature ventricular contractions (PVC), safety window pacing, hysteresis and noise mode. A systematic analysis of the pacemaker ECG almost always allows a probable diagnosis of arrhythmias and malfunctions to be made, which can be confirmed by pacemaker control and can often be corrected at the touch of the right button to the patient's benefit.

Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.

PubMed

Makki, Nader; Dollery, Jenn; Jones, Danielle; Crestanello, Juan; Lilly, Scott

Permanent pacemaker (PPM) placement occurs in 5-20% of patients after transcatheter aortic valve replacement (TAVR). Although predictors of pacemaker implantation have been established, features that predispose patients to pacemaker utilization on follow up have not been widely reported. We performed a retrospective review of patients undergoing commercial TAVR between 2011 and 2016. We collated patients that underwent in-hospital PPM implantation and had a follow up of at least 3months. Data abstraction was performed for electrophysiological studies (EPS), pacemaker indication, timing, and device interrogation for pacemaker dependency on follow up. A total of 24 patients received in-hospital PPM post-TAVR (14% of total cohort), and mean follow up was 22months. Indications for PPM included resting complete heart block (CHB; 15/24, 63%), left bundle branch block and abnormal electrophysiological study (EPS; 7/24, 29%), alternating bundle branch block (1/24, 4%) and tachy-brady syndrome (1/24, 4%). Pacemaker dependency (underlying ventricular asystole, complete heart block, or >50% pacing) occurred in 8/24 patients (33%) during follow-up, 7 of whom had resting CHB, and one with CHB invoked during EPS. Pacemaker dependency after TAVR is common among those that exhibited CHB, but not among those with a prolonged HV delay during EPS. Although preliminary, these observations are relevant to management of rhythm disturbances after TAVR, and may inform the practice of EPS-based PPM implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Neck Pain One Week after Pacemaker Generator Replacement.

PubMed

Graham, Ross F; Wightman, John M

2015-07-01

The incidence of cardiac pacemaker implantation has risen markedly in the past three decades, making awareness of possible postprocedural complications critical to the emergency physician. This case is the first documented instance of internal jugular (IJ) deep vein thrombosis (DVT) from an uncomplicated pacemaker generator replacement. A patient presented to an Emergency Department with a 2-day history of mild left temporal headache migrating to his left neck. The patient did not volunteer this information, but review of systems revealed a temporary transvenous pacemaker inserted through the right IJ vein 1 week previously during a routine exchange of a left-sided cardiac pacemaker generator. Manipulation of the existing pacemaker wires entering the left subclavian vein was minimal. Computed tomographic angiography of the neck demonstrated near-complete thrombotic occlusion of the entire length of his left IJ vein. This required hospital admission for observation and treatment with anticoagulation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DVT, with thrombotic extension into adjacent vessels anywhere along the course of pacemaker wires, should be considered by the emergency provider in the evaluation of head, neck, or upper extremity symptoms after recent or remote implantation or manipulation of a transvenous cardiac pacemaker, including generator replacement. Failure to identify and treat appropriately could result in significant morbidity and mortality from airway edema, septic thrombophlebitis, superior vena cava syndrome, superior sagittal sinus thrombosis, or pulmonary embolism. Published by Elsevier Inc.

Survival time with pacemaker implantation for dogs diagnosed with persistent atrial standstill.

PubMed

Cervenec, R M; Stauthammer, C D; Fine, D M; Kellihan, H B; Scansen, B A

2017-06-01

To evaluate survival time in dogs with persistent atrial standstill after pacemaker implantation and to compare the survival times for cardiac-related vs. non-cardiac deaths. Secondary objectives were to evaluate the effects of breed and the presence of congestive heart failure (CHF) at the time of diagnosis on survival time. Twenty dogs with persistent atrial standstill and pacemaker implantation. Medical records were searched to identify dogs diagnosed with persistent atrial standstill based on electrocardiogram that underwent pacemaker implantation. Survival after pacemaker implantation was analyzed using the Kaplan-Meier method. The median survival time after pacemaker implantation for all-cause mortality was 866 days. There was no significant difference (p=0.573) in median survival time for cardiac (506 days) vs. non-cardiac deaths (400 days). The presence of CHF at the time of diagnosis did not affect the survival time (P=0.854). No difference in median survival time was noted between breeds (P=0.126). Dogs with persistent atrial standstill have a median survival time of 866 days with pacemaker implantation, though a wide range of survival times was observed. There was no difference in the median survival time for dogs with cardiac-related deaths and those without. Patient breed and the presence of CHF before pacemaker implantation did not affect median survival time. Copyright © 2017 Elsevier B.V. All rights reserved.

Modulation of network pacemaker neurons by oxygen at the anaerobic threshold.

PubMed

Hill, Andrew A V; Simmers, John; Meyrand, Pierre; Massabuau, Jean-Charles

2012-07-01

Previous in vitro and in vivo studies showed that the frequency of rhythmic pyloric network activity in the lobster is modulated directly by oxygen partial pressure (PO(2)). We have extended these results by (1) increasing the period of exposure to low PO(2) and by (2) testing the sensitivity of the pyloric network to changes in PO(2) that are within the narrow range normally experienced by the lobster (1 to 6 kPa). We found that the pyloric network rhythm was indeed altered by changes in PO(2) within the range typically observed in vivo. Furthermore, a previous study showed that the lateral pyloric constrictor motor neuron (LP) contributes to the O(2) sensitivity of the pyloric network. Here, we expanded on this idea by testing the hypothesis that pyloric pacemaker neurons also contribute to pyloric O(2) sensitivity. A 2-h exposure to 1 kPa PO(2), which was twice the period used previously, decreased the frequency of an isolated group of pacemaker neurons, suggesting that changes in the rhythmogenic properties of these cells contribute to pyloric O(2) sensitivity during long-term near-anaerobic (anaerobic threshold, 0.7-1.2 kPa) conditions.

Performance of re-used pacemakers and implantable cardioverter defibrillators compared with new devices at Groote Schuur Hospital in Cape Town, South Africa

PubMed Central

Jama, Zimasa V; Chin, Ashley; Mayosi, Bongani M; Badri, Motasim

2015-01-01

Objectives Little is known about the performance of re-used pacemakers and implantable cardioverter defibrillators (ICDs) in Africa. We sought to compare the risk of infection and the rate of malfunction of re-used pacemakers and ICDs with new devices implanted at Groote Schuur Hospital in Cape Town, South Africa. Methods This was a retrospective case comparison study of the performance of re-used pacemakers and ICDs in comparison with new devices implanted at Groote Schuur Hospital over a 10-year period. The outcomes were incidence of device infection, device malfunction, early battery depletion, and device removal due to infection, malfunction, or early battery depletion. Results Data for 126 devices implanted in 126 patients between 2003 and 2013 were analysed, of which 102 (81%) were pacemakers (51 re-used and 51 new) and 24 (19%) were ICDs (12 re-used and 12 new). There was no device infection, malfunction, early battery depletion or device removal in either the re-used or new pacemaker groups over the median follow up of 15.1 months [interquartile range (IQR), 1.3–36.24 months] for the re-used pacemakers, and 55.8 months (IQR, 20.3–77.8 months) for the new pacemakers. In the ICD group, no device infection occurred over a median follow up of 35.9 months (IQR, 17.0–70.9 months) for the re-used ICDs and 45.7 months (IQR, 37.6–53.7 months) for the new ICDs. One device delivered inappropriate shocks, which resolved without intervention and with no harm to the patient. This re-used ICD subsequently needed generator replacement 14 months later. In both the pacemaker and ICD groups, there were no procedure-non-related infections documented for the respective follow-up periods. Conclusion No significant differences were found in performance between re-used and new pacemakers and ICDs with regard to infection rates, device malfunction, battery life and device removal for complications. Pacemaker and ICD re-use is feasible and safe and is a viable option for patients with bradyarrhythmias and tachyarrthythmias. PMID:26407220

The Drosophila Receptor Protein Tyrosine Phosphatase LAR Is Required for Development of Circadian Pacemaker Neuron Processes That Support Rhythmic Activity in Constant Darkness But Not during Light/Dark Cycles

PubMed Central

Agrawal, Parul

2016-01-01

In Drosophila, a transcriptional feedback loop that is activated by CLOCK-CYCLE (CLK-CYC) complexes and repressed by PERIOD-TIMELESS (PER-TIM) complexes keeps circadian time. The timing of CLK-CYC activation and PER-TIM repression is regulated post-translationally, in part through rhythmic phosphorylation of CLK, PER, and TIM. Although kinases that control PER, TIM, and CLK levels, activity, and/or subcellular localization have been identified, less is known about phosphatases that control clock protein dephosphorylation. To identify clock-relevant phosphatases, clock-cell-specific RNAi knockdowns of Drosophila phosphatases were screened for altered activity rhythms. One phosphatase that was identified, the receptor protein tyrosine phosphatase leukocyte-antigen-related (LAR), abolished activity rhythms in constant darkness (DD) without disrupting the timekeeping mechanism in brain pacemaker neurons. However, expression of the neuropeptide pigment-dispersing factor (PDF), which mediates pacemaker neuron synchrony and output, is eliminated in the dorsal projections from small ventral lateral (sLNv) pacemaker neurons when Lar expression is knocked down during development, but not in adults. Loss of Lar function eliminates sLNv dorsal projections, but PDF expression persists in sLNv and large ventral lateral neuron cell bodies and their remaining projections. In contrast to the defects in lights-on and lights-off anticipatory activity seen in flies that lack PDF, Lar RNAi knockdown flies anticipate the lights-on and lights-off transition normally. Our results demonstrate that Lar is required for sLNv dorsal projection development and suggest that PDF expression in LNv cell bodies and their remaining projections mediate anticipation of the lights-on and lights-off transitions during a light/dark cycle. SIGNIFICANCE STATEMENT In animals, circadian clocks drive daily rhythms in physiology, metabolism, and behavior via transcriptional feedback loops. Because key circadian transcriptional activators and repressors are regulated by phosphorylation, we screened for phosphatases that alter activity rhythms when their expression was reduced. One such phosphatase, leukocyte-antigen-related (LAR), abolishes activity rhythms, but does not disrupt feedback loop function. Rather, Lar disrupts clock output by eliminating axonal processes from clock neurons that release pigment-dispersing factor (PDF) neuropeptide into the dorsal brain, but PDF expression persists in their cell bodies and remaining projections. In contrast to flies that lack PDF, flies that lack Lar anticipate lights-on and lights-off transitions normally, which suggests that the remaining PDF expression mediates activity during light/dark cycles. PMID:27030770

21 CFR 870.3700 - Pacemaker programmers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker programmers. 870.3700 Section 870.3700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers...

Haemophilus parainfluenzae bacteremia associated with a pacemaker wire localized by gallium scan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenbaum, G.S.; Calubiran, O.; Cunha, B.A.

1990-05-01

A young woman with a history of sick sinus syndrome and placement of a permanent pacemaker 6 months before admission had fever and Haemophilus parainfluenzae bacteremia. A gallium scan localized the infection to the site of the pacemaker wire. Echocardiograms were negative for any vegetations. The patient responded to cefotaxime and trimethoprim-sulfamethoxazole therapy. We believe that this is the first case of H. parainfluenzae bacteremia associated with a pacemaker wire and localized by gallium scan.

Of pacemakers and statistics: the actuarial method extended.

PubMed

Dussel, J; Wolbarst, A B; Scott-Millar, R N; Obel, I W

1980-01-01

Pacemakers cease functioning because of either natural battery exhaustion (nbe) or component failure (cf). A study of four series of pacemakers shows that a simple extension of the actuarial method, so as to incorporate Normal statistics, makes possible a quantitative differentiation between the two modes of failure. This involves the separation of the overall failure probability density function PDF(t) into constituent parts pdfnbe(t) and pdfcf(t). The approach should allow a meaningful comparison of the characteristics of different pacemaker types.

Self-Diagnostics Digitally Controlled Pacemaker/Defibrillators: A Design Plan for Incorporating Diagnostics and Digital Control in the schema of a Pacemaker/Defibrillator Design

DTIC Science & Technology

2005-09-01

of a system to store and retrieve digital/ wireless communication information from a pacemaker/ defibrillator, or other device , and to alert medical... wireless communication information from a pacemaker/defibrillator, or other device , and to alert medical personnel when a person is experiencing...with heart, pacing, program, test, sensor , circuit) where the individual needs immediate attention an audible alert will go off at the nurse’s

Automatic management of atrial and ventricular stimulation in a contemporary unselected population of pacemaker recipients: the ESSENTIAL Registry.

PubMed

Biffi, Mauro; Bertini, Matteo; Saporito, Davide; Belotti, Giuseppina; Quartieri, Fabio; Piancastelli, Maurizio; Pucci, Angelo; Boggian, Giulio; Mazzocca, Gian Franco; Giorgi, Davide; Diotallevi, Paolo; Diemberger, Igor; Martignani, Cristian; Pancaldi, Stefano; Ziacchi, Matteo; Marcantoni, Lina; Toselli, Tiziano; Attala, Simone; Iori, Matteo; Bottoni, Nicola; Argnani, Selina; Tomasi, Corrado; Sassone, Biagio; Boriani, Giuseppe

2016-10-01

We investigated the applicability of the Ventricular Capture Control (VCC) and Atrial Capture Control (ACC) algorithms for automatic management of cardiac stimulation featured by Biotronik pacemakers in a broad, unselected population of pacemaker recipients. Ventricular Capture Control and Atrial Capture Control were programmed to work at a maximum adapted output voltage as 4.8 V in consecutive recipients of Biotronik pacemakers. Ambulatory threshold measurements were made 1 and 12 months after pacemaker implant/replacement in all possible pacing/sensing configurations, and were compared with manual measurements. Among 542 patients aged 80 (73-85) years, 382 had a pacemaker implant and 160 a pacemaker replacement. Ventricular Capture Control could work at long term in 97% of patients irrespectively of pacing indication, lead type, and lead service life, performance being superior with discordant pacing/sensing configurations. Atrial Capture Control could work in 93% of patients at 4.8 V maximum adapted voltage and at any pulse width, regardless of pacing indication, lead type, and service life. At 12-month follow-up, a ventricular threshold increase ≥1.5 V had occurred in 4.4% of patients uneventfully owing to VCC functioning. Projected pacemaker longevity at 1 month was strongly correlated with the 12-month estimate, and exceeded 13 years in >60% of patients. These algorithms for automatic management of pacing output ensure patient safety in the event of a huge increase of pacing threshold, while enabling maximization of battery longevity. Their applicability is quite broad in an unselected pacemaker population irrespectively of lead choice and service of life. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

The influence of cholinesterase inhibitor therapy for dementia on risk of cardiac pacemaker insertion: a retrospective, population-based, health administrative databases study in Ontario, Canada.

PubMed

Huang, Allen R; Redpath, Calum J; van Walraven, Carl

2015-04-28

Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion. We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study. 2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case-control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users. Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion.

Current use of implantable electrical devices in Sweden: data from the Swedish pacemaker and implantable cardioverter-defibrillator registry.

PubMed

Gadler, Fredrik; Valzania, Cinzia; Linde, Cecilia

2015-01-01

The National Swedish Pacemaker and Implantable Cardioverter-Defibrillator (ICD) Registry collects prospective data on all pacemaker and ICD implants in Sweden. We aimed to report the 2012 findings of the Registry concerning electrical devices implantation rates and changes over time, 1 year complications, long-term device longevity and patient survival. Forty-four Swedish implanting centres continuously contribute implantation of pacemakers and ICDs to the Registry by direct data entry on a specific website. Clinical and technical information on 2012 first implants and postoperative complications were analysed and compared with previous years. Patient survival data were obtained from the Swedish population register database. In 2012, the mean pacemaker and ICD first implantation rates were 697 and 136 per million inhabitants, respectively. The number of cardiac resynchronization therapy (CRT) first implantations/million capita was 41 (CRT pacemakers) and 55 (CRT defibrillators), with only a slight increase in CRT-ICD rate compared with 2011. Most device implantations were performed in men. Complication rates for pacemaker and ICD procedures were 5.3 and 10.1% at 1 year, respectively. Device and lead longevity differed among manufacturers. Pacemaker patients were older at the time of first implant and had generally worse survival rate than ICD patients (63 vs. 82% after 5 years). Pacemaker and ICD implantation rates seem to have reached a level phase in Sweden. Implantable cardioverter-defibrillator and CRT implantation rates are very low and do not reflect guideline indications. Gender differences in CRT and ICD implantations are pronounced. Device and patient survival rates are variable, and should be considered when deciding device type. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

A Fully Implantable Pacemaker for the Mouse: From Battery to Wireless Power

PubMed Central

Zellmer, Erik R.; Weinheimer, Carla J.; MacEwan, Matthew R.; Cui, Sophia X.; Nerbonne, Jeanne M.; Efimov, Igor R.

2013-01-01

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice. PMID:24194832

Effect of monopolar radiofrequency energy on pacemaker function.

PubMed

Govekar, Henry R; Robinson, Thomas N; Varosy, Paul D; Girard, Guillaume; Montero, Paul N; Dunn, Christina L; Jones, Edward L; Stiegmann, Greg V

2012-10-01

This study aimed to quantify the clinical parameters of mono- and bipolar instruments that inhibit pacemaker function. The specific aims were to quantify pacer inhibition resulting from the monopolar instrument by altering the generator power setting, the generator mode, the distance between the active electrode and the pacemaker, and the location of the dispersive electrode. A transvenous ventricular lead pacemaker overdrive paced the native heart rate of an anesthetized pig. The primary outcome variable was pacer inhibition quantified as the number of beats dropped by the pacemaker during 5 s of monopolar active electrode activation. Lowering the generator power setting from 60 to 30 W decreased the number of dropped paced events (2.3 ± 1.2 vs 1.6 ± 0.8 beats; p = 0.045). At 30 W of power, use of the cut mode decreased the number of dropped paced beats compared with the coagulation mode (0.6 ± 0.5 vs 1.6 ± 0.8; p = 0.015). At 30 W coagulation, firing the active electrode at different distances from the pacemaker generator (3.75, 7.5, 15, and 30 cm) did not change the number of dropped paced beats (p = 0.314, analysis of variance [ANOVA]). The dispersive electrode was placed in four locations (right/left gluteus, right/left shoulder). More paced beats were dropped when the current vector traveled through the pacemaker/leads than when it did not (1.5 ± 1.0 vs 0.2 ± 0.4; p < 0.001). Clinical parameters that reduce the inhibition of a pacemaker by monopolar instruments include lowering the generator power setting, using cut (vs coagulation) mode, and locating the dispersive electrode so the current vector does not traverse the pacemaker generator or leads.

Current facts on pacemaker electromagnetic interference and their application to clinical care

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sager, D.P.

1987-03-01

The development of the sensing demand cardiac pacemaker brought with it the problem of interference as a result of extraneous electric current and electromagnetic fields. This problem still deserves consideration, not only because harmful disruption of pacemaker function, while infrequent, can occur but also because myths and misunderstandings have flourished on the subject. Misinformation has often led to needless patient anxiety and unnecessary restrictions in activities of daily living. Similarly, when health care practitioners are misinformed about pacemaker interference, potentially hazardous situations can occur in the clinical environment. This article is a review of current information on the sources andmore » effects of electromagnetic interference (EMI) on pacemakers and includes a discussion of their application to patient care.« less

Congestive heart failure caused by transvenous pacemaker lead prolapse and associated right ventricular outflow tract obstruction in a dog.

PubMed

Djani, D M; Coleman, A E; Rapoport, G S; Schmiedt, C W; Layher, J; Thomason, J D

2016-12-01

A 16-year-old dog was presented for cough as well as increased respiratory rate and effort three years after implantation of a single-lead transvenous artificial pacemaker system. Thoracic radiographs and echocardiography disclosed prolapse of the pacemaker lead into the main pulmonary artery, causing severe pulmonary insufficiency and right-sided volume overload. Repositioning of the pacemaker lead led to improvement of pulmonary insufficiency and resolution of the dog's clinical signs and cavitary effusions. This case describes a late complication of pacemaker implantation that may be avoided by appropriate use of the manufacturer-provided anchoring sleeve and avoidance of excessive lead redundancy. Copyright © 2016 Elsevier B.V. All rights reserved.

Transcatheter leadless pacemaker implantation in a patient with a transvenous dual-chamber pacemaker already in place.

PubMed

Karjalainen, Pasi P; Nammas, Wail; Paana, Tuomas

2016-01-01

An 83-year-old lady had a DDDR pacemaker inserted in 1997 for symptomatic atrioventricular block. She underwent battery replacement in 2008. In 2010, she developed atrial fibrillation; the pacemaker was switched to VVIR mode. During the last 2years, ventricular lead threshold increased progressively. In December 2015, she presented for elective battery replacement. After successful battery replacement, the ventricular lead threshold remained high; therefore, we implanted a leadless transcatheter pacemaker, via femoral vein access, using a dedicated catheter delivery system. Electrical measurements at this stage revealed a pacing threshold of 0.28V at 0.24msec, and an impedance of 650Ω. Copyright © 2016 Elsevier Inc. All rights reserved.

Monitoring the radiation dose to a multiprogrammable pacemaker during radical radiation therapy: A case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muller-Runkel, R.; Orsolini, G.; Kalokhe, U.P.

1990-11-01

Multiprogrammable pacemakers, using complimentary metaloxide semiconductor (CMOS) circuitry, may fail during radiation therapy. We report about a patient who received 6,400 cGy for unresectable carcinoma of the left lung. In supine treatment position, arms raised above the head, the pacemaker was outside the treated area by a margin of at least 1 cm, shielded by cerrobend blocking mounted on a tray. From thermoluminescent dosimeter (TLD) measurements, we estimate that the pacemaker received 620 cGy in scatter doses. Its function was monitored before, during, and after completion of radiation therapy. The pacemaker was functioning normally until the patient's death 5 monthsmore » after completion of treatment. The relevant electrocardiograms (ECGs) are presented.« less

Histological differential diagnosis between lymph node toxoplasmosis and other benign lymph node hyperplasias.

PubMed

Miettinen, M

1981-03-01

The material from 667 lymph nodes, originally suspected of toxoplasmosis, was histologically re-examined, to evaluate criteria for diagnosis and differential diagnosis. The results showed that at least 80% of benign lymph node enlargements containing small groups of epithelioid cells were associated with high titres of Toxoplasma antibodies. Furthermore, 85--95% of the lymph nodes in association with high Toxoplasma antibodies showed the typical histological appearances of toxoplasmosis. The histological diagnosis of toxoplasmosis is thus both fairly specific and sensitive. Other lymph node lesions with small groups of epithelioid cells must be considered in the differential diagnosis. Sarcoidosis and tuberculosis usually have a predominance of distinct large epithelioid cell granulomata. Lymph nodes with sinus histiocytosis showing the formation of small groups of epithelioid cells, do not demonstrate prominent hyperplasia and include sparse germinal centres and were not associated with toxoplasmosis. Lymph nodes with disturbed general structure and small groups of epithelioid cells must be carefully assessed because of the significant possibility of malignancy.

21 CFR 870.3670 - Pacemaker charger.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker charger. 870.3670 Section 870.3670 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a...

Effects of Electroacupuncture on Interstitial Cells of Cajal (ICC) Ultrastructure and Connexin 43 Protein Expression in the Gastrointestinal Tract of Functional Dyspepsia (FD) Rats.

PubMed

Zhang, Guoshan; Xie, Shen; Hu, Wei; Liu, Yuer; Liu, Mailan; Liu, Mi; Chang, Xiaorong

2016-06-14

BACKGROUND Gastrointestinal motility disorder is the main clinical manifestation in functional dyspepsia (FD) patients. Electroacupuncture is effective in improving gastrointestinal motility disorder in FD; however, the underlying mechanism remains unclear. It has been demonstrated that interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract, and the pacemaker potential is transmitted to nearby cells through gap junctions between ICC or ICC and the smooth muscle. Therefore, this study aimed to assess the effects of electroacupuncture on ICC ultrastructure and expression of the gap junction protein connexin 43 (Cx43) in FD rats. MATERIAL AND METHODS The animals were randomized into 3 groups: control, model, and electroacupuncture. Electroacupuncture was applied at Zusanli (ST36) in the electroacupuncture group daily for 10 days, while no electroacupuncture was applied to model group animals. RESULTS Ultrastructure of ICC recovered normally in gastric antrum and small intestine specimens was improved, with Cx43 expression levels in these tissues significantly increased in the electroacupuncture group compared with the model group. CONCLUSIONS These findings indicated that electroacupuncture is effective in alleviating ICC damage and reduces Cx43 levels in FD rats, and suggest that ICC and Cx43 are involved in electroacupuncture treatment in rats with FD to improve gastrointestinal motility disorders.

Autonomic Modification of Intestinal Smooth Muscle Contractility

ERIC Educational Resources Information Center

Montgomery, Laura E. A.; Tansey, Etain A.; Johnson, Chris D.; Roe, Sean M.; Quinn, Joe G.

2016-01-01

Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe…

Tissue interactions with nonionizing electromagnetic fields. Final report, March 1979-February 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adey, W.R.; Bawin, S.M.; Byus, C.V.

1986-08-01

This report provides an overview of this research program focused on basic research in nervous system responses to electric fields at 60 Hz. The emphasis in this project was to determine the fundamental mechanisms underlying some phenomena of electric field interactions in neural systems. The five studies of the initial program were tests of behavioral responses in the rat based upon the hypothesis that electric field detection might follow psychophysical rules known from prior research with light, sound and other stimuli; tests of electrophysiological responses to ''normal'' forms of stimulation in rat brain tissue exposed in vitro to electric fields,more » based on the hypothesis that the excitability of brain tissue might be affected by fields in the extracellular environment; tests of electrophysiological responses of spontaneously active pacemaker neurons of the Aplysia abdominal ganglion, based on the hypothesis that electric field interactions at the cell membrane might affect the balance among the several membrane-related processes that govern pacemaker activity; studies of mechanisms of low frequency electromagnetic field interactions with bone cells in the context of field therapy of ununited fractures; and manipulation of cell surface receptor proteins in studies of their mobility during EM field exposure.« less

Electromechanical Wave Imaging of biologically and electrically paced canine hearts in vivo

PubMed Central

Costet, Alexandre; Provost, Jean; Gambhir, Alok; Bobkov, Yevgeniy; Danilo, Peter; Boink, Gerard J.J.; Rosen, Michael R.; Konofagou, Elisa

2014-01-01

Ultrasound-based, Electromechanical Wave (EW) Imaging (EWI) can directly and entirely noninvasively map the transmural electromechanical activation in all four cardiac chambers in vivo. In this study, we assessed EWI repeatability and reproducibility, as well as its capability in localizing electronic and, for the first time, biological pacemakers in closed-chest, conscious canines. Electromechanical activation was obtained in six conscious animals during normal sinus rhythm (NSR), and idioventricular rhythms occurring in dogs in heart block instrumented with electronic and biological pacemakers (EPM and BPM respectively). After AV node ablation, dogs were implanted with an EPM in the right ventricular (RV) endocardial apex (n=4) and two additionally received a BPM at the left ventricular (LV) epicardial base (n=2). EWI was performed transthoracically during NSR, BPM, and EPM pacing, in conscious dogs, using an unfocused transmit sequence at 2000 frames/second. During NSR, the EW originated at the right atrium (RA), propagated to the left atrium (LA) and emerged from multiple sources in both ventricles. During EPM, the EW originated at the RV apex and propagated throughout both ventricles. During BPM, the EW originated from the LV basal lateral wall and subsequently propagated throughout the ventricles. EWI differentiated BPM from EPM and NSR and identified the distinct pacing origins. Isochrone comparison demonstrated that EWI was repeatable and reliable. These findings thus indicate the EWI potential to serve as a simple, noninvasive and direct imaging technology for mapping and characterizing arrhythmias as well as the treatments thereof. PMID:24239363

Successful management of multiple permanent pacemaker complications – infection, 13 year old silent lead perforation and exteriorisation following failed percutaneous extraction, superior vena cava obstruction, tricuspid valve endocarditis, pulmonary embolism and prosthetic tricuspid valve thrombosis

PubMed Central

Kaul, Pankaj; Adluri, Krishna; Javangula, Kalyana; Baig, Wasir

2009-01-01

A 59 year old man underwent mechanical tricuspid valve replacement and removal of pacemaker generator along with 4 pacemaker leads for pacemaker endocarditis and superior vena cava obstruction after an earlier percutaneous extraction had to be abandoned, 13 years ago, due to cardiac arrest, accompanied by silent, unsuspected right atrial perforation and exteriorisation of lead. Postoperative course was complicated by tricuspid valve thrombosis and secondary pulmonary embolism requiring TPA thrombolysis which was instantly successful. A review of literature of pacemaker endocarditis and tricuspid thrombosis along with the relevant management strategies is presented. We believe this case report is unusual on account of non operative management of right atrial lead perforation following an unsuccessful attempt at percutaneous removal of right sided infected pacemaker leads and the incidental discovery of the perforated lead 13 years later at sternotomy, presentation of pacemaker endocarditis with a massive load of vegetations along the entire pacemaker lead tract in superior vena cava, right atrial endocardium, tricuspid valve and right ventricular endocardium, leading to a functional and structural SVC obstruction, requirement of an unusually large dose of warfarin postoperatively occasioned, in all probability, by antibiotic drug interactions, presentation of tricuspid prosthetic valve thrombosis uniquely as vasovagal syncope and isolated hypoxia and near instantaneous resolution of tricuspid prosthetic valve thrombosis with Alteplase thrombolysis. PMID:19239701

Tricuspid valve repair for severe tricuspid regurgitation due to pacemaker leads.

PubMed

Uehara, Kyokun; Minakata, Kenji; Watanabe, Kentaro; Sakaguchi, Hisashi; Yamazaki, Kazuhiro; Ikeda, Tadashi; Sakata, Ryuzo

2016-07-01

Tricuspid valve regurgitation due to pacemaker leads is a well-known complication. Although some reports have suggested that pacemaker leads should be surgically explanted, strongly adhered leads cannot always be removed. The aim of this study was to describe our tricuspid valve repair techniques with pacemaker leads left in situ. Our retrospective study investigated 6 consecutive patients who required tricuspid valve surgery for severe regurgitation induced by pacemaker leads. From the operative findings, we identified 3 patterns of tricuspid valve and pacemaker lead involvement. In 3 patients, the leads were caught in the chordae, in 2 patients, tricuspid regurgitation was caused by lead impingement on the septal leaflet, and in 3 patients, tricuspid valve leaflets had been perforated by the pacemaker leads. During surgery, all leads were left in situ after being separated from the leaflet or valvular apparatus. In addition, suture annuloplasty was performed for annular dilatation in all cases. In one patient, the lead was reaffixed to the annulus after the posterior leaflet was cut back towards the annulus, and the leaflet was then closed. There was one hospital death due to sepsis. The degree of tricuspid regurgitation was trivial in all surviving patients at discharge. During a mean follow-up of 21 months, one patient died from pneumonia 20 months after tricuspid valve repair. In patients undergoing tricuspid valve surgery due to severe tricuspid regurgitation caused by pacemaker leads, the leads can be left in situ after proper repair with annuloplasty. © The Author(s) 2016.

Outcome and management of pacemaker-induced superior vena cava syndrome.

PubMed

Fu, Hai-Xia; Huang, Xin-Miao; Zhong, Li; Osborn, Michael J; Bjarnason, Haraldur; Mulpuru, Siva; Zhao, Xian-Xian; Friedman, Paul A; Cha, Yong-Mei

2014-11-01

We aimed to determine the long-term outcomes of percutaneous lead extraction and stent placement in patients with pacemaker-induced superior vena cava (SVC) syndrome. The study retrospectively screened patients who underwent lead extraction followed by central vein stent implantation at Mayo Clinic (Rochester, MN, USA), from January 2005 to December 2012, to identify the patients with pacemaker-induced SVC syndrome. Demographic, clinical, and follow-up characteristics of those patients were collected from electronic medical records. Six cases were identified. The mean (standard deviation) age was 56 (15) years (male, 67%). All patients had permanent dual-chamber pacemakers, with a mean 11-year history of pacemaker placement. The entire device system was explanted in five patients; one patient had a 21-year-old pacemaker lead that could not be removed. Eight stents were implanted in six patients: five patients had one stent, one patient had three. A new pacemaker system was reimplanted through the stented vein in five patients. Technical success was achieved in all patients, without any complication. Symptoms rapidly resolved in all patients after stent deployment. The mean follow-up duration was 48 months (range, 10-100 months). Three patients remained symptom free. Reintervention with percutaneous balloon venoplasty was successful in three patients with symptom recurrence. Percutaneous stent implantation after lead removal followed by reimplantation of leads is a feasible alternative therapy for pacemaker-induced SVC syndrome, although some cases may require repeat intervention. ©2014 Wiley Periodicals, Inc.

Evaluation of Death among the Patients Undergoing Permanent Pacemaker Implantation: A Competing Risks Analysis.

PubMed

Ghaem, Haleh; Ghorbani, Mohammad; Zare Dorniani, Samira

2017-06-01

Permanent artificial pacemaker is one of the important therapies for treatment of cardiac conduction system problems. The present study aimed to determine the association between some predictive variables and all-cause and cause-specific mortality in the patients who had undergone pacemaker implantation. This study was conducted on 1207 patients who had undergone permanent pacemaker implantation in the hospitals affiliated with Shiraz University of Medical Sciences, Iran, from Mar 2002 to Mar 2012. The variables that existed in the patients' medical records included sex, diabetes mellitus, obesity, cerebrovascular accident, cardiomegaly, smoking, hypertension, ischemic heart disease, congenital heart disease, sick sinus syndrome, and atrial fibrillation. Competing risks model was used to assess the association between the predictive variables and cause-specific (i.e., cardiac and vascular) mortality. The patients' mean age was 66.32±17.92 yr (70.62±14.45 yr in the patients with single-chamber pacemakers vs. 61.91±17.69 yr in those with two-chamber pacemakers) ( P <0.001). Sick sinus syndrome and age increased the risk of all-cause mortality, while two-chamber pacemaker decreased this risk. Obesity increased the risk of cardiac death, and diabetes mellitus and heart valve disease increased the risk of vascular death. The variables predicting mortality in all-cause model were completely different from those in cause-specific model. Moreover, death in such patients may occur due to reasons other than pacemaker. Therefore, future studies, particularly prospective ones, are recommended to use competing risks models.

Neuropeptide Secreted from a Pacemaker Activates Neurons to Control a Rhythmic Behavior

PubMed Central

Wang, Han; Girskis, Kelly; Janssen, Tom; Chan, Jason P.; Dasgupta, Krishnakali; Knowles, James A.; Schoofs, Liliane; Sieburth, Derek

2013-01-01

Summary Background Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 seconds, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown. Results Here we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G protein-coupled receptor on the GABAergic neurons, as the receptor of NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo. Conclusions Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors. PMID:23583549

Beat-to-Beat Variation in Periodicity of Local Calcium Releases Contributes to Intrinsic Variations of Spontaneous Cycle Length in Isolated Single Sinoatrial Node Cells

PubMed Central

Monfredi, Oliver; Maltseva, Larissa A.; Spurgeon, Harold A.; Boyett, Mark R.; Lakatta, Edward G.; Maltsev, Victor A.

2013-01-01

Spontaneous, submembrane local Ca2+ releases (LCRs) generated by the sarcoplasmic reticulum in sinoatrial nodal cells, the cells of the primary cardiac pacemaker, activate inward Na+/Ca2+-exchange current to accelerate the diastolic depolarization rate, and therefore to impact on cycle length. Since LCRs are generated by Ca2+ release channel (i.e. ryanodine receptor) openings, they exhibit a degree of stochastic behavior, manifested as notable cycle-to-cycle variations in the time of their occurrence. Aim The present study tested whether variation in LCR periodicity contributes to intrinsic (beat-to-beat) cycle length variability in single sinoatrial nodal cells. Methods We imaged single rabbit sinoatrial nodal cells using a 2D-camera to capture LCRs over the entire cell, and, in selected cells, simultaneously measured action potentials by perforated patch clamp. Results LCRs begin to occur on the descending part of the action potential-induced whole-cell Ca2+ transient, at about the time of the maximum diastolic potential. Shortly after the maximum diastolic potential (mean 54±7.7 ms, n = 14), the ensemble of waxing LCR activity converts the decay of the global Ca2+ transient into a rise, resulting in a late, whole-cell diastolic Ca2+ elevation, accompanied by a notable acceleration in diastolic depolarization rate. On average, cells (n = 9) generate 13.2±3.7 LCRs per cycle (mean±SEM), varying in size (7.1±4.2 µm) and duration (44.2±27.1 ms), with both size and duration being greater for later-occurring LCRs. While the timing of each LCR occurrence also varies, the LCR period (i.e. the time from the preceding Ca2+ transient peak to an LCR’s subsequent occurrence) averaged for all LCRs in a given cycle closely predicts the time of occurrence of the next action potential, i.e. the cycle length. Conclusion Intrinsic cycle length variability in single sinoatrial nodal cells is linked to beat-to-beat variations in the average period of individual LCRs each cycle. PMID:23826247

A Novel Way Of Repair Of Insulation Breaks During Pacemaker Generator Replacement

PubMed Central

Manzoor Ali, Syed; Iqbal, Khurshid; Tramboo, Nisar A; Lone, Aijaz A; Kaul, Suresh; Kaul, Neelam; Hafiz, Imran

2009-01-01

Minor abrasions can occur while mobilising old lead during pacemaker generator replacement necesittating placement of additional lead adding to the financial burden and junk in heart. We describe a novel way of repair of old pacemaker lead preventing additional lead placement. PMID:19763196

21 CFR 870.3620 - Pacemaker lead adaptor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor...

21 CFR 870.3650 - Pacemaker polymeric mesh bag.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker polymeric mesh bag. 870.3650 Section 870.3650 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker generator function analyzer. 870.3630 Section 870.3630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker...

21 CFR 870.3690 - Pacemaker test magnet.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker test magnet. 870.3690 Section 870.3690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet...

21 CFR 870.3720 - Pacemaker electrode function tester.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker electrode function tester. 870.3720... electrode function tester. (a) Identification. A pacemaker electrode function tester is a device which is... measuring the patient's pacing threshold and intracardiac R-wave potential. (b) Classification. Class II...

Multicellular automaticity of cardiac cell monolayers: effects of density and spatial distribution of pacemaker cells

NASA Astrophysics Data System (ADS)

Elber Duverger, James; Boudreau-Béland, Jonathan; Le, Minh Duc; Comtois, Philippe

2014-11-01

Self-organization of pacemaker (PM) activity of interconnected elements is important to the general theory of reaction-diffusion systems as well as for applications such as PM activity in cardiac tissue to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes (NRVMs) are often used as experimental models in studies on cardiac electrophysiology. These monolayers exhibit automaticity (spontaneous activation) of their electrical activity. At low plated density, cells usually show a heterogeneous population consisting of PM and quiescent excitable cells (QECs). It is therefore highly probable that monolayers of NRVMs consist of a heterogeneous network of the two cell types. However, the effects of density and spatial distribution of the PM cells on spontaneous activity of monolayers remain unknown. Thus, a simple stochastic pattern formation algorithm was implemented to distribute PM and QECs in a binary-like 2D network. A FitzHugh-Nagumo excitable medium was used to simulate electrical spontaneous and propagating activity. Simulations showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of PM cells. In most simulations, the first initiation sites were found to be located near the substrate boundaries. Comparison with experimental data obtained from cardiomyocyte monolayers shows important similarities in the position of initiation site activity. However, limitations in the model that do not reflect the complex beat-to-beat variation found in experiments indicate the need for a more realistic cardiomyocyte representation.

Mesenteric Th1 polarization and monocyte TNF-alpha production: first steps to systemic inflammation in rats with cirrhosis.

PubMed

Muñoz, Leticia; Albillos, Agustín; Nieto, Mónica; Reyes, Eduardo; Lledó, Lourdes; Monserrat, Jorge; Sanz, Eva; de la Hera, Antonio; Alvarez-Mon, Melchor

2005-08-01

A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF-alpha) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis. We compared the activation status of immune cell subpopulations defined by 4-color cytometry in mesenteric and peripheral lymph nodes and blood of rats with CCl(4)-cirrhosis to define the immune response initiation site, the T-cell and monocyte contribution to pro-inflammatory cytokine production, as well as the pathogenic role of enteric bacteria in the cirrhosis immune response. Th1 cells and monocytes were expanded in the mesenteric nodes (P < .001) and blood (P < .001) of rats with cirrhosis, and activated to produce interferon gamma (P < .0001) and TNF-alpha (P < .0001), respectively. The greater numbers of recently activated CD134(+) Th cells in mesenteric nodes compared with blood, the correlation between their numbers in mesenteric nodes and blood (r = 0.66, P < .001), and the expansion of activated CD45RC(-) Th cells, which are unable to re-enter lymph nodes, in mesenteric nodes but not in blood or axillary nodes points to mesenteric nodes as the origin site of activated Th cells. Abrogation of bacterial translocation by bowel decontamination reduced the number of activated Th cells and monocytes, and normalized interferon gamma production by Th cells and TNF-alpha production by monocytes in mesenteric nodes and blood, respectively. In conclusion, in cirrhosis, enteric bacteria start off an orchestrated immune response cascade in mesenteric nodes involving Th1 polarization and monocyte activation to TNF-alpha production. Later, the recirculation of these activated effector immune cells into blood promotes systemic inflammation.

76 FR 64228 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-17

...: External Pacemaker Pulse Generator; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... entitled ``Class II Special Controls Guidance Document: External Pacemaker Pulse Generator.'' This draft guidance document describes a means by which external pacemaker pulse generators may comply with the...

Two hearts synchronized each other with a DDD pacemaker.

PubMed

Brunacci, Michele; Valbusa, Alberto; Brunelli, Claudio; Bertero, Giovanni

2016-12-01

: We describe the case of a patient with dyspnea and heterotopic cardiac transplant, ventricular fibrillation from the native heart and sinus rhythm from the transplanted one. The two hearts were synchronized with a pacemaker. Electric external cardioversion and a different type of pacemaker stimulation were successfully performed, with improving symptoms.

21 CFR 870.3710 - Pacemaker repair or replacement material.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker repair or replacement material. 870.3710 Section 870.3710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker...

Pacemaker failure associated with therapeutic radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brooks, C.; Mutter, M.

1988-11-01

A 48-year-old white man with a multiprogrammable Intramedics 259-01 pacemaker was treated for inoperable lung cancer with a course of cobalt-60 radiotherapy (total 3500 rad). Several weeks subsequent to his last radiation treatment, the patient presented to the emergency department with chest and abdominal pain, shortness of breath, hypotension, and tachycardia. A paced tachycardia was noted, and application of a magnet over the pacemaker completely inhibited its function, allowing a normal sinus rhythm to ensue and the patient's symptoms to be relieved. Pacemaker failure probably was a complication of radiotherapy.

The challenge of staphylococcal pacemaker endocarditis in a patient with transposition of the great arteries endocarditis in congenital heart disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ch'ng, Julie; Chan, William; Lee, Paul

2003-06-01

Staphylococcus aureus is a leading cause of septicaemia and infective endocarditis. The overall incidence of staphylococcal bacteraemia is increasing, contributing to 16% of all hospital-acquired bacteraemias. The use of cardiac pacemakers has revolutionized the management of rhythm disturbances, yet this has also resulted in a group of patients at risk of pacemaker lead endocarditis and seeding in the range of 1% to 7%. We describe a 26-year-old man with transposition of the great arteries who had a pacemaker implanted and presented with S. aureus septicaemia 2 years postpacemaker implantation and went on to develop pacemaker lead endocarditis. This report illustratesmore » the risk of endocarditis in the population with congenital heart disease and an intracardiac device.« less

Dual-chamber pacemakers for treating symptomatic bradycardia due to sick sinus syndrome without atrioventricular block: a systematic review and economic evaluation.

PubMed

Edwards, Steven J; Karner, Charlotta; Trevor, Nicola; Wakefield, Victoria; Salih, Fatima

2015-08-01

Bradycardia [resting heart rate below 60 beats per minute (b.p.m.)] can be caused by conditions affecting the natural pacemakers of the heart, such as sick sinus syndrome (SSS) and atrioventricular (AV) blocks. People suffering from bradycardia may present with palpitations, exercise intolerance and fainting. The only effective treatment for patients suffering from symptomatic bradycardia is implantation of a permanent pacemaker. To appraise the clinical effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber atrial pacemakers for treating symptomatic bradycardia in people with SSS and no evidence of AV block. All databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) were searched from inception to June 2014. A systematic review of the clinical and economic literature was carried out in accordance with the general principles published by the Centre for Reviews and Dissemination. Randomised controlled trials (RCTs) evaluating dual-chamber and single-chamber atrial pacemakers and economic evaluations were included. Pairwise meta-analysis was carried out. A de novo economic model was developed. Of 493 references, six RCTs were included in the review. The results were predominantly influenced by the largest trial DANPACE. Dual-chamber pacing was associated with a statistically significant reduction in reoperation [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.36 to 0.63] compared with single-chamber atrial pacing. The difference is primarily because of the development of AV block requiring upgrade to a dual-chamber device. The risk of paroxysmal atrial fibrillation was also reduced with dual-chamber pacing compared with single-chamber atrial pacing (OR 0.75, 95% CI 0.59 to 0.96). No statistically significant difference was found between the pacing modes for mortality, heart failure, stroke, chronic atrial fibrillation or quality of life. However, the risk of developing heart failure may vary with age and device. The de novo economic model shows that dual-chamber pacemakers are more expensive and more effective than single-chamber atrial devices, resulting in a base-case incremental cost-effectiveness ratio (ICER) of £6506. The ICER remains below £20,000 in probabilistic sensitivity analysis, structural sensitivity analysis and most scenario analyses and one-way sensitivity analyses. The risk of heart failure may have an impact on the decision to use dual-chamber or single-chamber atrial pacemakers. Results from an analysis based on age (> 75 years or ≤ 75 years) and risk of heart failure indicate that dual-chamber pacemakers dominate single-chamber atrial pacemakers (i.e. are less expensive and more effective) in older patients, whereas dual-chamber pacemakers are dominated by (i.e. more expensive and less effective) single-chamber atrial pacemakers in younger patients. However, these results are based on a subgroup analysis and should be treated with caution. In patients with SSS without evidence of impaired AV conduction, dual-chamber pacemakers appear to be cost-effective compared with single-chamber atrial pacemakers. The risk of developing a complete AV block and the lack of tools to identify patients at high risk of developing the condition argue for the implantation of a dual-chamber pacemaker programmed to minimise unnecessary ventricular pacing. However, considerations have to be made around the risk of developing heart failure, which may depend on age and device. This study is registered as PROSPERO CRD42013006708. The National Institute for Health Research Health Technology Assessment programme.

PRC2/EED-EZH2 Complex Is Up-Regulated in Breast Cancer Lymph Node Metastasis Compared to Primary Tumor and Correlates with Tumor Proliferation In Situ

PubMed Central

Yu, Hongxiang; Simons, Diana L.; Segall, Ilana; Carcamo-Cavazos, Valeria; Schwartz, Erich J.; Yan, Ning; Zuckerman, Neta S.; Dirbas, Frederick M.; Johnson, Denise L.; Holmes, Susan P.; Lee, Peter P.

2012-01-01

Background Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression. Methodology/Principal Findings We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors. Conclusions/Significance This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens up epigenetic drug development possibilities for the treatment and prevention of lymph node metastasis in breast cancer. PMID:23251464

[Sudden cardiac death due to sarcoidosis. Case report].

PubMed

Sejben, István; Som, Zoltán; Cserni, Gábor

2017-07-01

Sarcoidosis is a systemic granulomatous disease of unknown aetiology, which is characterized by bilateral hilar lymphadenopathy and pulmonary disease. Clinically detected cardiac involvement occurs in 5% of sarcoid patients, although cardiac manifestations are discovered in 25% of the cases at autopsy. Sarcoid heart disease frequently causes atrioventricular block. The authors present the case of a 44-year-old man with bradycardia. On admission, second degree Mobitz II, then third degree atrioventricular block was diagnosed. Coronarography showed normal coronary arteries. 2.5 years following artificial Biotronik Entovis DR type pacemaker implantation, sudden cardiac death occurred. Autopsy revealed sarcoidosis with cardiac, pulmonary, splenic, renal and lymph node involvement. In case of young or middle-aged patients with atrioventricular block, it is best to search for other causes if the most common coronary origin can be excluded. Orv Hetil. 2017; 158(27): 1067-1070.

Numeric pathologic lymph node classification shows prognostic superiority to topographic pN classification in esophageal squamous cell carcinoma.

PubMed

Sugawara, Kotaro; Yamashita, Hiroharu; Uemura, Yukari; Mitsui, Takashi; Yagi, Koichi; Nishida, Masato; Aikou, Susumu; Mori, Kazuhiko; Nomura, Sachiyo; Seto, Yasuyuki

2017-10-01

The current eighth tumor node metastasis lymph node category pathologic lymph node staging system for esophageal squamous cell carcinoma is based solely on the number of metastatic nodes and does not consider anatomic distribution. We aimed to assess the prognostic capability of the eighth tumor node metastasis pathologic lymph node staging system (numeric-based) compared with the 11th Japan Esophageal Society (topography-based) pathologic lymph node staging system in patients with esophageal squamous cell carcinoma. We retrospectively reviewed the clinical records of 289 patients with esophageal squamous cell carcinoma who underwent esophagectomy with extended lymph node dissection during the period from January 2006 through June 2016. We compared discrimination abilities for overall survival, recurrence-free survival, and cancer-specific survival between these 2 staging systems using C-statistics. The median number of dissected and metastatic nodes was 61 (25% to 75% quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3), respectively. The eighth tumor node metastasis pathologic lymph node staging system had a greater ability to accurately determine overall survival (C-statistics: tumor node metastasis classification, 0.69, 95% confidence interval, 0.62-0.76; Japan Esophageal Society classification; 0.65, 95% confidence interval, 0.58-0.71; P = .014) and cancer-specific survival (C-statistics: tumor node metastasis classification, 0.78, 95% confidence interval, 0.70-0.87; Japan Esophageal Society classification; 0.72, 95% confidence interval, 0.64-0.80; P = .018). Rates of total recurrence rose as the eighth tumor node metastasis pathologic lymph node stage increased, while stratification of patients according to the topography-based node classification system was not feasible. Numeric nodal staging is an essential tool for stratifying the oncologic outcomes of patients with esophageal squamous cell carcinoma even in the cohort in which adequate numbers of lymph nodes were harvested. Copyright © 2017 Elsevier Inc. All rights reserved.

Retrospective analysis of reasons for failure of DDD pacemaker implantation in patients operated on between 1993 and 2005.

PubMed

Lelakowski, Jacek; Majewski, Jacek; Małecka, Barbara; Bednarek, Jacek; Stypuła, Paweł; Szeglowski, Marcin

2007-01-01

During implantation of a DDD pacemaker the following difficulties may be encountered: venous anomalies (the absence of vessels of adequate calibre or difficulty in subclavian vein puncture), arrhythmias during implantation (episodes of atrial flutter/fibrillation while the atrial leads are being positioned), lack of mechanical stability of the electrode in the heart chamber and inability to achieve an acceptable pacing and sensing threshold during implantation. The purpose of the study was to analyse retrospectively the reasons for DDD pacemaker failure in patients operated on between 1993 and 2005. We reviewed retrospectively all implantation data from 1988 to 2005 to identify patients with primary failure of DDD pacemaker implantation. Further analysis included patients who had received a DDD pacemaker between 1993 and 2005, when this type of pacemaker made up between 9 and 40% of all pacemaker implantations. We implanted 7469 pacemakers, including 1958 (26.2%) dual-chamber pacemakers, in 783 patients with atrioventricular block (AVB), 392 with sick sinus syndrome (SSS), 450 with AVB +/- SSS and 333 with tachy-brady syndrome (TBS). The mean age of the patients was 65.5 +/- 17.3 years. DDD pacing was unsuccessful in 108 (1.4%) patients, including 32 with AVB, 22 with SSS, 16 with SSS +/- AVB and 38 with TBS. The mean age of these patients was 78.5 +/- 19.4 years. The reasons for failed implantation were venous anomalies in 12%, an arrhythmia episode in 27.8%, a high pacing threshold in the atrium in 17.6%, low atrial potential amplitude in 25.9% and lack of mechanical stability of the electrode in 16.7% of patients. The difficulties were encountered in elderly patients (p < 0.01), most frequently in patients with SSS and TBS (71). Between 2004 and 2005 venous anomalies and a high pacing threshold were the main causes of failure. Currently the main difficulties encountered during pacemaker implantation are venous anomalies and a high pacing threshold. Arrhythmia episodes, low atrial potential amplitude and lack of mechanical stability are of minor importance. Elderly patients with sick sinus syndrome and tachy-brady syndrome have the highest failure rate. (Cardiol J 2007; 14: 155-159).

Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior.

PubMed

Wang, Han; Girskis, Kelly; Janssen, Tom; Chan, Jason P; Dasgupta, Krishnakali; Knowles, James A; Schoofs, Liliane; Sieburth, Derek

2013-05-06

Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 s, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown. Here, we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G-protein-coupled receptor on the GABAergic neurons, as the receptor for NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo. Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Leadless Cardiac Pacemaker Implantation After Lead Extraction in Patients With Severe Device Infection.

PubMed

Kypta, Alexander; Blessberger, Hermann; Kammler, Juergen; Lambert, Thomas; Lichtenauer, Michael; Brandstaetter, Walter; Gabriel, Michael; Steinwender, Clemens

2016-09-01

Conventional pacemaker therapy is limited by short- and long-term complications, most notably device infection. Transcatheter pacing systems (TPS) may be beneficial in this kind of patients as they eliminate the need for a device pocket and leads and thus may reduce the risk of re-infection. We assessed a novel procedure in 6 patients with severe device infection who were pacemaker dependent. After lead extraction a single chamber TPS was implanted into the right ventricle. Of the 6 patients who underwent lead extraction due to severe device infection at our institution, 3 were diagnosed with a pocket infection only, whereas the other 3 showed symptoms of both pocket and lead infection. Successful lead extraction and TPS implantation was accomplished in all patients. Four patients were bridged with a temporary pacemaker between 2 hours and 2 days after lead extraction, whereas 2 patients had the TPS implanted during the same procedure just before traditional pacemaker system removal. All patients stayed free of infection during the follow-up period of 12 weeks. An additional positron emission tomography scan was performed in each patient and indicated no signs of an infection around the TPS. Transcather pacemaker implantation was safe and feasible in 6 patients and did not result in re-infection even if implanted before removal of the infected pacemaker system within the same procedure. Therefore, implantation of a TPS may be an option for patients with severe device infection, especially in those with blocked venous access or who are pacemaker dependent. © 2016 Wiley Periodicals, Inc.

Evaluation of Death among the Patients Undergoing Permanent Pacemaker Implantation: A Competing Risks Analysis

PubMed Central

GHAEM, Haleh; GHORBANI, Mohammad; ZARE DORNIANI, Samira

2017-01-01

Background: Permanent artificial pacemaker is one of the important therapies for treatment of cardiac conduction system problems. The present study aimed to determine the association between some predictive variables and all-cause and cause-specific mortality in the patients who had undergone pacemaker implantation. Methods: This study was conducted on 1207 patients who had undergone permanent pacemaker implantation in the hospitals affiliated with Shiraz University of Medical Sciences, Iran, from Mar 2002 to Mar 2012. The variables that existed in the patients’ medical records included sex, diabetes mellitus, obesity, cerebrovascular accident, cardiomegaly, smoking, hypertension, ischemic heart disease, congenital heart disease, sick sinus syndrome, and atrial fibrillation. Competing risks model was used to assess the association between the predictive variables and cause-specific (i.e., cardiac and vascular) mortality. Results: The patients’ mean age was 66.32±17.92 yr (70.62±14.45 yr in the patients with single-chamber pacemakers vs. 61.91±17.69 yr in those with two-chamber pacemakers) (P<0.001). Sick sinus syndrome and age increased the risk of all-cause mortality, while two-chamber pacemaker decreased this risk. Obesity increased the risk of cardiac death, and diabetes mellitus and heart valve disease increased the risk of vascular death. Conclusion: The variables predicting mortality in all-cause model were completely different from those in cause-specific model. Moreover, death in such patients may occur due to reasons other than pacemaker. Therefore, future studies, particularly prospective ones, are recommended to use competing risks models. PMID:28828325

SU-E-T-585: Optically-Stimulated Luminescent Dosimeters for Monitoring Pacemaker Dose in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Apicello, L; Riegel, A; Jamshidi, A

2015-06-15

Purpose: A sufficient amount of ionizing radiation can cause failure to components of pacemakers. Studies have shown that permanent damage can occur after a dose of 10 Gy and minor damage to functionality occurs at doses as low as 2 Gy. Optically stimulated thermoluminescent dosimeters (OSLDs) can be used as in vivo dosimeters to predict dose to be deposited throughout the treatment. The purpose of this work is to determine the effectiveness of using OSLDs for in vivo dosimetry of pacemaker dose. Methods: As part of a clinical in vivo dosimetry experience, OSLDs were placed at the site of themore » pacemaker by the therapist for one fraction of the radiation treatment. OSLD measurements were extrapolated to the total dose to be received by the pacemaker during treatment. A total of 79 measurements were collected from November 2011 to December 2013 on six linacs. Sixty-six (66) patients treated in various anatomical sites had the dose of their pacemakers monitored. Results: Of the 79 measurements recorded, 76 measurements (96 %) were below 2 Gy. The mean and standard deviation were 50.12 ± 76.41 cGy. Of the 3 measurements that exceeded 2 Gy, 2 measurements matched the dose predicted in the treatment plan and 1 was repeated after an unexpectedly high Result. The repeated measurement yielded a total dose less than 2 Gy. Conclusion: This analysis suggests OSLDs may be used for in vivo monitoring of pacemaker dose. Further research should be performed to assess the effect of increased backscatter from the pacemaker device.« less

Pacemaker failure resulting from radiation damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quertermous, T.; Megahy, M.S.; Das Gupta, D.S.

1983-07-01

The authors present a case of radiation-induced pacemaker failure. After 2000 rad (20 Gy) of photon irradiation for metastatic bronchogenic carcinoma, the pulse generator circuitry failed, producing a runaway rhythm. This suggests that present pacemaker circuitry may be more susceptible to irradiation than previously believed, and that even modest radiation doses can induce life-threatening arrhythmias.

Trypanosoma congolense: tissue distribution of long-term T- and B-cell responses in cattle.

PubMed

Lutje, V; Taylor, K A; Boulangé, A; Authié, E

1995-11-01

Memory T- and B-cell responses to trypanosome antigens were measured in peripheral blood mononuclear cells, spleen and lymph node cells obtained from four trypanotolerant N'Dama cattle which had been exposed to six experimental infections with Trypanosoma congolense. These cattle were treated with trypanocidal drugs following each infection and had remained aparasitemic for 3 years prior to this study. The antigens used were whole trypanosome lysate, variable surface glycoprotein, a 33-kDa cysteine protease (congopain) and a 70-kDa heat-shock protein. As parameters of T-cell-mediated immunity, we measured T-cell proliferation and IFN-gamma production. Lymph node cells, spleen cells and peripheral blood mononuclear cells all proliferated to a mitogenic stimulus (concanavalin A) but only lymph node cells responded to trypanosome antigens. Similarly, IFN-gamma was produced by both lymph node and spleen cells stimulated with concanavalin A but only by lymph node cells stimulated with variable surface glycoprotein and whole trypanosome lysate. T. congolense-specific antibodies were detected in sera and in supernatants of cultured lymph node and spleen cells after in vitro stimulation with lipopolysaccharide and recombinant bovine interleukin-2. In conclusion, we have demonstrated that memory T- and B-cell responses are detectable in various lymphoid organs in cattle 3 years following infection and treatment with T. congolense.

Dendritic cells control fibroblastic reticular network tension and lymph node expansion.

PubMed

Acton, Sophie E; Farrugia, Aaron J; Astarita, Jillian L; Mourão-Sá, Diego; Jenkins, Robert P; Nye, Emma; Hooper, Steven; van Blijswijk, Janneke; Rogers, Neil C; Snelgrove, Kathryn J; Rosewell, Ian; Moita, Luis F; Stamp, Gordon; Turley, Shannon J; Sahai, Erik; Reis e Sousa, Caetano

2014-10-23

After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion. Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion--driven by lymphocyte influx and proliferation--that is the critical hallmark of adaptive immunity.

Ethics and the cardiac pacemaker: more than just end-of-life issues.

PubMed

Hutchison, Katrina; Sparrow, Robert

2018-05-01

For many years, ethical debate about pacemakers has focused on whether and under what circumstances they may be turned off in end of life care. Several other important ethical issues have been neglected, perhaps because the dilemmas they pose for cardiologists are not so immediate. These include: potential conflicts of interest, particularly those arising from the role of industry employed allied professionals (IEAPs) in pacemaker care; unanticipated impacts of commercial competition and the device improvement cycle; risks associated with remotely accessible software; equity in access to healthcare; and questions about reuse of explanted pacemakers in low and middle income countries. This paper analyses these issues in order to facilitate a more comprehensive approach to ethics and the cardiac pacemaker. Cardiologists should be aware of all of these issues and contribute to ongoing discussions about how they are resolved.

Quantitative analysis of circadian single cell oscillations in response to temperature

PubMed Central

Kramer, Achim; Herzel, Hanspeter

2018-01-01

Body temperature rhythms synchronize circadian oscillations in different tissues, depending on the degree of cellular coupling: the responsiveness to temperature is higher when single circadian oscillators are uncoupled. So far, the role of coupling in temperature responsiveness has only been studied in organotypic tissue slices of the central circadian pacemaker, because it has been assumed that peripheral target organs behave like uncoupled multicellular oscillators. Since recent studies indicate that some peripheral tissues may exhibit cellular coupling as well, we asked whether peripheral network dynamics also influence temperature responsiveness. Using a novel technique for long-term, high-resolution bioluminescence imaging of primary cultured cells, exposed to repeated temperature cycles, we were able to quantitatively measure period, phase, and amplitude of central (suprachiasmatic nuclei neuron dispersals) and peripheral (mouse ear fibroblasts) single cell oscillations in response to temperature. Employing temperature cycles of different lengths, and different cell densities, we found that some circadian characteristics appear cell-autonomous, e.g. period responses, while others seem to depend on the quality/degree of cellular communication, e.g. phase relationships, robustness of the oscillation, and amplitude. Overall, our findings indicate a strong dependence on the cell’s ability for intercellular communication, which is not only true for neuronal pacemakers, but, importantly, also for cells in peripheral tissues. Hence, they stress the importance of comparative studies that evaluate the degree of coupling in a given tissue, before it may be used effectively as a target for meaningful circadian manipulation. PMID:29293562

Energy harvesting by implantable abiotically catalyzed glucose fuel cells

NASA Astrophysics Data System (ADS)

Kerzenmacher, S.; Ducrée, J.; Zengerle, R.; von Stetten, F.

Implantable glucose fuel cells are a promising approach to realize an autonomous energy supply for medical implants that solely relies on the electrochemical reaction of oxygen and glucose. Key advantage over conventional batteries is the abundant availability of both reactants in body fluids, rendering the need for regular replacement or external recharging mechanisms obsolete. Implantable glucose fuel cells, based on abiotic catalysts such as noble metals and activated carbon, have already been developed as power supply for cardiac pacemakers in the late-1960s. Whereas, in vitro and preliminary in vivo studies demonstrated their long-term stability, the performance of these fuel cells is limited to the μW-range. Consequently, no further developments have been reported since high-capacity lithium iodine batteries for cardiac pacemakers became available in the mid-1970s. In recent years research has been focused on enzymatically catalyzed glucose fuel cells. They offer higher power densities than their abiotically catalyzed counterparts, but the limited enzyme stability impedes long-term application. In this context, the trend towards increasingly energy-efficient low power MEMS (micro-electro-mechanical systems) implants has revived the interest in abiotic catalysts as a long-term stable alternative. This review covers the state-of-the-art in implantable abiotically catalyzed glucose fuel cells and their development since the 1960s. Different embodiment concepts are presented and the historical achievements of academic and industrial research groups are critically reviewed. Special regard is given to the applicability of the concept as sustainable micro-power generator for implantable devices.

Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

PubMed Central

Cele, Sandile; Ferreira, Isabella Markham; Young, Andrew C; Karim, Farina; Madansein, Rajhmun; Dullabh, Kaylesh J; Chen, Chih-Yuan; Buckels, Noel J; Ganga, Yashica; Khan, Khadija; Boulle, Mikael; Lustig, Gila; Neher, Richard A

2018-01-01

HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high. PMID:29555018

Transfer of space technology to industry

NASA Technical Reports Server (NTRS)

Hamilton, J. T.

1974-01-01

Some of the most significant applications of the NASA aerospace technology transfer to industry and other government agencies are briefly outlined. The technology utilization program encompasses computer programs for structural problems, life support systems, fuel cell development, and rechargeable cardiac pacemakers as well as reliability and quality research for oil recovery operations and pollution control.

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, J; Chung, J

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designedmore » for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.« less

Management and outcome of topical beta-blockerinduced atrioventricular block

PubMed Central

Özcan, Kazım Serhan; Güngör, Barış; Tekkeşin, Ahmet İlker; Altay, Servet; Ekmekçi, Ahmet; Toprak, Ercan; Yıldırım, Ersin; Çalık, Nazmi; Alper, Ahmet Taha; Gürkan, Kadir; Erdinler, İzzet; Osmonov, Damirbek

2015-01-01

Summary Background Topical beta-blockers have a well-established role in the treatment of glaucoma. We aimed to investigate the outcome of patients who developed symptomatic atrioventricular (AV) block induced by topical beta-blockers. Methods All patients admitted or discharged from our institution, the Siyami Ersek Training and Research Hospital, between January 2009 and January 2013 with a diagnosis of AV block were included in the study. Subjects using ophthalmic beta-blockers were recruited and followed for permanent pacemaker requirement during hospitalisation and for three months after discontinuation of the drug. A permanent pacemaker was implanted in patients in whom AV block persisted beyond 72 hours or recurred during the follow-up period. Results A total of 1 122 patients were hospitalised with a diagnosis of AV block and a permanent pacemaker was implanted in 946 cases (84.3%) during the study period. Thirteen patients using ophthalmic beta-blockers for the treatment of glaucoma and no other rate-limiting drugs were included in the study. On electrocardiography, eight patients had complete AV block and five had high-degree AV block. The ophthalmic beta-blockers used were timolol in seven patients (55%), betaxolol in four (30%), and cartelol in two cases (15%). The mean duration of ophthalmic beta-blocker treatment was 30.1 ± 15.9 months. After drug discontinuation, in 10 patients the block persisted and a permanent pacemaker was implanted. During follow up, one more patient required pacemaker implantation. Therefore in total, pacemakers were implanted in 11 out of 13 patients (84.6%). The pacemaker implantation rate did not differ according to the type of topical beta-blocker used (p = 0.37). The presence of infra-nodal block on electrocardiography was associated with higher rates of pacemaker implantation. Conclusion Our results indicate that topical beta-blockers for the treatment of glaucoma may cause severe conduction abnormalities and when AV block occurs, pacemaker implantation is required in a high percentage of the patients. PMID:26659434

The association of exosomes with lymph nodes.

PubMed

Hood, Joshua L

2017-07-01

Cells produce extracellular nanovesicles known as exosomes that transport information between tissue microenvironments. Exosomes can engage and regulate the function of various immune cell types facilitating both normal and pathological processes. It follows that exosomes should also associate with lymph nodes containing immune cells. Herein, data derived from investigations that incorporate experiments pertaining to the trafficking of exosomes to lymph nodes is reviewed. Within lymph nodes, direct evidence demonstrates that exosomes associate with dendritic cells, subcapsular sinus macrophages, B lymphocytes and stromal cells. Interactions with endothelial cells are also likely. The functional significance of these associations depends on exosome type. Continued investigations into the relationship between exosomes and lymph nodes will further our understanding of how exosomes regulate immune cells subsets and may serve to inspire new exosome based therapeutics to treat a variety of diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice.

PubMed

Poetschke, Christina; Dragicevic, Elena; Duda, Johanna; Benkert, Julia; Dougalis, Antonios; DeZio, Roberta; Snutch, Terrance P; Striessnig, Joerg; Liss, Birgit

2015-09-18

The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson's disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca(2+) burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary for SN DA pacemaker-activity at either age, but rather contributed to their pacemaker-precision. Moreover, juvenile Cav1.3 KO but not WT mice displayed adult wildtype-like, sensitised inhibitory dopamine-D2-autoreceptor (D2-AR) responses that depended upon both, interaction of the neuronal calcium sensor NCS-1 with D2-ARs, and on voltage-gated T-type calcium channel (TTCC) activity. This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age-dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L-type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age- and calcium-dependent activity-control of SN DA neurons and its pharmacological modulation.

Coupling mechanism in the gate and oscillator model of the SCN

NASA Astrophysics Data System (ADS)

Li, Ying; Liu, Zengrong

2016-09-01

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is considered as the master circadian pacemaker. The SCN is divided into two subgroups of gate and oscillator cells: the ventrolateral (VL) neurons, which receive the periodic light-dark (LD) signal, and the dorsomedial (DM) neurons, which are coupled to the VL cells. The fundamental question is how the individual cellular oscillators, expressing a wide range of periods, interact and assemble to create an integrated pacemaker that can govern behavioral and physiological rhythmicity and be reset by environmental light. The key is that the heterogeneous network formed by the cellular clocks within the SCN must synchronize to maintain timekeeping activity. Based on the structural and functional heterogeneity of the SCN, the authors bring forward a mathematical model including gate cells and oscillator cells with a wide range of periods. The gate neurons offer daily injection to oscillator neurons and the activation of gate is determined by the output of the oscillator neurons. In this model, the authors consider two kinds of coupling: interior coupling among the oscillator cells and exterior coupling from the gate cells to the oscillator cells. The authors mainly analyze the combined effects of these two kinds of coupling on the entrainment of the oscillator cells in the DM part. It is found that the interior coupling is conducive to entrainment, but a stronger coupling is not beneficial to entrainment. The gate mechanism in exterior coupling is more propitious to entrainment than continuous coupling. This study helps to understand collective circadian rhythm in the mammals.

Acute pericarditis with cardiac tamponade induced by pacemaker implantation.

PubMed

Shingaki, Masami; Kobayashi, Yutaka; Suzuki, Haruo

2015-11-01

An 87-year-old woman was diagnosed with third-degree atrioventricular block and underwent pacemaker implantation. On postoperative day 12, she experienced cardiac tamponade that was suspected on computed tomography to be caused by lead perforation; therefore, we performed open-heart surgery. However, we could not identify a perforation site on the heart, and drained a 400-mL exudative pericardial effusion. Subsequently, we diagnosed the pericardial effusion as due to pericarditis induced by pacemaker implantation. It is sometimes difficult to distinguish pericarditis from pacemaker lead perforation, so both should be included in the differential diagnosis. © The Author(s) 2014.

Nonlinear oscillations in a muscle pacemaker cell model

NASA Astrophysics Data System (ADS)

González-Miranda, J. M.

2017-02-01

This article presents a numerical simulation study of the nonlinear oscillations displayed by the Morris-Lecar model [Biophys. J. 35 (1981) 193] for the oscillations experimentally observed in the transmembrane potential of a muscle fiber subject to an external electrical stimulus. We consider the model in the case when there is no external stimulation, aiming to establish the ability of the model to display biophysically reasonable pacemaker dynamics. We obtain 2D bifurcation diagrams showing that indeed the model presents oscillatory dynamics, displaying the two main types of action potentials that are observed in muscle fibers. The results obtained are shown to be structurally stable; that is, robust against changes in the values of system parameters. Moreover, it is demonstrated how the model is appropriate to analyze the action potentials observed in terms of the transmembrane currents creating them.

Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis

PubMed Central

Wittmeier, Steffen; Song, Gang; Duffin, James; Poon, Chi-Sang

2008-01-01

Inspiratory and expiratory rhythms in mammals are thought to be generated by pacemaker-like neurons in 2 discrete brainstem regions: pre-Bötzinger complex (preBötC) and parafacial respiratory group (pFRG). How these putative pacemakers or pacemaker networks may interact to set the overall respiratory rhythm in synchrony remains unclear. Here, we show that a pacemakers 2-way “handshake” process comprising pFRG excitation of the preBötC, followed by reverse inhibition and postinhibitory rebound (PIR) excitation of the pFRG and postinspiratory feedback inhibition of the preBötC, can provide a phase-locked mechanism that sequentially resets and, hence, synchronizes the inspiratory and expiratory rhythms in neonates. The order of this handshake sequence and its progression vary depending on the relative excitabilities of the preBötC vs. the pFRG and resultant modulations of the PIR in various excited and depressed states, leading to complex inspiratory and expiratory phase-resetting behaviors in neonates and adults. This parsimonious model of pacemakers synchronization and mutual entrainment replicates key experimental data in vitro and in vivo that delineate the developmental changes in respiratory rhythm from neonates to maturity, elucidating their underlying mechanisms and suggesting hypotheses for further experimental testing. Such a pacemakers handshake process with conjugate excitation–inhibition and PIR provides a reinforcing and evolutionarily advantageous fail-safe mechanism for respiratory rhythmogenesis in mammals. PMID:19008356

Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act

PubMed Central

Tucker, Kristal R.; Huertas, Marco A.; Horn, John P.; Canavier, Carmen C.; Levitan, Edwin S.

2012-01-01

Midbrain dopamine (DA) neurons are slow intrinsic pacemakers that undergo depolarization (DP) block upon moderate stimulation. Understanding DP block is important because it has been correlated with the clinical efficacy of chronic antipsychotic drug treatment. Here we describe how voltage-gated sodium (NaV) channels regulate DP block and pacemaker activity in DA neurons of the substantia nigra using rat brain slices. The distribution, density and gating of NaV currents were manipulated by blocking native channels with tetrodotoxin and by creating virtual channels and anti-channels with dynamic clamp. Although action potentials initiate in the axon initial segment (AIS) and NaV channels are distributed in multiple dendrites, selective reduction of NaV channel activity in the soma was sufficient to decrease pacemaker frequency and increase susceptibility to DP block. Conversely, increasing somatic NaV current density raised pacemaker frequency and lowered susceptibility to DP block. Finally, when NaV currents were restricted to the soma, pacemaker activity occurred at abnormally high rates due to excessive local subthreshold NaV current. Together with computational simulations, these data show that both the slow pacemaker rate and the sensitivity to DP block that characterizes DA neurons result from the low density of somatic NaV channels. More generally, we conclude that the somatodendritic distribution of NaV channels is a major determinant of repetitive spiking frequency. PMID:23077037

Adaptations in Locus Coeruleus Induced by Post-Traumatic Stress Disorder

DTIC Science & Technology

2013-11-01

optogenetics, channelrhodopsin-2, fear conditioning, pacemaking , calcium, synaptic plasticity, corticotropin-releasing factor (CRF), endoplasmic...neurons revealed tonic, pacemaking activity was accompanied by an underlying membrane potential oscillation that was sensitive to the dihydropyridine...prominent, opening of these channels was not necessary to sustain normal pacemaking at rest. However, these channels help support LC spiking during

CD40L+ CD4+ memory T cells migrate in a CD62P-dependent fashion into reactive lymph nodes and license dendritic cells for T cell priming

PubMed Central

Martín-Fontecha, Alfonso; Baumjohann, Dirk; Guarda, Greta; Reboldi, Andrea; Hons, Miroslav; Lanzavecchia, Antonio; Sallusto, Federica

2008-01-01

There is growing evidence that the maturation state of dendritic cells (DCs) is a critical parameter determining the balance between tolerance and immunity. We report that mouse CD4+ effector memory T (TEM) cells, but not naive or central memory T cells, constitutively expressed CD40L at levels sufficient to induce DC maturation in vitro and in vivo in the absence of antigenic stimulation. CD4+ TEM cells were excluded from resting lymph nodes but migrated in a CD62P-dependent fashion into reactive lymph nodes that were induced to express CD62P, in a transient or sustained fashion, on high endothelial venules. Trafficking of CD4+ TEM cells into chronic reactive lymph nodes maintained resident DCs in a mature state and promoted naive T cell responses and experimental autoimmune encephalomyelitis (EAE) to antigens administered in the absence of adjuvants. Antibodies to CD62P, which blocked CD4+ TEM cell migration into reactive lymph nodes, inhibited DC maturation, T cell priming, and induction of EAE. These results show that TEM cells can behave as endogenous adjuvants and suggest a mechanistic link between lymphocyte traffic in lymph nodes and induction of autoimmunity. PMID:18838544

Lymph nodes

MedlinePlus Videos and Cool Tools

... and conveying lymph and by producing various blood cells. Lymph nodes play an important part in the ... the microorganisms being trapped inside collections of lymph cells or nodes. Eventually, these organisms are destroyed and ...

Analysis of interphase node proteins in fission yeast by quantitative and superresolution fluorescence microscopy

PubMed Central

Akamatsu, Matthew; Lin, Yu; Bewersdorf, Joerg; Pollard, Thomas D.

2017-01-01

We used quantitative confocal microscopy and FPALM superresolution microscopy of live fission yeast to investigate the structures and assembly of two types of interphase nodes—multiprotein complexes associated with the plasma membrane that merge together and mature into the precursors of the cytokinetic contractile ring. During the long G2 phase of the cell cycle, seven different interphase node proteins maintain constant concentrations as they accumulate in proportion to cell volume. During mitosis, the total numbers of type 1 node proteins (cell cycle kinases Cdr1p, Cdr2p, Wee1p, and anillin Mid1p) are constant even when the nodes disassemble. Quantitative measurements provide strong evidence that both types of nodes have defined sizes and numbers of constituent proteins, as observed for cytokinesis nodes. Type 1 nodes assemble in two phases—a burst at the end of mitosis, followed by steady increase during interphase to double the initial number. Type 2 nodes containing Blt1p, Rho-GEF Gef2p, and kinesin Klp8p remain intact throughout the cell cycle and are constituents of the contractile ring. They are released from the contractile ring as it disassembles and then associate with type 1 nodes around the equator of the cell during interphase. PMID:28539404

How smart should pacemakers Be?

PubMed

Saoudi, N; Appl, U; Anselme, F; Voglimacci, M; Cribier, A

1999-03-11

The concept of the "smart" pacemaker has been continuously changing during 40 years of progress in technology. When we talk today about smart pacemakers, it means optimal treatment, diagnosis, and follow-up for patients fitting the current indications for pacemakers. So what is smart today becomes accepted as "state of the art" tomorrow. Originally, implantable pacemakers were developed to save lives from prolonged episodes of bradycardia and/or complete heart block. Now, in addition, they improve quality of life via numerous different functions acting under specific conditions, thanks to the introduction of microprocessors. The devices have become smaller, with the miniaturization of the electrical components, without compromising longevity. Nevertheless, there are still some unmatched objectives for these devices, for example, the optimization of cardiac output and the management of atrial arrhythmias in dual-chamber devices. Furthermore, indications continue to evolve, which in turn require new, additional functions. These functions are often very complex, necessitating computerized programming to simplify application. In addition, the follow-up of these devices is time-consuming, as appropriate system performance has to be regularly monitored. A great many of these functions could be automatically performed and documented, thus enabling physicians and paramedical staff to avoid losing time with routine control procedures. In addition, modern pacemakers offer extensive diagnostic functions to help diagnose patient symptoms and pacemaker system problems. Different types of data are available, and their presentation differs from one company to the other. This huge amount of data can only be managed with automatic diagnostic functions. Thus, the smart pacemaker of the near future should offer high flexibility to permit easy programming of available therapies and follow-up, and extensive, easily comprehensible diagnostic functions.

The rationale and design of the Micra Transcatheter Pacing Study: safety and efficacy of a novel miniaturized pacemaker.

PubMed

Ritter, Philippe; Duray, Gabor Z; Zhang, Shu; Narasimhan, Calambur; Soejima, Kyoko; Omar, Razali; Laager, Verla; Stromberg, Kurt; Williams, Eric; Reynolds, Dwight

2015-05-01

Recent advances in miniaturization technologies and battery chemistries have made it possible to develop a pacemaker small enough to implant within the heart while still aiming to provide similar battery longevity to conventional pacemakers. The Micra Transcatheter Pacing System is a miniaturized single-chamber pacemaker system that is delivered via catheter through the femoral vein. The pacemaker is implanted directly inside the right ventricle of the heart, eliminating the need for a device pocket and insertion of a pacing lead, thereby potentially avoiding some of the complications associated with traditional pacing systems. The Micra Transcatheter Pacing Study is currently undergoing evaluation in a prospective, multi-site, single-arm study. Approximately 720 patients will be implanted at up to 70 centres around the world. The study is designed to have a continuously growing body of evidence and data analyses are planned at various time points. The primary safety and efficacy objectives at 6-month post-implant are to demonstrate that (i) the percentage of Micra patients free from major complications related to the Micra system or implant procedure is significantly higher than 83% and (ii) the percentage of Micra patients with both low and stable thresholds is significantly higher than 80%. The safety performance benchmark is based on a reference dataset of 977 subjects from 6 recent pacemaker studies. The Micra Transcatheter Pacing Study will assess the safety and efficacy of a miniaturized, totally endocardial pacemaker in patients with an indication for implantation of a single-chamber ventricular pacemaker. NCT02004873. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Case study thoracic radiotherapy in an elderly patient with pacemaker: The issue of pacing leads

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirova, Youlia M., E-mail: youlia.kirova@curie.net; Menard, Jean; Chargari, Cyrus

2012-07-01

To assess clinical outcome of patients with pacemaker treated with thoracic radiation therapy for T8-T9 paravertebral chloroma. A 92-year-old male patient with chloroma presenting as paravertebral painful and compressive (T8-T9) mass was referred for radiotherapy in the Department of Radiation Oncology, Institut Curie. The patient presented with cardiac dysfunction and a permanent pacemaker that had been implanted prior. The decision of Multidisciplinary Meeting was to deliver 30 Gy in 10 fractions for reducing the symptoms and controlling the tumor growth. The patient received a total dose of 30 Gy in 10 fractions using 4-field conformal radiotherapy with 20-MV photons. Themore » dose to pacemaker was 0.1 Gy but a part of the pacing leads was in the irradiation fields. The patient was treated the first time in the presence of his radiation oncologist and an intensive care unit doctor. Moreover, the function of his pacemaker was monitored during the entire radiotherapy course. No change in pacemaker function was observed during any of the radiotherapy fractions. The radiotherapy was very well tolerated without any side effects. The function of the pacemaker was checked before and after the radiotherapy treatment by the cardiologist and no pacemaker dysfunction was observed. Although updated guidelines are needed with acceptable dose criteria for implantable cardiac devices, it is possible to treat patients with these devices and parts encroaching on the radiation field. This case report shows we were able to safely treat our patient through a multidisciplinary approach, monitoring the patient during each step of the treatment.« less

Long-Term Mortality Effect of Early Pacemaker Implantation After Surgical Aortic Valve Replacement.

PubMed

Greason, Kevin L; Lahr, Brian D; Stulak, John M; Cha, Yong-Mei; Rea, Robert F; Schaff, Hartzell V; Dearani, Joseph A

2017-10-01

The need for pacemaker implantation is a well-described complication of aortic valve replacement. Not so well described is the effect such an event has on long-term outcome. This study reviewed a 21-year experience at the Mayo Clinic (Rochester, Minnesota) with aortic valve replacement to understand the influence of early postoperative pacemaker implantation on long-term mortality rates more clearly. This study retrospectively reviewed the records of 5,842 patients without previous pacemaker implantation who underwent surgical aortic valve replacement from January 1993 through June 2014. The median age of these patients was 73 years (range, 65 to 79 years), the median ejection fraction was 62% (range, 53% to 68%), 3,853 patients were male (66%), and coronary artery bypass graft operation was performed in 2,553 (44%) of the patients studied. Early pacemaker implantation occurred in 146 patients (2.5%) within 30 days of surgical aortic valve replacement. The median follow-up of patients was 11.1 years (range, 5.8 to 16.5 years), and all-cause mortality rates were 2.4% at 30 days, 6.4% at 1 year, 23.1% at 5 years, 48.3% at 10 years, and 67.9% at 15 years postoperatively. Early pacemaker implantation was associated with an increased risk of death after multivariable adjustment for baseline patients' characteristics (hazard ratio, 1.49; 95% confidence interval, 1.20, 1.84; p < 0.001). Early pacemaker implantation as a complication of surgical aortic valve replacement is associated with an increased risk of long-term death. Valve replacement-related pacemaker implantation rates should be important considerations with respect to new valve replacement paradigms, especially in younger and lower-risk patients. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Aggregatibacter aphrophilus pacemaker endocarditis: a case report.

PubMed

Patel, Sahil R; Patel, Nishi H; Borah, Amit; Saltzman, Heath

2014-12-08

Aggregatibacter bacteria are a rare cause of endocarditis in adults. They are part of a group of organisms known as HACEK--Haemophilus, Aggregatibacter, Cardiobacter, Eikenella, and Kingella. Among these organisms, several Haemophilus species have been reclassified under the genus Aggregatibacter. Very few cases of Aggregatibacter endocarditis in patients with pacemaker devices have been reported. We present here what we believe to be the first case of Aggregatibacter aphrophilus pacemaker endocarditis. A 62-year-old African American male with a medical history significant for dual-chamber pacemaker placement in 1996 for complete heart block with subsequent lead manipulation in 2007, presented to his primary care doctor with fever, chills, night sweats, fatigue, and ten-pound weight loss over a four-month period. Physical examination revealed a new murmur and jugular venous distension which prompted initiation of antibiotics for suspicion of endocarditis. Both sets of initial blood cultures were positive for A. aphrophilus. Transesophageal echocardiogram revealed vegetations on the tricuspid valve and the right ventricular pacemaker lead (Figure 1). This case highlights the importance of identifying rare causes of endocarditis and recognizing that treatment may not differ from the standard treatment for typical presentations. The patient received intravenous ceftriaxone for his endocarditis for a total of six weeks. Upon device removal, temporary jugular venous pacing wires were placed. After two weeks of antibiotic treatment and no clinical deterioration, a new permanent pacemaker was placed and the patient was discharged home. This is the first case of A. aphrophilus endocarditis in a patient with a permanent pacemaker. Our patient had no obvious risk factors other than poor dentition and a history of repeated pacemaker lead manipulation. This suggests that valvulopathies secondary to repeated lead manipulation can be clinically significant factors in morbidity and mortality in this patient population.

Late Outcome and Predictors of Adverse Events Related to the Implantation of a Permanent Pacemaker in Patients with Isolated Congenital Atrioventricular Block.

PubMed

de Oliveira, Grasiele Bess; de Oliveira, Fábio Silveira; Osório, Ana Paula Susin; Medeiros, Alexandre Kreling; Sant'anna, João Ricardo Michielin; Leiria, Tiago Luiz Luz

2016-10-01

Isolated congenital atrioventricular block (ICAVB) is a rare, and pacemaker implantation is the only effective treatment. We sought to identify the predictive factors of adverse events related to pacemaker implantation in ICAVB. This is a cohort study of patients diagnosed with ICAVB who underwent pacemaker implantation from 1980 to 2014 in a single center. During the studied period, a total of 647 patients underwent implantation of their first permanent cardiac pacemaker before 30 years of age. Of these, only 62 (9.5 %) were diagnosed with ICAVB. This condition was diagnosed in utero in 15 (24.2 %) cases, 5 (8.1 %) in the neonatal period, 32 (51.6 %) during childhood, and 10 (16.1 %) during adolescence and young adulthood. The presence of autoantibodies (anti-Ro/SSA) was observed in 41 % of mothers who underwent serological evaluation. Age at the time of the initial pacemaker implant was 9.8 ± 9 years. During a mean follow-up time of 15 years, 1 (1.7 %) death occurred due to infectious endocarditis. Complications related to pacemaker implant were reported in 24 patients (38.7 %). The number of complications was significantly higher in the group with an epimyocardial implantation site (HR 6; CI 2.45-14.95). Ventricular dysfunction occurred in 6 (11.7 %) patients; however, we were not able to identify any predictors of it. Our results showed a low mortality rate after permanent therapy. However, these patients exhibited high morbidity related to the pacemaker system, and the epimyocardial implant site was an independent predictor of complications. Predictors of left ventricular dysfunction were not found in the present study.

Clinical benefits of remote versus transtelephonic monitoring of implanted pacemakers.

PubMed

Crossley, George H; Chen, Jane; Choucair, Wassim; Cohen, Todd J; Gohn, Douglas C; Johnson, W Ben; Kennedy, Eleanor E; Mongeon, Luc R; Serwer, Gerald A; Qiao, Hongyan; Wilkoff, Bruce L

2009-11-24

The purpose of this study was to evaluate remote pacemaker interrogation for the earlier diagnosis of clinically actionable events compared with traditional transtelephonic monitoring and routine in-person evaluation. Pacemaker patient follow-up procedures have evolved from evaluating devices with little programmability and diagnostic information solely in person to transtelephonic rhythm strip recordings that allow monitoring of basic device function. More recently developed remote monitoring technology leverages expanded device capabilities, augmenting traditional transtelephonic monitoring to evaluate patients via full device interrogation. The time to first diagnosis of a clinically actionable event was compared in patients who were followed by remote interrogation (Remote) and those who were followed per standard of care with office visits augmented by transtelephonic monitoring (Control). Patients were randomized 2:1. Remote arm patients transmitted pacemaker information at 3-month intervals. Control arm patients with a single-chamber pacemaker transmitted at 2-month intervals. Control arm patients with dual-chamber devices transmitted at 2-month intervals with an office visit at 6 months. All patients were seen in office at 12 months. The mean time to first diagnosis of clinically actionable events was earlier in the Remote arm (5.7 months) than in the Control arm (7.7 months). Three (2%) of the 190 events in the Control arm and 446 (66%) of 676 events in the Remote arm were identified remotely. The strategic use of remote pacemaker interrogation follow-up detects actionable events that are potentially important more quickly and more frequently than transtelephonic rhythm strip recordings. The use of transtelephonic rhythm strips for pacemaker follow-up is of little value except for battery status determinations. (PREFER [Pacemaker Remote Follow-up Evaluation and Review]; NCT00294645).

Effects of Electroacupuncture on Interstitial Cells of Cajal (ICC) Ultrastructure and Connexin 43 Protein Expression in the Gastrointestinal Tract of Functional Dyspepsia (FD) Rats

PubMed Central

Zhang, Guoshan; Xie, Shen; Hu, Wei; Liu, Yuer; Liu, Mailan; Liu, Mi; Chang, Xiaorong

2016-01-01

Background Gastrointestinal motility disorder is the main clinical manifestation in functional dyspepsia (FD) patients. Electroacupuncture is effective in improving gastrointestinal motility disorder in FD; however, the underlying mechanism remains unclear. It has been demonstrated that interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract, and the pacemaker potential is transmitted to nearby cells through gap junctions between ICC or ICC and the smooth muscle. Therefore, this study aimed to assess the effects of electroacupuncture on ICC ultrastructure and expression of the gap junction protein connexin 43 (Cx43) in FD rats. Material/Methods The animals were randomized into 3 groups: control, model, and electroacupuncture. Electroacupuncture was applied at Zusanli (ST36) in the electroacupuncture group daily for 10 days, while no electroacupuncture was applied to model group animals. Results Ultrastructure of ICC recovered normally in gastric antrum and small intestine specimens was improved, with Cx43 expression levels in these tissues significantly increased in the electroacupuncture group compared with the model group. Conclusions These findings indicated that electroacupuncture is effective in alleviating ICC damage and reduces Cx43 levels in FD rats, and suggest that ICC and Cx43 are involved in electroacupuncture treatment in rats with FD to improve gastrointestinal motility disorders. PMID:27297942

Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons.

PubMed

Webb, Alexis B; Angelo, Nikhil; Huettner, James E; Herzog, Erik D

2009-09-22

Circadian rhythms are modeled as reliable and self-sustained oscillations generated by single cells. The mammalian suprachiasmatic nucleus (SCN) keeps near 24-h time in vivo and in vitro, but the identity of the individual cellular pacemakers is unknown. We tested the hypothesis that circadian cycling is intrinsic to a unique class of SCN neurons by measuring firing rate or Period2 gene expression in single neurons. We found that fully isolated SCN neurons can sustain circadian cycling for at least 1 week. Plating SCN neurons at <100 cells/mm(2) eliminated synaptic inputs and revealed circadian neurons that contained arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) or neither. Surprisingly, arrhythmic neurons (nearly 80% of recorded neurons) also expressed these neuropeptides. Furthermore, neurons were observed to lose or gain circadian rhythmicity in these dispersed cell cultures, both spontaneously and in response to forskolin stimulation. In SCN explants treated with tetrodotoxin to block spike-dependent signaling, neurons gained or lost circadian cycling over many days. The rate of PERIOD2 protein accumulation on the previous cycle reliably predicted the spontaneous onset of arrhythmicity. We conclude that individual SCN neurons can generate circadian oscillations; however, there is no evidence for a specialized or anatomically localized class of cell-autonomous pacemakers. Instead, these results indicate that AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling.

A morphological study of the pacemaker cells of the aganglionic intestine in Hirschsprung's disease utilizing ls/ls model mice.

PubMed

Taniguchi, Kan; Matsuura, Kimio; Matsuoka, Takanori; Nakatani, Hajime; Nakano, Takumi; Furuya, Yasuo; Sugimoto, Takeki; Kobayashi, Michiya; Araki, Keijiro

2005-06-01

Hirschsprung's disease is a congenital aganglionic neural disorder of the segmental distal intestine characterized by unsettled pathogenesis. The relationship between Hirschsprung's disease and pacemaker cells (PMC), which almost corresponds to that of the interstitial cells of Cajal (ICC), was morphologically observed at the level of the intermuscular layer corresponding to Auerbach's plexus using ls/ls mice. These mice are an ideal model because of their large intestinal aganglionosis and gene abnormalities, which are similar to the human form of the disease. Immunostaining using anti-c-kit receptor antibody (ACK2), a marker of PMC, applied to whole-mount muscle-layer specimens, revealed the presence of c-kit immunopositive multipolar cells with many cytoplasmic processes in normal mice. For ls/ls mice, however, there were significantly fewer processes. The average number of processes per positive cell of 2.5 for the aganglionic large intestine was fewer than 3.5 for the large and small intestine of normal mice, indicating the inability to form connections between nerves and PMC in the aganglionic intestine. For normal mice with an Auerbach's plexus, the process attachment of ICC to the Auerbach's plexus was observed by scanning electron microscopy. However, for ls/ls mice no attachment to the intermuscular nerve without Auerbach's plexus was found, although transmission electron microscopy showed no difference in the cell structure and organelles of the c-kit immunopositive cells between the normal and ls/ls mice. These findings suggest that in the aganglionic intestine of Hirschsprung's disease, aplasia of enteric ganglia induces secondary disturbances during the normal development of intestinal PMC.

Programmable Pacemaker

NASA Technical Reports Server (NTRS)

1996-01-01

Released in 1995, the Trilogy cardiac pacemaker is the fourth generation of a unit developed in the 1970s by NASA, Johns Hopkins Applied Physics Laboratory and St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.). The new system incorporates the company's PDx diagnostic and programming software and a powerful microprocessor that allows more functions to be fully automatic and gives more detailed information on the patient's health and the performance of the pacing systems. The pacemaker incorporates bidirectional telemetry used for space communications for noninvasive communication with the implanted pacemaker, smaller implantable pulse generators from space microminiaturization, and longer-life batteries from technology for spacecraft electrical power systems.

Reliable, responsive pacemaking and pattern generation with minimal cell numbers: the crustacean cardiac ganglion.

PubMed

Cooke, Ian M

2002-04-01

Investigations of the electrophysiology of crustacean cardiac ganglia over the last half-century are reviewed for their contributions to elucidating the cellular mechanisms and interactions by which a small (as few as nine cells) neuronal network accomplishes extremely reliable, rhythmical, patterned activation of muscular activity-in this case, beating of the neurogenic heart. This ganglion is thus a model for pacemaking and central pattern generation. Favorable anatomy has permitted voltage- and space-clamp analyses of voltage-dependent ionic currents that endow each neuron with the intrinsic ability to respond with rhythmical, patterned impulse activity to nonpatterned stimulation. The crustacean soma and initial axon segment do not support impulse generation but integrate input from stretch-sensitive dendrites and electrotonic and chemically mediated synapses on axonal processes in neuropils. The soma and initial axon produce a depolarization-activated, calcium-mediated, sustained potential, the "driver potential," so-called because it drives a train of impulses at the "trigger zone" of the axon. Extreme reliability results from redundancy and the electrotonic coupling and synaptic interaction among all the neurons. Complex modulation by central nervous system inputs and by neurohormones to adjust heart pumping to physiological demands has long been demonstrated, but much remains to be learned about the cellular and molecular mechanisms of action. The continuing relevance of the crustacean cardiac ganglion as a relatively simple model for pacemaking and central pattern generation is confirmed by the rapidly widening documentation of intrinsic potentials such as plateau potentials in neurons of all major animal groups. The suite of ionic currents (a slowly inactivating calcium current and various potassium currents, with variations) observed for the crustacean cardiac ganglion have been implicated in or proven to underlie a majority of the intrinsic potentials of neurons involved in pattern generation.

Circadian rhythmicity and light sensitivity of the zebrafish brain.

PubMed

Moore, Helen A; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated.

Circadian Rhythmicity and Light Sensitivity of the Zebrafish Brain

PubMed Central

Moore, Helen A.; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated. PMID:24465943

Changes in 42K efflux produced by alterations in transmembrane calcium movements in turtle cardiac pace-maker tissue.

PubMed Central

Fleming, B P; Giles, W

1981-01-01

1. 42K efflux has been measured from small strips of turtle sinus venosus which were electrically paced. Three different procedures for altering transmembrane calcium influx have been utilized to test whether changes in 42K efflux may be modulated by changes in intracellular calcium levels. 2. No significant changes in the 42K fractional escape rate (FER) were observed when external calcium was reduced to O mM or increased to 4 x normal (10 mM). In these experiments extracellular divalent cation concentration was held constant by adding or removing magnesium ions. 3. Application of 10 mM-Ba2+ also failed to alter 42K FER consistently. In red blood cells and snail neurones addition of barium ions has been shown to reduce significantly the calcium-mediated potassium current. 4. A tenfold increase in pacing rate (0.5-5 Hz) resulted in an augmented 42K FER, but repetition of this rate change in O mM-Ca2+ indicated that this increase in 42K FER was not strongly dependent on the amount of calcium entry. 5. Attempts to load the pace-maker cells with calcium by using the ionophore A23187 (10 micrograms ml . -1 of 2.0 x 10(-5) M) consistently resulted in very large increases in 42K FER. However, this effect (i) was blocked by atropine and (ii) was markedly reduced by pretreating the tissues with hemicholinium, indicating that A23187-induced release of acetylcholine from the endogenous nerve terminals was responsible for the observed increase in 42K FER. 6. In summary, three different experimental tests indicate that the majority of the 42K efflux is not tightly linked to transmembrane calcium movement in sinus venosus pace-maker tissue. PMID:6796675

A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking.

PubMed

Minegishi, Katsura; Hashimoto, Masakazu; Ajima, Rieko; Takaoka, Katsuyoshi; Shinohara, Kyosuke; Ikawa, Yayoi; Nishimura, Hiromi; McMahon, Andrew P; Willert, Karl; Okada, Yasushi; Sasaki, Hiroshi; Shi, Dongbo; Fujimori, Toshihiko; Ohtsuka, Toshihisa; Igarashi, Yasunobu; Yamaguchi, Terry P; Shimono, Akihiko; Shiratori, Hidetaka; Hamada, Hiroshi

2017-03-13

Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. How node cells become polarized has remained unknown, however. Wnt5a and Wnt5b are expressed posteriorly relative to the node, whereas genes for Sfrp inhibitors of Wnt signaling are expressed anteriorly. Here we show that polarization of node cells is impaired in Wnt5a -/- Wnt5b -/- and Sfrp mutant embryos, and also in the presence of a uniform distribution of Wnt5a or Sfrp1, suggesting that Wnt5 and Sfrp proteins act as instructive signals in this process. The absence of planar cell polarity (PCP) core proteins Prickle1 and Prickle2 in individual cells or local forced expression of Wnt5a perturbed polarization of neighboring wild-type cells. Our results suggest that opposing gradients of Wnt5a and Wnt5b and of their Sfrp inhibitors, together with intercellular signaling via PCP proteins, polarize node cells along the anterior-posterior axis for breaking of left-right symmetry. Copyright © 2017 Elsevier Inc. All rights reserved.

Implantable automatic scanning pacemaker for termination of supraventricular tachycardia.

PubMed

Spurrell, R A; Nathan, A W; Bexton, R S; Hellestrand, K J; Nappholz, T; Camm, A J

1982-03-01

Thirteen patients suffering from reentrant supraventricular tachycardia have undergone implantation of a scanning extrastimulus pacemaker. This pacemaker is fully implanted and automatic, and it requires no external control device to activate or control it. The pacemaker is activated when tachycardia occurs. After four cycles an extrastimulus is induced with a preset coupling time from a sensed intracardiac potential, and every four cycles thereafter a further extrastimulus occurs, but on each occasion there is a decrement in coupling cycle by 6 ms until 90 ms of the cardiac cycle has been scanned by extrastimuli. When necessary, two extrastimuli can be introduced with a fixed but preset coupling time between them. Every four beats two extrastimuli are induced but the coupling time between the spontaneous cardiac potential and the first stimulus is decreased by 6 ms until 90 ms of the cardiac cycle has been scanned. The coupling time between the two stimuli is fixed throughout the scan. When termination of tachycardia occurs the successful timing variables are retained in the pacemaker memory so that at the onset of the next episode of tachycardia these settings are used first. Pacemaker pulse width, sensitivity, tachycardia trigger rate, coupling intervals for both stimuli and the use of single or double extrastimuli are all programmable transcutaneously. Three patients required single, and seven patients double ventricular premature stimuli; three patients required double atrial premature stimuli for termination of tachycardia. Despite frequent attacks of tachycardia before implantation, only two patients had a sustained attack of tachycardia after pacemaker implantation.

Radioisotope-powered cardiac pacemaker program. Clinical studies of the nuclear pacemaker model NU-5. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-06-01

Beginning in February, 1970, the Nuclear Materials and Equipment Corporation (NUMEC) undertook a program to design, develop and manufacture a radioisotope powered cardiac pacemaker system. The scope of technical work was specified to be: establish system, component, and process cost reduction goals using the prototype Radioisotope Powered Cardiac Pacemaker (RCP) design and develop production techniques to achieve these cost reduction objectives; fabricate radioisotope powered fueled prototype cardiac pacemakers (RCP's) on a pilot production basis; conduct liaison with a Government-designated fueling facility for purposes of defining fueling requirements, fabrication and encapsulation procedures, safety design criteria and quality control and inspection requirements;more » develop and implement Quality Assurance and Reliability Programs; conduct performance, acceptance, lifetime and reliability tests of fueled RCP's in the laboratory; conduct liaison with the National Institutes of Health and with Government specified medical research institutions selected for the purpose of undertaking clinical evaluation of the RCP in humans; monitor and evaluate, on a continuing basis, all test data; and perform necessary safety analyses and tests. Pacemaker designs were developed and quality assurance and manufacturing procedures established. Prototype pacemakers were fabricated. A total of 126 radioisotope powered units were implanted and have been followed clinically for approximately seven years. Four (4) of these units have failed. Eighty-three (83) units remain implanted and satisfactorily operational. An overall failure rate of less than the target 0.15% per month has been achieved.« less

Characteristics and Prognosis of Pacemaker-Identified New-Onset Atrial Fibrillation in Japanese People.

PubMed

Ogino, Yutaka; Ishikawa, Toshiyuki; Ishigami, Tomoaki; Matsumoto, Katsumi; Hosoda, Junya; Iguchi, Kouhei; Matsushita, Hirooki; Taguchi, Yuka; Horiguchi, Yoriko; Kimura, Kazuo

2017-05-25

The characteristics and prognosis of implanted pacemaker-identified new-onset atrial fibrillation (AF) in Japanese people has not been well evaluated.Methods and Results:A total of 395 consecutive patients with newly implanted pacemakers were retrospectively analyzed between January 2010 and December 2015 at Yokohama City University Hospital. Patients with a prior history of AF, VVI mode pacemaker, congenital heart disease, severe valvular heart disease, and cardiovascular surgery before pacemaker implantation were excluded. Among the remaining patients, 44 (21.3%) developed new AF during follow-up (mean follow-up, 1,115±651 days; range, 9-2,176 days). Patients with new-onset AF had a significantly higher CHADS 2 score (2.09±1.27 vs. 1.31±1.08, P<0.001) and CHA 2 DS 2 -VASc score (3.00±1.39 vs. 2.26±1.19, P<0.001) compared with those without new-onset AF. On Cox regression analysis only age at implantation was significantly correlated with new-onset AF. Interestingly, the incidence of hospitalization due to heart failure was significantly higher in the new-onset AF than in the without new-onset AF group. A total of 21.3% of pacemaker-implanted patients with high CHADS 2 and CHA 2 DS 2 -VASc scores developed new-onset AF during a mean follow-up of 3.1 years; and pacemaker-identified AF was associated with an increased risk of worsening heart failure.

Successful treatment of pacemaker-induced stricture and thrombosis of the cranial vena cava in two dogs by use of anticoagulants and balloon venoplasty.

PubMed

Cunningham, Suzanne M; Ames, Marisa K; Rush, John E; Rozanski, Elizabeth A

2009-12-15

2 castrated male Labrador Retrievers (dogs 1 and 2) were evaluated 3 to 4 years after placement of a permanent pacemaker. Dog 1 was evaluated because of a large volume of chylous pleural effusion. Dog 2 was admitted for elective replacement of a pacemaker. Dog 1 had mild facial swelling and a rapidly recurring pleural effusion. Previously detected third-degree atrioventricular block had resolved. Cranial vena cava (CVC) syndrome secondary to pacemaker-induced thrombosis and stricture of the CVC was diagnosed on the basis of results of ultrasonography, computed tomography, and venous angiography. Dog 2 had persistent third-degree atrioventricular block. Intraluminal caval stricture and thrombosis were diagnosed at the time of pacemaker replacement. Radiographic evidence of pleural effusion consistent with CVC syndrome also was detected at that time. Dog 1 improved after treatment with unfractionated heparin and a local infusion of recombinant tissue-plasminogen activator. Balloon venoplasty was performed subsequently to relieve the persistent caval stricture. In dog 2, balloon dilatation of the caval stricture was necessary to allow for placement of a new pacing lead. Long-term anticoagulant treatment was initiated in both dogs. Long-term (> 6 months) resolution of clinical signs was achieved in both dogs. Thrombosis and stricture of the CVC are possible complications of a permanent pacemaker in dogs. Findings suggested that balloon venoplasty and anticoagulation administration with or without thrombolytic treatment can be effective in the treatment of dogs with pacemaker-induced CVC syndrome.

Genetic Elimination of GABAergic Neurotransmission Reveals Two Distinct Pacemakers for Spontaneous Waves of Activity in the Developing Mouse Cortex

PubMed Central

Easton, Curtis R.; Weir, Keiko; Scott, Adina; Moen, Samantha P.; Barger, Zeke; Folch, Albert; Hevner, Robert F.

2014-01-01

Many structures of the mammalian CNS generate propagating waves of electrical activity early in development. These waves are essential to CNS development, mediating a variety of developmental processes, such as axonal outgrowth and pathfinding, synaptogenesis, and the maturation of ion channel and receptor properties. In the mouse cerebral cortex, waves of activity occur between embryonic day 18 and postnatal day 8 and originate in pacemaker circuits in the septal nucleus and the piriform cortex. Here we show that genetic knock-out of the major synthetic enzyme for GABA, GAD67, selectively eliminates the picrotoxin-sensitive fraction of these waves. The waves that remain in the GAD67 knock-out have a much higher probability of propagating into the dorsal neocortex, as do the picrotoxin-resistant fraction of waves in controls. Field potential recordings at the point of wave initiation reveal different electrical signatures for GABAergic and glutamatergic waves. These data indicate that: (1) there are separate GABAergic and glutamatergic pacemaker circuits within the piriform cortex, each of which can initiate waves of activity; (2) the glutamatergic pacemaker initiates waves that preferentially propagate into the neocortex; and (3) the initial appearance of the glutamatergic pacemaker does not require preceding GABAergic waves. In the absence of GAD67, the electrical activity underlying glutamatergic waves shows greatly increased tendency to burst, indicating that GABAergic inputs inhibit the glutamatergic pacemaker, even at stages when GABAergic pacemaker circuitry can itself initiate waves. PMID:24623764

Pacemaker Implants in Children and Adolescents with Chagas Disease in Brazil: 18-Year Incidence

PubMed Central

Mizzaci, Carolina Christianini; Souza, Thiago Gonçalves Schroder e; Targueta, Gabriel Pelegrineti; Tótora, Ana Paula Frederico; Mateos, Juan Carlos Pachón; Mateos, José Carlos Pachon

2017-01-01

Background: Chagas disease continues to be a serious public health problem, and accounts for 25-30% of the indications for cardiac stimulation in Brazil. Objective: To assess clinical and epidemiological characteristics of patients with Chagas disease, younger than 18 years, who had undergone pacemaker implantation in Brazil between 1994 and 2011, and its temporal trend. Methods: This was a cross-sectional analysis of data from the Brazilian Pacemaker Registry database. The following variables were analyzed: year when pacemaker was implanted, location, age, sex, ethnic group, functional class and the main electrocardiographic findings at baseline. Results: In a total of 183,123 implants performed between 1994 and 2011, 214 implants of cardiac stimulation device in Chagas disease patients aged younger than 18 years were identified. Mean age at implantation was 5.6 ± 6.2 years. Second- and third-degree atrioventricular blocks corresponded to 71% of indications for pacemaker implantation. Fifty-six percent of the procedures were performed in the southeast region. Regarding the total number of pacemaker implants per year, there was a remarkable increase in the implants for all causes. However, time series analysis of the implants in Chagas disease patients younger than 18 years revealed a significant reduction in the annual number of implants. Conclusion: There has been an important reduction in the number of pacemaker implantations among children and adolescents with Chagas disease, suggesting a reduction in the vertical transmission of the parasite. PMID:28699977

Cervical lymph node metastases in squamous cell carcinoma of tongue and floor of mouth.

PubMed

Ehsan-ul-Haq, Muhammad; Warraich, Riaz Ahmed; Abid, Hina; Sajid, Malik Ali Hassan

2011-01-01

Oral squamous cell carcinoma has high chances of cervical lymph node metastasis. This case series describes the distribution of cervical lymph nodes in 50 cases of squamous cell carcinoma of tongue and floor of mouth. The mean age was 47.28±10.5 years. Thirty positive metastatic lymph nodes were found; 90% occurring at level I-II mostly in T4 size but also in T1 and T2 cases. The distribution of involved lymph nodes in oral cancer affects the neck dissection extent and is, therefore, an important pre-operative feature.

Intracellular esterase activity in living cells may distinguish between metastatic and tumor-free lymph nodes.

PubMed

Afrimzon, Elena; Deutsch, Assaf; Shafran, Yana; Zurgil, Naomi; Sandbank, Judith; Pappo, Itzhak; Deutsch, Mordechai

2008-01-01

One of the major clinical problems in breast cancer detection is the relatively high incidence of occult lymph node metastases undetectable by standard procedures. Since the ascertainment of breast cancer stage determines the following treatment, such a "hypo-diagnosis" leads to inadequate therapy, and hence is detrimental for the outcome and survival of the patients. The purpose of our study was to investigate functional metabolic characteristics of living cells derived from metastatic and tumor-free lymph nodes of breast cancer (BC) patients. Our methodology is based on the ability of living cells to hydrolyze fluorescein diacetate (FDA) by intracellular esterases and on the association of FDA hydrolysis rates with a specific cell status, both in physiological and pathological conditions. The present study demonstrates a significant difference in the ability to utilize FDA by lymph node cells derived from metastatic and tumor-free lymph nodes in general average, as well as in the metastatic and tumor-free lymph nodes of individual patients. Cells from metastatic lymph nodes had a higher capacity for FDA hydrolysis, and increased this activity after additional activation by autologous tumor tissue (tt). The association between increased FDA hydrolysis rate and activated T lymphocytes and antigen-presenting cells (APC) was shown. The results of the present study may contribute to predicting the risk of involvement of seemingly "tumor-free" axillary lymph nodes in occult metastatic processes, and to reducing false-negative results of axillary examination.

Axillary Lymph Nodes and Breast Cancer

MedlinePlus

... white blood cells that help fight illness. If breast cancer spreads, the lymph nodes in the underarm (called ... if they contain cancer cells. This helps determine breast cancer stage and guide treatment. Sentinel node biopsy and ...

Intracellular Calcium Dynamics and the Acceleration of Sinus Rhythm by β-Adrenergic Stimulation

PubMed Central

Joung, Boyoung; Tang, Liang; Maruyama, Mitsunori; Han, Seongwook; Chen, Zhenhui; Stucky, Marcelle; Jones, Larry R.; Fishbein, Michael C.; Weiss, James N.; Chen, Peng-Sheng; Lin, Shien-Fong

2009-01-01

Background Recent evidence indicates that membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. Here we test the hypothesis that sinus rate acceleration by β-adrenergic stimulation involves synergistic interactions between these clock mechanisms. Methods and Results We simultaneously mapped intracellular calcium (Cai) and membrane potential (Vm) in 25 isolated canine right atrium (RA), using previously described criteria of the timing of late diastolic Cai elevation (LDCAE) relative to the action potential (AP) upstroke to detect the Ca2+ clock. Before isoproterenol, the earliest pacemaking site occurred in the inferior SAN, and LDCAE was observed in only 4/25 preparations. Isoproterenol (1 μmol/L) increased sinus rate and shifted pacemaking site to superior SAN, concomitant with the appearance of LDCAE preceding the AP upstroke by 98 ± 31 ms. Caffeine had similar effects, while SR Ca2+ depletion with ryanodine and thapsigargin prevented isoproterenol-induced LDCAE and blunted sinus rate acceleration. Cai transient relaxation time during ISO was shorter in superior SAN (124 ± 34 ms) than inferior SAN (138 ± 24 ms, p = 0.01) or RA (164 ± 33 ms, p = 0.001), and was associated with a lower SR Ca2+ ATPase pump to phospholamban protein ratio in SAN than in RA. If current blockade with ZD 7288 modestly blunted, but did not prevent LDCAE or sinus rate acceleration by isoproterenol. Conclusions Acceleration of the Ca2+ clock in the superior SAN plays an important role in sinus acceleration during β-adrenergic stimulation, interacting synergistically with the voltage clock to increase sinus rate. PMID:19188501

Relationship between temperature change and the requirement for a permanent pacemaker implantation in bradyarrhythmias.

PubMed

Liu, I-Fan; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Kong, Chi-Woon; Wu, Tsu-Juey; Chiang, Chern-En; Chen, Shih-Ann; Lin, Yenn-Jiang

2011-09-01

Some cardiovascular diseases are associated with seasonal or meteorological factors. We tried to identify the relationship between meteorological parameters and the requirement for a permanent pacemaker (PPM) implantation for advanced sinus node dysfunction (SND) and atrioventricular block (AVB). This study enrolled 656 patients (67% male, age = 76 ± 11 years) who underwent a PPM implantation due to SND or AVB from January 2004 to December 2008. Using daily temperature, barometric pressure, humidity, and daylight hour records from Taipei, we evaluated the effect of these meteorological parameters within different time periods on the occurrence of SND and AVB. There were 355 patients in the SND group and 301 in the AVB group. In the AVB group, more patients presented in the spring than in other seasons (P = 0.003). In the SND group, there was no relationship with the seasons (P = 0.137). The proportion of patients with AVB did not depend on the average temperature, barometric pressure, humidity, or daylight hours within 3, 7, and 14 days prior to admission (P = NS). A temperature change of greater than 11°C within 30 days prior to admission was associated with a significantly higher proportion of patients with advanced AVB compared to those with advanced SND (P = 0.009). Extreme change in temperature was the most independent predictor of the development of advanced AVB. The peak occurrence of advanced AVB was in the spring. The occurrence of advanced AVB was associated with extreme temperature changes within 30 days, especially in the spring.

What Is a False Negative Sentinel Node Biopsy: Definition, Reasons and Ways to Minimize It?

PubMed

Kataria, Kamal; Srivastava, Anurag; Qaiser, Darakhshan

2016-10-01

Sentinel node biopsy helps in assessing the involvement of axillary lymph node without the morbidity of full axillary lymph node dissection, namely arm and shoulder pain, paraesthesia and lymphoedema. The various methods described in the literature identify the sentinel lymph nodes in approximately 96 % of cases and associated with a false negativity rate of 5 to 10 %. A false negative sentinel node is defined as the proportion of cases in whom sentinel node biopsy is reported as negative, but the rest of axillary lymph node(s) harbours cancer cells. The possible causes of a false negative sentinel lymph node may be because of blocked lymphatics either by cancer cells or following fibrosis of previous surgery/radiotherapy, and an alternative pathway opens draining the blue dye or isotope to another uninvolved node . The other reasons may be two lymphatic pathways for a tumour area, the one opening to a superficial node and the other in deep nodes. Sometimes, lymphatics do not relay into a node but traverse it going to a higher node. In some patients, the microscopic focus of metastasis inside a lymph node is so small-micrometastasis (i.e. between 0.2 and 2 mm) or isolated tumour cells (i.e. less than 0.2 mm) that is missed by the pathologist. The purpose of this review is to clear some fears lurking in the mind of most surgeons about the false negative sentinel lymph node (FNSLN).

Heparan sulfate storage in the cardiac conduction system triggers atrioventricular block.

PubMed

Kato, Rie; Miyahara, Hiroaki; Kawano, Tatsuya; Matsuzuka, Atsuko; Noda, Kimiko; Izumi, Tatsuro

2017-05-01

To elucidate the novel biological functions of heparan sulfate (HS) by clinic-pathologically studying a patient with paroxysmal atrioventricular (AV) block. A long-surviving male patient with Sanfilippo syndrome type A presented with paroxysmal AV block at age 33years. He then survived another 2.5years after the onset of paroxysmal AV block and pacemaker implantation. His cardiac histopathological examination at autopsy showed HS storage in the cardiac conduction system (CCS), especially in the atrioventricular node (AVN)-His bundle branches. HS storage in the CCS might trigger AV block, arising from below the AVN-His bundle branches. This is the first description to indicate that HS might be an essential constituent of life-long CCS plasticity and that its storage in the CCS results in AV block. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Initial dynamics of the EKG during an electrical defibrillation of the heart

NASA Technical Reports Server (NTRS)

Bikov, I. I.; Chebotarov, Y. P.; Nikolaev, V. G.

1980-01-01

In tests on 11 mature dogs, immobilized by means of an automatic blocking and synchronization system, artefact free EKG were obtained, beginning 0.04-0.06 sec after passage of a defibrillating current. Different versions of the start of fibrillation were noted, in application of the defibrillating stimulus in the early phase of the cardiac cycle. A swinging phenomenon, increasing amplitude, of fibrillation was noted for 0.4-1.5 sec after delivery of a subthreshold stimulus. Conditions for a positive outcome of repeated defibrillation were found, and a relationship was noted between the configuration of the exciting process with respect to the lines of force of the defibrillating current and the defibrillation threshold. It was shown that the initial EKG dynamics after defibrillation is based on a gradual shift of the pacemaker from the myocardium of the ventricles to the sinus node, through phases of atrioventricular and atrial automatism.

Percutaneous tricuspid valvotomy for pacemaker lead-induced tricuspid stenosis

PubMed Central

Patil, Devendra V.; Nabar, Ashish A.; Sabnis, Girish R.; Phadke, Milind S.; Lanjewar, Charan P.; Kerkar, Prafulla G.

2015-01-01

Permanent pacemaker lead-induced tricuspid regurgitation is extremely uncommon. We report a patient with severe tricuspid stenosis detected 10 years after permanent single chamber pacemaker implantation in surgically corrected congenital heart disease. The loop at the level of the tricuspid valve may have caused endothelial injury and eventually led to stenosis. Percutaneous balloon valvotomy for such stenosis has not been reported from India. PMID:26995417

Infectious endocarditis in pacemaker endocardial leads: report of three cases.

PubMed

Cruz-Cruz, F; Espinola-Zavaleta, N; Hernández Lara, J; Iturralde-Torres, P; González-Hermosillo, J A; Romero-Cárdenas, A; Keirns, C; Vargas-Barrón, J

1999-01-01

Three cases of endocarditis affecting endocardial leads of permanent pacemakers are presented with a review of the literature. Vegetations were identified using transesophageal echocardiography. Infection of pacemaker leads is far less common than infection at the site of the pulse generator with greater morbidity and mortality and generally requiring surgical removal of both electrodes and power source. The most frequent infective agents are stahylococcus varieties.

Clinical features and changes in epidemiology of infective endocarditis on pacemaker devices over a 27-year period (1987-2013).

PubMed

Carrasco, Francisco; Anguita, Manuel; Ruiz, Martín; Castillo, Juan Carlos; Delgado, Mónica; Mesa, Dolores; Romo, Elias; Pan, Manuel; Suárez de Lezo, Jose

2016-06-01

Use of cardiac pacing devices has grown in recent years. Our aim was to evaluate changes in epidemiology and clinical features of infective endocarditis (IE) involving pacemaker devices in a large series of IE over the last 27 years (1987-2013). From 1987 to December 2013, 413 consecutive IE cases were diagnosed in our hospital. During this period, 7424 pacemaker devices were implanted (6917 pacemakers, 239 implantable cardiac defibrillators, 158 resynchronization devices, and 110 resynchronization/defibrillator devices). All consecutive cases of IE on pacemaker devices were included and analysed. Infective endocarditis on pacemaker devices represented 6.1% of all endocarditis cases (25 patients), affecting 3.6/1000 of all implanted pacemakers. Its proportion increased from 1.25% of all endocarditis in 1987-1993 to 4.08% in 1994-2000, 7.69% in 2001-2007 and 9.32% in 2008-2013 (P < 0.01). Its incidence also increased from 1.4/1000 of all pacemaker implants in the period of 1987-1993 to 2.5/1000 in 1994-2000, 3.3/1000 in 2001-2007 and 4.5/1000 implanted devices in 2008-2013 (P < 0.05). Mean age of patients was 68 years, and 80% were male. Causative microorganisms predominantly were Staphylococci (84%: Staphylococcus aureus 48%, Staphylococcus epidermidis 36%). Rate of severe complications was high: persistent sepsis in 60% of cases, heart failure in 20%, and stroke in 12%. Device was removed in 19 patients (76%), mostly by surgery (18 of the 19 cases). Early mortality was 24% (33% of medically, 21% of surgically treated patients, P = 0.82). Infective endocarditis on pacemaker devices has shown an increasing incidence during the past decades, representing almost 10% of all IE in the last 6 years. This is a severe disease, with a high rate of severe complications and requiring removal of device in most cases. In spite of therapy, early mortality is high. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

PubMed

Klerkx, Wenche M; Geldof, Albert A; Heintz, A Peter; van Diest, Paul J; Visser, Fredy; Mali, Willem P; Veldhuis, Wouter B

2011-05-01

To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes. Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically. The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5-7 mm(3) at baseline to 25 mm(3) at day 14, while the control node remained 5 mm(3). The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%-32%), but this decrease was also seen in reactive nodes. Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values. Copyright © 2011 Wiley-Liss, Inc.

The Drosophila Circadian Pacemaker Circuit: Pas de Deux or Tarantella?

PubMed Central

Sheeba, Vasu; Kaneko, Maki; Sharma, Vijay Kumar; Holmes, Todd C.

2008-01-01

Molecular genetic analysis of the fruit fly Drosophila melanogaster has revolutionized our understanding of the transcription/translation loop mechanisms underlying the circadian molecular oscillator. More recently, Drosophila has been used to understand how different neuronal groups within the circadian pacemaker circuit interact to regulate the overall behavior of the fly in response to daily cyclic environmental cues as well as seasonal changes. Our present understanding of circadian timekeeping at the molecular and circuit level is discussed with a critical evaluation of the strengths and weaknesses of present models. Two models for circadian neural circuits are compared: one that posits that two anatomically distinct oscillators control the synchronization to the two major daily morning and evening transitions, versus a distributed network model that posits that many cell-autonomous oscillators are coordinated in a complex fashion and respond via plastic mechanisms to changes in environmental cues. PMID:18307108

Vaccine draining lymph nodes are a source of antigen-specific B cells.

PubMed

Pero, Stephanie C; Sun, Yu-Jing; Shukla, Girja S; Carman, Chelsea L; Krag, Christopher C; Teuscher, Cory; Krementsov, Dimitry N; Krag, David N

2017-03-01

Our research is focused on using vaccine draining lymph nodes as a source of immune cells to better understand the immune response and to attempt to generate new anti-cancer reagents. Following a vaccine, harvesting the lymph node can only be done once. We endeavored to determine the range of times that B cells secreting anti-KLH antibodies were present in the node of KLH-vaccinated mice. Following vaccination the total number of mononuclear cells (MNCs) increased in the vaccine-draining lymph node (VDN). The percentage of MNCs that were B cells nearly doubled. B cells recovered from the node that secreted anti-KLH antibodies were evident by day 7. The number continued to increase and then slowly decreased over the observed time range to 28days after vaccination. The VDN, compared to the spleen, the bone marrow and the nonVDN, contained a higher percentage of B cells that secreted anti-KLH antibodies. After a vaccine, there is a multi-week window of time when an increasing number of B cells are present in a VDN that secrete anti-KLH antibodies. These results support using the VDN as a source for B cells that secrete anti-vaccine antibodies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Subcarinal lymph node in upper lobe non-small cell lung cancer patients: is selective lymph node dissection valid?

PubMed

Aokage, Keiju; Yoshida, Junji; Ishii, Genichiro; Hishida, Tomoyuki; Nishimura, Mitsuyo; Nagai, Kanji

2010-11-01

Little is known about selective lymph node dissection in non-small cell lung cancer (NSCLC) patients. We sought to gain insight into subcarinal node involvement for its frequency and impact on outcome to evaluate whether it is valid to omit subcarinal lymph node dissection in upper lobe NSCLC patients. We reviewed node metastases distribution according to node region, tumor location, and histology among 1099 patients with upper lobe NSCLC. We paid special attention to subcarinal metastases patients without superior mediastinal node metastases, because their pathological stages would have been underdiagnosed if subcarinal node dissection had been omitted. We also assessed the outcome and the pattern of failure among subcarinal metastases patients. To identify subcarinal node involvement predictors, we analyzed 7 clinical factors. Subcarinal node metastases were found in 20 patients and were least frequent among squamous cell carcinoma patients (0.5%). Two of them were free from superior mediastinal metastases but died of the disease at 1 month and due to an unknown cause at 18 months, respectively. Seventeen of the 20 patients developed multi-site recurrence within 37 months. The 5-year survival rate of the 20 patients with subcarinal metastases was 9.0%, which was significantly lower than 32.0% of patients with only superior mediastinal metastases. Clinical diagnosis of node metastases was significantly predictive of subcarinal metastases. Subcarinal node metastases from upper lobe NSCLC were rare and predicted an extremely poor outcome. It appears valid to omit subcarinal node dissection in upper lobe NSCLC patients, especially in clinical N0 squamous cell carcinoma patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search

PubMed Central

Fricke, G. Matthew; Letendre, Kenneth A.; Moses, Melanie E.; Cannon, Judy L.

2016-01-01

Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1) a lognormal distribution of step lengths, 2) motion that is directionally persistent over short time scales, and 3) heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call “hotspots” within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search. PMID:26990103

A Sodium Leak Current Regulates Pacemaker Activity of Adult Central Pattern Generator Neurons in Lymnaea Stagnalis

PubMed Central

Lu, Tom Z.; Feng, Zhong-Ping

2011-01-01

The resting membrane potential of the pacemaker neurons is one of the essential mechanisms underlying rhythm generation. In this study, we described the biophysical properties of an uncharacterized channel (U-type channel) and investigated the role of the channel in the rhythmic activity of a respiratory pacemaker neuron and the respiratory behaviour in adult freshwater snail Lymnaea stagnalis. Our results show that the channel conducts an inward leak current carried by Na+ (ILeak-Na). The ILeak-Na contributed to the resting membrane potential and was required for maintaining rhythmic action potential bursting activity of the identified pacemaker RPeD1 neurons. Partial knockdown of the U-type channel suppressed the aerial respiratory behaviour of the adult snail in vivo. These findings identified the Na+ leak conductance via the U-type channel, likely a NALCN-like channel, as one of the fundamental mechanisms regulating rhythm activity of pacemaker neurons and respiratory behaviour in adult animals. PMID:21526173

Immune cell profile of sentinel lymph nodes in patients with malignant melanoma – FOXP3+ cell density in cases with positive sentinel node status is associated with unfavorable clinical outcome

PubMed Central

2013-01-01

Background Besides being a preferential site of early metastasis, the sentinel lymph node (SLN) is also a privileged site of T-cell priming, and may thus be an appropriate target for investigating cell types involved in antitumor immune reactions. Methods In this retrospective study we determined the prevalence of OX40+ activated T lymphocytes, FOXP3+ (forkhead box P3) regulatory T cells, DC-LAMP+ (dendritic cell-lysosomal associated membrane protein) mature dendritic cells (DCs) and CD123+ plasmacytoid DCs by immunohistochemistry in 100 SLNs from 60 melanoma patients. Density values of each cell type in SLNs were compared to those in non-sentinel nodes obtained from block dissections (n = 37), and analyzed with regard to associations with clinicopathological parameters and disease outcome. Results Sentinel nodes showed elevated amount of all cell types studied in comparison to non-sentinel nodes. Metastatic SLNs had higher density of OX40+ lymphocytes compared to tumor-negative nodes, while no significant difference was observed in the case of the other cell types studied. In patients with positive sentinel node status, high amount of FOXP3+ cells in SLNs was associated with shorter progression-free (P = 0.0011) and overall survival (P = 0.0014), while no significant correlation was found in the case of sentinel-negative patients. The density of OX40+, CD123+ or DC-LAMP+ cells did not show significant association with the outcome of the disease. Conclusions Taken together, our results are compatible with the hypothesis of functional competence of sentinel lymph nodes based on the prevalence of the studied immune cells. The density of FOXP3+ lymphocytes showed association with progression and survival in patients with positive SLN status, while the other immune markers studied did not prove of prognostic importance. These results, together with our previous findings on the prognostic value of activated T cells and mature DCs infiltrating primary melanomas, suggest that immune activation-associated markers in the primary tumor may have a higher impact than those in SLNs on the prognosis of the patients. On the other hand, FOXP3+ cell density in SLNs, but not in the primary tumor, was found predictive of disease outcome in melanoma patients. PMID:23418928

Venous obstruction in permanent pacemaker patients: an isotopic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pauletti, M.; Di Ricco, G.; Solfanelli, S.

1981-01-01

Isotope venography was used to study the venous circulation proximal to the superior vena cava in two groups of pacemaker patients, one with a single endocavitary electrode and the other with multiple pacing catheters. A control group of patients without pacemakers was also studied. Numerous abnormalities were found, especially in the group with multiple electrodes. These findings suggest that venous obstruction is a common complication of endocardial pacing.

Calcium Homeostatasis and Mitochondrial Dysfunction in Dopaminergic Neurons of the Substantia Nigra

DTIC Science & Technology

2010-03-01

discovery that calcium entry through L-type channels during normal pacemaking elevates the sensitivity of SNc dopaminergic neurons to toxins; • the...discovery that L-type calcium channels participate in but are not necessary for pacemaking; • the discovery that serum concentration of the...FDA approved doses; • the discovery that calcium entry through L-type channels during pacemaking elevates mitochondrial oxidant stress and leads

Safety of Laser Interstitial Thermal Therapy in Patients With Pacemakers.

PubMed

Grewal, Sanjeet S; Gorny, Krzysztof R; Favazza, Christopher P; Watson, Robert E; Kaufmann, Timothy J; Van Gompel, Jamie J

2018-02-10

Laser interstitial thermal therapy (LiTT) has increasingly been used as a treatment option for medically refractory epilepsy, tumors, and radiation necrosis. The use of LiTT requires intraoperative magnetic resonance (MR) thermography. This can become an issue in patients with other implanted therapeutic devices such as pacemakers and vagal nerve stimulators due to concerns regarding increases in the specific absorption rate (SAR). This is a technical case report demonstrating a successfully and safely performed LiTT in a 1.5-T magnetic resonance imaging (MRI) in a patient with a pacemaker for mesial temporal sclerosis. An 83-yr-old gentleman who had an implanted cardiac pacemaker presented with medically intractable epilepsy and was confirmed to have mesial temporal sclerosis on imaging. Video electroencephalography demonstrated concordant ipsilateral seizures and semiology. He underwent LiTT for ablation of the mesial temporal lobe. This was performed with the below described protocol with a cardiology nurse monitoring the patient's cardiac condition and a physicist monitoring SAR, and MR imaging quality without any adverse events. This study reports on a protocol of cardiac and MR SAR to safely perform MR-guided LiTT in the setting of traditional pacemakers in patients who are not pacemaker dependent. Copyright © 2018 by the Congress of Neurological Surgeons

Stimulation of Mucosal Mast Cell Growth in Normal and Nude Rat Bone Marrow Cultures

NASA Astrophysics Data System (ADS)

Haig, David M.; McMenamin, Christine; Gunneberg, Christian; Woodbury, Richard; Jarrett, Ellen E. E.

1983-07-01

Mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) appear and proliferate to form the predominant cell type in rat bone marrow cultures stimulated with factors from antigen- or mitogen-activated lymphocytes. Conditioned media causing a selective proliferation of MMC were derived from mesenteric lymph node cells of Nippostrongylus brasiliensis-infected rats restimulated in vitro with specific antigen or from normal or infected rat mesenteric lymph node cells stimulated with concanavalin A. MMC growth factor is not produced by T-cell-depleted mesenteric lymph node cells or by the mesenteric lymph node cells of athymic rats. By contrast, MMC precursors are present in the bone marrow of athymic rats and are normally receptive to the growth factor produced by the lymphocytes of thymus-intact rats. The thymus dependence of MMC hyperplasia is thus based on the requirement of a thymus-independent precursor for a T-cell-derived growth promoter.

An approach to ablate and pace:AV junction ablation and pacemaker implantation performed concurrently from the same venous access site.

PubMed

Issa, Ziad F

2007-09-01

Atrioventricular junction (AVJ) ablation combined with permanent pacemaker implantation (the "ablate and pace" approach) remains an acceptable alternative treatment strategy for symptomatic, drug-refractory atrial fibrillation (AF) with rapid ventricular response. This case series describes the feasibility and safety of catheter ablation of the AVJ via a superior vena caval approach performed during concurrent dual-chamber pacemaker implantation. A total of 17 consecutive patients with symptomatic, drug-refractory, paroxysmal AF underwent combined AVJ ablation and dual-chamber pacemaker implantation procedure using a left axillary venous approach. Two separate introducer sheaths were placed into the axillary vein. The first sheath was used for implantation of the pacemaker ventricular lead, which was then connected to the pulse generator. Subsequently, a standard ablation catheter was introduced through the second axillary venous sheath and used for radiofrequency (RF) ablation of the AVJ. After successful ablation, the catheter was withdrawn and the pacemaker atrial lead was advanced through that same sheath and implanted in the right atrium. Catheter ablation of the AVJ was successfully achieved in all patients. The median number of RF applications required to achieve complete AV block was three (range 1-10). In one patient, AV conduction recovered within the first hour after completion of the procedure, and AVJ ablation was then performed using the conventional femoral venous approach. There were no procedural complications. Catheter ablation of the AVJ can be performed successfully and safely via a superior vena caval approach in patients undergoing concurrent dual-chamber pacemaker implantation.

Living with a pacemaker: patient-reported outcome of a pacemaker system.

PubMed

Magnusson, Peter; Liv, Per

2018-06-04

The aim of this study was to assess among pacemaker patients their overall satisfaction with the pacemaker system, pain, soreness/discomfort, cosmetic results, restrictions due to impaired movement of the shoulder/arm/chest, related sleep disturbances, and concern about possible device malfunction. The seven-item questionnaire was mailed to patients from a single center who had a pacemaker implant or replacement between 2006 and 2016. A higher score indicated worse outcome on a visual analog scale (VAS) of 0-100 mm. The response rate was 75.5% and 342 questionniares were analyzed. Median age of respondents was 77.6 years and 57.0% were males. In total, 65 complications requiring surgery (10 pocket corrections (2.9%), 5 in females) occurred during a median follow-up of 5.6 years.The distribution of the primary outcome had a median score of 5 while the 75th percentile was 13. Cosmetic appearance was significantly associated with reoperation (but not other variables). Overall scores for men and women were 5 vs. 6, respectively, which achieved significance (p = 0.042). Median ratings of pain, soreness/discomfort, cosmetic appearance, range of motion, sleep, and concern about device malfunction were all ≤5. Females reported worse outcomes for all questions, except for cosmetic results and concern about malfunction. The vast majority of patients report excellent overall satisfaction with the pacemaker system, and are not affected by pain, soreness/discomfort, or concern about device malfunction. They also reported favourable outcomes with respect to cosmetic results, shoulder movement, and sleep. However, some patients underwent a surgical correction of the pacemaker pocket.

Histologic pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

PubMed Central

Ko, Jennifer S; Prieto, Victor G; Elson, Paul; Vilain, Ricardo E; Pulitzer, Melissa; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa; Ernstoff, Marc S; Gastman, Brian; Billings, Steven D

2016-01-01

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathologic predictors of outcome were sought. Five metastatic patterns were identified: 1, sheet-like (n=38, 59%); 2, non-solid parafollicular (n=4, 6%); 3, sinusoidal, (n=11, 17%); 4, perivascular hilar (n=1, 2%) and 5, rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21(33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2–5 metastases (p=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. 3 (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. 4 (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph node (1 or 2 versus >2, p<.0001), age (<70 versus ≥70, p=.01), sentinel lymph node metastasis pattern (patterns 2–5 versus 1, p=.02), and immune status (immunocompetent versus suppressed, p=.03) were independent predictors of outcome, and could be used to stratify Stage III patients into 3 groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathologic features facilitates risk stratification of Merkel cell carcinoma patients that may have management implications. PMID:26541273

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

PubMed

Ko, Jennifer S; Prieto, Victor G; Elson, Paul J; Vilain, Ricardo E; Pulitzer, Melissa P; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa P; Ernstoff, Marc S; Gastman, Brian R; Billings, Steven D

2016-02-01

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

Comparison of Node-Centered and Cell-Centered Unstructured Finite-Volume Discretizations. Part 1; Viscous Fluxes

NASA Technical Reports Server (NTRS)

Diskin, Boris; Thomas, James L.; Nielsen, Eric J.; Nishikawa, Hiroaki; White, Jeffery A.

2009-01-01

Discretization of the viscous terms in current finite-volume unstructured-grid schemes are compared using node-centered and cell-centered approaches in two dimensions. Accuracy and efficiency are studied for six nominally second-order accurate schemes: a node-centered scheme, cell-centered node-averaging schemes with and without clipping, and cell-centered schemes with unweighted, weighted, and approximately mapped least-square face gradient reconstruction. The grids considered range from structured (regular) grids to irregular grids composed of arbitrary mixtures of triangles and quadrilaterals, including random perturbations of the grid points to bring out the worst possible behavior of the solution. Two classes of tests are considered. The first class of tests involves smooth manufactured solutions on both isotropic and highly anisotropic grids with discontinuous metrics, typical of those encountered in grid adaptation. The second class concerns solutions and grids varying strongly anisotropically over a curved body, typical of those encountered in high-Reynolds number turbulent flow simulations. Results from the first class indicate the face least-square methods, the node-averaging method without clipping, and the node-centered method demonstrate second-order convergence of discretization errors with very similar accuracies per degree of freedom. The second class of tests are more discriminating. The node-centered scheme is always second order with an accuracy and complexity in linearization comparable to the best of the cell-centered schemes. In comparison, the cell-centered node-averaging schemes are less accurate, have a higher complexity in linearization, and can fail to converge to the exact solution when clipping of the node-averaged values is used. The cell-centered schemes using least-square face gradient reconstruction have more compact stencils with a complexity similar to the complexity of the node-centered scheme. For simulations on highly anisotropic curved grids, the least-square methods have to be amended either by introducing a local mapping of the surface anisotropy or modifying the scheme stencil to reflect the direction of strong coupling.

Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients: A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China.

PubMed

Xiang, Mei-Xiang; Wang, Dong-Qi; Xu, Jing; Zhang, Zheng; Hu, Jian-Xin; Wang, Dong-Mei; Gu, Xiang; Liu, He-Ping; Guo, Tao; Yang, Xiang-Jun; Ling, Feng; Lin, Jia-Feng; Cai, Shang-Lang; Zhu, Guo-Bin; Wang, Jian-An

2016-11-20

High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia, and a domestically developed pacemaker will help lower the burden. This study aimed to evaluate the safety and efficacy of Qinming8631 DR (Qinming Medical, Baoji, China), the first domestically developed dual-chamber pacemaker of China, compared with a commercially available pacemaker Talos DR (Biotronik, Berlin, Germany) in Chinese patients. A prospective randomized trial was conducted at 14 centers in China. Participants were randomized into trial (Qinming8631 DR) and control (Talos DR) groups. Parameters of the pacing systems were collected immediately after device implantation and during follow-ups. The effective pacing rate at 6-month follow-up was recorded as the primary end point. Electrical properties, magnet response, single- and double-pole polarity conversion, rate response function, and adverse events of the pacing system were analyzed. The Cochran-Mantel-Haenszel Chi-square test, paired t-test, and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data. A total of 225 patients with a diagnosis of bradyarrhythmia and eligible for this study were randomly enrolled into the trial (n = 113) and control (n = 112) groups. They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity. Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set (81.4% vs. 79.5%, P = 0.712 and 95.4% vs. 89.5%, P = 0.143, respectively). In both data sets, noninferiority of the trial group was above the predefined noninferiority limit(-9.5%). This study established the noninferiority of Qinming8631 DR to Talos DR. The safety and efficacy of Qinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

Long-term screening for sleep apnoea in paced patients: preliminary assessment of a novel patient management flowchart by using automatic pacemaker indexes and sleep lab polygraphy.

PubMed

Aimé, Ezio; Rovida, Marina; Contardi, Danilo; Ricci, Cristian; Gaeta, Maddalena; Innocenti, Ester; Cabral Tantchou-Tchoumi, Jacques

2014-10-01

The primary aim of this pilot study was to prospectively assess a flowchart to screen and diagnose paced patients (pts) affected by sleep apnoeas, by crosschecking indexes derived from pacemakers (minute ventilation sensor on-board) with Sleep-Lab Polygraphy (PG) outcomes. Secondarily, "smoothed" long-term pacemaker indexes (all the information between two consecutive follow-up visits) have been retrospectively compared vs. standard short-term pacemaker indexes (last 24h) at each follow-up (FU) visit, to test their correlation and diagnostic concordance. Data from long-term FU of 61 paced pts were collected. At each visit, the standard short-term apnoea+hypopnoea (PM_AHI) index was retrieved from the pacemaker memory. Patients showing PM_AHI ≥ 30 at least once during FU were proposed to undergo a PG for diagnostic confirmation. Smoothed pacemaker (PM_SAHI) indexes were calculated by averaging the overall number of apnoeas/hypopnoeas over the period between two FU visits, and retrospectively compared with standard PM_AHI. Data were available from 609 consecutive visits (overall 4.64 ± 1.78 years FU). PM_AHI indexes were positive during FU in 40/61 pts (65.6%); 26/40 pts (65%) accepted to undergo a PG recording; Sleep-Lab confirmed positivity in 22/26 pts (84.6% positive predictive value for PM_AHI). A strong correlation (r=0.73) and a high level of concordance were found between smoothed and standard indexes (multivariate analysis, Cohen's-k and Z-score tests). Pacemaker-derived indexes may help in screening paced pts potentially affected by sleep apnoeas. Long-term "smoothed" apnoea indexes could improve the accuracy of pacemaker screening capability, even though this hypothesis must be prospectively confirmed by larger studies. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Exploring the mechanism of action of the sperm-triggered calcium-wave pacemaker in ascidian zygotes.

PubMed

Carroll, Michael; Levasseur, Mark; Wood, Chris; Whitaker, Michael; Jones, Keith T; McDougall, Alex

2003-12-15

In ascidians, as in mammals, sperm trigger repetitive Ca2+-waves that originate from cortical pacemakers situated in the vegetal hemisphere of the zygotes. In ascidians, a vegetal protrusion termed the contraction pole (CP) acts as the Ca2+-wave pacemaker, but the mechanism that underlies the generation of a Ca2+-wave pacemaker is not known. Here, we tested four hypotheses to determine which factors at the CP are involved in setting the pace of the ascidian Ca2+-wave pacemaker: (1) localized Ca2+ influx; (2) accumulation of phosphatidylinositol (4,5)bisphosphate [PtdIns(4,5)P2]; (3) accumulation of cortical endoplasmic reticulum (cER); and (4) enrichment of the sperm activating factor. We developed a method of dynamically monitoring the location of the CP during fertilization using a plekstrin homology (PH) domain from phospholipase Cdelta1 coupled to green fluorescent protein (GFP) that binds PtdIns(4,5)P2. We found that eggs in Ca2+-free sea water displayed Ca2+ waves that originated from the CP, showing that enhanced CP Ca2+ influx does not determine the origin of the pacemaker. Also, disruption of the PH::GFP-labelled CP once it had formed did not dislodge the Ca2+-wave pacemaker from that site. Next, when we prevented the accumulation of cER at the CP, all of the Ca2+ waves came from the site of sperm-egg fusion and the frequency of Ca2+ oscillations was unaltered. These data show that local Ca2+ influx, the accumulation of PtdIns(4,5)P2 and cER at the CP are not required for Ca2+-wave pacemaker function and instead suggest that a factor associated with the sperm determines the site of the Ca2+-wave pacemaker. Finally, when we injected ascidian sperm extract into the centre of unfertilized ascidian eggs that had been treated with microfilament- and microtubule-disrupting drugs, all the Ca2+ waves still originated from near the plasma membrane, showing that the sperm factor does not require an intact cortex if it is enriched near the plasma membrane (PM). We suggest that the Ca2+-releasing sperm factor might be tethered near or on the PM and that following the cortical contraction, it is translocated to the vegetal CP, thus making that site act as a Ca2+-wave pacemaker.

Age-related changes in localization of injected radiolabelled lymphocytes in the lymph nodes of antigen-stimulated mice.

PubMed Central

Inchley, C J; Micklem, H S; Barrett, J; Hunter, J; Minty, C

1976-01-01

The localization of i.v. injected syngeneic lymph node cells, radiolabelled with 51Cr or 75Se-L-selenomethionine, was studied in male CBA/H mice aged between 3 and 30 months. The following results were obtained. (1) Localization of cells from young adult donors was greater in the s.c. lymph nodes of old than of young recipients, the main increase being between 15 and 17 months of age. Increases in lymph node weight and DNA-synthesis were also seen at this time; but the rise in cell localization was significant even when calculated per unit of tissue weight. Splenic localization either declined slightly with age or, like the liver, showed no significant change. (2) Local antigenic stimulation by a single injection of sheep erythrocytes into one front footpad, 24 hr before lymph node cell injection, resulted in increased localization in the regional lymph nodes of 3-17 month old, but rarely of 24-30 month old mice. (3) No consistent differences in localization were observed between lymph node cells from 4-month and 25-month old donors. Both age-related and antigen-related increases in cell localization were at least partly attributable to an enhanced rate of entry of lymphocytes from the blood to the lymph nodes. Although the changes underlying the decline in antigen-related localization of cells in old recipients have still to be clarified, it is probable that the defective immune responses of old mice result partly from this decline. PMID:991459

A conserved domain in the NH2 terminus important for assembly and functional expression of pacemaker channels.

PubMed

Tran, Neil; Proenza, Catherine; Macri, Vincenzo; Petigara, Fiona; Sloan, Erin; Samler, Shannon; Accili, Eric A

2002-11-15

Pacemaker channels are formed by co-assembly of hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits. Previously, we suggested that the NH(2) termini of the mouse HCN2 isoform were important for subunit co-assembly and functional channel expression. Using an alignment strategy together with yeast two-hybrid assays, patch clamp electrophysiology, and confocal imaging, we have now identified a domain within the NH(2) terminus of the HCN2 subunit that is responsible for interactions between NH(2) termini and promoting the trafficking of functional channels to the plasma membrane. This domain is composed of 52 amino acids, is located adjacent to the putative first transmembrane segment, and is highly conserved among the mammalian HCN isoforms. This conserved domain, but not the remaining unconserved NH(2)-terminal regions of HCN2, specifically interacted with itself in yeast two-hybrid assays. Moreover, the conserved domain was important for expression of currents. Whereas relatively normal whole cell HCN2 currents were produced by channels containing only the conserved domain, further deletion of this region, leaving only a more polar and putative coiled-coil segment, eliminated HCN2 currents and resulted in proteins that localized predominantly in perinuclear compartments. Thus, we suggest that this conserved domain is the critical NH(2)-terminal determinant of subunit co-assembly and trafficking of pacemaker channels.

Pacemaker channels produce an instantaneous current.

PubMed

Proenza, Catherine; Angoli, Damiano; Agranovich, Eugene; Macri, Vincenzo; Accili, Eric A

2002-02-15

Spontaneous rhythmic activity in mammalian heart and brain depends on pacemaker currents (I(h)), which are produced by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here, we report that the mouse HCN2 pacemaker channel isoform also produced a large instantaneous current (I(inst(HCN2))) in addition to the well characterized, slowly activating I(h). I(inst(HCN2)) was specific to expression of HCN2 on the plasma membrane and its amplitude was correlated with that of I(h). The two currents had similar reversal potentials, and both were modulated by changes in intracellular Cl(-) and cAMP. A mutation in the S4 domain of HCN2 (S306Q) decreased I(h) but did not alter I(inst(HCN2)), and instantaneous currents in cells expressing either wild type HCN2 or mutant S306Q channels were insensitive to block by Cs(+). Co-expression of HCN2 with the accessory subunit, MiRP1, decreased I(h) and increased I(inst(HCN2)), suggesting a mechanism for modulation of both currents in vivo. These data suggest that expression of HCN channels may be accompanied by a background conductance in native tissues and are consistent with at least two open states of HCN channels: I(inst(HCN2)) is produced by a Cs(+)-open state; hyperpolarization produces an additional Cs(+)-sensitive open state, which results in I(h).