Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?

PubMed

Li, R A

2012-06-01

Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of nodal pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential.

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.

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

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

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.

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.

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

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.

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.

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

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

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

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

Cardiac Resynchronization Therapy and phase resetting of the sinoatrial node: A conjecture

NASA Astrophysics Data System (ADS)

Cantini, Federico; Varanini, Maurizio; Macerata, Alberto; Piacenti, Marcello; Morales, Maria-Aurora; Balocchi, Rita

2007-03-01

Congestive heart failure is a severe chronic disease often associated with disorders that alter the mechanisms of excitation-contraction coupling that may result in an asynchronous left ventricular motion which may further impair the ability of the failing heart to eject blood. In recent years a therapeutic approach to resynchronize the ventricles (cardiac resynchronization therapy, CRT) has been performed through the use of a pacemaker device able to provide atrial-based biventricular stimulation. Atrial lead senses the spontaneous occurrence of cells depolarization and sends the information to the generator which, in turn, after a settled delay [atrioventricular (AV) delay], sends electrical impulses to both ventricles to stimulate their synchronous contraction. Recent studies performed on heart rate behavior of chronically implanted patients at different epochs after implantation have shown that CRT can lead to sustained overall improvement of heart function with a reduction in morbidity and mortality. At this moment, however, there are no studies about CRT effects on spontaneous heart activity of chronically implanted patients. We performed an experimental study in which the electrocardiographic signal of five subjects under chronic CRT was recorded during the activity of the pacemaker programmed at different AV delays and under spontaneous cardiac activity after pacemaker deactivation. The different behavior of heart rate variability during pacemaker activity and after pacemaker deactivation suggested the hypothesis of a phase resetting mechanism induced by the pacemaker stimulus on the sinoatrial (SA) node, a phenomenon already known in literature for aggregate of cardiac cells, but still unexplored in vivo. The constraints imposed by the nature of our study (in vivo tests) made it impossible to plan an experiment to prove our hypothesis directly. We therefore considered the best attainable result would be to prove the accordance of our data to the conjecture through the use of models and physical considerations. We first used the data of literature on far-field effects of cardiac defibrillators to prove that the pacemaker impulses delivered to the two ventricles were able to induce modifications in membrane voltage at the level of the SA node. To simulate a phase resetting mechanism of the SA node, we used a Van der Pol modified model to allow the possibility of changing the refractory period and the firing frequency of the cells separately. With appropriate parameters of the model we reproduced phase response curves that can account for our experimental data. Furthermore, the simulated curves closely resemble the functional form proposed in literature for perturbed aggregate of cardiac cells. Despite the small sample of subjects investigated and the limited number of ECG recordings at different AV delays, we think we have proved the plausibility of the proposed conjecture.

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.

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.

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.

Next-generation pacemakers: from small devices to biological pacemakers.

PubMed

Cingolani, Eugenio; Goldhaber, Joshua I; Marbán, Eduardo

2018-03-01

Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator. Modern pacemakers are generally reliable, and their programmability provides options for different pacing modes tailored to specific clinical needs. Advances in device technology will probably include alternative energy sources and dual-chamber leadless pacing in the not-too-distant future. Although effective, current electronic devices have limitations related to lead or generator malfunction, lack of autonomic responsiveness, undesirable interactions with strong magnetic fields, and device-related infections. Biological pacemakers, generated by somatic gene transfer, cell fusion, or cell transplantation, provide an alternative to electronic devices. Somatic reprogramming strategies, which involve transfer of genes encoding transcription factors to transform working myocardium into a surrogate sinoatrial node, are furthest along in the translational pipeline. Even as electronic pacemakers become smaller and less invasive, biological pacemakers might expand the therapeutic armamentarium for conduction system disorders.

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 ...

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.

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

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

Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.

PubMed

Monfredi, Oliver; Tsutsui, Kenta; Ziman, Bruce; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

2018-03-01

Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology, and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPCs) sampled from the paracristal, intercaval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. The beating rate was measured at baseline and after inhibition of the Ca 2+ pump with cyclopiazonic acid. Thereafter, in each cell, we consecutively measured the density of funny current ( I f ), delayed rectifier K + current ( I K ) (a surrogate of repolarization capacity), and L-type Ca 2+ current ( I Ca,L ) using whole cell patch clamp . The ionic current densities varied to a greater extent than previously appreciated, with some IPCs demonstrating very small or zero I f . The density of none of the currents was correlated with cell size, while I Ca,L and I f densities were related to baseline beating rates. I f density was correlated with I K density but not with that of I Ca,L . Inhibition of Ca 2+ cycling had a greater beating rate slowing effect in IPCs with lower I f densities. Our numerical model simulation indicated that 1) IPCs with small (or zero) I f or small I Ca,L can operate via a major contribution of Ca 2+ clock, 2) I f -Ca 2+ -clock interplay could be important for robust pacemaking function, and 3) coupled I f - I K function could regulate maximum diastolic potential. Thus, we have demonstrated marked electrophysiological heterogeneity of IPCs. This heterogeneity is manifested in basal beating rate and response to interference of Ca 2+ cycling, which is linked to I f . NEW & NOTEWORTHY In the present study, a hitherto unrecognized range of heterogeneity of ion currents in pacemaker cells from the intercaval region is demonstrated. Relationships between basal beating rate and L-type Ca 2+ current and funny current ( I f ) density are uncovered, along with a positive relationship between I f and delayed rectifier K + current. Links are shown between the response to Ca 2+ cycling blockade and I f density.

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.

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.

Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection

PubMed Central

Rimmbach, Christian; Jung, Julia J.; David, Robert

2015-01-01

Treatment of the “sick sinus syndrome” is based on artificial pacemakers. These bear hazards such as battery failure and infections. Moreover, they lack hormone responsiveness and the overall procedure is cost-intensive. “Biological pacemakers” generated from PSCs may become an alternative, yet the typical content of pacemaker cells in Embryoid Bodies (EBs) is extremely low. The described protocol combines “forward programming” of murine PSCs via the sinus node inducer TBX3 with Myh6-promoter based antibiotic selection. This yields cardiomyocyte aggregates consistent of >80% physiologically functional pacemaker cells. These “induced-sinoatrial-bodies” (“iSABs”) are spontaneously contracting at yet unreached frequencies (400-500 bpm) corresponding to nodal cells isolated from mouse hearts and are able to pace murine myocardium ex vivo. Using the described protocol highly pure sinus nodal single cells can be generated which e.g. can be used for in vitro drug testing. Furthermore, the iSABs generated according to this protocol may become a crucial step towards heart tissue engineering. PMID:25742394

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.

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

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.

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.

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.

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

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

Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking

PubMed Central

Unudurthi, Sathya D.; Wolf, Roseanne M.; Hund, Thomas J.

2014-01-01

Normal heart rhythm (sinus rhythm) depends on regular activity of the sinoatrial node (SAN), a heterogeneous collection of specialized myocytes in the right atrium. SAN cells, in general, possess a unique electrophysiological profile that promotes spontaneous electrical activity (automaticity). However, while automaticity is required for normal pacemaking, it is not necessarily sufficient. Less appreciated is the importance of the elaborate structure of the SAN complex for proper pacemaker function. Here, we review the important structural features of the SAN with a focus on how these elements help manage a precarious balance between electrical charge generated by the SAN (“source”) and the charge needed to excite the surrounding atrial tissue (“sink”). We also discuss how compromised “source-sink” balance due, for example to fibrosis, may promote SAN dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, in the setting of cardiovascular disease (e.g., heart failure, atrial fibrillation). Finally, we discuss implications of the “source-sink” balance in the SAN complex for cell and gene therapies aimed at creating a biological pacemaker as replacement or bridge to conventional electronic pacemakers. PMID:25505419

Embryological development of pacemaker hierarchy and membrane currents related to the function of the adult sinus node: implications for autonomic modulation of biopacemakers.

PubMed

Opthof, Tobias

2007-02-01

The sinus node is an inhomogeneous structure. In the embryonic heart all myocytes have sinus node type pacemaker channels (I (f)) in their sarcolemma. Shortly before birth, these channels disappear from the ventricular myocytes. The response of the adult sinus node to changes in the interstitium, in particular to (neuro)transmitters, results from the interplay between the responses of all of its constituent cells. The response of the whole sinus node cannot be simply deduced from these cellular responses, because all cells have different responses to specific agonists. A biological pacemaker will be more homogeneous. Therefore it can be anticipated that tuning of cycle length may be problematic. It is discussed that efforts to create a biological pacemaker responsive to vagal stimulation, may be counterproductive, because it may have the potential risk of 'standstill' of the biological pacemaker. A normal sinus node remains spontaneously active at high concentrations of acetylcholine, because it has areas that are unresponsive to acetylcholine. The same is pertinent to other substances with a negative chronotropic effect. Such functional inhomogeneity is lacking in biological pacemakers.

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.

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.

Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP mediated PKA-dependent Ca2+ cycling with surface membrane channels

PubMed Central

Vinogradova, Tatiana M.; Lakatta, Edward G.

2009-01-01

Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+-release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cells spontaneous firing. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker firing. Both the basal primary pacemaker beating rate and its modulation via β-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous firing of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during β-adrenergic receptor stimulation. PMID:19573534

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.

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

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.

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.

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.

Sick sinus syndrome in HCN1-deficient mice.

PubMed

Fenske, Stefanie; Krause, Stefanie C; Hassan, Sami I H; Becirovic, Elvir; Auer, Franziska; Bernard, Rebekka; Kupatt, Christian; Lange, Philipp; Ziegler, Tilman; Wotjak, Carsten T; Zhang, Henggui; Hammelmann, Verena; Paparizos, Christos; Biel, Martin; Wahl-Schott, Christian A

2013-12-17

Sinus node dysfunction (SND) is a major clinically relevant disease that is associated with sudden cardiac death and requires surgical implantation of electric pacemaker devices. Frequently, SND occurs in heart failure and hypertension, conditions that lead to electric instability of the heart. Although the pathologies of acquired SND have been studied extensively, little is known about the molecular and cellular mechanisms that cause congenital SND. Here, we show that the HCN1 protein is highly expressed in the sinoatrial node and is colocalized with HCN4, the main sinoatrial pacemaker channel isoform. To characterize the cardiac phenotype of HCN1-deficient mice, a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparation, telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology was performed. On the basis of these experiments we demonstrate that mice lacking the pacemaker channel HCN1 display congenital SND characterized by bradycardia, sinus dysrhythmia, prolonged sinoatrial node recovery time, increased sinoatrial conduction time, and recurrent sinus pauses. As a consequence of SND, HCN1-deficient mice display a severely reduced cardiac output. We propose that HCN1 stabilizes the leading pacemaker region within the sinoatrial node and hence is crucial for stable heart rate and regular beat-to-beat variation. Furthermore, we suggest that HCN1-deficient mice may be a valuable genetic disease model for human SND.

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

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

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

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

Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

PubMed

Kojima, Akiko; Ito, Yuki; Kitagawa, Hirotoshi; Matsuura, Hiroshi; Nosaka, Shuichi

2014-06-01

Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca currents (ICa,T and ICa,L, respectively), Na/Ca exchange current (INCX), and rapidly and slowly activating delayed rectifier K currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.

Human embryonic and induced pluripotent stem cell-derived cardiomyocytes exhibit beat rate variability and power-law behavior.

PubMed

Mandel, Yael; Weissman, Amir; Schick, Revital; Barad, Lili; Novak, Atara; Meiry, Gideon; Goldberg, Stanislav; Lorber, Avraham; Rosen, Michael R; Itskovitz-Eldor, Joseph; Binah, Ofer

2012-02-21

The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. Although an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess the suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electric activity of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) exhibit beat rate variability and power-law behavior comparable to those of human sinoatrial node. We recorded extracellular electrograms from hESC-CMs and iPSC-CMs under stable conditions for up to 15 days. The beat rate time series of the spontaneous activity were examined in terms of their power spectral density and additional methods derived from nonlinear dynamics. The major findings were that the mean beat rate of hESC-CMs and iPSC-CMs was stable throughout the 15-day follow-up period and was similar in both cell types, that hESC-CMs and iPSC-CMs exhibited intrinsic beat rate variability and fractal behavior, and that isoproterenol increased and carbamylcholine decreased the beating rate in both hESC-CMs and iPSC-CMs. This is the first study demonstrating that hESC-CMs and iPSC-CMs exhibit beat rate variability and power-law behavior as in humans, thus supporting the potential capability of these cell sources to serve as biological pacemakers. Our ability to generate sinoatrial-compatible spontaneous cardiomyocytes from the patient's own hair (via keratinocyte-derived iPSCs), thus eliminating the critical need for immunosuppression, renders these myocytes an attractive cell source as biological pacemakers.

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.

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.

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

If and SR Ca2+ release both contribute to pacemaker activity in canine sinoatrial node cells

PubMed Central

Gao, Zhan; Chen, Biyi; Joiner, Mei-ling A.; Wu, Yuejin; Guan, Xiaoqun; Koval, Olha M.; Chaudhary, Ashok K.; Cunha, Shane R.; Mohler, Peter J.; Martins, James B.; Song, Long-Sheng; Anderson, Mark E.

2010-01-01

Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a ‘voltage clock’ and a Ca2+ dependent process, or ‘Ca2+ clock.’ The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (If) is thought to be particularly important. A Ca2+ dependent process triggers APs when sarcoplasmic reticulum (SR) Ca2+ release activates inward current carried by the forward mode of the electrogenic Na+/Ca2+ exchanger (NCX). However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals. Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca2+ clock mechanisms in canine SAN pacemaker cells. We found that ZD7288, a selective If antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells. In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol. In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest (∼14%) and did not reach statistical significance. Importantly, pretreatment with ryanodine eliminated SR Ca2+ release, but did not affect basal or isoproterenol-enhanced If. Taken together, these results indicate that voltage and Ca2+ dependent automaticity mechanisms coexist in canine SAN cells, and suggest If and SR Ca2+ release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells. PMID:20380837

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.

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

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 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

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

Simulation of Ectopic Pacemakers in the Heart: Multiple Ectopic Beats Generated by Reentry inside Fibrotic Regions

PubMed Central

Gouvêa de Barros, Bruno; Weber dos Santos, Rodrigo; Alonso, Sergio

2015-01-01

The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies. PMID:26583127

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

[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).

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.

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

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.

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.

Field Markup Language: biological field representation in XML.

PubMed

Chang, David; Lovell, Nigel H; Dokos, Socrates

2007-01-01

With an ever increasing number of biological models available on the internet, a standardized modeling framework is required to allow information to be accessed or visualized. Based on the Physiome Modeling Framework, the Field Markup Language (FML) is being developed to describe and exchange field information for biological models. In this paper, we describe the basic features of FML, its supporting application framework and its ability to incorporate CellML models to construct tissue-scale biological models. As a typical application example, we present a spatially-heterogeneous cardiac pacemaker model which utilizes both FML and CellML to describe and solve the underlying equations of electrical activation and propagation.

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

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.

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

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

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.

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

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.

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.

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

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.

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.

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.

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.

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.

Modeling and experimental verification of a fan-folded vibration energy harvester for leadless pacemakers

NASA Astrophysics Data System (ADS)

Ansari, M. H.; Karami, M. Amin

2016-03-01

This paper studies energy harvesting from heartbeat vibrations for powering leadless pacemakers. Unlike traditional pacemakers, leadless pacemakers are implanted inside the heart and the pacemaker is in direct contact with the myocardium. A leadless pacemaker is in the shape of a cylinder. Thus, in order to utilize the available 3-dimensional space for the energy harvester, we choose a fan-folded 3D energy harvester. The proposed device consists of several piezoelectric beams stacked on top of each other. The volume of the energy harvester is 1 cm3 and its dimensions are 2 cm × 0.5 cm × 1 cm. Although high natural frequency is generally a major concern with micro-scale energy harvesters, by utilizing the fan-folded geometry and adding tip mass and link mass to the configuration, we reduced the natural frequency to the desired range. This fan-folded design makes it possible to generate more than 10 μ W of power per cubic centimeter. The proposed device is compatible with Magnetic Resonance Imaging. Although the proposed device is a linear energy harvester, it is relatively insensitive to the heart rate. The natural frequencies and the mode shapes of the device are calculated analytically. The accuracy of the analytical model is verified by experimental investigations. We use a closed loop shaker system to precisely replicate heartbeat vibrations in vitro.

An electrical description of the generation of slow waves in the antrum of the guinea-pig

PubMed Central

Edwards, FR; Hirst, GDS

2005-01-01

This paper provides an electrical description of the generation of slow waves in the guinea-pig gastric antrum. A short segment of a circular smooth muscle bundle with an attached network of myenteric interstitial cells of Cajal (ICC-MY) and longitudinal muscle sheet was modelled as three electrical compartments with resistive connexions between the ICC-MY compartment and each of the smooth muscle compartments. The circular smooth muscle layer contains a proportion of intramuscular interstitial cells of Cajal (ICC-IM), responsible for the regenerative component of the slow wave. Hence the equivalent cell representing the circular muscle layer incorporated a mechanism, modelled as a two stage reaction, which produces an intracellular messenger. The first stage of the reaction is proposed to be activated in a voltage-dependent manner as described by Hodgkin and Huxley. A similar mechanism was incorporated into the equivalent cell describing the ICC-MY network. Spontaneous discrete transient depolarizations, termed unitary potentials, are detected in records taken from either bundles of circular smooth muscle containing ICC-IM or from ICC-MY. In the simulation the mean rate of discharge of unitary potentials was allowed to vary with the concentration of messenger according to a conventional dose–effect relationship. Such a mechanism, which describes regenerative potentials generated by the circular muscle layer, also simulated the plateau component of the pacemaker potential in the ICC-MY network. A voltage-sensitive membrane conductance was included in the ICC-MY compartment; this was used to describe the primary component of the pacemaker potential. The model generates a range of membrane potential changes with properties similar to those generated by the three cell types present in the intact tissue. PMID:15613372

Computational Reconstruction of Pacemaking and Intrinsic Electroresponsiveness in Cerebellar Golgi Cells

PubMed Central

Solinas, Sergio; Forti, Lia; Cesana, Elisabetta; Mapelli, Jonathan; De Schutter, Erik; D'Angelo, Egidio

2007-01-01

The Golgi cells have been recently shown to beat regularly in vitro (Forti et al., 2006. J. Physiol. 574, 711–729). Four main currents were shown to be involved, namely a persistent sodium current (I Na-p), an h current (I h), an SK-type calcium-dependent potassium current (I K-AHP), and a slow M-like potassium current (I K-slow). These ionic currents could take part, together with others, also to different aspects of neuronal excitability like responses to depolarizing and hyperpolarizing current injection. However, the ionic mechanisms and their interactions remained largely hypothetical. In this work, we have investigated the mechanisms of Golgi cell excitability by developing a computational model. The model predicts that pacemaking is sustained by subthreshold oscillations tightly coupled to spikes. I Na-p and I K-slow emerged as the critical determinants of oscillations. I h also played a role by setting the oscillatory mechanism into the appropriate membrane potential range. I K-AHP, though taking part to the oscillation, appeared primarily involved in regulating the ISI following spikes. The combination with other currents, in particular a resurgent sodium current (I Na-r) and an A-current (I K-A), allowed a precise regulation of response frequency and delay. These results provide a coherent reconstruction of the ionic mechanisms determining Golgi cell intrinsic electroresponsiveness and suggests important implications for cerebellar signal processing, which will be fully developed in a companion paper (Solinas et al., 2008. Front. Neurosci. 2:4). PMID:18946520

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

A discrete model to study reaction-diffusion-mechanics systems.

PubMed

Weise, Louis D; Nash, Martyn P; Panfilov, Alexander V

2011-01-01

This article introduces a discrete reaction-diffusion-mechanics (dRDM) model to study the effects of deformation on reaction-diffusion (RD) processes. The dRDM framework employs a FitzHugh-Nagumo type RD model coupled to a mass-lattice model, that undergoes finite deformations. The dRDM model describes a material whose elastic properties are described by a generalized Hooke's law for finite deformations (Seth material). Numerically, the dRDM approach combines a finite difference approach for the RD equations with a Verlet integration scheme for the equations of the mass-lattice system. Using this framework results were reproduced on self-organized pacemaking activity that have been previously found with a continuous RD mechanics model. Mechanisms that determine the period of pacemakers and its dependency on the medium size are identified. Finally it is shown how the drift direction of pacemakers in RDM systems is related to the spatial distribution of deformation and curvature effects.

A Discrete Model to Study Reaction-Diffusion-Mechanics Systems

PubMed Central

Weise, Louis D.; Nash, Martyn P.; Panfilov, Alexander V.

2011-01-01

This article introduces a discrete reaction-diffusion-mechanics (dRDM) model to study the effects of deformation on reaction-diffusion (RD) processes. The dRDM framework employs a FitzHugh-Nagumo type RD model coupled to a mass-lattice model, that undergoes finite deformations. The dRDM model describes a material whose elastic properties are described by a generalized Hooke's law for finite deformations (Seth material). Numerically, the dRDM approach combines a finite difference approach for the RD equations with a Verlet integration scheme for the equations of the mass-lattice system. Using this framework results were reproduced on self-organized pacemaking activity that have been previously found with a continuous RD mechanics model. Mechanisms that determine the period of pacemakers and its dependency on the medium size are identified. Finally it is shown how the drift direction of pacemakers in RDM systems is related to the spatial distribution of deformation and curvature effects. PMID:21804911

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.

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

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

Refinement of a limit cycle oscillator model of the effects of light on the human circadian pacemaker

NASA Technical Reports Server (NTRS)

Jewett, M. E.; Kronauer, R. E.; Brown, E. N. (Principal Investigator)

1998-01-01

In 1990, Kronauer proposed a mathematical model of the effects of light on the human circadian pacemaker. Although this model predicted many general features of the response of the human circadian pacemaker to light exposure, additional data now available enable us to refine the original model. We first refined the original model by incorporating the results of a dose response curve to light into the model's predicted relationship between light intensity and the strength of the drive onto the pacemaker. Data from three bright light phase resetting experiments were then used to refine the amplitude recovery characteristics of the model. Finally, the model was tested and further refined using data from an extensive phase resetting experiment in which a 3-cycle bright light stimulus was presented against a background of dim light. In order to describe the results of the four resetting experiments, the following major refinements to the original model were necessary: (i) the relationship between light intensity (I) and drive onto the pacemaker was reduced from I1/3 to I0.23 for light levels between 150 and 10,000 lux; (ii) the van der Pol oscillator from the original model was replaced with a higher-order limit cycle oscillator so that amplitude recovery is slower near the singularity and faster near the limit cycle; (iii) a direct effect of light on circadian period (tau x) was incorporated into the model such that as I increases, tau x decreases, which is in accordance with "Aschoff's rule". This refined model generates the following testable predictions: it should be difficult to enhance normal circadian amplitude via bright light; near the critical point of a type 0 phase response curve (PRC) the slope should be steeper than it is in a type 1 PRC; and circadian period measured during forced desynchrony should be directly affected by ambient light intensity.

Phase diagram for the Winfree model of coupled nonlinear oscillators.

PubMed

Ariaratnam, J T; Strogatz, S H

2001-05-07

In 1967 Winfree proposed a mean-field model for the spontaneous synchronization of chorusing crickets, flashing fireflies, circadian pacemaker cells, or other large populations of biological oscillators. Here we give the first bifurcation analysis of the model, for a tractable special case. The system displays rich collective dynamics as a function of the coupling strength and the spread of natural frequencies. Besides incoherence, frequency locking, and oscillator death, there exist hybrid solutions that combine two or more of these states. We present the phase diagram and derive several of the stability boundaries analytically.

Phase Diagram for the Winfree Model of Coupled Nonlinear Oscillators

NASA Astrophysics Data System (ADS)

Ariaratnam, Joel T.; Strogatz, Steven H.

2001-05-01

In 1967 Winfree proposed a mean-field model for the spontaneous synchronization of chorusing crickets, flashing fireflies, circadian pacemaker cells, or other large populations of biological oscillators. Here we give the first bifurcation analysis of the model, for a tractable special case. The system displays rich collective dynamics as a function of the coupling strength and the spread of natural frequencies. Besides incoherence, frequency locking, and oscillator death, there exist hybrid solutions that combine two or more of these states. We present the phase diagram and derive several of the stability boundaries analytically.

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

Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias

PubMed Central

O'Grady, Gregory; Du, Peng; Paskaranandavadivel, Nira; Angeli, Timothy R.; Lammers, Wim JEP; Asirvatham, Samuel J.; Windsor, John A.; Farrugia, Gianrico; Pullan, Andrew J.; Cheng, Leo K.

2012-01-01

Background Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that: i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; iii) the driving network conductance might switch between ICC-MP and circular ICC-IM during circumferential propagation; iv) extracellular amplitudes and velocities are correlated. Methods An experimental-theoretical study was performed. HR gastric mapping was performed in pigs during normal activation, pacing and dysrhythmia. Activation profiles, velocities and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modelled as a function of membrane potentials. Key Results High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments, was faster than longitudinal propagation (8.9 vs 6.9 mm/s; p=0.004), and of higher amplitude (739 vs 528 μV; p=0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (p<0.001). Conclusions & Inferences The high-velocity and high-amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks. PMID:22709238

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.

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

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.

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.

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

Using an elastic magnifier to increase power output and performance of heart-beat harvesters

NASA Astrophysics Data System (ADS)

Galbier, Antonio C.; Karami, M. Amin

2017-09-01

Embedded piezoelectric energy harvesting (PEH) systems in medical pacemakers have been a growing and innovative research area. The goal of these systems, at present, is to remove the pacemaker battery, which makes up 60%-80% of the unit, and replace it with a sustainable power source. This requires that energy harvesting systems provide sufficient power, 1-3 μW, for operating a pacemaker. The goal of this work is to develop, test, and simulate cantilevered energy harvesters with a linear elastic magnifier (LEM). This research hopes to provide insight into the interaction between pacemaker energy harvesters and the heart. By introducing the elastic magnifier into linear and nonlinear systems oscillations of the tip are encouraged into high energy orbits and large tip deflections. A continuous nonlinear model is presented for the bistable piezoelectric energy harvesting (BPEH) system and a one-degree-of-freedom linear mass-spring-damper model is presented for the elastic magnifier. The elastic magnifier will not consider the damping negligible, unlike most models. A physical model was created for the bistable structure and formed to an elastic magnifier. A hydrogel was designed for the experimental model for the LEM. Experimental results show that the BPEH coupled with a LEM (BPEH + LEM) produces more power at certain input frequencies and operates a larger bandwidth than a PEH, BPEH, and a standard piezoelectric energy harvester with the elastic magnifier (PEH + LEM). Numerical simulations are consistent with these results. It was observed that the system enters high-energy and high orbit oscillations and that, ultimately, BPEH systems implemented in medical pacemakers can, if designed properly, have enhanced performance if positioned over the heart.

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.

Spatial Analysis of Slowly Oscillating Electric Activity in the Gut of Mice Using Low Impedance Arrayed Microelectrodes

PubMed Central

Taniguchi, Mizuki; Kajioka, Shunichi; Shozib, Habibul B.; Sawamura, Kenta; Nakayama, Shinsuke

2013-01-01

Smooth and elaborate gut motility is based on cellular cooperation, including smooth muscle, enteric neurons and special interstitial cells acting as pacemaker cells. Therefore, spatial characterization of electric activity in tissues containing these electric excitable cells is required for a precise understanding of gut motility. Furthermore, tools to evaluate spatial electric activity in a small area would be useful for the investigation of model animals. We thus employed a microelectrode array (MEA) system to simultaneously measure a set of 8×8 field potentials in a square area of ∼1 mm2. The size of each recording electrode was 50×50 µm2, however the surface area was increased by fixing platinum black particles. The impedance of microelectrode was sufficiently low to apply a high-pass filter of 0.1 Hz. Mapping of spectral power, and auto-correlation and cross-correlation parameters characterized the spatial properties of spontaneous electric activity in the ileum of wild-type (WT) and W/Wv mice, the latter serving as a model of impaired network of pacemaking interstitial cells. Namely, electric activities measured varied in both size and cooperativity in W/Wv mice, despite the small area. In the ileum of WT mice, procedures suppressing the excitability of smooth muscle and neurons altered the propagation of spontaneous electric activity, but had little change in the period of oscillations. In conclusion, MEA with low impedance electrodes enables to measure slowly oscillating electric activity, and is useful to evaluate both histological and functional changes in the spatio-temporal property of gut electric activity. PMID:24124480

Mathematical modeling in chronobiology.

PubMed

Bordyugov, G; Westermark, P O; Korenčič, A; Bernard, S; Herzel, H

2013-01-01

Circadian clocks are autonomous oscillators entrained by external Zeitgebers such as light-dark and temperature cycles. On the cellular level, rhythms are generated by negative transcriptional feedback loops. In mammals, the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus plays the role of the central circadian pacemaker. Coupling between individual neurons in the SCN leads to precise self-sustained oscillations even in the absence of external signals. These neuronal rhythms orchestrate the phasing of circadian oscillations in peripheral organs. Altogether, the mammalian circadian system can be regarded as a network of coupled oscillators. In order to understand the dynamic complexity of these rhythms, mathematical models successfully complement experimental investigations. Here we discuss basic ideas of modeling on three different levels (1) rhythm generation in single cells by delayed negative feedbacks, (2) synchronization of cells via external stimuli or cell-cell coupling, and (3) optimization of chronotherapy.

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.

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.

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

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.

Tropical Pacific variability as a key pacemaker of the global warming staircase

NASA Astrophysics Data System (ADS)

Kosaka, Y.; Xie, S. P.

2016-12-01

Global-mean surface temperature (GMST) has increased since the 19th century with notable interdecadal accelerations and slowdowns, forming the global-warming "staircase". The last step of this staircase is the surface warming slowdown since the late 1990s, for which the transition of the Interdecadal Pacific Oscillation (IPO) from a positive to negative state has been suggested as the leading mechanism. To examine the role of IPO in the entire warming staircase, a long pacemaker experiment is performed with a coupled climate model where tropical Pacific sea surface temperatures are forced to follow the observed evolution since the late 19th century. The pacemaker experiment successfully reproduces the staircase-like global warming remarkably well since 1900. Without the tropical Pacific effect, the same model produces a continual warming from the 1900s to the 1960 followed by rapid warming. The successful reproduction identifies the tropical Pacific decadal variability as a key pacemaker of the GMST staircase. We further propose a method to remove internal variability from observed GMST changes for real-time monitoring of anthropogenic warming.

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

Safety evaluation of a leadless transcatheter pacemaker for magnetic resonance imaging use.

PubMed

Soejima, Kyoko; Edmonson, Jonathan; Ellingson, Michael L; Herberg, Ben; Wiklund, Craig; Zhao, Jing

2016-10-01

Increased magnetic resonance imaging (MRI) adoption and demand are driving the need for device patients to have safe access to MRI. The aim of this study was to address the interactions of MRI with the Micra transcatheter pacemaker system. A strategy was developed to evaluate potential MRI risks including device heating, unintended cardiac stimulation, force, torque, vibration, and device malfunction. Assessment of MRI-induced device heating was conducted using a phantom containing gelled saline, and Monte Carlo simulations incorporating these results were conducted to simulate numerous combinations of human body models, position locations in the MRI scanner bore, and a variety of coil designs. Lastly, a patient with a Micra pacemaker who underwent a clinically indicated MRI scan is presented. Compared to traditional MRI conditional pacemakers, the overall risk with Micra was greatly reduced because of the small size of the device and the absence of a lead. The modeling results predicted that the nonperfused temperature rise of the device would be less than 0.4°C at 1.5 T and 0.5°C at 3 T and that the risk of device heating with multiple device implants was not increased as compared with a single device. The clinical case study revealed no MRI-related complications. The MRI safety assessment tests conducted for the Micra pacemaker demonstrate that patients with a single device or multiple devices can safely undergo MRI scans in both 1.5- and 3-T MRI scanners. No MRI-related complications were observed in a patient implanted with a Micra pacemaker undergoing a clinically indicated scan. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

A statistical model of the human core-temperature circadian rhythm

NASA Technical Reports Server (NTRS)

Brown, E. N.; Choe, Y.; Luithardt, H.; Czeisler, C. A.

2000-01-01

We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator ( approximately 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator.

Implications of cellular models of dopamine neurons for disease

PubMed Central

Evans, Rebekah C.; Oster, Andrew M.; Pissadaki, Eleftheria K.; Drion, Guillaume; Kuznetsov, Alexey S.; Gutkin, Boris S.

2016-01-01

This review addresses the present state of single-cell models of the firing pattern of midbrain dopamine neurons and the insights that can be gained from these models into the underlying mechanisms for diseases such as Parkinson's, addiction, and schizophrenia. We will explain the analytical technique of separation of time scales and show how it can produce insights into mechanisms using simplified single-compartment models. We also use morphologically realistic multicompartmental models to address spatially heterogeneous aspects of neural signaling and neural metabolism. Separation of time scale analyses are applied to pacemaking, bursting, and depolarization block in dopamine neurons. Differences in subpopulations with respect to metabolic load are addressed using multicompartmental models. PMID:27582295

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.

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

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.

[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

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.

Case studies on the effect of exercise and hot water submersion on intracardiac temperature and the performance of a pacemaker which varies pacing rate based on temperature.

PubMed

Fearnot, N E; Kitoh, O; Fujita, T; Okamura, H; Smith, H J; Calderini, M

1989-05-01

The effectiveness of using blood temperature change as an indicator to automatically vary heart rate physiologically was evaluated in 3 patients implanted with Model Sensor Kelvin 500 (Cook Pacemaker Corporation, Leechburg, PA, USA) pacemakers. Each patient performed two block-randomized treadmill exercise tests: one while programmed for temperature-based, rate-modulated pacing and the other while programmed without rate modulation. In 1 pacemaker patient and 4 volunteers, heart rates were recorded during exposure to a hot water bath. Blood temperature measured at 10 sec intervals and pacing rate measured at 1 min intervals were telemetered to a diagnostic programmer and data collector for storage and transfer to a computer. Observation comments and ECG-derived heart rates were manually recorded. The temperature-based pacemaker was shown to respond promptly not only to physical exertion but also to emotionally caused stress and submersion in a hot bath. These events cause increased heart rate in the normal heart. Using a suitable algorithm to process the measurement of blood temperature, it was possible to produce appropriate pacing rates in paced patients.

Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart

PubMed Central

Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

2012-01-01

BACKGROUND AND PURPOSE The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), and slowly activating delayed rectifier K+ current (IKs), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS In isolated SA node cells, sevoflurane (0.12–0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased If, ICa,T, ICa,L and IKs by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on If, ICa,T and ICa,L. These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings. PMID:22356456

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.

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.

Electromechanical integration of cardiomyocytes derived from human embryonic stem cells.

PubMed

Kehat, Izhak; Khimovich, Leonid; Caspi, Oren; Gepstein, Amira; Shofti, Rona; Arbel, Gil; Huber, Irit; Satin, Jonathan; Itskovitz-Eldor, Joseph; Gepstein, Lior

2004-10-01

Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.

The effects of temperature on the stability of a neuronal oscillator.

PubMed

Rinberg, Anatoly; Taylor, Adam L; Marder, Eve

2013-01-01

The crab Cancer borealis undergoes large daily fluctuations in environmental temperature (8-24°C) and must maintain appropriate neural function in the face of this perturbation. In the pyloric circuit of the crab stomatogastric ganglion, we pharmacologically isolated the pacemaker kernel (the AB and PD neurons) and characterized its behavior in response to temperature ramps from 7°C to 31°C. For moderate temperatures, the pacemaker displayed a frequency-temperature curve statistically indistinguishable from that of the intact circuit, and like the intact circuit maintained a constant duty cycle. At high temperatures (above 23°C), a variety of different behaviors were seen: in some preparations the pacemaker increased in frequency, in some it slowed, and in many preparations the pacemaker stopped oscillating ("crashed"). Furthermore, these crashes seemed to fall into two qualitatively different classes. Additionally, the animal-to-animal variability in frequency increased at high temperatures. We used a series of Morris-Lecar mathematical models to gain insight into these phenomena. The biophysical components of the final model have temperature sensitivities similar to those found in nature, and can crash via two qualitatively different mechanisms that resemble those observed experimentally. The crash type is determined by the precise parameters of the model at the reference temperature, 11°C, which could explain why some preparations seem to crash in one way and some in another. Furthermore, even models with very similar behavior at the reference temperature diverge greatly at high temperatures, resembling the experimental observations.

Mechanisms for the target patterns formation in a stochastic bistable excitable medium

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.

2018-04-01

We study the features of formation and evolution of spatiotemporal chaotic regime generated by autonomous pacemakers in excitable deterministic and stochastic bistable active media using the example of the FitzHugh - Nagumo biological neuron model under discrete medium conditions. The following possible mechanisms for the formation of autonomous pacemakers have been studied: 1) a temporal external force applied to a small region of the medium, 2) geometry of the solution region (the medium contains regions with Dirichlet or Neumann boundaries). In our work we explore the conditions for the emergence of pacemakers inducing target patterns in a stochastic bistable excitable system and propose the algorithm for their analysis.

Defibrillator/monitor/pacemakers.

PubMed

2002-02-01

Defibrillator/monitors allow operators to assess and monitor a patient's ECG and, when necessary, deliver a defibrillating shock to the heart. When integral noninvasive pacing capability is added, the resulting device is referred to as a defibrillator/monitor/pacemaker. In this Update Evaluation, we present our findings for one newly evaluated model, the Philips Heartstream XL, and we summarize our findings for the seven previously evaluated models that are still on the market. (Our previous Evaluations were published in the May-June 1993, February 1998, and September 2000 issues of Health Devices.) Defibrillator/monitor/pacemakers are used for a variety of applications within the hospital, as well as by emergency medical services (EMS) personnel and others in the prehospital environment. To help both hospital-based and prehospital users select an appropriate model, we rate the models (1) for each of three in-hospital applications--general crash-cart use, in-hospital transport use, and in-hospital use by basic as well as advanced users--and (2) for prehospital (EMS) use. For in-hospital use, we recommend four of the evaluated models. These received either Preferred or Acceptable ratings for all the applications considered. For prehospital use, we found that five of the models will meet most organizations' needs.

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

Neuronal Atrophy Early in Degenerative Ataxia Is a Compensatory Mechanism to Regulate Membrane Excitability

PubMed Central

Dell'Orco, James M.; Wasserman, Aaron H.; Chopra, Ravi; Ingram, Melissa A. C.; Hu, Yuan-Shih; Singh, Vikrant; Wulff, Heike; Opal, Puneet; Orr, Harry T.

2015-01-01

Neuronal atrophy in neurodegenerative diseases is commonly viewed as an early event in a continuum that ultimately results in neuronal loss. In a mouse model of the polyglutamine disorder spinocerebellar ataxia type 1 (SCA1), we tested the hypothesis that cerebellar Purkinje neuron atrophy serves an adaptive role rather than being simply a nonspecific response to injury. In acute cerebellar slices from SCA1 mice, we find that Purkinje neuron pacemaker firing is initially normal but, with the onset of motor dysfunction, becomes disrupted, accompanied by abnormal depolarization. Remarkably, subsequent Purkinje cell atrophy is associated with a restoration of pacemaker firing. The early inability of Purkinje neurons to support repetitive spiking is due to unopposed calcium currents resulting from a reduction in large-conductance calcium-activated potassium (BK) and subthreshold-activated potassium channels. The subsequent restoration of SCA1 Purkinje neuron firing correlates with the recovery of the density of these potassium channels that accompanies cell atrophy. Supporting a critical role for BK channels, viral-mediated increases in BK channel expression in SCA1 Purkinje neurons improves motor dysfunction and partially restores Purkinje neuron morphology. Cerebellar perfusion of flufenamic acid, an agent that restores the depolarized membrane potential of SCA1 Purkinje neurons by activating potassium channels, prevents Purkinje neuron dendritic atrophy. These results suggest that Purkinje neuron dendritic remodeling in ataxia is an adaptive response to increases in intrinsic membrane excitability. Similar adaptive remodeling could apply to other vulnerable neuronal populations in neurodegenerative disease. SIGNIFICANCE STATEMENT In neurodegenerative disease, neuronal atrophy has long been assumed to be an early nonspecific event preceding neuronal loss. However, in a mouse model of spinocerebellar ataxia type 1 (SCA1), we identify a previously unappreciated compensatory role for neuronal shrinkage. Purkinje neuron firing in these mice is initially normal, but is followed by abnormal membrane depolarization resulting from a reduction in potassium channels. Subsequently, these electrophysiological effects are counteracted by cell atrophy, which by restoring normal potassium channel membrane density, re-establishes pacemaker firing. Reversing the initial membrane depolarization improved motor function and Purkinje neuron morphology in the SCA1 mice. These results suggest that Purkinje neuron remodeling in ataxia is an active compensatory response that serves to normalize intrinsic membrane excitability. PMID:26269637

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

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

Selective vibration sensing: a new concept for activity-sensing rate-responsive pacing.

PubMed

Lau, C P; Stott, J R; Toff, W D; Zetlein, M B; Ward, D E; Camm, A J

1988-09-01

A clinically available model of an activity-sensing, rate-responsive pacemaker (Activitrax, Medtronic) utilizes body vibration during exercise as an indicator of the need for a rate increase. Although having the advantage of rapid onset of rate response, this system lacks specificity and the rate response does not closely correlate with the level of exertion. In addition, this pacemaker is susceptible to the effects of extraneous vibration. In this study involving 20 normal subjects fitted with an external Activitrax pacemaker, the rate responses to a variety of exercises were studied and were compared with the corresponding sinus rates. The vibration generated at the level of the pacemaker was also measured by accelerometers in three axes. Only a fair correlation (r = 0.51) was achieved between the pacemaker rate and the sinus rate. The total root mean square value of acceleration in either the anteroposterior or the vertical axes was found to have a better correlation (r = 0.8). As the main accelerations during physical activities were in the lower frequency range (0.1-4 Hz), a low-pass filter was used to reduce the influence of extraneous vibration. Selective sensing of the acceleration level may be usefully implemented in an algorithm for activity pacing.

MRI-conditional pacemakers: current perspectives.

PubMed

Ferreira, António M; Costa, Francisco; Tralhão, António; Marques, Hugo; Cardim, Nuno; Adragão, Pedro

2014-01-01

Use of both magnetic resonance imaging (MRI) and pacing devices has undergone remarkable growth in recent years, and it is estimated that the majority of patients with pacemakers will need an MRI during their lifetime. These investigations will generally be denied due to the potentially dangerous interactions between cardiac devices and the magnetic fields and radio frequency energy used in MRI. Despite the increasing reports of uneventful scanning in selected patients with conventional pacemakers under close surveillance, MRI is still contraindicated in those circumstances and cannot be considered a routine procedure. These limitations prompted a series of modifications in generator and lead engineering, designed to minimize interactions that could compromise device function and patient safety. The resulting MRI-conditional pacemakers were first introduced in 2008 and the clinical experience gathered so far supports their safety in the MRI environment if certain conditions are fulfilled. With this technology, new questions and controversies arise regarding patient selection, clinical impact, and cost-effectiveness. In this review, we discuss the potential risks of MRI in patients with electronic cardiac devices and present updated information regarding the features of MRI-conditional pacemakers and the clinical experience with currently available models. Finally, we provide some guidance on how to scan patients who have these devices and discuss future directions in the field.

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

[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

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

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.

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.

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.

Endocardial Energy Harvesting by Electromagnetic Induction.

PubMed

Zurbuchen, Adrian; Haeberlin, Andreas; Bereuter, Lukas; Pfenniger, Alois; Bosshard, Simon; Kernen, Micha; Philipp Heinisch, Paul; Fuhrer, Juerg; Vogel, Rolf

2018-02-01

cardiac pacemakers require regular medical follow-ups to ensure proper functioning. However, device replacements due to battery depletion are common and account for ∼25% of all implantation procedures. Furthermore, conventional pacemakers require pacemaker leads which are prone to fractures, dislocations or isolation defects. The ensuing surgical interventions increase risks for the patients and costs that need to be avoided. in this study, we present a method to harvest energy from endocardial heart motions. We developed a novel generator, which converts the heart's mechanical into electrical energy by electromagnetic induction. A mathematical model has been introduced to identify design parameters strongly related to the energy conversion efficiency of heart motions and fit the geometrical constraints for a miniaturized transcatheter deployable device. The implemented final design was tested on the bench and in vivo. the mathematical model proved an accurate method to estimate the harvested energy. For three previously recorded heart motions, the model predicted a mean output power of 14.5, 41.9, and 16.9 μW. During an animal experiment, the implanted device harvested a mean output power of 0.78 and 1.7 μW at a heart rate of 84 and 160 bpm, respectively. harvesting kinetic energy from endocardial motions seems feasible. Implanted at an energetically favorable location, such systems might become a welcome alternative to extend the lifetime of cardiac implantable electronic device. the presented endocardial energy harvesting concept has the potential to turn pacemakers into battery- and leadless systems and thereby eliminate two major drawbacks of contemporary systems.

Phase shifting two coupled circadian pacemakers - Implications for jet lag

NASA Technical Reports Server (NTRS)

Gander, P. H.; Kronauer, R. E.; Graeber, R. C.

1985-01-01

Two Van der Pol oscillators with reciprocal linear velocity coupling are utilized to model the response of the human circadian timing system to abrupt displacements of the environmental time cues (zeitgebers). The core temperature rhythm and sleep-wake cycle simulated by the model are examined. The relationship between the masking of circadian rhythms by environmental variables and behavioral and physiological events and the rates of resynchronization is studied. The effects of zeitgeber phase shifts and zeitgeber strength on the resynchronization rates are analyzed. The influence of intrinsic pacemakers periods and coupling strength on resynchronization are investigated. The simulated data reveal that: resynchronization after a time zone shift depends on the magnitude of the shift; the time of day of the shift has little influence on resynchronization; the strength of zeitgebers affects the rate and direction of the resynchronization; the intrinsic pacemaker periods have a significant effect on resynchronization; and increasing the coupling between the oscillators results in an increase in the rate of resynchronization. The model data are compared to transmeridian flight studies data and similar resynchronization patterns are observed.

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.

Ten-year Survival and Its Associated Factors in the Patients Undergoing Pacemaker Implantation in Hospitals Affiliated to Shiraz University of Medical Sciences During 2002 - 2012

PubMed Central

Rajaeefard, Abdolreza; Ghorbani, Mohammad; Babaee Baigi, Mohammad Ali; Tabatabae, Hamidreza

2015-01-01

Background: Heart failure is a prevalent disease affecting about 4.9 million people in the U.S. and more than 22 million individuals worldwide. Using electric pacemaker is the most common treatment for the patients with heart conduction problems. The present study aimed to determine the factors affecting survival in the patients undergoing pacemaker implantation in the hospitals affiliated to Shiraz University of Medical Sciences. Objectives: The aim of the present study was to identify the factors affecting the survival of the patients suffering from arrhythmia. Patients and Methods: This retrospective survival analysis was conducted on all 1207 patients with heart failure who had undergone permanent pacemaker implantation in the hospitals affiliated to Shiraz University of Medical Sciences from 2002 to 2012. The data were analyzed using non-parametric methods such as Kaplan-Meier method, life table, and Cox regression model. The risk factors of mortality were determined using multivariate Cox proportional hazards method. Results: Survival data were available for 1030 (80%) patients (median age = 71 years [5th to 95th percentile range: 26 - 86 years]) and follow-up was completed for 84.28% of them. According to the results, 56% of the patients had received dual-chamber systems, while 44% had been implanted by single-chamber ventricular systems. Moreover, sick sinus syndrome and pacemaker mode were independent predictors of increased mortality. Conclusions: In this study, sick sinus syndrome and pacemaker mode followed by syncope were independently associated with increased mortality. PMID:26734484

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.

Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis

NASA Astrophysics Data System (ADS)

Tang, Ming; Wang, Mingjie; Shi, Changji; Iglesias, Pablo A.; Devreotes, Peter N.; Huang, Chuan-Hsiang

2014-10-01

Numerous models explain how cells sense and migrate towards shallow chemoattractant gradients. Studies show that an excitable signal transduction network acts as a pacemaker that controls the cytoskeleton to drive motility. Here we show that this network is required to link stimuli to actin polymerization and chemotactic motility and we distinguish the various models of chemotaxis. First, signalling activity is suppressed towards the low side in a gradient or following removal of uniform chemoattractant. Second, signalling activities display a rapid shut off and a slower adaptation during which responsiveness to subsequent test stimuli decline. Simulations of various models indicate that these properties require coupled adaptive and excitable networks. Adaptation involves a G-protein-independent inhibitor, as stimulation of cells lacking G-protein function suppresses basal activities. The salient features of the coupled networks were observed for different chemoattractants in Dictyostelium and in human neutrophils, suggesting an evolutionarily conserved mechanism for eukaryotic chemotaxis.

Frozen shoulder syndrome associated with subpectoral defibrillator implantation.

PubMed

Burke, M C; Drinan, K; Kopp, D E; Kall, J G; Verdino, R J; Paydak, H; Wilber, D J

1999-10-01

Pectoral implantation of transvenous non-thoracotomy internal cardioverter defibrillators (ICD) has resulted in very few complications whether placed subpectorally or subcutaneously. We report the case of a 68 year old man with a subpectorally implanted MINI-plus (Cardiac Pacemakers, Incorporated, St. Paul, Mn.) transvenous ICD who developed nearly instantaneous severe ipsilateral shoulder pain and immobilization. The symptoms progressed despite aggressive physical therapy. We elected to remove the device from the pectoral site and place it in a traditional abdominal position due to the severity, duration and refractoriness of his symptoms. This procedure utilized the chronic Endotak DSP (Model 0125, Cardiac Pacemakers, Incorporated) transvenous lead, a compatible Endotak DSP lead extender (Model 6952, Cardiac Pacemakers, Incorporated) and the above described ICD. Immediate relief of symptoms was accomplished by relocation of the device to an abdominal site. This intervention should be reserved for patients with severely debilitating symptoms. Prospective comparison of subpectoral and subcutaneous surgical approaches with respect to patient comfort and acceptance and complications may be warranted.

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

Complications of pacemaker therapy in adults with congenital heart disease: a multicenter study.

PubMed

Opić, Petra; van Kranenburg, Matthijs; Yap, Sing-Chien; van Dijk, Arie P; Budts, Werner; Vliegen, Hubert W; van Erven, Lieselot; Can, Anil; Sahin, Gulhan; Theuns, Dominic A M J; Witsenburg, Maarten; Roos-Hesselink, Jolien W

2013-10-09

This study aims to investigate indications and complications of permanent cardiac pacing in adults with congenital heart disease (CHD). Two-hundred and seventy-four CHD patients were identified who underwent permanent pacemaker implantation between 1972 and 2009. The indication for pacing was acquired sinus node or AV node conduction disease (63%), sinus node or AV node conduction disease after cardiac surgery (28%), and drug/arrhythmia-related indications (9%). Patients with complex CHD received a pacemaker at younger age (23 versus 31 years, p<0.0001) and more often received an epicardial pacing system (51% versus 23%, p<0.0001) compared to those with simple or moderate CHD. Twenty-nine patients (10.6%) had a periprocedural complication during the primary pacemaker implantation (general population: 5.2%). The most common acute complications were lead dysfunction (4.0%), bleeding (2.6%), pocket infection (1.5%) and pneumothorax (1.5%). During a median follow-up of 12 years, pacemaker-related complications requiring intervention occurred in 95 patients (34.6%). The most common late pacemaker-related complications included lead failure (24.8%), pacemaker dysfunction/early battery depletion (5.1%), pacemaker migration (4.7%) and erosion (4.7%). Pacemaker implantation at younger age (<18 years) was an independent predictor of late pacemaker-related complication (adjusted hazard ratio 1.68, 95% confidence interval 1.07 to 2.63, p=0.023). The risk of periprocedural complications seems higher in the CHD population compared to the general population and more than one-third of CHD patients encountered a pacemaker-related complication during long-term follow-up. This risk increases for those who receive a pacemaker at younger age. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

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...

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...

In vitro developmental model of the gastrointestinal tract from mouse embryonic stem cells.

PubMed

Torihashi, Shigeko; Kuwahara, Masaki; Kurahashi, Masaaki

2007-10-01

Mouse embryonic stem (ES) cells are pluripotent and retain their potential to form cells, tissues and organs originated from three embryonic germ layers. Recently, we developed in vitro organ--gut-like structures--from mouse ES cells. They had basically similar morphological features to a mouse gastrointestinal tract in vivo composed of three distinct layers (i.e., epithelium, connective tissue and musculature). Gut-like structures showed spontaneous contractions derived from pacemaker cells (interstitial cells of Cajal) in the musculature. We also examined their formation process and expression pattern of transcription factors crucial for gut organogenesis such as Id2, Sox17, HNF3beta/Foxa2 and GATA4. We found that they mimic the development of embryonic gut in vivo and showed a similar expression pattern of common transcription factors. They also maintain their developmental potential after transplantation to a renal capsule. Therefore, gut-like structures are suitable for in vitro models of gastrointestinal tracts and their development. In addition, we pointed out several unique features different from gut in vivo that provide useful and advantageous tools to investigate the developmental mechanism of the gastrointestinal tract.

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.

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.

Transfemoral access when superior venous approach is not feasible equals overall success of permanent pacemaker implantation. Ten-year series.

PubMed

García Guerrero, Juan J; Fernández de la Concha Castañeda, Joaquín; Doblado Calatrava, Manuel; Redondo Méndez, Ángel; Lázaro Medrano, Manuel; Merchán Herrera, Antonio

2017-06-01

When permanent pacemaker implantation is not possible or advisable via superior venous access (i.e., axillary or subclavian veins), safe and feasible surgical alternatives are required. The femoral approach is relatively unknown and seldom studied. This single-center study analyzed 10-year outcomes of a femoral implantation approach. Data about the implantation procedure (indication, approach, lead and pacemaker models, complications), patient characteristics (age, sex, medications, comorbidities), and follow-up were analyzed for all permanent pacemaker implantations using the femoral approach between June 2001 and June 2011. A permanent pacemaker was implanted with the femoral approach in 50 patients (mean age, 76 years [range: 45-96], 31 [61%] men). The most frequent indication was atrioventricular block, associated with sinus rhythm in 30 patients and with atrial fibrillation in eight patients. Overall, 20 patients (40%) were treated with oral anticoagulants postimplantation. Mean implantation time was 64 minutes (range: 20-210) and mean fluoroscopy time was 6.7 minutes (range: 0.2-50). Minimum follow-up window was 1 year (June 2012), with a mean of 50 months [range: 1-113]). No deaths, septic episodes, or severe complications were associated with the procedure, acute or long-term. Follow-up data were available for 46 patients, of who 21 (46%) died during follow-up (mean age, 87 years [range: 73-101]). No cause of death was associated with the femoral technique. Permanent pacemaker implantation through femoral access is not difficult for an experienced implant surgeon. Outcomes were comparable to systems implanted by superior venous approach, and no severe complications were observed at 10-year follow-up. © 2017 Wiley Periodicals, Inc.

Are pacemaker properties required for respiratory rhythm generation in adult turtle brain stems in vitro?

PubMed

Johnson, Stephen M; Wiegel, Liana M; Majewski, David J

2007-08-01

The role of pacemaker properties in vertebrate respiratory rhythm generation is not well understood. To address this question from a comparative perspective, brain stems from adult turtles were isolated in vitro, and respiratory motor bursts were recorded on hypoglossal (XII) nerve rootlets. The goal was to test whether burst frequency could be altered by conditions known to alter respiratory pacemaker neuron activity in mammals (e.g., increased bath KCl or blockade of specific inward currents). While bathed in artificial cerebrospinal fluid (aCSF), respiratory burst frequency was not correlated with changes in bath KCl (0.5-10.0 mM). Riluzole (50 microM; persistent Na(+) channel blocker) increased burst frequency by 31 +/- 5% (P < 0.05) and decreased burst amplitude by 42 +/- 4% (P < 0.05). In contrast, flufenamic acid (FFA, 20-500 microM; Ca(2+)-activated cation channel blocker) reduced and abolished burst frequency in a dose- and time-dependent manner (P < 0.05). During synaptic inhibition blockade with bicuculline (50 microM; GABA(A) channel blocker) and strychnine (50 muM; glycine receptor blocker), rhythmic motor activity persisted, and burst frequency was directly correlated with extracellular KCl (0.5-10.0 mM; P = 0.005). During synaptic inhibition blockade, riluzole (50 microM) did not alter burst frequency, whereas FFA (100 microM) abolished burst frequency (P < 0.05). These data are most consistent with the hypothesis that turtle respiratory rhythm generation requires Ca(2+)-activated cation channels but not pacemaker neurons, which thereby favors the group-pacemaker model. During synaptic inhibition blockade, however, the rhythm generator appears to be transformed into a pacemaker-driven network that requires Ca(2+)-activated cation channels.

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.

Failure rates of leads, pulse generators, and programmers have not diminished over the last 20 years: formal monitoring of performance is still needed. BILITCH Registry and STIMAREC.

PubMed

Kawanishi, D T; Song, S; Furman, S; Parsonnet, V; Pioger, G; Petitot, J C; Godin, J F

1996-11-01

Formal Monitoring of Performance is Still Needed. In order to detect trends in the number of device or component failures that have occurred among permanent pacemaker systems since the 1970s, we reviewed the data of the five largest pacemaker manufacturers from the Bilitch Registry of permanent pacemaker pulse generators, the Stimarec failure registry, the general accounting office summaries of the United States Veterans Administration (VA) Registry of Pacemaker Leads, and the Implantable Lead Registry, from the Cleveland Clinic Lead registry, and the recalls and safety alerts issued by the United States Food and Drug Administration (FDA) over the last 20 years. The definition of failure followed the criterion, or criteria, developed within each registry and differed significantly between the registries. The 20-year period between 1976 and 1995 was divided into 5-year quartiles (QT): QT 1 = 1976-1980; QT2 = 1981-1985; QT3 = 1986-1990; and QT4 = 1991-1995. For pulse generators, the number of models with failures in each quartile in the Bilitch Registry were: QT 1 = 9; QT 2 = 11; QT3 = 17; QT4 = 13. In Stimarec, the number of units reported as having reached a dangerous condition were: QT1 = 710; QT2 = 212; QT3 = 114; QT4 = 310. From the FDA reports, the number of units included in recalls or safety alerts were: QT3 = 6,085; QT4 = 135,766. For permanent pacemaker leads, the numbers of failed or dangerous leads recorded in Stimarec were: QT3 = 16; QT4 = 32. In the VA Registry, the number of models having a below average survival was 2/92 (2.7%). In the Implantable Lead Registry, the number of models having a below average survival was 3/21 (14%). In the Cleveland Clinic series, 6/13 (46%) of lead models were recognized to have some failure involving the conductor, insulation, or connector. In the FDA reports, the number of leads involved in either recall or safety alert were: QT3 = 20,354; QT4 = 332,105. For programmers, the number of units involved either in a recall or safety alert were: QT3 = 11,124; QT4 = 3,528. In all of these series, each of the five largest manufacturers had some models or units involved in each time period. This review of programs has revealed: 1. The incidence of failures, recalls, or safety alerts did not decline over time; and 2. Despite changes in technology, formal monitoring of pacemaker systems is still warranted.

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.

Corrosion resistance of lithium/iodine batteries fabricated in an extremely dry environment

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

Brown, W.R.; Holmes, C.F.; Stinebring, R.C.

1981-10-01

Early lithium/iodine pacemaker batteries employed considerable amounts of inert plastic materials to encase the active ingredients inside the stainless steel case. Several years ago the Wilson Greatbatch Ltd. (WGL) Model 755 cell was introduced and represented a significant change in lithium/iodine battery construction. In this design (1) the iodinepolyvinylpyridine (PVP) depolarizer material was placed in direct contact with the 304L stainless steel case and much of the inert material was eliminated. This change resulted in obtaining substantially more depolarizer in the battery thereby greatly increasing the electrical capacity for the same cell volume. A study was instituted to evaluate possiblemore » corrosion effects between the iodine in the depolarizer and the stainless steel case.« less

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.

Inhibitory and modulatory inputs to the vocal central pattern generator of a teleost fish

PubMed Central

Rosner, Elisabeth; Rohmann, Kevin N.; Bass, Andrew H.

2018-01-01

Abstract Vocalization is a behavioral feature that is shared among multiple vertebrate lineages, including fish. The temporal patterning of vocal communication signals is set, in part, by central pattern generators (CPGs). Toadfishes are well‐established models for CPG coding of vocalization at the hindbrain level. The vocal CPG comprises three topographically separate nuclei: pre‐pacemaker, pacemaker, motor. While the connectivity between these nuclei is well understood, their neurochemical profile remains largely unexplored. The highly vocal Gulf toadfish, Opsanus beta, has been the subject of previous behavioral, neuroanatomical and neurophysiological studies. Combining transneuronal neurobiotin‐labeling with immunohistochemistry, we map the distribution of inhibitory neurotransmitters and neuromodulators along with gap junctions in the vocal CPG of this species. Dense GABAergic and glycinergic label is found throughout the CPG, with labeled somata immediately adjacent to or within CPG nuclei, including a distinct subset of pacemaker neurons co‐labeled with neurobiotin and glycine. Neurobiotin‐labeled motor and pacemaker neurons are densely co‐labeled with the gap junction protein connexin 35/36, supporting the hypothesis that transneuronal neurobiotin‐labeling occurs, at least in part, via gap junction coupling. Serotonergic and catecholaminergic label is also robust within the entire vocal CPG, with additional cholinergic label in pacemaker and prepacemaker nuclei. Likely sources of these putative modulatory inputs are neurons within or immediately adjacent to vocal CPG neurons. Together with prior neurophysiological investigations, the results reveal potential mechanisms for generating multiple classes of social context‐dependent vocalizations with widely divergent temporal and spectral properties. PMID:29424431

A sub-cc nonlinear piezoelectric energy harvester for powering leadless pacemakers

PubMed Central

Ansari, MH; Karami, M Amin

2018-01-01

A miniature nonlinear piezoelectric energy harvester is developed to power state of the art leadless cardiac pacemakers from cardiac motions. The energy harvester is integrated in the leadless pacemaker and is connected to the myocardium. The energy harvester converts myocardial motions to electricity to power leadless pacemakers. The energy is stored in a battery or supercapacitor and is used for pacing. The device is composed of a bimorph piezoelectric beam confined in a gray iron frame. The system is assembled at high temperature and operated at the body temperature. The mismatch in the coefficients of thermal expansion of the beam and the frame causes the beam to buckle in body temperature. This intentional buckling makes the beam unstable and improves the power production and robustness of the device. Having high natural frequency is a major problem in microelectromechanical systems energy harvesters. Considering the small size of the energy harvester, 0.5 cm3, the natural frequency is expected to be high. In our design, the natural frequency is lowered significantly using a buckled beam and a proof mass. Since the beam is buckled, the design is bistable and nonlinear, which could increase the output power. In this article, the device is analytically modeled, and the natural frequencies and mode shapes of the energy harvester are analytically derived. The terms corresponding to geometric nonlinearities are included in the electromechanical coupled governing equations. The simulations show that the device generates sufficient electricity to power leadless pacemakers. PMID:29674842

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.

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.

Simulations of light effects on the human circadian pacemaker: implications for assessment of intrinsic period

NASA Technical Reports Server (NTRS)

Klerman, E. B.; Dijk, D. J.; Kronauer, R. E.; Czeisler, C. A.

1996-01-01

The sensitivity of the human circadian system to light has been the subject of considerable debate. Using computer simulations of a recent quantitative model for the effects of light on the human circadian system, we investigated these effects of light during different experimental protocols. The results of the simulations indicate that the nonuniform distribution over the circadian cycle of exposure to ordinary room light seen in classical free-run studies, in which subjects select their exposure to light and darkness, can result in an observed period of approximately 25 h, even when the intrinsic period of the subject's endogenous circadian pacemaker is much closer to 24 h. Other simulation results suggest that accurate assessment of the true intrinsic period of the human circadian pacemaker requires low ambient light intensities (approximately 10-15 lx) during scheduled wake episodes, desynchrony of the imposed light-dark cycle from the endogenous circadian oscillator, and a study length of at least 20 days. Although these simulations await further experimental substantiation, they highlight the sensitivity to light of the human circadian system and the potential confounding influence of light on the assessment of the intrinsic period of the circadian pacemaker.

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.

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

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... 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.

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.

[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.

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.

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.

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 ...

Computational model of electrically coupled, intrinsically distinct pacemaker neurons.

PubMed

Soto-Treviño, Cristina; Rabbah, Pascale; Marder, Eve; Nadim, Farzan

2005-07-01

Electrical coupling between neurons with similar properties is often studied. Nonetheless, the role of electrical coupling between neurons with widely different intrinsic properties also occurs, but is less well understood. Inspired by the pacemaker group of the crustacean pyloric network, we developed a multicompartment, conductance-based model of a small network of intrinsically distinct, electrically coupled neurons. In the pyloric network, a small intrinsically bursting neuron, through gap junctions, drives 2 larger, tonically spiking neurons to reliably burst in-phase with it. Each model neuron has 2 compartments, one responsible for spike generation and the other for producing a slow, large-amplitude oscillation. We illustrate how these compartments interact and determine the dynamics of the model neurons. Our model captures the dynamic oscillation range measured from the isolated and coupled biological neurons. At the network level, we explore the range of coupling strengths for which synchronous bursting oscillations are possible. The spatial segregation of ionic currents significantly enhances the ability of the 2 neurons to burst synchronously, and the oscillation range of the model pacemaker network depends not only on the strength of the electrical synapse but also on the identity of the neuron receiving inputs. We also compare the activity of the electrically coupled, distinct neurons with that of a network of coupled identical bursting neurons. For small to moderate coupling strengths, the network of identical elements, when receiving asymmetrical inputs, can have a smaller dynamic range of oscillation than that of its constituent neurons in isolation.

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.

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

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.

Sex Differences in the Relationship Between Amiodarone Use and the Need for Permanent Pacing in Patients With Atrial Fibrillation

PubMed Central

Essebag, Vidal; Reynolds, Matthew R.; Hadjis, Tom; Lemery, Robert; Olshansky, Brian; Buxton, Alfred E.; Josephson, Mark E.; Zimetbaum, Peter

2008-01-01

Background Amiodarone use was associated with an increased need for pacemaker insertion in a retrospective study of patients with atrial fibrillation (AF) and prior myocardial infarction. The aims of this study were to determine prospectively whether amiodarone increases the need for pacemakers in a general population of patients with AF and whether this effect is modified by sex. Methods The study included 1005 patients with new-onset AF who were enrolled in the Fibrillation Registry Assessing Costs, Therapies, Adverse events, and Lifestyle (FRACTAL). Multivariable Cox regression models, including time-dependent covariates accounting for medication exposure, were used to evaluate the risk of pacemaker insertion associated with amiodarone use. Results Amiodarone use was associated with an increased risk of pacemaker insertion (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.08–3.76) after adjustment for age, sex, atrial flutter, coronary artery disease, heart failure, and hypertension. The effect of amiodarone use was modified by sex, with a significant risk in women but not in men (HR, 4.69; 95% CI, 1.99–11.05 vs HR, 1.05; 95% CI, 0.42–2.58 [P = .02]). This interaction remained significant after adjustment for weight, body mass index, weight-adjusted amiodarone dose, and use of other antiarrhythmic or rate control drugs. Conclusion The risk of bradyarrhythmia requiring pacemaker insertion associated with amiodarone use for AF is significantly greater in women than in men, independent of weight or body mass index. PMID:17698688

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.

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.

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

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.

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.

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.

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.

[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.

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

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...

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

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.

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.

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

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...

Structural basis for modulation and agonist specificity of HCN pacemaker channels.

PubMed

Zagotta, William N; Olivier, Nelson B; Black, Kevin D; Young, Edgar C; Olson, Rich; Gouaux, Eric

2003-09-11

The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.

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

Comparative Efficacy of Nebivolol and Metoprolol to Prevent Tachycardia-Induced Cardiomyopathy in a Porcine Model.

PubMed

Nazeri, Alireza; Elayda, MacArthur A; Segura, Ana Maria; Stainback, Raymond F; Nathan, Joanna; Lee, Vei-Vei; Bove, Christina; Sampaio, Luiz; Grace, Brian; Massumi, Ali; Razavi, Mehdi

2016-12-01

Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model. Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were obtained at baseline and at the end of the study. At the end of week 8, the pigs were euthanized, and complete histopathologic studies were performed. All the pigs developed left ventricular cardiomyopathy but remained hemodynamically stable and survived to the end of the study. The mean left ventricular ejection fraction decreased from baseline by 34%, 20%, and 20% in the nebivolol, metoprolol, and placebo groups, respectively. These changes did not differ significantly among the 3 groups ( P =0.51). Histopathologic analysis revealed mild left ventricular perivascular fibrosis with cardiomyocyte hypertrophy in 14 of the 15 pigs. Both nebivolol and metoprolol failed to prevent cardiomyopathy in our animal model of persistent tachycardia and a high catecholamine state.

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).

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

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.

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.

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.

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.

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.

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

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.

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.

[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.

Experimental investigation of fan-folded piezoelectric energy harvesters for powering pacemakers

PubMed Central

Ansari, M H; Karami, M Amin

2018-01-01

This paper studies the fabrication and testing of a magnet free piezoelectric energy harvester (EH) for powering biomedical devices and sensors inside the body. The design for the EH is a fan-folded structure consisting of bimorph piezoelectric beams folding on top of each other. An actual size experimental prototype is fabricated to verify the developed analytical models. The model is verified by matching the analytical results of the tip acceleration frequency response functions (FRF) and voltage FRF with the experimental results. The generated electricity is measured when the EH is excited by the heartbeat. A closed loop shaker system is utilized to reproduce the heartbeat vibrations. Achieving low fundamental natural frequency is a key factor to generate sufficient energy for pacemakers using heartbeat vibrations. It is shown that the natural frequency of the small-scale device is less than 20 Hz due to its unique fan-folded design. The experimental results show that the small-scale EH generates sufficient power for state of the art pacemakers. The 1 cm3 EH with18.4 gr tip mass generates more than16 μW of power from a normal heartbeat waveform. The robustness of the device to the heart rate is also studied by measuring the relation between the power output and the heart rate. PMID:29674807

Experimental investigation of fan-folded piezoelectric energy harvesters for powering pacemakers.

PubMed

Ansari, M H; Karami, M Amin

2017-06-01

This paper studies the fabrication and testing of a magnet free piezoelectric energy harvester (EH) for powering biomedical devices and sensors inside the body. The design for the EH is a fan-folded structure consisting of bimorph piezoelectric beams folding on top of each other. An actual size experimental prototype is fabricated to verify the developed analytical models. The model is verified by matching the analytical results of the tip acceleration frequency response functions (FRF) and voltage FRF with the experimental results. The generated electricity is measured when the EH is excited by the heartbeat. A closed loop shaker system is utilized to reproduce the heartbeat vibrations. Achieving low fundamental natural frequency is a key factor to generate sufficient energy for pacemakers using heartbeat vibrations. It is shown that the natural frequency of the small-scale device is less than 20 Hz due to its unique fan-folded design. The experimental results show that the small-scale EH generates sufficient power for state of the art pacemakers. The 1 cm 3 EH with18.4 gr tip mass generates more than16 μ W of power from a normal heartbeat waveform. The robustness of the device to the heart rate is also studied by measuring the relation between the power output and the heart rate.

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

A Percutaneously Implantable Fetal Pacemaker

PubMed Central

Zhou, Li; Vest, Adriana N.; Chmait, Ramen H.; Bar-Cohen, Yaniv; Pruetz, Jay; Silka, Michael; Zheng, Kaihui; Peck, Ray; Loeb, Gerald E.

2015-01-01

A miniaturized, self-contained pacemaker that could be implanted with a minimally invasive technique would dramatically improve the survival rate for fetuses that develop hydrops fetalis as a result of congenital heart block. We are currently validating a device that we developed to address this bradyarrhythmia. Preclinical studies in a fetal sheep model are underway to demonstrate that the device can be implanted via a minimally invasive approach, can mechanically withstand the harsh bodily environment, can induce effective contractions of the heart muscle with an adequate safety factor, and can successfully operate for the required device lifetime of three months using the previously-developed closed loop transcutaneous recharging system. PMID:25570982

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

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.

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).

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.

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

Capacity of dental equipment to interfere with cardiac implantable electrical devices.

PubMed

Lahor-Soler, Eduard; Miranda-Rius, Jaume; Brunet-Llobet, Lluís; Sabaté de la Cruz, Xavier

2015-06-01

Patients with cardiac implantable electrical devices should take precautions when exposed to electromagnetic fields. Possible interference as a result of proximity to electromagnets or electricity flow from electronic tools employed in clinical odontology remains controversial. The objective of this study was to examine in vitro the capacity of dental equipment to provoke electromagnetic interference in pacemakers and implantable cardioverter defibrillators. Six electronic dental instruments were tested on three implantable cardioverter defibrillators and three pacemakers from different manufacturers. A simulator model, submerged in physiological saline, with elements that reproduced life-size anatomic structures was used. The instruments were analyzed at differing distances and for different time periods of application. The dental instruments studied displayed significant differences in their capacity to trigger electromagnetic interference. Significant differences in the quantity of registered interference were observed with respect to the variables manufacturer, type of cardiac implant, and application distance but not with the variable time of application. The electronic dental equipment tested at a clinical application distance (20 cm) provoked only slight interference in the pacemakers and implantable cardioverter defibrillators employed, irrespective of manufacturer. © 2015 Eur J Oral Sci.

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.

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

Oscillators that sync and swarm.

PubMed

O'Keeffe, Kevin P; Hong, Hyunsuk; Strogatz, Steven H

2017-11-15

Synchronization occurs in many natural and technological systems, from cardiac pacemaker cells to coupled lasers. In the synchronized state, the individual cells or lasers coordinate the timing of their oscillations, but they do not move through space. A complementary form of self-organization occurs among swarming insects, flocking birds, or schooling fish; now the individuals move through space, but without conspicuously altering their internal states. Here we explore systems in which both synchronization and swarming occur together. Specifically, we consider oscillators whose phase dynamics and spatial dynamics are coupled. We call them swarmalators, to highlight their dual character. A case study of a generalized Kuramoto model predicts five collective states as possible long-term modes of organization. These states may be observable in groups of sperm, Japanese tree frogs, colloidal suspensions of magnetic particles, and other biological and physical systems in which self-assembly and synchronization interact.

Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model.

PubMed

Kaese, Sven; Bögeholz, Nils; Pauls, Paul; Dechering, Dirk; Olligs, Jan; Kölker, Katharina; Badawi, Sascha; Frommeyer, Gerrit; Pott, Christian; Eckardt, Lars

2017-08-01

The cardiac sodium/calcium (Na + /Ca 2+ ) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 μM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P <.001). ISO led to a significant shortening of the anterograde and retrograde AVN-WCL without differences between NCX-OE and WT. This study is the first to demonstrate that increased NCX activity enhances beta-adrenergic increase of heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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.

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

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

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.

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.

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.

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).

Visualization and appearance of artifacts of leadless pacemaker systems in cardiac MRI : An experimental ex vivo study.

PubMed

Edlinger, Christoph; Granitz, Marcel; Paar, Vera; Jung, Christian; Pfeil, Alexander; Eder, Sarah; Wernly, Bernhard; Kammler, Jürgen; Hergan, Klaus; Hoppe, Uta C; Steinwender, Clemens; Lichtenauer, Michael; Kypta, Alexander

2018-05-23

Leadless pacemaker systems are an important upcoming device in clinical rhythmology. Currently two different products are available with the Micra system (Medtronic) being the most used in the clinical setting to date. The possibility to perform magnetic resonance imaging (MRI) is an important feature of modern pacemaker devices. Even though the Micra system is suitable for MRI, little is yet known about its impact on artifacts within the images. The aim of our ex vivo study was to perform cardiac MRI to quantify the artifacts and to evaluate if artifacts limit or inhibit the assessment of the surrounding myocardium. After ex vivo implantation of the leadless pacemaker (LP) in a porcine model, hearts were filled with saline solution and fixed on wooden sticks on a plastic container. The model was examined at 1.5 T and at 3 T using conventional sequences and T2 mapping sequences. In addition, conventional X‑rays and computed tomography (CT) scans were performed. Correct implantation of the LP could be performed in all hearts. In almost all MRI sequences the right ventricle and the septal region surrounding the (LP) were altered by an artifact and therefore would sustain limited assessment; however, the rest of the myocardium remained free of artifacts and evaluable for common radiologic diagnoses. A characteristic shamrock-shaped artifact was generated which appeared to be even more intense in magnitude and brightness when using 3 T compared to 1.5 T. The use of the Micra system in cardiac MRI appeared to be feasible. In our opinion, it will still be possible to make important clinical cardiac MRI diagnoses (the detection of major ischemic areas or inflammatory processes) in patients using the Micra system. We suggest the use of 1.5 T as the preferred method in clinical practice.

Pacemakers and implantable cardioverter-defibrillators in pediatric patients.

PubMed

Silka, Michael J; Bar-Cohen, Yaniv

2006-11-01

The use of pacemakers and implantable cardioverter-defibrillators (ICDs) in infants, children, and patients with congenital heart disease presents unique challenges and considerations. They include uncommon indications for device implantation, innovative approaches to lead implantation and configuration, and age-dependent and disease-specific aspects of device programming. In this review, the current indications for pacemaker and ICD implantation in young patients are discussed, followed by consideration of the approaches to lead and device placement in very small patients and those with complex congenital heart disease, in whom unique problems may be encountered. The limitations of programmability of current pacemakers and ICDs when used in young patients are discussed, followed by an analysis of long-term device follow-up and potential late complications.

Periodically-modulated inhibition of living pacemaker neurons--III. The heterogeneity of the postsynaptic spike trains, and how control parameters affect it.

PubMed

Segundo, J P; Vibert, J F; Stiber, M

1998-11-01

Codings involving spike trains at synapses with inhibitory postsynaptic potentials on pacemakers were examined in crayfish stretch receptor organs by modulating presynaptic instantaneous rates periodically (triangles or sines; frequencies, slopes and depths under, respectively, 5.0 Hz, 40.0/s/s and 25.0/s). Timings were described by interspike and cross-intervals ("phases"); patterns (dispersions, sequences) and forms (timing classes) were identified using pooled graphs (instant along the cycle when a spike occurs vs preceding interval) and return maps (plots of successive intervals). A remarkable heterogeneity of postsynaptic intervals and phases characterizes each modulation. All cycles separate into the same portions: each contains a particular form and switches abruptly to the next. Forms differ in irregularity and predictability: they are (see text) "p:q alternations", "intermittent", "phase walk-throughs", "messy erratic" and "messy stammering". Postsynaptic cycles are asymmetric (hysteresis). This contrasts with the presynaptic homogeneity, smoothness and symmetry. All control parameters are, individually and jointly, strongly influential. Presynaptic slopes, say, act through a postsynaptic sensitivity to their magnitude and sign; when increasing, hysteresis augments and forms change or disappear. Appropriate noise attenuates between-train contrasts, providing modulations are under 0.5 Hz. Postsynaptic natural intervals impose critical time bases, separating presynaptic intervals (around, above or below them) with dissimilar consequences. Coding rules are numerous and have restricted domains; generalizations are misleading. Modulation-driven forms are trendy pacemaker-driven forms. However, dissimilarities, slight when patterns are almost pacemaker, increase as inhibition departs from pacemaker and incorporate unpredictable features. Physiological significance-(1) Pacemaker-driven forms, simple and ubiquitous, appear to be elementary building blocks of synaptic codings, present always but in each case distorted typically. (2) Synapses are prototype: similar behaviours should be widespread, and networks simulations benefit by nonlinear units generating all forms. (3) Relevant to periodic functions are that few variables need be involved in form selection, that distortions are susceptible to noise levels and, if periods are heterogeneous, that simple input cycles impose heterogeneous outputs. (4) Slow Na inactivations are necessary for obtaining complex forms and hysteresis. Formal significance--(1) Pacemaker-driven forms and presumably their modulation-driven counterparts, pertain to universal periodic, intermittent, quasiperiodic and chaotic categories whose formal properties carry physiological connotations. (2) Only relatively elaborate, nonlinear geometric models show all forms; simpler ones, show only alternations and walk-throughs. (3) Bifurcations resemble those of simple maps that can provide useful guidelines. (4) Heterogeneity poses the unanswered question of whether or not the entire cycle and all portions have the same behaviours: therefore, whether trajectories are continuous or have discontinuities and/or singular points.

Heart pacemaker - discharge

MedlinePlus

... table saws) Electric lawnmowers and leaf blowers Slot machines Stereo speakers Tell all providers that you have a pacemaker before any tests are done. Some medical equipment may interfere with ...

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.

Beam Profile Disturbances from Implantable Pacemakers or Implantable Cardioverter-Defibrillator Interactions

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

Gossman, Michael S., E-mail: mgossman@tsrcc.com; Comprehensive Heart and Vascular Associates, Heart and Vascular Center, Ashland, KY; Medtronic, Inc., External Research Program, Mounds View, MN

2011-01-01

The medical community is advocating for progressive improvement in the design of implantable cardioverter-defibrillators and implantable pacemakers to accommodate elevations in dose limitation criteria. With advancement already made for magnetic resonance imaging compatibility in some, a greater need is present to inform the radiation oncologist and medical physicist regarding treatment planning beam profile changes when such devices are in the field of a therapeutic radiation beam. Treatment plan modeling was conducted to simulate effects induced by Medtronic, Inc.-manufactured devices on therapeutic radiation beams. As a continuation of grant-supported research, we show that radial and transverse open beam profiles of amore » medical accelerator were altered when compared with profiles resulting when implantable pacemakers and cardioverter-defibrillators are placed directly in the beam. Results are markedly different between the 2 devices in the axial plane and the sagittal planes. Vast differences are also presented for the therapeutic beams at 6-MV and 18-MV x-ray energies. Maximum changes in percentage depth dose are observed for the implantable cardioverter-defibrillator as 9.3% at 6 MV and 10.1% at 18 MV, with worst distance to agreement of isodose lines at 2.3 cm and 1.3 cm, respectively. For the implantable pacemaker, the maximum changes in percentage depth dose were observed as 10.7% at 6 MV and 6.9% at 18 MV, with worst distance to agreement of isodose lines at 2.5 cm and 1.9 cm, respectively. No differences were discernible for the defibrillation leads and the pacing lead.« less

Clinical and electrophysiological characteristics of patients with paroxysmal intra-His block with narrow QRS complexes.

PubMed

Ragupathi, Loheetha; Johnson, Drew; Greenspon, Arnold; Frisch, Daniel; Ho, Reginald T; Pavri, Behzad B

2018-04-18

Atrioventricular (AV) block is usually due to infranodal disease and associated with a wide QRS complex; such patients often progress to complete AV block and pacemaker dependency. Uncommonly, infranodal AV block can occur within the His bundle with a narrow QRS complex. The aims of this study were to define clinical/echocardiographic characteristics of patients with AV block within the His bundle and report progression to pacemaker dependency. We retrospectively identified patients with narrow QRS complexes and documented intra-His delay or block at electrophysiology study (group A) or with electrocardiogram-documented Mobitz II AV block/paroxysmal AV block (group B). Clinical, electrophysiological, and echocardiographic variables at presentation and pacemaker parameters at the last follow-up visit were evaluated. Twenty-seven patients (19 women) were identified (mean age 64 ± 13 years; range, 38-85 years). Four patients who had <1 month of follow-up were excluded. There were 12 patients in group A and 11 in group B; 21 of 23 presented with syncope/presyncope. All patients received pacemakers: 8 single chamber and 15 dual chamber. After a median follow-up of 6.4 years, the median percentage of ventricular pacing was 1% (interquartile range 0%-4.66%). One patient developed true pacemaker dependency. Aortic and/or mitral annular calcification was present in 13 of 22 patients with available echocardiograms. Patients who present with syncope and narrow QRS complexes with intra-His delay or Mobitz II paroxysmal AV block with narrow QRS complexes rarely progress to pacemaker dependency and require infrequent pacing. This entity is more common in women, with a higher prevalence of aortic and/or mitral annular calcification. If confirmed by additional studies, single-chamber pacemaker may be sufficient. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Zero-fluoroscopy permanent pacemaker implantation using Ensite NavX system: Clinical viability or fanciful technique?

PubMed

Guo, Ping; Qiu, Jie; Wang, Yan; Chen, Guangzhi; Proietti, Riccardo; Fadhle, Al-Selmi; Zhao, Chunxia; Wen Wang, Dao

2018-02-01

Fluoroscopy is the imaging modality routinely used for cardiac device implantation and electrophysiological procedures. Due to the rising concern regarding the harmful effects of radiation exposure to both the patients and operation staffs, novel 3D mapping systems have been developed and implemented in electrophysiological procedure for the navigation of catheters inside the heart chambers. Their applicability in cardiac device implantation has been rarely reported. Our aim is to evaluate the feasibility and safety of permanent pacemaker implantation without fluoroscopy. From January 2012 to June 2016, six patients (50 ± 15 years, four of six were female, one of who was at the 25th week of gestation) who underwent permanent pacemaker implantation were included (zero-fluoroscopy group). Data from 20 consecutive cases of implantation performed under fluoroscopy guidance were chosen as a control group (fluoroscopy group). Total implantation procedure time for single-chamber pacemaker was 51.3 ± 13.1 minutes in the zero-fluoroscopy group and 42.6 ± 7.4 minutes in the fluoroscopy group (P  =  0.155). The implantation procedural time for a dual-chamber pacemaker was 88.3 ± 19.6 minutes and 67.3 ± 7.6 minutes in the zero-fluoroscopy and fluoroscopy groups (P  =  0.013), respectively. No complications were observed during the procedure and the follow-up in the two groups, and all pacemakers worked with satisfactory parameters. Ensite NavX system can be used as a reliable and safe zero-fluoroscopy approach for the implantation of single- or dual-chamber permanent pacemakers in specific patients, such as pregnant women or in extreme situations when the x-ray machine is not available. © 2017 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals, Inc.

Safety of implantable pacemakers and cardioverter defibrillators in the magnetic field of a novel remote magnetic navigation system.

PubMed

Jilek, Clemens; Tzeis, Stylianos; Reents, Tilko; Estner, Heidi-Luise; Fichtner, Stephanie; Ammar, Sonia; Wu, Jinjin; Hessling, Gabriele; Deisenhofer, Isabel; Kolb, Christof

2010-10-01

Electromagnetic interference with pacemaker and implantable cardioverter defibrillator (ICD) systems may cause temporary or permanent system malfunction of implanted devices. The aim of this study was to evaluate potential interference of a novel magnetic navigation system with implantable rhythm devices. A total of 121 devices (77 pacemakers, 44 ICDs) were exposed to an activated NIOBE II® Magnetic Navigation System (Stereotaxis, St. Louis, MO, USA) at the maximal magnetic field strength of 0.1 Tesla and evaluated in vitro with respect to changes in parameter settings of the device, changes of the battery status/detection of elective replacement indication, or alterations of data stored in the device. A total of 115 out of 121 (95%) devices were free of changes in parameter settings, battery status, and internally stored data after repeated exposition to the electromagnetic field of the remote magnetic navigation system. Interference with the magnetic navigation field was observed in 6 pacemakers, resulting in reprogramming to a power-on-reset mode with or without detection of the elective replacement indication in 5 devices and abnormal variance of battery status in one device. All pacemakers could be reprogrammed to the initial modes and the battery status proved to be normal some minutes after the pacemakers had been removed from the magnetic field. Interference of a remote magnetic navigation system (at maximal field strength) with pacemakers and ICDs not connected to leads with antitachycardic detection and therapies turned off is rare. Occurring functional abnormalities could be reprogrammed in our sample. An in vitro study will give information about interference of devices connected to leads. © 2010 Wiley Periodicals, Inc.

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

Management and outcome of patients with acute myocardial infarction presenting with pacemaker rhythm.

PubMed

Bertel, Noemi; Witassek, Fabienne; Puhan, Milo; Erne, Paul; Rickli, Hans; Naegeli, Barbara; Pedrazzini, Giovanni; Stauffer, Jean-Christophe; Radovanovic, Dragana

2017-03-01

Diagnosis of acute myocardial infarction (MI) is challenging in pacemaker patients. Little is known about this patient group. Patients with MI enrolled in the Swiss national AMIS Plus registry between January 2005 and December 2015 were analyzed. All patients with either paced ventricular rhythm or sinus rhythm with intrinsic ventricular conduction (IVC) were included in this study. Outcomes using crude data and propensity score matching were compared between patients with pacemaker rhythm and patients with IVC. The primary endpoint was in-hospital death. Data from 300 patients with paced rhythm and 27,595 with IVC were analyzed. Patients with pacemaker rhythm were older (78.2y vs 65.4y; p<0.001), had more comorbidities (Charlson Index (CCI)>1: 54.0% vs 21.1%; p<0.001) and a higher rate of heart failure upon presentation (Killip class>2, 11.0% vs 5.9%; p<0.001) compared to patients with IVC. Door to balloon time in patients undergoing acute PCI is markedly delayed in contrast to patients with IVC (280min vs 85min; p<0.001). Consequently, crude mortality in patients with pacemakers was high (11.3% vs 4.6%; p<0.001). However, when analyzed with propensity matching for gender, age, CCI>1 and Killip>2, mortality was similar (11.2% vs 10.5%; p=0.70). Pacemaker patients with acute MI represent a high-risk group with doubled crude mortality compared to patients without pacemakers, due to higher age and higher Killip class. Diagnosis is difficult and results in delayed treatment. Treatment algorithms for MI with paced rhythm should possibly be adapted to those used for STEMI or new left bundle branch block. NCT01305785. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Global health resource utilization associated with pacemaker complications.

PubMed

Waweru, Catherine; Steenrod, Anna; Wolff, Claudia; Eggington, Simon; Wright, David Jay; Wyrwich, Kathleen W

2017-07-01

To estimate health resource utilization (HRU) associated with the management of pacemaker complications in various healthcare systems. Electrophysiologists (EPs) from four geographical regions (Western Europe, Australia, Japan, and North America) were invited to participate. Survey questions focused on HRU in the management of three chronic pacemaker complications (i.e. pacemaker infections requiring extraction, lead fractures/insulation breaches requiring replacement, and upper extremity deep venous thrombosis [DVT]). Panelists completed a maximum of two web-based surveys (iterative rounds). Mean, median values, and interquartile ranges were calculated and used to establish consensus. Overall, 32 and 29 panelists participated in the first and second rounds of the Delphi panel, respectively. Consensus was reached on treatment and HRU associated with a typical pacemaker implantation and complications. HRU was similar across regions, except for Japan, where panelists reported the longest duration of hospital stay in all scenarios. Infections were the most resource-intensive complications and were characterized by intravenous antibiotics days of 9.6?13.5 days and 21.3?29.2 days for pocket and lead infections respectively; laboratory and diagnostic tests, and system extraction and replacement procedures. DVT, on the other hand, was the least resource intensive complication. The results of the panel represent the views of the respondents who participated and may not be generalizable outside of this panel. The surveys were limited in scope and, therefore, did not include questions on management of acute complications (e.g. hematoma, pneumothorax). The Delphi technique provided a reliable and efficient approach to estimating resource utilization associated with chronic pacemaker complications. Estimates from the Delphi panel can be used to generate costs of pacemaker complications in various regions.

Low permanent pacemaker rates following Lotus device implantation for transcatheter aortic valve replacement due to modified implantation protocol.

PubMed

Krackhardt, Florian; Kherad, Behrouz; Krisper, Maximilian; Pieske, Burkert; Laule, Michael; Tschöpe, Carsten

2017-01-01

Conduction disturbances requiring permanent pacemaker implantation following transcatheter aortic valve replacement (TAVR) are a common problem. Pacemaker implantation rates after TAVR appear to be higher compared to conventional aortic valve replacement. The aim of this study was to analyze whether a high annulus implantation conveys the benefit of a decreased rate of permanent pacemaker implantation while being safe and successful according to Valve Academic Research Consortium 2 (VARC2)-criteria. A total of 23 patients with symptomatic severe aortic valve stenosis, an aortic annulus of 19-27 mm and at high risk for surgery were treated with the Lotus valve. In all patients the valve was implanted in a high annulus position via femoral access. The primary device performance endpoint was VARC2-defined device success after 30 days and the primary safety endpoint was the need for permanent pacemaker implantation. The mean age was 73.23 ± 7.65 years, 46% were female, 38% were New York Heart Association class III/IV at baseline. Thirty-day follow-up data were available for all patients. The VARC2-defined device success rate after 30 days was 22/23 (96%). 2/21 (10%) patients required a newly implanted pacemaker due to 3rd degree atrioventricular block. 25% of the patients developed a new left bundle branch block after valvuloplasty or device implantation. 21 of the 23 patients (96%) had no other signs of conduction disturbances after 30 days. The approach of the modified implantation technique of Lotus TAVR device was safe and effective. The incidence of need for a permanent pacemaker following TAVR could be significantly reduced due to adopted implantation protocol.

Autaptic pacemaker mediated propagation of weak rhythmic activity across small-world neuronal networks

NASA Astrophysics Data System (ADS)

Yilmaz, Ergin; Baysal, Veli; Ozer, Mahmut; Perc, Matjaž

2016-02-01

We study the effects of an autapse, which is mathematically described as a self-feedback loop, on the propagation of weak, localized pacemaker activity across a Newman-Watts small-world network consisting of stochastic Hodgkin-Huxley neurons. We consider that only the pacemaker neuron, which is stimulated by a subthreshold periodic signal, has an electrical autapse that is characterized by a coupling strength and a delay time. We focus on the impact of the coupling strength, the network structure, the properties of the weak periodic stimulus, and the properties of the autapse on the transmission of localized pacemaker activity. Obtained results indicate the existence of optimal channel noise intensity for the propagation of the localized rhythm. Under optimal conditions, the autapse can significantly improve the propagation of pacemaker activity, but only for a specific range of the autaptic coupling strength. Moreover, the autaptic delay time has to be equal to the intrinsic oscillation period of the Hodgkin-Huxley neuron or its integer multiples. We analyze the inter-spike interval histogram and show that the autapse enhances or suppresses the propagation of the localized rhythm by increasing or decreasing the phase locking between the spiking of the pacemaker neuron and the weak periodic signal. In particular, when the autaptic delay time is equal to the intrinsic period of oscillations an optimal phase locking takes place, resulting in a dominant time scale of the spiking activity. We also investigate the effects of the network structure and the coupling strength on the propagation of pacemaker activity. We find that there exist an optimal coupling strength and an optimal network structure that together warrant an optimal propagation of the localized rhythm.

Percutaneous Resection of Renal Urothelial Carcinoma Using Bipolar Electrocautery

PubMed Central

Kwan, Kevin G.; Chew, Ben H.; Luke, Patrick P.W.; Denstedt, John D.

2006-01-01

Percutaneous approaches to upper tract urothelial cancers have been performed in patients unsuitable for radical nephroureterectomy. We present the case of an 82-year-old man with significant comorbidities including dependency on a cardiac pacemaker. Without deactivating the pacemaker, we used bipolar cautery to percutaneously resect a large upper tract urothelial tumor in the renal pelvis. Bipolar cautery is a suitable method of percutaneous or transurethral resection in patients who are pacemaker dependent. PMID:17575777

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

Circadian locomotor rhythms in the cricket, Gryllodes sigillatus. II. Interactions between bilaterally paired circadian pacemakers.

PubMed

Ushirogawa, H; Abe, Y; Tomioka, K

1997-10-01

The optic lobe is essential for circadian locomotor rhythms in the cricket, Gryllodes sigillatus. We examined potential interactions between the bilaterally paired optic lobes in circadian rhythm generation. When one optic lobe was removed, the free-running period of the locomotor rhythm slightly but significantly lengthened. When exposed to light-dark cycles (LD) with 26 hr period, intact and sham operated animals were clearly entrained to the light cycle, but a large number of animals receiving unilateral optic nerve severance showed rhythm dissociation. In the dissociation, two rhythmic components appeared; one was readily entrained to the given LD and the other free-ran with a period shorter than 24 hr, and activity was expressed only when they were inphase. The period of the free-running component was significantly longer than that of the animals with a single blinded pacemaker kept in LD13:13, suggesting that the pacemaker on the intact side had some influence on the blinded pacemaker even in the dissociated state. The ratio of animals with rhythm dissociation was greater with the lower light intensity of the LD. The results suggest that the bilaterally distributed pacemakers are only weakly coupled to one another but strongly suppress the activity driven by the partner pacemaker during their subjective day. The strong suppression of activity would be advantageous to keep a stable nocturnality for this cricket living indoors.

The effect of hyperkalaemia on cardiac rhythm devices.

PubMed

Barold, S Serge; Herweg, Bengt

2014-04-01

In patients with pacemakers, hyperkalaemia causes three important abnormalities that usually become manifest when the K level exceeds 7 mEq/L: (i) widening of the paced QRS complex from delayed intraventricular conduction velocity, (ii) Increased atrial and ventricular pacing thresholds that may cause failure to capture. In this respect, the atria are more susceptible to loss of capture than the ventricles, and (iii) Increased latency (usually with ventricular pacing) manifested by a greater delay of the interval from the pacemaker stimulus to the onset of depolarization. First-degree ventricular pacemaker exit block may progress to second-degree Wenckebach (type I) exit block characterized by gradual prolongation of the interval from the pacemaker stimulus to the onset of the paced QRS complex ultimately resulting in an ineffectual stimulus. The disturbance may then progress to 2 : 1, 3 : 1 pacemaker exit block, etc., and eventually to complete exit block with total lack of capture. Ventricular undersensing is uncommonly observed because of frequent antibradycardia pacing. During managed ventricular pacing, hyperkalaemia-induced marked first-degree atrioventricular block may induce a pacemaker syndrome. With implantable cardioverter-defibrillators (ICDs) oversensing of the paced or spontaneous T-wave may occur. The latter may cause inappropriate shocks. A raised impedance from the right ventricular coil to the superior vena cava coil may become an important sign of hyperkalaemia in the asymptomatic or the minimally symptomatic ICD patient.

Surgical outcome of Fontan conversion and arrhythmia surgery: Need a pacemaker?

PubMed

Terada, Takafumi; Sakurai, Hajime; Nonaka, Toshimichi; Sakurai, Takahisa; Sugiura, Junya; Taneichi, Tetsuyoshi; Ohtsuka, Ryohei

2014-07-01

Atrial tachyarrhythmias are frequent complications in the late period after the Fontan procedure, and important risk factors for a poor prognosis. The impact of Fontan conversion and arrhythmia surgery in failed Fontan patients has been described in many reports. We evaluated our experience with Fontan conversion procedures, concomitant arrhythmia surgery, and pacemaker implantation. We reviewed the hospital records of 25 consecutive patients who underwent a Fontan conversion procedure from January 2004 to March 2012. Twenty-four patients had arrhythmia surgery using cryoablation and radiofrequency ablation at the time of conversion. A bilateral atrial maze procedure was performed in 6 patients, right-side maze in 15, and isthmus block in 3. Three patients with a diagnosis of corrected transposition of the great arteries underwent simultaneous pacemaker implantation electively. There was no early death and one late death during a mean follow-up period of 21.2 months. Three tachyarrhythmia recurrences developed, and there were 4 occurrences of sinus bradycardia. Five of these patients required postoperative pacemaker implantation. The mid-term results of Fontan conversion and arrhythmia surgery in our institute were satisfactory. The occurrence of unexpected postoperative pacemaker requirement was high in the patients who underwent a right atrial or bilateral atrial maze procedure. Pacemaker or lead implantation is recommended for patients planned to undergo a right-side or full maze procedure. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Comparison of DDD versus VVIR pacing modes in elderly patients with atrioventricular block.

PubMed

Kılıçaslan, Barış; Vatansever Ağca, Fahriye; Kılıçaslan, Esin Evren; Kınay, Ozan; Tigen, Kürşat; Cakır, Cayan; Nazlı, Cem; Ergene, Oktay

2012-06-01

Dual-chamber pacing is believed to have an advantage over single-chamber ventricular pacing. The aim of this study was to determine whether elderly patients who have implanted pacemakers for complete atrioventricular block gain significant benefits from dual-chamber (DDD) pacemakers compared with single chamber ventricular (VVIR) pacemakers. This study was designed as a randomized, two-period crossover study-each pacing mode was maintained for 1 month. Thirty patients (16 men, mean age 68.87 ± 6.89 years) with implanted DDD pacemakers were submitted to a standard protocol, which included an interview, pacemaker syndrome assessment, health related quality of life (HRQoL) questionnaires assessed by an SF-36 test, 6-minute walk test (6MWT), and transthoracic echocardiographic examinations. All of these parameters were obtained on both DDD and VVIR mode pacing. Paired data were compared. HRQoL scores were similar, and 6MWT results did not differ between the two groups. VVIR pacing elicited significant enlargement of the left atrium and impaired left ventricular diastolic functions as compared with DDD pacing. Two patients reported subclinical pacemaker syndrome, but this was not statistically significant. Our study revealed that in active elderly patients with complete heart block, DDD pacing and VVIR pacing yielded similar improvements in QoL and exercise performance. However, after a short follow-up period, we noted that VVIR pacing caused significant left atrial enlargement and impaired left ventricular diastolic functions.

Sequential establishment of stripe patterns in an expanding cell population.

PubMed

Liu, Chenli; Fu, Xiongfei; Liu, Lizhong; Ren, Xiaojing; Chau, Carlos K L; Li, Sihong; Xiang, Lu; Zeng, Hualing; Chen, Guanhua; Tang, Lei-Han; Lenz, Peter; Cui, Xiaodong; Huang, Wei; Hwa, Terence; Huang, Jian-Dong

2011-10-14

Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.

Conditional Deletion of Bmal1 in Ovarian Theca Cells Disrupts Ovulation in Female Mice.

PubMed

Mereness, Amanda L; Murphy, Zachary C; Forrestel, Andrew C; Butler, Susan; Ko, CheMyong; Richards, JoAnne S; Sellix, Michael T

2016-02-01

Rhythmic events in female reproductive physiology, including ovulation, are tightly controlled by the circadian timing system. The molecular clock, a feedback loop oscillator of clock gene transcription factors, dictates rhythms of gene expression in the hypothalamo-pituitary-ovarian axis. Circadian disruption due to environmental factors (eg, shift work) or genetic manipulation of the clock has negative impacts on fertility. Although the central pacemaker in the suprachiasmatic nucleus classically regulates the timing of ovulation, we have shown that this rhythm also depends on phasic sensitivity to LH. We hypothesized that this rhythm relies on clock function in a specific cellular compartment of the ovarian follicle. To test this hypothesis we generated mice with deletion of the Bmal1 locus in ovarian granulosa cells (GCs) (Granulosa Cell Bmal1 KO; GCKO) or theca cells (TCs) (Theca Cell Bmal1 KO; TCKO). Reproductive cycles, preovulatory LH secretion, ovarian morphology and behavior were not grossly altered in GCKO or TCKO mice. We detected phasic sensitivity to LH in wild-type littermate control (LC) and GCKO mice but not TCKO mice. This decline in sensitivity to LH is coincident with impaired fertility and altered patterns of LH receptor (Lhcgr) mRNA abundance in the ovary of TCKO mice. These data suggest that the TC is a pacemaker that contributes to the timing and amplitude of ovulation by modulating phasic sensitivity to LH. The TC clock may play a critical role in circadian disruption-mediated reproductive pathology and could be a target for chronobiotic management of infertility due to environmental circadian disruption and/or hormone-dependent reprogramming in women.

Efficiency of lithium pacemaker batteries as a function of discharge rate and iodine:P2VP cathode composition

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

Helgeson, W.D.; Fester, K.E.

1980-01-01

Electrochemical discharge data for Li/I/sub 2/-P2VP pacemaker batteries at various discharge currents show the efficiency of the battery to be a function of discharge current. Depending on the iodine:P2VP cathode composition, the optimum current drain occurs between discharge currents of 100 to 200 /mu/a. As current drain is reduced to pacemaker application drains, 15-25 /mu/a, the efficiency of the Li/I/sub 2/-P2VP battery decreases. The loss in efficiency at pacemaker rates is attributed primarily to self-discharge. The efficiency of Li/I/sub 2/-P2VP batteries is improved by increasing the percent of iodine in the cathode. I/sub 2/:P2VP weight ratios of 10:1, 15:1 andmore » 20:1 have been discharged at various currents and the data indicate that there is significant improvement in efficiency at pacemaker rate in going from 10:1 to 20:1 cathode weight ratio. 2 refs.« less

The membrane pacemaker hypothesis: novel tests during the ontogeny of endothermy.

PubMed

Price, Edwin R; Sirsat, Tushar S; Sirsat, Sarah K G; Curran, Thomas; Venables, Barney J; Dzialowski, Edward M

2018-03-29

The 'membrane pacemaker' hypothesis proposes a biochemical explanation for among-species variation in resting metabolism, based on the positive correlation between membrane docosahexaenoic acid (DHA) and metabolic rate. We tested this hypothesis using a novel model, altricial red-winged blackbird nestlings, predicting that the proportion of DHA in muscle and liver membranes should increase with the increasing metabolic rate of the nestling as it develops endothermy. We also used a dietary manipulation, supplementing the natural diet with fish oil (high DHA) or sunflower oil (high linoleic acid) to alter membrane composition and then assessed metabolic rate. In support of the membrane pacemaker hypothesis, DHA proportions increased in membranes from pectoralis muscle, muscle mitochondria and liver during post-hatch development. By contrast, elevated dietary DHA had no effect on resting metabolic rate, despite causing significant changes to membrane lipid composition. During cold challenges, higher metabolic rates were achieved by birds that had lower DHA and higher linoleic acid in membrane phospholipids. Given the mixed support for this hypothesis, we conclude that correlations between membrane DHA and metabolic rate are likely spurious, and should be attributed to a still-unidentified confounding variable. © 2018. Published by The Company of Biologists Ltd.

Microfluidic glucose stimulation reveals limited coordination of intracellular Ca2+ activity oscillations in pancreatic islets

PubMed Central

Rocheleau, Jonathan V.; Walker, Glenn M.; Head, W. Steven; McGuinness, Owen P.; Piston, David W.

2004-01-01

The pancreatic islet is a functional microorgan involved in maintaining normoglycemia through regulated secretion of insulin and other hormones. Extracellular glucose stimulates insulin secretion from islet β cells through an increase in redox state, which can be measured by NAD(P)H autofluorescence. Glucose concentrations over ≈7 mM generate synchronous oscillations in β cell intracellular Ca2+ concentration ([Ca2+]i), which lead to pulsatile insulin secretion. Prevailing models assume that the pancreatic islet acts as a functional syncytium, and the whole islet [Ca2+]i response has been modeled in terms of islet bursting and pacemaker models. To test these models, we developed a microfluidic device capable of partially stimulating an islet, while allowing observation of the NAD(P)H and [Ca2+]i responses. We show that β cell [Ca2+]i oscillations occur only within regions stimulated with more than ≈6.6 mM glucose. Furthermore, we show that tolbutamide, an antagonist of the ATP-sensitive K+ channel, allows these oscillations to travel farther into the nonstimulated regions of the islet. Our approach shows that the extent of Ca2+ propagation across the islet depends on a delicate interaction between the degree of coupling and the extent of ATP-sensitive K+-channel activation and illustrates an experimental paradigm that will have utility for many other biological systems. PMID:15317941

Expression and distribution of voltage-gated ion channels in ferret sinoatrial node.

PubMed

Brahmajothi, Mulugu V; Morales, Michael J; Campbell, Donald L; Steenbergen, Charles; Strauss, Harold C

2010-10-01

Spontaneous diastolic depolarization in the sinoatrial (SA) node enables it to serve as pacemaker of the heart. The variable cell morphology within the SA node predicts that ion channel expression would be heterogeneous and different from that in the atrium. To evaluate ion channel heterogeneity within the SA node, we used fluorescent in situ hybridization to examine ion channel expression in the ferret SA node region and atrial appendage. SA nodal cells were distinguished from surrounding cardiac myocytes by expression of the slow (SA node) and cardiac (surrounding tissue) forms of troponin I. Nerve cells in the sections were identified by detection of GAP-43 and cytoskeletal middle neurofilament. Transcript expression was characterized for the 4 hyperpolarization-activated cation channels, 6 voltage-gated Na(+) channels, 3 voltage-gated Ca(2+) channels, 24 voltage-gated K(+) channel α-subunits, and 3 ancillary subunits. To ensure that transcript expression was representative of protein expression, immunofluorescence was used to verify localization patterns of voltage-dependent K(+) channels. Colocalizations were performed to observe any preferential patterns. Some overlapping and nonoverlapping binding patterns were observed. Measurement of different cation channel transcripts showed heterogeneous expression with many different patterns of expression, attesting to the complexity of electrical activity in the SA node. This study provides insight into the possible role ion channel heterogeneity plays in SA node pacemaker activity.

Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior.

PubMed

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-03-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(-) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per⁰¹ mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per⁰¹ flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output.

Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior

PubMed Central

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-01-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(−) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(−) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per01 mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per01 flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

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.

Pacemaker-neuron–dependent disturbance of the molecular clockwork by a Drosophila CLOCK mutant homologous to the mouse Clock mutation

PubMed Central

Lee, Euna; Cho, Eunjoo; Kang, Doo Hyun; Jeong, Eun Hee; Chen, Zheng; Yoo, Seung-Hee; Kim, Eun Young

2016-01-01

Circadian clocks are composed of transcriptional/translational feedback loops (TTFLs) at the cellular level. In Drosophila TTFLs, the transcription factor dCLOCK (dCLK)/CYCLE (CYC) activates clock target gene expression, which is repressed by the physical interaction with PERIOD (PER). Here, we show that amino acids (AA) 657–707 of dCLK, a region that is homologous to the mouse Clock exon 19-encoded region, is crucial for PER binding and E-box–dependent transactivation in S2 cells. Consistently, in transgenic flies expressing dCLK with an AA657–707 deletion in the Clock (Clkout) genetic background (p{dClk-Δ};Clkout), oscillation of core clock genes’ mRNAs displayed diminished amplitude compared with control flies, and the highly abundant dCLKΔ657–707 showed significantly decreased binding to PER. Behaviorally, the p{dClk-Δ};Clkout flies exhibited arrhythmic locomotor behavior in the photic entrainment condition but showed anticipatory activities of temperature transition and improved free-running rhythms in the temperature entrainment condition. Surprisingly, p{dClk-Δ};Clkout flies showed pacemaker-neuron–dependent alterations in molecular rhythms; the abundance of dCLK target clock proteins was reduced in ventral lateral neurons (LNvs) but not in dorsal neurons (DNs) in both entrainment conditions. In p{dClk-Δ};Clkout flies, however, strong but delayed molecular oscillations in temperature cycle-sensitive pacemaker neurons, such as DN1s and DN2s, were correlated with delayed anticipatory activities of temperature transition. Taken together, our study reveals that the LNv molecular clockwork is more sensitive than the clockwork of DNs to dysregulation of dCLK by AA657–707 deletion. Therefore, we propose that the dCLK/CYC-controlled TTFL operates differently in subsets of pacemaker neurons, which may contribute to their specific functions. PMID:27489346

Battery Malfunction of a Leadless Cardiac Pacemaker - A Worrisome Single-Center Experience.

PubMed

Richter, Sergio; Döring, Michael; Ebert, Micaela; Bode, Kerstin; Müssigbrodt, Andreas; Sommer, Philipp; Husser, Daniela; Hindricks, Gerhard

2018-03-14

Leadless cardiac pacemaker (LCP) therapy has been established clinically as a feasible and safe alternative to conventional transvenous pacemaker therapy for patients with an indication for single-chamber right-ventricular pacing. 1-3 However, reports on loss of telemetry and pacing output due to abrupt battery failure called the safety of one of the two commercially available systems seriously into question. The initial battery advisory with the Nanostim™ LCP was issued by the manufacturer in October 2016, who instantly called a global stop to Nanostim™ implants. To this day, similar battery issues have not been described for the Micra™ transcatheter pacing system. Therefore, we thought to analyze the long-term pacemaker performance and rate of battery malfunction of the Nanostim™ LCP in our patient population.

Ductal carcinoma of the breast in the pacemaker generator's pocket.

PubMed

Zonca, P; Herokova, J; Cambal, M; Jacobi, C A

2009-01-01

Authors present a case of a 78-year-old female patient with invasive ductal adenocarcinoma in the pacemaker, s pocket. A decubitus-like tumor had developed in this place, and has been missinterpretated as a benign lesion for 5 months. Diagnosis was done with a time delay. An excisional biopsy revealed annvasive ductal adenocarcinoma. The first step was the implantation of a new pacemaker generator performed on the opposite side. The second step was a modified radical mastectomy, according to Madden, and the removal of the originally implanted pacemaker generator. Radiotherapy and hormonal adjuvant therapy were applied after surgery. The patient was followed-up at an out-patient clinic, and died 25 months after diagnosis because of generalization of the disease (Fig. 2, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

Characterization of piezoelectric device for implanted pacemaker energy harvesting

NASA Astrophysics Data System (ADS)

Jay, Sunny; Caballero, Manuel; Quinn, William; Barrett, John; Hill, Martin

2016-10-01

Novel implanted cardiac pacemakers that are powered by energy harvesters driven by the cardiac motion and have a 40 year lifetime are currently under development. To satisfy space constraints and energy requirements of the device, silicon-based MEMS energy harvesters are being developed in the EU project (MANpower1). Such MEMS harvesters for vibration frequencies below 50 Hz have not been widely reported. In this paper, an analytical model and a 3D finite element model (FEM) to predict displacement and open circuit voltage, validated through experimental analysis using an off-the-shelf low frequency energy harvester, are presented. The harvester was excited through constant amplitude sinusoidal base displacement over a range of 20 to 70 Hz passing through its first mode natural frequency at 47 Hz. At resonance both models predict displacements with an error of less than 2% when compared to the experimental result. Comparing the two models, the application of the experimentally measured damping ratio differs for accurate displacement prediction and the differences in symmetry in the measured and modelled displacement and voltage data around the resonance frequency indicate the two piezoelectric voltage models use different fundamental equations.

Implantable Medical Devices

MedlinePlus

... Also known as ICD ) - An ICD is a battery-powered device placed under the skin that keeps ... Pacemaker (Also known as Artificial Pacemaker) - A small battery-operated device that helps the heart beat in ...

Engineered Biological Pacemakers | NCI Technology Transfer Center | TTC

Cancer.gov

The National Institute on Aging's Cellular Biophysics Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize biological pacemakers.

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 ...

Complete removal of infected devices and simultaneous implantation of new devices for infective endocarditis after pacemaker implantation.

PubMed

Miura, Takuya; Inoue, Kazushige; Yokota, Takenori; Iwata, Takashi; Yoshitatsu, Masao

2017-02-01

Two cases of infective endocarditis after pacemaker implantation were reported. Complete removal of infected devices was performed under cardiopulmonary bypass, and simultaneous implantation of new devices was performed using epicardial leads and generator on the abdominal wall. The postoperative course was uneventful and recurrence was not recognized. These procedures may be suitable for the patients who depend on the pacemaker or who have repeat bacteremia with other infectious disease or conditions.

On Variations in the Level of PER in Glial Clocks of Drosophila Optic Lobe and Its Negative Regulation by PDF Signaling.

PubMed

Górska-Andrzejak, Jolanta; Chwastek, Elżbieta M; Walkowicz, Lucyna; Witek, Kacper

2018-01-01

We show that the level of the core protein of the circadian clock Period (PER) expressed by glial peripheral oscillators depends on their location in the Drosophila optic lobe. It appears to be controlled by the ventral lateral neurons (LNvs) that release the circadian neurotransmitter Pigment Dispersing Factor (PDF). We demonstrate that glial cells of the distal medulla neuropil (dMnGl) that lie in the vicinity of the PDF-releasing terminals of the LNvs possess receptors for PDF (PDFRs) and express PER at significantly higher level than other types of glia. Surprisingly, the amplitude of PER molecular oscillations in dMnGl is increased twofold in PDF-free environment, that is in Pdf 0 mutants. The Pdf 0 mutants also reveal an increased level of glia-specific protein REPO in dMnGl. The photoreceptors of the compound eye (R-cells) of the PDF-null flies, on the other hand, exhibit de-synchrony of PER molecular oscillations, which manifests itself as increased variability of PER-specific immunofluorescence among the R-cells. Moreover, the daily pattern of expression of the presynaptic protein Bruchpilot (BRP) in the lamina terminals of the R-cells is changed in Pdf 0 mutant. Considering that PDFRs are also expressed by the marginal glia of the lamina that surround the R-cell terminals, the LNv pacemakers appear to be the likely modulators of molecular cycling in the peripheral clocks of both the glial cells and the photoreceptors of the compound eye. Consequently, some form of PDF-based coupling of the glial clocks and the photoreceptors of the eye with the central LNv pacemakers must be operational.

On Variations in the Level of PER in Glial Clocks of Drosophila Optic Lobe and Its Negative Regulation by PDF Signaling

PubMed Central

Górska-Andrzejak, Jolanta; Chwastek, Elżbieta M.; Walkowicz, Lucyna; Witek, Kacper

2018-01-01

We show that the level of the core protein of the circadian clock Period (PER) expressed by glial peripheral oscillators depends on their location in the Drosophila optic lobe. It appears to be controlled by the ventral lateral neurons (LNvs) that release the circadian neurotransmitter Pigment Dispersing Factor (PDF). We demonstrate that glial cells of the distal medulla neuropil (dMnGl) that lie in the vicinity of the PDF-releasing terminals of the LNvs possess receptors for PDF (PDFRs) and express PER at significantly higher level than other types of glia. Surprisingly, the amplitude of PER molecular oscillations in dMnGl is increased twofold in PDF-free environment, that is in Pdf0 mutants. The Pdf0 mutants also reveal an increased level of glia-specific protein REPO in dMnGl. The photoreceptors of the compound eye (R-cells) of the PDF-null flies, on the other hand, exhibit de-synchrony of PER molecular oscillations, which manifests itself as increased variability of PER-specific immunofluorescence among the R-cells. Moreover, the daily pattern of expression of the presynaptic protein Bruchpilot (BRP) in the lamina terminals of the R-cells is changed in Pdf0 mutant. Considering that PDFRs are also expressed by the marginal glia of the lamina that surround the R-cell terminals, the LNv pacemakers appear to be the likely modulators of molecular cycling in the peripheral clocks of both the glial cells and the photoreceptors of the compound eye. Consequently, some form of PDF-based coupling of the glial clocks and the photoreceptors of the eye with the central LNv pacemakers must be operational. PMID:29615925

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.

Pacemaker

MedlinePlus

... check for changes in your heart's electrical activity. Battery Replacement Pacemaker batteries last between 5 and 15 years (average 6 ... doctor will replace the generator along with the battery before the battery starts to run down. Replacing ...

Implantable cardioverter defibrillator - discharge

MedlinePlus

... defibrillation. This device can also work as a pacemaker. What to Expect at Home When you leave ... pubmed/23265327 . Swerdlow CD, Wang PL, Zipes DP. Pacemakers and implantable cardioverter-defibrillators. In: Mann DL, Zipes ...

Reciprocal links between metabolic and ionic events in islet cells. Their relevance to the rhythmics of insulin release.

PubMed

Malaisse, W J

1998-02-01

The notion of reciprocal links between metabolic and ionic events in islet cells and the rhythmics of insulin release is based on (i) the rhythmic pattern of hormonal release from isolated perfused rat pancreas, which supports the concept of an intrapancreatic pacemaker; (ii) the assumption that this phasic pattern is due to the integration of secretory activity in distinct functional units, e.g. distinct islets; and (iii) the fact that reciprocal coupling between metabolic and ionic events is operative in the secretory sequence.

CaV3.1 is a tremor rhythm pacemaker in the inferior olive

PubMed Central

Park, Young-Gyun; Park, Hye-Yeon; Lee, C. Justin; Choi, Soonwook; Jo, Seonmi; Choi, Hansol; Kim, Yang-Hann; Shin, Hee-Sup; Llinas, Rodolfo R.; Kim, Daesoo

2010-01-01

The rhythmic motor pathway activation by pacemaker neurons or circuits in the brain has been proposed as the mechanism for the timing of motor coordination, and the abnormal potentiation of this mechanism may lead to a pathological tremor. Here, we show that the potentiation of CaV3.1 T-type Ca2+ channels in the inferior olive contributes to the onset of the tremor in a pharmacological model of essential tremor. After administration of harmaline, 4- to 10-Hz synchronous neuronal activities arose from the IO and then propagated to cerebellar motor circuits in wild-type mice, but those rhythmic activities were absent in mice lacking CaV3.1 gene. Intracellular recordings in brain-stem slices revealed that the CaV3.1-deficient inferior olive neurons lacked the subthreshold oscillation of membrane potentials and failed to trigger 4- to 10-Hz rhythmic burst discharges in the presence of harmaline. In addition, the selective knockdown of CaV3.1 gene in the inferior olive by shRNA efficiently suppressed the harmaline-induced tremor in wild-type mice. A mathematical model constructed based on data obtained from patch-clamping experiments indicated that harmaline could efficiently potentiate CaV3.1 channels by changing voltage-dependent responsiveness in the hyperpolarizing direction. Thus, CaV3.1 is a molecular pacemaker substrate for intrinsic neuronal oscillations of inferior olive neurons, and the potentiation of this mechanism can be considered as a pathological cause of essential tremor. PMID:20498062

Strong attachment of circadian pacemaker neurons on modified ultrananocrystalline diamond surfaces.

PubMed

Voss, Alexandra; Wei, HongYing; Zhang, Yi; Turner, Stuart; Ceccone, Giacomo; Reithmaier, Johann Peter; Stengl, Monika; Popov, Cyril

2016-07-01

Diamond is a promising material for a number of bio-applications, including the fabrication of platforms for attachment and investigation of neurons and of neuroprostheses, such as retinal implants. In the current work ultrananocrystalline diamond (UNCD) films were deposited by microwave plasma chemical vapor deposition, modified by UV/O3 treatment or NH3 plasma, and comprehensively characterized with respect to their bulk and surface properties, such as crystallinity, topography, composition and chemical bonding nature. The interactions of insect circadian pacemaker neurons with UNCD surfaces with H-, O- and NH2-terminations were investigated with respect to cell density and viability. The fast and strong attachment achieved without application of adhesion proteins allowed for advantageous modification of dispersion protocols for the preparation of primary cell cultures. Centrifugation steps, which are employed for pelletizing dispersed cells to separate them from dispersing enzymes, easily damage neurons. Now centrifugation can be avoided since dispersed neurons quickly and strongly attach to the UNCD surfaces. Enzyme solutions can be easily washed off without losing many of the dispersed cells. No adverse effects on the cell viability and physiological responses were observed as revealed by calcium imaging. Furthermore, the enhanced attachment of the neurons, especially on the modified UNCD surfaces, was especially advantageous for the immunocytochemical procedures with the cell cultures. The cell losses during washing steps were significantly reduced by one order of magnitude in comparison to controls. In addition, the integration of a titanium grid structure under the UNCD films allowed for individual assignment of physiologically characterized neurons to immunocytochemically stained cells. Thus, employing UNCD surfaces free of foreign proteins improves cell culture protocols and immunocytochemistry with cultured cells. The fast and strong attachment of neurons was attributed to a favorable combination of topography, surface chemistry and wettability. Copyright © 2016 Elsevier B.V. All rights reserved.

A Low-Cost Simulation Model for R-Wave Synchronized Atrial Pacing in Pediatric Patients with Postoperative Junctional Ectopic Tachycardia

PubMed Central

Michel, Miriam; Egender, Friedemann; Heßling, Vera; Dähnert, Ingo; Gebauer, Roman

2016-01-01

Background Postoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing. Methods A simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps. Results Four testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial. Conclusions A realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique. PMID:26943363

Prevention and Treatment of Arrhythmia

MedlinePlus

... your pulse – especially if you have an artificial pacemaker. Put the second and third fingers of one ... Ablation Devices for Arrhythmia - Implantable Cardioverter Defibrillator (ICD) - Pacemaker Treating Arrhythmias in Children • Arrhythmia Tools & Resources Watch, ...

[Hyperkalemia-induced failure of pacemaker capture and sensing: a case report].

PubMed

Wang, Y P; Chen, B X; Su, K J; Sun, L J; Zhang, Y; Guo, L J; Gao, W

2014-12-18

Hyperkalemia may induce serious cardiac arrhythmia, with possible life-threatening effects. It may cause cardiac pacemaker (PMK) malfunctioning due to a reduction of the electronegativity of the resting myocardial potential. We report the case of a 71-year-old woman who had a previous history of chronic heart failure, chronic renal failure and DDI pacemaker. She was admitted for disturbance of consciousness. During hospitalization, she was observed for extreme hypotension, acute hyperkalemia, ventricular escape rhythm, associated with failure of pacemaker capture and sensing. She was treated with calcium chloride injection, followed by insulin/glucose and sodium bicarbonate infusions; the electrocardiogram recordings showed an correction of the PMK malfunctioning and serial improvement of the intraventricular conduction. This case supports that hyperkalemia should be closely monitored in the chronic heart failure patients combined with chronic renal failure.

Minimally Invasive Epicardial Pacemaker Implantation in Neonates with Congenital Heart Block.

PubMed

Costa, Roberto; Silva, Katia Regina da; Martinelli Filho, Martino; Carrillo, Roger

2017-10-01

Few studies have characterized the surgical outcomes following epicardial pacemaker implantation in neonates with congenital complete atrioventricular block (CCAVB). This study sought to assess the long-term outcomes of a minimally invasive epicardial approach using a subxiphoid access for pacemaker implantation in neonates. Between July 2002 and February 2015, 16 consecutive neonates underwent epicardial pacemaker implantation due to CCAVB. Among these, 12 (75.0%) had congenital heart defects associated with CCAVB. The patients had a mean age of 4.7 ± 5.3 days and nine (56.3%) were female. Bipolar steroid-eluting epicardial leads were implanted in all patients through a minimally invasive subxiphoid approach and fixed on the diaphragmatic ventricular surface. The pulse generator was placed in an epigastric submuscular position. All procedures were successful, with no perioperative complications or early deaths. Mean operating time was 90.2 ± 16.8 minutes. None of the patients displayed pacing or sensing dysfunction, and all parameters remained stable throughout the follow-up period of 4.1 ± 3.9 years. Three children underwent pulse generator replacement due to normal battery depletion at 4.0, 7.2, and 9.0 years of age without the need of ventricular lead replacement. There were two deaths at 12 and 325 days after pacemaker implantation due to bleeding from thrombolytic use and progressive refractory heart failure, respectively. Epicardial pacemaker implantation through a subxiphoid approach in neonates with CCAVB is technically feasible and associated with excellent surgical outcomes and pacing lead longevity.

Outcomes of cardiac pacing in adult patients after a Fontan operation.

PubMed

Egbe, Alexander C; Huntley, Geoffery D; Connolly, Heidi M; Ammash, Naser M; Deshmukh, Abhishek J; Khan, Arooj R; Said, Sameh M; Akintoye, Emmanuel; Warnes, Carole A; Kapa, Suraj

2017-12-01

Cardiac pacing can be challenging after a Fontan operation, and limited data exist regarding pacing in adult Fontan patients. The objectives of our study were to determine risk factors for pacing and occurrence of device-related complications (DRCs) and pacemaker reinterventions. We performed a retrospective review of Fontan patients from 1994 through 2014. We defined DRCs as lead failure, lead recall, cardiac perforation, lead thrombus/vegetation, or device-related infection, and cardiovascular adverse events (CAEs) as venous thrombosis, stroke, death, or heart transplant. Pacemaker reintervention was defined as lead failure or recall. Of 439 patients, 166 (38%) had pacemakers implanted (79 during childhood; 87, adulthood); 114 patients (69%) received epicardial leads initially, and 52 (31%), endocardial leads. Pacing was initially atrial in 52 patients (31%); ventricular, 30 (18%); or dual chamber, 84 (51%). There were 37 reinterventions (1.9% per year) and 48 DRCs (2.4% per year). Pacemaker implantation during childhood was a risk factor for DRCs (hazard ratio, 2.01 [CI, 1.22-5.63]; P = .03). There were 70 CAEs (venous thrombosis, 5; stroke, 11; transplant, 8; and death, 46), yielding a rate of 3.5% per year. DRCs, CAEs, and reintervention rates were comparable for patients with epicardial or endocardial leads. More than one-third of adult Fontan patients referred to Mayo Clinic had pacemaker implantation. Epicardial leads were associated with high rate of pacemaker reinterventions but similar DRC rates in comparison to endocardial leads. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

Effect of 1. 5 tesla nuclear magnetic resonance imaging scanner on implanted permanent pacemakers

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

Hayes, D.L.; Holmes, D.R. Jr.; Gray, J.E.

1987-10-01

Patients with a permanent pacemaker are currently restricted from diagnostic nuclear magnetic resonance (NMR) imaging because of potential adverse effects on the pacemaker by the magnet. Previous work has shown that NMR imaging will result in asynchronous pacing of the pulse generator within a given distance of the magnet. The radiofrequency signal generated by the system may also result in rapid cardiac pacing, which may have deleterious effects. This study utilized a 1.5 tesla unit in an in vivo laboratory animal to evaluate the unit's effects on eight different pulse generators from two manufacturers. All pacemakers functioned in an asynchronousmore » mode when placed within a certain distance of the magnet. In addition, transient reed switch inhibition was observed. Seven of the eight pulse generators paced rapidly when exposed to the radiofrequency signal and there was a dramatic decrease in arterial blood pressure. Whether effective rapid cardiac pacing would occur could not be predicted before exposure to the magnetic resonance unit. Nuclear magnetic resonance imaging with high magnetic fields in patients with a pacemaker should continue to be avoided until the mechanism of the rapid cardiac pacing can be further delineated and either predicted or prevented.« less

Optimal Pulse Configuration Design for Heart Stimulation. A Theoretical, Numerical and Experimental Study.

NASA Astrophysics Data System (ADS)

Hardy, Neil; Dvir, Hila; Fenton, Flavio

Existing pacemakers consider the rectangular pulse to be the optimal form of stimulation current. However, other waveforms for the use of pacemakers could save energy while still stimulating the heart. We aim to find the optimal waveform for pacemaker use, and to offer a theoretical explanation for its advantage. Since the pacemaker battery is a charge source, here we probe the stimulation current waveforms with respect to the total charge delivery. In this talk we present theoretical analysis and numerical simulations of myocyte ion-channel currents acting as an additional source of charge that adds to the external stimulating charge for stimulation purposes. Therefore, we find that as the action potential emerges, the external stimulating current can be reduced accordingly exponentially. We then performed experimental studies in rabbit and cat hearts and showed that indeed exponential truncated pulses with less total charge can still induce activation in the heart. From the experiments, we present curves showing the savings in charge as a function of exponential waveform and we calculated that the longevity of the pacemaker battery would be ten times higher for the exponential current compared to the rectangular waveforms. Thanks to Petit Undergraduate Research Scholars Program and NSF# 1413037.

Decreased human circadian pacemaker influence after 100 days in space: a case study

NASA Technical Reports Server (NTRS)

Monk, T. H.; Kennedy, K. S.; Rose, L. R.; Linenger, J. M.

2001-01-01

OBJECTIVE: The objectives of this study were (1) to assess the circadian rhythms and sleep of a healthy, 42-year-old male astronaut experiencing microgravity (weightlessness) for nearly 5 months while living aboard Space Station Mir as it orbited Earth and (2) to determine the effects of prolonged space flight on the endogenous circadian pacemaker, as indicated by oral temperature and subjective alertness rhythms, and their ramifications for sleep, alertness, and performance. METHODS: For three 12- to 14-day blocks of time (spread throughout the mission), oral temperatures were taken and subjective alertness was self-rated five times per day. Sleep diaries and performance tests were also completed daily during each block. RESULTS: Examination of the subject's circadian alertness and oral temperature rhythms suggested that the endogenous circadian pacemaker seemed to function quite well up to 90 days in space. Thereafter (on days 110-122), the influence of the endogenous circadian pacemaker on oral temperature and subjective alertness circadian rhythms was considerably weakened, with consequent disruptions in sleep. CONCLUSIONS: Space missions lasting more than 3 months might result in diminished circadian pacemaker influence in astronauts, leading to eventual sleep problems.

Pacemakers and Implantable Defibrillators: MedlinePlus Health Topic

MedlinePlus

... pattern. Most arrhythmias result from problems in the electrical system of the heart. If your arrhythmia is ... pacemaker helps control abnormal heart rhythms. It uses electrical pulses to prompt the heart to beat at ...

42 CFR 410.10 - Medical and other health services: Included services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... vaccinations. (m) Outpatient physical therapy and speech pathology services. (n) Cardiac pacemakers and pacemaker leads. (o) Additional services furnished to enrollees of HMOs or CMPs, as described in § 410.58...

42 CFR 410.10 - Medical and other health services: Included services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... vaccinations. (m) Outpatient physical therapy and speech pathology services. (n) Cardiac pacemakers and pacemaker leads. (o) Additional services furnished to enrollees of HMOs or CMPs, as described in § 410.58...

42 CFR 410.10 - Medical and other health services: Included services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... vaccinations. (m) Outpatient physical therapy and speech pathology services. (n) Cardiac pacemakers and pacemaker leads. (o) Additional services furnished to enrollees of HMOs or CMPs, as described in § 410.58...

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.

The use of lithium batteries in biomedical devices

NASA Astrophysics Data System (ADS)

Owens, Boone B.

1989-06-01

Lithium batteries have played an important role in the development of useful implantable biomedical devices. The cardiac pacemaker is the most well known of these devices and high energy, long-life reliable lithium primary cells have effectively replaced all of the alkaline cells previously used in these electronic systems. The recent development of higher power devices such as drug pumps and cardiac defibrillators require the use of batteries with higher energy and power capabilities. High rate rechargeable batteries that can be configured as flat prismatic cells would be especially useful in some of these new applications. Lithium polymer electrolyte batteries may find a useful role in these new areas.

New transmitters and new targets in the autonomic nervous system.

PubMed

Barajas-López, C; Huizinga, J D

1993-12-01

Several recent findings have made research into the autonomic nervous system even more exciting, such as the revelation that nitric oxide is a major neurotransmitter, the delineation of the physiological roles for purines and vasoactive intestinal peptide, and the discovery that the interstitial cells of Cajal are major target cells for enteric innervation. Nitric oxide is probably the major neurotransmitter evoking inhibitory junction potentials in smooth muscle. ATP is a mediator of non-adrenergic non-cholinergic enteric innervation, as well as being a fast neurotransmitter in peripheral and autonomic neuro-neuronal synapses. The interactions between enteric nerves and both immune cells and interstitial cells of Cajal (as pacemaker cells of gut smooth muscle) are forcing a rethink of many aspects of gut physiology.

Modeling bipolar stimulation of cardiac tissue

NASA Astrophysics Data System (ADS)

Galappaththige, Suran K.; Gray, Richard A.; Roth, Bradley J.

2017-09-01

Unipolar stimulation of cardiac tissue is often used in the design of cardiac pacemakers because of the low current required to depolarize the surrounding tissue at rest. However, the advantages of unipolar over bipolar stimulation are not obvious at shorter coupling intervals when the tissue near the pacing electrode is relatively refractory. Therefore, this paper analyzes bipolar stimulation of cardiac tissue. The strength-interval relationship for bipolar stimulation is calculated using the bidomain model and a recently developed parsimonious ionic current model. The strength-interval curves obtained using different electrode separations and arrangements (electrodes placed parallel to the fibers versus perpendicular to the fibers) indicate that bipolar stimulation results in more complex activation patterns compared to unipolar stimulation. An unusually low threshold stimulus current is observed when the electrodes are close to each other (a separation of 1 mm) because of break excitation. Unlike for unipolar stimulation, anode make excitation is not present during bipolar stimulation, and an abrupt switch from anode break to cathode make excitation can cause dramatic changes in threshold with very small changes in the interval. These results could impact the design of implantable pacemakers and defibrillators.

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

James, J; Place, V; Panda, A

Purpose: Several institutions have developed MRI guidelines for patients with MR-unsafe or MR-conditional pacemakers. Here we highlight the role of a medical physicist in implementing these guidelines for non-pacemaker dependent patients. Guidelines: Implementing these guidelines requires involvement from several medical specialties and a strong collaboration with the site MRI supervisor to develop a structured workflow. A medical physicist is required to be present during the scan to supervise the MR scanning and to maintain a safety checklist that ensures: 1) uninterrupted patient communication with the technologist, 2) continuous patient physiologic monitoring (e.g. blood pressure and electrocardiography) by a trained nurse,more » 3) redundant patient vitals monitoring (e.g. pulse oximetry) due to the possibility of in vivo electrocardiography reading fluctuations during image acquisition. A radiologist is strongly recommended to be available to review the images before patients are discharged from the scanner. Pacemaker MRI should be restricted to 1.5T field strength. The MRI sequences should be optimized by the physicist with regards to: a) SAR: limited to <1.5 W/Kg for MR-unsafe pacemakers in normal operating mode, b) RF exposure time: <30 min, c) Coils: use T/R coils but not restricted to such, d) Artifacts: further optimization of sequences whenever image quality is compromised due to the pacemaker. In particular, cardiac, breast and left-shoulder MRIs are most susceptible to these artifacts. Possible strategies to lower the SAR include: a) BW reduction, 2) echo-train-length reduction, 3) increase TR, 4) decrease number of averages, 5) decrease flip angle, 6) reduce slices and/or a combination of all the options. Conclusion: A medical physicist in collaboration with the MR supervisor plays an important role in the supervision/implementation of safe MR scanning of pacemaker patients. Developing and establishing a workflow has enabled our institution to scan over 30 patients with pacemakers without complications, including 3 cardiac MR exams.« less

Pacemaker replacement in nonagenarians: Procedural safety and long-term follow-up.

PubMed

Loirat, Aurélie; Fénéon, Damien; Behaghel, Albin; Behar, Nathalie; Le Helloco, Alain; Mabo, Philippe; Daubert, Jean-Claude; Leclercq, Christophe; Martins, Raphaël P

2015-01-01

The rate of pacemaker implantation is rising. Given that the life expectancy of the population is projected to increase, a large number of elderly patients are likely to be implanted in the future. As pacemaker batteries can last for 8-10years, an increasing number of pacemaker recipients will require replacement of their devices when they become nonagenarians. To analyse the short- and long-term outcomes after device replacement in nonagenarians. Patients aged≥90years referred to a tertiary centre for pacemaker replacement from January 2004 to July 2014 were included retrospectively. Clinical follow-up data were obtained from clinical visits or telephone interviews with patients or their families. The primary clinical endpoint was total mortality. Secondary endpoints included early and delayed procedure-related complications and predictive risk factors for total mortality. Sixty-two patients were included (mean age 93.3±2.9years at time of pacemaker replacement). Mean procedure duration was 35.7±17.2minutes. Mean hospital stay was 2.2±1.1days. One patient died from a perioperative complication. Thirty-seven patients (59.7%) died during a median follow-up of 22.1months (interquartile range, 11.8-39.8months). Survival rates were 84.2% (95% confidence interval [CI] 71.8-91.5%) at 1year, 66.9% (95% CI 51.8-78.2%) at 2years and 22.7% (95% CI 10.6-37.7%) at 5years. Atrial fibrillation (hazard ratio 2.47, 95% CI 1.1-5.6) and non-physiological pacing (i.e. VVI pacing in patients in sinus rhythm) (hazard ratio 2.20, 95% CI 1.0-4.9) were predictors of mortality. Pacemaker replacement in nonagenarians is a safe and straightforward procedure. These data suggest that procedures can be performed securely in this old and frail population, with patients living for a median of 30months afterwards. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Runtime Verification of Pacemaker Functionality Using Hierarchical Fuzzy Colored Petri-nets.

PubMed

Majma, Negar; Babamir, Seyed Morteza; Monadjemi, Amirhassan

2017-02-01

Today, implanted medical devices are increasingly used for many patients and in case of diverse health problems. However, several runtime problems and errors are reported by the relevant organizations, even resulting in patient death. One of those devices is the pacemaker. The pacemaker is a device helping the patient to regulate the heartbeat by connecting to the cardiac vessels. This device is directed by its software, so any failure in this software causes a serious malfunction. Therefore, this study aims to a better way to monitor the device's software behavior to decrease the failure risk. Accordingly, we supervise the runtime function and status of the software. The software verification means examining limitations and needs of the system users by the system running software. In this paper, a method to verify the pacemaker software, based on the fuzzy function of the device, is presented. So, the function limitations of the device are identified and presented as fuzzy rules and then the device is verified based on the hierarchical Fuzzy Colored Petri-net (FCPN), which is formed considering the software limits. Regarding the experiences of using: 1) Fuzzy Petri-nets (FPN) to verify insulin pumps, 2) Colored Petri-nets (CPN) to verify the pacemaker and 3) To verify the pacemaker by a software agent with Petri-network based knowledge, which we gained during the previous studies, the runtime behavior of the pacemaker software is examined by HFCPN, in this paper. This is considered a developing step compared to the earlier work. HFCPN in this paper, compared to the FPN and CPN used in our previous studies reduces the complexity. By presenting the Petri-net (PN) in a hierarchical form, the verification runtime, decreased as 90.61% compared to the verification runtime in the earlier work. Since we need an inference engine in the runtime verification, we used the HFCPN to enhance the performance of the inference engine.

Right bundle branch block without overt heart disease predicts higher risk of pacemaker implantation: the study of atomic-bomb survivors.

PubMed

Kusumoto, Saburo; Kawano, Hiroaki; Makita, Naomasa; Ichimaru, Shinichiro; Kaku, Takashi; Haruta, Daisuke; Hida, Ayumi; Sera, Nobuko; Imaizumi, Misa; Nakashima, Eiji; Maemura, Koji; Akahoshi, Masazumi

2014-06-01

We investigated the clinical course of complete right bundle branch block (RBBB) or RBBB with axis deviation (AD) in terms of subsequent pacemaker implantation for high-degree atrioventricular (AV) block or sick sinus syndrome (SSS). Among the 16,170 atomic-bomb survivors in our biennial health examination between July 1967 and December 2010, we detected 520 newly-acquired RBBB subjects with no organic heart disease, and selected 1038 age- (at RBBB diagnosis) and sex-matched subjects without RBBB to serve as comparison subjects. Multivariate Cox regression analysis was used to estimate the hazard ratios (HRs) for the risk of pacemaker implantation due to all causes, AV block or SSS between RBBB and comparison subjects and between RBBB subjects with and without AD. The risk of pacemaker implantation for RBBB was 4.79 (95% confidence interval [CI] 1.89-12.58; P=0.001), 3.77 (95% CI, 1.09-13.07; P=0.036), and 6.28 (95% CI, 1.24-31.73, P=0.026) when implantation was for all causes, AV block and SSS, respectively. RBBB subjects with AD had a higher risk for all-cause pacemaker implantation than subjects without AD (HR, 3.03; 95% CI, 1.00-9.13, P=0.049). RBBB subjects with AD were younger than subjects without AD at the time of RBBB diagnosis (59.4±7.6 vs 74.4±3.1 years old, P=0.019), and their progression from diagnosis to pacemaker implantation took longer (15.1±6.6 vs 6.4±3.0 years, P=0.032). RBBB, especially with AD, progresses to AV block and SSS that requires pacemaker implantation; the mechanisms by which the conduction defect progresses differ among patients with and without AD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.