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Sinoatrial Node (sinoatrial + node)
Selected AbstractsSustained Inward Current and Pacemaker Activity of Mammalian Sinoatrial NodeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002HENGGUI ZHANG Ph.D. Sustained Inward Current in the Sinoatrial Node.Introduction: A novel sustained inward Na+ current ist, which sensitive to Ca2+ -antagonists and potentiated by beta-adrenergic stimulation, has been described in pacemaker cells of rabbit, guinea pig, and rat sinoatrial node, as well as rabbit AV node. Although ist has been suggested to be an important pacemaker current, this has never been tested experimentally because of the lack of a specific blocker. In this study, we address the role of ist in the pacemaker activity of the sinoatrial node cell using computer models. Methods and Results: The newly developed models of Zhang et al. for peripheral and central rabbit sinoatrial node cells and models of Noble and Noble, Demir et al., Wilders et al., and Dokos et al. for typical rabbit sinoatrial node cells were modified to incorporate equations for ist. The conductance gst was chosen to give a current density-voltage relationship consistent with experimental data. In the models of Zhang et al. (periphery), Noble and Noble, and Dokos et al., in which ist was smaller or about the same amplitude as other inward currents, ist increased the pacemaking rate by 0.6%, 2.2%, and 0.8%, respectively. In the models of Zhang et al. (center), Demir et al., and Wilders et al., in which ist was larger than some other inward ionic currents, ist increased the pacemaking rate by 7%, 20%, and 14%, respectively. Conclusion: ist has the potential to be a regulator of pacemaker activity, although its importance will depend on the amplitude of ist relative to the amplitude of other inward currents involved in pacemaker activity. [source] Modulation of rabbit sinoatrial node activation sequence by acetylcholine and isoproterenol investigated with optical mapping techniqueACTA PHYSIOLOGICA, Issue 4 2009D. V. Abramochkin Abstract Aims:, Changes in the rabbit sinoatrial node (SAN) activation sequence with the cholinergic and adrenergic factors were studied. The correlation between the sinus rhythm rate and the leading pacemaker site shift was determined. The hypothesis concerning the cholinergic suppression of nodal cell excitability as one of the mechanisms associated with pacemaker shift was tested. Methods:, A high-resolution optical mapping technique was used to register beat-to-beat changes in the SAN activation pattern under the influence of the cholinergic and adrenergic factors. Results:, Acetylcholine (10 ,m) and strong intramural parasympathetic nerve stimulation caused a pacemaker shift as well as rhythmic slowing and the formation of an inexcitable region in the central part of SAN. In this region the generation of action potentials was suppressed. The slowing of the sinus rhythm (which exceeded 12.8 ± 3.1% of the rhythm control rate) always accompanied the pacemaker shift. Isoproterenol (10, 100 nm, 1 ,m) and sympathetic postganglionic nerve stimulation also evoked a pacemaker shift but without formation of an inexcitable zone. The acceleration of the sinus rhythm, which exceeded 10.5 ± 1.3% of the control rate of the rhythm, always accompanied the shift. Conclusions:, Both cholinergic and adrenergic factors cause pacemaker shifts in the rabbit SAN. While modest changes in the sinus rhythm do not coincide with the pacemaker shift, greater changes always accompany the shift and may be caused by it, according to one hypothesis. The formation of an inexcitable zone at the place where the leading pacemaker is situated is one of the mechanisms associated with pacemaker shift. [source] Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissuesFEBS JOURNAL, Issue 6 2001Sven Moosmang Hyperpolarization-activated cation currents (Ih) have been identified in cardiac pacemaker cells and a variety of central and peripheral neurons. Four members of a gene family encoding hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCN1,4) have been cloned recently. Native Ih currents recorded from different cell types exhibit distinct activation kinetics. To determine if this diversity of Ih currents may be caused by differential expression of HCN channel isoforms, we investigated the cellular distribution of the transcripts of HCN1,4 in the murine sinoatrial node, retina and dorsal root ganglion (DRG) by in situ hybridization. In the sinoatrial node, the most prominently expressed HCN channel is HCN4, whereas HCN2 and HCN1 are detected there at moderate and low levels, respectively. Retinal photoreceptors express high levels of HCN1, whereas HCN2, 3 and 4 were not found in these cells. In DRG neurons, the dominant HCN transcript is HCN1, followed by HCN2. We next determined the functional properties of recombinant HCN1,4 channels expressed in HEK293 cells. All four channel types gave rise to Ih currents but displayed marked differences in their activation kinetics. Our results suggest that the heterogeneity of native Ih currents is generated, at least in part, by the tissue-specific expression of HCN channel genes. [source] One-Dimensional Rabbit Sinoatrial Node Models:JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2003Benefits, Limitations Introduction: Cardiac multicellular modeling has traditionally focused on ventricular electromechanics. More recently, models of the atria have started to emerge, and there is much interest in addressing sinoatrial node structure and function. Methods and Results: We implemented a variety of one-dimensional sinoatrial models consisting of descriptions of central, transitional, and peripheral sinoatrial node cells, as well as rabbit or human atrial cells. These one-dimensional models were implemented using CMISS on an SGI® Origin® 2000 supercomputer. Intercellular coupling parameters recorded in experimental studies on sinoatrial node and atrial cell-pairs under-represent the electrotonic interactions that any cardiomyocyte would have in a multidimensional setting. Unsurprisingly, cell-to-cell coupling had to be scaled-up (by a factor of 5) in order to obtain a stable leading pacemaker site in the sinoatrial node center. Further critical parameters include the gradual increase in intercellular coupling from sinoatrial node center to periphery, and the presence of electrotonic interaction with atrial cells. Interestingly, the electrotonic effect of the atrium on sinoatrial node periphery is best described as opposing depolarization, rather than necessarily hyperpolarizing, as often assumed. Conclusion: Multicellular one-dimensional models of sinoatrial node and atrium can provide useful insight into the origin and spread of normal cardiac excitation. They require larger than "physiologic" intercellular conductivities in order to make up for a lack of "anatomical" spatial scaling. Multicellular models for more in-depth quantitative studies will require more realistic anatomico-physiologic properties. (J Cardiovasc Electrophysiol, Vol. 14, pp. S121-S132, October 2003, Suppl.) [source] Identification and Characterization of Atrioventricular Parasympathetic Innervation in HumansJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002KARA J. QUAN M.D. AV Parasympathetic Innervation.Introduction: We hypothesized that in humans there is an epicardial fat pad from which parasympathetic ganglia supply the AV node. We also hypothesized that the parasympathetic nerves innervating the AV node also innervate the right atrium, and the greatest density of innervation is near the AV nodal fat pad. Methods and Results: An epicardial fat pad near the junction of the left atrium and right inferior pulmonary vein was identified during cardiac surgery in seven patients. A ring electrode was used to stimulate this fat pad intraoperatively during sinus rhythm to produce transient complete heart block. Subsequently, temporary epicardial wire electrodes were sutured in pairs on this epicardial fat pad, the high right atrium, and the right ventricle by direct visualization during coronary artery bypass surgery in seven patients. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness at each catheter site was determined in the presence and absence of parasympathetic nerve stimulation (via the epicardial wires). In all seven patients, an AV nodal fat pad was identified. Fat pad stimulation during and after surgery caused complete heart block but no change in sinus rate. Fat pad stimulation decreased the right atrial effective refractory period at 1 cm (280 ± 42 msec to 242 ± 39 msec) and 2 cm (235 ± 21 msec to 201 ± 11 msec) from the fat pad (P = 0.04, compared with baseline). No significant change in atrial refractoriness occurred at distances > 2 cm. The response to stimulation decreased as the distance from the fat pad increased. Conclusion: For the first time in humans, an epicardial fat pad was identified from which parasympathetic nerve fibers selectively innervate the AV node but not the sinoatrial node. Nerves in this fat pad also innervate the surrounding right atrium. [source] Sustained Inward Current and Pacemaker Activity of Mammalian Sinoatrial NodeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002HENGGUI ZHANG Ph.D. Sustained Inward Current in the Sinoatrial Node.Introduction: A novel sustained inward Na+ current ist, which sensitive to Ca2+ -antagonists and potentiated by beta-adrenergic stimulation, has been described in pacemaker cells of rabbit, guinea pig, and rat sinoatrial node, as well as rabbit AV node. Although ist has been suggested to be an important pacemaker current, this has never been tested experimentally because of the lack of a specific blocker. In this study, we address the role of ist in the pacemaker activity of the sinoatrial node cell using computer models. Methods and Results: The newly developed models of Zhang et al. for peripheral and central rabbit sinoatrial node cells and models of Noble and Noble, Demir et al., Wilders et al., and Dokos et al. for typical rabbit sinoatrial node cells were modified to incorporate equations for ist. The conductance gst was chosen to give a current density-voltage relationship consistent with experimental data. In the models of Zhang et al. (periphery), Noble and Noble, and Dokos et al., in which ist was smaller or about the same amplitude as other inward currents, ist increased the pacemaking rate by 0.6%, 2.2%, and 0.8%, respectively. In the models of Zhang et al. (center), Demir et al., and Wilders et al., in which ist was larger than some other inward ionic currents, ist increased the pacemaking rate by 7%, 20%, and 14%, respectively. Conclusion: ist has the potential to be a regulator of pacemaker activity, although its importance will depend on the amplitude of ist relative to the amplitude of other inward currents involved in pacemaker activity. [source] Independent Autonomic Modulation of Sinus Node and Ventricular Myocardium in Healthy Young Men During SleepJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2000PETER KOWALLIK M.D. Autonomic Modulation of Sinus Node and Ventricle. Introduction. The aim of this study was to investigate whether autonomic modulation of ventricular repolarization may spontaneousiy differ from that of the sinoatrial node. Methods and Results. Onset of P waves. QRS complexes, and the apex and end of T waves were detected heat to heat in high-resolution ECGs from nine healthy young men during the night. There were time-dependent fluctuations in the QT/RR slopes of consecutive 5-minute segments that could not he explained by the mean RR cycle length of the respective segment. Because the variahility found in QT intervals could not be explained hy either possible effects of rate dependence or hysteresis, autonomic effects were obvious. Power speetral analysis was performed for consecutive 5-minute segments of PP and QT techograms. In a given subject. trends in the time course of low-frequency (LF) and high-frequency (HF) power in PP and QT often were similar, but they were quite different at other times. The mean LF/HF ratio for QTend (0.75 ± 0.1) was different from that of PP (1.8 ± 0.2; P = 0.002), indicating differences in sympathovagal balance at the different anatomic sites. Furthermore, at a given mean heart rate, averaged QT intervals were different on a time scale of several minutes to hours. The QT/RR slope of 5-minute segments correlated significantly with the HF power of QT variability but not with that of PP variability, indicating effects of the autonomic nervous system on ventricular action potential restitution. Conclusion. These differences demonstrate that changes in sinus node automaticity are not necessarily indicative of the autonomic control of ventricular myocardium. (J Cardiavasc Electrophysiol, Vol. II, pp. 1063-1070. October 2000) [source] Ageing to arrhythmias: conundrums of connections in the ageing heartJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2006Sandra A. Jones The proportion of the population that is elderly continues to increase, leading to an increasing need to address problems chiefly associated with old age. Progressive ageing of the heart is associated with an increasing incidence of arrhythmias and disorders of the normal origin of the heartbeat, the sinoatrial node. This intrinsic pacemaker of the heart has an increasing tendency with age to lose its dominant role in pacing the heart, and regulation of heart rate becomes erratic. This ,sick sinus syndrome' is associated with fainting, palpitations, shortness of breath and sudden death. Current treatment of this condition is by implantation of an artificial pacemaker, an intervention increasingly required with age. The current evidence suggests that the normal heartbeat fails due to changes in the expression of critical proteins that ensure the correct production and conduction of the cardiac action potential. Depletion of a protein directly responsible for providing electrical connections between the cells of the heart, connexin 43, appears to leave the normal cardiac pacemaker disconnected and unable to drive the heart. This process may be associated with age-dependent changes in stress-related signalling. Simple interventions such as exercise could impact on the processes hypothesized to be involved and may offer a means to preserve the stability of the electrical activity of the heart into old age without pharmacological manipulation. [source] Atrial, SA Nodal, and AV Nodal Electrophysiology in Standing Horses: Normal Findings and Electrophysiologic Effects of Quinidine and DiltiazemJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2007Colin C. Schwarzwald Background: Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied. Hypotheses: Standard electrophysiologic methods can be used to study drug effects in horses. Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment. Animals: Fourteen healthy horses. Methods: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during programmed electrical stimulation at baseline, after administration of quinidine gluconate (10 mg/kg IV over 30 minutes, n = 7; and 12 mg/kg IV over 5 minutes followed by 5 mg/kg/h constant rate infusion for the remaining duration of the study, n = 7), and after coadministration of diltiazem (0.125 mg/kg IV over 2 minutes repeated every 12 minutes to effect). Results: Quinidine significantly prolonged the atrial effective refractory period, shortened the functional refractory period (FRP) of the AV node, and increased the ventricular response rate during atrial pacing. Diltiazem increased the FRP, controlled ventricular rate in a rate-dependent manner, caused dose-dependent suppression of the sinoatrial node and produced a significant, but well tolerated decrease in blood pressure. Effective doses of diltiazem ranged from 0.125 to 1.125 mg/kg. Conclusions and Clinical Importance: Standard electrophysiologic techniques allow characterization of drug effects in standing horses. Diltiazem is effective for ventricular rate control in this pacing model of supraventricular tachycardia. The use of diltiazem for rate control in horses with atrial fibrillation merits further investigation. [source] High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus TachycardiaPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4p1 2003TIM R. BETTS BETTS, T.R., et al.: High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus Tachycardia.Previous mapping studies of sinus rhythm suggest faster rates arise from more cranial sites within the lateral right atrium. In the intact, beating heart, mapping has been limited to epicardial plaques or single endocardial catheters. The present study was designed to examine shifts in the site of the earliest endocardial depolarization during sinus rhythm and sinus tachycardia using high density activation mapping. Noncontact mapping of the right atrium during sinus rhythm was performed on ten anesthetized swine. Recordings were made during sinus rhythm, phenylephrine infusion, and isoproterenol infusion. The hearts were then excised and the histological sinus node identified. The mean minimum and maximum cycle lengths recorded were355 ± 43and717 ± 108 ms. A median of three (range two to five) sites of earliest endocardial depolarization were documented in each animal. With increasing heart rate the site of earliest endocardial depolarization remained stationary until a sudden shift in a cranial or caudal direction, often to sites beyond the histological sinoatrial node. The endocardial shift was unpredictable with considerable variation between animals; however, faster rates arose from more cranial sites(r = 0.46, P = 0.023). There was no difference in the mean cycle length of sinus rhythm originating from specific positions on the terminal crest(r = 0.44, P = 0.17). Cranial sites displayed a more diffuse pattern of early depolarization than caudal sites. In the porcine heart the relationship between heart rate and site of earliest endocardial depolarization shows considerable variation between individual animals. These findings may have implications for clinical mapping and ablation procedures. (PACE 2003; 26[Pt. I]:874,882) [source] TBX3 and its splice variant TBX3 + exon 2a are functionally similarPIGMENT CELL & MELANOMA RESEARCH, Issue 3 2008Willem M.H. Hoogaars Summary Tbx3, a member of the conserved family of T-box developmental transcription factors, is a transcriptional repressor required during cardiogenesis for the formation and specification of the sinoatrial node, the pacemaker of the heart. Both the TBX3 and the highly related TBX2 genes are also associated with several cancers, most likely as a consequence of their powerful anti-senescence properties mediated via suppression p14Arf and p21CIP expression. In melanoma, the TBX2 gene is frequently amplified and inhibition of Tbx2 function leads to senescence and up-regulation of p21CIP, a Tbx2 target gene. Tbx3 + 2a is a splice variant containing an extra 20 amino acids encoded by exon 2a inserted into the highly conserved T-box DNA-binding domain. We find here that Tbx3 + 2a is evolutionary conserved and that similar insertions are largely absent from the T-box domains of other T-box factors. Tbx3 + 2a has been reported to lack DNA-binding ability and act as a functional antagonist of Tbx3. By contrast, we now demonstrate that both Tbx3 and Tbx3 + 2a bind the consensus T-element, the p21CIP1 promoter, and the Nppa cardiac target gene. Both isoforms also function as repressors of p21CIP1 and Nppa promoter activity and interact with homeobox factor Nkx2-5. When ectopically expressed in the embryonic heart of mice, Tbx3 and Tbx3 + 2a both suppressed chamber formation and repressed expression of cardiac chamber markers Nppa and Cx40. The results suggest that in the assays used, Tbx3 and Tbx3 + 2a are functionally equivalent and that like Tbx2, Tbx3 may also function as an anti-senescence factor in melanoma. [source] Engineering physiologically controlled pacemaker cells with lentiviral HCN4 gene transferTHE JOURNAL OF GENE MEDICINE, Issue 5 2008Gerard J. J. Boink Abstract Background Research on biological pacemakers for the heart has so far mainly focused on short-term gene and cell therapies. To develop a clinically relevant biological pacemaker, long-term function and incorporation of autonomic modulation are crucial. Lentiviral vectors can mediate long-term gene expression, while isoform 4 of the Hyperpolarization-activated Cyclic Nucleotide-gated channel (encoded by HCN4) contributes to pacemaker function and responds maximally to cAMP, the second messenger in autonomic modulation. Material and Methods Action potential (AP) properties and pacemaker current (If) were studied in single neonatal rat ventricular myocytes that overexpressed HCN4 after lentiviral gene transduction. Autonomic responsiveness and cycle length stability were studied using extracellular electrograms of confluent cultured monolayers. Results Perforated patch-clamp experiments demonstrated that HCN4-transduced single cardiac myocytes exhibited a 10-fold higher If than non-transduced single myocytes, along with slow diastolic depolarization, comparable to pacemaker cells of the sinoatrial node, the dominant native pacemaker. HCN4-transduced monolayers exhibited a 47% increase in beating rate, compared to controls. Upon addition of DBcAMP, HCN4-transduced monolayers had beating rates which were 54% faster than baseline and significantly more regular than controls. Conclusions Lentiviral vectors efficiently transduce cardiac myocytes and mediate functional gene expression. Because HCN4-transduced myocytes demonstrate an increase in spontaneous beating rate and responsiveness to autonomic modulation, this approach may be useful to create a biological pacemaker. Copyright © 2008 John Wiley & Sons, Ltd. [source] Famous discoveries by medical studentsANZ JOURNAL OF SURGERY, Issue 12 2009Mark D. Stringer Abstract Heparin, insulin, the sinoatrial node and ether anaesthesia are just some of the major discoveries made by medical students, all of which have had a huge impact on the practice of surgery. This paper explores the breadth and depth of some of these talented individuals and their extraordinary contributions to medicine. While some continued to enjoy brilliant careers, others became embroiled in damaging disputes about priority or were overtaken by illness or personal problems. Regardless of their fate, their contributions are a potent reminder of what can be achieved by gifted and determined medical students undertaking a period of basic scientific or clinical research. [source] | |||||||||||||