bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical and Experimental Study of Sawtooth Effect in Isolated Cardiac Cell‐Pairs
Authors: SHARMA VINOD , TUNG LESLIE 
Published: August 2003

Sawtooth Effect in Cell‐Pairs.
Introduction: The question of how a defibrillation shock affects the myocardium far (> ~1 mm; the space constant of continuum tissue models) from the electrode is not fully understood. According to a long‐standing, yet to be verified, hypothesis, the relatively high‐resistance intercellular gap junctions may help in coupling the shock effect to the distant myocardium by redistributing the defibrillation current and creating a sawtooth pattern of polarization in which every cell undergoes hyperpolarization and depolarization. The goal of this study was to conduct an in‐depth theoretical and experimental investigation of the sawtooth effect in the simplest coupled system, that of an isolated cell‐pair. Methods and Results: Theoretically, we present a relationship between sawtooth amplitude (STA) and junctional resistance (Rj), and show that, in a cell‐pair with two cells of different lengths, the sawtooth effect may not necessarily appear as a reversal in polarization across the junction when Rj is below a critical value. Experimentally, we optically mapped transmembrane potential responses along the lengths of enzymatically isolated guinea pig cell‐pairs at 10– or 17–μm resolution, and estimated STA as the magnitude of discontinuity in responses at the intercellular junction. From 14 cell‐pairs, STA was estimated to be ~11 mV for a nominal 10 V/cm field. Based on our theoretical results, this value corresponds to an Rj of ~18 M Ω. Conclusion: The intercellular junction induces a measurable sawtooth effect in the simplest system of an isolated cell‐pair. An accounting for the sawtooth effect might be essential for understanding fieldtissue interaction far from the electrode and to accurately predict tissue response during field stimulation.
Entrainment by an Extracellular AC Stimulus in a Computational Model of Cardiac Tissue
Authors: MEUNIER JASON M. , TRAYANOVA NATALIA A. , GRAY RICHARD A. 
Published: August 2003

Sinusoidal Stimulation of Cardiac Sheet.
Introduction: Cardiac tissue can be entrained when subjected to sinusoidal stimuli, often responding with action potentials sustained for the duration of the stimulus. To investigate mechanisms responsible for both entrainment and extended action potential duration, computer simulations of a two‐dimensional grid of cardiac cells subjected to sinusoidal extracellular stimulation were performed. Methods and Results: The tissue is represented as a bidomain with unequal anisotropy ratios. Cardiac membrane dynamics are governed by a modified Beeler‐Reuter model. The stimulus, delivered by a bipolar electrode, has a duration of 750 to 1,000 msec, an amplitude range of 800 to 3,200 μA/cm, and a frequency range of 10 to 60 Hz. The applied stimuli create virtual electrode polarization (VEP) throughout the sheet. The simulations demonstrate that periodic extracellular stimulation results in entrainment of the tissue. This phase‐locking of the membrane potential to the stimulus is dependent on the location in the sheet and the magnitude of the stimulus. Near the electrodes, the oscillations are 1:1 or 1:2 phase‐locked; at the middle of the sheet, the oscillations are 1:2 or 1:4 phase‐locked and occur on the extended plateau of an action potential. The 1:2 behavior near the electrodes is due to periodic change in the voltage gradient between VEP of opposite polarity; at the middle of the sheet, it is due to spread of electrotonic current following the collision of a propagating wave with refractory tissue. Conclusion: The simulations suggest that formation of VEP in cardiac tissue subjected to periodic extracellular stimulation is of paramount importance to tissue entrainment and formation of an extended oscillatory action potential plateau.
Report of the NASPE Policy Conference on Arrhythmias and the Athlete
Authors: ESTES N.A. MARK , LINK MARK S. , CANNOM DAVID , NACCARELLI GERALD V. , PRYSTOWSKY ERIC N. , MARON BARRY J. , OLSHANSKY BRIAN 
Published: August 2003

Arrhythmias and the Athlete.
Introduction: This consensus statement summarizes the proceedings of The Expert Consensus Conference on Arrhythmias in the Athlete of the North American Society of Pacing and Electrophysiology (NASPE) on detecting, evaluating, and treating athletes with cardiovascular disorders that predispose to cardiac arrhythmias. Methods and Results: The participants in the open policy conference were selected by the codirectors (Drs. Estes and Olshansky) based on expertise and contributions to the literature. All participants provided a referenced summary of their presentation. The writing group used the information from all published scientific studies, clinical trials, registries, clinical experience, and expert opinion to make recommendations regarding screening, evaluation, management, eligibility for competition, and a range of other medical, social, and legal issues regarding the recreational and competitive athlete. The codirectors of the symposium synthesized the participants' reports for this and made revisions according to suggestions of all members of the writing committee. The manuscript was reviewed by four independent reviewers assigned by the NASPE Committee for the Development of Position Statements and NASPE Board of Trustees. Conclusion: Despite considerable advances in knowledge regarding the diagnosis, therapy, and mechanisms of arrhythmias in the athlete, much remains unknown. Continued basic, clinical, and epidemiologic research is needed. Current screening techniques to detect athletes lack sensitivity and specificity. Evaluation of standardized screening programs with tracking of long‐term outcomes is needed. Officials from athletic, academic, medical, and legal institutions need to form strategic partnerships to develop policy related to assessment of risk and assumption of responsibility for athletic activities.
Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life‐Threatening Arrhythmias
Authors: KUBOTA TOMOYUKI , HORIE MINORU , TAKANO MAKOTO , YOSHIDA HIDETADA , TAKENAKA KOTOE , WATANABE EIICHI , TSUCHIYA TAKESHI , OTANI HIDEO , SASAYAMA SHIGETAKE 
Published: August 2003

Ion Channel Polymorphism and Cardiac Arrhythmia.
Introduction: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS‐associated genes might modify arrhythmia susceptibility in potential gene carriers. Methods and Results: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon‐specific polymerase chain reaction single‐strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in ˜ 11% of the Japanese population. This 1727G> A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage‐clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S‐KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild‐type (WT) channels. Coexpression of WT‐KCNQ1 and G643S‐KCNQ1 with KCNE1 resulted in ˜ 30% reduction in the slow delayed rectifier K+ current IKs without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant‐negative effect on the heteromultimeric channel complexes. Conclusion: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild IKs dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life‐threatening arrhythmias in a specific population.
Relation Between Body Surface Mapping and Endocardial Spread of Ventricular Activation in Postinfarction Heart
Authors: VAN DESSEL PASCAL F.H.M. , VAN HEMEL NORBERT M. , DE BAKKER JACQUES M.T. , LINNENBANK ANDRÉ C. , POTSE MARK , JESSURUN EMILE R. , SIPPENSGROENEWEGEN ARNE , WEVER ERIC F.D. 
Published: August 2003

Body Surface Mapping and Endocardial Activation Patterns.
Introduction: Body surface mapping (BSM) can be used to identify the site of earliest endocardial activation of ventricular tachycardias (VTs). The multielectrode QRS morphology during VT is determined by both the site of earliest activation and the subsequent spread of electrical activation through the ventricles. This study investigated the relationship between the site of earliest endocardial activation, endocardial spread of activation, and the morphology of the multielectrode surface map in patients with remote myocardial infarction. Methods and Results: In 14 patients with VT late (8.2 ± 5.2 years) after myocardial infarction, BSM and simultaneous left ventricular 64‐site basket endocardial mapping was performed during a total of 17 monomorphic VTs. In addition, multisite pacing by sequential use of the 64 basket electrodes was performed in 9 patients. BSM and basket mapping revealed the same endocardial breakthrough sites in 8 (47%) of 17 VTs and 189 (59%) of 322 pacing sites; adjacent sites were found in 2 (12%) of 17 VTs and 36 (11%) of 322 pacing sites. Large zones of conduction block explained the mismatch in localization in 2 (12%) of 17 VTs and 52 (16%) of 322 pacing sites. Regional differences in endocardial electrogram amplitudes were found as a cause for dissimilarity in 3 (18%) of 17 VTs and 73 (23%) of 322 pacing sites. Multiple endocardial breakthrough sites were found in 1 (6%) of 17 VTs and 8 (2%) of 322 pacing sites Finally, an epicardial exit site was suggested in 3 (18%) of 17 VTs as an explanation for mismatch, as no early endocardial activity could be recorded. Conclusion: Zones of conduction block, regional differences in signal amplitude, and multiple endocardial breakthrough sites are frequent causes for mismatch between BSM and basket catheter activation mapping.
Hyperventilation Facilitates Induction of Supraventricular Tachycardia: A Novel Method and the Possible Mechanism
Authors: CHEN CHIEN‐CHENG , CHEN SHIH‐ANN , TAI CHING‐TAI , KUO TERRY B.J. , CHANG MAU‐SONG , PRYSTOWSKY ERIC N. 
Published: August 2003

Hyperventilation and Supraventricular Tachycardia.
Introduction: Hyperventilation has been demonstrated to alter autonomic function. Sympathomimetic drugs (isoproterenol) and parasympatholytic drugs (atropine) may be needed to facilitate induction of supraventricular tachycardia (SVT). The aim of this study was to test the clinical utility and mechanisms of hyperventilation to facilitate SVT initiation. Methods and Results: Fourteen patients with clinically documented SVT (9 AV nodal reentrant tachycardia and 5 AV reciprocating tachycardia) but noninducible during baseline electrophysiologic study were included. Immediately after hyperventilation test (at least 30 respirations/min) for 2 minutes, systolic blood pressure, sinus cycle length, anterograde and retrograde 1:1 conduction, and induced SVT were measured. Arterial blood gas, pH, and heart rate variability before and after hyperventilation were measured. Seven of nine patients with AV nodal reentrant tachycardia and 3 of 5 patients with AV reciprocating tachycardia could be induced immediately after the hyperventilation test. After hyperventilation, anterograde AV and retrograde VA 1:1 conduction were improved, sinus cycle length was decreased, and heart rate variability were decreased in both groups. Conclusion: Hyperventilation can facilitate induction of SVT. Improvement of conduction properties and changes of autonomic function are the possible mechanisms.
Clinical Experience with a Dual‐Chamber Implantable Cardioverter Defibrillator to Treat Atrial Tachyarrhythmias
Authors: GOLD MICHAEL R. , SULKE NEIL , SCHWARTZMAN DAVID S. , MEHRA RAHUL , EULER DAVID E. 
Published: August 2003

Dual‐Chamber ICD and Atrial Tachyarrhythmia.
Introduction: This study evaluated the safety and efficacy of a new dual‐chamber implantable cardioverter defibrillator (ICD) to detect and treat atrial tachyarrhythmias in patients with drug‐refractory atrial fibrillation (AF) and no indication for a ventricular ICD. Methods and Results: A dual‐chamber ICD (Medtronic 7250 Jewel AF) was implanted in 144 of 146 patients. The device discriminates atrial tachycardia from AF based on cycle length and regularity, and uses atrial overdrive pacing as well as shocks to terminate tachyarrhythmia episodes. Patients were followed for an average of 12.6 ± 6.2 months. Use of antiarrhythmic drugs was 63% at baseline and did not change over time. Kaplan‐Meier estimates of 12‐month complication‐free survival, device therapy survival, and patient survival were 85%, 91%, and 98%, respectively. Positive predictive accuracy of spontaneous atrial tachyarrhythmia detection was 99%, while atrial overdrive pacing and shocks terminated 40% and 87% of treated episodes, respectively. Median duration of successfully treated episodes was 8.9 minutes versus 144 minutes for the therapy failures. There was no reduction in the use of patient‐activated shock therapy over time; at the 12‐month follow‐up evaluation, 94% of patients were in sinus rhythm. Ventricular tachyarrhythmias (67 episodes) were detected and appropriately treated in 7.6% of patients. Conclusion: This dual‐chamber ICD appears to be safe and well tolerated in patients with drug‐refractory symptomatic atrial tachyarrhythmias. The device, used in combination with drugs, effectively treats atrial tachyarrhythmias with pacing and/or shock therapies and decreases the median episode duration. In addition, the device protects from ventricular tachyarrhythmias in patients with AF and structural heart disease.
Ventricular Echo Beats and Retrograde Atrioventricular Nodal Exits in the Dog Heart: Multiplicity in Their Electrophysiologic and Anatomic Characteristics
Authors: TOSHIDA NOBUO , HIRAO KENZO , YAMAMOTO NAOHITO , TANAKA MICHIO , SUZUKI FUMIO , ISOBE MITSUAKI 
Published: August 2003

Ventricular Echo Beats and Retrograde AV Nodal Exits.
Introduction: A single ventricular echo beat frequently is induced in the dog heart by ventricular pacing, but it has not been investigated using a concomitant ablative technique. We studied the effects of ablating the anterior atrial input to the AV node on ventricular echo beats induced in the dog heart to evaluate their electrophysiologic characteristics, the anatomic reentrant circuit, and the retrograde AV nodal exits. Methods and Results: In 20 dogs, an epicardial radiofrequency current was applied to the right anterior septum in an attempt to ablate the anterior input to the AV node. Ventricular programmed stimulation was performed to evaluate the ventricular echo beat and the retrograde AV nodal exit before and after ablation. The AV junction was examined with light microscopy. Seventeen dogs in which the PR interval was prolonged significantly from 108 ± 17 msec to 153 ± 19 msec (P < 0.001) were selected for ventricular echo evaluation; 3 dogs in which persistent second‐ or third‐degree AV block was induced by ablation were excluded. Ventricular echo beats, which were induced in 13 of 17 dogs, were classified into the anterior type (n = 6) or posterior type (n = 7) according to the earliest atrial activation site during the echo beat. The retrograde AV nodal exit site showed anterior‐exit only (n = 10), posterior‐exit only (n = 2), and dual‐exit (n = 5) patterns. After ablation, the anterior‐type ventricular echo beat was noninducible in all 6 dogs, whereas the posterior‐type ventricular echo beat was noninducible in only 3 of 7 dogs. In 17 dogs, VA conduction was not demonstrated after ablation in 3 dogs, all of which showed the anterior‐exit only pattern. Conclusion: The effect of ablation on the ventricular echo beats and retrograde AV nodal exit site suggests multiplicity in their electrophysiologic and anatomic characteristics in the dog heart.
Evolution of Action Potential Propagation and Repolarization in Cultured Neonatal Rat Ventricular Myocytes
Authors: MEIRY GIDEON , REISNER YOTAM , FELD YAIR , GOLDBERG STANISLAV , ROSEN MICHAEL , ZIV NOAM , BINAH OFER 
Published: August 2003

Maturation of Cultured Neonatal Rat Ventricular Myocytes.
Introduction: Cultured neonatal rat ventricular myocytes (NRVM) reestablish gap junctions as they form synchronously and spontaneously beating monolayers, thus providing a useful model for studying activation and repolarization. Methods and Results: We used the multielectrode array data acquisition system with 60 unipolar electrodes to investigate the functional organization of cultured NRVM, by determining propagation and repolarization patterns. Activation maps were constructed from the local activation times at each electrode. During days 3 to 8 in culture, QRS amplitude and dV/dtmax increased with age. Concomitantly, with the culture maturation, QT interval (representing action potential duration) decreased, and T wave amplitude and slopes of the T wave ascending and descending limbs progressively increased. The changes in conduction velocity were different than those of the electrogram properties, slightly increasing during the first 3 to 5 days and gradually declining toward day 8 in culture. Conclusion: Establishment of uniform activation patterns in spontaneously firing or driven myocytes in monolayer cultures is accompanied by organization of activation and repolarization whose evolution appears in concert with that of a mature connexin43 staining pattern. The experimental techniques developed in this study provide useful tools to investigate the complex relations among gap junctions, conduction velocity, and propagation patterns, as well as a means to learn how gap junctional remodeling under pathophysiologic conditions predisposes the myocardium to arrhythmias.
Feasibility of a Left Atrial Electrical Disconnection Procedure for Atrial Fibrillation Using Transcatheter Radiofrequency Ablation
Authors: BETTS TIM R. , ROBERTS PAUL R. , MORGAN JOHN M. 
Published: August 2003

Transcatheter Left Atrial Electrical Disconnection.
Introduction: An effective, catheter‐based treatment for persistent atrial fibrillation (AF) remains elusive. This study assessed the feasibility of transcatheter left atrial (LA) electrical disconnection and its effect on AF inducibility. Method and Results: Thirteen anesthetized swine underwent noncontact mapping of the right atrium (RA) during coronary sinus (CS) pacing. Sites of earliest RA activation were identified using isopotential maps. An ablation catheter was navigated to these sites and a cluster of radiofrequency (RF) lesions applied until earliest activation shifted to a new site. The procedure was repeated until the atria were electrically disconnected. AF induction was attempted before and after ablation. Earliest RA activation was the CS os during proximal CS pacing and Bachmann's bundle during distal CS pacing. These two sites were successfully ablated in all 13 animals. Earliest activation then shifted to the fossa ovalis. RF energy was applied at a median of 2.5 sites (range 1 to 5) around the fossa, then at sites in the triangle of Koch, septum, cavotricuspid isthmus, and posterior wall. Atrial electrical disconnection was achieved in 10 of 13 animals (5 LA electrical disconnection, 3 RA electrical disconnection, 2 biatrial electrical disconnection with complete heart block). After atrial electrical disconnection, the LA became electrically silent. Before ablation, AF was inducible in every animal. After atrial electrical disconnection, AF was inducible in 3 of 10 animals. Conclusion: Atrial electrical disconnection is feasible using noncontact mapping and RF ablation. Successful electrical disconnection of the atria reduces AF inducibility. This approach is worthy of further evaluation as a management strategy for persistent AF, combined with device therapies.
Monophasic Action Potential Recordings from Intact Mouse Heart: Validation, Regional Heterogeneity, and Relation to Refractoriness
Authors: KNOLLMANN BJÖRN C. , KATCHMAN ALEXANDER N. , FRANZ MICHAEL R. 
Published: August 2003

MAP Recordings from Mouse Heart.
Introduction: The monophasic action potential (MAP) technique has been validated in humans and larger animals, but, in mice, MAP recordings available to date show little resemblance to the murine ventricular transmembrane action potential (TAP) measured by conventional microelectrodes. We developed a miniaturized MAP contact electrode technique to establish in isolated mouse hearts: (1) optimal electrode size; (2) validation against TAP; (3) relationship between repolarization and refractoriness; and (4) regional repolarization differences. Methods and Results: In 30 Langendorff‐perfused mouse hearts, MAP electrodes of tip diameter 1.5, 1.0, and 0.25 mm were tested by comparing MAPs and TAPs from epicardial and endocardial surfaces of both ventricles. Only the MAP contact electrode of 0.25‐mm tip diameter consistently produced MAP recordings that had wave shapes nearly identical to TAP recordings. MAP durations measured at 30%, 50%, 70%, and 90% repolarization (APD30, APD50, APD70, APD90) highly correlated with TAP measurements (r = 0.97, P < 0.00001). APD50 was significantly longer in endocardial than in epicardial recordings (right ventricle: 9.3 ± 1.1 msec vs 3.9 ± 1.1 msec; left
ventricle: 9.9 ± 2.1 msec vs 6.2 ± 1.9 msec; both P < 0.001), demonstrating transmural repolarization differences. Effective refractory period (ERP) determined at basic cycle lengths from 70 to 200 msec correlated with 80% ± 6% of total repolarization, with an ERP/APD90 ratio of 0.85 ± 0.14. Conclusion: Murine myocardial repolarization, regional repolarization heterogeneity, and relation to refractoriness can be assessed reliably by this miniaturized MAP contact electrode technique, which renders action potential wave shapes similar to that of intracellular microelectrodes. This technique may be useful for exploring repolarization abnormalities in genetically altered mice.