bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Experience with the Siemens Pacesetter Siecure
Authors: SOWTON EDGAR , SULKE NEIL
Published: May 2007

Siemens Pacesetter Siecure. The Siemens Pacesetter P59 “Siecure” is a third‐generation implantable cardioverter defibrillator offering tiered therapy for termination of tachyarrhythmias. The device is highly programmable and is software loaded allowing telemetry upgrade. It has unique algorithms allowing‘'step up or down” of response according to the nature of the tachycardia. Extensive memory, analysis, and Holter monitoring functions afford excellent opportunities to monitor tachycardias and device response postimplantation. This article reports on the first six patients in whom the device was implanted (five male, one female, 33 to 65 years, mean 49). All had electrophysiologic study‐proven, hemodynamically unstable, drug refractory ventricular arrhythmias. The devices were implanted transthoraci‐cally with no peri‐ or postoperative complications. All patients had malignant arrhythmias induced perioperatively and noninvasively 6 weeks postoperatively, confirming appropriate device response and excellent tachycardia sensing functions. One patient has required reintroduction of amiodarone due to increasing frequency of ventricular tachycardia hut the remainder remain free of antiarrhythmic drug therapy up to 1 year postimplantation. The antitachycardia pacing function was used successfully six times to terminate arrhythmias in these patients, avoiding the need for cardioversion or defibrillation, which are more unpleasant and energy consuming modalities of treatment. (J Cardiovasc Electrophysiol, Vol. 3, pp. 515–522, October 1992)
Simulated Ischemia Does Not Protect Against Efferent Sympathetic Denervation Following Acute Myocardial Infarction in Canine Hearts
Authors: RUBART MICHAEL , PRIDE HARALD P. , KROEKER TIMOTHY S. , WARNER MARGARET R. , ZIPES DOUGLAS P.
Published: May 2007

Effect of Simulated Preconditioning on Neural Response During Ischemia. Introduction: Preconditioning the myocardium with brief episodes of ischemia preserves efferent autonomic responsiveness of noninfarcted myocardium apical to a site of acute transmural ischemia by mechanism(s) still unknown. We hypothesized that repeated brief exposure of the myocardium to a simulated ischemic milieu including hypoxia, high K. low pH, and adenosine would be as effective as brief coronary occlusions in creating this protection.

Methods and Results: Open chest anesthetized dogs received an extra corporeal bypass between the left carotid artery and a diagonal branch of the left anterior descending coronary artery. We analyzed the effects of simulated ischemia on the time course and extent of efferent sympathetic denervation during a subsequent 3‐hour sustained ischemia in three groups of dogs: two groups of dogs underwent four cycles of 5‐minute intracoronary perfusion with either hypoxic altered Tyrode's solution (12 mM K+, 6.8 pH, and 10 μ adenosine; n = 11) or normal Tyrode's solution mil. Each Tyrode's perfusion was separated by 5 minutes of blood perfusion prior to permanent coronary occlusion by latex remobilization of the annulated coronary artery. A third group received a continuous 3‐hour blood perfusion before the final ischemic episode (n = 5). Shortening of effective refractory periods (ERPs) induced by bilateral ansae subelaviae stimulation (2 to 4 Hz) basal and apical to the intervention site was determined before and after perfusions and 20, 60, 120, and 180 minutes after sustained occlusion. In all groups, sympathetically‐induced ERP shortening was unchanged at basal sites throughout the experiment. ERP shortening at apical sites was unchanged after perfusions with either the altered or normal Tyrode's solution or after a continuous 3‐hour blood perfusion. However, EKP shortening became significantly attenuated at apical sites after coronary occlusion in all groups. Neither the size in reduction of sympathetically‐induced ERP shortening at apical test sites nor the cumulative percentage of denervated apical test sites (≤ 2‐msec shortening) during a 3‐hour period of permanent ischemia differed significantly among groups (P = 0.052 and P = 0.752, respectively). The degree of subepicardial involvement in the myocardial infarction was comparable among groups.

Conclusion: Thus, brief exposure of the left ventricular myocardium to ischemic metabolites prior to a subsequent permanent coronary occlusion does not trigger mechanism(s) that are responsible for protection against efferent sympathetic denervation apical to an area of trans‐mural myocardial infarction/ischemia.
Drug‐Induced Afterdepolarizations and Triggered Activity Occur in a Discrete Subpopulation of Ventricular Muscle Cells (M Cells) in the Canine Heart:
Authors: SICOURI SERGE , ANTZELEVITCH CHARLES
Published: May 2007

EADs and DADs in M Cells. Introduction: Oscillations of membrane potential that attend or follow the cardiac action potential and depend on preceding Tran membrane activity for their manifestation are known as aflerdepolarizations. Early aflerdepolarizations (EADs) interrupt or retard repolarization of the cardiac action potential, whereas delayed afterdepolarizations (DADs) arise after full repolarization. EADs and DADs can give rise to spontaneous action potentials or triggered activity believed to be responsible for a variety of cardiac arrhythmias. Recent studies from our laboratory have highlighted differences in the electrophysiology and pharmacology of three functionally distinct myocardial cell types found in the canine ventricle. Epicardial, M region, and endocardia tissues and cells show distinct, sometimes opposite, responses to a variety of drugs, including those capable of inducing EADs and DADs.

Methods and Results: In the present study, we used standard microelectrode techniques to examine the pharmacologic response of these cellular subtypes to therapeutic levels of quinidine and toxic levels of digitalis. Quinidine readily produced prominent EADs and EAD induced triggered activity in tissue preparations from the M region (deep subepicardium), but not in those from epicardium. endocardium, or deep subendocardium of the canine ventricle. Acetylstrophanthidin produced prominent DADs in M cell preparations and subendocardiat Purkinje fibers but only minute DADs, if any, in epicardium, endocardium, or deep subendocardium. DAD‐induced triggered activity was observed to arise only in Purkinje and M cells and never in myocardial tissues from the epicardial, endocardial, or deep subendocardial regions of the ventricular wall.

Conclusion: We conclude that EADs, DADs, and triggered activity caused by therapeutic levels of quinidine and toxic levels of digitalis are limited to or much more readily induced in a select population of cells in the deep subepicardial (M cell) region of the canine ventricle in addition to the Purkinje system of the heart.
Sotalol
Authors: RUFFY RODOLPHE
Published: May 2007

Sotalol. Sotalol causes noncardioselective beta‐adrenergic antagonism and prolongation of repolarization of cardiac tissues (Class III electrophysiologic action). This dual pharmacologic profile confers unprecedented antiarrhythmic properties to the drug. Sotalol is highly bioavailable when administered orally in the fasting state and is mostly cleared unchanged in the urine with an apparent half‐life of elimination of 15 to 17 hours. It has heen found effective in the suppression of nearly all cardiac arrhythmias, with the exception of those precipitated by prolongation of ventricular repolarization. Its safety and efficacy relative to other antiarrhythmic drugs need to be examined more fully in randomized controlled trials of unselected patients. The adverse effects potentially associated with the use of sotalol are those commonly observed with beta‐adrenergic blockade, as well as those resulting from excessive prolongation of the QT interval. The occurrence of torsade de pointes during treatment with sotalol may be minimized by limiting doses to no more than 640 nig/day and by strictly avoiding the development of hypokalemia. (J Cardiovasc Electrophysiol. Vol. 4, pp. 81–98. February 19931
Spread of Excitation in a Myocardial Volume:
Authors: FRANZONE PIERO COLLI , GUERRI LUCIANO , TACCARDI BRUNO
Published: May 2007

Spread of Excitation in a Myocardial Volume.Introduction:The purpose of this study was to present simulations of excitation wavefronts spreading through a parallelepipedal slab of ventricular tissue measuring 6.5 × 6.5 × 1.0cm.

Methods and Results:The slab incorporates the anisotropic properties of the myocardium including the transmural counterclockwise fiber rotation from epicardium to endocardium. Simulations were based on an eikonal model that determines excitation times throughout the ventricular wall, which is represented as an anisotropic bidomain. Excitation was initiated by delivering ectopic stimuli at various intramural depths. We also investigated the effect of a simplified Purkinje network on excitation patterns. Excitation wavefronts in the plane of pacing, parallel to epicardial‐endocardial surfaces, were oblong with the major axis approximately oriented along the local fiber direction, with bulges and deformations due to attraction from rotating fibers in adjacent planes. The oblong intersections of the wavefront with planes at increasing distance from pacing plane rotated clockwise or counterclockwise, depending on pacing depth, but wavefront rotation was always less than fiber rotation in the same plane. For all pacing depths, excitation returned toward the plane of pacing. Return occurred in multiple, varying sectors of the slab depending on pacing depth, and was observed as close as 6 mm to the pacing site.

Conclusion:Curvature of wavefronts and collision with boundaries of slab markedly affected local velocities. Shape and separation of epicardial isochrones and spatial distribution of epicardial velocities varied as a function of site and depth of pacing. When the Purkinje network was added to the model, epicardial velocities revealed the subendocardial location of the Purkinje‐myocardial junctions. Considerable insight into intramural events could be obtained from epicardial isochrones. If validated experimentally, results may be applicable to epicardial isochrones recorded at surgery.
The Response of Paroxysmal Supraventricular Tachycardia to Overdrive Atrial and Ventricular Pacing:
Authors: KADISH ALAN H. , MORADY FRED
Published: May 2007

Pacing During Supraventricular Tachycardia. Introduction: Standard electrophysiologic techniques generally allow discrimination among mechanisms of paroxysmal Supraventricular tachycardia. The purpose of this study was to determine whether the response of paroxysmal Supraventricular tachycardia to atrial and ventricular overdrive pacing can help determine the tachycardia mechanism.

Methods and Results: Fifty‐three patients with paroxysmal Supraventricular tachycardia were studied. Twenty‐two patients had the typical form of atrioventricular (AV) junctional (nodal) reentry, 18 patients had orthodromic AV reentrant tachycardia, 10 patients had atrial tachycardia, and 3 patients had the atypical form of AV nodal reentrant tachycardia. After paroxysmal Supraventricular tachycardia was induced, 15‐beat trains were introduced in the high right atrium and right ventricular apex sequentially with cycle lengths beginning 10 msec shorter than the spontaneous tachycardia cycle length. The pacing cycle length was shortened in successive trains until a cycle of 200 msec was reached or until tachycardia was terminated. Several responses of paroxysmal Supraventricular tachycardia to overdrive pacing were useful in distinguishing atrial tachycardia from other mechanisms of paroxysmal Supraventricular tachycardia. During decremental atrial overdrive pacing, the curve relating the pacing cycle length to the VA interval on the first beat following the cessation of atrial pacing was flat or upsloping in patients with AV junctional reentry or AV reentrant tachycardia, but variable in patients with atrial tachycardia. AV reentry and AV junctional reentry could always be terminated by overdrive ventricular pacing whereas atrial tachycardia was terminated in only one of ten patients (P < 0.001). The curve relting the ventricular pacing cycle length to the VA interval on the first postpacing beat was flat or upsloping in patients with AV junctional reentry and AV reentry, but variable in patients with atrial tachycardia. The typical form of AV junctional reentry could occasionally be distinguished from other forms of paroxysmal Supraventricular tachycardia by the shortening of the AH interval following tachycardia termination during constant rate atrial pacing.

Conclusions: Atrial and ventricular overdrive pacing can rapidly and reliably distinguish atrial tachycardia from other mechanisms of paroxysmal Supraventricular tachycardia and occasionally assist in the diagnosis of other tachycardia mechanisms. In particular, the ability to exclude atrial tachycardia as a potential mechanism for paroxysmal Supraventricular tachycardia has important implications for the use of catheter ablation techniques to cure paroxysmal Supraventricular tachycardia.
Bundle Branch Reentrant Ventricular Tachycardia:
Authors: BLANCK ZALMEN , DHALA ANWER , DESHPANDE SANJAY , SRA JASBIR , JAZAYERI MOHAMMAD , AKHTAR MASOOD
Published: May 2007

Sustained Bundle Branch Reentrant Tachycardia. introduction: The clinical, electrophysiologic features and follow‐up of 48 patients with inducible bundle branch reentrant (BBR) tachycardia are presented.

Methods and Results: Forty‐eight patients were identified in whom a diagnosis of BBR tachycardia was made during electrophysiologic evaluation. The clinical presentation was syncope or sudden death in 38 patients, and sustained palpitations during wide QRS complex tachycardia in 5 patients. Electrophysiologic studies were performed in 5 additional patients for various other reasons. Structural heart disease was present in 45 patients. Idiopathic dilated cardiomyopathy and coronary artery disease were the anatomical substrates in 19 (39%) and 24 (50%) patients, respectively, severe aortic regurgitation was present in 2 patients, and no organic heart disease was identified in 3. All 48 patients had evidence of His‐Purkinje system disease. BBR tachycardia with left and right bundle branch block morphologies was induced in 46 and 5 patients, respectively, and interfascicular BBR tachycardia was initiated in 2 patients. Ventricular tachycardia of a myocardial origin was induced in 11 patients. Management of BBR tachycardia included transcatheter bundle branch ablation in 28 patients, and antiarrhythmic drug therapy in 16 patients. Four patients were treated with implantablc defibrillators. After a mean follow‐up of 15.8 months in 42 patients, there were 13 deaths due to congestive heart failure, 4 sudden cardiac deaths, 3 nonsudden cardiac deaths, and 3 noncardiac related deaths.

Conclusion: Sustained BBR, a form of monomorphic ventricular tachycardia, is a highly malignant arrhythmia usually seen in patients with structural heart disease. Three different types of BBR tachycardia are described. If distinguished from ventricular tachycardia of a myocardial origin, catheter ablation of the right bundle branch can be easily performed and effectively eliminates BBR. During follow‐up, congestive heart failure is the most common cause of death in this population.
Retrograde (Transseptal) Activation of Right Bundle Branch During Sinus Rhythm
Authors: JAZAYERI MOHAMMAD R. , DESHPANDE SANJAY S. , SRA JASBIR S. , AKHTAR MASOOD
Published: May 2007

Retrograde Right Bundle Branch Activation. A 40‐year‐old man undergoing electro‐physiologic study for recurrent palpitations was found to have a right bundle branch block during sinus rhythm and right bundle potentials occurring after ventricular activation. The sequence of activation of the proximal and distal right bundle potentials was suggestive of a retrograde invasion of the right bundle during sinus rhythm. This transseptal activation of the right bundle via the left bundle exhibited decremental conduction characteristics during atrial as well as ventricular stimulation. Observations made in this case may provide some important information concerning the electrophysiologic behavior of transseptal impulses.
Aggravation of Arrhythmia:
Authors: PODRID PHILIP J.
Published: May 2007

Aggravation of Arrhythmia. Aggravation of arrhythmia, denned as worsening of a preexisting arrhythmia or the occurrence of a new arrhythmia, is a common complication of antiarrhythmic drug therapy. Although it is largely an unpredictable event, patients at greatest risk are those with a history of congestive heart failure due to systolic dysfunction who present with a sustained ventricular tachyarrhythmia. As a rule, aggravation of arrhythmia is an early event, occurring within the first few days of initiating therapy. However, in the Cardiac Arrhythmia Suppression Trial (CAST), the increased sudden death mortality due to drug therapy, which was a result of arrhythmia aggravation, occurred throughout the entire duration of the trial, suggesting that arrhythmia aggravation can also be a late complication of therapy. Also disturbing was the fact that patients in CAST were low risk and did not have congestive heart failure or a serious ventricular tachyarrhythmia. This suggests that another important risk factor is myocardial ischemia and its potentially dangerous interaction with antiarrhythmic drugs. In patients with heart disease, especially those with coronary artery disease, antiarrhythmic drugs must therefore be used cautiously. Close and continuous follow‐up is mandatory.
“AV Nodal” Reentry:
Authors: JANSE MICHIEL J. , H ROBERT , McGUIRE MARK A. , YEN HO SIEW
Published: May 2007

“AV Nodal” Reentry. This review is the first of a two‐part series of articles on “atrioven‐tricular [AV] nodal reentry,” The early clinical literature as well as the experimental studiesare reviewed, and more recent morphologic data are presented, with the aim of clarifyingwhether the reentrant circuit is contined to the AV node, or consists in part of extranodal components. Most of the evidence supports the concept that atrial tissue is an essential link in thereentrant pathway. Arguments will be presented to indicate that within the AV node, the separation between antegrade and retrograde pathways is functional, not anatomical, and that bothpathways are in electrotonic contact.
Double Retrograde Atrial Response After Radiofrequency Ablation of Typical AV Nodal Reentrant Tachycardia
Authors: KALBFLEISCH STEVEN J. , STRICKBERGER S. ADAM , HUMMEL JOHN D. , WILLIAMSON BRIAN D. , MAN K. CHING , VORPERIAN VICKEN R. , LANGBERG JONATHAN J. , MORADY FRED
Published: May 2007

Double Atrial Response. This case report describes a patient in whom a single ventricular depolarization resulted in a double atrial response and the initiation of atypical A V nodal reentrant tachycardia after successful radiofrequency ablation of typical AV nodal reentrant tachycardia using the slow pathway approach. (J Cardiovasc Electrophysiol, Vol. 4, pp. 695–701, December 1993)
Spiral Wave Activity:
Authors: DAVTDENKO JORGE M.
Published: May 2007

Spiral Waves. Several mechanisms have been proposed to explain the electrocardiographic patterns observed during various forms of polymorphic ventricular tachycardias, including torsades de pointes. Such mechanisms include the coexistence of either multiple foci or multiple exit pathways from single foci giving rise to various forms of aberrant ventricular activation sequences. For example, the simultaneous firing of two widely spaced foci at slightly different frequencies has heen used to explain the undulating electrocardiogram that is characteristic of torsades de pointes. However, in spite of some supporting experimental evidence, such an idea remains conjectural from the clinical point of view. Here I discuss a mechanism that has heen proposed recently to explain both monomorpbic and polymorpbic patterns (including undulating patterns) of ventricular tachycardia. the hypothesis is derived from tbf theory of spiral wave activity in excitable media, and from recent experiments using bigh resolution optical mapping in isolated two‐dimensional ventricular muscle preparations tbat demonstrate tbat spiral wave activity may account for self‐sustaining reentrant activation. Sucb studies bave led to the observation that the behavior of the spiral center, the core, plays a key role in determining the electrocardiograpbic manifestation of the arrhythmia. Indeed, a stationary position of the core results in a monomorphic pattern of activation. On the other band, beat‐to‐beat changes in the core position (i.e., drifting) leads to irregular patterns of activation. In fact, when drifting occurs in one direction, it gives rise to a Doppler shift in the excitation period in such a way that two coexisting frequencies are manifest, one ahead of and one behind the drifting core. the activation frequency in the region ahead of the core is always higher than that behind the core. Under such conditions, electrocardiographic recordings of the activity demonstrate an undulating pattern, which resembles that of torsades de pointes. When the core drifts in various directions, a potymorpbic pattern is manifest. Thus, depending on spiral core dynamics, monomorphic. undulating, or completely irregular patterns maybe observed. Moreover, transitions between such patterns can also occur. For example, drifting spirals giving rise to polymorphic activation can become stationary and result in monomorphic activation as a result of anchoring of the core to a small discontinuity (e.g., an artery or small scar) in the tissue. Direct extrapolation of such results to clinical cases is not appropriate. However, the observations discussed in this article offer a new testable hypothesis in which a common mechanism is postulated for the electrocardiograpbic patterns associated with monomorphic and polymorphic tachycardias.
Effects of Overdrive Stimulation on Functional Reentrant Circuits Causing Ventricular Tachycardia in the Canine Heart:
Authors: DILLON STEPHEN M. , COROMILAS JAMES , WALDECKER BERND , WIT ANDREW L.
Published: May 2007

Overdrive Stimulation and Functional Reentry, introduction: The purpose of the experiments described in this article was to investigate the effects of overdrive stimulation on functional anisotropic reentrant circuits causing ventricular tachycardia in infarcted canine ventricles. We determined how overdrive stimuli affect reentrant circuits to alter characteristics of the tachycardia.

Methods and Results: Activation patterns were determined In mapping excitation with a 192 bipolar electrode array. We found that overdrive stimuli could activate the circuits with the same pattern as the reentrant wavefront and that after overdrive stopped either the last or the next to last stimulated wavefront continued propagating through the circuit as a new reentrant impulse and tachycardia continued. When the circuit was not altered after overdrive, the exit route that the stimulated wavefront took from the circuit to activate the rest of the ventricles was also not altered and the tachycardia after overdrive had the same cycle length and QRS morphology as prior to overdrive. In some experiments, however, the overdrive stimuli did not follow the original reentrant pathway but led to the formation of a different circuit with a different exit route to the ventricles. As a result, after overdrive stimulation tachycardia had a different QRS morphology and cycle length than prior to stimulation. When the new circuit after overdrive was small and the revolution time of the reentrant impulse around the circuit was short, fibrillation occurred.

Conclusion: Functional reentrant circuits can either be maintained or altered after a period of overdrive stimulation. The results explain many of the effects that have been seen during overdrive stimulation of clinical ventricular tachycardia.
Potential Distributions Generated By Point Stimulation in a Myocardial Volume:
Authors: FRANZONE PIERO COLLI , GUERRI LUCIANO , TACCARDI BRUNO
Published: May 2007

Potential Patterns in a 3‐D Cardiac Depolarization Model,introduction:We present simulations of extracellular potential patterns elicited by delivering ectopic stimuli to a parallelepipedal slab of ventricular tissue represented as an anisotropic bidomain incorporating epiendocardial fiber rotation.

Methods and Results:Simulations were based on an eikonal model that determines wave‐front shapes throughout the slab at every time instant during the depolarization phase, coupled with an approximate model of the action potential profile. The endocardial face of the slab was in contact with blood and the composite volume was surrounded by an insulating medium. The effect of a simplified Purkinje network was also studied. Results: (1) For all pacing depths, except endocardial pacing, a central negative area and two potential maxima were observed at QKS onset in all intramural planes parallel to the cpicardium. In all planes, the axis joining the two maxima was approximately aligned with the direction of fibers in the plane of pacing. Endocardial pacing generated a different pattern, but only when blood was present; (2) During later stages of excitation, outflowing currents (from the wavefront toward the resting tissue) were always emitted, at all intramural depths, only from those portions of the wavefront that spread along fibers. At any given instant, the position of the two potential maxima in a series of planes parallel to the epicardium and intersecting the wavefront rotated as a function of depth, following the rotating direction of intramural fibers. Purkinje involvement modified the above patterns.

Conclusion:Epicardial and endocardial potential maps provided information on pacing site and depth and on subsequent intramural propagation by reflecting the clockwise or counterclockwise rotation of the deep positivity. Results may be applicable to epicardial and endocardial potential maps recorded at surgery or from endocavitary probes.
The Clinical Significance of Nonsustained Ventricular Tachycardia
Authors: MITRA RAMAN L. , BUXTON ALFRED E.
Published: May 2007

Nonsustained Ventricular Tachycardia. Nonsustained ventricular tachycardia (NSVT) is an arrhythmia not often associated with symptoms; however, its occurrence in patients with structural heart disease is a prognostic indicator of an increased risk of mortality and sudden death. The management of asymptomatic patients with NSVT should first attempt to identify which patients are at highest risk for cardiac arrest, and second, devise a treatment that can reduce the incidence and/or mortality of cardiac arrest in this group. In patients with chronic coronary artery disease (CAD) and NSVT, programmed electrical stimulation identifies both a low and high risk group with respect to occurrence of ventricular arrhythmias. The negative predictive value of programmed electrical stimulation in patients with CAD and NSVT has been well established; however, uncertainty remains as to the optimal therapy for CAD patients with inducible ventricular arrhythmias. A number of reports suggest that patients whose inducible ventricular arrhythmias are rendered noninducible with antiarrhythmic drugs have a much lower risk of sudden death. It is yet to be resolved whether arrhythmias rendered noninducible identify a subgroup at low risk for cardiac arrest, independent of treatment. There is some evidence to suggest that the frequency of NSVT in patients with nonischemic dilated cardiomyopathy identifies a group at higher risk of sudden death. Programmed electrical stimulation adds little in helping to identify which of these patients are most likely to have cardiac arrest. The presence of NSVT in asymptomatic patients with hypertrophic cardiomyopathy may identify a group at higher risk for cardiac arrest. Further clinical studies are needed to define the best management strategy for NSVT in different types of structural heart disease.
On Establishing Primary Cultures of Neonatal Rat Ventricular Myocytes for Analysis Over Long Periods
Authors: LOKUTA ANDREW , KIRBY MARK S. , GAA SHIRLEY T. , LEDERER W. JONATHAN , ROGERS TERRY B.
Published: May 2007

Neonatal Rat Ventricular Myocyte Cultures. Introduction: Primary cultures of neonatal rat ventricular myocytes include a population of rapidly dividing nonmyocardial cells that can alter the properties of myocytes and complicate experimental interpretations. Without any intervention, nonmyocyte proliferation restricts the utility of primary cultures in biochemical and electrophysiologic studies to 4–5 days. However, with the recent interest in regulation of cardiac gene expression and the effects of growth factors on cardiac function, long‐term studies with stable heart cultures are warranted.

Methods and Results: In the present study an immunohistochemical staining strategy was developed that allowed for reliable quantitation of myocytes and nonmyocytes in cultures maintained for extended periods under different culture conditions. Density gradient purification of myocytes was found valuable in limiting nonmyocyte levels to < 20% at early times. Further treatment of cultures with a mitotic inhibitor, 0.1 mM bromodeoxyuridine, or 3500 rads of γ‐irradiation effectively blocked the proliferation of nonmyocardial cells, while it had no effect on cardiocyte levels. However, bromodeoxyuridine displayed side effects on the myocytes; the spontaneous beating rate and intracellular glycogen content were markedly depressed. In contrast, a systematic investigation of the properties of the irradiated myocytes, including spontaneous beating rates, dihydropyridinc receptors, glycogen content, sarcoplasmic reticulum function, and phosphoinositide signaling, revealed that irradiation did not alter cardiac cell function. Although ionizing radiation can stimulate gene expression in some cell types, γ‐irradiation did not evoke c‐fos expression or cause sarcomere formation, responses seen in cardiac cells to several trophic factors.

Conclusion: This study establishes a system of stable, functional, primary cultured cardiac cells that can be used in long‐term molecular and electrophysiologic studies of at least 2 weeks.
Distribution of M Cells in the Canine Ventricle
Authors: SICOURI SERGE , FISH JEFFREY , ANTZELEVITCH CHARLES
Published: May 2007

Distribution of M Cells. Introduction: M cells and transitional cells residing in the deep structures of the ventricular free walls are distinguished by the ability of their action potentials to prolong disproportionately to those of other ventricular cells at relatively slow rates. This feature of the M cell due, at least in part, to a smaller contribution of the slowly activating component of the delayed rectifier current (Iks) is thought to contribute to the unique pharmacologic responsiveness of M cells, making them the primary targets in ventricular myocardium lor agents that cause action potential prolongation and induce early and delayed afterdepolarizations and triggered activity. Previous studies dealt exclusively with the characteristics and distribution of M cells in the canine right and left ventricular free wall near the base of the ventricles. The present study uses standard microelectrode techniques to define their behavior and distribution in the apical region of the ventricular wall as well as in the endocardial structures of the ventricle, including the interventricular septum, papillary muscles, and trabeculae.

Methods and Results: Action potentials recorded from the M region (deep subepicardium) displayed similar characteristics (steep action potential duration [APD]‐rate relations) in the base and apex. However, important differences were apparent in the other regions. In epicardium. (he spike and dome morphology of the action potential was less accentuated and the rate dependence of APD more pronounced in the apex versus the base. In endocardium, and especially deep subendocardium, rate dependence of APD was considerably more pronounced in the apex. Transmembrane recordings from the subsurface layers of the septum, trabeculae, and papillary muscles revealed M cell behavior (steep APD‐rate relations) in the deep subendocardium. Epicardial and transitional behavior were also observed in the deep layers of these endocardial structures.

Conclusion: Our results indicate that M cells reside throughout the deep subepicardial layers of the free wall of the canine left ventricle as well as in the deep subendocardiat layers of the septum, papillary muscles, and trabeculae. The data also demonstrate prominent transmural as well as apicobasal gradients of phase I and phase 3 repolarization. These findings may have implications relative to our understanding of the electrocardiographs J wave, T wave, U wave, and long QTV intervals.
Radiofrequency Catheter Ablation of an Atriofascicular Pathway During Atrial Fibrillation:
Authors: MILLER JOHN M. , HARPER GLENN R. , ROTHMAN STEVEN A. , HSIA HENRY H.
Published: May 2007

Atriofascicular Ablation During Fibrillation. Introduction: A male patient with an atriofascicular pathway underwent catheter ablation of the atriofascicular pathway during atrial fibrillation.

Methods and Results: The patient had preexcited atrial fibrillation both clinically and repeatedly during electrophysioiogic study. A preexcited tachycardia with a 1:1 AV relationship and regular RR intervals was also induced. Catheter ablation of the atriofascicular pathway could only be performed during persistent atrial fibrillation, based on mapping of the pathway's insertion into the right bundle branch. Following successful ablation and cardioversion to sinus rhythm, a regular QRS tachycardia (atrioventricular [AV] nodal reentry) having (he same rate, atrial activation sequence, and His‐atrial time as the regular preexcited tachycardia noted preablation was initiated. An AV nodal slow pathway modification eliminated this tachycardia. Neither atrial fibrillation nor AV nodal reentry has recurred on follow‐up.

Conclusion: This is the first report of atriofascicular mapping and ablation performed exclusively during atrial fibrillation and illustrates the utility of mapping the pathway's ventricular insertion. Other unusual features (“bystander” pathway activation during AV nodal reentry, possible role of the pathway in genesis of atrial fibrillation) are discussed.
Basic Aspects of Radiofrequency Catheter Ablation
Authors: NATH SUNIL , DiMARCO JOHN P. , HAINES DAVID E.
Published: May 2007

RF Ablation. Radiofrequency (RF) catheter ablation has become the treatment of choice for many symptomatic cardiac arrhythmias. It is presumed that the primary cause of tissue injury by RF ablation is thermally mediated, resulting in a relatively discrete homogeneous lesion. The mechanism by which RF current heats tissue is resistive heating of a narrow rim (< 1 mm) of tissue that is in direct contact with the ablation electrode. Deeper tissue heating occurs as a result of passive heat conduction from this small region of volume heating. Lesion size is proportional to the temperature at the electrode‐tissue interface and the size of the ablation electrode. Temperatures above 50°C are required for irreversible myocardial injury, but temperatures above 100°C result in coagulum formation on the ablation electrode, a rapid rise in electrical impedance, and loss of effective tissue heating. Lesion formation is also dependent on optimal electrode‐tissue contact and duration of RF delivery. Newer developments in RF ablation include temperature monitoring, longer ablation electrodes coupled to high‐powered RF generators, and novel ablation electrode designs.
Ventricular Fibrillation and Polymorphic Ventricular Tachycardia with Critical Coronary Artery Stenosis:
Authors: NATALE ANDREA , SRA JASBIR , AXTELL KATHI , MAGLIO CHERYL , DHALA ANWER , BLANCK ZALMEN , DESHPANDE SANJAY , JAZAYERI MOHAMMAD , AKHTAR MASOOD
Published: May 2007

ICD Therapy and CABG for Sudden Death. Introduction: Previous studies have suggested that coronary artery bypass surgery is sufficient to prevent recurrence of sudden death in patients with critical coronary artery stenosis presenting with ventricular fibrillation or polymorphic ventricular tachycardia. We present our experience in patients with one or more episodes of sudden death associated with documented ventricular fibrillation or polymorphic ventricular tachycardia and severe operable coronary artery disease who underwent defibrillator implant at the time of bypass surgery.

Methods and Results: Fifty‐eight consecutive patients (age 63 ± 8 years) were included in this study. Eighteen of the 58 patients had no evidence of previous myocardial infarction. The mean ejection fraction was 37 ± 13%. All patients underwent electrophysiologic study before and after revascularization. At the time of first defibrillator discharge, each patient was reevaluated to exclude the presence of ischemia. The benefits of defibrillator implant were estimated comparing the projected survival based upon defibrillator discharge preceded by syncope or presyncope with survival curves generated including total death and sudden plus cardiac death. After a mean follow‐up of 4.6 ± 2 years, 22 patients received appropriate shocks preceded by syncope or presyncope, and an additional 19 patients received asymptomatic shocks. At 4 years, survival free of total death was 71.2%, and the projected survival was 58.8% (P < 0.05). Multivariate analysis showed that ejection fraction lower than 30% and induction of arrhythmia with one or two extrastimuii (S2, S3) were independent predictors for defibrillator discharge. None of the remaining variables including age, gender, number of bypasses, history of myocardial infarction, and type of arrhythmias induced were predictive for death and occurrence of shocks.

Conclusions: In patients with ventricular fibrillation and polymorphic ventricular tachycardia, bypass surgery does not protect from recurrence of life‐threatening arrhythmias, and, as in our population, defibrillator implant may have significant impact on survival.
Pharmacologic Properties of the Swelling‐Induced Chloride Current of Dog Atrial Myocytes
Authors: SOROTA STEVE
Published: May 2007

Pharmacology of Swelling‐Induced Chloride Current. Introduction: Swelling‐induced chloride currents may contribute to cardiac electrical activity and cell volume regulation. Identification of selective Mockers would aid in understanding the functional contribution(s) of this current.

Methods and Results: Dog atrial cells were used to investigate the pharmacologic properties of the swelling‐induced chloride current. Whole cell patch clamp was used. Swelling‐induced chloride current was activated by osmotic stress. Initially, the chloride selectivity and calcium independence of the swelling‐induced current in dog atrial cells was demonstrated. Subsequently, a number of putative chloride channel blockers were examined. Anthracene‐9‐earboxylic acid (1mM) and dideoxyforskolin (1000 μ) and extracellular cAMP (5mM) were found to partially inhibit the swelling‐induced chloride current (∼50%, 80%, and 10% inhibition, respectively). Niflumic acid (100 μ), nitrophenylpropylamino benzoate (NPPB; 10 to 40 μ), and (+) 2‐[(2‐cydopentyl‐6,7‐dichloro‐2,3‐dihydro‐2‐melhyl‐1‐oxy‐1H‐inden‐5‐yl)oxy] acetic acid (indanyloxyacetic acid; IAA‐94; 100 μ) could fully inhibit the swelling‐induced chloride current without decreasing cell size. DIDS (100 μ) and dinitrostilbene disulfonic acid (DNDS;5 mM) fully inhibited outward currents but only partially inhibited inward current.

Conclusions: Niflumic acid, IAA‐94, and NPPB were identified as full blockers of cardiac swelling‐induced chloride current. Nonspecific effects were identified for each of the full blockers. Experiments that use these agents as functional antagonists should be carefully designed and interpreted with caution.
Biphasic Waveform Defibrillation Using a Three‐Electrode Transvenous Lead System in Humans
Authors: MARKS MELINDA L. , JOHNSON GEORGE , HOFER BRADLEY O. , BARDY GUST H.
Published: May 2007

Biphasic Transvenous Defibrillation. Introduction: Biphasic waveform defibrillation is not always more efficacious than monophasic waveform defibrillation.

Methods and Results: Waveform efficacy appears to vary with the lead system used. In this prospective, randomized study, defibrillation efficacy with biphasic and monophasic single capacitor 120μF, 65% tilt pulses was compared for a lead system consisting of right ventricular (RV), chest patch (CP), and superior vena cava (SVC) electrodes. Although this lead system is commonly used with monophasic pulses in transvenous defibrillators, few studies have examined the defibrillation efficacy of this lead system in man for biphasic waveform defibrillation. Fourteen cardiac arrest survivors undergoing defibrillator implantation were included in the study using pulses delivered from a cathodal RV electrode simultaneously to anodal SVC and CP electrodes. Biphasic and monophasic waveforms were recorded oscilloscopically to acquire defibrillation threshold (DFT) data on leading edge voltage requirements and for stored energy. The monophasic DFT voltage was 661 ± 177 V compared to the biphasic DFT voltage of 451± 185 V (P < 0.0001). The monophasic DFT stored energy was 28.0 ± 13.4 J compared to the biphasic DFT stored energy of 14.1 ± 12.4 J (P ± 0.0001). The stored energy DFT was < 15 J in only 2 of 14 patients (15%) with monophasic defibrillation but < 15 J in 10 of 14 (71%) patients with biphasic defibrillation.

Conclusion: These findings indicate that biphasic defibrillation with an RV, SVC, CP transvenous electrode system is substantially more efficient than monophasic defibrillation. allowing for higher numbers of patients to receive transvenous defibrillators with a relatively simple lead system at a satisfactory cutoff DFT safety margin of 15 J.
Bedside Recordings of His‐Bundle Electrograms Using Conventional Twelve‐Lead Surface Electrocardiography
Authors: GÜRSOY SINAN , STEURER GUNTER , SOUZA OLGA , BRUGADA PEDRO
Published: May 2007

Bedside Recording of His Potentials. Introduction: Endocavitary His‐bundle electro‐grams are usually recorded using high fidelity amplifiers and special filters.

Methods and Results: To evaluate whether similar recordings could be obtained using a 12‐lead surface electrocardiograph, we compared recordings obtained during an electrophysiologic study in 33 patients to those obtained by connecting the two poles of the bipolar catheter, used during the study as the His catheter, to the right and left arm leads of the surface electrocardiograph. We recorded His‐bundle electrograms using both techniques in all patients. There were no differences in measurements obtained between the two techniques.

Conclusion: His‐bundle electrograms can be recorded reliably with a conventional electro‐gram without sophisticated systems.
Antibodies to Beta‐Adrenergic Receptors Disclosing Agonist‐Like Properties in Idiopathic Dilated Cardiomyopathy and Chagas’ Heart Disease
Authors: ROSENBAUM MAURICIO B. , CHIALE PABLO A. , SCHEJTMAN DALIA , LEVIN MARIANO , ELIZARI MARCELO V.
Published: May 2007

Antibodies to Beta‐Adrenergic Receptors. Recent studies confirm the existence of antibodies (Abs) to β adrenoceptors in patients with idiopathic dilated cardiomyopathy and Chagas’ heart disease. These Abs can be shown to exert both stimulatory and inhibitory effects, which may play a role in the development of the cardiac abnormalities known to occur in these diseases, including advanced heart failure. The hypothesis is advanced that Chagas’ heart disease and some forms of idiopathic dilated cardiomyopathy may represent, at least partially, a form of “adrenergic cardiomyopathy.”
Computer Aided Development of Antiarrhythmic Agents with Class IIIa Properties
Authors: HONDEGHEM LUC M.
Published: May 2007

Antiarrhythmic Agents. Most antiarrhythmic agents were discovered accidentally. In the last decade, the understanding of the mechanisms of action of agents with electrophysioiogic activity has progressed greatly. As a result, it was possible to compute, before the CAST trial, that the agents selected for the trial would not be effective against tachycardias and that the drugs would be unsafe. Extension of these computations to existing Class 1 agents indicated that they were all poor suppressors of ventricular tachycardia. Furthermore, a Class I agent with an optimal electrophysioiogic profile still computes to be a two‐edged sword, possessing both antiarrhythmic and p roar rhythmic properties. Fortunately, it is possible to conceive of drug profiles that would be purer antiarrhythmic agents. For example, a drug that only upon the development of a tachycardia lengthens action potential duration in a use‐dependent manner until the refractory period exceeds the tachycardia cycle length will render continuation of the tachycardia impossible. Recognition of chemicals that have Class III, properties with the appropriate kinetics is a challenging task. However, today's microprocessors have become powerful enough to characterize the Class HI kinetics. A system that fully automatically screens for effective antiarrhythmic agents is described. It is expected that chemicals selected for optimal basic electro‐physiologic properties will yield safer and more effective antiarrhythmic agents.
Additions to the Wavelet Hypothesis of Cardiac Fibrillation
Authors: ABILDSKOV J.A.
Published: May 2007

Wavelet Hypothesis. Introduction: The wavelet hypothesis of Moe relates the initiation of cardiac fibrillation to nonuniform propagation of premature responses in the presence of nonuniform recovery of excitability. Fibrillation itself is characterized by multiple spatially discrete activation fronts (wavelets) resulting in reentry at changing locations.

Methods and Results: A computer model originally used to demonstrate the hypothesis has been used in further studies of fibrillation and the findings add new details to the hypothesis. The model simulated propagation, cycle length dependent recovery of excitability, and slow propagation of premature responses. Additions to the hypothesis were definition of the different mechanisms by which refractory period (RP) range and mean duration affect vulnerability, explanation of the onset of the vulnerable period later than earliest propagation, and definition of effects of conduction defects on vulnerability. They also include evidence that RP range and duration affect the degree of nonuniform excitation required for fibrillation.

Conclusion: Findings indicate that mean RP duration affects vulnerability by means of the number of premature responses possible per unit time while RP range affects nonuniformity of propagation per premature response. They also suggest that effects of conduction defects on vulnerability depend on associated RPs and that the degree of nonuniform excitation required to initiate fibrillation varies with recovery properties. In addition, they provide an explanation for onset of (he vulnerable period after propagation is possible.