bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemia‐Induced Changes of the Signal‐Averaged Electrocardiogram:
Authors: STEINBIGLER PETER , HABERL RALPH , STEINBECK GERHARD
Published: April 2007

Late Potential Changes with Ischemia. Introduction: The influence of myocardial ischemia on the detection of an arrhythmogenic substrate with the signal‐averaged ECG is unclear.

Methods and Results: In 80 patients with single vessel coronary artery disease and a critical stenosis of the left anterior descending vessel selected after coronary angiography in whom percutaneous transluminal coronary angioplasty (PTCA) was planned, we retrospectively investigated the signal‐averaged ECGs in the time domain before, during, and after occlusion of the coronary artery by the PTCA balloon. Forty patients were resuscitated from ventricular fibrillation (VF group), and 40 patients had no ventricular arrhythmia (non‐VF group). Late potentials were seen at rest in 26 of 40 patients in the VF group. During ischemia, the duration of the filtered QRS complex and the duration of low‐amplitude signals < 40 μV increased significantly. In another 14 patients in the VE group, late potentials were observed only during ischemia. In 4 of 26 patients in the VE group without prior infarction hut with severe ischemia present at rest, successful PTCA eliminated preexistent late potentials. In the non‐VF group, one patient had late potentials present at rest. In two patients with prior infarction, late potentials were provokable only during transmural ischemia.

Conclusion: Myocardial ischemia is able to modify detection of an arrhythmogenic substrate with the signal‐averaged ECG.
No Evidence of Chaos in the Heart Rate Variability of Normal and Cardiac Transplant Human Subjects
Authors: COSTA MADALENA , PIMENTEL IVETA R. , SANTIAGO TERESA , SARREIRA PEDRO , MELO JOÃO , DUCLA‐SOARES EDUARDO
Published: April 2007

Heart Rate in Normal and Cardiac Transplant Subjects. Introduction: The variability observed in the heart rate may reflect fundamental aspects of cardiac activity. It has been under discussion whether heart rate variability (HRV) is due to noise or chaos, which is irregular behavior occurring in deterministic nonlinear systems.

Methods and Results: Using chaos analysis techniques, we analyzed HRV of five normal and five human cardiac transplant subjects at rest. HRV is studied using the beat‐to‐beat RR interval time series extracted from the ECG. The cardiac transplant subjects exhibited a much smaller HRV than the normal subjects because of heart denervation. We present the map and correlation dimension estimation for the RR time series. To test for nonlinear correlations in the dynamics, we built surrogate time series that have the same power spectra as the experimental time series, but also have randomized phases. The experimental and the surrogate data were compared using the correlation integral. No correlation dimension was found for the RR time series of either the normal or the cardiac transplant subjects. Nevertheless, nonlinear correlations were detected in the HRV of the normal subjects but not in HRV of the cardiac transplant subjects. For the latter, no significant changes were observed in the correlation integral as a function of time after transplantation.

Conclusion: We found no evidence of low‐dimensional chaos in the HRV of normal and cardiac transplant subjects. However, some nonlinear correlations were detected in the HRV of the normal subjects, which may be associated with autonomic nervous system influence.
Inspiration Induced by Phrenic Nerve Stimulation Increases Internal Defibrillation Energy Requirements
Authors: EULER DAVID E. , WHITMAN TERESA A. , KALLOK MICHAEL J.
Published: April 2007

Active Inspiration Affects Defibrillation. Introduction: The purpose of this study was to systematically evaluate the effects of active inspiration induced by phrenic nerve stimulation on the energy required for 50% successful defibrillation (E50).

Methods and Results: Shocks (95‐μF biphasic waveform) were delivered after 10 seconds of ventricular fibrillation between a right ventricular coil and left pectoral test can in ten anesthetized pigs (25 to 37 kg). Using a 1‐J step size, the E50 was determined with an up/down, three‐reversal method. Positive‐pressure ventilation was halted just before fibrillation, and shocks were delivered during expiration or at the end of 2 seconds of bilateral phrenic stimulation (50 Hz, 0.3 msec, 5 to 6 V). Phrenic stimulation produced inspiratory volumes that were 15.3 ± 1.7 mL/kg (mean ± SD). The E50 was 9.8 ± 1.9 J during expiration and increased to 13.0 ± 1.7 during inspiration (P = 0.001). The leading‐edge voltage at the K50 was 451 ± 46 V during expiration and 519 ± 33 V during inspiration (P = 0.001). The leading‐edge current at the E50 was 9.7 ± 1.0 A during expiration and increased to 11.3 ± 1.4 A during inspiration (P = 0.002). The average impedance was 47.8 ± 2.7 Ω during expiration and 47.3 ± 3.3 Ω during inspiration (P = 0.12).

Conclusion: Inspiration induced by phrenic stimulation results in a 31% increase in the E50 compared with expiration. The decrease in shock efficacy occurs in the absence of a change in impedance. Active inspiration may alter the distribution of the electrical field leading to a decrease in shock efficacy.
Cell Coupling and Impulse Propagation in the Failing Heart
Authors: DE MELLO WALMOR C.
Published: April 2007

Cell Coupling and Impulse Propagation. Cell coupling and impulse propagation were investigated in the ventricle of cardiomyopathic hamsters at an advanced stage of heart failure. An appreciable decline in junctional conductance was found, a phenomenon in part related to activation of the plasma and cardiac renin‐angiotensin systems. Decreased expression of conucxin43 or an alteration of junctional proteins also might be implicated in the decreased cell coupling. Morphologic abnormalities such as fibrosis, necrosis, and rupture of cell contacts contribute to the decline of conduction velocity or to the blockade of impulse propagation in some areas of the ventricle, creating the conditions for anisotropic conduction and cardiac arrhythmias. The decrease in membrane potential found in myopathic cells is related in part to depression of Na‐KATPase activity, and the lack of action of beta‐adrenergic agonists on junctional conductance is explained by down‐regulation of beta receptors and an abnormality of adenyl cyclase.
Insights into the Mechanism of Sustained Ventricular Tachycardia after Myocardial Infarction in a Closed Chest Porcine Model Using a Multielectrode “Basket” Catheter
Authors: GREENSPON ARNOLD J. , HSU STEVE S. , BORGE RICHARD , SMITH MICHAEL R , ELDAR MICHAEL
Published: April 2007

Mechanism of Sustained VT. Introduction: Accurate analysis of the arrhythmia substrate is important for successful radiofrequency ablation of sustained ventricular tachycardia (VT) after myocardial infarction (MI).

Methods and Results: A multielectrode “basket” catheter capable of endocardial recording and pacing was inserted percutaneously into the left ventricle of post‐MI swine for analysis of the mechanism of sustained VT. Sustained VT was induced in 42 of 61 pigs that survived an acute MI produced by percutaneous transluminal coronary angioplasty balloon occlusion of the left anterior descending coronary artery and injection of agarose gel beads. A multielectrode “basket” catheter (Constellation™) with 64 electrodes was inserted in 35 of these animals for analysis of the VT. Induced VT had a cycle length of 179 ± 25 msec at control and 230 ± 43 msec after administration of intravenous procainamide. Presystolic electrical activity was recorded from at least 1 of 32 bipolar pairs of electrodes at a mean 40.7 ± 23.6 msec prior to QRS onset. Isolated mid‐diastolic potentials were recorded in 26 of 35 animals. In 22 animals, there were multiple isolated potentials recorded from adjacent electrode pairs. Isochronal maps demonstrated that these potentials returned to the systolic site of origin. Resetting of sustained VT by single premature ventricular stimuli was observed in 6 of 12 animals. Entrainment with overdrive pacing was seen in 19 of 26 animals with induced VT. Concealed entrainment was observed in ten animals. The mean stimulus to QRS interval was 45 ± 28 msec. Concealed entrainment was observed from adjacent electrode pairs with different stimulus to QRS intervals.

Conclusion: These data suggest that sustained VT in this model is due to reentry with an excitable gap. A multielectrode “basket” catheter is useful for analyzing the zone of slow conduction participating in the tachycardia circuit. Such analysis may provide useful information to guide successful catheter ablation of sustained VT after MI.
Transvenous Parasympathetic Cardiac Nerve Stimulation:
Authors: SCHAUERTE PATRICK N. , SCHERLAG BENJAMIN J. , SCHERLAG MICHAEL A. , GOLI SUNIL , JACKMAN WARREN , LAZZARA RALPH
Published: April 2007

Transvenous Parasympathetic Cardiac Nerve Stimulation. Introduction: Epicardial electrical stimulation of parasympathetic nerves innervating the sinus node has been shown to decrease sinus rate. We investigated whether intravascular parasympathetic cardiac nerve stimulation (IPS) can be achieved over a relatively long‐term period to slow the supraventricular rate.

Methods and Results: Fifteen dogs were investigated. IPS was performed with rectangular stimuli (0.05‐msec duration, 20 Hz) using a catheter with an expandable electrode basket. The catheter was positioned in the superior vena cava (SVC; n = 9) or right pulmonary artery (RPA; n = 6). The basket then was expanded to hold the catheter in place. Nonfluoroscopic identification of effective IPS sites was achieved within 5 minutes in the SVC. Increasing IPS voltage resulted in a graded response of supraventricular rate slowing. A 50% prolongation of the baseline atrial cycle length was achieved with 28 V in the SVC (1,056 ± 355 msec vs 489 ± 154 msec; P < 0.001) and 25 V in the RPA (1,181 ± 306 msec vs 518 ± 138 msec; P < 0.01). The rate slowing started immediately after IPS onset, terminated abruptly after IPS cessation, and could be maintained over 10 hours. A rate slowing effect also was observed when the sinus rate was increased by isoproterenol (SVC: 304 ± 8 msec/RPA: 341 ± 9 msec with isoproterenol vs SVC: 635 ± 12 msec with isoproterenol + IPS at 39 V/ RPA: 584 ± 16 msec with isoproterenol + IPS at 38 V; n = 6).

Conclusion: IPS results in a significant supraventricular rate slowing that is stable over a relatively long period and may be applied to slow undesirable sinus tachycardia in acute ischemic syndromes or to counteract undesirable chronotropic effects of catecholamines during treatment of cardiogenic or septic shock and acute congestive heart failure.
Evaluation of Antiarrhythmic Drug Efficacy in Patients with an ICD:
Authors: PRATT CRAIG M. , CAMM A. JOHN , BIGGER J. THOMAS , BREITHARDT GÜNTER , CAMPBELL RONALD W.F. , EPSTEIN ANDREW E. , KAPPENBERGER LUKAS J. , KUCK KARL‐HEINZ , POCOCK STUART , SAKSENA SANJEEV , WALDO ALBERT L.
Published: April 2007

Antiarrhythmic Drug Efficacy in Patients with an ICD. There are a number of novel ways in which implantable cardioverter defibrillator (ICD) endpoints can he used in clinical trials to evaluate antiarrhythmic drugs. The advances in ICD technology (storage, retrieval, and accurate interpretation of ICD electrograms) expand the potential to include the use of an ICD endpoint as a clinical surrogate for sudden death. The ICD also provides the necessary safety net to test new drugs. The frequent need for‘antiarrhythmic drugs in patients already fitted with an ICD (e.g., for atrial fibrillation) necessitates knowledge of the drugs' effect on defibrillator threshold. There are interpretative problems and challenges associated with all types of ICD trials. A particular difficult issue is the degree to which the results of data on antiarrhythmic drug efficacy and safety acquired in the context of an ICD endpoint trial might he extrapolated to patient populations in which the device is not used. These and other challenging issues are discussed, with the goal of enhancing the design and interpretation of clinical trials featuring ICD endpoints.
Droperidol Lengthens Cardiac Repolarization due to Block of the Rapid Component of the Delayed Rectifier Potassium Current
Authors: DROLET BENOIT , ZHANG SHETUAN , DESCHÊNES DOMINIC , RAIL JIMMY , NADEAU SYLVIE , ZHOU ZHENGFENG , JANUARY CRAIG T. , TURGEON JACQUES
Published: April 2007

Droperidol Blocks Cardiac IKr.Introduction: Torsades de pointes have been observed during treatment with droperidol, a butyrophenone neuroleptic agent. Our objectives were (1) to characterize the effects of droperidol on cardiac repolarization and (2) to evaluate effects of droperidol on a major time‐dependent outward potassium current involved in cardiac repolarization (IKr).

Methods and Results: Isolated, buffer‐perfused guinea pig hearts (n = 32) were stimulated at different pacing cycle lengths (150 to 250 msec) and exposed to droperidol in concentrations ranging from 10 to 300 nmol/L. Droperidol increased monophasic action potential duration measured at 90% repolarization (MAPD90) in a concentration‐dependent manner by 9.8 ± 2.3 msec (73%± 0.7%) at 10 nmol/L but by 32.7 ± 3.6 msec (25.7%± 2.2%) at 300 nmol/L (250‐msec cycle length). Increase in MAPDW90also was reverse frequency dependent As noted previously, droperidol 300 nmol/L increased MAPD90by 32.7 ± 3.6 msec (25.7%± 2.2%) at a pacing cycle length of 250 msec but by only 14.1 ± 1.3 msec (13.6%± 2.3%) at a pacing cycle length of 150 msec. Patch clamp experiments performed in isolated guinea pig ventricular myocytes demostrated that droperidol decreases the time‐dependent outward K+current elicited by short depolarizations (250 msec; 1k250) in a concentration‐dependent manner. Estimated IC50for IK250, which mostly underlies IKr, was 28 nmol/L. Finally, HERG K+current elicited in HEK293 cells expressing high levels of HERG protein was decreased 50% by droperidol 32.2 nmol/L.

Conclusion: Potent block of IKrby droperidol is likely to underlie QT prolongation observed in patients treated at therapeutic plasma concentrations (10 to 400 nmol/L) of the drug.
Transient QT Prolongation with Torsades de Pointes Tachycardia after Ablation of Permanent Junctional Reciprocating Tachycardia
Authors: GRIMM WOLFRAM , HOFFMANN JÜRGEN , MENZ VOLKER , MAISCH BERNHARD
Published: April 2007

Torsades de Pointes after PJRT Ablation. Introduction: Catheter ablation with radiofrequency energy is a curative therapy in patients with permanent junctional reciprocating tachycardia (PJRT).

Methods and Results: For the first time, we report a case of transient QT prolongation with torsades de pointes tachycardia 18 hours after successful radiofrequency energy ablation of PJRT in a 25‐year‐old woman with tachycardia‐induced cardiomyopathy. Of note, the torsades de pointes occurred in the absence of bradycardia, electrolyte disturbances, or QT‐prolonging drugs. This patient initially was thought to have a hereditary long QT syndrome that was unmasked by PJRT ablation. Therefore, the patient received an implantable defibrillator in addition to beta‐blocker therapy, which was discontinued 6 months later. Surprisingly, the QT interval completely normalized within 1 week after PJRT ablation, and the patient remained free of arrhythmias during a follow‐up period of 4.5 years.

Conclusion: Patients with incessant tachyarrhythmias should undergo ECG monitoring for at least 24 hours following successful radiofrequency catheter ablation because transient QT prolongation with torsades de pointes may occur even in the absence of bradycardia, QT‐prolonging drugs, or electrolyte disturbances.
Incessant Nonreentrant Atrioventricular Nodal Tachycardia Due to Multiple Nodal Pathways Treated by Radiofrequency Ablation of the Slow Pathways
Authors: ARENA GIUSEPPE , BONGIORNI MARIA GRAZIA , SOLDATI EZIO , GHERARDUCCI GHERARDO , MARIANI MARIO
Published: April 2007

Incessant Nonreentrant AVNT by Multiple Pathways. In patients with dual AV nodal physiology, simultaneous anterograde fast and slow pathway conduction resulting in an unusual form of nonreentrant A V nodal tachycardia has been observed. We describe the case of a young patient with an incessant form of complex supraventricular tachycardia who underwent electrophysiologic evaluation, which showed simultaneous conduction via multiple AV nodal pathways that caused a unique form of incessant nonreentrant AV nodal tachycardia. Radiofreqeuncy ablation of the spatially closed intermediate and slow pathways effectively treated the tachycardia. The electrophysiologic determinants of simultaneous conduction through the multiple nodal pathways and the apparently different behavior of the fast pathway before and after ablation are discussed.
Inherited Long QT Syndromes:
Authors: RODEN DAN M. , SPOONER PETER M.
Published: April 2007

LQTS as a Paradigm. The inherited long QT syndrome (LQTS) is a familial disease characterized by QT interval changes that often are labile, syncope, and sudden death due to arrhythmias, predominantly in young people. Multiple mutations in five genes encoding structural subunits of cardiac ion channels now have been identified in families with LQTS. Correlations are being described between genotype and specific clinical features in LQTS. However, increasing screening of affected families and sporadic cases has identified incomplete penetrance with highly variable clinical manifestations, even among individuals carrying the same mutations. The identification of LQTS disease genes represents a crucial first step in developing an understanding of the molecular basis for normal cardiac repolarization. This information will be important not only for identifying new therapies in LQTS, but also in further understanding arrhythmias, and their potential therapies, in situations such as heart failure, cardiac hypertrophy, myocardial infarction, or sudden infant death syndrome, where abnormal repolarization has been linked to sudden death. LQTS thus presents a new paradigm to cardiac electrophysiology, in which new molecular information is being brought to bear both on clinical management of patients and on development of a new framework to study the fundamental causes of arrhythmias and new approaches to therapy.
Electrophysiologic Characteristics of Accessory Atrioventricular Connections in an Inherited Form of Wolff‐Parkinson‐White Syndrome
Authors: MEHDIRAD ALI A. , FATKIN DIANE , DiMARCO JOHN P. , MacRAE CALUM A. , WASE ABDUL , SEIDMAN J.G. , SEIDMAN CHRISTINE E. , BENSON D. WOODROW
Published: April 2007

EP Characteristics in Familial WPW. Introduction: A familial form of Wolff‐Parkinson‐White syndrome (WPW) occurs in association with hypertrophic cardiomyopathy and intraventricular conduction ahnormalities. This syndrome, demonstrating autosomal dominant inheritance and segregating with a high degree of penetrance but variable expressivity, has been genetically linked to chromosome 7q3. The purpose of this study is to detail the electrophysiologic characteristics of accessory atrioventricular connections (AC) in four members of a kindred with this syndrome.

Methods and Results: We clinically evaluated 32 members of a single kindred and identified 20 individuals with ventricular preexcitation, abnormal intraventricular conduction including complete AV block and/or ventricular hypertrophy, Genetic linkage analysis mapped the disease gene in this kindred to the chromosome 7q3 locus (maximum logarithm of the odds score = 6.88, θ= 0); recombination events in affected individuals reduced the genetic interval from 7 centimorgans (cM) to 5 cM. Electrophysiologic study of four individuals with preexcitation, identified seven AC (1 right sided, 3 septal, and 3 left sided). All four individuals had inducible orthodromic tachycardia; while three had multiple AC. Bidirectional conduction was demonstrated in 6 of 7 AC. Successful ablation was accomplished in 5 of 7 AC.

Conclusion: The electrophysiologic characteristics and location of AC in family members having this complex cardiac phenotype are similar to those seen in individuals with isolated WPW. Identification of WPW in more than one family member should prompt clinical evaluation of relatives for additional findings of ventricular hypertrophy or conduction abnormalities.(J Cardiovasc Electrophysiol. Vol. 10, pp. 629‐635, May 1999)
Low‐Power Radiofrequency Application and Intracardiac Echocardiography for Creation of Continuous Left Atrial Linear Lesions
Authors: ROITHINGER FRANZ X. , STEINER PAUL R. , GOSEKI YOSHINARI , LIESE KARL S. , SCHOLTZ DINA B. , SIPPENSGROENEWEGEN ARNE , URSELL PHILIP , LESH MICHAEL D.
Published: April 2007

Prediction of Left Atrial Linear Lesions. Introduction: Continuity of radiofrequency (RF) lesions for a catheter‐based cure of atrial fibrillation is essential in order to avoid reentrant tachycardias. In the present study, we assessed the value of intracardiac echocardiography and preablation electrode‐tissue interface parameters for creation of left atrial linear lesions.

Methods and Results: In six healthy dogs, two left atrial linear lesions (lesion 1, along the inferior posterior left atrium; lesion 2, from the appendage to the left atrial roof) were attempted via a transseptal approach using a deflectable catheter with six 7‐mm coil electrodes. In a randomized fashion, one lesion was performed under echocardiographic guidance and one with blinded echocardiographic monitoring. The following preablation parameters were assessed for every coil electrode: (1) mean atrial electrogram amplitude of six consecutive sinus beats; (2) diastolic pacing threshold; and (3) temperature response to application of 5 W for 10 seconds. After ablation (target temperature 70°C, maximum power 50 W, duration 60 sec), the excised left atrium was examined macroscopically and histologically for lesion length, continuity, and presence or absence of lesions associated with each coil.

Out of 12 attempted RF lesions, 7 were continuous (length, 47 ± 5 mm, lesion 2, n = 6) and 5 were discontinuous (lesion 1, n = 5). Fifty‐two of 70 coil electrodes (74%) had pathologic evidence of lesion creation. Intracardiac echocardiography was superior to fluoroscopy with respect to the actual number of coil electrodes creating lesions, and lesion continuity was correctly predicted in 9 of 12 lesions. Intracardiac echocardiography was 85% sensitive and 54% specific in predicting lesions created by individual coils. The correlation between the mean 60‐second ablation temperature and the preablation parameters was 0.45 for the electrogram amplitude, ‐0.67 for the pacing threshold, and 0.81 for the temperature response to low‐power application. Sensitivity and specificity for prediction of lesions created by individual coils, respectively, were 84% and 48% for the electrogram amplitude. 90% and 68% for the pacing threshold, and 96% and 76% for the low‐power RF application.

Conclusion: Long linear lesions can be safely and effectively performed in the canine left atrium, using a tip‐deflectable multielectrode catheter. Intracardiac echocardiography may be helpful for positioning the ablation catheter in some parts of the left atrium, and preablation parameters, especially a nontraumatic low‐power RF application, are able to predict ultimate lesion creation with high accuracy.
Unitary Current Analysis of L‐type Ca2+ Channels in Human Fetal Ventricular Myocytes
Authors: CHEN LONG , EL‐SHERIF NABIL , BOUTJDIR MOHAMED
Published: April 2007

Calcium Channels in Human Fetal Heart. Introduction: L‐type calcium channels were studied in cell‐attached patches from ventricular cell membranes of human fetal heart.

Methods and Results: Experiments were performed in the presence of 70 mM Ba2+ as the charge carrier at 22°C to 24°C. Unitary current sweeps were evoked by 300‐msec depolarizing pulses to 0 mV from a holding potential of ‐50 mV at 0.5 Hz. Recorded currents were blocked by nisoldipine (I μM) and stimulated by (‐)Bay K 8644 (1 μM). During control, channel activity was seen in 13.9%μ 4.2% of the total 200 sweeps. Ensemble average current amplitude was 0.03 ± 0.01 pA (n = 6) and average conductance was 20.4 ± 0.2 pS (n = 5). Analysis of single channel kinetics showed open time and closed time histograms were best fit by one and two exponentials, respectively. Mean open time was τo= 0.99 ± 0.05 msec (n = 6). Mean closed time fast (τcf) and slow (τcs) component values were τcr= 0.85 ± 0.09 msec and τcs= 8.0 ± 0.94 msec (n = 6), respectively. With intrapipette (‐)Bay K 8644 (1 μM), mean open time was best fit by two exponentials, τcf= 0.9 ± 0.2 msec (n = 10) and τos= 13.4 ± 2.6 msec (n = 10); mean close time values were τcf= 0.6 ± 0.1 msec (n = 10) and τcf= 9.8 ± 1.9 msec (n = 10), respectively. With (‐)Bay K 8644, channel activity was 66.5%± 7.4%, the ensemble average current was 0.52 ± 0.04 pA (n = 10) and the conductance 20.7 ± 0.5 pS (n = 5).

Conclusion: (1) the data establishes the characteristics of L‐type Ca channels of human fetal hearts and their modulation by dihydropyridines; (2) the open time kinetics differ from those of avian embryonic and rat fetal hearts; and (3) the findings provide new and relevant information for understanding the physiologic behavior of unitary Ca2+ channels in the developing human heart and the baseline comparison for diseases that implicate Ca2+ channels in their etiology, such as autoimmune‐associated congenital heart block.
Coexisting Preexcitation Syndrome and Intermittent Heart Block Presenting as Neonatal Seizures
Authors: KANTER RONALD J. , DEL RIO ALFREDO , MIRETTI CARLOS , GONZALEZ‐ZUELGARAY JORGE
Published: April 2007

Preexcitation Plus Intermittent Heart Block. An infant presented with neonatal syncope and seizures. An ECG showed a preexcitation pattern, most compatible with Wolff‐Parkinson‐White (WPW) syndrome. Rhythm monitoring during an event demonstrated prolonged periods of complete AV block with no ventricular escape mechanism. We postulated that ventricular asystole was initiated by mechanism or autonomic influences on the accessory pathway and sustained by electrophysiologic interactions between the accessory pathway and the junctional escape focus. This is the first case report of a newborn having coexisting congenital AV block and WPW syndrome.
Verification of Linear Lesions Using a Noncontact Multielectrode Array Catheter versus Conventional Contact Mapping Techniques
Authors: SCHUMACHER BURGHARD , JUNG WERNER , LEWALTER THORSTEN , WOLPERT CHRISTIAN , LÜDERITZ BERNDT
Published: April 2007

Noncontact Verification of Linear Lesions. Introduction: Creation of linear lesions is an established ablation goal. Verification of complete conduction block at the ablation line is required to determine ablation success. Conventional mapping techniques are sequential endocardial activation mapping and documentation of double potentials. Recently, a noncontact multielectrode array catheter was developed that allows instantaneous three‐dimensional mapping by simultaneous reconstruction of > 3, 000 electrograms. In this study, we prospectively compared the accuracy of noncontact mapping to identify discontinuities in linear lesions and to verify a conduction block with that of conventional mapping techniques.

Methods and Results: In 12 patients with atrial flutter, radiofrequency pulses were applied between the tricuspid annulus and either the inferior vena cava or the eustachian ridge. Following each application, pulse propagation at the ablation line was determined during pacing by conventional mapping techniques. The findings were compared to high‐density isopotential mapping using the noncontact multielectrode array catheter. It was found that noncontact mapping reliably distinguished conduction delays from a conduction block as defined by contact mapping. In addition, noncontact mapping instantaneously identified the area where a discontinuity in the line of block was present. In these patients, complete conduction block was achieved by radiofrequency pulses guided by the noncontact mapping system.

Conclusion: Noncontact mapping is highly accurate in distinguishing conduction delays from a complete conduction block. By providing an instantaneous high‐density propagation vector at all sites along the ablation line, three‐dimensional isopotential mapping is helpful in localizing discontinuities of linear lesions and, thus, may facilitate the creation of a complete conduction block.
Characteristics of IK and its Response to Quinidine in Experimental Healed Myocardial Infarction
Authors: YUAN FENG , PINTO JUDITH M.B. , LI Ql , WASSERLAUF BERNARD J. , YANG XIANGJUN , BASSETT ARTHUR L. , MYERBURG ROBERT J.
Published: April 2007

I*, and Quinidine in Healed Infarction. Introduction: Mechanisms and drug treatment of serious ventricular arrhythmias in patients with healed myocardial infarction (HMI) are incompletely understood, in part because the electrophysiology and pharmacology of myocytes from noninfarcted regions of HMI hearts are not well characterized.

Methods and Results: We studied the delayed rectifier potassium current (IK) and quinidine responsiveness of single left ventricular subendocardial myocytes isolated from the region remote to the border zone of healed infarct myocardium (4 to 6 mm from scar edge) in cat hearts 2 months after coronary artery occlusion. Subendocardial cells isolated from corresponding regions of normal cat hearts provided controls. IK activation and tail currents were recorded using whole cell, voltage clamp techniques. Membrane capacitance of cells remote to HMI (187 ± 7 pF) was significantly greater than normal (155 ± 6 pF; P < 0.001). Action potential durations (APDs) recorded from myocytes in remote regions were prolonged (APD90= 247 ± 10 msec) compared to normal (214 ± 11 msec; P < 0.05). Quinidine (1 μM) significantly prolonged APD90 in normal cells but not in remote cells. Density of IK, (tail current) was significantly decreased in remote cells (3.1 ± 0.3 pA/pF) compared to normal (3.9 ± 0.3 pA/pF; P < 0.05). and voltage‐dependent activation of IK was shifted in the positive direction. Quinidine had significantly less incremental blocking effect on IK already blunted by regional hypertrophy compared to its effect on normal cells in remote cells. IC550 shifted to 0.95 μM in remote cells compared with 0.50 μM in normal cells.

Conclusion: Cells in noninfarct region remote from the scar are hypertrophied and display altered electrophysiology. Their reduced IK responsiveness to quinidine may explain, in part, failure of quinidine to prolong APD in such cells. Moreover, dispersion of repolarization may be decreased by the effect of quinidine on normal cells.
The Role of Atrial Electrical Remodeling in the Progression of Focal Atrial Ectopy to Persistent Atrial Fibrillation
Authors: HOBBS W. JULIAN C. , Van GELDER ISABELLE C. , FITZPATRICK ADAM P. , CRIJNS HARRY J.G.M. , GARRATT CLIFFORD J.
Published: April 2007

Focal Atrial Fibrillation and Electrical Remodeling. Although atrial fibrillation‐ (AF) induced changes in atrial refractoriness (atrial electrical remodeling) have been demonstrated in a number of different animal models, the clinical significance of this process is unknown. We describe a patient in whom there has been documented progression of atrial ectopy to persistent AF accompanied by evidence of atrial electrical remodeling, with reversal of remodeling following successful ablation of the focal source of AF. A second patient with focal AF, but with a “nonfocal” appearance on the ECG, is also described. These cases illustrate: (1) the possibility that a significant proportion of younger patients with idiopathic persistent AF may well have a focal source as the underlying abnormality; and (2) atrial electrical remodeling reverses following ablation of the underlying source.
Relation Between Cellular Repolarization Characteristics and Critical Mass for Human Ventricular Fibrillation
Authors: WU TSU‐JUEY , YASHIMA MASAAKI , DOSHI RAHUL , KIM YOUNG‐HOON , ATHILL CHARLES A. , ONG JAMES J.C. , CZER LAWRENCE , TRENTO ALFREDO , BLANCHE CARLOS , KASS ROBERT M. , GARFINKEL ALAN , WEISS JAMES N. , FISHBEIN MICHAEL C. , KARAGUEUZIAN HRAYR S. , CHEN PENG‐SHENG
Published: April 2007

Critical Mass for Human Ventricular Fibrillation. Introduction: The critical mass for human ventricular fibrillation (VF) and its electrical determinants are unclear. The goal of this study was to evaluate the relationship between repolarization characteristics and critical mass for VF in diseased human cardiac tissues.

Methods and Results: Fight native hearts from transplant recipients were studied. The right ventricle was immediately excised, then perfused (n = 6) or superfused (n = 2) with Tyrode's solution at 36° C. The action potential duration (APD) restitution curve was determined by an S1‐S2 method. Programmed stimulation and burst pacing were used to induce VF. In 3 of 8 tissues, 10 μM cromakalim, au ATP‐sensitive potassium channel opener, was added to the perfusate and the stimulation protocol repeated. Results show that, at baseline, VF did not occur either spontaneously or during rewarming, and it could not he induced by aggressive electrical stimulation in any tissue. The mean APD at 90% depolarization (APD90) at a cycle length of 600 msec was 227 ± 49 msec, and the mean slope of the APD restitution curve was 0.22 ± 0.08. Among the six tissues perfused, five were not treated with any antiarrhythmic agent. The weight of these five heart samples averaged 111 ± 23 g (range 85 to 138). However, after cromakalim infusion, sustained VF (> 30 min in duration) was consistently induced. As compared with baseline in the same tissues, cromakalim shortened the APD90 from 243 ± 32 msec to 55 ± 18 msec (P < 0.001) and increased the maximum slope of the APD restitution curve from 0.24 ± 0.11 to 1.43 ± 0.10 (P < 0.01).

Conclusion: At baseline, the critical mass for VF in diseased human hearts in vitro is > 111 g. However, the critical mass for VF can vary, as it can he reduced by shortening APD and increasing the slope of the APD restitution curve.
Characteristics of Ischemic and Peri‐Ischemic Regions During Ventricular Fibrillation in the Canine Heart
Authors: RANKOVIC VLADIMIR , PATEL NIKHIL , JAIN SANDEEP , ROBINSON NIKKI , GOLDBERGER JEFEREY , HORVATH GEORGE , KADISH ALAN
Published: April 2007

Ischemic Ventricular Fibrillation. Introduction: Although premature heats originating in areas of ischemia have been shown to he important in initiating ventricular fibrillation (VF), the participation of the ischemic zone in maintenance of VF has not been investigated.

Methods and Results: Ten normal dogs underwent induction of two separate episodes of VF, before and 10 minutes after left anterior descending coronary artery ligation. Ischemic VF was allowed to occur spontaneously or was induced by burst pacing after 10 minutes of ischemia. Unipolar epicardial electrograms were recorded using an 8 × 14 plaque electrode array (interelectrode distance 2.5 mm) placed over the anterior wall. Activation during VF was characterized by VF cycle length (CL) and wavefront organization based on linking analysis of epicardial activation directions at adjacent sites. Individual plaque sites were separated into regions based on electrogram morphology during ischemia: R1 = no ischemia; R2 = mild‐to‐moderate ischemia (minor ST elevation and QRS widening); and R3 = severe ischemia (marked ST elevation and QRS widening). Percent conduction block was calculated based on the percent of cycles during which sites were not activated during VF. There were no significant differences noted in mean CL or mean percent conduction block in the peri‐ischemic region R1 compared to the same region under nonischemic (control) conditions. During ischemia, the mean CL was noted to increase in R2 from 111 ± 14 msec (control) to 128 ± 29 msec (ischemia) and in R3 from 113 ± 14 msec (control) to 150 ± 42 msec (ischemia) (P < 0.05). The percentage conduction block in R2 increased from 6%± 11% (control) to 14%± 16% (ischemia) and in R3 from 4%± 6% (control) to 44%± 21% (ischemia) (P < 0.05). Linking analysis revealed no significant changes in VF organization at distances of 2.5 mm in regions R1 and R2 under both control and ischemic conditions. Premature heats initiating fibrillation originated at the border between the normal and mildly ischemic zones.

Conclusions: (1) Some VF characteristics are altered in ischemic regions including a longer VFCL and greater percentage of functional block. (2) VF characteristics are unchanged in immediately adjacent nonischemic myocardium. (3) Although the ischemic zone may he involved in the initiation of VF and has unique activation characteristics during VF, it does not affect VF characteristics in the adjacent nonischemic zone, suggesting that it may not play a major role in VF maintenance.
Repetitive Electrical Remodeling by Paroxysms of Atrial Fibrillation in the Goat:
Authors: GARRATT CLIFFORD J. , DUYTSCHAEVER MATTIAS , KILLIAN MATTHUS , DORLAND RICK , MAST FRANS , ALLFSSIE MAURITS A.
Published: April 2007

Repetitive Atrial Electrical Remodeling. introduction: Episodes of atrial fibrillation (AF) are known to cause both a rapid reduction in atrial refractoriness (atrial electrical remodeling) and a more delayed increase in AF stability in the chronic goat model. The aims of this study were to examine (1) the hypothesis that an AF‐induced increase in AF stability might be due to a mechanism with a longer onset and offset than that of changes in refractoriness and (2) the possibility that repeated paroxysms of maintained AF might cause a cumulative increase in AF stability independent of changes in atrial refractoriness.

Methods and Results: AF was maintained by rapid atrial pacing in seven goats for three consecutive 5‐day periods, each separated from each other by 48 hours of sinus rhythm. Assessments of atrial refractory periods, conduction velocity, AF inducibility, and duration of individual episodes of AF were attempted at intervals throughout the protocol. Forty‐eight hours of sinus rhythm was just sufficient for refractoriness changes to fully reverse in all goats, with no evidence of any “residual” increase in AF inducibility. There was no significant difference among any of the three periods of pacing‐maintained AF with regard to time to develop episodes of AF of 60‐second duration (22.1 ± 13, 23.8 ± 16, and 30.3 ± 29 hours), 1‐hour duration (56.6 ± 28, 61.3 ± 31, and 60.1 ± 32 hours), or 24‐hour duration (84.0 ± 31, 87.0 ± 33, and 83.5 ± 32 hours).

Conclusion: There is no evidence for a cumulative effect of AF paroxysms on AF inducibility or stability independent of changes in refractoriness. These findings highlight the importance of atrial refractoriness as a potential target for antiarrhythmic strategies aimed at inhibiting the self‐perpetuation of AF.
The M Cell:
Authors: ANTZELEVITCH CHARLES , SHIMIZU WATARU , YAN GAN‐XIN , SICOURI SERGE , WEISSENBURGER JACQUES , NESTERENKO VLADISLAV V. , BURASHNIKOV ALEXANDER , DI DIEGO JOSE , SAFFITZ JEFEREY , THOMAS GEORGE P.
Published: April 2007

Characteristics of the M Cell. The discovery and characterization of the M cell, a unique cell type residing in the deep layers of the ventricular myocardium, has opened a new door in our understanding of the electrophysiology and pharmacology of the heart in both health and disease. The hallmark of the M cell is the ability of its action potential to prolong much more than that of other ventricular myocardial cells in response to a slowing of rate and/or in response to agents that act to prolong action potential duration. Our goal in this review is to provide a comprehensive characterization of the M cell, its contribution to transmural heterogeneity, and its role in the normal electrical function of the heart, in the inscription of the ECG (particularly the T wave), and in the development of QT dispersion, T wave alternans, long QT intervals, and cardiac arrhythmias, such as torsades de pointes. Our secondary goal is to address the controversy that has arisen relative to the functional importance of the M cell in the normal heart. The controversy derives largely from the failure of some investigators to demonstrate transmural heterogeneity of repolarization in the dog in vivo under control conditions and after administration of quinidine. The inability to demonstrate transmural heterogeneity under these conditions may he due to the use of bipolar recording techniques that, in our experience, seriously underestimate transmural dispersion of repolarization (TDK). The use of sodium pentobarhital and α‐chloralose as anesthesia also is problematic, because these agents reduce or eliminate TDR by affecting a variety of ion channel currents. Finally, attempts to amplify transmural dispersion of repolarization with an agent such as quinidine must take into account that relatively high concentrations can result in effects opposite to those desired due to drug inhibition of multiple ion channels. These observations may explain the inability of earlier studies to detect the M cell.
Persistent Atrial Flutter in Patients Treated for Atrial Fibrillation with Amiodarone and Propafenone:
Authors: TAI CHING‐TAI , CHIANG CHERN‐EN , LEE SHIH‐HUANG , CHEN YI‐JEN , YU WEN‐CHUNG , FENG AN‐NING , DING YU‐AN , CHANG MAU‐SONG , CHEN SHIH‐ANN
Published: April 2007

Antiarrhythmic Drug‐Related Atrial Flutter. introduction: Antiarrhythmic drugs have been reported to promote the conversion of atrial fibrillation to atrial flutter inn patients with paroxysmal atrial fibrillation. However, information about the electrophysiologic mechanism and response to radiofrequency ablation of these drug‐induced atrial flutters is limited. Furthermore, the determinants of the development of persistent atrial flutter in patients treated for atrial fibrillation with antiarrhythmic drugs are still unknown.

Methods and Results: Among the 136 patients treated for atrial fibrillation with amiodarone (n = 96) or propafenone (n = 40), 15 (11%, mean age 65.5 ± 12.3 years) were identified to have subsequent development of persistent atrial flutter based on surface ECG characteristics during antiarrhythmic drug treatment. The mean interval between the beginning of drug treatment and the onset of atrial flutter was 5.0 ± 5.5 months. Intracardiac mapping and entrainment studies revealed that 11 patients had counterclockwise typical atrial flutter, and 4 had clockwise typical atrial flutter. All 15 patients underwent successful ablation with creation of complete bidirectional isthmus conduction block. After a mean follow‐up of 12.3 ± 4.2 months, 14 (93%) of 15 patients who underwent successful ablation and continued taking antiarrhythmic drugs have remained in sinus rhythm. Univariate analysis of clinical variables demonstrated that only atrial enlargement was significantly related to the occurrence of persistent atrial flutter.

Conclusion: In patients with atrial fibrillation, persistent typical atrial flutter might occur during antiarrhythmic drug treatment, and atrial enlargement was a risk factor for the development of such an arrhythmia. Radiofrequency ablation and continuation of pharmacologic therapy offered a safe and effective means of achieving and maintaining sinus rhythm.
Localization of the Sites of Conduction Abnormalities in a Mouse Model of Myotonic Dystrophy
Authors: SABA SAMIR , VANDERBRFNK BRIAN A. , LUCIANO BRENDA , ARONOVITZ MARK J. , BERUL CHARLES I. , REDDY SITA , HOUSMAN DAVID , MENDELSOHN MICHAEL E. , ESTES MARK , WANG PAUL J.
Published: April 2007

Heart Block in a Mouse Model of Myotonic Dystrophy. Introduction: A mouse strain lacking functional myotonic dystrophy protein kinase (DMPK) has recently been developed. DMPK‐/‐ mice exhibit muscular and conduction abnormalities consistent with the disease; however, the site of abnormal cardiac conduction is unknown.

Methods and Results: Nine homozygous DMPK‐/‐ mice and seven age matched wild‐type (WT) controls underwent in vivo electrophysiologic studies using an endocardial 2‐French catheter. Baseline intervals as well as Wenckebach and 2:1 cycle lengths were measured to assess AV and ventriculoatrial (VA) conduction. Effective refractory periods (ERP) and functional refractory periods were determined during atrial and ventricular premature stimulation. His‐bundle recordings were obtained on all the studied animals (16/16). DMPK‐/‐ mice bad significantly prolonged PR (48.1 ± 5.5 vs 40.9 ± 3.9 msec, P = 0.010) and AH (36.7 ± 4.0 vs 31.6 ± 4.8 msec, P = 0.037) intervals compared to WT controls. HV intervals were very significantly prolonged as well (14.7 ± 2.0 vs 10.3 ± 0.8 msec; P < 0.0001). Three of 9 DMPK‐/‐ and I of 7 WT mice exhibited VA block. Atrial ERP was reached before AV node ERP in 2 (22%) of 9 of the knockout mice and 5 (71%) of 7 of the controls (P = 0.06). Only one mouse (DMPK‐/‐) exhibited infra‐Hisian block on premature atrial stimulation.

Conclusion: In this mouse model of myotonic dystrophy, AV conduction abnormalities were localized to the supra‐Hisian and infra‐Hisian conduction tissues, with a higher predilection to the latter, a finding similar to the human form of the disease.
Canine Ventricular Myocyte β2‐Adrenoceptors Are Not Functionally Coupled to L‐Type Calcium Current
Authors: NAGYKALDI ZSOLT , KEM DAVID , LAZZARA RALPH , SZABO BELA
Published: April 2007

Selective Stimulation of β AR Subtypes and ICaL.Introduction: To establish the functional coupling of beta adrenoceptor (βAR) subtypes β1, AR and β2AR to L‐type calcium current (ICaL)we investigated the nonselective agonist isoproterenol (ISO) and the relatively selective β1AR antagonists zinterol (ZIN) and salbutamol (SAL) on ICaLin isolated canine ventricular myocytes in the presence and absence of CGP 20712A (CGP) and atenolol (AT), selective β1AR antagonists, and ICI 118,551 (ICI) a selective β2AR antagonist.

Methods and Results: Peak ICaLdetermined using “patch type” microelectrodes and whole cell voltage clamp. ISO (0.5 μM) increased ICaL, maximally 3.5 ± 0.67 fold. ZIN (10.0 μM) and SAL (10.0 μM) increased ICaLmaximally 1.5 ± 0.2 fold (n = 5) and 1.4 ± 0.1 fold (n = 5) respectively. These effects were fully inhibited by CGP (0.3 μM) and AT (1.0 μM), which are inhibitors of β1AR, but not by ICI (0.1 μM), which is a β2AR inhibitor. ZIN at relatively lower concentrations (≤0.1 μM) did not increase ICaL. CGP (0.3 μM) but not AT and ICI inhibited ICaLin the absence of βAR agonists. CGP inhibition of ICaL, was absent in the presence of forskolin (1.0 μM), which increases cAMP levels and ICaLby directly stimulating the adenylate cyclase. These data indicate that none of the antagonists affect ICaLthrough an action downstream βAR.

Conclusion: β‐Adrenergic agonists increase ICaLvia β1AR but not β2AR in canine ventricular myocytes.