bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
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.
Characterization of a Novel Missense Mutation in the Pore of HERG in a Patient with Long QT Syndrome
Authors: YOSHIDA HIDETADA , HORIE MINORU , OTANI HIDEO , TAKANO MAKOTO , TSUJI KEIKO , KUBOTA TOMOYUKI , FUKUNAMI MASATAKE , SASAYAMA SHIGETAKE 
Published: April 2007

HERG Mutation and Long QT Syndrome. introduction: A new strategy to elucidate the molecular mechanisms underlying the long QT syndrome (LQTS) is now available with genetic mutational analyses and characterization of ion channel mutations. Methods and Results: In a 26‐year‐old woman with LQTS, we identified a novel missense mutation in the pore of HERG by using polymerase chain reaction/single‐strand conformation polymorphism (PCR/SSCF) and sequencing of her genomic DNA. The mutation resulted in an amino acid substitution of a positively charged lysine for a highly conserved uncharged asparagine at codon 629 (N629K). Whole cell, patch clamp studies were conducted in COS7 cells by transfecting with wild‐type (WT) and/or the mutant N629K HERG. The WT HERG produced an IKr‐like, E‐4031‐sensitive conductance with an inward rectification. In contrast, the cells transfected with the N629K HERG did not display any time‐dependent current. Cotransfection of WT and N629K HERG (at a ratio of 1:1) produced a significantly smaller conductance when compared with WT HERG (WT 59.9 ± 7.3 pA/pF [n = 22] vs WT+N629K 5.5 ± 2.3 pA/pF [n = 11]; P < 0.01), but did not alter K+ ion selectivity and tail current‐voltage dependence. Because aprindine hydrochloride was effective in preventing ventricular tachycardias, we also tested the effect of the drug on WT HERG (IKr) and KvLQT1/KCNE1 (IKs) currents expressed in COS7. Conclusion: Functional analyses of a novel missense mutation in the pore of HERG suggest that the mutation causes marked reduction of IKr via a dominant negative effect.
Determinants of Efficacy of Atrial Pacing in Preventing Atrial Fibrillation Recurrences
Authors: STABILE GIUSEPPE , SENATORE GAETANO , De SIMONE ANTONIO , TURCO PIETRO , COLTORTI FERNANDO , NOCERINO PASQUALE , VITALE DINO FRANCO , CHIARIELLO MASSIMO 
Published: April 2007

Atrial Pacing in Atrial Fibrillation. Introduction: Several studies have shown that single or dual site atrial pacing is effective in reducing he frequency of recurrent atrial fibrillation (AF) in selected patients. However, it is still unclear what the best predictors are of long‐term efficacy of atrial pacing. Methods and Results: Forty‐seven patients with paroxysmal AF requiring demand pacing underwent electrophysiologic study and dual chamber pacemaker implant. After 4 months of follow‐up, patients were divided into two groups according to the presence (group 1) or absence (group 2) of symptomatic AF recurrences. Atrial pacing markedly reduced AF recurrences in all patients. Twenty‐four patients were free of arrhythmia. The basal state conduction times (CTs) and the incremental conduction times (ICTs), during programmed electric stimulation between the high right atrium (HRA) and the coronary sinus ostium (CSos) but not between the HRA and the His‐bundle region, were significantly longer in group 1. There was no statistical difference in the effective refractory period (ERP) recorded at the HRA, the low right atrium (LRA), and the CSs between the two groups, whereas the differences between the greatest and least recorded ERPs measured from the HRA, LRA, and CSos (δERP) were significantly greater in group 1 patients. Two parameters were selected by discriminant multivariate analysis, namely δCTos (ICT‐CT between HRA and CSos and δERP. The first bad a greater relative importance in predicting AF recurrence (r2= 0.33 and r2= O.1, respectively). Conclusion: Single site atrial pacing is effective in reducing AF recurrences, with decreasing efficacy in patients with greater right atrial conduction delay and wider refractoriness dispersion.