bluuebunny/crossref_metadata_2025 huggingface dataset:
Function, Regulation, Pharmacology, and Molecular Structure of ATP‐Sensitive K+ Channels in the Cardiovascular System
Authors: ISOMOTO SHOJIRO , KURACHI YOSHIHISA
Published: April 2007

KATP Channels in Cardiovascular System. ATP‐sensitive K+ (KATP) channels are inhibited by intracellular ATP and activated by intracellular nucleoside diphosphates, and thus provide a link between cellular metabolism and excitability. KATP channels are widely distributed in various tissues and may be associated with diverse cellular functions. In the heart, the KATP channel appears to be activated during ischemic or hypoxic conditions and may be responsible for the increase of K+ efflux and shortening of the action potential duration. Therefore, opening of this channel may result in cardioprotective as well as proarrhythmic effects. In the vascular smooth muscle, the KATP channel is believed to mediate the relaxation of vascular tone. Thus, KATP channels play important regulatory roles in the cardiovascular system. Furthermore, KATP channels are the targets of two important classes of drugs, i.e., the antidiabetic sulfonylureas, which block the channels, and a series of vasorelaxants called “K+ channel openers,” which tend to maintain the channels in an open conformation. Recently, the molecular structure of KATP channels has been clarified. The KATP channel in pancreatic β‐cells is a complex composed of at least two subunits, a member of inwardly rectifying K+ channels and a sulfonylurea receptor. Subsequently, two additional homologs of the sulfonylurea receptor, which form cardiac and smooth muscle type KATP channels, respectively, have been reported. Further works are now in progress to understand the molecular mechanisms of KATP channel function.
Magnetocardiography and 32‐Lead Potential Mapping
Authors: BROCKMEIER KONRAD , SCHMITZ LOTHAR , CHAVEZ JOSÉ DE JESUS BOBADILLA , BURGHOFF MARTIN , KOCH HANS , ZIMMERMANN ROGER , TRAHMS LUTZ
Published: April 2007

Repolarization of the Magnetocardiogram. Signals from 37 magnetocardiographic sensors and simultaneously recorded 32 ECG leads were obtained in three healthy male subjects (including two reinvestigations). After recordings at rest, the heart rate was increased by pharmacologic stress (117 to 142 beats/min). Comparison of the repolarization of rest and stress showed substantial changes in the magnetocardiogram (MCG) up to T wave inversions during stress. In the ECG only junctional ST‐T segment shifts were present. Eor quantification, correlation coefficients between pairs of rest and stress MCG and rest and stress ECG distributions were calculated for the same time instant at the beginning of T wave under rest and stress conditions. In addition, equivalent electrical current dipole moment and magnetic dipole moment vectors were calculated from the MCG, and their cbange from rest to stress evaluated. Correlation coefficients for MCG comparison ranged from 0.3 to 0.5; ECG comparison suggested much less change from stress, ranging from 0.7 to 1.0. Current dipole moment changes at T wave onset were marginal; in contrast, the magnetic dipole moment changed substantially. Since the magnetic dipole refiects vortex currents, changes in its intensity and/or orientation during repolarization suggest this as the biophysical basis of the striking difference in the response of the MCG and ECG to pharmacologic stress. Normal ECG findings at rest and under stress in healthy subjects support the conclusion that the repolarization changes in the MCG were of nonpathologic origin.
Effects of Slow Pathway Ablation on Fast Pathway Function in Patients with Atrioventricular Nodal Reentrant Tachycardia
Authors: SHEN WIN‐KUANG , MUNGER THOMAS M. , STANTON MARSHALL S. , OSBORN MICHAEL J. , HAMMILL STEPHEN C. , PACKER DOUGLAS L.
Published: April 2007

Effects of Slow Pathway Ablation. Introduction: This study investigated whether fast pathway conduction properties are altered by slow pathway ablation in patients with AV nodal reentrant tacbycardia.

Methods and Results: Forty consecutive patients who underwent successful ablation of the slow pathway were prospective subjects for the study. Isoproterenol was used to enhance conduction and to differentiate interactive mechanisms. Potential electrotonic interactions were assessed by comparing patients with and those without residual dual AV node pbysiology after slow pathway ablation. Paired and unpaired t‐tests were used when appropriate. P < 0.05 was considered statistically significant. In the entire study population, heart rates were not significantly different before and after slow pathway ablation (RR = 770 ± 114 msec before and 745 ± 99 msec after, P = 0.07). Anterograde fast pathway conduction properties were unchanged after slow pathway ablation (effective refractory period, 348 ± 84 msec before and 336 ± 86 msec after, P = 0.13; shortest 1:1 conduction, 410 ± 93 msec before and 400 ± 82 msec after, P = 0.39). Retrograde fast pathway characteristics also were similar before and after ablation. Neither anterograde nor retrograde last pathway conduction properties during isoproterenol infusion were changed by slow pathway ablation. When the study population was further divided into patients with (n= 13) or without (n = 27) residual dual AV node pbysiology, no significant change was detected in fast pathway function in either group after slow patbway ablation.

Conclusions: Fast pathway conduction characteristics were not affected by slow pathway ablation. In patients with AV nodal reentrant tachycardia, observations suggest that fast and slow pathways are functionally distinct.
Responses to Norepinephrine of Normal and “Ischemic” Canine Purkinje Fibers are Consistent with Activation of Different α1‐Receptor Subtypes
Authors: ANYUKHOVSKY EVGENY P. , GUO SHI‐DUO , DANILO PETER , ROSEN MICHAEL R.
Published: April 2007

α1‐Receptor Subtype Stimulation of Purkinje Fibers. Introduction: Previously we found that WB4101 (WB) 10‐7 M competitively blocks three α1‐adrenergic receptor‐effector responses: the increase in normal automaticity occurring in Purkinje fibers (PF) at high membrane potentials: the increase in abnormal automaticity occurring in PF at depolarized membrane potentials; and the prolongation of PF action potential duration. These observations are consistent with two different hypotheses: (1) WB blocks a single α1‐receptor subtype, which subserves different effector pathways; and (2) WB blocks different receptor subtypes, eacb of which subserves an independent patbway. The aim of this study was to test both hypotheses.

Methods and Results: We used standard microelectrode techniques to study the concentration‐dependent actions of three α1‐adrenoreceptor blockers (WB (α1A≫α1D], 5‐methylurapidil [5‐MU] [α1A, ≫α1D], and UK52,046 [nonselective]) on norepinephrine (NK) effects in normal PF and in PF depolarized with a simulated ischemic solution ([K+]o= 10 mM; pO2 < 20 mmHg; pH 6.8; maximum diastolic potential ‐60 ± 1 mV). In normally polarized PF, concentration‐dependent actions of all blockers on both the positive cbronotropic response and the prolongation of action potential duration completely coincide. In contrast, the response to NE of abnormal automaticity in “ischemic” PF differs from normals: there is a bigh sensitivity to WB and 5‐MU and no response to UK52,046.

Conclusions: (1) A single receptor subtype appears responsible for botb the α1‐induced prolongation of repolarization and the positive chronotropic effect in normal PF. (2) Two different receptor subtypes may be responsible for the α1‐induced effects on automaticity in normal and ischemic fibers. It is likely that the latter one is α1A, and that consideration of antiarrhythmic therapy with α1‐adrenergic blockers should focus on this subtype as a potential target.
Early Afterdepolarizations Produced by d,1‐Sotalol and Clofilium
Authors: PATTERSON EUGENE , SCHERLAG BENJAMIN J. , LAZZARA RALPH
Published: April 2007

EAD Formation by Class III Drugs. Introduction: The roles for L‐type calcium current and Na‐Ca exchange in early afterdepolarizations (EADs) attending d, l‐sotalol and clofilium were examined in canine Purkinje fibers and in enzymatically dispersed myocytes from canine subepicardium.

Methods and Results: Spontaneous EADs were compared to EAD formation potentiated by stimulation of Na‐Ca exchange and facilitation of ICa‐L (Bay K8644). Bay K8644 (10‐8 M) and stimulation of Na‐Ca exchange potentiated bradycardia‐dependent EADs. Stimulation of Na‐Ca exchange in Pnrkinje fibers pretreated with d, l‐sotalol (10‐5 M) and clofilium (10‐7 M) induced EADs at takeoff potentials negative (‐63 ± 4 and ‐62 ± 4 mV, respectively) to EADs potentiated by Bay K8644 (10‐8 M) (‐33 ± 2 and ‐34 ± 2 mV, respectively, P < 0.05), or EADs induced by Bay K8644 alone (10‐6 M) (‐31 ± 5 mV). In myocytes, Bay K8644 (10‐8 M) potentiated EADs in d, l‐sotalol‐ (10‐6 to 10‐4M) or clofilium‐treated (10‐9 to 10‐7 M) cells at reduced potentials (‐10 ± 3 and ‐10 ± 4 mV, respectively) compared to EADs elicited by clofilium or d, l‐sotalol alone (‐25 ± 3 and ‐24 ± 3 mV, respectively), or stimulation of Na‐Ca exchange in the presence of d, l‐sotalol or clofilium (‐26 ± 4 and ‐26 ± 4 mV, respectively). Spontaneous EADs or EADs elicited by stimulation of Na‐Ca exchange coincident with drug treatment were suppressed by increasing Cao2+ but were not suppressed by nifedipine (10‐7 M).

Conclusion: EADs elicited by d, l‐sotalol and clolllium in canine Purkinje tissue and epicardial myocytes are dependent upon Na‐Ca excbange rather than ICa‐L“window current.”
Role of Intracellular Sodium Overload in the Genesis of Cardiac Arrhythmias
Authors: LEVI ALLAN J. , DALTON GEOFF R. , HANCOX JULES C. , MITCHESON JOHN S. , ISSBERNER JON , BATES JENNIFER A. , EVANS STEPHEN J. , HOWARTH F. CHRIS , HOBAI ION A. , JONES JOHN V
Published: April 2007

Intracellular Na and Arrhythmia. A number of clinical cardiac disorders may be associated with a rise of the intracellular Na concentration (Nai) in heart muscle. A clear example is digitalis toxicity, in which excessive inhibition of the Na/K pump causes the Nai concentration to become raised above the normal level. Especially in digitalis toxicity, but also in many other situations, the rise of Nai may be an important (or contributory) cause of increased cardiac arrhythmias. In this review, we consider the mechanisms by which a raised Nai may cause cardiac arrhythmias. First, we describe the factors that regulate Nai, and we demonstrate that the equilibrium level of Nai is determined by a balance between Na entry into the cell, and Na extrusion from the cell. A numher of mechanisms are responsible for Na entry into the cell, whereas the Na/K pump appears to be the main mechanism for Na extrusion. We then consider the processes by which an increased level of Nai might contrihute to cardiac arrhythmias. A rise of Nai is well known to result in an increase of intracellular Ca, via the important and influential Na/Ca exchange mechanism in the cell membrane of cardiac muscle cells. A rise of intracellular Ca modulates the activity of a numher of sarcolemmal ion channels and aflects release of intracellular Ca from the sarcoplasmic reticulum, all of which might be involved in causing arrhythmia. It is possible that the increase in contractile force that results from the rise of intracellular Ca may initiate or exacerbate arrhythmia, since this will increase wall stress and energy demands in the ventricle, and an increase in wall stress may be arrhythmogenic. In addition, the rise of Nai is anticipated to modulate directly a number of ion channels and to affect the regulation of intracellular pH, which also may be involved in causing arrhythmia. We also present experiments in tbis review, carried out on the working rat heart preparation, which suggest that a rise of Nai causes an increase of wall stress‐induced arrhythmia in this model. In addition, we have investigated the effect on wall stress‐induced arrhythmia of maneuvers that might be anticipated to change intracellular Ca, and this has allowed identification of some of the factors involved in causing arrhythmia in the working rat heart.
Reproducibility of the Adenosine‐5′‐Triphosphate Test in Vasovagal Syndrome
Authors: FLAMMANG DANIEL , CHASSING ANNICK , DONAL ERWAN , HAMANI DJAMEL , ERICKSON MARK , McCARVILLE SALLY
Published: April 2007

Vasovagal Syndrome: ATP Test Reproducibility. Introduction: Adenosine‐5′‐triphosphate (ATP) provokes negative chronotropic and dromotropic vagal effects. In vasovagal syndrome, ATP test (20‐mg IV bolus infusion) represents a promising technique for identifying patients at risk of severe cardioinhibitory response of vagal origin. The electrocardiographic and related symptom reproducibility of this descriptive test must be assessed.

Methods and Results: In order to achieve this objective, ATP tests were performed twice in 80 patients (44 men, 36 women; mean age 72.3 ± 12.2 years) by using the recently published test procedure and criteria of positivity. The second test was repeated shortly after the initial test (mean: 7 days) in 43 patients and long‐term (mean: 3.7 years) in 37 patients. The initial ATP test provoked a cardiac pause > 10 seconds in 31 patients (39%) and a short cardiac pause (< 10 sec) or n pause in 49 patients (61%). The electrocardiographic outcome was reproduced during the second ATP test in 36 patients (84%) of the short‐term group and in 29 patients (78%) of the long‐term group. Similarly, symptoms were reproduced in 38 patients (88%) of the short‐term group and 29 patients (78%) of the long‐term group, reflecting the severity of the electrocardiographic outcome.

Conclusion: The negative chronotropic and dromotropic vagal effect of ATP can he reproduced short term and long term in 84% and 78% of patients, respectively. Associated symptoms were related to the severity of the electrocardiographic outcome.
Retrograde Purkinje Potential Activation During Sinus Rhythm Following Catheter Ablation of Idiopathic Left Ventricular Tachycardia
Authors: TADA HIROSHI , NOGAMI AKIHIKO , NAITO SHIGETO , TOMITA TOMOYUKI , OSHIMA SHIGERU , TANIGUCHI KOICHI , AONUMA KAZUTAKA , IESAKA YOSHITO
Published: April 2007

Idiopathic Left VT and Purkinje Potentials. We describe two patients with idiopathic left ventricular tachycardia that were cured by radiofrequency catheter ablation. Tachycardia was inducible by ventricular stimulation and was verapamil sensitive. Two distinct presystolic potentials (PI and P2) were recorded during tachycardia in the mid‐septal or inferoapical area, but only one potential (P2) was recorded during sinus rhythm. After catheter ablation at this site, the PI potential was noted after the QRS complex during sinus rhythm, while the P2 was still observed before the QRS complex. The P1 potential showed a decremental property during atrial or ventricular pacing. These data suggest that Purkinje tissue with decremental properties was responsible for the tachycardia mechanism, and that the reentry circuit involving this tissue is likely to be of considerable size.
Verapamil‐Sensitive Left Anterior Fascicular Ventricular Tachycardia: Results of Radiofrequency Ablation in Six Patients
Authors: NOGAMI AKIHIKO , NAITO SHIGETO , TADA HIROSHI , OSHIMA SHIGERU , TANIGUCHI KOICHI , AONUMA KAZUTAKA , IESAKA YOSHITO
Published: April 2007

Verapamil‐Sensitive Left Anterior Fascicular VT. Introduction: Verapamil‐sensitive left ventricular tachycardia (VT) with a right bundle branch block (RBBB) configuration and left‐axis deviation bas been demonstrated to arise from the left posterior fascicle, and can be cured by catheter ablation guided by Purkinje potentials. Verapamil‐sensitive VT with an RBBB configuration and right‐axis deviation is rare, and may originate in the left anterior fascicle.

Methods and Results: Six patients (five men and one woman, mean age 54 ± 15 years) with a history of sustained VT with an RBBB configuration and right‐axis deviation underwent electrophysiologic study and radiofrequency (RF) ablation. VT was slowed and terminated by intravenous administration of verapamil in all six patients. Left ventricular endocardial mapping during VT identified the earliest ventricular activation in the anterolateral wall of the left ventricle in all patients. RF current delivered to this site suppressed the VT in three patients (ablation at the VT exit). The fused Purkinje potential was recorded at that site, and preceded the QRS complex by 35, 30, and 20 msec, with pace mapping showing an optimal match between the paced rhythm and the clinical VT. In the remaining three patients, RF catheter ablation at the site of the earliest ventricular activation was unsuccessful. In these three patients, Purkinje potential was recorded in the diastolic phase during VT at the mid‐anterior left ventricular septum. The Purkinje potential preceded the QRS during VT by 66, 56, and 63 msec, and catheter ablation at these sites was successful (ablation at the zone of slow conduction). During 19 to 46 months of follow‐up (mean 32 ± 9 months), one patient in the group of ablation at the VT exit bad sustained VT with a left bundle branch block configuration and an inferior axis, and one patient in the group of ablation at the zone of slow conduction experienced typical idiopathic VT with an RBBB configuration and left‐axis deviation.

Conclusion: Verapamil‐sensitive VT with an RBBB configuration and right‐axis deviation originates close to the anterior fascicle. RF catheter ablation can be performed successfully from the VT exit site or the zone of slow conduction where the Purkinje potential was recorded in the diastolic phase.
Lead Fixation in Dogs Achieved with RF Energy
Authors: BONNER MATTHEW , MEHRA RAHUL , ZIPES DOUGLAS P.
Published: April 2007

Lead Fixation in Dogs Achieved with RF Energy. Introduction: The purpose of this study was to test whether radiofrequency (RF) energy could be used to fixate leads to the endocardium.

Methods and Results: In six dogs we measured the dislodgment force and pacing threshold before and after RF Fixation in the coronary sinus (CS) and right ventricle (RV). RF fixation was achieved with a CardioRhythm Atakr* ablation unit. The dislodgment force of CS leads fixed with RF energy was 1.63 ± 0.65 oz, compared with < 0.1 oz for similar leads placed in the CS of six separate dogs. In the RV, leads fixed with RF energy had a dislodgment force of 1.29 ± 0.27 oz, compared with 0.48 ± 0.28 oz. for urethane (P < 0.01) and 1.01 ± 0.21 oz for silicone (P= 0.41) tined leads. In the CS, the pacing threshold for RF fixed leads increased significantly from 2.2 ± 1.1 V (0.5 msec) before fixation to 4.2 ± 1.3 V after fixation (P < 0.01), while in the RV, the pacing threshold increased from 0.41 ± 0.05 V (0.5 msec) before fixation to a mean of 2.03 ± 0.44 V after fixation (P < 0.01). In another group of six dogs studied for 12 weeks. 5 of 6 RF fixed CS leads remained attached, as did 8 of 10 RF fixed RV leads. For the RV leads, the mean pacing threshold was 0.90 ± 0.35 V, compared with 0.53 ± 0.18 V (0.5 msec) for similar tined leads (P= 0.02) and 1.2 ± 0.30 V (0.5 msec) for screw leads (P= 0.18) in the RV.

Conclusion: We conclude that RF energy can be used to attach leads to the RV and CS endocardium. While the RV pacing thresholds increased acutely, the mean chronic thresholds were not significantly different for RF fixed leads and standard tined or screw leads.
Evolution of the Organization of Epicardial Activation Patterns During Ventricular Fibrillation
Authors: HUANG JIAN , ROGERS JACK M. , KENKNIGHT BRUCE H. , ROLLINS DENNIS L. , SMITH WILLIAM M. , IDEKER RAYMOND E.
Published: April 2007

Activation During Ventricular Fibrillation. Introduction: This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF).

Activation During Ventricular Fibrillation. Introduction: This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF).

Methods and Results: Unipolar potentials were mapped from a 504 (24 × 21) electrode array (2‐mm interelectrode spacing) on the anterior right ventricle (RV) and left ventricle (LV) epicardium. The array covered approximately 20% of the epicardial surface. In each of seven pigs, six episodes of VF were induced by premature stimulation. One‐half second epochs of VF were analyzed, starting 0, 10, 20, 30, and 40 seconds post induction and using novel pattern analysis algorithms. Eight parameters were quantified: (1) the number of wavefronts; (2) the epicardial area activated by wavefronts; (3) the fraction of wavefronts arising from epicardial breakthrough or from a focus; (4) the fraction of wavefronts terminated by conduction block; (5) the multiplicity index (number of distinct activation pathways in the rhythm); (6) the repeatability index (number of times activation pathways are traversed); (7) the activation rate; and (8) the wavefront propagation velocity. The results showed that VF patterns were less organized at 10 than at 0 seconds, with more, smaller wavefronts traversing a larger variety of pathways for fewer repetitions. VF activation patterns then gradually reorganized up to 40 seconds, but by a different mechanism: the spatial size of subpatterns grew, but the dynamics otherwise appeared unchanged. During both transitions, both activation rate and propagation velocity slowed monotonically.

Conclusion: Thus, changes in organization during VF can occur by multiple mechanisms.
Radiofrequency Current Application on Immature Porcine Atrial Myocardium: No Evidence of Areas of Slow Conduction After 12‐Month Follow‐Up
Authors: WINDHAGEN‐MAHNERT BRITTA , BOKENKAMP REGINA , BERTRAM HARALD , PEUSTER MATTHIAS , HAUSDORF GERD , PAUL THOMAS
Published: April 2007

Electrophysiologic Sequelae 12 Months After Radiofrequency Current Application. Introduction: Radiofrequency current (RFC) application is a widely used procedure for treatment of supraventricular arrhythmias. The purpose of this study was to investigate late electrophysiologic sequelae of RFC lesions at immature atrial myocardium in pigs, as they have not yet been systematically investigated in vitro.

Methods and Results: RFC application (temperature guided) was performed in seven piglets (mean age 6 weeks) by a steerahle 6‐French electrode catheter positioned at the lateral aspect of the tricuspid valve annulus. After 12 months, hearts were removed, and lesions with surrounding tissue were isolated. The viable tissue at the border of the specimen was paced with a cycle length of 500 and 600 msec. One hundred fifty impalements were performed on each specimen using capillary microelectrodes to record action potential characteristics from the lesion's surface and the surrounding tissue. In all seven specimens, no transmembrane action potentials from the fibrotic surface of each of the lesions could be recorded. The surrounding viable tissue was sharply demarcated electrically. No areas of slow conduction were detected. Action potential characteristics as mean maximum diastolic transmembrane potential, mean action potential duration at 90% repolarization, and upstroke velocity of phase 0 of the action potential were all normal.

Conclusion: No evidence of areas of slow conduction 12 months after RFC application at immature atrial myocardium suggests that this technique is safe regarding occurrence of late atrial tachyarrhythmias after the procedure.
Effect of Skin Electrode Location on Radiofrequency Ablation Lesions: An In Vivo and a Three‐Dimensional Finite Element Study
Authors: JAIN MUDIT K. , TOMASSONI GERY , RILEY RICHARD E. , WOLF PATRICK D.
Published: April 2007

Skin Electrode Location Affects RF Ablation Lesions. Introduction: Objectives: To assess the effect of skin electrode location on radiofrequency (RF) ablation lesion dimensions and energy requirements. Background: Little is known about the effects of skin electrode location on RF ablation lesion dimensions and efficiency.

Methods and Results: Temperature‐controlled ablation at 60°C for 60 seconds was performed in six sheep. Paired lesions were created in the lateral, anterior, posterior, and septal walls of both the ventricles. For group 1 lesions, the skin electrode was positioned directly opposite the catheter tip (optimal). For group 2 lesions, we used either the standard posterior location or an anterior location if the posterior skin electrode location was used for group 1. Group 1 lesions were 5.8 × 0.8 mm deep and 9.3 × 1.9 mm wide, compared with 4.6 × 1.0 m deep and 7.7 × 1.9 mm wide group 2 lesions (P < 0.001). Group 1 lesion dimensions also bad less variability. A finite element model was used to simulate temperature‐controlled ablation and to study the effect of skin electrode locations on lesion dimensions, ablation efficiency, and blood beating. The optimal location was 1.6 times more efficient, and the volume of blood heating to ≥ 90° C was 0.005 mm3 for optimal versus 2.2 mm3 for the nonoptimal location.

Conclusion: Optimal skin electrode placement: (1) creates deeper and larger lesions; (2) reduces lesion size variability; and (3) decreases blood beating.
Cytochalasin D as Excitation‐Contraction Uncoupler for Optically Mapping Action Potentials in Wedges of Ventricular Myocardium
Authors: WU JIASHIN , BIERMANN MARTIN , RUBART MICHAEL , ZIPES DOUGLAS P.
Published: April 2007

Myocardium Immobilization for Repolarization Mapping. Introduction: Cytochalasin D In tissue bath superfusate inhihits the contraction of isolated thin trabeculae from canine right ventricle without affecting the intracellular action potential recorded with glass microelectrode. The purpose of this study was to test whether cytochalasin D could also be used to immobilize perfused wedges of ventricular muscle without affecting the action potential duration or propagation, and also to determine the optimal concentration and time duration of drug in the perfusate.

Methods and Results: Using a membrane potential sensitive dye, di‐4‐ANEPPS, and a high‐resolution photodiode optical mapping system at a rate of 1,000 frames/sec, we recorded action potentials on the transmural surface of arterially perfused wedges of muscle from the canine left ventricular free wall. We also recorded arterial pulse pressure as a surrogate for tissue contraction. Cytochalasin D at ≥ 20 μmol/L in the perfusate for ≥ 6 minutes reduced the arterial pulse pressure to approximately one tenth of its initial value and significantly reduced or eliminated motion artifacts in the action potentials. A sustained concentration of 10μmol/L cytochalasin D in the perfusate prevented contraction from recurring after the tissue was immobilized with an initial concentration of 25 μmol/L. Cytochalasin D had little effect on the action potential duration and on its transmural gradient, and did not slow the transmural velocity of excitation propagation.

Conclusion: Cytochalasin D can be used to uncouple excitation and contraction in perfused canine cardiac muscle for the fluorescent‐optical mapping of action potentials without affecting action potential duration or slowing transmural propagation.
Differential Effects of Cytochalasin D and 2, 3 Butanedione Monoxime on Isometric Twitch Force and Transmembrane Action Potential in Isolated Ventricular Muscle: Implications for Optical Measurements of Cardiac Repolarization
Authors: BIERMANN MARTIN , RUBART MICHAEL , MORENO ALONSO , WU JIASHIN , JOSIAH‐DURANT AVONELLE , ZIPES DOUGLAS P.
Published: April 2007

Cytochalasin D Induced Cardiac Contraction Failure. Introduction: 2,3‐Butanedione monoxime (BDM) has been widely used to inhibit contraction during optical recordings of cardiac membrane voltage changes, even though it markedly abbreviates cardiac action potentials.

Methods and Results: We compared the effects of BDM and of the F‐actin disrupter cytochalasin D (cyto D) on isometric twitch force and transmembrane action potentials in isolated canine right ventricular trabeculae superfused with Tyrode's solution (2 mmol/L CaCl2, 37°C) and stimulated at 0.5 Hz. BDM at 10 mmol/L and cyto D at 80 μmol/L were equally effective in reducing peak isometric force to 10%± 3% (n = 6; mean ± SEM) and 8%± 1% (n = 8), respectively. Neither agent significantly altered resting tension. While 10 mmol/L BDM markedly shortened the action potential duration at 90% repolarization (APD90) from 198 ± 7 msec to 146 ± 9 msec (P < 0.001), 80 μmol/L cyto D had no significant effects on APD90 or on any other action potential parameter. The effects of BDM on peak isometric force and APD were completely reversible after 15 minutes of washout, whereas in the cyto D group contractile force continued to be reduced (13%± 3%) and action potential characteristics did not show significant changes from control values after a 60‐minute period of superfusion with cyto D‐free Tyrode's solution.

Conclusion: We conclude that cyto D should be considered an alternative excitation‐contraction uncoupler for optical mapping studies of cardiac repolarization.
Atrial Electrophysiologic Remodeling: Another Vicious Circle?
Authors: ALLESSIE MAURITS A.
Published: April 2007

AF‐Induced Electrophysiologic Remodeling. Introduction: With few exceptions, acquired heart di.sease is the result of (gradual changes in the heart, progressing during several months or years. This also includes certain cardiac arrhythmias, as for instance atrial fihrillation (AF). In spite of the important role of slowly progressing pathologic processes, most of our knowledge about mechanisms of cardiac arrhythmias is hased on acute experiments. Only recently, the attention also is more focused on long‐term adaptation processes like cardiac memory, electrical remodeling, and tachycardia‐induced cardiomyopathy. In experimental animal models, it has heen shown that AF induces a vicious circle of electrophysiologic and structural changes that inevitahly leads to “domestication” of the arrhythmia (“AF begets AF”). In this article, the studies on AF‐induced electrophysiologic and cellular remodeling are discussed.
Effect of Ventricular Shock Strength on Cardiac Hemodynamics
Authors: TOKANO TAKASHI , BACH DAVID , CHANG JASON , DAVIS JAMES , SOUZA JOSEPH J. , ZIVIN ADAM , KNIGHT BRADLEY P. , GOYAL RAJIVA , MAN K. CHING , MORADY FRED , STRICKBERGER S. ADAM
Published: April 2007

Ventricular Defibrillation and Cardiac Function. Introduction: The effect of implantable defibrillator shocks on cardiac hemodynamics is poorly understood. The purpose of this study was to test the hypothesis that ventricular defibrillator shocks adversely effect cardiac hemodynamics.

Methods and Results: The cardiac index was determined by calculating the mitral valve inflow with transesophogeal Doppler during nonthoracotomy defibrillator implantation in 17 patients. The cardiac index was determined before, and immediately, 1 minute, 2 minutes, and 4 minutes after shocks were delivered during defibrillation energy requirement testing with 27‐ to 34‐, 15‐, 10‐, 5‐, 3‐, or 1‐J shocks. The cardiac Index was also measured at the same time points after 27‐ to 34‐, and 1‐J shocks delivered during the baseline rhythm. The cardiac index decreased from 2.30 ± 0.40 L/min per m2 before a 27‐ to 34‐J shock during defibrillation energy requirement testing to 2.14 ± 0.45 L/min per m2 immediately afterwards (P= 0.001). This effect persisted for >4 minutes. An adverse hemodynamic effect of similar magnitude occurred after 15 J (P= 0.003) and 10‐J shocks (P= 0.01), but dissipated after 4 minutes and within 2 minutes, respectively. There was a significant correlation between shock strength and the percent change in cardiac index (r = 0.3, P= 0.03). The cardiac index decreased 14% after a 27‐ to 34‐J shock during the baseline rhythm (P < 0.0001). This effect persisted for <4 minutes. A 1‐ J shock during the baseline rhythm did not effect the cardiac index.

Conclusion: Defibrillator shocks >9 J delivered during the baseline rhythm or during defibrillation energy requirement testing result in a 10% to 15% reduction in cardiac index, whereas smaller energy shocks do not affect cardiac hemodynamics. The duration and extent of the adverse effect are proportional to the shock strength. Shock strength, and not ventricular fibrillation, appears to be most responsible for This effect. Therefore, the detrimental hemodynamic effects of high‐energy shocks may be avoided when low‐energy defibrillation is used.
Delayed Activation of Cardiac Swelling‐Induced Chloride Current After Step Changes in Cell Size
Authors: SOROTA STEVE , DU XIAO‐YI
Published: April 2007

Cardiac ICl,swelling Activation Time Course.
Introduction: A lag phase has been reported for the activation of cardiac swelling‐induced chloride currents. Prior demonstrations of this lag used methods that produce gradual changes in cell size, making interpretation and quantification of the time course problematic.

Methods and Results: Isolated dog atrial cells were studied using the whole cell, patch clamp technique. Step changes in cell size were produced by application of transient pulses of positive pressure, and the time course for activation of the swelling‐induced chloride current was observed. There was a distinct temporal dissociation between size changes and current activation that was temperature sensitive. Activation half‐times were 98 ± 31 seconds and 586 ± 112 seconds at 36°C and room temperature, respectively. Swelling‐induced chloride currents were evoked in a higher percentage of cells at 36° (83%) compared with room temperature (50%).

Conclusion: Cardiac swelling‐induced chloride current activates with a distinct lag after step changes in cell size. The activation time course is temperature sensitive. These observations are consistent with the notion that signal transduction events, and not simply membrane stretch, are required for the activation of cardiac swelling‐induced chloride current.
Class IC Antiarrhythmic Drugs, Flecainide and Pilsicainide, Produce ST Segment Elevation Simulating Inferior Myocardial Ischemia
Authors: NAKAMURA WAKO , SEGAWA KAZUHIKO , ITO HIROYUKI , TANAKA SHUGO , YOSHIMOTO NOBUO
Published: April 2007

ST Elevation with Flecainide and Pilsicainide. Flecainide and pilsicainide, Class IC antiarrhythmic drugs with slow kinetics, were administered to a 64‐year‐old man experiencing ventricular tachycardia. Both drugs suppressed the arrhythmia, but caused ST segment elevation in leads II, III, and aVF. No evidence of ischemic heart disease was detected. Withdrawal of the drugs eliminated the ST change. Because these drugs frequently are used to treat tachyarrhythmias in patients who may present with chest pain, this rare ECG manifestation of Class IC drugs should he recognized to avoid misdiagnosis of acute interior myocardial infarction.
Beat‐to‐Beat Repolarization Lability Identifies Patients at Risk for Sudden Cardiac Death
Authors: ATIGA WALTER L. , CALKINS HUGH , LAWRENCE JOHN H. , TOMASELLI GORDON F. , SMITH JOSEPH M. , BERGER RONALD D.
Published: April 2007

QT Interval Variability and Sudden Death. Introduction: Recent studies have implicated repolarization lability in the genesis of malignant ventricular arrhythmias. However, few data exist on assessment of temporal QT interval variability and its relation to arrhythmogenesis. We tested the ability of the QT variability index (QTVI), a measure of beat‐to‐beat QT interval fluctuations measured on a single ECG lead, to identify patients presenting with malignant ventricular arrhythmias and predict their subsequent occurrences.

Methods and Results: We measured the QTVI in 95 patients presenting for electrophysiologic study (EPS). The ability of the QTVI to identify patients with sudden cardiac death (SCD) or sustained monomorphic ventricular tachycardia (MVT) on presentation and during follow‐up of 23.7 ± 14.3 months was compared with spatial QT dispersion, T wave alternans ratio during atrial pacing, MVT inducibility at EPS, signal‐averaged ECG, heart rate variability, and ejection fraction. The QTVI was higher in patients with heart disease than in controls (‐0.7 ± 0.7 vs −1.1 ± 0.5, P < 0.05), and higher in patients presenting with SCD than in other patients with heart disease (0.0 ± 0.6 vs −0.8 ± 0.5, P < 0.05). The QTVI was the only clinical variable that identified patients who presented with SCD (P= 0.004, odds ratio = 12.5) on stepwise, logistic multiple regression. Fourteen patients had arrhythmic events during follow‐up. In a Kaplan‐Meier analysis of arrhythmic events, QTVI ≥ 0.1 was a discriminator for higher risk of arrhythmic events (P < 0.05).

Conclusions: (1) This noninvasive measure of temporal repolarization lability identified patients with SCD and predicted arrhythmia‐free survival. (2) Further studies are needed to determine the mechanisms that mediate beat‐to‐beat QT interval variability.
Cesium‐Induced Atrial Tachycardia Degenerating into Atrial Fibrillation in Dogs: Atrial Torsades de Pointes?
Authors: SATOH TADASHI , ZIPES DOUGLAS P.
Published: April 2007

Atrial Torsades de Pointes?Introduction: In this study, we investigated whether the potassium channel blocker, cesium chloride (CsC1), which is capable of producing early afterdepolarizations (EADs) and polymorphic ventricular tachyarrhythmias resembling torsades de pointes, might exert similar effects in the atria.

Methods and Results: In nine anesthetized open chest dogs, 5 mL of CsC1 in incremental doses (0.05, 0.1, 0.15, 0.2, 0.25 mM/mL) was injected into the sinus node artery to induce atrial arrhythmias. A polymorphic atrial tachycardia (P‐AT) apparently triggered by an EAD and degenerating into atrial fibrillation resulted after CsC1 administration in six dogs, but not in the remaining three dogs at any dose of CsC1. The P‐AT developed during a normal atrial rate (110 ± 13.5 beats/min) on six occasions and during atrial bradycardia (58.6 ± 17.9 heat/min) five times. P‐AT that occurred during a normal atrial rate had the last normal P wave temporally closely related to ventricular activation, with a VA interval of almost zero (1.3 ± 3.3 msec), whereas P‐AT induced from an atrial hradycardia had no relation to ventricular activation. The%EAD in the atrial hradycardia group (13.9 ± 2.5) exceeded that in the normal atrial rate group (10.9 ± 1.8) (P < 0.05).

Conclusion: CsC1 induces atrial EADs that provoke P‐AT that degenerates into atrial fibrillation. P‐AT has some characteristics similar to ventricular torsades de pointes.
Optimization of Shocking Lead Configuration for Transvenous Atrial Defibrillation
Authors: KRUM DAVID , HARE JOHN , MUGHAL KASHEF , JAZAYERI MOHAMMAD R. , DESHPANDE SANJAY , DHALA ANWER , BLANCK ZALMEN , AKHTAR MASOOD , SRA JASBIR
Published: April 2007

Optimum Electrodes for Atrial Defibrillation. Introduction: High atrial defibrillation energy requirements (ADER) in patients with chronic atrial fibrillation (AF) may limit the acceptance of transvenous atrial defibrillation. We evaluated an optimized defibrillation electrode configuration that could help to reduce the ADKR in patients with AF.

Methods and Results: We tested ten different configurations in nine dogs with AF (3.33 ± 2.92 days) induced by rapid atrial pacing. The configurations were: right atrial (RA) appendage as anode und coronary sinus (CS) as cathode; RA and innominate vein (I) as anode to CS (cathode); RA‐CS (anode) to I (cathode); I‐CS (anode) to RA (cathode); RA and left lateral subcutaneous patch (P) as anode to CS (cathode); RA‐CS (anode) to P (cathode); P‐CS (anode) to RA (cathode); superior vena cava (SVC) and CS (anode) to RA (cathode); RA‐CS (anode) to SVC (cathode); and RA‐SVC (anode) to CS (cathode). ADER was defined as the voltage needed to defibrillate the atria in 10% to 90% of 20 consecutive shocks. Three lead systems had ADER lower than the RA (anode) to CS (cathode) configuration, which required a mean of 143 ± 58 volts. These three were: RA‐SVC (anode) to CS (cathode) 103 ± 29 V; I‐CS (anode) to RA (cathode) 129 ± 39 V; and P‐CS (anode) to RA (cathode) 130 ± 38 V. The remaining configurations had ADER higher than the RA (anode) to CS (cathode) configuration.

Conclusion: Adding an additional shocking electrode may reduce ADER when compared with the RA (anode) to CS (cathode) configuration. This concept could he incorporated into future implantable atrial defibrillators or used for refractory patients undergoing temporary transvenous cardioversion.
Mid‐Diastolic Potential is Related to the Reentrant Circuit in a Patient with Verapamil‐Sensitive Idiopathic Left Ventricular Tachycardia
Authors: AIBA TAKESHI , SUYAMA KAZUHIRO , MATSUO KIYOTAKA , TAGUCHI ATSUSHI , SHIMIZU WATARU , KURITA TAKASHI , AIHARA NAOHIKO , KAMAKURA SHIRO
Published: April 2007

Mid‐Diastolic Potential in Idiopathic VT. We report a case of verapamil‐sensitive idiopathic ventricular tachycardia in which a mid‐diastolic potential (MDP) 45 msec preceding the Purkinje potential (P potential) was recorded. Pacing during the tachycardia caused concealed entrainment, and the stimulus–QRS interval was equal to the P potential–QRS interval. The interval between the last pacing stimulus and the next P potential (postpacing interval) was longer than the ventricular tachycardia cycle length, but the MDP was orthodromically activated. These findings suggest that the MDP was on the reentrant circuit and the P potential was not on the reentrant circuit, but a bystander.
Runaway Pacemaker in an Implantable Cardioverter Defibrillator
Authors: CARPENTER CHARLES M. , GALVIN JOSEPH , GUY MARY , McGOVERN BRIAN A.
Published: April 2007

Runaway Pacemaker in an ICD. Introduction: Runaway pacemaker is a potentially catastrophic complication of any permanent pacing system.

Methods and Results: A 70‐year‐old man was found to have erratic behavior of his implantable cardioverter defibrillator (ICD) during a routine outpatient interrogation. His device was turned off, and he was hospitalized in preparation for a pulse generator replacement. During his hospitalization, his ICD unexpectedly began pacing rapidly. Despite prompt resuscitation attempts, the patient died. Postmortem examination of the device demonstrated a crystal oscillator failure.

Conclusion: A previously unrecognized component malfunction is a potentially lethal complication of ICDs.
Development and Validation of an ECG Algorithm for Identifying Accessory Pathway Ablation Site in Wolff‐Parkinson‐White Syndrome
Authors: ARRUDA MAURICIO S. , McCLELLAND JAMES H. , WANG XANZHUNG , BECKMAN KAREN J. , WIDMAN LAWRENCE E. , GONZALEZ MARIO D. , NAKAGAWA HIROSHI , LAZZARA RALPH , JACKMAN WARREN M.
Published: April 2007

ECG Localization of Accessory AV Pathways. Introduction: Delta wave morphology correlates with the site of ventricular insertion of accessory AV pathways. Because lesions due to radiofrequency (RF) current are small and well defined, it may allow precise localization of accessory pathways. The purpose of this study was to use RF catheter ablation to develop an ECG algorithm to predict accessory pathway location.

Methods and Results: An algorithm was developed by correlating a resting 12‐lead ECG with the successful RF ablation site in 135 consecutive patients with a single, anterogradely conducting accessory pathway (Retrospective phase). This algorithm was subsequently tested prospectively in 121 consecutive patients (Prospective phase). The ECG findings included the initial 20 msec of the delta wave in leads I, II, aVF, and V1 [classified as positive (+), negative (‐), or isoelectric (±)] and the ratio of R and S wave amplitudes in leads III and V1 (classified as R ≥ S or R < S). When tested prospectively, the ECG algorithm accurately localized the accessory pathway to 1 of 10 sites around the tricuspid and mitral annuli or at subepicardial locations within the venous system of the heart. Overall sensitivity was 90% and specificity was 99%. The algorithm was particularly useful in correctly localizing anteroseptal (sensitivity 75%, specificity 99%), and mid‐septal (sensitivity 100%, specificity 98%) accessory pathways as well as pathways requiring ablation from within ventricular venous branches or anomalies of the coronary sinus (sensitivity 100%, specificity 100%).

Conclusion: A simple ECG algorithm identifies accessory pathway ablation site in Wolff‐Parkinson‐White syndrome. A truly negative delta wave in lead II predicts ablation within the coronary venous system.
Acute Effects of Intraoperative Multisite Ventricular Pacing on Left Ventricular Function and Activation/Contraction Sequence in Patients with Depressed Ventricular Function
Authors: SAXON LESLIE A. , KERWIN WALTER F. , CAHALAN MICHAEL K. , KALMAN JONATHAN M. , OLGIN JEEEREY E. , FOSTER ELYSE , SCHILLER NELSON B. , SHINBANE JEROLD S. , LESH MICHAEL D. , MERRICK SCOT H.
Published: April 2007

Multisite Pacing Effect on LV Function. Introduction: We hypothesized that simultaneous right and left ventricular apical pacing would result in improvement in left ventricular function due to improved coordination of segmental ventricular contraction. Structural changes in ventricular muscle present in dilated cardiomyopathy compromise ventricular excitation and mechanical contraction.

Methods and Results: Eleven patients with depressed left ventricular function having cardiac surgery underwent epicardial multisite pacing with continuous transesophageal echocardiographic imaging. Quantitative measurement of percent fractional area change was performed, and segmental changes in contraction sequence resulting from simultaneous right and left ventricular pacing were assessed by application of phase analysis to recorded transesophageal images. There was no statistically significant difference between the paced QRS duration achieved with simultaneous right and left ventricular apical pacing and the native QRS duration (139 ± 39 msec vs 106 ± 18 msec, P = NS), but all other paced modes resulted in longer QRS durations. Percent fractional area change improved with simultaneous right and left ventricular apical pacing hut not with other paced modes (41.5 ± 11.9 vs 34.3 ± 9.7, P < 0.01). Phase analysis demonstrated a resequencing of segmental left ventricular activation/contraction when compared to baseline ventricular activation.

Conclusion: Simultaneous right and left ventricular apical pacing results in acute improvements in global ventricular performance in patients with depressed ventricular function. Improvements may result from pacing‐induced global coordination through recruitment of left and right ventricular apical and septal segments critical to effective ventricular contraction.
A New Classification Algorithm for Discrimination of Ventricular from Supraventricular Tachycardia in a Dual Chamher Implantable Cardioverter Defibrillator
Authors: KORTE THOMAS , JUNG WERNER , WOLPERT CHRISTIAN , SPEHL SUSANNE , SCHUMACHER BURGHARD , ESMAILZADEH BAHMAN , LÜDERITZ BERNDT
Published: April 2007

New Atrioventricular Classification Algorithm. Introduction: The high incidence of inappropriate therapies due to supraventricular tachycardia remains a major unsolved problem of implantable cardioverter defibrillators. We report a new detection formula for discrimination of ventricular tachycardia from supraventricular tachycardia in a patient with a dual chamber implantable cardioverter defibritlator and a new atrioventricular classification algorithm.

Methods and Results: The enhanced detection algorithm performs a stepwise arrhythmia analysis. The rhythm is first classified on the basis of cycle length. Each episode is then classified as supraventricular or ventricular on the basis of atrioventricular association, stability of circle length, and origin of acceleration, Sophisticated diagnostic information is provided by atrioventricular markers and electrogram recordings. Successful discrimination of two spontaneous episodes of ventricular tachycardia and supraventricular tachycardia is demonstrated.

Conclusion: This new dual chamber detection algorithm may significantly improve the specificity of tachyarrhythmia detection without sacrificing sensitivity, thereby reducing the number of spurious shocks in patients with recurrent supraventricular tachycardias. Further studies are needed to assess the sensitivity and specificity of this detection atgorithm.