bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrotonic Inhibition and Active Facilitation of Excitability in Ventricular Muscle
Authors: DAVIDENKO JORGE M. , DELMAR MARIO , BEAUMONT JACQUES , MICHAELS DONALD C. , LORENTE PACO , JALIFE JOSÉ 
Published: May 2007

Inhibition and Facilitation in Cardiac Muscle. Introduction: The effects of subthreshold electrical pulses on the response to subsequent stimulation have been described previously in experimental animal studies as well as in the human heart. In addition, previous studies in cardiac Purkinje fibers have shown that diastolic excitability may decrease after activity (active inhibition) and, to a lesser extent, following subthreshold responses (electrotonic inhibition). However, such dynamic changes in excitability have not been explored in isolated ventricular muscle, and it is uncertain whether similar phenomena may play any role in the activation pal‐terns associated with propagation abnormalities in the myocardium. Methods and Results: Experiments were performed in isolated sheep Purkinje fibers and papillary muscles, and in enzymatically dissociated guinea pig ventricular myocytes. In all types of preparations introduction of a conditioning subthreshold pulse between two subthreshold pulses was followed by a transient decay in excitability (electrotonic inhibition). The degree of inhibition was directly related to the amplitude and duration of the conditioning pulse and inversely related to the postconditioning interval. Yet, inhibition could be demonstrated long after (> 1 sec) the end of the conditioning pulse. Electrotonic inhibition was found at all diastolic intervals and did not depend on the presence of a previous action potential. In Purkinje fibers, conditioning action potentials led to active inhibition of subsequent responses. In contrast, in muscle cells, such action potentials had a facilitating effect (active facilitation). Electrotonic inhibition and active facilitation were observed in both sheep ventricular muscle and guinea pig ventricular myocytes. Accordingly, during repetitive stimulation with pulses of barely threshold intensity, we observed: (1) bistability (i.e., with the same stimulating parameters, stimulus: response patterns were either 1:1 or 1:0, depending on previous history), and (2) abrupt transitions between 1:1 and 1:0 (absence of intermediate wenckebach‐like patterns). Simulations utilizing an ionic model of cardiac myocytes support the hypothesis that electrotonic inhibition in well‐polarized ventricular muscle is the result of partial activation of Ik following subthreshold pulses. On the other hand, active facilitation may be the result of an activity‐induced decrease in the conductance of IK1. Conclusion: Diastolic excitability of well‐polarized ventricular myocardium may be transiently depressed following local responses and transiently enhanced following action potentials. On the other hand, diastolic excitability decreases during quiescence. Active facilitation and electrotonic inhibition may have an important role in determining the dynamics of excitation of the myocardium in the presence of propagation abnormalities.
Characterization of an E4031‐Sensitive Potassium Current in Quiescent AT‐1 Cells
Authors: LIU YANING , TAFFET STEVEN M. , ANUMONWO JUSTUS M.B. , DELMAR MARIO 
Published: May 2007

IKr in Quiescent AT‐1 Cells. Introduction; A cardiac culture cell line (AT‐1) recently has been generated from transgenic mice. Initial studies have yielded opposing results as to the nature of the major repolarizing current(s) in these cells. The present study describes the ion selectivity, voltage dependence, and E4031 sensitivity of the major time‐dependent outward current present in AT‐1 cells. In addition, we have determined whether an outward current with the characteristics we observed could be capable of modulating action potential duration in a frequency‐dependent manner (for stimulation cycle lengths between 250 and 1000 msec). Methods and Results: Action potentials and membrane currents were recorded from nonconffuent cultures of quiescent AT‐1 cells using the “perforated patch” technique. AT‐1 cells showed a round appearance 1 or 2 days after plating. An E4031‐insensitive transient outward current seemed to be absent in these cells. The main time‐dependent outward current was a rapidly activating and rectifying potassium current with properties similar to those of IKr. Most of the potassium current was sensitive to the benzenesulfonamide E4031 (5 μM). The same concentration of E4031 led to a 38% increase in action potential duration. Action potential parameters were independent of the stimulation cycle length within the range of 250 to 1000 msec, thus suggesting that the membrane currents involved in the action potential of AT‐1 cells are completely reset within a diastolic interval of approximately 150 msec. Conclusion: AT‐1 cells present a unique electrophysiologic phenotype, which is clearly different from that reported for freshly dissociated adult atrial or ventricular myocytes from other species. AT‐1 cells may be a good model to study IKr, since there seems to be minimal contamination by other outward conductances (such as ik). In addition, the feasibility of culturing AT‐1 cells provides us with a system where electrophysiologic experiments on IKr currents could be combined with biochemical or molecular biological studies requiring significant periods of incubation in a cell culture system.
Reversibility of Electrophysiologic Abnormalities of Subendocardial Purkinje Fibers Induced by Ischemia
Authors: REN XIAO‐LI , HOFFMAN BRIAN F. 
Published: May 2007

Subendocardial Purkinje Fibers. Introduction: During the subacute phase of infarction in the canine heart, the Subendocardial Purkinje fibers subtended by the infarct show depolarization greater than can be accounted for by the decrease in (K), and generate abnormal action potentials and spontaneous rhythms due to abnormal automaticity. We have used pinacidil to hyperpolarize these fibers and evaluate the extent to which an increase in resting potential can normalize action potential generation. Methods and Results: Twenty‐four hours after two‐stage ligation of the canine left anterior descending coronary artery, preparations of Subendocardial Purkinje fibers were studied in vitro by recording transmembrane potentials through standard microelectrodes and exposing the preparation to pinacidil and increases in (K+)0. Pinacidil increased resting potential to the estimated value of EK, abolished the abnormal automaticity, and restored action potentials of normal amplitude with normal values of Vmax. This effect often persisted after washout of pinucidil. Elevation of (K+), from 4.0 to 20.0 mM slightly increased maximum diastolic potential, suggesting (hat the excess (over the change in EK) depolarization was caused by a decrease in gKl. Conclusion: The ventricular arrhythmias seen during the subacute stage of infarction probably are caused by abnormal automaticity. Our findings support the conclusion that this abnormal automaticity arises in partially depolarized suhendocardial Purkinje fibers. This loss of resting potential is due in large part to a decrease in gK1. Restoration of resting potential to the value of Ek permits the Purkinje fibers to develop essentially normal action potentials. An agent capable of reversing the partial block of 1K1, thus might be an effective drug for some types of arrhythmias.
Failure of Impulse Propagation in a Mathematically Simulated Ischemic Border Zone: Influence of Direction of Propagation and Cell‐to‐Cell Electrical Coupling
Authors: MULLER‐BORER BARBARA J. , JOHNSON TIMOTHY A. , GETTES LEONARD S. , CASCIO WAYNE E. 
Published: May 2007

Propagation in a Modeled Ischemic Border Zone. Introduction: It is suggested that heterogeneous extracellular potassium concentration, cell‐to‐cell coupling, and geometric nonuniformities of the ischemic border zone contribute to the incidence of unidirectional block and subsequent development of lethal ventricular arrhythmias. Method and Results: A discrete electrical network was used to model a single cardiac fiber with a [K+]e gradient characteristic of an ischemic border zone. Directional differences in propagation were evaluated by creating discrete regions with increased gap junctional resistance within the [K+]e gradient. Furthermore, the effect of homogeneity/heterogeneity of cell length on impulse propagation through the [K+]e gradient in the presence of increased gap junctional resistance was evaluated. The results indicate that failure of impulse propagation occurs at the junction between partially uncoupled and normally coupled cells. Furthermore, propagation failure was more likely to occur as the impulse propagated from a region of high [K+]e to low [K+]e. Heterogeneity in cell length contributes to the variability in the occurrence of unidirectional and bidirectional block. Conclusions: The onset of cellular uncoupling in an ischemic border zone may interact with the inherent [K+]e gradient leading to unidirectional conduction block. This mechanism may be important for the generation of reentrant arrhythmias at the ischemic border zone.
Computation of Heart Surface Potentials Using the Surface Source Model
Authors: SIMMS HOWARD D. , GESELOWITZ DAVID B. 
Published: May 2007

Heart Surface Source Model. Introduction: The bidomain model of the heart leads to the result that the volume density of cardiac current source moment is proportional to the gradient of the macroscopic transmembrane action potential distribution. If the anisotropy ratios of the inner and outer domains (syncytia) of the myocardium are equal, then the volume distribution of cardiac sources can be replaced by an appropriate double layer on the heart surface. The double layer source distribution (heart surface source model) provides a basis for calculating heart surface potentials from cardiac sources. Methods and Results: The heart surface model was used to calculate epicardial potentials for the normal heart as well as for a case of ischemia and of infarction. The model was also used to determine the effect of insulating the heart surface. Insulating the heart surface caused an almost fourfold increase in peak‐to‐peak amplitude of simulated electrograms, with little change in waveshape. Simulated electrograms showed good agreement with recorded electrograms reported in the literature. Conclusion: The heart surface source model appears to provide a basis for relating heart surface potentials to the distribution of cellular action potential.
Reperfusion Arrhythmias: Role of Early Afterdepolarizations Studied by Monophasic Action Potential Recordings in the Intact Canine Heart During Autonomically Denervated and Stimulated States
Authors: VERA ZAKAUDDIN , PRIDE HARALD P. , ZIPES DOUGLAS P. 
Published: May 2007

Reperfusion Arrhythmias and Afterdepolarizations. Introduction: The precise mechanism of reperfusion arrhythmias is not established. The role of early afterdepolarizations (EADs) and triggered activity in the genesis of reperfusion ventricular arrhythmia was investigated. Methods and Results: Monophasic action potentials (MAPs) were recorded in the canine heart using Ag‐AgCl contact electrodes from the left and right ventricular endocardium and the left ventricular epicardial border zone during 10 minutes of occlusion of the proximal left anterior descending coronary artery followed by 2 minutes of reperfusion. Ventricular arrhythmias during ischemia and reperfusion were studied in three autonomically varied groups. Group 1 (n = 8) had intact autonomic neural innervation; group 2 (n =8) had bilateral transection of ansae subclavii and vagi; and group 3 (n =8) underwent bilateral transaction of ansae subclavii and vagi with bilateral ansae subclavii stimulation during reperfusion. Ventricular fibrillation (VF) on reperfusion occurred in 2, 3, and 5 animals in the innervated, denervated, and sympathetically stimulated groups, respectively. Rapid ventricular tachycardia during ansae subclavii stimulation, antecedent to VF, occurred in 4 of 5 episodes in the sympathetically stimulated group. The frequency of premature ventricular complexes, couplets, and triplets on reperfusion was not significantly different among the three groups. Phase 2 or phase 3 EADs were noted during the acute ischemic phase in 6 of 8, 7 of 8, and 7 of S animals in the three groups, respectively (and persisted during reperfusion in the majority). Thus, these EADs were not a de novo phenomenon during reperfusion. Of the 72 MAP recording sites, only one demonstrated de novo phase 2 EADs during reperfusion. EADs disappeared during reperfusion in 6 animals (prior to the onset of VF in 4), and 5 dogs developed reperfusion VF without EADs being recorded. There was no direct correlation between tbe presence of EADs during repertusion and the development of VF. The prevalence and onset of reperfusion VT was not significantly different in tbe presence of sympathetic stimulation. Conclusion: This study demonstrates that EADs can be recorded in the majority of dogs during both ischemia and reperfusion and do not appear to be a major mechanism responsible for reperfusion ventricular tachycardia and VF.
A Quantitative Fluoroscopic Comparison of the Coronary Sinus Ostium in Patients With and Without AV Nodal Reentrant Tachycardia
Authors: HUMMEL JOHN D. , STRICKBERGER S. ADAM , MAN K. CHING , DAOUD EMILE , NIEBAUER MARK , MORADY FRED 
Published: May 2007

Coronary Sinus Ostium. Introduction: The purpose of this study was to perform a quantitative fluoroscopic analysis of the coronary sinus ostium and its relationship to the His bundle in patients with and without AV nodal reentrant tachycardia. Sites of slow pathway ablation are often near the coronary sinus ostium, which can be located within a few millimeters of the His bundle. Whether such close proximity of the coronary sinus ostium to the His bundle is unique to patients with AV nodal reentrant tachycardia is unknown. Methods and Results: Fifty consecutive patients (mean age 39 ± 14 years) with no structural heart disease underwent electrophysiologic testing and radiofrequency ablation. The study group consisted of 28 patients with inducible AV nodal reentrant tachycardia or dual AV nodal physiology and 22 patients in the control group. A coronary sinus venogram was performed in each patient. The coronary sinus ostium was similar in size in the study group (11.4 ± 4.5 mm) and in the control group (10.5 ± 3.6 mm, P = 0.2). The coronary sinus ostium was funnel shaped in half of the study patients and in half of the control patients (P = 1.0). The mean distance from the upper lip of the coronary sinus ostium to the tip of the His bundle catheter was 9.7 ± 5.5 mm in the study group and 10.4 ± 5.1 mm in the control group (P = 0.7). The mean distance from the lower lip of the coronary sinus ostium to the tip of the His‐bundle catheter in the study group was 20.1 ± 6.1 mm and 19.5 ± 5.6 mm in the control group (P =0.7). Conclusion: This study demonstrates a wide range of normal coronary sinus ostium diameters, morphology, and anatomic relationships with surrounding structures, with no demonstrable correlation to the presence or absence of dual AV node physiology or AV nodal reentrant tachycardia.
Slowing of the Ventricular Rate During Atrial Fibrillation by Ablation of the Slow Pathway of AV Nodal Reentrant Tachycardia
Authors: TEBBENJOHANNS JÜRGEN , PFEIFFER DIETRICH , SCHUMACHER BURGHARD , JUNG WERNER , MANZ MATTHIAS , LÜDERITZ BERNDT 
Published: May 2007

Influence of Slow Pathway Ablation on Atrial Fibrillation. Introduction: The mechanisms whereby radiofrequency catheter modification of AV nodal conduction slows the ventricular response are not well defined. Whether a successful modification procedure can be achieved by ablating posterior inputs to the AV node or by partial ablation of the compact AV node is unclear. We hypothesized that ablation of the well‐defined slow pathway in patients with AV nodal reentrant tachycardia would slow the ventricular response during atrial fibrillation. Methods and Results: In 34 patients with dual AV physiology and inducible AV nodal reentrant tachycardia, atrial fibrillation was induced at baseline and immediately after successful slow pathway ablation and at 1‐week follow‐up. The minimal, maximal, and mean RR intervals during atrial fibrillation increased from 353 ± 76,500 ± 121, and 405 ± 91 msec to 429 ± 84 (P < 0.01), 673 ± 161 (P < 0.01), and 535 ± 98 msec (P < 0.01), respectively. These effects remained stable during follow‐up at 1 week. The AV block cycle length increased from 343 ± 68 msec to 375 ± 60 msec (P < 0.05) immediately and to 400 ± 56 msec (P < 0.01) at 1‐week follow‐up. The effective refractory period of the AV node prolonged from 282 ± 83 msec to 312 ± 89 msec and to 318 ± 81 msec after 1 week (P < 0.05), respectively. Conclusion: This study shows a decrease in ventricular response to pacing‐induced atrial fibrillation after ablation of the slow pathway in patients with AV nodal reentrant tachycardia. Since the AV nodal conduction properties could be defined, this study supports the hypothesis that the main mechanism of AV nodal modification in chronic atrial fibrillation is caused by ablation of posterior inputs to the AV node.
Temperature Monitoring in Radiofrequency Catheter Ablation of Atrial Flutter Using the Linear Ablation Technique
Authors: WEN ZU‐CHI , CHEN SHIH‐ANN , TAI CHING‐TAI , CHIANG CHERN‐EN , LEE SHIH‐HUANG , CHEN YI‐JEN , YU WEN‐CHUNG , HUANG JIN‐LONG , CHANG MAU‐SONG 
Published: May 2007

Temperature Monitoring of Ablation. Introduction: Information about temperature and impedance monitoring during radiofrequency catheter linear ablation of atrial flutter bas not been reported. We proposed that a radiofrequency catheter ablation system using a closed‐loop temperature control model could decrease the incidence of coagulum formation and shorten the radiation exposure and procedure times compared with those found in a power control model. Methods and Results: Forty patients (8 women and 32 men; mean age 64 ± 7 years) with atrial flutter were referred for radiofrequency ablation. The patients were randomized into two groups: group I patients underwent radiofrequency catheter linear ablation of atrial flutter using a power control of energy output model; and group II patients underwent the closed‐loop temperature control model with a target electrode temperature of 70°C. As compared with group II, group I patients bad a higher incidence of coagulum formation (12% vs 2%, P < 0.05), temperature shutdown (11% vs 0%, P < 0.01), and impedance shutdown (16% vs 3%, P < 0.01), more radiofrequency applications (7 ± 3 vs 4 ± 2, P < 0.01), and longer procedure time (100 ± 25 vs 75 ± 23 minutes, P < 0.05) and radiation exposure time (31 ± 10 vs 20 ± 7 minutes, P < 0.05) required for successful ablation. Larger deviations of temperature (9.0°± 2.4°C vs 5.0°± 1.2°C, P < 0.0001) and impedance (9.2 ± 2.6 ω vs 5.3 ± 1.6 ω, P < 0.0001) were also found in group I patients compared with those in group II. Conclusions: This study demonstrated that a closed‐loop temperature control model could facilitate the effects of radiofrequency catheter ablation of the atrial flutter circuit by decreasing coagulum formation, temperature and impedance shutdown, and procedure and radiation exposure times.
Alteration of Human Placental Vascular Tone by Antiarrhythmic Medications In Vitro
Authors: OMAR HATIM A. , RHODES LARRY A. , RAMIREZ ROLANDO , ARSICH JELICA , EINZIG STANLEY 
Published: May 2007

Antiarrhythmic and Placental Vessels. Introduction: Antiarrhythmic medications are commonly used during pregnancy for treatment of maternal or fetal arrhythmias, but little is known about their effect on human placental vascular tone and, consequently, placental blood flow. The objective of this study was to evaluate the tone responses caused by antiarrhythmic medications in human placental vessels from normal term pregnancies in vitro. Methods and Results: Isolated human placental arteries and veins from uncomplicated term pregnancies incubated in Krebs'‐bicarbonate under 5% oxygen/5% carbon dioxide/balance nitrogen (PO2 35 to 38 torr) were exposed to cumulative doses of quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, digoxin, and adenosine after submaximal contraction with 5‐hydroxytryptamine. The study was conducted both in the presence and absence of endothelium. The addition of the tested medications caused a significant, dose‐dependent relaxation of human placental arteries and veins except for adenosine, which induced a sustained, dose‐dependent contraction of human placental vessels regardless of the presence or absence of tone. Removal of the endothelium did not alter these responses. Conclusions: Based on these results, the medications tested should have no decremental effect on placental blood flow, with the possible exception of adenosine, which causes significant. dosedependent contraction of human placental vessels in vitro. Should similar contraction be present in vivo, it may have an adverse effect on the fetus when administering adenosine to pregnant women at term or during labor.
Plateau Waveform Shape Allows a Much Higher Patient Shock Energy Tolerance in AF Patients
Authors: BORIANI GIUSEPPE , EDVARDSSON NILS , BIFFI MAURO , SILVESTRI PAOLO , MARTIGNANI CRISTIAN , VALZANIA CINZIA , DIEMBERGER IGOR , CHRISTOPHER MOULDER J. , MOUCHAWAR GABRIEL , POCI DRITAN , BRANZI ANGELO , KROLL MARK W. 
Published: May 2007

Objectives: To evaluate the possible pain reduction of the plateau waveform in atrial fibrillation (AF) patients. Background: Previous studies have indicated that reduced amplitude waveforms would be less painful than a conventional (65/65% tilt) biphasic waveform. Computer modeling suggested that a moderately long (10–12 msec) plateau (flat topped) shock waveform would deliver equivalent effectiveness with the lowest possible peak amplitude. Methods: We enrolled 27 patients at two sites with persistent AF with a total of 220 shocks delivered during internal atrial cardioversion using an interleaved crossover design. Patient response was scored in three ways: (1) a verbally reported discomfort score, (2) visual analog scale (VAS), and (3) a blinded observer reporting a contraction score. Results: All scores were significantly reduced (P < 0.0001) by the plateau waveform with impressive statistics: Verbal discomfort (3.51 ± 0.13 to 2.89 ± 0.12), VAS (7.00 ± 0.56 to 5.91 ± 0.36), and contraction scores (1.94 ± 0.12 to 1.62 ± 0.12). The average pain threshold shift (TS) for the Verbal score was 2.34, while that for the VAS score was 2.30. (This means that the patient typically could tolerate 2.34 times as much energy with the plateau waveform for the same level of verbally reported discomfort.) The contraction TS was less at 1.57. Response scores were also corrected for the shock sequence number to control for the sensitization effect from multiple shocks. This increased the TS for the Verbal score to 3.58, but the shock number was not significant for the VAS. A pulmonary artery electrode return was associated with lower pain compared with a coronary sinus position. Conclusion: A plateau shaped biphasic waveform resulted in significantly increased shock energy pain tolerances. Controlling for session sensitization, patients tolerated over three times as much energy for the same verbally reported discomfort score.