bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural substrates of microstimulation‐evoked tingling: a chronaxie study in human somatosensory thalamus
Authors: Kiss Zelma H. T. , Anderson Trent , Hansen Terry , Kirstein Dolen , Suchowersky Oksana , Hu Bin 
Published: August 2003

AbstractIntra‐operative micro‐electrode stimulation of sensorimotor thalamus produces paraesthesia or tingling in various body regions and is used to map somatotopy prior to implantation of deep brain‐stimulating electrodes in awake patients. The neural elements affected by such microstimulation are unknown. Using paraesthesia as the behavioural–physiological response threshold, we measured chronaxie times for microstimuli applied to both somatosensory thalamic nuclei (cellular region) and its axonal afferents, the medial lemniscus. White matter chronaxie times were relatively unimodal, whereas two different clusters of chronaxie times were identified in grey matter: one corresponding to that of the medial lemniscus and the other about five times longer and compatible with that obtained from cell somata. Therefore, excitations of local axons and/or cell bodies can both contribute to the paraesthesia evoked during intra‐operative thalamic mapping.
A role for the periaqueductal grey in opioidergic inhibition of maternal behaviour
Authors: Miranda‐Paiva Cláudia M. , Ribeiro‐Barbosa Erika R. , Canteras Newton S. , Felicio Luciano F. 
Published: August 2003

AbstractOpiates are known to be involved in the regulation of various events surrounding parturition and lactation, such as maternal behaviour in rats. The onset of this behaviour has been closely linked to opiate action in the medial pre‐optic area, where administration of morphine disrupts maternal behaviour during lactation. By combining the use of Fos protein immunohistochemical detection and pharmacological manipulations, in the present paper we show that the periaqueductal grey (PAG) is another region critically involved in the opioidergic blockade of maternal behaviour. According to our observations, a critical level of morphine‐induced activation of the rostral lateral PAG appears to be required to inhibit maternal behaviour in lactating rats. This hypothesis was further confirmed in experiments showing that morphine's inhibitory effect on maternal responsiveness was blocked by unilateral naloxone injection into the rostral PAG, but not into nearby regions of the mesencephalic reticular nucleus. Therefore, only a partial inhibition of the opiate's effect on the rostral PAG was needed to block the inhibitory effect of morphine on maternal behaviour. Further studies are needed to ascertain whether the rostral lateral PAG plays a role in the natural onset of maternal behaviour, playing a complementary role to the medial pre‐optic area, or merely inhibits maternal behaviour in response to this specific pharmacological challenge. Conversely, the present findings may well reflect a more general role of the PAG, seemingly providing an important piece of information for proposing a hitherto unexplored concept of the PAG as an important centre for the selection of adaptive behavioural responses.
Myocardial Connections Between Left Atrial Myocardium and Coronary Sinus Musculature in Man
Authors: KASAI ATSUNOBU , ANSELME FREDERIC , SAOUDI NADIR 
Published: August 2003

Connections Between LA Myocardium and CS Musculature.
Introduction: Anatomic studies have shown that muscle morphologically identical to that of the atrial myocardium consistently surrounds the coronary sinus (CS). The CS musculature is connected to the left atrial (LA) myocardium in a variable fashion, with fewer connections in its distal portion. The aim of this study was to document the presence of connections between the LA myocardium and the CS musculature, using pacing maneuvers in man, and to study their potential association with natural atrial arrhythmia occurrence. Methods and Results: Thirty patients (19 men; mean age 50.5 years) underwent electrophysiologic study, during which a decapolar catheter with 2‐mm interelectrode spacing every 10 mm was inserted into the CS, with the proximal electrode pair positioned at the ostium. Associated atrial arrhythmias were paroxysmal atrial fibrillation in 5, typical atrial flutter in 13, LA flutter in 1, and other in 11. Baseline S1 and a single extrastimulus were delivered during distal and proximal CS pacing, while recordings were obtained from the four remaining bipoles. During distal CS pacing, double potentials with increasing interpotential interval from proximal to distal CS as a function of extrastimulus prematurity were detected in nine patients, suggesting block in a discrete local pathway distally connecting the CS to the LA and leading to reversion of low LA activation. Local delay in this pathway without complete CS‐LA block resulting in LA activation fusion was observed in eight patients. A single nonfractionated potential at the distal CS, even at the shortest attainable S1‐S2 coupling interval, which was interpreted as no block within distal CS‐LA connection(s), was observed in the other 13 patients. History of atrial fibrillation or atypical atrial flutter was found in 8 of 9 patients with block at the distal CS‐LA connection but in only 3 of 13 patients with no CS‐LA connection block (P = 0.004). Conclusion: The ability to dissociate the LA from the distal CS suggests the presence of discrete connections between these structures in man. This observation appears to be associated with the clinical occurrence of atrial arrhythmias.
Effect of Gender on Atrial Electrophysiologic Changes Induced by Rapid Atrial Pacing and Elevation of Atrial Pressure
Authors: TSE HUNG‐FAT , ORAL HAKAN , PELOSI FRANK , KNIGHT BRADLEY P. , STRICKBERGER S. ADAM , MORADY FRED 
Published: August 2003

Atrial Electrical Remodeling.
Introduction: The incidence of atrial fibrillation is greater in men than in women, but the reasons for this gender difference are unclear. The purpose of this study was to evaluate the effects of gender on the atrial electrophysiologic effects of rapid atrial pacing and an increase in atrial pressure. Methods and Results: Right atrial pressure and effective refractory period (ERP) were measured during sinus rhythm and during atrial and simultaneous AV pacing at a cycle length of 300 msec in 10 premenopausal women, 11 postmenopausal women, and 24 men. The postmenopausal women were significantly older than the premenopausal women (61 ± 8 years vs 34 ± 10 years; P < 0.01). During sinus rhythm, mean atrial ERP in premenopausal women was shorter (211 ± 19 msec) than in postmenopausal women and age‐matched men (242 ± 18 msec and 246 ± 34 msec, respectively; P < 0.05). Atrial ERPs in all patients shortened significantly during atrial and simultaneous AV pacing. However, the degree of shortening during atrial pacing (43 ± 8 msec vs 70 ± 20 msec and 74 ± 21 msec; P < 0.05) and during simultaneous AV pacing (48 ± 16 msec vs 91 ± 27 msec and 84 ± 26 msec; P < 0.05) was significantly less in premenopausal women than in postmenopausal women or age‐matched men. Conclusion: The results of this study demonstrate a significant gender difference in atrial electrophysiologic changes in response to rapid atrial pacing and an increase in atrial pressure. The effect of menopause on the observed changes suggests that the gender differences may be mediated by the effects of estrogen on atrial electrophysiologic properties.
Follow‐Up of Patients with Unexplained Syncope and Inducible Ventricular Tachyarrhythmias: Analysis of the AVID Registry and an AVID Substudy
Authors: STEINBERG JONATHAN S. , BECKMAN KAREN , GREENE H. LEON , MARINCHAK ROGER , KLEIN RICHARD C. , GREER STEPHEN G. , EHLERT FREDERICK , FOSTER PETER , MENCHAVEZ EDITH , RAITT MERRITT , WATHEN MARK S. , MORRIS MARY , HALLSTROM ALFRED 
Published: August 2003

Unexplained Syncope in AVID.
Introduction: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. Methods and Results: Included in the AVID registry were patients from all participating sites who had “out of hospital syncope with structural heart disease and EP‐inducible VT/VF with symptoms.” In addition, 13 collaborating sites provided more in‐depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT < 200 beats/min, and 48 patients (60%) had sustained monomorphic VT ≥200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study‐induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). Conclusion: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.
Flecainide Widens the Excitable Gap at Pivot Points of Premature Turning Wavefronts in Rabbit Ventricular Myocardium
Authors: DANSE PETER W. , GARRATT CLIFFORD J. , ALLESSIE MAURITS A. 
Published: August 2003

Widening of the Excitable Gap by Flecainide.
Introduction: The mechanisms by which Class IC drugs slow the rate of functional reentrant arrhythmias are not completely understood. We hypothesized that flecainide widens the excitable gap beyond the pivot point of premature turning wavefronts. Methods and Results: In eight perfused subepicardial layers of rabbit left ventricle, a linear lesion was made by radiofrequency (RF) ablation parallel to the fiber orientation. One end of the RF lesion was extended by a short incision. Pacing next to the lesion induced a wavefront propagating with a sharp U‐turn around the end of the lesion in either the clockwise or counterclockwise direction. A high‐density mapping electrode (240 electrodes, 350‐μm resolution) was used to record unipolar electrograms at the pivot point. During control, the shortest V1‐V2 interval proximal to the pivot point was 162 ± 12 msec compared with 173 ± 13 msec distal to the pivot point (difference 11 ± 8 msec; P < 0.01). After infusion of flecainide 2 mg/L, the shortest V1‐V2 interval proximal and distal to the pivot point were 217 ± 29 msec and 244 ± 36 msec (difference 27 ± 16 msec; P < 0.01). Due to the increase in V1‐V2 interval at the pivot point, flecainide widened the temporal excitable gap in the returning limb of the turning wavefront from 30 ± 11 msec to 55 ± 22 msec (P < 0.01). High‐density mapping at the pivot point revealed that this widening of the excitable gap was due to both macroscopic discontinuous conduction and functional conduction block at the pivot point. Conclusion: Flecainide widens the excitable gap in the returning limb of premature U‐turning wavefronts by causing macroscopic discontinuous conduction and functional conduction block at the pivot point.
Efficacy of Azimilide and Dofetilide in the Dog Right Atrial Enlargement Model of Atrial Flutter
Authors: RESTIVO MARK , HEGAZY MAHA , EL‐HAMAMI MOUSTAFA , YIN HONG , CAREF EDWARD B. , ASSADI MAHSHID A. , BROOKS ROBERT R. , EL‐SHERIF NABIL 
Published: August 2003

Azimilide and Dofetilide Atrial Flutter Efficacy.
Introduction: Azimilide dihydrochloride blocks both the rapid (IKr) and slow (IKs) components of the delayed rectified K+ current; dofetilide blocks only IKr. Their efficacies were assessed on atrial flutter reentrant circuits in dogs with surgically induced right atrial enlargement. Methods and Results: Multiple biopsies of the tricuspid valve and banding of the pulmonary artery in male mongrel dogs made them susceptible, about 3 weeks postoperatively, to stimulation‐induced sustained (5 min or longer) atrial flutter. Azimilide 3 mg/kg administered intravenously (IV) terminated flutter in 8 of 8 dogs, but a slower, nonsustained arrhythmia could be reinduced in 5. In these 5 dogs, azimilide 10 mg/kg terminated flutter and prevented reinduction. This dose increased effective refractory period significantly more in the slow conduction zone (25%) than in the normal zone (17%) and increased flutter cycle length (37%). Termination followed progressive conduction delay in the slow zone of the reentrant circuit. Dofetilide 1 μg/kg IV terminated flutter in 6 of 6 dogs, but the arrhythmia could be reinduced. At 3 μg/kg, flutter terminated in all dogs and could not be reinduced. Dofetilide also increased the effective refractory period significantly more in the slow zone (17%) than in the normal zone (12%) and increased cycle length (33%), leading to interruption of the arrhythmia circuit. Conclusion: In the canine right atrial enlargement model of circus movement atrial flutter, both azimilide 10 mg/kg IV and dofetilide 3 μg/kg IV were 100% effective in terminating flutter and preventing reinduction. Efficacy relied on a similar mechanism of differentially prolonged refractoriness in the slow conduction component of the reentrant circuit where drug‐induced termination occurred.
Effects of Azimilide, a New Class III Antiarrhythmic Drug, on Reentrant Circuits Causing Ventricular Tachycardia and Fibrillation in a Canine Model of Myocardial Infarction
Authors: SCHMITT HEIKO , CABO CANDIDO , COROMILAS JAMES C. , WIT ANDREW L. 
Published: August 2003

Effects of Azimilide on Reentrant Circuits.
Introduction: Azimilide blocks the slow (IKs) and fast (IKr) components of the delayed rectifier potassium channel. It also has blocking effects on sodium (INa) and calcium currents (ICaL). Its effects on reentrant circuits in infarct border zones causing ventricular tachyarrhythmias are unknown. Methods and Results: Activation in reentrant circuits causing sustained ventricular tachycardia (SVT) and the initial polymorphic tachycardia that leads to ventricular fibrillation (VF) was mapped in the epicardial border zone (EBZ) of 4‐day‐old canine infarcts. Azimilide prolonged the effective refractory period (ERP) in both normal myocardium and EBZ, but reverse use‐dependence in EBZ was prominent. Azimilide abolished SVT initiation by programmed electrical stimulation by prolonging the ERP at the site of stimulation either in normal or EBZ, preventing the occurrence of early premature impulses and the formation of lines of block in the EBZ necessary for formation of reentrant circuits. Azimilide prevented VF initiation by programmed electrical stimulation by causing conduction block of reentrant impulses in the EBZ during the initial beats of rapid polymorphic ventricular tachycardia, despite the reverse use‐dependent effects on ERP. Conclusion: Azimilide has antiarrhythmic effects to prevent reentry causing SVT and VF in a canine infarct model.
Effects of Linear, Irrigated‐Tip Radiofrequency Ablation in Porcine Healed Anterior Infarction
Authors: CALLANS DAVID J. , REN JIAN‐FANG , NARULA NAVNEET , MICHELE JOHN , MARCHLINSKI FRANCIS E. , DILLON STEPHEN M. 
Published: August 2003

Irrigated‐Tip Ablation in Infarcted Myocardium.
Introduction: Radiofrequency (RF) catheter ablation for ventricular tachycardia (VT) in healed infarction is modestly successful. More extensive, anatomically based procedures and irrigated RF delivery may improve outcome. However, limited data exist regarding the characteristics of irrigated RF lesions in infarcted myocardium. This study addresses this shortcoming. Methods and Results: Linear lesions were created at the medial border of a healed anterior infarct in eight pigs using irrigated RF energy guided by sinus rhythm electroanatomic voltage mapping and intracardiac echocardiography (ICE). Lesion morphology and effects on ventricular function were assessed with ICE imaging and pathologic analysis (n = 5). The response to programmed stimulation also was determined before and after linear lesions (n = 6). A mean of 9.4 ± 1.3 RF applications created linear lesions 37.0 ± 10.6 mm long, 5 to 12 mm wide, and 4 to 8 mm deep. Thrombus formation was not observed. Lesion delivery resulted acutely in increased local wall thickness at the RF site (26.9% ± 27.5%; P < 0.0001) and transient systolic dysfunction in adjacent normal myocardium (fractional shortening − 38% ± 34%; P < 0.01). Uniform sustained VT (cycle length 232 ± 41 msec) was induced in 4 of 6 pigs before ablation, but sustained VT could not be induced afterward. Conclusion: Irrigated RF energy produced relatively large lesions in infarcted myocardium without thrombus formation. Changes in tissue thickness and echo density observed with ICE verify irrigated RF lesion delivery. Temporary left ventricular dysfunction is consistently observed in the normal myocardium adjacent to the linear lesion.
Reentry in a Morphologically Realistic Atrial Model
Authors: VIGMOND EDWARD J. , RUCKDESCHEL RACHEL , TRAYANOVA NATALIA 
Published: August 2003

Reentry in Morphologically Realistic Atria.
Introduction: Atrial fibrillation is the most common cardiac arrhythmia. In ablation procedures, identification of the reentrant pathways is vital. This has proven difficult because of the complex morphology of the atria. The purpose of this study was to ascertain the role of specific anatomic structures on reentry induction and maintenance. Method and Results: A computationally efficient, morphologically realistic, computer model of the atria was developed that incorporates its major structural features, including discrete electrical connections between the right and left atria, physiologic fiber orientation in three dimensions, muscle structures representing the crista terminalis (CT) and pectinate muscles, and openings for the veins and AV valves. Reentries were induced near the venous openings in the left and right atria, the mouth of the coronary sinus, and the free wall of the right atrium. The roles of certain muscular structures were ascertained by selectively removing the structures and observing how the propagation of activity was affected. Conclusion: (1) The muscular sheath of the coronary sinus acts as a pathway for a reentrant circuit and stabilizes any circuits that utilize the isthmus near the inferior vena cava. (2) Poor trans‐CT coupling serves to stabilize flutter circuits. (3) Wall thickness is an important factor in the propagation of electrical activity, especially in the left atrium. (4) The openings of the inferior and superior venae cavae form natural anatomic anchors that make reentry easier to initiate by allowing for smaller ectopic beats to induce reentry.
Simulation of Protective Zones During Quatrefoil Reentry in Cardiac Tissue
Authors: HILDEBRANDT MARISA C. , ROTH BRADLEY J. 
Published: August 2003

Protective Zones During Quatrefoil Reentry.
Introduction: An S3 stimulus can exert a protective effect by terminating reentry induced by an S2 stimulus. Our goal was to examine the mechanism by which an S3 pulse terminates reentry and the role that virtual electrodes and break excitation play in this process. Methods and Results: In our simulation, the bidomain model represents the electrical properties of the tissue and the Beeler‐Reuter model represents the membrane kinetics. Quatrefoil reentry is initiated by S1‐S2 stimulation, and then a third stimulus S3 is applied at different intervals after S2. All stimuli are applied through the same unipolar electrode. For some S2‐S3 intervals, the S2 and S3 wavefronts interact destructively, terminating reentry (protective zones). For other S2‐S3 intervals, S2 and S3 wavefronts interact constructively, and reentry continues. Protective zones appear recurrently, with approximately the period of the S2 reentrant circuit. The protective zones are wider for anodal stimulation than for cathodal stimulation. Conclusion: Virtual electrodes, break excitation, and S2‐S3 timing all play important roles in determining the electrical response of the tissue.
Modulation of QT Interval by Cardiac Sympathetic Nerve Sprouting and the Mechanisms of Ventricular Arrhythmia in a Canine Model of Sudden Cardiac Death
Authors: ZHOU SHENGMEI , CAO JI‐MIN , TEBB ZACH D. , OHARA TOSHIHIKO , HUANG HSUN‐LUN A. , OMICHI CHIKAYA , LEE MOON‐HYOUNG , KENKNIGHT BRUCE H. , CHEN LAN S. , FISHBEIN MICHAEL C. , KARAGUEUZIAN HRAYR S. , CHEN PENG‐SHENG 
Published: August 2003

QT Interval and Sudden Cardiac Death.
Introduction: We previously reported that there is a high incidence of sudden cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD was unclear. Methods and Results: We analyzed QT intervals in three groups of dogs. All dogs had CAVB and MI. The LSG group (n = 9) and right stellate ganglion (RSG) group (n = 6) received NGF infusion via the osmotic pumps over a 5‐week period to LSG and RSG, respectively. The control group (n = 6) received no NGF. The dogs either died suddenly or were sacrificed within 2 to 3 months after MI. Heart rhythm and QT and RR intervals were monitored using implantable cardioverter defibrillator ECG recordings. There was a time‐dependent increase of QTc intervals in the LSG group and a time‐dependent decrease of QTc intervals in the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 ± 41 msec) were significantly longer than those in the control (350 ± 41 msec; P < 0.05) and RSG groups (294 ± 23 msec; P < 0.01). In the LSG group, 4 of 9 dogs died of SCD. There was no SCD in either the RSG or control group. Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left and right ventricular sympathetic nerve sprouting and hyperinnervation, respectively. Conclusion: NGF infusion to the LSG in dogs with MI and CAVB resulted in increased QT interval and incidence of ventricular tachycardia, ventricular fibrillation, and SCD, whereas NGF infusion to the RSG shortened QT interval and reduced the incidence of ventricular tachycardia. These findings indicate that QT interval prolongation is causally related to the occurrence of ventricular arrhythmia in dogs with nerve sprouting, MI, and CAVB.