bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous Occlusion of the Access Vein in Patients Referred for Lead Extraction:
Authors: BRACKE FRANK , MEIJER ALBERT , VAN GELDER BERRY
Published: July 2003

The aim of this study was to determine the effect of patient and lead characteristics on occlusion of the access vein in pacemaker and ICD patients. Contrast venography of the access vein was obtained in 89 patients (17 patients with an ICD) scheduled for lead extraction. The indication for extraction was infection in 57 patients (systemic infection in 9) and lead malfunction in 32 patients. In 6 of the 89 patients, leads were introduced in both the right and left subpectoral area, resulting in a total of 95 venous entry sites. In 22 of these entry sites one lead was present, in 61 two leads, in 11 three, and in 1 four leads. The vessel patency was graded open or occluded. Occlusion of the subclavian vein occurred in four (13%) patients with lead malfunction versus 18 (32%) patients with infection (P = 0.07). In patients with systemic infection, 5 of 9 showed venous occlusion (P = 0.01 when compared to patients with malfunction, odds ratio 8.75, 95% confidence interval 1.21–64.11). Considered per entry site, the incidence of occlusion was 7 of 22 with one lead present, 17 of 61 with two leads, 0 of 11 with three leads, and 0 of 1 with four leads (P = 0.13). No patient had a superior vena caval occlusion. Patients with systemic infection have an increased risk of occlusion of the access vein. On the contrary, the study found no support for the concept that the risk of venous occlusion increases with a higher number of leads present. (PACE 2003; 26:1649–1652)
Can Lesion Size During Radiofrequency Ablation Be Predicted By the Temperature Rise to a Low Power Test Pulse in Vitro?
Authors: PETERSEN HELEN HØGH , SVENDSEN JESPER HASTRUP
Published: July 2003

During radiofrequency ablation sufficient power must be delivered to achieve a proper lesion, while tissue temperatures are kept below 100°C. Tissue temperature and hence lesion size are determined by electrode to tissue contact and convective cooling, which vary with any obtained electrode position in the beating heart. A tool for evaluation of the combined effect of these parameters prior to ablation to predict the resulting lesion size for any actually obtained electrode position would be valuable. A low power pulse prior to ablation will cause a small increase in tip temperature, which will reflect tissue contact and convective cooling of the tip for that particular electrode position and may thereby predict lesion dimensions after subsequent ablation at that site. Ablation was performed in vitro on strips of left ventricular porcine myocardium during different levels of convective cooling, variable contact pressure, and two electrode orientations in temperature‐controlled and power‐controlled modes. A 4‐mm tip catheter was used. Prior to ablation a 30‐second, 0.6‐W test pulse was delivered and the increase in tip temperature (ΔT) registered. The study found that ΔT and lesion size were mainly affected by the external cooling of the electrode tip and less by the electrode to tissue contact. Increased cooling caused a lower ΔT (P < 0.001), and the effect on lesion dimensions depended on the ablation mode. For temperature‐controlled ablation a larger lesion due to increased power output was obtained (P < 0.0001) for increased cooling, whereas for power‐controlled ablation a smaller lesion was obtained for increased cooling (P < 0.05). ΔT can predict lesion size, but the interpretation of ΔT depends on the ablation mode. For temperature‐controlled ablation a high ΔT indicates a small lesion and for power‐controlled ablation a high ΔT indicates a large lesion. (PACE 2003; 26:1653–1659)
Catecholamine‐Provoked Microvoltage T Wave Alternans in Genotyped Long QT Syndrome
Authors: NEMEC JAN , ACKERMAN MICHAEL J. , TESTER DAVID J. , HEJLIK JOSEPH , SHEN WIN‐KUANG
Published: July 2003

Macrovoltage T wave alternans (TWA) has been described in congenital long QT syndrome (LQTS). Microvoltage T wave alternans (μV‐TWA) at low heart rate (HR) is a marker of arrhythmogenic risk in many conditions, but its significance in LQTS has not been established. Twenty‐three genotypically heterogeneous patients with LQTS and 16 control subjects were studied at rest and during phenylephrine and dobutamine provocation. Genotyping was established by PCR amplification and DNA sequencing of the three most common LQTS genes; KCNQ1/KVLQT1 (LQT1), KCNH2/HERG (LQT2), and SCN5A (LQT3). μV‐TWA was determined using Fast Fourier transform. Precluded by ectopy, μV‐TWA could not be assessed in 8 of 23 patients with LQTS. In the remaining 15 patients with LQTS, μV‐TWA occurred at lower HR in LQTS than in controls (

117 ± 49

vs

153 ± 37  beats/min; P < 0.05

). Patients with LQTS developed μV‐TWA at HR < 150 beats/min more often than controls (10/15 vs 2/16; P = 0.003). However, μV‐TWA was not detected in the 3 individuals with a history of out‐of‐hospital cardiac arrest including a 14‐year‐old male with an F339del‐KVLQT1 mutation (LQT1) who had dobutamine‐provoked polymorphic ventricular tachycardia requiring external defibrillation. Catecholamine‐provoked μV‐TWA occurs at lower HR in patients with LQTS than in healthy people but does not identify high risk subjects. (PACE 2003; 26:1660–1667)
Paroxysmal Atrial Fibrillation:
Authors: JENSEN THOMAS J. , HAARBO JENS , PEHRSON STEEN M. , THOMSEN POUL E.B.
Published: July 2003

Catheter ablation is a promising approach in severely symptomatic patients with paroxysmal atrial fibrillation (PAF). Until this time it has only been performed in highly selected patients with weekly episodes and frequent premature atrial contractions (PACs). The aim of the present study was to estimate the prevalence of severely symptomatic patients with PAF and to evaluate the significance of PACs. The files of 7,447 consecutive patients were screened and 1,357 PAF patients identified. Holter recordings were performed in 108 patients with ≥2 spontaneous AF episodes. Despite antiarrhythmic treatment, 6.5% (1.8–11.1%) had a history of weekly PAF episodes. 29.2% of patients and 10% of healthy, age‐matched controls had more than 700 PACs. The number of PACs was inversely related to the reported numbers of previous episodes and directly related to age and size of left atrium. We estimate that about 6.5% of patients with PAF are severely symptomatic and might benefit from catheter ablation. Our data suggest that the number of PACs should not be used as a selection criterion for catheter ablation. Frequent PACs are seen in a substantial proportion of elderly healthy individuals. (PACE; 26:1668–1674)
Patients with an ICD Can Safely Resume Work in Industrial Facilities Following Simple Screening for Electromagnetic Interference
Authors: GUREVITZ OSNAT , FOGEL RICHARD I. , HERNER MARK E. , SAMPLE ROSS , STRICKBERGER ADAM S. , DAOUD EMILE G. , MORADY FRED , PRYSTOWSKY ERIC N.
Published: July 2003

Patients with ICDs are commonly advised to quit industrial jobs because of concerns that strong electromagnetic fields operating in the industrial environment might interfere with ICD functions. This study was done to assess interactions between industrial equipment and ICDs, and to devise a simple low risk screening protocol. We studied 18 patients carrying nine different ICD models who were met at their workplace by a clinical technician and were asked to walk through their workplace and perform typical duties while sensing status was monitored by listening to the ICD's beeper. All devices were interrogated at the completion of testing. At follow‐up, patients were contacted by phone and were asked about employment status and history of ICD discharges or syncope. One hundred eighty‐four contacts with 114 types of industrial equipment in 13 different industrial facilities (including 31 contacts with arc welding machines) were monitored. Interference with ICD's function occurred in only one contact (0.5%), when ICD therapy was temporarily suspended while a worker was attaching a huge electromagnet to a crane. At follow‐up 46.0 ± 6.0 months after testing, 7 patients (41%) are still holding the same job, 7 have retired because of reasons unrelated to their ICD, and 3 patients were transferred to a nonindustrial job. None of the patients had either an ICD shock or syncope during work. The use of a simple screening procedure can safely identify sources of electromagnetic interference that may affect ICD operation, and can predict long‐term safety of working in an industrial workplace for ICD patients. (PACE 2003; 26:1675–1678)
Radiofrequency Ablation of Probable Atrioventricular Nodal Reentrant Tachycardia in Children with Documented Supraventricular Tachycardia Without Inducible Tachycardia
Authors: FISHBERGER STEVEN B.
Published: July 2003

The reproducible induction of supraventricular tachycardia (SVT) during electrophysiological study is critical for the diagnosis of atrioventricular nodal reentry tachycardia (AVNRT), and for determining a therapeutic endpoint for catheter ablation. In the sedated state, there are patients with reentry SVT due to AVNRT who are not inducible at electrophysiological study. This article reports on the empiric slow pathway modification for AVNRT in six pediatric patients (age 6–17, mean 13.3 years) with documented, recurrent, paroxysmal SVT in the setting of a structurally normal heart who were not inducible at electrophysiological study. Atrial and ventricular burst and extrastimulus pacing at multiple drive cycle lengths were performed in the baseline state, during an isuprel infusion, and during isuprel elimination. Single AV nodal (AVN) echo beats were present in all patients, while classic dual AVN physiology was present in three of six patients. Radiofrequency energy was administered in the right posteroseptal AV groove resulting in accelerated junctional rhythm in five of six patients. Postablation testing demonstrated the elimination of echo beats in four patients, while dual AVN physiology and echo beats persisted in two patients. At follow‐up (22–49 months, mean 29.5 months), all patients are asymptomatic without recurrence of SVT and are not taking any antiarrhythmic medication. In selected patients, empiric slow pathway modification may be offered as a potential cure in children with recurrent paroxysmal SVT who are not inducible at electrophysiological study. Elimination of slow pathway conduction may serve as a surrogate endpoint, though is not necessary for long‐term success. (PACE 2003; 26:1679–1683)
A Randomized Prospective Study of Single Coil Versus Dual Coil Defibrillation in Patients with Ventricular Arrhythmias Undergoing Implantable Cardioverter Defibrillator Therapy
Authors: RINALDI C. ALDO , SIMON RON D.B. , GEELEN PETER , REEK SVEN , BASZKO ARTUR , KUEHL MARTIN , GILL JASWINDER S.
Published: July 2003

ICD implantation is standard therapy for malignant ventricular arrhythmias. The advantage of dual and single coil defibrillator leads in the successful conversion of arrhythmias is unclear. This study compared the effectiveness of dual versus single coil defibrillation leads. The study was a prospective, multicenter, randomized study comparing a dual with a single coil defibrillation system as part of an ICD using an active pectoral electrode. Seventy‐six patients (64 men, 12 women; age

61 ± 11 years

) were implanted with a dual (group 1, n = 38) or single coil lead system (group 2,

n = 38

). The patients represented a typical ICD cohort: 60% presented with ischemic cardiomyopathy as their primary cardiac disease, the mean left ventricular ejection fraction was

0.406 ± 0.158

. The primary tachyarrhythmia was monomorphic ventricular tachyarrhythmia in 52.6% patients and ventricular fibrillation in 38.4%. There was no significant difference in terms of P and R wave amplitudes, pacing thresholds, and lead impedance at implantation and follow‐up in the two groups. There was similarly no difference in terms of defibrillation thresholds (DFT) at implantation. Patients in group 1 had an average DFT of

10.2 ± 5.2 J

compared to

10.3 ± 4.1 J

in Group 2, P = NS. This study demonstrates no significant advantage of a dual coil lead system over a single coil system in terms of lead values and defibrillation thresholds. This may have important bearing on the choice of lead systems when implanting ICDs. (PACE 2003; 26:1684–1690)
Incidence and Rate Characteristics of Atrial Tachyarrhythmias in Patients with a Dual Chamber Defibrillator
Authors: WOLPERT CHRISTIAN , JUNG WERNER , SPEHL SUSANNE , SCHIMPF RAINER , OMRAN HEYDER , SCHUMACHER BURGHARD , ESMAILZADEH BAHMAN , TENZER DIRK , MEHRA RAHUL , LÜDERITZ BERNDT
Published: July 2003

Atrial tachyarrhythmias play an important role in the treatment of patients with malignant ventricular tachyarrhythmias not only with respect to inappropriate discharges but also to left ventricular function and stroke risk. A combined dual chamber defibrillator provides separate therapies for atrial and ventricular tachyarrhythmias. To assess the incidence of atrial tachyarrhythmias in patients with this dual chamber implantable defibrillator, 40 patients with ventricular tachyarrhythmias and concomitant atrial tachyarrhythmias and/or AV conduction disturbances were included in a prospective study. During a mean follow‐up of

25 ± 11 months

, 26 of 40 patients had a total of 1,430 recurrences of atrial tachyarrhythmias. The vast majority of the atrial tachyarrhythmias with regular atrial cycles had a mean median atrial cycle length of

235 ± 37 ms

and a mean duration of

34 ± 144 minutes

. Atrial tachyarrhythmias with irregular atrial cycles exhibited a median atrial cycle length of

198 ± 31 ms

and had a mean duration of

246 ± 1,264 minutes

. In addition, 67% of 375 tachyarrhythmias, in which the median ventricular cycle length during the ongoing episode could be documented, had a ventricular rate <100 beats/min. Continuous atrial arrhythmia detection with a dual chamber ICD reveals a high incidence of atrial tachyarrhythmias with a predominantly short duration of paroxysmal recurrences <1 hour in the vast majority of episodes. (PACE 2003; 26:1691–1698)
Spatial Distribution of Repolarization Times in Patients with Coronary Artery Disease
Authors: LEEUWEN PETER VAN , HAILER BIRGIT , LANGE SILKE , GRÖNEMEYER DIETRICH
Published: July 2003

The potential clinical value of QT dispersion (QTd), a measure of the interlead range of QT interval duration in the surface 12‐lead ECG, remains ambiguous. The aim of the study was the temporal and spatial analysis of the QT interval in healthy subjects and in patients with coronary artery disease (CAD) using magnetocardiography (MCG) and surface ECG. Standard 12‐lead ECG and 37‐channel MCG were performed in 20 healthy subjects, 23 patients with CAD without prior myocardial infarction (MI), 31 MI patients and 11 MI patients with ventricular tachycardia (VT). QTd was increased in CAD without MI compared to normals (ECG

46.1 ± 6.0

vs

42.8 ± 5.0, P < 0.05

; MCG

66.8 ± 20.3

vs

49.7 ± 10.8, P < 0.01

) and in VT compared to MI (ECG

66.8 ± 16.5

vs

51.9 ± 16.6, P < 0.05

; MCG

93.6 ± 29.6

vs

66.8 ± 20.8, P < 0.005

). In MCG, spatial distribution of QT intervals in patient groups differed from those in healthy subjects in three ways: (1) greater dispersion, (2) greater local variability, and (3) a change in overall pattern. This was quantified on the basis of smoothness indexes (SI). Normalized SI was higher in CAD without MI compared to normals (

3.8 ± 1.1

vs

2.7 ± 0.6, P < 0.001

) and in VT compared to MI (

6.4 ± 1.6

vs

4.2 ± 1.4, P < 0.0005

). For the normal‐CAD comparison a sensitivity of 74% and a specificity of 80% was obtained, for MI‐VT, 100% and 77%, respectively. The results suggest that examining the spatial interlead variability in multichannel MCG may aid in the initial identification of CAD patients with unimpaired left ventricular function and the identification of post‐MI patients with augmented risk for VT. (PACE 2003; 26:1706–1714)
Are Electrophysiological Studies Needed Prior to Defibrillator Implantation?
Authors: BECKER RUEDIGER , MELKUMOV MICHAIL , SENGES‐BECKER JULIA C. , VOSS FREDERIK , BAUER ALEXANDER , MICHAELSEN JOCHEN , WERETKA SLAWOMIR , NIROOMAND FERAYDOON , KATUS HUGO A. , SCHOELS WOLFGANG
Published: July 2003

At present, patients with documented sustained VT or resuscitated cardiac arrest (CA) are treated with ICDs. The aim of this study was to retrospectively evaluate if a routine electrophysiological study should be recommended prior to ICD implantation. In 462 patients referred for ICD implantation because of supposedly documented VT

(n = 223)

or CA

(n = 239)

, electrophysiological study was routinely performed. In 48% of the patients with CA, sustained VT or VF was inducible. Electrophysiological study suggested conduction abnormalities

(n = 11)

or supraventricular tachyarrhythmias

(n = 3)

in conjunction with severely impaired left ventricular function to have been the most likely cause of CA in 14 (5.9%) of 239 patients. Likewise, sustained VT was only inducible in 48% of patients with supposedly documented VT. Of these inducible VTs, nine were diagnosed as right ventricular outflow tract tachycardia or as bundle branch reentry tachycardia. Supraventricular tachyarrhythmias judged to represent the clinical event were the only inducible arrhythmia in 35 (16%) patients (AV nodal reentrant tachycardia

[n = 7]

, AV reentry tachycardia

[n = 4]

, atrial flutter

[n = 19]

, and atrial tachycardia

[n = 5]

). Based on findings from the electrophysiological study, ICD implantation was withheld in 14 (5.9%) of 239 patients with CA and in 44 (19.7%) of 223 patients with supposedly documented VT. During electrophysiological study, VT or VF was only reproducible in about 50% of patients with supposedly documented VT or CA. Electrophysiological study revealed other, potentially curable causes for CA or supposedly documented VT in 12.6% (58/462) of all patients, indicating that ICD implantation can potentially be avoided or at least postponed in some of these patients. Based on these retrospective data, routine electrophysiological study prior to ICD implantation seems to be advisable. (PACE 2003; 26:1715–1721)
The Relationship Between Electrocardiographic Abnormalities and Location of the Intracranial Aneurysm in Subarachnoid Hemorrhage
Authors: LORSHEYD A. , SIMMERS T.A. , DE MEDINA E.O. ROBLES
Published: July 2003

The purpose of this study was to determine the value of the ECG in subarachnoid hemorrhage (SAH) in predicting poor outcome, and to define if specific ECG changes are related to the location of the aneurysm in SAH. A retrospective cohort study was performed on 97 patients with symptoms of SAH. An ECG and an initial computer tomograph (CT) scan were the two major inclusion criteria. The primary endpoint was in hospital mortality. ECG changes were correlated with mortality and severity of hemorrhage expressed as the Hijdra score. A prolonged QTc interval occurred more frequently in patients who had experienced a severe hemorrhage (RR = 3.18; 95%  CI = 1.07–10.22; P < 0.05). LV hypertrophy criteria were strongly related to an aneurysm in the anterior communicating artery. U wave presence showed a statistically significant relationship with the posterior communicating artery and the middle cerebral artery. A prolonged QTc interval is observed more frequently in patients with severe hemorrhage. Specific ECG abnormalities were seen to be associated with the location of the aneurysm in the circle of Willis in SAH. (PACE 2003; 26:1722–1728)
Safety and Efficacy of Radiofrequency Ablation of Common Atrial Flutter in Elderly Patients:
Authors: COSTA ANTOINE DA , ZARQANE‐SLIMAN NAÏMA , ROMEYER‐BOUCHARD CÉCILE , GONTHIER RÈGIS , SAMUEL BERNARD , MESSIER MARC , KHIEL ABDEL , ISAAZ KARL
Published: July 2003

Little data is available concerning the invasive treatment of atrial flutter (AFL) in elderly patients. The purpose of this prospective study was to evaluate the risks, safety, and follow‐up of radiofrequency (RF) catheter ablation of common AFL in patients >75 years old (n = 61) (Group I) compared to patients younger than 75 years (n = 187) (Group II). The study population consisted of 248 patients (81% men/19% women), 21 to 96 years old (mean 66.3 ± 12 years) with AFL, referred for RF from June 1999 to June 2001. RF endpoint was the assessment of the bidirectional block. The cumulative risk of atrial fibrillation (AF) was analyzed by the Kaplan‐Meier method and log‐rank test. The mean follow‐up was 12.4 ± 9 months. No complication occurred. Group I (80.1 ± 4.5 years) did not differ significantly from Group II (61 ± 11 years) regarding: AF history before ablation (34.4% vs 39.8%), structural heart disease (54% vs 42%), LVEF (57%± 12% vs 58%± 12%), left atrial size (43.8 ± 7 vs 42.5 ± 7), cava‐tricuspid isthmus dimension (40 ± 10 vs 39 ± 4 mm), bidirectional block (100% vs 96.2%), RF application (12.5 ± 10 vs 13.5 ± 12 minutes), AFL recurrence (3.3% vs 5.3%), antiarrhythmic agents at hospital discharge (34.4% vs 38.9%), mean follow‐up (12 ± 9 vs 13 ± 9 months) and AF occurrence (29.5% vs 20.3%; P = 0.2). Of these, the incidence of AF in patients without prior history (n = 150) was 7 (18%) of 39 for Group I and 11 (10%) of 111 for Group II (P = 0.1) after follow‐up. Catheter ablation of AFL in very elderly patients appears to be a reasonable approach regarding feasibility, effectiveness, and low procedural risk. (PACE 2003; 26:1729–1734)
Inducible Atrioventricular Nodal Reentry Tachycardia in Infants with a History of Neonatal Orthodromic Reciprocating Tachycardia
Authors: KANNANKERIL PRINCE J. , JOHNS JAMES A. , FISH FRANK A.
Published: July 2003

Atrioventricular nodal reentry tachycardia (AVNRT) is an uncommon mechanism of supraventricular tachycardia in neonates in whom orthodromic reciprocating tachycardia (ORT) predominates. We report three patients with structurally normal hearts who presented with neonatal ORT, documented by transesophageal electrophysiology studies at 2 to 3 weeks of age. At follow‐up study at 8–12 months of age, no infant had inducible ORT, suggesting spontaneous regression of congenital accessory pathways; however, each had inducible tachycardia consistent with the typical form of AVNRT. The clinical significance of this finding is unknown and warrants further study. (PACE 2003; 26:1735–1737)
Threshold Measurements:
Authors: IRNICH WERNER
Published: July 2003

The following rules for professionally measuring thresholds are derived and discussed:

RULE 1: Thresholds should be expressed as voltage averaged over pulse duration to get reproducible and comparable results!

RULE 2: Pacing threshold measurements with exponentially decaying pulses should not be extended beyond 1.4 ms as that portion of the pulse below rheobase does not contribute to the stimulation effect!

RULE 3: Threshold measurements are best carried out with fixed pulse duration and variable voltage!

RULE 4: If threshold measurements are carried out in discrete steps, the steps should be chosen such that the relative step size is as equal as possible!

RULE 5: Accuracy of threshold measurements is highly increased if the arithmetically averaged value of the last effective and the first ineffective pulse is defined as threshold!

RULE 6: To determine strength‐duration‐curves, a linear regression of the quantity versus pulse duration should be calculated which yields simply the numerical values of the chronaxie and rheobase!

RULE 7: To reach representative strength‐duration‐curves, measurements with at least four pairs of values must be carried out!

RULE 8: Measuring defibrillation thresholds, the relative voltage step size should be chosen equally to have equal accuracy for all steps.

RULE 9: If the result of a defibrillation threshold investigation does not reach significance, a too large voltage step size could be an explanation!

RULE 10: Comparing intraindividually the threshold of two different defibrillation systems or parameter settings, the threshold ratios should be formed and averaged!

Obeying these rules guaranties professional threshold measurements expressed as “rheobase” and “chronaxie” even with devices with discrete steps in parameter programming. (PACE 2003; 26:1738–1746)
Electrical Disconnection of an Arrhythmogenic Superior Vena Cava with Discrete Radiofrequency Current Lesions Guided by Noncontact Mapping
Authors: WEISS CHRISTIAN , WILLEMS STEPHAN , ROSTOCK THOMAS , RISIUS TIM , VENTURA RODOLPHO , MEINERTZ THOMAS
Published: July 2003

This case describes a 54‐year‐old patient with paroxysmal atrial fibrillation and atrial flutter. Conventionally recorded local electrogram demonstrated a cycle length of 245 ms in the SVC which was conducted to the right atrium in a 2:1 fashion. The analysis of the virtual unipolar local electrogram from the noncontact mapping system demonstrated slow conduction between SVC and right atrium orthogonal to the atrial breakthrough in the upper part of the crista terminalis. RF ablation at the atrial breakthrough induced the electrical disconnection between the CVC and the right atrium. (PACE 2003; 26:1758–1761)
Pseudo‐Cross‐Stimulation due to First Degree AV Block
Authors: SHEREV DIMITRI A. , HONGO RICHARD H. , GOLDSCHLAGER NORA
Published: July 2003

During routine interrogation of a dual chamber pacemaker, atrial pacing stimulus outputs were found to coincide with surface electrogram QRS complexes raising concern for cross‐stimulation. Scrutiny of the native rhythm, however, confirmed this to be “pseudo‐cross‐stimulation” where marked first degree AV block resulted in alignment of atrial stimulus outputs with preceding QRS complexes. Although cross‐stimulation is rare, familiarity with cross‐stimulation and pseudo‐cross‐stimulation is important because its recognition will avoid erroneous diagnoses of lead dislodgment or device malfunction. (PACE 2003; 26:1762–1764)
New‐Onset QT Prolongation and Torsades De Pointes Accompanied by Left Ventricular Dysfunction Secondary to Acute Pancreatitis
Authors: MOFRAD PIROOZ S. , RASHID HAROON , TRACY CYNTHIA M.
Published: July 2003

A 70‐year‐old woman presented with acute pancreatitis and new‐onset QT prolongation with subsequent torsades de pointes. Coronary catheterization was performed and was unremarkable. After persistent QT prolongation, despite temporary atrial pacing, a permanent dual chamber cardioverter defibrillator was implanted. In addition to the QT prolongation, significant depression in the left ventricular function was noted. Both resolved once the pancreatitis abated. (PACE 2003; 26:1765–1768)
Atrial Fibrillation with a Very Rapid Ventricular Response as the First Clinical Arrhythmia in a 76‐Year‐Old Man
Authors: BREMBILLA‐PERROT BÉATRICE , HOURIEZ PIERRE , BEURRIER DANIEL , LOUIS PIERRE , BOURSIER MICHEL , KHALIFÉ KHALIFÉ
Published: July 2003

The interest of electrohysiological study for the prognostic evaluation of asymptomatic Wolff‐Parkinson‐White (WPW) syndrome remains controversial. We report the case of an asymptomatic 67‐year‐old man without heart disease in whom a type A WPW syndrome was noted. Because the WPW was unchanged during exercise testing, transesophageal EPS was performed. In basal state, 1/1 conduction through the Kent bundle was noted up to a rate of 210 beats/min. After infusion of 30 μg of isoproterenol, atrial pacing was associated with a 1/1 conduction throught the Kent bundle at a rate at 300 beats/min and induced rapid atrial fibrillation which was stopped by flecainide. No treatment was indicated. Nine years later, at age 76, the patient developed syncope related to rapid atrial fibrillation requiring cardioversion. In conclusion, the occurrence of a potentially lethal supraventricular tachyarrhythmia in a previously asymptomatic patient with WPW syndrome might be encountered in elderly patients. Transesophageal electrophysiological evaluation is a useful means to predict this risk. (PACE 2003; 26:1769–1770)
Endocardial Flap of Left Atrial Dissection Following Radiofrequency Ablation
Authors: RAMAKRISHNA GAUTAM , COTE ANNIE V. , CHANDRASEKARAN KRISHNASWAMY , MALOUF JOSEPH F.
Published: July 2003

This report describes an unusual mobile strand found by transesophageal echocardiography prior to a patient's second radiofrequency ablation for paroxysmal atrial fibrillation. This structure arose from the limbus of the left upper pulmonary vein, a location where radiofrequency energy bursts were delivered during the first ablation procedure. After seven months of therapeutic anticoagulation, there was no evidence of change in the size of the mass or of thromboembolism and the patient underwent radiofrequency ablation without complication. We believe this structure most likely represents an endocardial flap of left atrial dissection temporally related to radiofrequency ablation. (PACE 2003; 26:1771–1773)
Fracture of a Circular Mapping Catheter After Entrapment in the Mitral Valve Apparatus During Segmental Pulmonary Vein Isolation
Authors: TAVERNIER RENE , DUYTSCHAEVER MATTIAS , TAEYMANS YVES
Published: July 2003

We report on the entrapment of a circular mapping catheter in the mitral valve apparatus during segmental pulmonary vein isolation. In an attempt to remove the catheter by using mild traction in combination with clockwise and counter‐clockwise rotation, the circular part and the shaft of the catheter separated. The circular part could be removed without sequelae using a transseptally positioned vascular extraction nipper in combination with a basket catheter. (PACE 2003; 26:1774–1775)
R Wave Undersensing Caused by an Algorithm Intended to Enhance Sensing Specifity in an Implantable Cardioverter Defibrillator
Authors: EBERHARDT FRANK , PETERS WERNER , BODE FRANK , WIEGAND UWE K.H.
Published: July 2003

This article reports on a case of ventricular undersensing despite normal R wave amplitudes during sinus rhythm in an ICD patient. Undersensing of ventricular signals was noted without any evidence of lead dislocation or variation in signal amplitude. Undersensing was due to an exceptionally small R wave signal width and a feature of the Biotronik sensing algorithm designed to avoid oversensing. This algorithm, intended to enhance the sensing specifity of the device, requires registration of two consecutive points above the maximum programmed sensitivity for a ventricular sense event. After modifying the algorithm to a single point registration undersensing disappeared. (PACE 2003; 26:1776–1777)
Metabotropic glutamate type 1α receptor localizes in low‐density caveolin‐rich plasma membrane fractions
Authors: Burgueño Javier , Enrich Carlos , Canela Enric I. , Mallol Josefa , Lluis Carmen , Franco Rafael , Ciruela Francisco
Published: July 2003

Recent evidence suggest that many G protein‐coupled receptors (GPCR) and signalling molecules localize in microdomains of the plasma membrane. In this study, flotation gradient analysis in the absence of detergents demonstrated the presence of the metabotropic glutamate receptor type 1α (mGlu1α) in low‐density caveolin‐enriched membrane fractions (CEMF) in permanently transfected BHK cells. BHK‐1α cells exhibit a similar pattern of staining for caveolin‐1 and caveolin‐2, and these two proteins show a high degree of co‐localization with mGlu1α receptor as demonstrated by immunogold and confocal laser microscopy. The presence of mGlu1α in CEMF was also demonstrated by co‐immunoprecipitation of mGlu1α receptor using antibodies against caveolin proteins. Activation of the mGlu1α receptor by agonist increased extracellular signal‐regulated kinases phosphorylation in CEMF and not in high‐density membrane fractions (HDMF), suggesting that mGlu1α receptor‐mediated signal transduction could occur in caveolae‐like domains. Overall, these results clearly show a molecular and functional association of mGlu1α receptor with caveolins.
CREB is required for acquisition of ischemic tolerance in gerbil hippocampal CA1 region
Authors: Hara Tsuyoshi , Hamada Jun‐ichiro , Yano Shigetoshi , Morioka Motohiro , Kai Yutaka , Ushio Yukitaka
Published: July 2003

Ischemic tolerance is well known as a neuroprotective effect of pre‐conditioning ischemia against delayed neuronal death, however, the mechanism or mechanisms underlying this effect are not fully understood. We investigated the relationship between CREB and ischemic tolerance in gerbil hippocampal CA1 neurons using CRE decoy oligonucleotide. Sublethal ischemia led to an increase in the level of CREB phosphorylation in CA1 regions while lethal ischemia did not. Experiments with NG108‐15 cells showed that adding CRE decoy oligonucleotide to culture media significantly inhibited the cell growth rate. The administration of CRE decoy oligonucleotide into gerbil cerebral ventricle decreased CREB‐DNA binding activity to 38% of the control. Pre‐treatment with CRE decoy oligonucleotide 24 h before the induction of ischemic tolerance decreased CA1 neuronal cell survival to 21% of the control. The present findings suggest that a CREB‐mediated transcription system is necessary for the induction of ischemic tolerance.
Dynorphin A(1–17) biotransformation in striatum of freely moving rats using microdialysis and matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Reed Brian , Zhang Yong , Chait Brian T. , Kreek Mary Jeanne
Published: July 2003

The biotransformation of the opioid peptide dynorphin A(1–17) was investigated in striatum of freely moving Fischer rats, by direct infusion of this peptide, followed by recovery of the resulting biotransformation products via microdialysis and identification using matrix‐assisted laser desorption/ionization mass spectrometry. The observed peptides are consistent with enzymatic cleavage at the Arg7‐Ile8 position of dynorphin A(1–17), followed by terminal degradation of the resulting dynorphin A(1–7) and dynorphin A(8–17) peptides. Unexpectedly, novel post‐translational modifications were found on C‐terminal fragments of dynorphin A(1–17). Using tandem mass spectrometry, a covalent modification of mass 172 Da, the nature of which is not understood, was found on the tryptophan residue of C‐terminal fragments (Trp14). Additional modifications, of mass 42 and 113 Da, were also found on the N‐terminus (Ile8 or Pro10) of these same C‐terminal fragments. The role of these modifications of C‐terminal fragments has not yet been characterized.
Distinct cleavage patterns of normal and pathologic forms of α‐synuclein by calpain I in vitro
Authors: Mishizen‐Eberz Amanda J. , Guttmann Rodney P. , Giasson Benoit I. , Day George A. , Hodara Roberto , Ischiropoulos Harry , Lee Virginia M.‐Y. , Trojanowski John Q. , Lynch David R.
Published: July 2003

Parkinson's disease (PD) is characterized by fibrillary neuronal inclusions called Lewy bodies (LBs) consisting largely of alpha‐synuclein (α‐syn), the protein mutated in some patients with familial PD. The mechanisms of α‐syn fibrillization and LB formation are unknown, but may involve aberrant degradation or turnover. We examined the ability of calpain I to cleave α‐syn in vitro. Calpain I cleaved wild‐type α‐syn predominantly after amino acid 57 and within the non‐amyloid component (NAC) region. In contrast, calpain I cleaved fibrillized α‐syn primarily in the region of amino acid 120 to generate fragments like those that increase susceptibility to dopamine toxicity and oxidative stress. Further, while calpain I cleaved wild‐type α‐syn after amino acid 57, this did not occur in mutant A53T α‐syn. This paucity of proteolysis could increase the stability of A53T α‐syn, suggesting that calpain I might protect cells from forming LBs by specific cleavages of soluble wild‐type α‐syn. However, once α‐syn has polymerized into fibrils, calpain I may contribute to toxicity of these forms of α‐syn by cleaving at aberrant sites within the C‐terminal region. Elucidating the role of calpain I in the proteolytic processing of α‐syn in normal and diseased brains may clarify mechanisms of neurodegenerative α‐synucleinopathies.
Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum
Authors: Ghoumari A. M. , Ibanez C. , El‐Etr M. , Leclerc P. , Eychenne B. , O'Malley B. W. , Baulieu E. E. , Schumacher M.
Published: July 2003

We have previously shown that progesterone (PROG) is synthesized by Schwann cells and promotes myelin formation in the peripheral nervous system (PNS). We now report that this neurosteroid also stimulates myelination in organotypic slice cultures of 7‐day‐old (P7) rat and mouse cerebellum. Myelination was evaluated by immunofluorescence analysis of the myelin basic protein (MBP). After 7 days in culture (7DIV), we found that adding PROG (2–5 × 10−5 M) to the culture medium caused a fourfold increase in MBP expression when compared to control slices. The effect of PROG on MBP expression involves the classical intracellular PROG receptor (PR): the selective PR agonist R5020 significantly increased MBP expression and the PR antagonist mifepristone (RU486) completely abolished the effect of PROG on this MBP expression. Moreover, treatment of P7‐cerebellar slice cultures from PR knockout (PRKO) mice with PROG had no significant effect on MBP expression. PROG was metabolized in the cerebellar slices to 5α‐dihydroprogesterone (5α‐DHP) and to the GABAA receptor‐active metabolite 3α,5α‐tetrahydroprogesterone (3α,5α‐THP, allopregnanolone). The 5α‐reductase inhibitor L685‐273 partially inhibited the effect of PROG, and 3α,5α‐THP (2–5 × 10−5 M) significantly stimulated the MBP expression, although to a lesser extent than PROG. The increase in MBP expression by 3α,5α‐THP involved GABAA receptors, as it could be inhibited by the selective GABAA receptor antagonist bicuculline. These findings suggest that progestins stimulate MBP expression and consequently suggest an increase in CNS myelination via two signalling systems, the intracellular PR and membrane GABAA receptors, and they confirm a new role of GABAA receptors in myelination.
Effect of middle cerebral artery occlusion on mRNA expression for the sodium‐coupled vitamin C transporter SVCT2 in rat brain
Authors: Berger Urs V. , Lu Xi‐Chun M. , Liu Weilin , Tang Zhaocheng , Slusher Barbara S. , Hediger Matthias A.
Published: July 2003

The sodium‐vitamin C co‐transporter SVCT2 is primarily responsible for the accumulation of the important antioxidant ascorbate into brain cells. In vitro studies have demonstrated strong expression of this transporter in cultured astrocytes, whereas in situ hybridization analysis has so far detected SVCT2 only in neurons. In the present study, we examined the response of SVCT2 mRNA expression in the brain to focal ischemia induced for 2 h by unilateral middle cerebral artery occlusion. The mRNA expression patterns of SVCT2 and the glutamate‐activated immediate early gene Arc were investigated at 2 and 22 h after ischemia. SVCT2 and Arc mRNA expression was lost in the ischemic core at both time points. In areas outside the core, Arc was strongly up‐regulated, primarily at 2 h, whereas SVCT2 showed an increase at 2 and 22 h. SVCT2 expression was increased in neurons as well as in astrocytes, providing the first evidence for SVCT2 expression in astrocytes in situ. These findings underscore the importance of ascorbate as a neuroprotective agent and may have implications for therapeutic strategies. In addition, the increase of SVCT2 in astrocytes after ischemia suggests that cultured astrocytes are exposed to chronic oxidative stress.
Cloning and characterization of a Caenorhabditis elegans D2‐like dopamine receptor
Authors: Suo Satoshi , Sasagawa Noboru , Ishiura Shoichi
Published: July 2003

The neurotransmitter dopamine plays an important role in the regulation of behavior in both vertebrates and invertebrates. In mammals, dopamine binds and activates two classes of dopamine receptors, D1‐like and D2‐like receptors. However, D2‐like dopamine receptors in Caenorhabditis elegans have not yet been characterized. We have cloned a cDNA encoding a putative C. elegans D2‐like dopamine receptor. The deduced amino acid sequence of the cloned cDNA shows higher sequence similarities to vertebrate D2‐like dopamine receptors than to D1‐like receptors. Two splice variants that differ in the length of their predicted third intracellular loops were identified. The receptor heterologously expressed in cultured cells showed high affinity binding to [125I]iodo‐lysergic acid diethylamide. Dopamine showed the highest affinity for this receptor among several amine neurotransmitters tested. Activation of the heterologously expressed receptor led to the inhibition of cyclic AMP production, confirming that this receptor has the functional property of a D2‐like receptor. We have also analyzed the expression pattern of this receptor and found that the receptor is expressed in several neurons including all the dopaminergic neurons in C. elegans.
Phorbol ester induces CYP2E1 in astrocytes, through a protein kinase C‐ and tyrosine kinase‐dependent mechanism
Authors: Tindberg Niclas
Published: July 2003

Cytochrome P450 2E1 (CYP2E1) is highly inducible in a subset of astrocytes in vivo following ischemic or mechanical injury and in vitro by lipopolysaccharide or interleukin‐1β. In the present study, phorbol‐12,13‐dibutyrate (PDBu) was found to induce catalytically active CYP2E1 more than fourfold in cortical glial cultures. Little induction was seen up to 12 h, and full effects only at 21–24 h of PDBu treatment. CYP2E1 expression in PDBu‐treated cells was enriched in a subset of astrocytes. The protein kinase C inhibitors, staurosporine and calphostin C, and the tyrosine kinase inhibitor genistein, but not its inactive analogue daidzein, prevented the induction of CYP2E1 by PDBu. It is suggested that CYP2E1, together with interleukin‐6 and ciliary neurotrophic factor, is part of a response of astrocytes to cellular stress elicited by, e.g. cerebral injury, cytokines or phorbol ester, and mediated in part through protein kinase C.
Mitochondrial apoptotic cell death and moderate superoxide generation upon selective activation of non‐desensitizing AMPA receptors in hippocampal cultures
Authors: Rego A. Cristina , Monteiro Nuno M. , Silva Ana P. , Gil Joana , Malva João O. , Oliveira Catarina R.
Published: July 2003

In the present work we investigated the effect of selective stimulation of non‐desensitizing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptors in the intracellular processes leading to hippocampal neuronal death and production of reactive oxygen species (ROS). Activation of AMPA receptors in the presence of cyclothiazide (CYZ), a blocker of AMPA receptor desensitization, resulted in the death of approximately 25% of neurones, which was prevented by 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo(f)quinoxaline (NBQX), an AMPA‐preferring receptor antagonist. (+)‐5‐Methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine hydrogen maleate (MK‐801) protected the neurones from necrotic death induced by AMPA or NMDA receptor activation. Neurodegeneration caused by selective activation of non‐desensitizing AMPA receptors, in the presence of AMPA, CYZ and MK‐801, significantly decreased the number of Co2+‐positive neurones, used as a cytochemical marker of Ca2+‐permeable AMPA receptors, but maintained intracellular ATP/ADP. The AMPA‐mediated apoptotic cell death involved mitochondrial cytochrome c release and the activation of caspases‐1 and ‐3, which was prevented by NBQX. Interestingly, although selective activation of AMPA receptors was not associated with production of intracellular peroxides, a moderate increase in superoxide production was observed upon exposure to antimycin A (AA). Furthermore, increased activity of Mn‐ superoxide dismutase (SOD) was observed on selective activation of non‐desensitizing AMPA receptors. Taken together, these data make important contributions to the elucidation of the downstream pathways activated in AMPA receptor‐mediated excitotoxicity in cultured rat hippocampal neurones.
Functional coupling of serotonin and noradrenaline transporters
Authors: Horschitz Sandra , Hummerich René , Schloss Patrick
Published: July 2003

Re‐uptake of the neurotransmitters serotonin and noradrenaline out of the synaptic cleft is mediated by selective transporter proteins, the serotonin transporter and the noradrenaline transporter respectively. Both are integral membrane proteins that are have a high degree of homology and represent members of a larger neurotransmitter transporter superfamily. Several studies have indicated that the serotonin transporter has an an oligomeric structure. To determine whether monoamine transporters can also function in oligomeric structures in situ, we constructed a concatenate consisting of one molecule of serotonin transporter covalently linked to one molecule of noradrenaline transporter. Heterologous expression of this hybrid construct allowed us to analyse the function, i.e. transport activity, and the structure, i.e. the molecular weight of the total construct and of its single components, at the same time. We showed that serotonin–noradrenaline transporter fusion proteins are fully active and exhibit the pharmacological profile of both their individual components. These findings support the hypothesis that monoamine transporters are expressed and may function as oligomeric proteins composed of non‐interacting monomers.
Microdialysis of dopamine interpreted with quantitative model incorporating probe implantation trauma
Authors: Bungay Peter M. , Newton‐Vinson Paige , Isele Wanda , Garris Paul A. , Justice Joseph B.
Published: July 2003

Although microdialysis is widely used to sample endogenous and exogenous substances in vivo, interpretation of the results obtained by this technique remains controversial. The goal of the present study was to examine recent criticism of microdialysis in the specific case of dopamine (DA) measurements in the brain extracellular microenvironment. The apparent steady‐state basal extracellular concentration and extraction fraction of DA were determined in anesthetized rat striatum by the concentration difference (no‐net‐flux) microdialysis technique. A rate constant for extracellular clearance of DA calculated from the extraction fraction was smaller than the previously determined estimate by fast‐scan cyclic voltammetry for cellular uptake of DA. Because the relatively small size of the voltammetric microsensor produces little tissue damage, the discrepancy between the uptake rate constants may be a consequence of trauma from microdialysis probe implantation. The trauma layer has previously been identified by histology and proposed to distort measurements of extracellular DA levels by the no‐net‐flux method. To address this issue, an existing quantitative mathematical model for microdialysis was modified to incorporate a traumatized tissue layer interposed between the probe and surrounding normal tissue. The tissue layers are hypothesized to differ in their rates of neurotransmitter release and uptake. A post‐implantation traumatized layer with reduced uptake and no release can reconcile the discrepancy between DA uptake measured by microdialysis and voltammetry. The model predicts that this trauma layer would cause the DA extraction fraction obtained from microdialysis in vivo calibration techniques, such as no‐net‐flux, to differ from the DA relative recovery and lead to an underestimation of the DA extracellular concentration in the surrounding normal tissue.