bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participation of dorsal raphe nucleus in the behavioral alteration observed after discontinuation of chronic diazepam administration: Possible neural circuitry involved
Authors: Almirón Romina Soledad , Ramírez Oscar Angel 
Published: February 2005

AbstractPrevious findings from our laboratory have demonstrated a positive correlation between the development of tolerance to diazepam (DZ) 5 mg/kg/day over 4 days, and increased hippocampal synaptic plasticity. It seems likely that a similar plastic phenomenon may occur on hippocampal formation after chronic (18 days) DZ administration. We postulate hippocampal long‐term potentiation (LTP) underlying substrate to the behavioral alteration observed after chronic DZ administration. In the present study, we investigated the involvement of the serotonergic (5‐HT) system in the possible neural circuitry recruited during DZ withdrawal and in the increased hippocampal synaptic plasticity associated with the discontinuation of chronic DZ administration. The results of the current research demonstrate an increased neuronal activity in the dorsal raphe nucleus (DRN) during withdrawal. Previous MK‐801 administration impairs the development of anxiety signs observed during withdrawal and the concomitant increased electrical activity on 5‐HT neurons on DRN. These results are discussed in terms of the participation of 5‐HT system in the modulation of hippocampal plasticity developed on DZ withdrawal. Synapse 56:61–68, 2005. © 2005 Wiley‐Liss, Inc.
Short Atrioventricular Mahaim Fibers: Observations on Their Clinical, Electrocardiographic, and Electrophysiologic Profile
Authors: STERNICK EDUARDO BACK , FAGUNDES MÁRCIO L. , CRUZ FERNANDO E.S. , TIMMERMANS CARL , SOSA EDUARDO A. , RODRIGUEZ LUZ‐MARIA , GERKEN LUIZ M. , SCANAVACCA MAURÍCIO I. , WELLENS HEIN J.J. 
Published: February 2005

Introduction: A short atrioventricular decrementally conducting accessory pathway is an uncommon variant of preexcitation. Available data from small series suggest that their decremental properties might not be caused by A‐V nodal‐like tissue. Methods: We compared clinical, electrocardiographic and electrophysiologic parameters in two groups of patients: 8 patients with a short A‐V Mahaim pathway (Group A), and 33 patients with atriofascicular pathways (Group B). Radiofrequency catheter ablation was carried out guided by activation mapping at the annulus in Group A patients and targeting the “M” potential in Group B patients. Results: After ablation of all associated rapidly conducting bypass tracts, 7 of the 8 Group A patients showed clear preexcitation. In only 1 of 8 patients the short A‐V Mahaim fiber was actively engaged in a reentrant tachycardia circuit. During radiofrequency catheter ablation an automatic rhythm occurred in 4 of 8 patients. Intravenous adenosine caused conduction a block in the Mahaim fiber in 3 of the 5 patients tested. In group B, no patient showed clear preexcitation (P < 00001) while 72% had a minimal preexcitation pattern. Twenty‐nine of the 33 patients had a circus movement tachycardia with AV conduction over the atriofascicular fiber. During radiofrequency catheter ablation 30 of 33 patients showed accessory pathway automaticity. Adenosine caused transient block at the atriofascicular pathway in 11 (92%) of the 12 patients tested. Conclusions: While short decrementally conducting right‐sided accessory pathways show a typical ECG pattern different from atriofascicular pathways, their electrophysiologic properties do not seem to be uniform. Those pathways can be successfully interrupted by catheter ablation.
Mechanism of Propensity to Atrial Fibrillation in Patients Undergoing Isthmus Ablation for Typical Atrial Flutter
Authors: RAMANNA HEMANTH , DE BAKKER JACQUES M.T. , HAUER RICHARD N.W. 
Published: February 2005

Background: Patients undergoing isthmus ablation for atrial flutter (AFL) may reveal postablation atrial fibrillation (AF). The electrophysiological mechanism is unclear. In patients with idiopathic AF, enhanced spatial dispersion of right atrial refractoriness was the substrate for the initiation of AF. We hypothesize that dispersion of right atrial refractoriness in patients undergoing AFL ablation is the major cause of postablation AF. Methods: Consecutive patients (n = 42) undergoing isthmus ablation for typical AFL were included. Twelve right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol, starting with one extrastimulus, followed by more aggressive pacing until AF was induced. Mean fibrillatory intervals were used to assess local refractoriness of each recording site. Spatial dispersion of right atrial refractoriness was calculated as the coefficient of dispersion (CD‐value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). A CD‐value of 3.0 or less was defined as normal, whereas CD‐value greater than 3.0 was considered enhanced dispersion. PES and refractoriness analysis were followed by isthmus ablation. Results: Of the 42 patients, 29 had CD‐value of 3.0 or less. In these 29 patients, AF was induced with 1 extrastimulus in only 1 patient, with 2 extrastimuli in 4 patients and burst pacing was required to induce AF in 24 of these 29 patients. Prior to the procedure, 5 of 29 patients had AF episodes, after ablation 6 of 29 patients. Of the 42 patients, 13 had CD‐value greater than 3.0, AF was induced with a single extrastimulus in 11 patients, with 2 extrastimuli in the remaining 2 patients. Of the 13 patients, 11 had AF episodes both before and after ablation (P < 0.001). Conclusion: Enhanced spatial dispersion of right atrial refractoriness may be the substrate for propensity to AF in patients with AFL. The substrate was associated with enhanced inducibility of atrial fibrillation.
Defibrillation Depends on Conductivity Fluctuations and the Degree of Disorganization in Reentry Patterns
Authors: PLANK GERNOT , LEON L. JOSHUA , KIMBER SHANE , VIGMOND EDWARD J. 
Published: February 2005

Introduction: Cardiac fibrillation is the deterioration of the heart's normally well‐organized activity into one or more meandering spiral waves, which subsequently break up into many meandering wave fronts. Delivery of an electric shock (defibrillation) is the only effective way of restoring the normal rhythm. This study focuses on examining whether higher degrees of disorganization requires higher shock strengths to defibrillate and whether microscopic conductivity fluctuations favor shock success. Methods and Results: We developed a three‐dimensional computer bidomain model of a block of cardiac tissue with straight fibers immersed in a conductive bath. The membrane behavior was described by the Courtemanche human atrial action potential model incorporating electroporation and an acetylcholine‐ (ACh) dependent potassium current. Intracellular conductivities were varied stochastically around nominal values with variations of up to 50%. A single rotor reentry was initiated and, by adjusting the spatial ACh variation, the level of organization could be controlled. The single rotor could be stabilized or spiral wave breakup could be provoked leading to fibrillatory‐like activity. For each level of organization, multiple shock timings and strengths were applied to compute the probability of shock success as a function of shock strength. Conclusions: Our results suggest that the level of the small‐scale conductivity fluctuations is a very important factor in defibrillation. A higher variation significantly lowers the required shock strength. Further, we demonstrated that success also heavily depends on the level of organization of the fibrillatory episode. In general, higher levels of disorganization require higher shock strengths to defibrillate.
Response to Pharmacological Challenge of Dissociated Pulmonary Vein Rhythm
Authors: MARROUCHE NASSIR , WAZNI OUSSAMA M. , MARTIN DAVID O. , ROSSILLO ANTONIO , SALIBA WALID , ERCIYES DEMET , SCHWEIKERT ROBERT , KHAYKIN YAARIV , BURKHARDT DAVID , BHARGAVA MANDEEP , VERMA ATUL , ABDUL‐KARIM AHMAD , NATALE ANDREA 
Published: February 2005

Introduction: Characterization of the electrophysiologic behavior of the pulmonary vein (PV) triggers initiating atrial fibrillation (AF) is still lacking. We conducted the current study to evaluate the behavior of the dissociated PV rhythm (PVD) observed after electrical disconnection from the left atrium of the PV responsible for initiation of AF. Methods and Results: Four hundred and seven consecutive patients (102 women; mean age 55 ± 11 years) presented for ablation of symptomatic AF to our laboratory. After isolation, sustained dissociated rhythm (>10 minutes) was documented in 2.1% (34 of 1568 PVs) of the PVs (initiating AF prior to isolation). Adenosine (18 mg IV bolus), verapamil (10 mg IV bolus), phenylephrine (200 mcg bolus followed by infusion at 100 mcg/hour), and isoproterenol (infusion rate of 15 mcg/hour) were administered in these patients. The cycle length of the PV rhythm before and after the administration of drugs was measured. Adenosine prolonged the sinus node (SN) cycle length (from 750 ± 105 to 1,900 ± 200 ms; P < 0.05) and suppressed the PVD. Isoproterenol shortened both the SN (from 750 ± 105 to 420 ± 150 ms; P < 0.05) and the PVD (from 2,225 ± 300 to 800 ± 190 ms; P < 0.05) cycle length. A similar response to adenosine and isoproterenol of the PV firing was observed prior to isolating the arrhythmogenic PV. Phenylephrine prolonged the cycle length of both the SN (from 740 ± 115 to 960 ± 90 ms; P < 0.05) and the PV rhythm (from 2,200 ± 300 to 2,355 ± 280 ms; P = 0.87). Verapamil did not cause a significant change either in the SN or in the PVD cycle length. Conclusion: Our data suggest that the PVD within isolated PV responsible for initiating AF exhibits a response to pharmacologic agents similar to the SN cells.
Calcium Channel Antagonism Reduces Exercise‐Induced Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia Patients with RyR2 Mutations
Authors: SWAN HEIKKI , LAITINEN PÄIVI , KONTULA KIMMO , TOIVONEN LAURI 
Published: February 2005

Introduction: Recently, gain‐of‐function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise‐induced ventricular arrhythmias in patients with RyR2 mutations. Methods and Results: Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on β‐adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76 ± 17% (P < 0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119 ± 21 vs. 127 ± 27 min−1, P < 0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. Conclusions: This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.
Effects of Temporal Application Parameters on Lesion Dimensions During Transvenous Catheter Cryoablation
Authors: TSE HUNG‐FAT , RIPLEY KENNETH L. , LEE KATHY L.F. , SIU CHUNG‐WAH , VAN VLEET JOHN F. , PELKEY WILLIAM L. , LAU CHU‐PAK 
Published: February 2005

Background: Transvenous catheter cryoablation is a novel technique for treating cardiac arrhythmias. However, the relative importance of temporal application parameters on lesion dimension and clinical efficacy has not been studied. Methods and Results: We investigated the effects of (1) application duration: single 2.5 (2.5 × 1) versus single 5 versus double 2.5 (2.5 × 2) versus double 5 (5 × 2) minutes, (2) number of freeze–thaw cycles: single versus double, and (3) electrode contact area: horizontal versus vertical orientation, on the lesion diameter and depth during catheter cryoablation (10F, 6.5‐mm tip‐electrode, CryoCor™, San Diego) in a thigh muscle preparation. A total of 175 lesions (horizontal = 90, vertical = 85) were created in thigh muscle preparations on 10 swine. The lesion diameter and depth were significantly greater using 2.5 × 2 and 5 × 2 application modes as compared with 2.5 × 1 applications (P < 0.05). Horizontal tip‐electrode orientation produced larger lesion diameter (P < 0.05), but not lesion depth as compared with vertical orientation. Multivariate analysis demonstrated that both tip‐electrode orientation and duration of freeze >2.5 minutes were independent predictors for lesion diameter (P < 0.001). However, only duration of freeze >2.5 minutes was an independent predictor for lesion depth (P < 0.001). Conclusions: The dimensions of lesions created by catheter cryoablation are affected by mode of cryoablation application and electrode orientation. Increasing the duration of application, employing multiple freeze–thaw cycles at shorter cycle durations, and orienting the catheter to enhance/increase tissue contact can create a larger lesion.
Topographic Variability of the Esophageal Left Atrial Relation Influencing Ablation Lines in Patients with Atrial Fibrillation
Authors: KOTTKAMP HANS , PIORKOWSKI CHRISTOPHER , TANNER HILDEGARD , KOBZA RICHARD , DORSZEWSKI ANJA , SCHIRDEWAHN PETRA , GERDS‐LI JIN‐HONG , HINDRICKS GERHARD 
Published: February 2005

Introduction: The close anatomic relationship of the posterior wall of the left atrium (LA) and the thermosensitive esophagus creates a potential hazard in catheter ablation procedures. Methods and Results: In 30 patients (pts) with atrial fibrillation (AF) undergoing catheter ablation, we prospectively studied the course and contact of the esophagus in relation to LA and the topographic proximity to ablation lines encircling the right‐sided and left‐sided pulmonary veins (PV) as well as to the posterior line connecting the encircling lines using the electromagnetic mapping system for reconstruction of LA and for tagging of the esophagus. This new technique of anatomic tagging of the esophagus was validated against the CT scan as a standard imaging procedure. The esophageal course was highly variable, extending from courses in direct vicinity to the left‐ or right‐sided PV as well as in the midportion of the posterior LA. In order to avoid energy application in direct proximity to the esophagus, adjustments of the left and right PV encircling lines were necessary in 14/30 pts (47%) and 3/30 (10%). In 30 pts (100%), the mid‐ to inferior areas of the posterior LA revealed contact with the esophagus. Therefore, posterior and inferior linear ablation lines were abandoned and shifted to superior in 29 pts (97%). Conclusions: Anatomic tagging of esophagus revealed a highly variable proximity to different areas of the posterior LA suggesting individual adjustment of encircling and linear ablation lines in AF ablation procedures to avoid the life threatening complication of esophagus perforation.
Right and Left Ventricular Activation Sequence in Patients with Heart Failure and Right Bundle Branch Block: A Detailed Analysis Using Three‐Dimensional Non‐Fluoroscopic Electroanatomic Mapping System
Authors: FANTONI CECILIA , KAWABATA MIHOKO , MASSARO RAIMONDO , REGOLI FRANCOIS , RAFFA SANTI , ARORA VANITA , SALERNO‐URIARTE JORGE A. , KLEIN HELMUT U. , AURICCHIO ANGELO 
Published: February 2005

Introduction: Recently, right bundle branch block (RBBB) was proved to be an important predictor of mortality in heart failure (HF) patients as much as left bundle branch block (LBBB). We characterized endocardial right ventricular (RV) and left ventricular (LV) activation sequence in HF patients with RBBB using a three‐dimensional non‐fluoroscopic electroanatomic contact mapping system (3D‐Map) in order to provide the electrophysiological background to understand whether these patients can benefit from cardiac resynchronization therapy (CRT). Methods and Results: Using 3D‐Map, RV and LV activation sequences were studied in 100 consecutive HF patients. Six of these patients presented with RBBB QRS morphology. The maps of these patients were analyzed and compared post hoc with those of the other 94 HF patients presenting with LBBB. Clinical and hemodynamic profile was significantly worse in RBBB group compared to LBBB. Patients with RBBB showed significantly longer time to RV breakthrough (P < 0.001), longer activation times of RV anterior and lateral regions (P < 0.001), and longer total RV endocardial activation time (P < 0.02) compared to patients with LBBB. Time to LV breakthrough was significantly shorter in patients with RBBB (P < 0.001), while total and regional LV endocardial activation times were not significantly different between the two groups. Conclusions: Degree of LV activation delay is similar between HF patients with LBBB and RBBB. Moreover, patients with RBBB have larger right‐sided conduction delay compared to patients with LBBB. The assessment of these electrical abnormalities is important to understand the rationale for delivering CRT in HF patients with RBBB.
Response to Mivacurium in Patients Carrying the K Variant in the Butyrylcholinesterase Gene
Authors: Gätke Mona R. , Viby-Mogensen Jørgen , Østergaard Doris , Bundgaard Jens R. 
Published: February 2005

Background
Mivacurium is hydrolyzed by the butyrylcholinesterase enzyme, and patients with hereditary changes of the enzyme often have prolonged duration of action of mivacurium. In this study, the authors investigated the significance of the most commonly occurring variant, the Kalow (K) variant, established using DNA analysis, for the response to mivacurium.

Methods
A total of 58 patients carrying either the wild-type butyrylcholinesterase or different combinations of the atypical (A) variant and the K variant were included. Patients who were homozygous for the A variant were given 0.03 mg/kg mivacurium. All other patients received 0.2 mg/kg mivacurium. The neuromuscular block was measured using train-of-four nerve stimulation and mechanomyography. Genotyping was performed with complete nucleotide sequencing.

Results
Heterozygosity of the K variant prolonged the time to train-of-four 0.70 from 26.6 to 34.5 min (30%; not significant) as compared with the wild type. Heterozygosity of the K variant linked to the A variant prolonged the corresponding time from 32 to 42.7 min (33%; P = 0.03) as compared with patients who were heterozygous for solely an A allele. For eight patients who were homozygous for both the A and K variants, the time to 25% recovery was 78-89 min as compared with 44-57 min in patients who were homozygous for the A variant or had only one linked K variant.

Conclusion
The K variant prolongs the duration of action of mivacurium. The current results indicate that the effect is modest when the K variant occurs heterozygously with the wild type or the A variant but is marked in patients who are homozygous for both the A and K variants.
Screening of the Entire Ryanodine Receptor Type 1 Coding Region for Sequence Variants Associated with Malignant Hyperthermia Susceptibility in the North American Population
Authors: Sambuughin Nyamkhishig , Holley Heather , Muldoon Sheila , Brandom Barbara W. , de Bantel Astrid M. , Tobin Joseph R. , Nelson Tom E. , Goldfarb Lev G. 
Published: February 2005

Background
Malignant hyperthermia (MH) is a life-threatening and frequently fatal disorder triggered by commonly used anesthetics. MH susceptibility is a genetically determined predisposition to the development of MH. Mutations in the ryanodine receptor type 1 (RYR1) gene are the major cause of MH susceptibility. The authors sought to develop a reliable genetic screening strategy based on efficient and relatively inexpensive mutation-detection procedures.

Methods
A cohort (n = 30) of North American MH patients and MH-susceptible individuals was studied. RNA and DNA extracted from muscle tissue or blood lymphocytes were used for analysis. The entire RYR1 coding region was amplified in 57 overlapping fragments and subjected to denaturing high-performance liquid chromatography analysis followed by direct nucleotide sequencing to characterize RYR1 alterations.

Results
Nine previously reported and nine unknown RYR1 mutations were identified in 21 of 30 studied patients (70%). Some of the new mutations were located outside of known mutational "hot spots," suggesting that RYR1 contains previously unknown mutation-prone areas requiring analysis. The North American MH/MH-susceptible population is characterized by a high RYR1 allelic heterogeneity.

Conclusions
Denaturing high-performance liquid chromatography analysis of RNA samples extracted from the biopsied skeletal muscle followed by DNA sequencing is a highly efficient methodology for RYR1 mutation detection. This approach allows increasing the rate of mutation detection to 70% and identifying mutations in the entire RYR1 coding region.
Polymorphism of μ-Opioid Receptor Gene (OPRM1:c.118A>G ) Does Not Protect Against Opioid-induced Respiratory Depression despite Reduced Analgesic Response
Authors: Romberg Raymonda R. , Olofsen Erik , Bijl Hans , Taschner Peter E. M. , Teppema Luc J. , Sarton Elise Y. , van Kleef Jack W. , Dahan Albert 
Published: February 2005

Background
The effect of a single nucleotide polymorphism of the mu-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) was investigated on morphine-6-glucuronide (M6G)-induced analgesia and respiratory depression in a group of healthy volunteers.

Methods
Sixteen subjects of either sex received 0.4 mg/kg (n = 8) or 0.6 mg/kg M6G (n = 8). At regular time intervals, the isocapnic acute hypoxic ventilatory response, pain tolerance (derived from a transcutaneous electrical acute pain model), and arterial blood samples were obtained. Data acquisition continued for 14 h after drug infusion. Population pharmacokinetic-pharmacodynamic sigmoid Emax models were applied to the respiratory and pain data. All collected data were analyzed using the statistical program NONMEM (San Francisco, CA).

Results
Four of the subjects were OPRM1:c.118GA heterozygotes, and the remainder of the subjects were OPRM1:c.118AA homozygotes. M6G analgesia: In contrast to analgesic responses in OPRM1:c.118AA homozygotes, responses were small and inconsistent in OPRM1:c.118GA heterozygotes and best described by the function Effect(t) = baseline (P < 0.01 vs. OPRM1:c.118AA homozygotes). Emax and C50 values in heterozygotes equaled 0.55 +/- 0.18 (or a 55% increase in current above baseline) and 161 +/- 42 ng/ml, respectively. M6G-induced respiratory depression: For the acute hypoxic response, neither Emax nor C50 (value = 282 +/- 72 ng/ml) differed between genotypes.

Conclusions
The data indicate that the OPRM1:c.118A>G polymorphism affects opioid analgesic and respiratory effects differentially. Despite reduced analgesic responses to M6G the OPRM1:c.118A>G single-nucleotide polymorphism does not protect against the toxic effects of the tested opioid. However, some caution in the interpretation of the data is needed because of the small sample size. Further studies are needed to explore the link between this polymorphism and respiratory/analgesic responses beyond the small human sample. In OPRM1:c.118AA homozygotes, the potency parameters differed by a factor of 2 for analgesic versus respiratory effect. In this respect, M6G differs favorably from morphine.