Biomedical subjects

W Jung

Publications and source records attributed to W Jung.

At least 55 records · Page 3Linked to original sources

PubMed2000

The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy.

OBJECTIVES: We sought to assess the impact of intermittent atrial fibrillation (AF) on health-related quality of life (QoL). BACKGROUND: Intermittent AF is a common condition with little data on health-related QoL questionnaires to guide investigational therapies. METHODS: Outpatients from four centers, with documented AF (n = 152), completed validated QoL questionnaires (Medical Outcomes Study Short Form 36 [SF-36], Specific Activity, Symptom Checklist, Illness Intrusiveness and University of Toronto AF Severity Scales). Comparison groups were made up of healthy individuals (n = 47) and four cardiac control groups: published (n = 78) and created for study (n = 69) percutaneous transluminal coronary angioplasty (PTCA); published heart failure (n = 216) and published postmyocardial infarction (MI) (n = 107). RESULTS: Across all domains of the SF-36, AF patients reported substantially worse QoL than healthy controls (1.3 to 2.0 standard deviation units), with scores of 24%, 23%, 16% and 30% lower than healthy individuals on measures of physical and social functioning, mental and general health, respectively (all p < 0.001). Patients with AF were either significantly worse (p < 0.05, published controls) or as impaired (study controls) as either PTCA or post-MI patients on all domains of the SF-36 and the same as heart failure controls on SF-36 psychological subscales. Patients with AF were as impaired or worse than study PTCA controls on measures of illness intrusiveness, activity limitations and symptoms. Associations between objective disease indexes and subjective QoL measures had poor correlations and accounted for <6% of the total variability in QoL scores. CONCLUSIONS: Quality of life is as impaired in patients with intermittent AF as in patients with significant structural heart disease. Patients' perception of QoL is not dependent on the objective measures of disease severity that are usually employed.

Anti-Arrhythmia Agents↗

PubMed2000

Clinical experience with implantable atrial and combined atrioventricular defibrillators.

UNLABELLED: The high prevalence of atrial fibrillation (AF) and its clinical complications, the poor efficacy of medical therapy for preventing recurrences, and dissatisfaction with alternative modes of therapy stimulated interest in implantable atrial and combined atrioventricular defibrillators. In a multicenter study, the safety and efficacy of a stand alone implantable atrial defibrillator, the Metrix system, were evaluated. The device was implanted in 51 patients with highly symptomatic episodes of AF refractory to pharmacological treatment. During a follow-up of 9 months, 96% of 227 spontaneous AF episodes were successfully converted to sinus rhythm in 41 patients. In 62 episodes (27%), several shocks and/or additional drug treatment were required to maintain stable sinus rhythm because of early recurrences of AF. A total of 3719 shocks were delivered and no induction of ventricular proarrhythmia or inaccurately synchronized shocks occurred. The AF detection algorithm exhibited a 100% specificity for the recognition of sinus rhythm and a 92.3% sensitivity for the detection of AF. The combined atrioventricular defibrillator, Jewel AF 7250, was evaluated in a multicenter, randomized, cross-over trial. The primary study objectives included: overall safety as determined by complications-free survival at 6 months, efficacy of tiered atrial pacing and defibrillation therapies for termination of spontaneous atrial tachycardias (AT) and AF, and relative sensitivity of a new dual-chamber detection algorithm. The device was implanted in 211 patients with either a history of ventricular tachyarrhythmias (VT/VF) alone or with a history of both AT/AF and VT/VF. During a mean follow-up of 4.5 months, it has been shown that the Jewel AF is safe and effective in treating atrial and ventricular tachyarrhythmias. Pace termination of 85% of AT episodes were achieved with painless delivery of antitachycardia pacing; additional 35% of AT episodes were terminated by high frequency burst pacing. CONCLUSIONS: The stand alone implantable atrial defibrillator may be safe and clinically useful in selected patients for the treatment of highly symptomatic, drug resistant recurrences of AF. The combined atrioventricular defibrillator may be particularly indicated in patients presenting with both a history of atrial and ventricular tachyarrhythmias.

Aged↗

PubMed2000

Quality of life in atrial fibrillation.

In patients with atrial fibrillation (AF), the restoration and maintenance of sinus rhythm is the primary therapeutic goal. Once sinus rhythm is maintained, physiological rate control is restored, and left ventricular ejection fraction, cardiac output, and exercise capacity are increased. This improved cardiovascular performance thereby enhances the patient's ability to perform the functions of normal daily life. The primary intervention for maintaining sinus rhythm after restoration is the use of anti-arrhythmic agents. Although physicians mostly use class 1A anti-arrhythmic drugs, these oral agents only maintain sinus rhythm in a limited number of cases and are accompanied by considerable side effects. Therefore, more effective tools are needed. Effective treatment for AF is based on the above objective criteria, but subjective criteria such as the quality of life are growing in importance. To address these quality-of-life issues, we have initiated a prospective study in which patients are assigned to one of two groups: those with paroxysmal AF who are candidates for permanent implantable atrial defibrillators and those with chronic or paroxysmal AF who are not candidates for atrial defibrillators. Specifically designed questionnaires and various standardized and validated instruments are used to measure quality of life. The questionnaires cover social demographic data, including age, education, occupation level, driving behavior, return to work, and sexual activity. Quality of life is a multidimensional construct, and thus its definition must consider the many factors mentioned above. In the final analysis, therefore, both objective and subjective criteria are necessary to define appropriate treatment of AF.

Adaptation, Psychological↗

PubMed2000

Predictors of success in radiofrequency catheter ablation of atrial flutter.

Radiofrequency catheter ablation of typical atrial flutter at the isthmus between the tricuspid annulus and the inferior vena cava is established. However in selected patients, the creation of a continuous linear lesion at the targeted isthmus requires a lengthened procedure or is not feasible at all and atrial flutter recurrences are common. In a retrospective analysis, we found that an intraoperatively determined distance between the tricuspid annulus and the inferior vena cava of <.2.5 cm is an independent predictor of a lengthened or failed ablation procedure. Additional equipment, e.g., long introducer sheaths, adapted ablation catheter design, or irrigated tip ablation, as well as alternative ablation approaches, e.g., linear lesions between the tricuspid annulus and Eustachian ridge, have been invented in order to increase the acute success rate or decrease fluoroscopy and procedure time. In a prospective study on the effects of various conduction properties at the isthmus between tricuspid annulus and inferior vena cava following radiofrequency ablation of atrial flutter, we showed previously that others than a complete bidirectional conduction block predicts a high recurrence rate of atrial flutter. For determination of transisthmal conduction properties following ablation, established mapping approaches are documentation of double potentials at the ablation line and right atrial activation sequence following posteroseptal and low lateral right atrial pacing. Novel threedimensional mapping systems, i.e., Carto(R) and EnSite(R), may further enhance the accuracy of conventional mapping techniques.

Atrial Flutter↗

PubMed2000

Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes.

Isoflavones have drawn much attention because of their benefits to human health. These compounds, which are produced almost exclusively in legumes, have natural roles in plant defense and root nodulation. Isoflavone synthase catalyzes the first committed step of isoflavone biosynthesis, a branch of the phenylpropanoid pathway. To identify the gene encoding this enzyme, we used a yeast expression assay to screen soybean ESTs encoding cytochrome P450 proteins. We identified two soybean genes encoding isoflavone synthase, and used them to isolate homologous genes from other leguminous species including red clover, white clover, hairy vetch, mung bean, alfalfa, lentil, snow pea, and lupine, as well as from the nonleguminous sugarbeet. We expressed soybean isoflavone synthase in Arabidopsis thaliana, which led to production of the isoflavone genistein in this nonlegume plant. Identification of the isoflavone synthase gene should allow manipulation of the phenylpropanoid pathway for agronomic and nutritional purposes.

Anthocyanins↗

PubMed2000

Gene-modified spontaneous Epstein-Barr virus-transformed lymphoblastoid cell lines as autologous cancer vaccines: mutated p21 ras oncogene as a model.

The transfer of genes coding for tumor antigens (Ags) into Ag-presenting cells is a promising strategy to develop cancer vaccines for patients not limited by major histocompatibility complex restriction. To test whether autologous lymphoblastoid cell lines (LCL) can be used as an alternative to dendritic cells for Ag presentation, we established LCL by spontaneous growth in cyclosporin-containing medium in vitro (SP-LCL). SP-LCL, which have an advantage over B95-8-transfected LCL in that they carry no risk of introducing a new infectious agent when used for vaccination, served as a permanent source for transfection with an episomal Epstein-Barr virus-based expression vector encoding the Ki-ras p21 oncogene carrying a point mutation at codon 12 (muRas) as a model tumor Ag. The ability of muRas-transfected SP-LCL (muRas-LCL) to induce immunoreactivity was determined in vitro. After electroporation with an optimized protocol, muRas-LCL expressed mutated ras peptides for a considerable period of time (at least 8 weeks) on the cell surface. The transfection procedure did not affect the expression of the costimulatory molecules B7.1, intercellular adhesion molecule-1, and leukocyte function associated Ag-3 by SP-LCL. muRas-LCL were able to induce muRas-specific cytotoxic T lymphocytes from three of three healthy donors and one of one patient with pancreatic carcinoma. Our results suggest that the gene transfer of muRas sequences to SP-LCL leads to an endogenous processing of this Ag in the major histocompatibility complex class I pathway and to functional presentation of antigenic peptides to CD8+ T lymphocytes. Autologous SP-LCL can serve as an unlimited renewable source for autologous cellular vaccines and appear to be good candidates as presenters for a wide range of human tumor Ags.

B7-1 Antigen↗

PubMed2000

Hospital readmission after transvenous cardioverter/defibrillator implantation; a single centre study.

AIMS: Hospital readmission after implantation of cardioverter/defibrillators has a major impact on quality of life and cost-effectiveness in defibrillator patients. Rehospitalization has not been studied in large patient populations with modern transvenous defibrillation systems. METHODS AND RESULTS: We report on incidence, reasons, time in follow-up, duration and predictors of hospital readmission in 180 patients after transvenous implantation of a cardioverter/defibrillator during a follow-up period of 25+/-18 months. There were 156 readmissions in 79 patients with a 0.87 readmission rate per patient during the time followed, a 0.46 readmission rate per patient-year of follow-up and a 0.38 readmission rate per patient-year of follow-up for cardiac reasons. The majority of readmissions was caused by multiple appropriate shock interventions (26%), battery depletion (19%) and lead- and device-related complications (14%). The time to first hospital readmission was 12+/-9 months for arrhythmia-related and 20+/-16 months for other cardiac-related reasons (P<0.05), and could not be predicted by clinical variables, respectively. The duration of rehospitalization was 14+/-15 days for cardiac-related reasons and 12+/-17 days for arrhythmia-related reasons. Age >60 years was an independent predictor of rehospitalization time per patient-year of follow-up for both cardiac-related (P<0.005) and arrhythmia-related reasons (P<0.05). CONCLUSION: The rate of hospital readmission per patient-year of follow-up is as high as 0.46 after implantation of a modern cardioverter/defibrillator. Rehospitalization time in such patients is significantly longer in the patient cohort >60 years. The majority of readmissions is caused by multiple appropriate shock treatments. Further studies are needed to systematically investigate strategies for the prevention of rehospitalization in modern ICD therapy.

Adolescent↗

PubMed2000

Comparison of spontaneous atrial fibrillation electrogram potentials with the P-wave electrogram amplitude in dual chamber pacing with unipolar atrial sensing.

AIMS: Although bipolar sensing is recommended and desirable in patients with dual chamber pacemakers (DDD) and intermittent atrial fibrillation (AF) it is a clinical reality that some patients who are given unipolar atrial leads without a prior history of AF may develop intermittent AF during follow-up. It was therefore the purpose of this prospective study to compare the electrogram amplitudes of AF potentials with sinus rhythm P-wave potentials as a relevant factor for appropriate mode switching in dual chamber pacing with unipolar atrial sensing. METHODS AND RESULTS: Forty-two patients with dual chamber pacemakers, unipolar atrial leads and intermittent AF were studied. Aside from measuring the P-wave potential, it was possible in 14 patients (4 women, 10 men; mean age: 61.8 (+/- 13.3) years) additionally to document spontaneous AF electrogram potentials using pacemaker telemetry. A prospective survey study was performed including a 6 month follow-up period with an outpatient clinic visit every 2-3 weeks. The mean P-wave electrogram amplitude was 3.4 (+/- 1.8) mV (range: 1.4-7.4) compared with the mean amplitude during AF of 2.04 (+/- 1.26) mV (range: 0.8-5.2 mV) indicating a significant attenuation of 40% during AF (P < 0.0001). A linear correlation regression analysis revealed that there was a significant correlation between the P-wave and the AF amplitude (P < 0.0001), with a correlation coefficient of r = 0.867. CONCLUSION: Once it is known that a substantial reduction exists in electrogram amplitude, compared with the P wave electrogram potential, an estimate can be made of whether AF potentials will be sensed, if the programming of atrial sensitivity is congruent with the P-wave characteristics and the presence or absence of myopotential triggering.

Atrial Fibrillation↗

PubMed2000

Diagnostic assessment of recurrent unexplained syncope with a new subcutaneously implantable loop recorder. Reveal-Investigators.

AIM: Patients with recurrent syncope undiagnosed after extensive non-invasive and invasive testing pose a diagnostic and therapeutic dilemma. Holter monitoring is nondiagnostic in 90% of cases. Recent developments in loop recorder technology permit long-term ECG monitoring in patients with recurrent unexplained syncope. The aim of this study was to report the worldwide experience with a new subcutaneously implantable loop recorder, implanted in 133 patients with unexplained syncope and negative laboratory investigations. METHODS AND RESULTS: The implantable loop recorder monitors continuously a single lead electrogram using two sensing electrodes on the device shell. The device was implanted in 133 patients, 67 male and 66 female with recurrent syncope. During a mean follow-up of 10.8 +/- 4.3 months after device implantation, 83 patients (62%) experienced syncope or pre-syncope. In the remaining 50 patients no diagnosis could be made because either no events occurred, the patients were lost to follow-up, had adverse events, or died prior to diagnosis. In 72 of the 83 patients with syncope during follow-up (87%), loop recording definitively determined whether an arrhythmia was the cause of symptoms or not. Diagnosis included bradycardia in 21 patients, pacemaker dysfunction in one patient, and tachycardia in 10 patients. One patient experienced multiple rhythm disturbances. Syncope was non-arrhythmic in 40 patients. The remaining 11 patients failed to press the activator. Therapy was instituted in all patients, in whom an arrhythmic cause was found. Severe anticipated device related complications occurred in three patients. CONCLUSION: An implantable loop recorder is useful for establishing a diagnosis when symptoms are recurrent but too infrequent for conventional monitoring techniques.

Equipment Design↗

PubMed2000

Ischemic preconditioning and infarct mass: the effect of hypercholesterolemia and endothelial dysfunction.

In an experimental model of atherosclerosis we investigated whether rabbits fed an atherogenic diet (0.25% cholesterol, 3% coconut oil) develop endothelial dysfunction accompanied with increased infarct mass compared to normal fed rabbits and, whether hypercholesterolemia would interfere with the beneficial outcome of ischemic preconditioning observed in normal rabbits. After four weeks on either a normal or an atherogenic diet, New Zealand White rabbits (n=7 in each group) were subjected to 30 min of myocardial ischemia by occlusion of a branch of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion (infarct studies). For ischemic preconditioning experiments, LAD was additionally occluded twice for 5 min followed by 10 min reperfusion before the long-lasting (30 min) ischemia. Infarct mass was evaluated by triphenyl-tetrazolium staining. Besides the assessment of aortic endothelium-dependent function and NO-release, aortic and cardiac vessels were inspected for atherosclerotic lesions. Total cholesterol serum levels in rabbits on an atherogenic diet were significantly higher (15.3+/-2.7 mmol/L) than those on a standard diet (0.65+/-0.08 mmol/L). The aortas and heart vessels were without any histological evidence of atherosclerosis, whereas endothelial dysfunction and significantly reduced calcium-ionophore stimulated endothelial NO-release were found in isolated aortic rings of hypercholesterolemic animals. Rabbits on a standard diet showed an infarct mass (related to the area at risk) of 41+/-33%, which was reduced to 21+/-2% by ischemic preconditioning (49% decrease, p<0.05). In rabbits on an atherogenic diet, infarct mass was significantly increased to 63+/-3% (52% increase versus standard diet). Interestingly, hypercholesterolemia did not affect the beneficial influence of ischemic preconditioning; infarct mass (21+/-3%, p<0.05 vs hypercholesterolemia) was similar to rabbits on a standard diet with ischemic preconditioning. Our results show that experimental hypercholesterolemia increases infarct mass in nonpreconditioned hearts but it does not interfere with the reduction of infarct mass elicited by preconditioning. This may suggest that NO produced by the endothelium is not a prime factor in the cardioprotective mechanism of preconditioning.

Animals↗

PubMed2000

Production of the isoflavones genistein and daidzein in non-legume dicot and monocot tissues.

Metabolic engineering for production of isoflavones in non-legume plants may provide the health benefits of these phytoestrogens from consumption of more widely used grains. In legumes, isoflavones function in both the symbiotic relationship with rhizobial bacteria and the plant defense response. Expression of a soybean isoflavone synthase (IFS) gene in Arabidopsis plants was previously shown to result in the synthesis and accumulation of the isoflavone genistein in leaf and stem tissue (Jung et al., 2000). Here we further investigate the ability of the heterologous IFS enzyme to interact with the endogenous phenylpropanoid pathway, which provides the substrate for IFS, and produces genistein in several plant tissue systems. In tobacco (Nicotiana tabacum) floral tissue that synthesizes anthocyanins, genistein production was increased relative to leaves. Induction of the flavonoid/anthocyanin branch of the phenylpropanoid pathway through UV-B treatment also enhanced genistein production in Arabidopsis. In a monocot cell system, introduced expression of a transcription factor regulating genes of the anthocyanin pathway was effective in conferring the ability to produce genistein in the presence of the IFS gene. Introduction of a third gene, chalcone reductase, provided the ability to synthesize an additional substrate of IFS resulting in production of the isoflavone daidzein in this system. The genistein produced in tobacco, Arabidopsis, and maize (Zea mays) cells was present in conjugated forms, indicating that endogenous enzymes were capable of recognizing genistein as a substrate. This study provides insight into requirements for metabolic engineering for isoflavone production in non-legume dicot and monocot tissues.

Alcohol Oxidoreductases↗

PubMed2000

Efficacy of single lead VDD pacing in patients with impaired and normal left ventricular function.

Atrial synchronous ventricular pacing seems to be the best pacing mode for patients with advanced AV block and impaired LV function. The long-term follow-up of single lead VDD pacing was studied in 33 patients with impaired LV function and compared to 42 patients with normal LV function. All patients received the same VDD lead and VDDR pacemaker. The lead model with 13-cm AV spacing between the atrial and ventricular electrode was implanted in 89% of the patients. Follow-ups were 1, 3, 6, and 12 months after implantation. The percentage of atrial sensing and the P wave amplitude were determined at each follow-up. Minimal P wave amplitude at implantation was 2.0 +/- 1.4 mV in patients with impaired and 1.7 +/- 0.9 mV with normal LV function (not significant). At the 12-month follow-up, 33 patients with normal and 23 patients with depressed LV function remained paced in the VDD mode. The remaining patients died in five (impaired LV function) and seven cases (normal LV function) or their pacemakers were programmed to the VVI/VVIR pacing mode in four (impaired LV function) and three cases (normal LV function). P wave amplitude did not differ in the two groups (e.g., at month 12: impaired: 1.17 +/- 0.42 mV; normal: 1.09 +/- 0.49 mV). The atrial sensitivity was programmed in most patients to sensitive settings with no differences between the two groups (e.g., at month 12: impaired: 0.13 +/- 0.06 mV; normal: 0.13 +/- 0.05 mV). The diagnostic counters indicated nearly permanent atrial sensing (e.g., at month 12: impaired: 99.3 +/- 2.2%; normal: 99.0 +/- 1.0 mV). In conclusions, single lead VDD pacing restored AV synchronous ventricular pacing in patients with normal and with impaired LV function indicating that it could be an alternative to DDD pacemakers, but not to dual-chamber pacing.

Aged↗

PubMed2000

MR imaging and cardiac pacemakers: in-vitro evaluation and in-vivo studies in 51 patients at 0.5 T.

PURPOSE: To evaluate the safety and feasibility of magnetic resonance (MR) imaging at 0.5 T in patients with implanted cardiac pacemakers. MATERIALS AND METHODS: Twenty-one models of pacemakers and 44 pacemaker electrodes were exposed to in vitro MR imaging with continuous registration of pacemaker output and temperature at the lead tip. Prior to MR imaging examination, pacemakers were programmed to an asynchronous mode (A00, V00, or D00). Pacemakers were examined before and after MR imaging. Forty-four patients with implanted pacemakers underwent 51 MR imaging examinations under cardiologic surveillance, continuous electrocardiography, pulse oximetry, and capnographic monitoring. RESULTS: MR imaging was safely performed in all patients. None of the pacemakers displayed a pacing dysfunction at MR imaging. No changes occurred in the programmed parameters in any device tested in vivo or in vitro. Maximum increases in the temperature at the lead tips were 8.90 degrees C at a specific absorption rate (SAR) of 0.6 W/kg and 23.50 degrees C under a worst-case radio-frequency (RF) heating condition with an SAR of 1.3 W/kg. CONCLUSION: MR imaging at 0.5 T can be safely performed in patients with implanted pacemakers in carefully selected clinical circumstances when appropriate strategies (programming to an asynchronous mode, adequate monitoring techniques, limited RF exposure) are used.

Capnography↗

PubMed2000

[Theory and practical approaches in catheter ablation of atrial flutter].

Atrial flutter can be understood as atrial tachycardia due to a single intraatrial macroreentrant circuit that is determined by fixed or functional boundaries. In various types of atrial flutter, radiofrequency ablation became an established curative therapy. During the course of an ablation procedure, initially, the reentrant circuit has to be determined, e.g. by activation and entrainment mapping. Subsequently, the boundaries have to be identified. By connecting two appropriate boundaries with a linear lesion, the intraatrial reentrant circuit can be inhibited. Finally, it should be proven that the linear lesion results in a complete line of conduction block. Doing so, the acute and long-term results of atrial flutter ablation are comparable to those of other supraventricular tachycardias.

Atrial Flutter↗

PubMed2000

[Atrial defibrillator].

Atrial fibrillation (AF) is a frequent and costly health care problem representing the most common arrhythmia resulting in hospital admission. Total mortality and cardiovascular mortality are significantly increased in patients with AF compared to controls. In addition to symptoms of palpitations, patients with AF have an increased risk of stroke and may also develop decreased exercise tolerance and left ventricular dysfunction. All of these problems may be reversed with restoration and maintenance of sinus rhythm. External electrical cardioversion has been a remarkably effective and safe method for termination of this arrhythmia. Originally described by Lown et al. in 1963, it has been a well accepted mode of acute therapy. However, this technique requires general anesthesia or heavy sedation. Internal atrial defibrillation has been evaluated as an alternative approach to the external technique for over 2 decades. Recent studies have shown that low-energy internal atrial defibrillation using biphasic shocks is an effective and safe means in restoring sinus rhythm in patients with AF and should be considered especially in patients in whom external cardioversion attempts have failed. Implantable Atrial Defibrillator: Recently, a stand alone IAD, the Metrix System (models 3000 and 3020), has entered clinical investigation. Atrial defibrillation is accomplished by a shock delivered between electrodes in the right atrium and the coronary sinus. The right atrium lead has an active fixation in the right atrium. The coronary sinus lead has a natural spiral configuration for retention in the coronary sinus, and can be straightened with a stylet. Both leads are 7 French in diameter and the defibrillation coils are each 6 cm in length. The electrodes may be placed using separate leads, or very soon by using a single bipolar lead. A separate bipolar right ventricular lead is used for R wave synchronization and post shock pacing. The Metrix defibrillator can be used to induce AF by using R wave synchronous shocks and can store intracardiac electrograms (EGMs) for up to 2 minutes from the most recent 6 AF episodes. The device can be programmed into one of the following operating modes: fully automatic, patient activated, monitor mode, bradycardia pacing only, and off. As AF is not life-threatening, in the automatic mode the device is only intermittently active in detecting and treating AF, and this "sleep wake-up" cycle interval is programmable. The device employs extensive processing both for detection and R wave synchronization. In April 1996, the phase I Metrix multicenter clinical trial was started. As of May 1997, a total of 51 Metrix systems had been implanted as part of the phase I multicenter clinical trial. Preliminary data suggest that both defibrillation thresholds and electrograms are stable over time (implant to 3 months). Detection accuracy has been excellent (100% specificity, 92.3% sensitivity) and there have been no errors of R wave selection for synchronization. No proarrhythmias have resulted from over 3700 shocks delivered. The device is effective in electrically converting 96% of the spontaneous episodes of AF. In 27% of episodes several shocks were required because of early recurrence of AF. In 5 patients, the atrial defibrillator was removed: 2 infections, 1 cardiac tamponade, 1 permanent loss of telemetry, 1 patient required His-Bundle ablation because of frequent episodes of drug refractory AF with rapid ventricular response. Initial clinical experience under controlled conditions with the Metrix system suggests that the implantable atrial defibrillator may offer a therapeutic alternative for a subgroup of patients with drug refractory, symptomatic, long lasting, and infrequent episodes of AF. Further efforts must be undertaken to reduce the patient discomfort associated with internal atrial defibrillation in an attempt to make this new therapy acceptable to a larger patient population with AF. (ABSTRACT TRUNCATED)

Algorithms↗

PubMed2000

Characterization and regulation of rat microglial Ca(2+) release-activated Ca(2+) (CRAC) channel by protein kinases.

We measured the activity of the Ca(2+) release-activated Ca(2+) (CRAC) channel present in cultured rat microglia, using the whole-cell mode of patch clamp technique. When the concentration of divalent cations in external solution was reduced to the micromolar range, and Ca(2+) chelating agent BAPTA was included in the pipette solution, we were able to record Na(+) current through CRAC channels in single-channel levels. The unitary Na(+) conductance through CRAC channel was 42.5 pS, which was similar to that of Jurkat cell. The Na(+) current activated slowly, reaching the maximal current level in about 10 min after whole-cell patches were made. The time required for the half-maximal activation of the current was 205 s (+/-31), while it was reduced to 84.3 s (+/-17.7) by including IP(3) in the pipette solution as well. The peak currents ranged from 320 to 985 pA, which corresponded to 64-197 channels per cell. We studied the regulation of the current by protein kinase A (PKA) and protein kinase C (PKC). The current was enhanced by the addition of membrane-permeant analogue of cAMP, dibutyryl cAMP. Pretreating cells with PKA inhibitor, H-89, prevented the effect of dibutyryl cAMP. By contrast, the addition of PKC activator, PDBu, reduced the current. Staurosporine, a PKC inhibitor, prevented the effect of PDBu. These results suggest that CRAC channel in rat microglia is under the regulation of PKA and PKC in opposite directions.

Animals↗

PubMed1999

Right atrial appendage thrombosis in atrial fibrillation: its frequency and its clinical predictors.

This study assesses the incidence of right atrial (RA) chamber and appendage thrombosis in patients with atrial fibrillation (AF) in relation to RA appendage morphology and function. Transthoracic and multiplane transesophageal echocardiography were performed in 102 patients with AF to assess the incidence of RA and left atrial (LA) thrombi and spontaneous echo contrast. Both right and left ventricular sizes, atrial chamber and appendage sizes and function were measured. Twenty-two patients in sinus rhythm served as the control group (SR). Complete visualization of the RA appendage was feasible in 90 patients with AF. Patients with AF had lower tricuspid annular excursion (p = 0.008) and larger RA chamber area (p = 0.0001) than patients in SR. In addition, RA appendage areas were larger (p <0.05) and RA ejection fraction and peak emptying velocities (both p <0.0001) were lower in patients with AF patients than in those in SR. Equivalent differences were found for the LA appendage. Six thrombi were found in the RA appendage and 11 thrombi in the LA appendage in AF patients. Spontaneous echo contrast was found in 57% and 66% in the right atrium and in the left atrium, respectively. AF patients with RA appendage thrombi had a larger RA area (p = 0.0001), and lower RA appendage ejection fraction and emptying velocities (both p = 0.0001) than patients without thrombi. Spontaneous echo contrast was detected in all patients with thrombi. Spontaneous echo contrast was the only independent predictor of RA (p = 0.03) and LA appendage thrombosis (p = 0.036). In conclusion, multiplane transesophageal echocardiography allows the assessment of RA appendage morphology and function. RA spontaneous echo contrast is the only independent predictor of RA appendage thrombosis.

Adult↗

PubMed1999

Hemodynamic and cardiorespiratory function following internal atrial defibrillation for chronic atrial fibrillation.

Internal atrial defibrillation (IAD) is able to restore sinus rhythm in patients with chronic atrial fibrillation (AF) and failed external electrical and/or pharmacologic cardioversion. To assess whether cardiorespiratory and hemodynamic function improve after IAD, 35 patients were prospectively investigated during constant workload exercise by spiroergometry and Doppler echocardiography before IAD, and 1 day and 1 month after IAD. Oxygen uptake kinetics, ventilation, left atrial mechanical function, and pulmonary artery pressure were determined simultaneously at rest and during steady state. During the serial follow-up, 20 patients maintained sinus rhythm. The time interval for achieving the steady state (146 +/- 53 vs 132 +/- 42 seconds; p = 0.5) and the oxygen deficit (645 +/- 190 vs 670 +/- 174 ml; p = 0.7) were not different before and 1 day after IAD, but decreased significantly after 1 month (98 +/- 16 seconds, p = 0.01 and 487 +/- 72 ml, p = 0.02). Exercise pulmonary artery systolic pressures were 38 +/- 13 mm Hg before IAD, increased significantly to 46 +/- 11 mm Hg on day 1 (p = 0.03), and decreased below baseline values at 1 month to 31 +/- 12 mm Hg (p = 0.07). Peak A-wave velocities increased from 0.51 +/- 0.1 m/s after 1 day to 0.67 +/- 0.2 m/s after 1 month (p = 0.03). Restoration of sinus rhythm in patients with AF resistant to external electrical and/or pharmacologic cardioversion improves hemodynamic and cardiorespiratory function at daily activity exercise levels.

Atrial Fibrillation↗