Search PubMed⌕ Search

Biomedical subjects

S A Chen

Publications and source records attributed to S A Chen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Dependence of electrogram duration in right posteroseptal atrium and atrium-pulmonary vein junction on pacing site: mechanism and implications regarding atrioventricular nodal reentrant tachycardia and paroxysmal atrial fibrillation.

INTRODUCTION: The fractionated atrial electrogram, a signal helpful in identifying the target site for radiofrequency catheter ablation of the slow AV nodal pathway, is considered to arise from nonuniform anisotropic electrical activity. However, the effects of pacing sites and radiofrequency ablation on these electrograms are not clear. Similarly, the nature of the fractionated atrial electrogram in the atrium-pulmonary vein junction has yet to be determined. METHODS AND RESULTS: Two experiments were performed in this study. Experiment 1 evaluated the fractionated atrial electrogram at target sites before and after slow AV nodal pathway ablation during sinus rhythm or during pacing from different sites. Group 1A consisted of 16 patients with dual AV nodal pathway physiology and AV nodal reentrant tachycardia who underwent successful ablation without residual slow AV nodal pathway. Group 1B consisted of 7 patients who underwent successful elimination of AV nodal reentry but with residual dual AV nodal pathway physiology. Group 1C consisted of 6 patients who still had AV nodal reentrant tachycardia after two applications of radiofrequency energy. In group 1D, there were 16 patients with dual AV nodal pathway physiology, but without inducible AV nodal reentrant tachycardia. In group 1E, there were 15 patients without dual AV nodal pathway physiology. Experiment 2 investigated the fractionated atrial electrogram in the ostium of the left and right superior pulmonary veins in 18 patients with paroxysmal atrial fibrillation (2A) and in 8 patients without paroxysmal atrial fibrillation (2B). Before radiofrequency ablation, electrogram duration in the right posteroseptal atrium during pacing from the middle coronary sinus or the right posterolateral atrium was shorter than that during pacing from the high right atrium (HRA) in all group 1 patients. After the successful elimination of the slow AV nodal pathway conduction in group 1A, atrial electrogram duration during HRA pacing was shorter than that before ablation. In experiment 2 patients, electrogram duration during pacing from the proximal or distal coronary sinus was shorter than that during pacing from HRA or sinus rhythm. CONCLUSION: These findings suggest that the fractionated atrial electrograms in the right posteroseptal atrium and ostium of left or right superior pulmonary veins are potentially consistent with nonuniform anisotropic propagation. Alternations of electrogram characteristics after successful radiofrequency ablation of the slow AV nodal pathway may arise from the changes of nonuniform anisotropic activity in the right posteroseptal atrium.

Aged↗
PubMed2000

Atrial tachycardias originating from the atrial septum: electrophysiologic characteristics and radiofrequency ablation.

INTRODUCTION: The characteristics of atrial tachycardia (AT) have varied widely among different reports. The anatomic locations of ATs may bias the results. We propose that septal ATs and free-wall ATs have different characteristics. METHODS AND RESULTS: One hundred forty-one patients with AT underwent electropharmacologic study, endocardial mapping, and radiofrequency ablation. Forty-nine (34.7%) patients had septal AT originating from the anteroseptal, mid-septal, and posteroseptal areas. Tachycardia cycle length was similar between septal AT and free-wall AT (367 +/- 46 msec vs 366 +/- 58 msec, P > 0.05). More patients with septal AT required isoproterenol to facilitate induction (44.9% vs 31.5%, P <.0.05). Septal AT was more sensitive to adenosine than free-wall AT (84.4% vs 67.8%, P < 0.05). Only posteroseptal AT showed a positive P wave in lead V1 and negative P wave in all the inferior leads (II, III, aVF). Radiofrequency catheter ablation had a comparable success rate for septal AT and free-wall AT (96% vs 95%) without impairment of AV conduction. During follow-up of 49 +/- 13 months (range 17 to 85), the recurrence rate was similar for septal AT and free-wall AT (3.2% vs 4.6%, P = 0.08). CONCLUSION: Septal AT has electrophysiologic characteristics that are distinct from those of free-wall AT. Catheter ablation of the septal AT is safe and effective.

Adult↗
PubMed2000

Predicting the arrhythmogenic foci of atrial fibrillation before atrial transseptal procedure: implication for catheter ablation.

INTRODUCTION: Use of endocardial atrial activation sequences from recording catheters in the right atrium, His bundle, and coronary sinus to predict the location of initiating foci of atrial fibrillation (AF) before an atrial transseptal procedure has not been reported. The purpose of the present study was to develop an algorithm using endocardial atrial activation sequences to predict the location of initiating foci of AF before transseptal procedure. METHODS AND RESULTS: Seventy-five patients (60 men and 15 women, age 68 +/- 12 years) with frequent episodes of paroxysmal AF were referred for radiofrequency ablation. By retrospective analysis, characteristics of the endocardial atrial activation sequences of right atrial, His-bundle, and coronary sinus catheters from the initial 37 patients were correlated with the location of initiating foci of AF, which were confirmed by successful ablation. The endocardial atrial activation sequences of the other 38 patients were evaluated prospectively to predict the location of initiating foci of AF before transseptal procedure using the algorithm derived from the retrospective analysis. Accuracy of the value <0 msec (obtained by subtracting the time interval between high right atrium and His-bundle atrial activation during atrial premature beats from that obtained during sinus rhythm) for discriminating the superior vena cava or upper portion of the crista terminalis from the pulmonary vein (PV) foci was 100%. When the interval between atrial activation of ostial and distal pairs of the coronary sinus catheter of the atrial premature beats was <0 msec, the accuracy for discriminating left PV foci from right PV foci was 92% in the 24 foci from the left PVs and 100% in the 19 foci from the right PVs. CONCLUSION: Endocardial atrial activation sequences from right atrial, His-bundle, and coronary sinus catheters can accurately predict the location of initiating foci of AF before transseptal procedure. This may facilitate mapping and radiofrequency ablation of paroxysmal AF.

Adult↗
PubMed2000

Pulmonary vein electrogram characteristics in patients with focal sources of paroxysmal atrial fibrillation.

INTRODUCTION: The major source of ectopic beats initiating paroxysmal atrial fibrillation (AF) is from pulmonary veins (PVs). However, the electrogram characteristics of PVs are not well defined. METHODS AND RESULTS: Group I consisted of 129 patients with paroxysmal AF. Group II consisted of 10 patients with a concealed left-sided free-wall accessory pathway. All group I patients had spontaneous AF initiated by ectopic beats, including 169 ectopic foci originating from the PVs. We analyzed PV electrograms from the 169 ectopic foci during sinus beats and ectopic beats. During AF initiation, most (70%) ectopic beats showed PV spike potential followed by atrial potential; 16% of ectopic beats showed PV fragmented potential followed by atrial potential; and 14% showed fusion potentials. The coupling interval between the sinus beat and the ectopic beat was significantly shorter in the inferior PVs than in the superior PVs (171 +/- 48 msec vs 222 +/- 63 msec, P = 0.001) and was significantly shorter in the distal foci than in the ostial foci of PVs (206 +/- 52 msec vs 230 +/- 56 msec, P = 0.01). The incidence of conduction block in the PVs during AF initiation was significantly higher in the inferior PVs than in the superior PVs (12/24 vs 37/145, P = 0.03) and was significantly higher in the distal foci than in the ostial foci of PVs (43/121 vs 6/48, P = 0.04). The maximal amplitude of PV potential was significantly larger in the left PVs than in the right PVs, and the maximal duration of PV potential was significantly longer in the superior PVs than in the inferior PVs during sinus beats in both group I and II patients. CONCLUSION: PV electrogram characteristics were different among the four PVs. Detailed mapping and careful interpretation are the most important steps in ablation of paroxysmal AF originating from PVs.

Adult↗
PubMed2000

Radiofrequency catheter modification of atrioventricular junction in patients with COPD and medically refractory multifocal atrial tachycardia.

BACKGROUND: Multifocal atrial tachycardia (MAT) is a difficult clinical problem generally associated with acute cardiorespiratory illness. The purpose of this study was to assess the feasibility and clinical usefulness of atrioventricular (AV) junction modification as a nonpharmacologic therapy for medically refractory MAT. METHODS AND RESULTS: Thirteen patients with COPD and medically refractory MAT underwent AV junction modification. Complications and outcome of this procedure were monitored. Subjective perceptions of quality of life assessed by a semiquantitative questionnaire and cardiac performance study were obtained before ablation (baseline) and 1 and 6 months after ablation. Radiofrequency energy was applied until the average ventricular rate fell to < 100 beats/min. Ablation procedures controlled the ventricular response in 11 of 13 patients (84%). One patient had unsuccessful modification. Another patient developed delayed complete AV block on the second day after ablation. In these 13 patients, average ventricular rate was reduced from a mean of 145 +/- 11 to 89 +/- 22 beats/min immediately after the ablation (p < 0.01). One patient had recurrent symptomatic MAT at 1 month after ablation; this patient underwent a second procedure without late recurrence. All patients were followed up for at least 6 months (mean, 11 +/- 5 months; range, 6 to 18 months). General quality of life and frequency of significant symptoms improved significantly in patients with successful modification at 1 and 6 months. The left ventricular ejection fraction increased significantly after ablation (44.5 +/- 7.3% at baseline, 49.4 +/- 4. 2% at 1 month, and 50.0 +/- 4.9% at 6 months; all p < 0.05). However, right ventricular ejection fraction remained unchanged (34.7 +/- 6. 2% at baseline, 35.7 +/- 4.4% at 1 month, and 34.3 +/- 4.6% at 6 months; all p > 0.05). The consumption of health-care resources (including frequency of hospital admission and emergency department attendance, antiarrhythmic drug trials) decreased significantly 6 months after AV junction modification. Pulmonary function and theophylline level remained unchanged during follow-up. CONCLUSIONS: AV junction modification offers an effective therapy for controlling ventricular rate in medically refractory MAT. This procedure improves the quality of life and left ventricular function in selected patients with symptomatic and medically refractory MAT.

Aged↗
PubMed2000

Plasma and lymph pharmacokinetics of recombinant human interleukin-2 and polyethylene glycol-modified interleukin-2 in pigs.

Modification of recombinant human interleukin-2 (IL-2) with polyethylene glycol (PEG-IL-2) decreases clearance and might favor absorption into the lymphatics, due to its increased molecular weight. In the present study, we compared the plasma and lymph concentrations of IL-2 and PEG-IL-2 in Yorkshire pigs. The IL-2 regimens were i.v. bolus (0.1-1.6 x 10(6) I.U., MIU/kg), 15-min i.v. infusion (0.1 MIU/kg), or s.c. bolus (0.1-3.0 MIU/kg). The PEG-IL-2 doses were 15-min i.v. infusion (0.01 MIU/kg) or s.c. bolus (0.01-0. 10 MIU/kg). Lymph and plasma data were analyzed using noncompartmental methods and NONMEM. Bioavailability of IL-2 was route- and dose-dependent. Bioavailability of i.v. bolus doses of >/=0.16 MIU/kg was complete but only 39% at 0.1 MIU/kg. For the infusion and s.c. doses, bioavailability was 28 and 42%, respectively. Noncompartmental and NONMEM estimates of clearance and volume of distribution at steady state agreed: 300 ml/h/kg and 570 ml/kg, respectively, for IL-2. The ratio of the area under the curve in lymph and plasma increased from 0.67 to 3.4 when comparing i.v. and s.c. routes, and the s.c. delivery advantage (ratio of dose-normalized ratio of the area under the curve in lymph after s.c. and i.v. administration) was 6.6 to 16. For PEG-IL-2, bioavailability was 100%, clearance was 5.9 ml/h/kg, and volume of distribution at steady state was 370 ml/kg. The ratio of the area under the curve in lymph and plasma increased from 0.33 (i.v.) to 1. 2 (s.c.), and the s.c. delivery advantage was 3.8. Subcutaneous dosing would be favored over i.v. dosing, and IL-2 would be favored over PEG-IL-2 to maximize lymph and minimize plasma exposure. Because IL-2 efficacy may be related to lymph concentrations, dosing regimens can now be designed to test this hypothesis.

Animals↗
PubMed2000

Induction of antitumor immunity with combination of HER2/neu DNA vaccine and interleukin 2 gene-modified tumor vaccine.

The therapeutic effects of both cytokine-secreting tumor vaccine and DNA vaccine were studied using mouse MBT-2 bladder cancer cells as a model. Cytokine-secreting MBT-2 cells were obtained by infecting cells with retroviral particles containing interleukin (IL) 2-, IL-4-, or granulocyte-macrophage colony-stimulating factor (GM-CSF)-expression vector. The MBT-2-IL-2 cells were not tumorigenic in syngenic C3H mice at all. Tumor formation decreased significantly for the MBT-2-GM-CSF cells. MBT-2-IL-2, -IL-4, and -GM-CSF cells were killed by irradiation and tested as tumor vaccines. The irradiated MBT2-IL-2 cells could complete protect mice from the growth of the preexisting tumor cells, and the immune memory lasted for 8 months. On the other hand, irradiated MBT-2-IL-4 and MBT-2-GM-CSF cells were less effective. When the loading tumor mass increased, all tumor vaccines lost protective effects. DNA vaccine encoding the tumor antigen neu was additionally tested to improve the therapeutic efficacy. Coinjection of 60 microg pSV-neu DNA was effective in enhancing the antitumor effects of MBT2-IL-2; however, DNA vaccine alone cannot prevent the progression of the preexisting tumor. Immunohistochemical analysis of tumor infiltrate revealed massive increase of CD4+ lymphoid cells in the group of mice treated with both DNA vaccine and IL-2-secreted tumor vaccine. Western blotting demonstrated the presence of anti-neu antibody in the serum from immunized mice. In contrast, combination of DNA vaccine and MBT-2-GM-CSF has no additive effect. The results indicate the combination of DNA vaccine and IL-2-secreting tumor vaccine can additionally improve therapeutic efficacy, and the efficacy is correlated with the increase of CD4+ T lymphocytes and anti-neu antibody.

Animals↗
PubMed1999

Alterations of heart rate variability after radiofrequency catheter ablation of focal atrial fibrillation originating from pulmonary veins.

BACKGROUND: Transient sinus bradycardia and hypotension have been reported as complications during radiofrequency (RF) ablation of focal atrial fibrillation (AF) originating from pulmonary veins (PVs). This study used heart rate variability (HRV) to evaluate the effects of focal PVs ablation on autonomic function. METHODS AND RESULTS: Thirty-seven patients with paroxysmal AF were referred for ablation. The study group included 30 patients who underwent transseptal ablation of PVs, and the control group included 7 patients who underwent the transseptal procedure without ablation. The mean sinus rate and time-domain (standard deviation of RR intervals and root-mean-square of differences of adjacent RR intervals) and frequency-domain (low frequency, high frequency, and low-frequency/high-frequency ratio) analyses of HRV were obtained by use of 24-hour Holter monitoring before and 1 week, 1 month, and 6 months after ablation. All the triggering points of AF were from PVs, and they were successfully ablated. Severe bradycardia and hypotension were noted during ablation of PVs in 6 patients (group IA); 24 patients without the above complication belonged to group IB. Compared with preablation values, a significant increase in mean sinus rate and low-frequency/high-frequency ratio and a significant decrease in standard deviation of RR intervals, root-mean-square of differences of adjacent RR intervals, low frequency, and high frequency were noted in groups IA and IB patients 1 week after ablation. The changes in HR and HRV recovered spontaneously in the 2 subgroups by 1 month later. These parameters of HRV did not change in the control group after the transseptal procedure. CONCLUSIONS: Transient autonomic dysfunction with alterations in HR and HRV occurred after ablation of focal AF originating from PVs.

Adult↗
PubMed1999

Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation.

BACKGROUND: Atrial fibrillation (AF) can be initiated by ectopic beats originating from the atrial or great venous tissues. This study investigated the anatomic characteristics and electrophysiological properties of pulmonary veins (PVs), as well as the possible mechanisms and response to drugs of ectopic foci, and assessed the effects of radiofrequency (RF) ablation on AF initiated by ectopic beats originating from PVs. METHODS AND RESULTS: Seventy-nine patients with frequent episodes of paroxysmal AF and 10 control patients were included. Distal PVs showed the shortest effective refractory periods (ERPs), and right superior PVs showed a higher incidence of intra-PV conduction block than left superior PVs. Superior and left PVs had longer myocardial sleeves than inferior and right PVs, respectively. These electrophysiological characteristics were similar between AF and control patients. Propranolol, verapamil, and procainamide suppressed ectopic beats that originated from the PVs. Of 116 ectopic foci that initiated AF, 103 (88.8%) originated from PVs. A mean of 7+/-3 RF applications completely eliminated 110 ectopic foci (94.8%). During the 6+/-2-month follow-up period, 68 patients (86. 1%) were free of AF without any antiarrhythmic drugs. Follow-up transesophageal echocardiogram showed 42.4% of ablated PVs had focal stenosis. One patient had mild exertional dyspnea after ablation, but it resolved 3 months later; 1 patient had onset of mild exertional dyspnea 5 months after ablation. CONCLUSIONS: Electrophysiological characteristics of PVs are different from those in the atria. Ectopic beats from PVs can initiate AF, and beta-adrenergic receptor blocker, calcium channel blockers, and sodium channel blockers can suppress these ectopic beats. Careful mapping and elimination of these ectopic foci can cure paroxysmal AF.

Adult↗
PubMed1999

Is 8-mm more effective than 4-mm tip electrode catheter for ablation of typical atrial flutter?

BACKGROUND: The prospective, randomized study comparing 4- with 8-mm tip electrodes for radiofrequency linear ablation of typical atrial flutter is not available. METHODS AND RESULTS: A total of 104 consecutive patients with typical atrial flutter were randomly assigned to undergo radiofrequency linear ablation using a 4- (Group I, n=54) or 8-mm tip electrode (Group II, n=50) catheter (temperature-control model, preset 70 degrees C). If complete bidirectional isthmus block could not be achieved after 5 pulses, the ablation catheter was changed to the other type; the maximal radiofrequency pulse number was limited to <10 pulses. Complete or incomplete isthmus conduction block was assessed by activation sequence in a multielectrode Halo catheter during low lateral right atrial and proximal coronary sinus pacing. Before shifting to the other catheter type, the 8-mm electrode catheter achieved higher complete isthmus block rate (92% versus 67%, P<0.05) with fewer pulses (2+/-1 versus 3+/-1, P<0.05), shorter procedure time (24+/-15 versus 31+/-12 minutes, P<0.05), and shorter fluoroscopic time (14+/-10 versus 23+/-15 minutes, P<0.05). After 5 failed ablation pulses, 12 (67%) of 18 patients in group I attained complete isthmus block by using an 8-mm tip catheter, but none of 4 patients in group II achieved complete block by changing to a 4-mm tip catheter. CONCLUSIONS: The 8-mm tip electrodes are more effective than the standard 4-mm length electrodes in linear ablation for typical atrial flutter. This clinical benefit may be of particular value for some patients with broad and/or thick isthmus.

Aged↗
PubMed1999

Effects of radiofrequency catheter ablation on quality of life in patients with atrial flutter.

The long-term effects of radiofrequency catheter ablation on quality of life in patients with typical atrial flutter are still unknown. This study included 100 consecutive patients with clinically documented typical atrial flutter. Subjective perception of quality of life was assessed by a semiquantitative questionnaire before, and 1 and 6 months after ablation. Ablation of typical atrial flutter was associated with a significant improvement in the general quality of life, frequency of significant symptoms, and symptoms during attacks. The frequency of hospital admission and emergency room visits, and number of antiarrhythmic drugs significantly decreased after ablation. Activity capacity significantly improved after ablation in patients with depressed left ventricular function. All improvements after ablation were maintained over 6-month follow-up. However, patients with atrial fibrillation compared with those without atrial fibrillation before ablation had less improvement in the general quality of life, frequency of significant symptoms, and symptoms during attacks (including palpitation, asthenia, effort, dyspnea, rest dyspnea, and dizziness). Furthermore, patients with atrial fibrillation before ablation needed more antiarrhythmic drugs, and had a higher frequency of hospital admission and emergent room visits at 6-month follow-up (all variables p <0.01). Multivariate analysis demonstrated that only the presence of atrial fibrillation before ablation could independently predict improvement in general quality of life (p = 0.03), frequency of significant symptoms (p = 0.03), symptoms during attacks (p = 0.04), and decrease in the consumption of health care resources including antiarrhythmic drugs (p = 0.01), hospital admission (p = 0.02), and emergency room visits (p = 0.02). Ablation of typical atrial flutter could significantly improve quality of life, but patients who had atrial flutter associated with atrial fibrillation before ablation had less improvement than those without atrial fibrillation.

Activities of Daily Living↗
PubMed1999

Regional differences in the recovery course of tachycardia-induced changes of atrial electrophysiological properties.

BACKGROUND: Regional differences in recovery of tachycardia-induced changes of atrial electrophysiological properties have not been well studied. METHODS AND RESULTS: In the control group (5 dogs), atrial effective refractory period (AERP) and inducibility of atrial fibrillation (AF) were assessed before and every 4 hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8-week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF were assessed before and after complete AVJ ablation with 8-week rapid right atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs), AERP and inducibility of AF were assessed before and after 8-week rapid left atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were obtained from 7 epicardial sites. In the control group, atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change. In the 2 experimental groups, recovery of atrial electrophysiological properties included a progressive recovery of AERP shortening, recovery of AERP maladaptation, and decrease of duration and episodes of reinduced AF. However, recovery of shortening and maladaptation of AERP and inducibility of AF was slower at the LA than at the RA and Bachmann's bundle. CONCLUSIONS: The LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties, and this might play a critical role in initiation of AF.

Animals↗
PubMed1999

Stimulation of large-conductance Ca2+-activated K+ channels by Evans blue in cultured endothelial cells of human umbilical veins.

The effect of Evans blue (EB) on large-conductance Ca2+-activated K+ (BKCa) channels was investigated in cultured endothelial cells of human umbilical veins. In whole-cell configuration, EB (50 microM) reversibly increased the amplitude of K+ outward currents (IK). When the patch pipettes were filled with 10 mM EGTA, its stimulatory effect on IK was unaltered. Further application of EB in the presence of suramin, a blocker of P2-purinergic receptor, or AOPCP, an inhibitor of 5'-nucleotidase, still increased IK. However, charybdotoxin (100 nM) suppressed EB-induced increase in IK. In inside-out configuration, bath application of EB (50 microM) did not change single channel conductance but significantly increased the activity of BKCa channels. The EB-induced increase in the activity of BKCa channels was independent on internal Ca2+. EB (50 microM) shifted the activation curve of BKCa channels to less positive membrane potentials by approximately 20 mV. The change in the kinetic behavior of BKCa channels caused by EB in these cells is due to an increase in mean open time and a decrease in mean closed time. These results indicate that EB can stimulate the activity of BKCa channel in endothelial cells. This effect is unrelated to its blockade of P2-purinergic receptors or inhibition of 5'-nucleotidase. The direct stimulation of these ionic channels by EB may contribute to its effect on capillary permeability.

Adenosine Diphosphate↗
PubMed1999

Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man.

BACKGROUND: In animal studies, atrial fibrillation has been shown to shorten the atrial refractory period and impair its rate adaptation. However, little is known about the effects of chronic atrial fibrillation on atrial electrophysiology and its recovery course in humans. METHODS AND RESULTS: Nineteen patients, mean age 64 +/- 14 years, with chronic atrial fibrillation of more than six months duration were included in this study. All of them were successfully converted to sinus rhythm with an external defibrillator. Atrial effective refractory periods at right atrial appendage and distal coronary sinus were determined with five pacing cycle lengths (300, 400, 500, 600 and 700 ms) at 30 min after cardioversion and once a day for four days. The atrial conduction properties, including P wave duration of surface ECG, and right and left atrial conduction times, were also measured at the same time interval. Twenty age-matched patients without a history of atrial tachyarrhythmia were evaluated as controls. In comparison with controls, chronic atrial fibrillation significantly shortened the atrial effective refractory period, impaired its rate adaptation response, especially at distal coronary sinus, and depressed the conduction properties of atria. The atrial conduction properties did not change during the four-day follow-up period; however, the atrial effective refractory period was gradually prolonged and its rate adaptation response improved after restoration of sinus rhythm. CONCLUSIONS: In humans, chronic atrial fibrillation significantly shortened the atrial effective refractory period, and impaired its rate adaptation response. Restoration and maintenance of sinus rhythm could reverse these electrophysiological changes.

Aged↗
PubMed1999

Electropharmacologic characteristics of ventricular proarrhythmia induced by ibutilide.

The purpose of this study was to evaluate in vivo the proarrhythmic effects of ibutilide in dogs with or without ventricular hypertrophy. Fourteen dogs received repeated experiments both during the acute and chronic phases (8 weeks, with ventricular hypertrophy) of complete atrioventricular (AV) block. Twelve-lead ECG, monophasic action potentials in the left and right ventricle were recorded before and after each dose of ibutilide (0.01-0.08 mg/kg) during different ventricular rates. In these dogs, ibutilide increased QT interval, biventricular APD90, interventricular deltaAPD90 (difference between the left and right ventricular APD90), and QT dispersion, and induced early afterdepolarizations in a dose-dependent manner. The interventricular deltaAPD90, QT dispersion, and increases of QT interval were more pronounced during slower ventricular rates. There were greater QT interval, biventricular APD90 interventricular deltaAPD90, and QT dispersion values during chronic AV block than during acute AV block. Moreover, ibutilide can induce higher incidences of early afterdepolarizations and torsades de pointes [six (43%) of 14 versus 0 of 14; p < 0.05] during chronic AV block than during acute AV block. In conclusion, ibutilide can prolong ventricular repolarization and increase dispersion of ventricular repolarization in a dose-dependent and reverse rate-dependent manner. The high incidence of torsades de pointes in the dogs during chronic AV block suggests the importance of ventricular hypertrophy in the occurrence of ibutilide-induced proarrhythmia.

Action Potentials↗