Association of QRS Complex Fragmentation with QT Interval Prolongation in Patients with Ischemic Heart Disease.

BACKGROUND: The fragmented QRS complex (FQRS) was found to be associated to malignant ventricular arrhythmias and sudden death in patients with hypertrophic cardiomyopathy and other entities. There is scant data available correlating the presence of FQRS with QT interval prolongation in patients with ischemic heart disease (IHD). METHODS: A descriptive, retrospective, cross-sectional study was performed in 123 patients with IHD to analyze and correlate the presence of FQRS with QT interval prolongation in the conventional 12-leads electrocardiogram in patients with documented chronic IHD. RESULTS: There were 62% male patients. The mean age was 63.8±12.6 years. Thirty six (44%) patients had fragmented QRS (64% men and 36% women). The duration of QT and QTc, the mean values were 413±59ms, and 463±67ms, respectively. Of the 36 patients with FQRS, 23 patients have prolongation of the QTc interval, and 13 patients did not present it. Of the 45 patients without FQRS, 21 of them have prolongation of the QTc interval, and 24 patients did not have it. These data resulted in a sensitivity of 52% with a moderate SnNout, a specificity of 65% with moderate SpPin, a positive predictive accuracy of 64%, a negative predictive accuracy of 53%. These data resulted in a prevalence of 54%. CONCLUSION: the presence of FQRS in the ECG has a moderate sensitivity and specificity, as well as, moderate negative and positive predictive value of the existence of QT interval prolongation in patients with ischemic heart disease.

Synthesis and bioactivity evaluation of brassinosteroid analogs.

Four new analogs of 28-homocastasterone have been synthesized and completely characterized for the first time from stigmasterol. (22R, 23R,24S)-3beta-acetoxy-22,23-dihydroxy-5alpha-stigmastan+ ++-6-one (17), (22R,23R,24S)-3beta-bromo-22,23-dihydroxy-5alpha-stigmast an-6-one (18), (22R,23R,24S)-3beta-acetoxy-5,22, 23-trihydroxy-5alpha-stigmastan-6-one (20), and (22R,23R, 24S)-3beta-bromo-5,22,23-trihydroxy-5alpha-stigmastan-6-one (21), were obtained through a synthetic route based on regioselective Delta(5) epoxidation. Compounds 17 and 18, bearing a 5alphaH moiety, were prepared through a reductive opening of the 5beta,6beta epoxy precursor, and compounds 20 and 21, analogs with a 5alphaOH moiety were obtained by hydrolytic opening of a mixture of 5alpha,6alpha and 5beta,6beta epoxy precursors. Known compounds 19 and 22 were also obtained following the described synthetic routes, respectively. The new compounds were tested with the traditional auxin-like bioassay for brassinosteroids with 19 and 22 as standards. All compounds were comparatively evaluated for their inhibitory effect on the replication of DNA (HSV-1) virus.

Unmasking of fast and slow atrioventricular nodal pathways by successful radiofrequency ablation of two accessory atrioventricular connections.

Electrophysiologic findings suggesting the coexistence of dual atrioventricular (AV) nodal pathways and accessory AV connections have been previously described. Anterograde conduction through the accessory pathway (AP) may preclude the diagnosis of AV nodal dual pathway physiology during atrial stimulation. This study reports on a patient with manifest Wolff-Parkinson-White syndrome with clinically documented paroxysmal atrial fibrillation, in whom dual AV nodal pathways were unmasked after successful radiofrequency ablation of two accessory AV connections. In spite of detailed investigation, fast and slow AV nodal pathways were not detected in the first electrophysiologic study 8 years before ablation, nor were they detected during preablation study because of exclusive anomalous anterograde conduction. The anterograde AP effective refractory period was shorter than that of the fast and slow AV nodal pathways, and was limited by atrial refractoriness at 190 ms. The present findings strongly suggest the necessity for a careful postablation eletrophysiologic study before and after isoproterenol administration with specific evaluation of AV nodal conduction. This is the first documented report on the finding of AV nodal dual pathway physiology and reentry after successful radiofrequency ablation of two APs. This finding may be of great therapeutic significance in light of the feasibility of slow pathway ablation also during a single session, had AV nodal reentry been induced in a sustained manner after ablation of the AP to prevent late recurrence of tachycardia.

Electrophysiological effects of MS-551 in humans: a class III antiarrhythmic agent.

To investigate the clinical effects of MS-551, a Class III antiarrhythmic agent, 11 patients underwent electrophysiological study. MS-551 was given intravenously as an initial dose of 0.2 or 0.3 mg/kg for 5 minutes followed by the continuous infusion at 0.2 or 0.3 mg/kg for 30 minutes, respectively, in all patients. The rate corrected QT interval increased significantly from 3 minutes after the beginning of MS-551 infusion. The sinus heart rate decreased significantly by 8% at 10 minutes after the drug administration (P < 0.025). Mean PR and QRS intervals, and blood pressure were not significantly affected by the drug. Mean PA, AH, and HV intervals during sinus rhythm were also not affected. The effective refractory periods (ERPs) of the atrium and ventricle were significantly prolonged by 13% from 202 +/- 24 ms to 231 +/- 26 ms (P < 0.0005), and by 7% from 238 +/- 11 ms to 257 +/- 13 ms (P < 0.002), respectively, by MS-551. The ERP of the atrioventricular node and sinoatrial nodal recovery time were not changed significantly by the drug. This is a report of the effects of MS-551 in humans. This agent could be useful for treatment of tachyarrhythmias by prolongation of ERPs of the atrium and ventricle without significant variations of blood pressure and intracardiac conduction times. It is noteworthy that MS-551 slightly but significantly decreased heart rate.

Cleavage reaction of 5 beta, 6 beta steroidal epoxides carrying different groups at C-3.

The particular behavior of 5 beta, 6 beta steroidal epoxides carrying different groups at C-3 was studied. These epoxides may exhibit different cleavage behavior according to the nature of the solvent, the acid-base state of the medium, and the leaving abilities of the C-3 substituent. Results and alternative mechanisms are presented.

Effects of aprindine on electrophysiological properties of the atrial muscle in man.

The effects of aprindine on atrial vulnerability were studied in 11 patients; 9 with paroxysmal atrial fibrillation (PAF), and 2 with Wolff-Parkinson-White syndrome, aged 19 to 69 (55.9 +/- 16.5; mean +/- SD). Before and 10 min after the intravenous injection of aprindine (1.5 mg/kg), programmed extrastimulation was performed from the right atrial appendage. Atrial vulnerability was assessed by evaluating the repetitive atrial firing zone (RAFZ), conduction delay zone (CDZ), maximum conduction delay (Max. CD) and fragmented atrial activity zone (FAAZ). After the injection, the duration of the P wave and QTc interval was significantly prolonged without any change in blood pressure or heart rate. RAF was observed in 8 patients under control conditions. However, after the injection of aprindine, the RAFZ completely disappeared in 2 patients, was narrowed in 4, and became wider in 1. AF was induced in the remaining patient. The zone significantly reduced (p < 0.01) without any change in CDZ or Max. CD. While FAA was observed in 5 patients under control conditions, it completely disappeared in 2 patients, was narrowed in 1, and did not change in the remaining 7 after the injection of aprindine. In patients whose RAFZ narrowed after administration of aprindine, the wavelength, as determined from the atrial effective refractory period and conduction velocity, was augmented. These results indicate that aprindine suppresses atrial vulnerability with an augmentation of the wavelength. However aprindine exaggerated atrial vulnerability in some patients, such that atrial fibrillation was induced.

Radiofrequency catheter ablation for atrioventricular node reentry tachycardia with multiple slow atrioventricular node pathways.

Catheter ablation was attempted in 2 patients with atrioventricular node reentry tachycardia which showed fast, intermediate and slow anterograde atrioventricular node pathways. Radiofrequency currents were applied within a restricted area of the tricuspid annulus between the His bundle and the ostium of the coronary sinus where presumed slow pathway potentials were identified. Elimination of both the intermediate and the slow pathways, with preservation of anterograde and retrograde fast pathway conduction, was achieved in both patients.

Possible role of supernormal atrial conduction in the genesis of atrial fibrillation in patients with idiopathic paroxysmal atrial fibrillation.

OBJECTIVE: The occurrence of supernormal excitability and conduction in the atrium has been attributed to the internodal pathways in several animal experiments. However, little is known about the role of supernormal atrial conduction (SNC) in the genesis of arrhythmias. The specific aim of this study was to evaluate prospectively the relationship between SNC, atrial conduction defects and atrial fibrillation in patients with idiopathic paroxysmal atrial fibrillation. METHODS: Programmed atrial stimulation was performed in 38 control patients (group 1), and 21 patients with idiopathic paroxysmal atrial fibrillation (group 2) to assess some determinants of atrial conduction defects, SNC, and atrial fibrillation inducibility. RESULTS: The mean P-wave duration was 99 +/- 8 ms in group 1, and 110 +/- 12 ms in group 2; p < 0.001. The maximum interatrial conduction delay was 36 +/- 40 ms in group 1, and 56 +/- 21 ms in group 2; p < 0.005. Supernormal atrial conduction was observed in 27 (71 percent) patients of group 1, and in 5 (24 percent) of group 2; p < 0.0003. The SNC zone was 70 +/- 29 ms in group 1, and 16 +/- 31 ms in group 2; p < 0.0001. The maximum decrease in conduction time during the period of SNC was 12 +/- 4 ms in group 1 and 3 +/- 6 ms in group 2; p < 0.0005. The SNC zone showed a significant inverse correlation with the P-wave duration (r = -0.53; p < 0.0005), and with the maximum conduction delay (r = -0.38; p < 0.005). CONCLUSIONS: Patients with idiopathic paroxysmal atrial fibrillation have a significantly decreased incidence of SNC than controls. There is an inverse relation between the atrial conduction defects and the SNC. The association of the absence of SNC with defects in atrial conduction may play some role in the development of atrial fibrillation in patients with idiopathic paroxysmal atrial fibrillation.

Supernormal atrial conduction and its relation to atrial vulnerability and atrial fibrillation in patients with sick sinus syndrome and paroxysmal atrial fibrillation.

The purpose of this study was to evaluate prospectively the relationship between supernormal atrial conduction (SNC) and the atrial vulnerability to fibrillation in patients with sick sinus syndrome (SSS) and paroxysmal atrial fibrillation (PAF). Programmed atrial stimulation was performed in 32 age-matched control patients (group I), 26 with SSS but without tachyarrhythmias (group II), and 24 with both SSS and PAF (group III) to assess some determinants of atrial vulnerability, SNC, and atrial fibrillation inducibility. Supernormal atrial conduction was observed in 20 (63%) patients of group I, 12 (46%) patients of group II, and 5 (21%) patients of group III (group I vs group III; p < 0.002). The SNC zone was 46 +/- 44 msec in group I, 36 +/- 42 msec in group II, and 12 +/- 24 msec in group III. (group I vs group III; p < 0.001). The absence of SNC showed a specificity of 89% and a positive predictive accuracy of 79% in predicting inducibility of atrial fibrillation. The sensitivity was 33% and the negative predictive accuracy was 52%. The SNC zone showed a significant inverse correlation with P wave duration (r = -0.32; p < 0.003), intraatrial conduction time (r = -0.28; p < 0.02), and maximum conduction delay (r = -0.23; p < 0.05). The maximum decrease in conduction time during supernormal conduction showed a significant inverse correlation with P wave duration (r = -0.27; p < 0.02), intraatrial conduction time (r = -0.26; p < 0.02), and with the maximum conduction delay (r = -0.27; p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic demonstration of anterograde fast and slow pathways within the His bundle in patients with normal intraventricular conduction.

Electrophysiological evidence of functional longitudinal dissociation has been shown in different structures of the normal conduction system of the heart and in anomalous atrioventricular (AV) pathways. The typical sudden fast-to-slow jump phenomenon, which is commonly observed in patients with dual AV nodal pathways, has not been demonstrated so far within the normal His bundle. Herein we report unusual electrophysiological properties of the His bundle in two patients with normal intraventricular conduction. Of 86 patients with discontinuous anterograde AV function curves, programmed atrial stimulation revealed dual anterograde His bundle pathways in only 2 (2.3%) patients. Extrastimuli introduced at critically timed coupling intervals produced a sudden marked increase in H2-V2 interval suggesting failure of fast pathway with conduction proceeding through a slower pathway with shorter refractory period. With further decreasing coupling intervals, the second H2-V2 curve showed decremental conduction which allowed a type II gap phenomenon in the right bundle branch to occur in one of the patients. No echo beats were observed. These results provide the first electrophysiological demonstration, in patients with normal intraventricular conduction, of anterograde failure of a fast His bundle pathway with subsequent conduction through a slow His bundle pathway. His bundle duality was manifested by dual conduction times and refractory periods. These observations further expand our knowledge on the electrophysiologic properties of the His bundle.

Repetitive atrial firing and fragmented atrial activity elicited by extrastimuli in the sick sinus syndrome with and without abnormal atrial electrograms.

Endocardial catheter mapping of the right atrium during sinus rhythm and programmed atrial stimulation were performed in 50 patients with sick sinus syndrome to investigate the relationship between abnormal atrial electrograms recorded during sinus rhythm and some determinants of the atrial vulnerability such as repetitive atrial firing and fragmented atrial activity elicited by single extrastimulus. The patients were divided into 2 groups on the basis of the presence (Group I) or absence (Group II) of abnormal atrial electrograms recorded during sinus rhythm. In Group I (N = 32), repetitive atrial firing was induced in 23 (72%) patients, and in Group II (N = 18) in 6 (33%) patients; p less than 0.01. The repetitive atrial firing zone was 41 +/- 37 ms in Group I and 12 +/- 18 ms in Group II; p less than 0.001. Fragmented atrial activity was induced in 30 (94%) patients from Group I, and in 8 (44%) patients from Group II; p less than 0.0001. The fragmented atrial activity zone was 47 +/- 42 ms in Group I and 14 +/- 19 ms in Group II; p less than 0.0001. The atrial electrogram width at the premature beat (A2; p < 0.02) and the maximum A2/A1 ratio (p < 0.002) were 178 +/- 53 ms and 196% +/- 40%, respectively in Group I, and 141 +/- 36 ms and 159% +/- 30%, respectively in Group II. Atrial fibrillation was induced in 13 (41%) patients from Group I, and in 1 (6%) patient from Group II (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of the suppression of repetitive atrial firing by isoproterenol--comparison with disopyramide.

To investigate whether isoproterenol (Iso) could suppress the initiation of repetitive atrial firing (RAF), we investigated its effect on RAF in comparison with that of disopyramide (Diso). Extrastimuli at a basic cycle length of 500 ms were delivered from the high right atrium in 49 patients who received an intravenous infusion of Iso (0.01 microgram/kg per min) and in 39 patients given intravenous Diso (2 mg/kg per 10 min). Induction of RAF, the atrial effective refractory period (A-ERP), and the maximum conduction delay (MCD) were measured. Iso abolished the induction of RAF in 13/19 (68%) patients, while Diso did so in 13/22 (59%) patients. Thirty-four of the 41 patients with RAF in the baseline study had an A-ERP < 250 ms and an MCD > 40 ms. Iso significantly decreased the A-ERP from 205 +/- 26 to 194 +/- 23 ms (P < 0.01) and significantly decreased the MCD from 67 +/- 24 to 39 +/- 16 ms (P < 0.0001) in 19 patients with RAF. On the other hand, Diso significantly increased the A-ERP from 203 +/- 31 to 235 +/- 36 ms (P < 0.0001), and significantly diminished the MCD from 68 +/- 31 to 55 +/- 30 ms (P < 0.01) in 22 patients with RAF. In patients with new RAF (n = 7) or re-induced RAF (n = 14) during Iso or after Diso, the MCD was more than 40 ms. Our results suggest that there are two different modes of RAF suppression, i.e. shortening or lengthening of the A-ERP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravenous verapamil on atrial vulnerability.

To investigate the effects of verapamil on indicators of atrial vulnerability, we examined 30 patients with paroxysmal supraventricular tachycardia who received intravenous verapamil during an electrophysiologic study. Single atrial extrastimuli were given before and after intravenous administration of verapamil to induce repetitive atrial firing (RAF) or atrial fibrillation, and to examine the maximum A2/A1, which was defined as the maximum ratio of the duration of the atrial electrogram resulting from premature stimulation (A2) to that resulting from the basic drive beat (A1). The maximum A2/A1 increased from 145 +/- 20% to 154 +/- 25% (p < 0.02) after verapamil administration. The maximum A2/A1 in patients in whom neither RAF nor atrial fibrillation were induced both before and after verapamil were smaller than those in patients in whom RAF was induced only after verapamil (before; 138 +/- 20% vs 165 +/- 15%, p < 0.02. after; 144 +/- 22% vs 172 +/- 17%, p < 0.05). RAF or atrial fibrillation was induced only after verapamil in 6 patients, who showed a maximum A2/A1 before verapamil of 150% or more. These data suggest that verapamil may induce repetitive atrial firing and possibly atrial fibrillation in some predisposed patients, especially in those that have a greater maximum A2/A1, which may be an indicator of local intraatrial conduction delay before drug infusion.

Evidence of quadruple anterograde atrioventricular nodal pathways in a patient with atrioventricular node reentry.

Functional longitudinal dissociation of the atrioventricular (AV) node exhibiting two discrete discontinuities in AV nodal conduction curves suggestive of triple AV nodal pathways has been described. The authors report here unusual electrophysiologic properties of the AV node in a patient with documented episodes of paroxysmal supraventricular tachycardia. Programmed atrial extrastimuli introduced at A1-A2 coupling intervals of 390 ms with a driven cycle length of 500 ms produced a sudden marked increase of 75 ms at the A2-H2 intervals suggesting failure of the fast pathway with conduction proceeding through a slower pathway with a shorter refractory period. With further decreasing coupling intervals, a second sudden jump of 70 ms and a third one of 150 ms occurred at A1-A2 coupling intervals of 330 and 290 ms, respectively. Beyond the first sudden jump, atrial echoes occurred when sufficiently slow pathway delay permitted recovery of the fast pathway for retrograde conduction. The atrial echo zone was 170 ms. These electrophysiologic demonstrations of reentry within the AV node in a patient with clinically documented supraventricular tachycardia and the existence of four ranges of AH conduction times and refractory periods strongly suggest the presence of quadruple anterograde AV nodal pathways and a variety of potential loops available for the development of sustained AV nodal reentrant tachycardia.

Incidence and electrophysiologic characteristics of supernormal atrial conduction in humans.

The incidence and electrophysiologic characteristics of supernormal atrial conduction (SNC) were examined by cardiac stimulation in 53 control subjects. Their ages ranged from 15 to 71 years (mean age, 50 +/- 21 years) (mean +/- SD). There were 27 women and 26 men in the study. Conduction of premature atrial responses from the sinus node to the atrioventricular node (intraatrial conduction time) was supernormal in 27 (51%) subjects and conduction to the left atrium (interatrial conduction time) was supernormal in 35 (66%) subjects (difference not significant). At coupling intervals ranging between 440 and 240 ms, the conduction time of the premature beats was as much as 25 ms shorter than that of the basic driven beats. The maximum decrease in interatrial conduction time during the period of SNC was 13 +/- 5 ms and the maximum decrease in intraatrial conduction time was 9 +/- 3 ms (P < .001). The supernormal interatrial conduction zone was 71 +/- 29 ms and the supernormal intraatrial conduction zone was 57 +/- 25 ms (P < .05). There was a significant positive correlation between the SNC zone and the maximum decrease in conduction time (r = .82; P < .001). Supernormal atrial conduction was stable, reproducible, and remained constant in individual patients. Supernormal atrial conduction was found to be a relatively frequent phenomenon. There was a significantly greater SNC zone and maximum decrease in conduction time in interartrial conduction than in intraatrial conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between atrial conduction defects and fractionated atrial endocardial electrograms in patients with sick sinus syndrome.

The relationship between abnormal atrial electrograms (AAE) recorded during sinus rhythm by endocardial catheter mapping of the right atrium and the atrial conduction defects of sinus impulses or single atrial extrastimuli was investigated in 44 patients with sick sinus syndrome. The patients were divided into two groups on the basis of the presence (n = 29) or absence (n = 15) of AAE recorded during sinus rhythm. The P wave duration in the AAE (+) Group patients was 137 +/- 14 msec, and 125 +/- 15 msec in the AAE (-) Group; P < 0.02. The intraatrial conduction time of sinus impulses in the AAE (+) Group was 54 +/- 12 msec, and 39 +/- 9 msec in the AAE (-) Group; P < 0.001. The interatrial conduction time in the AAE (+) Group was 101 +/- 14 msec, and 78 +/- 16 msec in the AAE (-) Group; P < 0.001. In the AAE (+) Group, 11 (38%) patients had a sinus node recovery time > 4 seconds, whereas in the AAE (-) Group there was only one (6%) patient; P < 0.03. AAE showed a specificity of 93% and a positive predictive accuracy of 91% in predicting inducibility of atrial fibrillation. The sensitivity was 35% and the negative predictive accuracy was 42%. Sustained atrial fibrillation was induced in ten (35%) patients of the AAE (+) Group, and in one (7%) patient of the AAE (-) Group; P < 0.05. These data suggest that in patients with sick sinus syndrome who possess abnormal endocardial electrograms in sinus rhythm within the right atrium have: (1) a significantly longer P wave duration; (2) a significantly longer intraatrial and interatrial conduction time of sinus impulses; and (3) a significantly greater sinus node dysfunction and higher incidence of induction of sustained atrial fibrillation. It is concluded that there are significantly greater atrial conduction defects in patients with sick sinus syndrome who possess AAE within the right atrium during sinus rhythm.

Electrophysiological effects of a new class III antiarrhythmic agent (E-4031) on the conduction and refractoriness of the in vivo human atrium.

OBJECTIVE: The aim was to test the efficacy of a new class III drug, E-4031, on human atrial muscle in vivo. METHODS: Electrophysiological measurements were performed in 10 patients, age 54(SD 11) years, before and during the continuous infusion of E-4031 (0.15 microgram.kg-1.min-1) which followed an initial dose of 9 micrograms.kg-1 x 5 min-1. Extrastimuli at 500 ms were delivered from the right atrial appendage, high lateral right atrium, and low lateral right atrium. The effective refractory period, repetitive atrial firing zone, and fragmented atrial activity zone were assessed at three sites in the right atrium. The conduction delay zone from the stimulus artefact to the distal electrode pair at the coronary sinus was also measured. RESULTS: E-4031 caused a significant increase in overall right atrial effective refractory period from 210(SD 29) to 232(26) ms (p < 0.001, n = 30 sites). There were significant decreases in the incidence of repetitive atrial firing (67% to 37%: p < 0.005), in the repetitive atrial firing zone [23(20) to 11(22) ms: p < 0.01], and in the fragmented atrial activity zone [15(22) to 3(8) ms: p < 0.005], but no significant change in the conduction delay zone. However, E-4031 significantly prolonged the longest coupling interval that elicited conduction delay, from 249(31) ms to 267(28) ms (p < 0.01). E-4031 had no effect on the conduction time except at coupling intervals close to the atrial effective refractory period. CONCLUSION: These results suggest that E-4031 has a potential effect in the treatment of human paroxysmal atrial fibrillation.

Electrophysiologic effects of a new class III antiarrhythmic agent, E-4031, on atrial flutter, atrial refractoriness, and conduction delay in a canine sterile pericarditis model.

Numerous studies have shown that E-4031 generally prolongs the atrial effective refractory period (AERP) without affecting cardiac conduction. The effects of E-4031 on AERP and cardiac conduction at short cycle lengths (CLs) close to the AERP were measured in 12 dogs with sterile pericarditis. Three pairs of electrodes were sutured at three sites in the atria 4 days after the model was created. We measured AERP and maximum conduction delay (MCD) after 8 beats train at CLs of 400, 300, 200 and 150 ms before and during continuous infusion of E-4031 (0.1 microgram/kg/min) that followed an initial dose of 10 micrograms/kg/min/5 min. E-4031 interrupted sustained atrial flutter (AF) (> or = 10 min) in 4 of 5 episodes and atrial fibrillation (> or = 10 min) in 4 of 4. The CL of AF defined as a rapid atrial rhythm (rate > or = 240 beats/min) in five episodes studied in the sterile pericarditis model was significantly (p < 0.005) prolonged from 120 +/- 8 to 160 +/- 17 ms. There were significant (p < 0.005) increases in AERP at each CL, and prolongation of AERP was 39 +/- 18, 31 +/- 14, 23 +/- 14, and 16 +/- 14 ms at CL 400, 300, 200, and 150 ms, respectively. E-4031 produced less prolongation of AERP at short pacing CLs and had no effect on conduction time during atrial rapid pacing at CLs > 150 ms. E-4031 did not prolong MCD at CL 400 ms, but did prolong MCD at CLs of 300, 200, and 150 ms, despite prolongation of AERP.(ABSTRACT TRUNCATED AT 250 WORDS)