Inhomogeneity of ventricular refractory period in canine heart with quinidine-induced long QT interval: a comparative study on effects of heart rate, isoprenaline, and lignocaine

In anaesthetised open chest dogs, 30 mg . kg-1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. The sinus node was crushed. Effective refractory period (ERP) was determined at eight test points of the right ventricle using extra-stimuli after every seven basic ventricular pacings. Stimuli were of 2 ms duration and 1.5 times diastolic threshold. Temporal dispersion was estimated as the difference between the maximum and the minimum ERP of eight test points. Cycle lengths of basic ventricular drive were 700, 600, 500, and 400 ms. Time course of changes in ERP and its temporal dispersion was tested in five dogs. The effect of a 2 mg . kg-1 bolus injection followed by 70 micrograms . kg-1 . min-1 drip infusion lignocaine, on quinidine-induced changes in ERP was studied in eight dogs, and that of a 0.06 microgram . kg-1 . min-1 infusion of isoprenaline, was tested in six dogs. ERP was significantly prolonged after quinidine injection (220 +/- 20 vs 258 +/- 25 ms n = 19, basic cycle length = 500 ms, p less than 0.001). Temporal dispersion was also increased after quinidine (18 +/- 9 vs 33 +/- 12 ms n = 19, basic cycle length = 500 ms, p less than 0.001). With shortening of basic cycle length (BCL), ERPs were shortened significantly. Temporal dispersion, however, did not change. Lignocaine prolonged ERP even further (250 +/- 25 vs 273 +/- 16 ms BCL = 500 ms, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of atrioventricular block on ventricular fibrillation threshold in dog.

The effects of complete atrioventricular block (CAVB) on ventricular vulnerability were studied 1 week after a transcatheter electrical ablation of the AV junction in 18 closed-chest dogs. All dogs exhibited CAVB and a stable ventricular escape rhythm with a mean cycle length of 1795 +/- 600 ms. Although QT interval during CAVB was significantly prolonged compared with that during the sinus rhythm, QTc interval was significantly shortened. The ventricular fibrillation threshold was significantly elevated after creation of the block (from 9.35 +/- 2.28 to 12.3 +/- 3.69 mA, p less than 0.01). Thus, CAVB which is not associated with QTc prolongation would be even less likely to play an important role in producing ventricular fibrillation presumably including torsades de pointes or polymorphous ventricular tachycardia.     

Effects of dibutyryl cyclic AMP on ventricular vulnerability during atrioventricular block in dog.

The effects of dibutyryl cyclic AMP (DBcAMP) on ventricular vulnerability during complete atrioventricular block (CAVB) were studied one week after transarterial electrical ablation of the AV junction in 18 closed-chest dogs. All dogs exhibited CAVB and a stable ventricular escape rhythm with a mean cycle length of 1812 +/- 638 ms. After the administration of DBcAMP at a rate of 0.1 mg/kg/min for 30 min, the ventricular cycle length was significantly shortened, and the QTc interval was slightly prolonged, although the QT interval did not change. The ventricular fibrillation threshold after the administration of DBcAMP was significantly increased (from 12.2 +/- 3 84 to 18.4 +/- 5.08 mA, p less than 0.01). Thus, it was demonstrated that DBcAMP exhibited suppressive effects on the ventricular vulnerability in the experimentally induced CAVB.     

Effects of atrial pacing, isoprenaline and lignocaine on experimental polymorphous ventricular tachycardia

In 22 anaesthetised dogs, iv, administration of quinidine sulphate (30 mg X kg-1) over 5 min produced bradycardia and marked prolongation of the QT interval. Right ventricular extrastimulations, four times diastolic threshold, provoked polymorphous ventricular tachycardia in 18 dogs, and typical torsade de pointes was observed in four of these 18 dogs. Ventricular flutter was induced in another four dogs. In one of these 22 dogs, double stimuli were required to induce ventricular tachyarrhythmias, in 19 dogs triple stimuli, and in two dogs quadruple stimuli. Using this experimental model, effects of interventions including atrial pacing, isoprenaline, and lignocaine on the QT interval and induction of polymorphous ventricular tachycardia by extrastimuli were studied. Atrial pacing shortened QT interval only slightly and did not prevent induction of polymorphous ventricular tachycardia in nine dogs studied. Isoprenaline infusion definitely shortened QT interval, and in four out of nine dogs triple stimuli could not elicit polymorphous ventricular tachycardia. By contrast, although the QT interval was not shortened, lignocaine was effective in preventing induction of polymorphous ventricular tachycardia by triple stimuli in three out of nine dogs. These results indicate atrial pacing is an ineffective means of preventing induction of polymorphous ventricular tachycardia by extrastimuli in dogs with a long QT interval, but that isoprenaline and lignocaine are effective in some dogs.     

Determinants of the ventricular rate during atrial fibrillation

Determinants of the ventricular cycle length during atrial fibrillation were examined in 52 patients. Thirty-three patients had structural heart disease and none had an accessory atrioventricular (AV) connection. The AV node effective and functional refractory periods, the shortest atrial pacing cycle length associated with 1:1 conduction, the AV node conduction time and indexes of concealed conduction in the AV node were measured in the baseline state (36 patients) and after modification of sympathetic tone by infusion of isoproterenol or propranolol (8 patients each). Atrial fibrillation was then induced with rapid atrial pacing, and the mean, shortest and longest ventricular cycle lengths were measured. Variables that correlated most strongly with the mean RR interval during atrial fibrillation were the AV node effective refractory period (r = 0.93; p less than 0.001), AV node functional refractory period (r = 0.87; p less than 0.001) and shortest atrial pacing cycle length associated with 1:1 conduction (r = 0.91; p less than 0.001). The AH interval during sinus rhythm (r = 0.74; p less than 0.001) and during atrial pacing at the shortest cycle length with 1:1 conduction (r = 0.52; p less than 0.001) had weaker correlations. Measures of concealed conduction did not improve the prediction of the mean or longest ventricular cycle length during atrial fibrillation. In conclusion, the refractory periods and conductivity of the AV node are the best indicators of the potential of the node to transmit atrial impulses to the ventricles during atrial fibrillation. The degree of concealed conduction in the AV node is a less important determinant of the mean ventricular rate during atrial fibrillation.     

Effects of bretylium tosylate on inhomogeneity of refractoriness and ventricular fibrillation threshold in canine hearts with quinidine-induced long QT interval

We studied effects of bretylium tosylate (6 mg X kg-1, injected intravenously over 60s) on ventricular refractoriness and its inhomogeneity, and ventricular fibrillation threshold (VFT) in canine hearts with quinidine-induced long QT interval. In 3 anaesthetised open chest dogs, 30 mg X kg-1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. Effective refractory period (ERP) was determined at 8 test points of the right ventricle using extrastimuli. Temporal dispersion as an expression of inhomogeneity of ventricular refractoriness was estimated as the difference between the longest and the shortest ERP. VFT was determined using a train of pulses, 4 ms in duration and at 10 ms intervals. Effects of bretylium were determined from 30 to 60 min after injection. Quinidine-induced long QT interval did not change after bretylium (358 +/- 37 vs 348 +/- 26 ms) when transiently elevated blood pressure returned to the pre-bretylium level. Bretylium shortened ERP slightly (278 +/- 16 vs 268 +/- 14 ms, p less than 0.02) but did not shorten ERP after premature depolarisation (209 +/- 14 vs 209 +/- 15). However, temporal dispersion was significantly decreased by bretylium. VFT, which was lowered by quinidine (14.5 +/- 5.0 vs 8.5 +/- 2.9 mA, p less than 0.01), was elevated significantly by bretylium (21.9 +/- 6.9, p less than 0.001). These effects of bretylium might be attributed to the combination of its direct electrophysiology and indirect adrenergic actions.     

Effect of flestolol on ventricular rate during atrial fibrillation in Wolff-Parkinson-White syndrome

The ultrashort-acting beta blocker flestolol was studied during atrial pacing and atrial fibrillation (AF) in 10 patients with Wolff-Parkinson-White syndrome. Flestolol was given as a 100-micrograms/kg bolus followed by a 10-micrograms/kg/min infusion for 15 minutes. The drug did not alter the antegrade effective refractory period of the accessory pathway or the atrial paced cycle length at which block occurred in the accessory pathway. After flestolol, the percent of preexcited QRS complexes during AF increased (60 +/- 10 vs 87 +/- 5%, p = 0.01). Despite this, the ventricular rate slowed, with increases in mean RR interval (382 +/- 20 vs 416 +/- 22 ms, p = 0.02) and in the shortest interval between preexcited QRS complexes (251 +/- 18 vs 270 +/- 17 ms, p less than 0.01). The effect of isoproterenol 3 to 5 micrograms/min was studied in 5 patients. During atrial pacing, isoproterenol decreased the antegrade refractory period and the atrial paced cycle length of block in the accessory pathway (p less than or equal to 0.05). During AF, it decreased the percent of preexcited QRS complexes, mean RR interval and shortest interval between preexcited QRS complexes (p less than 0.05). Flestolol reversed the effects of isoproterenol both during atrial pacing and AF. Thus, flestolol does not alter conduction over the accessory pathway during atrial pacing, but during AF it slows conduction over the accessory pathway and prevents isoproterenol-mediated increases in ventricular rate. This suggests that in patients with Wolff-Parkinson-White syndrome sympathetic stimulation after the onset of AF enhances conduction over the accessory pathway and is an important determinant of ventricular rate.     

Divergence of Endocardial QT Interval Components during Programmed Electrical Stimulation Including Observations during Induction of Sustained Ventricular Tachyarrhythmias

Measurements were made in 12 normal subjects and during induction ofsustained ventricular tachyarrhythmias in 31 patients with remote myocardialinfarction. QT interval measurements were made semiautomatically withcomputer assistance and the total QT interval was divided into early (QT 1 )and late (QT 2 ) components. QT intervals and QT interval dispersion betweentwo right ventricular endocardial sites were plotted against the degree ofprematurity of the last extrastimulus (S 2 , S 3 , or S 4 ). In the controlgroup, total QT and QT 1 intervals shortened with increasing prematurity ofthe last extrastimulus (p , 0.001). Slopes (positive) were steeper withfaster pacing rates (600, 500, or 400 ms) and more extrastimuli (1 to 3).The relationship between QT 2 intervals and prematurity of the lastextrastimulus was flat, but the slope was slightly negative (p=0.05to,0.001) and did not vary with changes in pacing cycle length or number ofextrastimuli. QT interval dispersion in the control group was minor(95% CI 0-40 ms). During induction of sustained ventriculartachyarrhythmias, total QT and QT 1 intervals were longer (y intercepts)than in the control group (p , 0.05 at 400-ms pacing cycle length) and theirdispersion was increased (p , 0.05). Generally, QT 2 intervals were shorter(p , 0.05 at 600-ms pacing cycle length) during induction of ventriculararrhythmias in comparison with the control group but dispersion wasincreased (p , 0.05 at 400-ms pacing cycle length). QT intervals and QTinterval dispersion show an orderly and predictable relationship withprematurity of the last extrastimulus in normal subjects. These patternsdiffer during induction of sustained ventricular tachyarrhythmias. Suchdifferences may be exploited to derive clinically predictive and usefulmeasurements.     

Effects of upright posture on anterograde and retrograde atrioventricular conduction in patients with coronary artery disease, mitral valve prolapse or no structural heart disease

To assess the effects of posture on anterograde and retrograde atrioventricular conduction, electrophysiologic testing was performed in 25 patients in both the supine and 45 degrees upright positions on a tilt table. Retrograde conduction was present during ventricular pacing in 17 patients in the supine position; all 17 continued to manifest retrograde conduction in the upright position. In all patients with absent retrograde conduction while supine, retrograde conduction could not be demonstrated while upright. Upright posture significantly (p less than 0.05) shortened the sinus cycle length (from 808 +/- 34 to 678 +/- 26 ms, mean +/- standard error of the mean), AH interval during sinus rhythm (78 +/- 6 to 69 +/- 6 ms), and AH interval during atrial pacing at cycle length 500 ms (123 +/- 13 to 91 +/- 9 ms). Total atrioventricular conduction time during atrial pacing shortened significantly (from 169 +/- 13 to 136 +/- 10 ms), as did ventriculoatrial conduction time during ventricular pacing (from 192 +/- 9 to 178 +/- 7 ms). Upright posture also significantly shortened both anterograde block cycle length (390 +/- 20 to 328 +/- 17 ms) and retrograde block cycle length (466 +/- 27 to 354 +/- 18 ms). However, the effect of upright posture on retrograde block cycle length was significantly greater than on anterograde block cycle length: a 21% decrease retrograde vs a 14% decrease anterograde (p less than 0.05). These effects may produce clinically important changes in characteristics of arrhythmias that depend on the properties of anterograde and retrograde conduction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of heart rate on QT interval in children and adolescents.

OBJECTIVE: To study the effect of sympathetic stimulation and increase in heart rate on the QT and QTc intervals. DESIGN: Prospective non-randomised study of eight consecutive patients. SETTING: Electrophysiology laboratory at a tertiary centre. PATIENTS: Eight patients aged 10-20 years (median 12.5) undergoing repeat electrophysiological study after previously successful catheter ablation (n = 6) or presumed supraventricular tachycardia (n = 2) with negative studies. INTERVENTIONS: Electrocardiograms were obtained (a) at baseline, (b) during atrial pacing at 450 ms cycle length, (c) during isoprenaline infusion at 0.025 microgram/kg/min, (d) adding atrial pacing (450 ms cycle length) to isoprenaline at 0.025 microgram/kg/min, and (e) isoprenaline at 0.05 microgram/kg/min. MAIN OUTCOME MEASURES: QT and QTc intervals at each of the above mentioned stages. RESULTS: The QT interval was reduced from a mean value of 350 ms to around 315-325 ms by each of the above manoeuvres. Correspondingly, the QTc increased from a mean of 407 ms to around 445-470 ms. Pacing was as effective as isoprenaline in shortening the QT interval and prolonging the QTc intervals. CONCLUSIONS: Heart rate directly influences QT and QTc intervals in children and adolescents. The QT is shortened, but QTc is prolonged. Hence, reliance on the QTc alone could lead to mistaken diagnosis of long QT syndrome.     

Pirmenol: an antiarrhythmic drug with unique electrocardiographic features--a double-blind placebo-controlled comparison with quinidine

Previous reports have stated that pirmenol is a Class IA antiarrhythmic drug that prolongs the QT interval, but did not use computerized electrocardiography. We randomized 18 patients with frequent ventricular ectopic depolarizations to pirmenol (8 patients) or quinidine (10 patients). Pirmenol was effective and tolerated for suppression of arrhythmia in all 7 patients treated (1 patient withdrew for personal reasons) but quinidine was effective and tolerated for 4 weeks in only 5 of 10 patients (p less than 0.05). Using computerized 12-lead electrocardiography, the mean change in PR interval from placebo to treatment was 5 +/- 18 ms for quinidine and 5 +/- 11 ms for pirmenol (p = NS). The mean change in QRS interval was 5 +/- 14 ms for quinidine and 10 +/- 5 ms for pirmenol (p = NS). The mean change in QT interval was 46 +/- 30 ms for quinidine and 8 +/- 9 ms for pirmenol (p less than 0.01) and the mean change in JT interval was 41 +/- 36 ms for quinidine and -2 +/- 10 ms for pirmenol (p less than 0.01). After the double-blind phase, 4 quinidine patients had computerized electrocardiographic intervals measured on pirmenol; the above findings were confirmed. These electrocardiographic features of pirmenol clearly distinguish it from quinidine, the prototype Class IA drug. However, pirmenol has minimal effect on the PR and QRS intervals, and thus does not appear to be a Class IC drug either. Although its electrocardiographic features are closest to Class IB, its electrophysiology in isolated cells and its antiarrhythmic and side effect profile are atypical for a IB agent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Importance of the pacing mode in the initiation of ventricular tachyarrhythmia in a canine model of chronic myocardial infarction

The use of unipolar anodal or bipolar pacing, as compared with unipolar cathodal pacing, purportedly increases the likelihood of inducing inadvertent ventricular fibrillation in susceptible patients. In this study, the ability to initiate sustained ventricular tachycardia or fibrillation with unipolar cathodal, unipolar anodal and bipolar pacing modes was compared using programmed ventricular stimulation at 82 subendocardial periinfarction sites in 11 dogs with chronic myocardial infarction. The late diastolic excitability threshold was significantly higher and the ventricular refractory period was significantly shorter (p less than 0.001) with anodal pacing (mean 0.62 mA, 156 ms, respectively) than with pacing in either the cathodal (0.12 mA, 174 ms) or the bipolar (0.13 mA, 173 ms) mode. At a current intensity twice that of the excitability threshold, the introduction of one or two extrastimuli induced ventricular tachycardia and ventricular fibrillation comparably among the three pacing modes. However, when three extrastimuli were used, ventricular fibrillation was induced with anodal pacing twice as frequently (50 [61%] of 82 sites) as with either of the other two pacing modes (each 23 [28%] of 82 sites, p less than 0.001), whereas the induction of ventricular tachycardia remained comparable with anodal pacing (15 [18%] of 82 sites) and cathodal and bipolar pacing (each 14 [17%] of 82 sites). Furthermore, a similarly high incidence of inducibility of ventricular fibrillation was observed with both cathodal pacing (56 [68%] of 82 sites) and bipolar pacing (40 [49%] of 82 sites) when an increased current equal to twice the anodal excitability threshold (1.23 mA) was used.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of quinidine versus procainamide on the QT interval

Eighteen patients were given quinidine and procainamide separately to evaluate whether prolongation of the QT interval by type Ia antiarrhythmic agents is a drug-specific phenomenon. Doses were titrated to achieve standard trough therapeutic levels of quinidine (2 to 5 micrograms/ml) and procainamide (4 to 12 micrograms/ml). In 16 of the 18 patients, the increase in corrected QT interval (QTc) was greater with quinidine than with procainamide, averaging 78 +/- 10 ms (+/- standard error of the mean) with quinidine and 39 +/- 7 ms with procainamide (p less than 0.001). The greater degree of QTc prolongation with quinidine than with procainamide was not due to differences in sinus cycle length, QRS duration, serum potassium level or concomitant drug therapy. Differences in relative drug level did not appear to account for the greater effect of quinidine. Thus, at frequently used plasma levels, quinidine prolongs QTc to a greater degree than does procainamide. This effect does not appear to be due to the comparison of "nonequivalent" drug levels.     

The electrophysiological effects of flosequinan.

We have evaluated the acute electrophysiological effects of flosequinan in 18 patients with normal ventricular function. Following intravenous infusion of flosequinan 100 mg over 1 h, mean (SD) systolic blood pressure fell from 131 +/- 19 to 120 +/- 22 mmHg (P less than 0.02) and there was significant shortening of sinus cycle length (732 +/- 151 to 575 +/- 93 ms, P less than 0.001), AH interval (110 +/- 45 to 71 +/- 19 ms, P less than 0.01), QRS duration (98 +/- 28 to 91 +/- 26 ms, P less than 0.02) and QT interval (373 +/- 47 to 337 +/- 35 ms, P less than 0.001), but no change in sinus node recovery time, intra-atrial conduction time, HV interval or the corrected QTc interval. There was a reduction in both anterograde atrioventricular Wenckebach cycle length (299 +/- 53 to 259 +/- 52 ms, P less than 0.01) and retrograde ventriculoatrial Wenckebach cycle length (375 +/- 77 to 300 +/- 56 ms, P less than 0.01). There was no change in atrial or ventricular effective refractory period (ERP) but atrial functional refractory period (FRP) shortened (233 +/- 31 to 212 +/- 24 ms, P = 0.07) as did ventricular FRP (249 +/- 24 to 234 +/- 21 ms, P less than 0.01). Patients received an oral dose of flosequinan 50 mg 12 h later. By 24 h, sinus cycle length, QRS duration and the QT interval had all returned towards baseline values, but ventricular ERP had lengthened (199 +/- 22 to 215 +/- 26 ms, P less than 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of pacing cycle length and autonomic blockade on sinus node refractoriness

Sinus node (SN) refractoriness can be measured indirectly by observing the return responses after the introduction of progressively earlier atrial premature beats. The SN effective refractory period (ERP) is defined as the longest premature interval resulting in an interpolated atrial return response. In the present study, SNERP was analyzed in 71 subjects--51 control persons and 20 patients with evidence of SN dysfunction. SNERP could be measured in 40 of 51 control subjects and was shown to prolong at shorter basic pacing cycle lengths. At a basic cycle length of 600 ms, SNERP was 330 +/- 40 ms, whereas at 500 ms it was 350 +/- 50 ms (p less than 0.05). At a basic cycle length of 600 ms, SNERP was measured in 31 control subjects and 7 patients with SN dysfunction. The values of 330 +/- 40 and 520 +/- 20 ms, respectively, in these 2 groups suggested that this method can be used to differentiate patients with SN dysfunction (p less than 0.001). In 12 control subjects, SNERP was measured before and after partial autonomic blockade with propranolol and atropine. SNERP shortened from 360 +/- 40 to 320 +/- 40 ms (p less than 0.05). It shortened with atropine and prolonged with propranolol. Thus, SNERP prolongs with a shorter basic pacing cycle length and is affected by autonomic manipulation, in a fashion analogous to the atrioventricular node.     

Effects of upright posture on atrioventricular accessory pathway conduction

The electrophysiologic effects of 45 degrees head-up tilt were studied in 19 patients with atrioventricular accessory pathways. Upright posture enhanced both anterograde and retrograde accessory pathway conduction when compared to the supine position: the anterograde block cycle length decreased from 374 +/- 52 ms (mean +/- standard error) (supine) to 303 +/- 33 ms (tilt) (p less than 0.05); anterograde effective refractory period decreased from 286 +/- 17 to 249 +/- 10 ms (p less than 0.05); retrograde block cycle length shortened from 331 +/- 36 to 291 +/- 35 ms (p less than 0.05); retrograde effective refractory period decreased from 312 +/- 26 ms to 274 +/- 15 ms (p less than 0.05). During induced atrial fibrillation the mean RR interval and the shortest RR interval between preexcited beats decreased approximately 10% with head-up tilt. During orthodromic reciprocating tachycardia, tachycardia cycle length shortened 15%. Tachycardia rate during electrophysiologic study in the head-up position more closely approximated the rate of clinical tachycardia than did the rate in the supine position. Head-up tilt significantly enhances anterograde and retrograde accessory pathway conduction, increases the rate of arrhythmias using an accessory pathway and may be clinically useful in the assessment of patients with an accessory pathway.     

Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome.

BACKGROUND. Several recent experimental and clinical studies have shown that early afterdepolarizations (EADs) are important in the genesis of QTU prolongation and ventricular tachyarrhythmias (VTs) in patients with long QT syndrome. On the other hand, sympathetic stimulation is well known to contribute to the genesis of QTU prolongation and VTs in patients with congenital long QT syndrome. The present study was performed to examine the influence of isoproterenol on the genesis of EADs and on the action potential durations and QTU intervals in patients with congenital long QT syndrome. METHODS AND RESULTS. We recorded monophasic action potentials (MAPs) with a contact electrode during right atrial pacing at a constant cycle length of 500 msec before and after continuous isoproterenol infusion (1 microgram/min). MAPs were obtained from the right and left ventricular endocardium in six patients with congenital long QT syndrome (LQT group, 18 recording sites) and in eight control patients (control group, 19 recording sites). Although no EADs were recorded from either group during the control state, MAP duration at 90% repolarization (MAPD90) was significantly longer in the LQT group (n = 18) than in the control group (n = 19) (275 +/- 36 versus 231 +/- 22 msec; p less than 0.0005). Isoproterenol induced EADs in four of the six LQT patients (five of 18 recording sites) but not in the eight control patients (zero of 19 recording sites). The appearance of EADs in the LQT group was associated with an increased amplitude of the late component of the TU complex, and the corrected QT (QTc) interval was prolonged by isoproterenol from 543 +/- 53 to 600 +/- 30 msec 1/2 (n = 6; p less than 0.05). Isoproterenol also prolonged the MAPD90 from 275 +/- 36 to 304 +/- 50 msec in the LQT group (n = 18; p less than 0.005), whereas it shortened the MAPD90 from 231 +/- 22 to 224 +/- 25 msec in the control group (n = 19; p less than 0.05). Moreover, isoproterenol increased the dispersion of MAPD90 (difference between the longest MAPD90 and the shortest MAPD90 in each patient) from 30 +/- 5 to 62 +/- 35 msec in the LQT group (n = 6; p = 0.08), whereas it did not change the dispersion of MAPD90 in the control group (n = 8; 25 +/- 14 versus 27 +/- 14 msec). CONCLUSIONS. These results suggest that patients with congenital long QT syndrome have primary repolarization abnormalities and that EADs induced by isoproterenol play an important role in the exaggeration of these repolarization abnormalities.     

Electrophysiologic study of cibenzoline in patients with paroxysmal atrial fibrillation with special reference to atrial fibrillation threshold]

Electrophysiologic effects of cibenzoline were studied in 7 patients (6 males and one female) aged from 40 to 69 years (mean +/- SD; 52 +/- 10) with paroxysmal atrial fibrillation which was documented by 12 leads ECG or by 24 hours Holter monitoring. No organic heart diseases were found except in one patient with dilated cardiomyopathy and sick sinus syndrome (SSS). Cibenzoline (200mg) given orally increased P wave duration, PR interval and QRS duration significantly. The duration of P wave was gradually increased as the pacing frequency was increased. Neither sinus cycle length, nor sinus node recovery time (SRT), nor Wenkebach cycle length, nor atrial effective refractory period, nor QT interval was changed by the drug. One patient with SSS showed increase in SRT from 2,303 msec to 5,150 msec. The minimum current which was required to induce atrial fibrillation by rapid atrial stimulation (50 Hz, 1 sec) lasting more than 30 sec was defined as atrial fibrillation threshold (AFT). The AFT was 4.0 +/- 2.2 mA at the baseline state in 7 patients. After the oral administration of cibenzoline, 5 patients showed increase in AFT, while 1 patient showed decrease and another patient showed no change in AFT. Statistically, AFT was significantly increased to 7.3 +/- 3.4 mA in 7 patients. The results suggest that cibenzoline might be effective to prevent paroxysmal atrial fibrillation in patients without organic heart diseases.     

Effect of pacing current strength on indexes of myocardial activation in humans: influence of chronic infarction and polarity of pacing

The effects of current strength (threshold to 20 mA) and pacing polarity (bipolar versus unipolar) on indexes of ventricular activation during endocardial pacing (cycle length 400 to 500 ms) from 10 normal and 17 abnormal left ventricular sites were assessed in 19 patients. Abnormal sites were infarcted and demonstrated an electrogram duration greater than 70 ms and amplitude less than 3 mV during sinus rhythm. Bipolar pacing was performed from poles 1 (cathode) and 3 (1 cm interelectrode distance) of a quadripolar catheter. Unipolar cathodal pacing was performed from the tip electrode (pole 1). Local activation was indexed by the interval from the pacing stimulus to 1) the onset of the QRS complex, 2) the largest rapid deflection of the local electrogram, and 3) the end (total duration) of the local electrogram recorded from poles 2 and 4 of the quadripolar catheter used for left ventricular pacing. Distant activation was indexed by the interval from pacing stimulus to electrograms recorded at the right ventricular apex and outflow tract. Bipolar and unipolar pacing of normal sites produced a modest homogeneous reduction of all activation times by 3 to 11 ms (median) with increments in current strength from threshold (0.8 mA) to 20 mA. Bipolar pacing of abnormal sites showed marked (up to 110 ms) and heterogeneous changes in local (median 22 to 30 ms) as well as distant (median 14 to 23 ms) activation times with increases in current strength from threshold (2.7 mA) to 20 mA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic and vagal influences on rate-dependent changes of QT interval in healthy subjects

Dependence of QT interval duration on cardiac heart rate has been well established and is considered to be an intrinsic property of ventricular myocardium. Conclusive results of autonomic influences on such phenomena are lacking. To evaluate whether rate-dependent changes of QT interval are conditioned by the autonomic nervous system, 28 normal subjects with no heart disease and a normal QT interval were electrophysiologically assessed. The QT interval was calculated at 6 paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) during the basal state, and after beta blockade (propranolol 0.2 mg/kg) and autonomic blockade (propranolol plus atropine 0.04 mg/kg). Because of atrioventricular nodal conduction limits, intrapatient cross-comparisons were performed in 10 subjects (aged 42 +/- 15 years). Single regression lines, evaluated in each subject, showing correlation between pacing cycle length and QT duration at each of the 3 states were analyzed. The mean slope observed after autonomic blockade (b = 0.10 +/- 0.04) was significantly lower than that seen during the basal state (b = 0.22 +/- 0.12, p less than 0.05) and after beta blockade (b = 0.23 +/- 0.08, p less than 0.05); nonsignificant differences were found between slopes during the basal state and after beta blockade. Results showed that vagal tone increased intrinsic dependence of QT at increasing cycle length, whereas sympathetic tone did not seem to interfere significantly. Since (in each subject) beta blockade was performed--or achieved--before atropine administration, the vagal influences are likely to be directly exerted on the ventricular electrophysiologic substrate.