Increased vagal cardiac nerve traffic prolongs ventricular refractoriness in patients undergoing electrophysiology testing

Stimulation of the vagus nerve in animals causes prolongation of sinus cycle length, atrioventricular nodal conduction and ventricular refractoriness. Vagal stimulation appears to have a protective effect in animal models of sudden death. The electrophysiologic effects of enhanced vagal activity on right ventricular (RV) refractoriness in man have not been studied previously. The comparative effects of enhanced vagal tone (neck suction to -60 mm Hg) on sinus cycle length and RV refractoriness were assessed in 26 patients. The electrophysiologic effects of vagal activation by stimulation of carotid baroreceptors with neck suction were compared to the effect of carotid and aortic baroreceptor stimulation with phenylephrine infusion in 12 patients. During neck suction, mean sinus cycle length (819 +/- 32 ms) was prolonged by 146 +/- 20 ms (p less than 0.0001). The mean RV effective refractory period (ERP) and functional refractory period (FRP) were prolonged by 4 +/- 1 ms and 5 +/- 1 ms (p = 0.0001 and 0.0002, respectively). The mean change in RV ERP and FRP correlated with the peak change in sinus cycle length during neck suction (r = 0.46 and r = 0.58, respectively). During intravenous phenylephrine infusion, the mean change in RV ERP and FRP was 5 +/- 2 ms (p less than 0.04) and 10 +/- 3 ms (p less than 0.01), respectively. These results show that reflex vagal stimulation with neck suction or phenylephrine infusion causes a small but significant prolongation in RV refractoriness. These findings imply that the potential benefits of enhanced vagal tone in preventing sudden death may be indirectly mediated by changes in ventricular refractoriness.     

Postvagal tachycardia

Twenty-one patients were studied to investigate whether cardiac acceleration above control values occurred after cessation of enhanced vagal tone (postvagal tachycardia), and to determine the effects of selective autonomic blockade on postvagal tachycardia. Patients had neither sinus arrhythmia nor sinus nodal dysfunction. Enhanced vagal tone was induced by neck suction using a lead neck collar connected to a vacuum source. For each patient intracollar negative pressures of 50 to 60 mm Hg were induced for 2 seconds on 10 occasions. For all patients, sinus cycle length increased from 821 +/- 99 to 1,067 +/- 241 ms (p less than 0.001) during neck suction and decreased to 760 +/- 96 ms after termination of neck suction, a value significantly (p less than 0.001) less than control. Five of 16 patients had no postvagal tachycardia. Maximal shortening of sinus cycle length occurred 3 to 8 complexes after cessation of neck suction. Neck suction was induced in 7 patients before and during propranolol administration, 0.15 mg/kg intravenously, and the degree of postvagal tachycardia was unchanged. Atropine, 0.03 mg/kg intravenously, prevented neck suction-induced sinus slowing and acceleration in 3 of 3 patients. We conclude that postvagal tachycardia occurs and is not mediated through beta-adrenergic activity, but is inhibited by muscarinic blockade.     

Contraction-excitation feedback in the atria: a cause of changes in refractoriness

The purpose of this study was to investigate the immediate effects of an increase in atrial pressure on atrial refractoriness by determining the relation between the atrial pressure and effective refractory period of the atrium. In 21 open chest anesthetized dogs, after the blocking of atrioventricular (AV) conduction by formalin injection, the left atrium and left ventricle were paced sequentially at a fixed cycle length of 300 ms. The AV interval was varied from 0 to 280 ms in 20 ms steps during the recording of aortic and left atrial pressures and refractory period of the left atrium. Mean left atrial pressure was lowest (8.0 +/- 0.4 mm Hg, all values mean +/- SEM) at an AV interval of 47 +/- 3 ms, when refractory period was 135.5 +/- 2.6 ms. Mean left atrial pressure was highest (13.3 +/- 0.5 mm Hg) at an AV interval of 147 +/- 5 ms, when refractory period was 137.9 +/- 2.4 ms (p less than 0.01). Left atrial diameter measured by echocardiography increased from 33.7 +/- 1.8 mm at an AV interval of 47 ms to 37.8 +/- 1.8 mm (p less than 0.01, n = 10) at an AV interval of 147 ms, and mean aortic pressure decreased from 109 +/- 4 to 101 +/- 4 mm Hg. After surgical decentralization of vagal and sympathetic innervation to eliminate baroreflex influence on refractoriness, left atrial refractory period prolonged from 141.6 +/- 3.4 to 145.4 +/- 3.4 ms (p less than 0.01) when mean left atrial pressure increased from 9.5 +/- 0.4 to 15.2 +/- 0.6 mm Hg. A similar relation was noted between right atrial pressure and right atrial refractory period (n = 10) and between left atrial pressure and refractory period of the interatrial septum (n = 12). In six chronically instrumented conscious dogs, left atrial refractory period prolonged from 116.3 +/- 2.3 to 124.2 +/- 1.7 ms (p less than 0.01) when mean left atrial pressure increased from 4.0 +/- 0.8 to 9.0 +/- 0.3 mm Hg. Therefore, an increase in atrial pressure lengthens refractory period of both atria and the interatrial septum in anesthetized and conscious dogs.     

Dispersion of atrial refractoriness in patients with sinus node dysfunction.

Abnormal atrial refractoriness was examined as a cause of atrial fibrillation/flutter (AFF) in patients with bradycardia. Refractory periods at three disparate right atrial sites were compared in 17 patients with sinus node dysfunction (SND) and 16 controls. Atrial pacing shortened refractory periods, but failed to decrease dispersion of refractoriness significantly. During sinus rhythm, duration and dispersion of refractoriness were greater in SND patients than in controls. These differences persisted with atrial pacing. For example, at the paced rate, dispersion of effective refractory periods in SND patients was greater than in controls (62.9 +/- 34 vs 36.6 +/- 21 msec, p less than 0.01). Six SND patients had AFF, but they did not have greater dispersion than other SND patients, or unusually short or long refractory periods. Thus, prolonged and nonuniform refractoriness were features of SND. Abnormal refractoriness in SND reflected atrial disease and persisted with pacing. These abnormalities were not unique to patients with AFF.     

Effect of phenylephrine infusion on atrial electrophysiological properties.

OBJECTIVE: To determine the effect of changes in autonomic tone induced by phenylephrine infusion on atrial refractoriness and conduction. DESIGN: Left and right atrial electrophysiological properties were measured before and after a constant phenylephrine infusion designed to increase sinus cycle length by 25%. SUBJECTS: 20 patients, aged 53 (SD 6) years, undergoing electrophysiological study for investigation of idiopathic paroxysmal atrial fibrillation (seven patients) or for routine follow up after successful catheter ablation of supraventricular tachycardia (13 patients). MAIN OUTCOME MEASURES: Changes in left and right atrial effective refractory periods, atrial activation times, and frequency of induction of atrial fibrillation. RESULTS: Phenylephrine (mean dose 69 (SD 18) mg/min) increased mean blood pressure by 22 (12) mm Hg (range 7 to 44) and lengthened sinus cycle length by 223 (94) ms (20 to 430). Left atrial effective refractory period lengthened following phenylephrine infusion from 250 (25) to 264 (21) ms (P < 0.001) but there was no significant change in right atrial effective refractory period: 200 (20) v 206 (29), P = 0.11. There was a significant relation between the effect of phenylephrine on sinus cycle length and on right atrial refractoriness (r = 0.6, P = 0.005) with shortening of right atrial refractoriness in patients with the greatest prolongation in sinus cycle length. During phenylephrine infusion, the right atrial stimulus to left atrial activation time at the basic pacing cycle length of 600 ms was unchanged, at 130 (18) v 131 (17) ms, but activation delay with a premature extrastimulus increased: 212 (28) v 227 (38) ms, P = 0.002. Atrial fibrillation was induced by two of 58 refractory period measurements at baseline and by 12 of 61 measurements during phenylephrine infusion (P < 0.01). Phenylephrine increased the difference between left and right atrial refractory periods by 22.8 (19.4) ms in the five patients with induced atrial fibrillation after phenylephrine compared to 0.9 (16.2) ms in the 13 patients without induced atrial fibrillation after phenylephrine infusion (P = 0.02). CONCLUSIONS: Phenylephrine infusion increased left atrial refractoriness and intra-atrial conduction delay following a premature right atrial extrastimulus. Induction of atrial fibrillation during phenylephrine infusion was associated with non-uniform changes in atrial refractoriness. These data support the concept that changes in autonomic tone may precipitate atrial fibrillation in susceptible individuals.     

Antiarrhythmic and proarrhythmic properties of diazepam demonstrated by electrophysiological study in humans

We evaluated the electrophysiological parameters before and after the intravenous infusion of diazepam (0.2 mg/kg) in 20 cardiac patients to investigate the drug's antiarrhythmic effect. Diazepam did not significantly change the arterial pressure. After the intravenous infusion of diazepam, the sinus cycle length significantly shortened from 847 +/- 132 to 747 +/- 155 ms (p less than 0.01). No significant change in the maximal sinus node recovery time was noted. The AH interval at the atrial pacing length of 600 ms shortened significantly from 140 +/- 40 to 127 +/- 39 ms (p less than 0.05). However, there was no significant change after the administration of diazepam in the longest atrial pacing rate associated with Wenckebach conduction in the atrioventricular (AV) node, effective and functional refractory periods of the AV node, HV interval, and QRS width during ventricular pacing at the cycle length of 600 ms. The atrial and ventricular effective refractory periods remained unchanged after the administration of diazepam. Six of the eight patients who showed dual AV nodal refractory period curves in the control study did not demonstrate them after diazepam administration by increasing the atrial or AV node effective refractory period. Thus, diazepam showed significant electrophysiological effects of the heart including shortening of the sinus cycle length, improvement in AV node conduction, and no significant effect on the His-Purkinje or intraventricular conduction and refractoriness of the atrium, AV node and ventricle. On the other hand, diazepam may influence the inducibility of supraventricular reentrant tachycardia incorporating the AV node.     

Maturational changes in ventriculoatrial conduction in the intact canine heart

This study reports on the changes in ventriculoatrial (VA) conduction that occur with maturation. Programmed atrial and ventricular premature extra-stimulation (coupled to a fixed paced cycle length) and rapid atrial pacing were performed in three groups of dogs: Group I = 8 neonates aged 5 to 14 days, Group II = 9 young dogs aged 6 to 9 weeks and Group III = 10 adult dogs. High right atrial, His bundle and right ventricular electrograms were recorded. There were no differences in the AH intervals at rest. In all but five animals, atrioventricular conduction was limited by the atrial functional refractory period (Group I, 109 +/- 12 ms; Group II, 152 +/- 22 ms; Group III, 167 +/- 19 ms). As expected, with rapid atrial pacing, Wenckebach conduction developed at a shorter cycle length in the younger animals (Group I, 145 +/- 20 ms; Group II, 153 +/- 15 ms; Group III, 200 +/- 25 ms, p less than 0.01). Ventriculoatrial conduction was documented in 87% of Group I puppies and 100% of Group II, but only 40% of Group III dogs. The effective and functional refractory periods of the VA conduction system were significantly shorter in the more immature groups of dogs (effective/functional: Group I, 124 +/- 27/168 +/- 22 ms; Group II, 139 +/- 23/202 +/- 13 ms; Group III, 270 +/- 28/326 +/- 25 ms; p less than 0.01). Relative to the adult dog, the immature heart showed a greater incidence of VA conduction and shorter VA refractory periods. This enhanced VA conduction may be of physiologic importance in the initiation and perpetuation of certain supraventricular arrhythmias.     

Effects of magnesium sulfate on cardiac conduction and refractoriness in humans

Magnesium has been used empirically for several decades in the treatment of atrial and ventricular arrhythmias in patients with normal and decreased serum magnesium levels. However, a systematic evaluation of the effects of magnesium on cardiac conduction and refractoriness in humans has not been described. In this study, the electrocardiographic and electrophysiologic effects of magnesium were determined in 10 patients with normal baseline serum magnesium and other electrolyte levels. Six grams of magnesium sulfate was administered intravenously over 6 minutes followed by a continuous infusion of 1 additional gram over 1 hour. Serum magnesium levels rose significantly from a baseline of 2.0 +/- 0.2 to 5.4 +/- 0.4 mg/dl (p less than 0.001). No significant change occurred in heart rate at rest, or in duration of the QRS complex or QT or QTc intervals during sinus rhythm. There were significant increases in sinus node recovery time (1,000 +/- 211 to 1,106 +/- 223 ms, p less than 0.01) and corrected sinus node recovery time (279 +/- 87 to 336 +/- 104 ms, p less than 0.05). Significant increases occurred in atrioventricular (AV) node conduction time during sinus rhythm (82 +/- 22 to 97 +/- 17 ms, p less than 0.02), in the atrial paced cycle length at which AV node Wenckebach block occurred (350 +/- 46 to 419 +/- 65 ms, p less than 0.01) and in the AV node relative refractory period (397 +/- 27 to 422 +/- 18 ms, p less than 0.05), functional refractory period (395 +/- 41 to 415 +/- 33 ms, p less than 0.05) and effective refractory period (306 +/- 67 to 338 +/- 38 ms, p less than 0.05).     

Electrophysiologic effects of diprafenone in supraventricular and ventricular tachycardia

The electrophysiologic effects of diprafenone were evaluated in 31 patients (9 X AV nodal reentrant tachycardia, 9 X Wolff-Parkinson-White syndrome, 4 X paroxysmal atrial fibrillation, 10 X recurrent ventricular tachycardia). Electrophysiologic studies were performed before and after intravenous infusion of 1.5 mg/kg body weight diprafenone in a period of 10 minutes. Diprafenone prolonged the mean RR interval during sinus rhythm from 690 +/- 109 ms to 789 +/- 93 ms and the maximal sinus node recovery time from 1081 +/- 216 ms to 1300 +/- 398 ms (p less than 0.001). The effective refractory period of the right atrium increased from 195 +/- 22 ms to 210 +/- 28 ms (p less than 0.01) and of the right ventricle from 220 +/- 20 ms to 235 +/- 20 ms (p less than 0.001). Diprafenone produced a prolongation of the antegrade effective refractory period of the AV node from 260 +/- 35 ms to 294 +/- 39 ms (p less than 0.01) and of the retrograde effective refractory period from 265 +/- 76 ms to 400 +/- 130 ms (p less than 0.001). The effective refractory periods of the Kent bundle increased: antegrade from 299 +/- 45 ms to 413 +/- 133 ms, retrograde from 252 +/- 33 ms to 286 +/- 169 ms (p less than 0.05). Suppression of inducibility was observed in 12 of 17 patients with supraventricular reentrant tachycardia, in 5 of 8 patients with atrial fibrillation and in 7 of 10 patients with recurrent ventricular tachycardia. The rate of supraventricular tachycardias decreased under the influence of the substance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic effects of atropine on human sinus node and atrium.

Electrophysiologic studies were conducted in 17 patients without apparent sinus node disease before and after intravenous administration of 1 to 2 mg of atropine. Mean values in milliseconds (+/- standard error of the mean) before and after administration of atropine were as follows: sinus cycle length 846 +/- 26.4 versus 647 +/- 20.0 (P less than 0.001); sinus nodal recovery time 1,029 +/- 37 versus 774 +/- 36 (P less than 0.001); mean calculated sinoatrial (S-A) conduction time 103 +/- 5.7 versus 58 +/- 3.9 (P less than 0.001); mean P-A interval 34 +/- 1.5 msec versus 31 +/- 1.5 (P less than 0.05); mean atrial effective and functional refractory periods during sinus rhythm 285 +/- 11.3 versus 238 +/- 7.9 and 331 +/0 11.6 versus 280 +/- 8.6, respectively (P less than 0.001 for both); mean atrial effective and functional refractory periods measured at equivalent driven cycle length 239 +/- 7.7 versus 213 +/- 7.4 and 277 +/- 11.4 versus 245 +/- 9.5, respectively (P less than 0.001 for both). In conclusion, atropine shortened sinus cycle length, sinus nodal recovery time and calculated S-A conduction time. The shortening of atrial refractory periods with atropine implies that vagotonia prolongs atrial refractoriness in man.     

In vivo electrophysiological effects of a selective slow delayed-rectifier potassium channel blocker in anesthetized dogs: potential insights into class III actions

OBJECTIVES: This study evaluated the in vivo electrophysiological effects of a highly selective slow delayed-rectifier K+-current blocker, HMR 1556, to gain insights into the consequences of selectively inhibiting the slow delayed-rectifier current in vivo. METHODS: Atrial and ventricular effective refractory periods, sinus node recovery time, Wenckebach cycle-length, atrial fibrillation duration and electrocardiographic intervals were measured before and after intravenous HMR 1556. RESULTS: HMR 1556 increased atrial and ventricular refractory periods (e.g. by 6 +/- 4% and 27 +/- 6% at cycle lengths of 360 and 400 ms, respectively), QT intervals and sinus-node recovery times. Beta-adrenoceptor blockade with nadolol abolished all effects except those on ventricular refractoriness and changed positive use-dependent effects on refractoriness to reverse use-dependent ones. In the presence of dofetilide to block rapid delayed-rectifier current, HMR 1556 effects were potentiated (e.g. atrial and ventricular refractory periods increased by 26 +/- 3% and 34 +/- 3% at cycle lengths of 360 and 400 ms, respectively). HMR 1556 reduced vagal atrial fibrillation duration from 1077 +/- 81 to 471 +/- 38 s, an effect abolished by nadolol and greatly potentiated by dofetilide (duration 77 +/- 30 s). HMR 1556 increased Wenckebach cycle length only in the presence of dofetilide. CONCLUSIONS: Slowed delayed-rectifier current inhibition affects atrial repolarization, sinus node function and atrial fibrillation in vivo, but only in the presence of intact beta-adrenergic tone, and delays ventricular repolarization even when beta-adrenoceptors are blocked. The slow delayed-rectifier current is particularly important when rapid delayed-rectifier current is suppressed, illustrating the importance of repolarization reserve.     

Electrophysiologic studies in atrial fibrillation. Slow conduction of premature impulses: a possible manifestation of the background for reentry

Extrastimulus-induced intraatrial conduction delays were measured in 12 patients with documented episodes of atrial fibrillation (AF) by recording atrial electrograms at the high right atrium, His bundle region, and coronary sinus. Seventeen patients with and without heart disease, but without atrial arrhythmias served as the control group. During baseline-paced atrial rhythms, a conduction delay zone could be delineated, near the atrial effective refractory period, during which all extrastimuli produced conduction delays. When compared at the same paced cycle lengths (500 to 650 ms), the patients with AF had shorter atrial effective refractory periods (mean +/- standard deviation 206 +/- 24.1 versus 233 +/- 28.2 in control patients, p less than 0.02), wider conduction delay zones (79 +/- 21.7 ms versus 52 +/- 21 in control patients, p less than 0.01), and longer conduction delays both to the His bundle region (64 +/- 18.3 ms versus 35 +/- 21.7 in control patients, p less than 0.005) and the coronary sinus (76 +/- 18.9 ms versus 35 +/- 16.1 in control patients, p less than 0.001). Repetitive atrial responses were recorded in 6 patients with AF and in 9 control subjects. Sinus nodal function abnormalities were detected in 6 of the patients with fibrillation. Patients with AF had a higher tendency than control subjects to develop slow intraatrial conduction, as well as shorter effective refractory periods. Since both features would favor reentry, they may be the electrophysiologic manifestations of the abnormalities making these patients prone to atrial reentrant arrhythmias. Repetitive atrial responses were of no predictive value. Sinus nodal dysfunction was frequently found, but was not essential for the occurrence of AF.     

Influence of the site of stimulation on atrioventricular nodal refractory periods and the effect of verapamil

The refractory periods of the atrioventricular (AV) node appear dependent on the pattern of AV nodal input. In 21 superfused AV rabbit heart preparations stimulated from each of the 2 principal input regions, crista terminalis or atrial septum, the effect of changing the site of stimulation of the AV nodal refractoriness and the relative effect of verapamil on AV nodal refractoriness was determined. In 6 of 21 preparations the functional AV refractory curve became discontinuous only when stimulation was applied at the atrial septum and suggested dual AV nodal pathways (dual pathways group). In the 15 other preparations no interruption of the curve occurred with either crista terminalis or atrial septal stimulation (normal conduction group). In the normal conduction group, the difference in the effective refractory period of the AV node obtained by crista terminalis vs atrial septal stimulation was not significant (154 +/- 25 vs 150 +/- 28 ms). However, the functional refractory period was significantly longer with crista terminalis vs atrial septal stimulation (232 +/- 19 vs 239 +/- 19 ms, p less than 0.001). After verapamil administration, the effective and functional refractory periods during crista terminalis vs atrial septal stimulation were prolonged to 270 +/- 49 vs 285 +/- 55 ms (p less than 0.01) and 335 +/- 43 vs 351 +/- 41 ms (p less than 0.001), respectively. Thus, the difference in refractory periods associated with changing the stimulation site was exaggerated with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic effects of intravenous metoprolol

We evaluated the electrophysiologic effects of intravenous metoprolol, a selective beta-1-blocking agent, in 12 patients. Electrophysiologic parameters were measured during the control period, immediately following, and 4 to 6 hours after infusion of 0.15 mg/kg. Metoprolol serum concentration was serially measured in 6 of the 12 patients. Immediately after metoprolol infusion, the sinus cycle length increased by 20% from 738 +/- 166 msec to 885 +/- 181 msec (p less than 0.01), AH interval during sinus rhythm increased by 34% from 83 +/- 27 msec to 112 +/- 37 msec (p less than 0.01), and antegrade atrioventricular (AV) nodal Wenckebach cycle length increased by 20% from 360 +/- 188 msec to 432 +/- 199 msec (p less than 0.01). Sinus node recovery time and sinoatrial conduction time did not become abnormally prolonged in any patient. His-Purkinje conduction was unaltered. High atrial and ventricular refractory periods were modestly increased (less than 15 msec); the increase in refractoriness reached statistical significance when repeat measurements were made at 4 to 6 hours. No adverse effects were noted. Metoprolol serum concentration at the time of peak measured electrophysiologic effect was 54.6 +/- 15.2 ng/ml. We conclude that at this dose, intravenous metoprolol significantly prolongs sinus cycle length and AV nodal conduction, may modestly increase atrial and ventricular refractoriness, and appears to have electrophysiologic potency similar to propranolol. It is well tolerated following intravenous administration and may be of particular value in the acute treatment of supraventricular tachycardia when beta-receptor selectivity is desired.     

Effect of basic pacing cycle length on sinus node refractoriness in the rabbit

The effect of basic pacing cycle length on sinus node refractoriness was investigated. In 18 rabbit right atrial preparations, the sinus node effective refractory period (SNERP) was measured at multiple basic pacing cycle lengths. In 14 experiments SNERP was measured at basic pacing cycle lengths of 400, 350 and 300 ms. The mean SNERP (+/- standard deviation) prolonged from 168 +/- 31 ms at 400 ms to 181 +/- 37 ms at 350 ms to 196 +/- 40 ms at 400 ms (p less than 0.001). To rule out the possibility that rapid stimulation might release acetylcholine and thus prolong refractoriness, 4 more experiments were conducted in the presence of atropine (2 X 10(-6) M), and similar results were obtained. The spatial orientation of refractoriness was examined in 7 experiments. At the same premature interval, shorter basic pacing cycle lengths resulted in block of the premature impulse at a greater distance from the sinus node. Therefore, in sinus node tissue refractoriness increases with shortening of basic pacing cycle length, a response similar to that of the atrioventricular node.     

Functional bundle branch block: Discordant response of right and left bundle branches to changes in heart rate

Faster heart rates shorten refractoriness more in some tissues than in others. This study investigates whether faster heart rates shorten relative refractoriness more in the right than left bundle branch in humans. Premature atrial stimulation at 2 or more basic cycle lengths was performed in 314 patients with no evidence of atrioventricular conduction system disease. In 10 patients, both functional right and left bundle branch block (BBB) developed with premature atrial stimulation. Functional right BBB occurred at the longer basic cycle length, and functional left BBB at the shorter cycle length in 8 patients. In 2 patients functional right and functional left BBB were present at the same cycle length, but functional left BBB occurred at a shorter premature atrial coupling interval. For all patients, the mean functional right bundle branch relative refractoriness was 438 ms at a basic cycle length of 847 ms, and functional left bundle branch relative refractoriness was 357 ms at a cycle length of 622 ms (p <0.01). The HV interval was 45 ± 15 ms at control and increased with functional left BBB to 77 ± 19 ms (p <0.01), but not with functional right BBB. Thus, relative refractoriness of the right and left bundle branches are rate-dependent and discordant. At longer cycle lengths, relative refractoriness of the right bundle branch is greater than that of the left bundle branch, and at shorter cycle lengths relative refractoriness of the left bundle branch is greater than that of the right bundle branch. The relative refractory period curves “cross over” and can explain the presence of both functional right and left BBB in the same patient.     

Cibenzoline: electrophysiologic effects of a new class I anti-arrhythmia agents in supraventricular tachycardia

Cibenzoline, an imidazoline derivate, is a new class 1 antiarrhythmic agent. The electrophysiologic effects and antiarrhythmic properties of cibenzoline (100 mg i.v.) were evaluated in 22 patients with paroxysmal supraventricular tachycardia: 12x Wolff-Parkinson-White Syndrome, 9x AV nodal reentrant tachycardia, 1x atrial tachycardia. Cibenzoline shortened the sinus cycle length from 742 +/- 103 ms to 661 +/- 87 ms (p less than 0.001) and the sinus node recovery time from 1026 +/- 106 ms to 926 +/- 135 ms (p less than 0.001). The substance lengthened the AH interval from 93 +/- 19 ms to 112 +/- 24 ms (p less than 0.001) and the HV interval from 42 +/- 12 ms to 61 +/- 14 ms (p less than 0.001). The effective refractory periods of the atrium and right ventricle did not change significantly, but the effective refractory period of the AV node in antegrade (269 +/- 42 ms vs 278 +/- 46 ms; p less than 0.05) and retrograde direction (281 +/- 57 ms vs 413 +/- 124 ms; p less than 0.001) increased markedly. Cibenzoline prolonged the effective refractory period of the accessory pathway in retrograde direction from 263 +/- 41 ms to 428 +/- 101 ms (p less than 0.001). The effective refractory period of the antegrade accessory pathway did not change. During atrial stimulation inducibility of the reentrant tachycardia was suppressed in 14 of 22 patients and the inducibility of atrial fibrillation in 7 of 12 patients. The RR interval of the reentrant tachycardia was prolonged from 353 +/- 57 ms to 420 +/- 57 ms (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic effects of N-acetylprocainamide in human beings

The electrophysiologic properties of N-acetylprocainamide (NAPA) were studied in 10 patients undergoing cardiac catheterization. Each patient received two successive intravenous infusions: one loading infusion over 15 minutes and one maintenance infusion at a slower rate for 30 minutes. Eight patients received 10.5 mg/kg body weight and two received larger doses (16 and 21 mg/kg, respectively). NAPA plasma concentration was measured at 5 minute intervals from 0 to 25 minutes, and then at 15 and 30 minutes of the second infusion. Mean blood pressure and electrophysiologic data obtained by programmed stimulation were recorded before drug administration and at 15 and 30 minutes of the infusion when the concentration of NAPA was nearly constant in each patient (range 12 to 35 microgram/ml). NAPA decreased blood pressure (p less than 0.005), increased corrected Q-T interval (p less than 0.01) and increased the atrial and ventricular effective refractory periods from 267 +/- 40 to 307 +/- 41 ms (p less than 0.01) and from 278 +/- 37 to 301 +/- 32.8 ms (p less than 0.05), respectively. NAPA did not significantly change sinus cycle length or sinus nodal recovery time, conduction intervals (A-H, H-V, P-R, QRS), atrioventricular nodal functional refractory period or nodal Wenckebach cycle length. The patient receiving the largest dose experienced mild nausea when the plasma concentration was above 35 microgram/ml. These data show that the electrophysiology of NAPA in human beings is different from that reported for procainamide. At the plasma concentrations studied NAPA increases atrial and ventricular refractory periods without increasing cardiac conduction times     

The electrophysiological effects of intravenous magnesium on human sinus node, atrioventricular node, atrium, and ventricle

The effects of intravenously (IV) administered magnesium chloride (MgCl) on electrophysiologic and electrocardiographic variables were studied in 13 patients undergoing a routine electrophysiologic assessment for clinical indications. An infusion of 12 mmol of MgCl was given during a 10-min period and relevant electrophysiologic variables were determined before and after the infusion. Serum Mg levels increased from 0.78 +/- 0.03 (mean +/- SEM) before to 1.52 +/- 0.08 ms after the infusion (p less than 0.0001). Magnesium treatment caused a significant prolongation in PR interval (from 151 +/- 8 to 174 +/- 8 ms, p less than 0.001) as well as in QRS duration (from 90 +/- 4 to 101 +/- 6 ms, p less than 0.05). Likewise, intra-atrial (PA) as well as atrioventricular (AV) nodal (AH) conduction times were significantly prolonged (from 33 +/- 3 to 46 +/- 3 ms, p less than 0.01, and from 85 +/- 6 to 94 +/- 6 ms, p less than 0.05, respectively). Mean effective and functional atrial refractory periods increased (from 228 +/- 8 to 256 +/- 10 ms, p less than 0.01 and from 292 +/- 9 to 320 +/- 11 ms, p less than 0.01, respectively), as did mean AV node functional refractory period (from 399 +/- 29 to 422 +/- 27 ms, p less than 0.02). No significant change occurred with regard to sinus node function (as estimated from heart rate, sinus node recovery time, and calculated sinoatrial conduction time) or ventricular refractoriness. It is concluded that IV Mg has several electrophysiologic effects that may be beneficial in the treatment/prevention of supraventricular tachyarrhythmias.     

Increased dispersion and shortened refractoriness caused by verapamil in chronic atrial fibrillation

OBJECTIVES: The objective was to assess the effect ofverapamil on atrial fibrillation (AF) cycle length and spatial dispersion of refractoriness in patients with chronic AF. BACKGROUND: Previous studies have suggested that verapamil prevents acute remodeling by AF. The effects of verapamil in chronic AF are unknown. METHODS: During electrophysiologic study in 15 patients with chronic AF (duration >1 year), 12 unipolar electrograms were recorded from right atrial free wall, right atrial appendage and coronary sinus, along with monophasic action potential recordings from the right atrial appendage. The mean fibrillatory interval at each atrial recording site was used as an index for local refractoriness. Dispersion of refractoriness was calculated as the standard deviation of all local mean fibrillatory intervals expressed as a percentage of the overall mean fibrillatory interval. After baseline measurements, verapamil (0.075 mg/kg intravenous in 10 min) was infused and the measurements were repeated. RESULTS: After administration ofverapamil, mean fibrillatory intervals shortened by a mean of 16.6 +/- 3.3 ms (p < 0.001) at the right free wall, 15.0 +/- 3.5 ms (p < 0.001) at the appendage and 17.1 +/- 3.2 ms (p < 0.01) in the coronary sinus. Monophasic action potential duration decreased by 15.9 +/- 4.0 ms (p < 0.01). Dispersion of refractoriness increased in all patients from 3.8 +/- 0.8 to 5.1 +/- 1.8 (p < 0.001). A strong correlation between mean fibrillatory intervals and action potential duration was found, both before and after verapamil. CONCLUSIONS: Verapamil caused shortening of refractoriness and increase in spatial dispersion of refractoriness in patients with chronic AF. This implies that verapamil is not useful in reversing the remodeling process in these patients.