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)     

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.     

Electrophysiologic effects of intravenous magnesium in patients with normal conduction systems and no clinical evidence of significant cardiac disease

Parenteral magnesium has been used for several decades in the empiric treatment of various arrhythmias, but the data on its electrophysiologic effects in man are limited. We evaluated the electrophysiologic effects of magnesium sulfate (MgSO4) administration in eight normomagnesemic patients with normal mononuclear cell magnesium content, who had no clinically significant heart disease and had normal baseline electrophysiologic properties. After administration of intravenous MgSO4, serum magnesium rose significantly from 1.9 +/- 0.1 to 4.4 +/- 1.7 mg/dl (p less than 0.02). During a maintenance magnesium infusion, we observed significant prolongation of the ECG PR interval (145 +/- 18 to 155 +/- 26 msec, p less than 0.05), AH interval (77 +/- 27 to 83 +/- 26 msec, p less than 0.002), antegrade atrioventricular (AV) nodal effective refractory period (278 +/- 67 to 293 +/- 67 msec, p less than 0.05), and sinoatrial conduction time (60 +/- 34 to 76 +/- 32 msec, p less than 0.02). No significant effect was observed on sinus cycle length, sinus node recovery time, intra-atrial or intraventricular conduction times, QRS duration (during both sinus rhythm and ventricular pacing), QT interval, HV interval, paced cycle length resulting in AV nodal Wenckebach block, AV nodal functional refractory period, retrograde ventriculoatrial (VA) effective refractory period, or atrial and ventricular refractory periods. These findings, in conjunction with the demonstrated ability of magnesium to block slow channels for sodium movement, may provide an explanation of the mechanism by which magnesium exerts its effect in the treatment of atrial and junctional arrhythmias.     

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)     

Effects of upright posture on atrioventricular nodal reentry and dual atrioventricular nodal pathways

The electrophysiologic effects of upright posture (45 degrees upright tilt) were studied in 17 patients with dual atrioventricular (AV) nodal pathways, AV nodal reentry or both. Discontinuous AV nodal conduction curves were observed in 16 patients while supine, but in only 11 patients while upright. Fast pathway refractoriness was shortened: the anterograde fast pathway effective refractory period decreased from 360 +/- 22 to 275 +/- 14 ms (mean +/- standard error of the mean), the anterograde fast pathway block cycle length shortened from 448 +/- 28 to 348 +/- 20 ms and the retrograde fast pathway block cycle length shortened from 425 +/- 29 to 338 +/- 24 ms (all p less than 0.01). The anterograde slow pathway block cycle length shortened from 378 +/- 29 to 316 +/- 17 ms (p less than 0.05). AV nodal reentrant tachycardia was induced in 5 patients while supine (2 sustained, 3 nonsustained) and in 6 patients while upright (4 sustained, 2 nonsustained). Tachycardia cycle length shortened during upright posture, from 413 +/- 30 to 345 +/- 22 ms (p less than 0.01), primarily due to shortened anterograde slow pathway conduction time, from 322 +/- 23 to 268 +/- 20 ms (p less than 0.05). Upright posture thus enhances conduction in patients with dual AV nodal pathways, facilitating AV nodal reentry. Electrophysiologic testing in the upright position may yield additional clinical important information in patients with dual AV nodal pathways.     

The electrophysiologic characteristics of the transplanted human heart

The electrophysiologic characteristics of the denervated human heart were assessed in 14 cardiac transplant recipients. Conduction intervals and refractory periods were measured at pacing cycle lengths of 500 msec and 400 msec. The faster pacing rate caused lengthening of the AH interval (83 +/- 23 msec to 116 +/- 41 msec, p less than 0.01) and shortening of the QT (338 +/- 27 msec to 313 +/- 22 msec, p less than 0.001) and JT (249 +/- 21 msec to 229 +/- 19 msec, p less than 0.001) intervals. There was no change in the SA, HV, or QRS durations. Wenckebach periodicity occurred at a longer cycle length in the retrograde than in the anterograde direction (409 +/- 96 msec vs 318 +/- 46 msec, p less than 0.01) and anterograde conduction was better than retrograde conduction in 13 of the 14 patients (93%). Increasing pacing cycle length resulted in shortening of the atrial effective (203 +/- 28 msec to 190 +/- 25 msec, p less than 0.001), ventricular effective (224 +/- 18 msec to 211 +/- 17 msec, p less than 0.01), and AV nodal functional (367 +/- 38 msec to 357 +/- 36 msec, NS) refractory periods. The AV nodal effective refractory period lengthened (294 +/- 31 msec to 314 +/- 52 msec, p less than 0.05). There was a close correlation between AV Wenckebach cycle length and the functional refractory period of the AV node (r = 0.853, p less than 0.001). These results are qualitatively and quantitatively similar to those reported in the innervated heart. The autonomic nervous system appears to have little influence on the resting electrophysiologic characteristics of the atrioventricular conduction system in the innervated heart.     

Electrophysiologic effects and clinical efficacy of oral propafenone therapy in patients with ventricular tachycardia

The effects of the antiarrhythmic agent propafenone were evaluated in 25 patients with recurrent symptomatic ventricular tachycardia. Oral propafenone was given to a maximal dose of 300 mg every 8 hours. Ten of the 25 patients developed side effects or had inadequate suppression of spontaneous ventricular arrhythmias during propafenone therapy. Electrophysiologic studies were performed before and during drug therapy on the 15 patients who had a satisfactory clinical response. Propafenone increased the PR interval from 168 +/- 46 to 188 +/- 25 ms (p less than 0.007), the HV interval from 47 +/- 10 to 65 +/- 13 ms (p less than 0.005), the shortest atrial pacing cycle length to maintain 1:1 atrioventricular (AV) nodal conduction from 385 +/- 44 to 436 +/- 42 ms (p less than 0.005), the ventricular effective refractory period from 231 +/- 17 to 255 +/- 19 ms (p less than 0.001) and the ventricular functional refractory period from 260 +/- 15 to 278 +/- 17 ms (p less than 0.002). Before propafenone therapy, all 15 patients had ventricular tachycardia induced by programmed ventricular stimulation. During propafenone treatment, 12 patients still had ventricular tachycardia induced, and the tachycardia cycle length significantly increased from 236 +/- 44 to 374 +/- 103 ms (p less than 0.001). Ten patients were considered to have satisfactory electrophysiologic response to propafenone on the basis of either the inability to initiate ventricular tachycardia or a marked increase in ventricular tachycardia cycle length associated with lack of symptoms during the induced tachycardia. These patients were discharged receiving propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of acebutolol on paroxysmal atrioventricular reentrant tachycardia in patients with manifest or concealed accessory pathways

Electrophysiologic studies before and after administration of 50 mg of intravenous (IV) acebutolol were performed in 20 patients. Four of the 20 had persistent preexcitation, two had intermittent preexcitation, and 14 had a concealed retrogradely conducting accessory pathway (AP). Acebutolol depressed anterograde AP conduction with loss of preexcitation in one patient and increased the effective refractory period of AP in the remaining three; in most, it depressed anterograde normal pathway conduction. The longest atrial paced cycle length producing atrioventricular (AV) nodal block increased from 290 +/- 7 to 39 +/- 6 msec (mean +/- SEM) after acebutolol (p less than 0.01). Acebutolol had no significant effect on retrograde AP conduction. Sustained AV reentrant tachycardia was inducible in all 20 patients before acebutolol and in 19 after acebutolol. The cycle length of tachycardia increased from 323 +/- 8 to 352 +/- 8 msec after acebutolol (p less than 0.01), reflecting an increment of A-H interval from 148 +/- 8 to 174 +/- 9 msec (p less than 0.01). Electrophysiologic studies were reported after 800 mg of oral acebutolol given in four divided doses at six-hour intervals in eight patients. The results were comparable to those of IV acebutolol. Thus, acebutolol depresses AV nodal conduction and slows the rate of AV reentrant tachycardia, but is generally ineffective in inhibiting the induction of sustained tachycardia. It occasionally depresses anterograde AP conduction.     

Acute electrophysiologic effects of inhaled salbutamol in humans

STUDY OBJECTIVES: Although inhaled beta2-agonists are in widespread use, several reports question their potential arrhythmogenic effects. The purpose of this study was to evaluate the cardiac electrophysiologic effects of a single, regular dose of an inhaled beta2-agonist in humans. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Six patients with bronchial asthma and 12 patients with mild COPD. INTERVENTIONS: All patients underwent an electrophysiologic study before and after the administration of salbutamol solution (5 mg in a single dose). MEASUREMENTS AND RESULTS: Sinus cycle length, sinus node recovery time (SNRT), interval from the earliest reproducible rapid deflection of the atrial electrogram in the His bundle recording to the onset of the His deflection (AH), interval from the His deflection to the onset of ventricular depolarization (HV), Wenckebach cycle length (WCL), atrial effective refractory period (AERP), and ventricular effective refractory period (VERP) were evaluated just before and 30 min after the scheduled intervention. Salbutamol, a selective beta2-agonist, administered by nebulizer had significant electrophysiologic effects on the atrium, nodes, and ventricle. The AH length decreased from 86.1 +/- 19.5 ms at baseline to 78.8 +/- 18.4 ms (p < 0.001), and the WCL decreased from 354.4 +/- 44.2 to 336.6 +/- 41.7 ms (p = 0.001). Salbutamol significantly decreased the AERP and VERP too while leaving the HV unchanged. Additionally, inhaled salbutamol increased heart rate (from 75.5 +/- 12.8 beats/min at baseline to 93.1 +/- 16 beats/min, p < 0.001) and shortened the SNRT (from 1,073.5 +/- 178.7 to 925.2 +/- 204.9 ms, p = 0.001). CONCLUSION: Inhaled salbutamol results in significant changes of cardiac electrophysiologic properties. Salbutamol enhances atrioventricular (AV) nodal conduction and decreases AV nodal, atrial, and ventricular refractoriness in addition to its positive chronotropic effects. These alterations could contribute to the generation of spontaneous arrhythmias.     

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.     

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.     

Use of adenosine as a diagnostic tool for dual atrioventricular nodal pathways: response of control patients to incremental doses of adenosine

BACKGROUND: Adenosine at low doses preferentially blocks fast over slow pathway conduction in patients with dual atrioventricular (AV) nodal physiology and typical AV nodal reentrant tachycardia (AVNRT). During atrial pacing, this effect is manifested as an abrupt increase in the AH interval with low doses of adenosine. This demonstration of dual AV nodal physiology may be useful as a diagnostic tool during electrophysiologic studies in patients with supraventricular tachycardia who are not easily inducible, as clear demonstration of dual AV nodal pathways may indicate that AVNRT is a likely diagnosis and that further attempts at arrhythmia induction should be tailored in that direction. However, to be a useful test, adenosine should not cause an abrupt increase in AH interval in patients without dual AV nodal physiology. HYPOTHESIS: This study was designed to investigate the prevalence of dual AV nodal pathways with administration of adenosine in patients with no history suggestive of AVNRT. METHODS: Thirty-seven patients who had no prior history of AVNRT and were undergoing electrophysiologic study for standard indications were enrolled. Baseline Wenckebach cycle length (WCL) and AV nodal effective refractory periods were measured at atrial pacing cycle lengths of 400 and 600 ms. The atrium was then paced at WCL + 50 ms, and WCL + 100 ms, while incrementally larger doses of intravenous adenosine were administered until AV nodal block occurred. RESULTS: The mean (+/- standard deviation) doses of adenosine required to cause AV nodal block while pacing at WCL + 50 ms and WCL + 100 ms were 7.1 +/- 3.9 and 7.4 +/- 4.5 mg, respectively. In 1 of 37 patients (2.7%, 95% confidence interval 0-8%), an abrupt prolongation of the AH interval was seen with the administration of adenosine during atrial pacing as well as during the atrial refractory period determination. In all other patients, no dual AV nodal physiology was demonstrated during the refractory period determination, and there were only gradual changes in the AH interval with atrial pacing during administration of adenosine. CONCLUSION: Among patients with no history suggestive of AV nodal reentrant tachycardia, only 2.7% have clinically silent dual AV nodal pathways using this method. Incremental adenosine infusion during electrophysiologic study can be used as a highly specific diagnostic tool for patients with dual AV nodal pathways.     

Comparison of the ventricular response during atrial fibrillation in patients with enhanced atrioventricular node conduction and Wolff-Parkinson-White syndrome

Although ventricular fibrillation is a well known sequel to atrial fibrillation in the Wolff-Parkinson-White syndrome, ventricular fibrillation is not generally associated with supraventricular tachycardia in the presence of enhanced atrioventricular (AV) node conduction without pre-excitation. It was hypothesized that the ventricular response during atrial fibrillation may be less in patients with enhanced AV node conduction than in their counterparts with Wolff-Parkinson-White syndrome matched for anterograde effective refractory period. Slower ventricular rates during atrial fibrillation would suggest an increased propensity for concealed conduction in the enhanced AV node conduction group than in the group with an accessory pathway. Three groups of patients aged 16 to 65 years underwent electrophysiologic testing for supraventricular tachycardia or after surgical correction of Wolff-Parkinson-White syndrome. Sixteen patients had enhanced AV node conduction, 16 had Wolff-Parkinson-White syndrome and 16 had normal AV node conduction. Patients with enhanced AV node conduction and Wolff-Parkinson-White syndrome were well matched for anterograde effective refractory period (245 +/- 22 versus 258 +/- 25 ms) and minimal cycle length, maintaining 1:1 anterograde conduction (261 +/- 21 versus 260 +/- 40). There was no difference in intervals during atrial fibrillation (average RR interval = 372 +/- 37 versus 346 +/- 66) or shortest RR interval (266 +/- 27 versus 243 +/- 51). Thus, patients with Wolff-Parkinson-White syndrome and those with enhanced AV node conduction matched for anterograde refractory period exhibit similar ventricular rates during atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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 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     

Electrophysiologic study of the effects of aminophylline and metaproterenol on canine myocardium.

Aminophylline and beta-adrenergic agonists are widely used in the treatment of obstructive lung diseases. It has been suggested that combined aminophylline and beta-agonist therapy may promote the development of atrial and ventricular arrhythmias. The effects of these agents in combination on myocardial conduction and tissue refractoriness have not been documented. We evaluated the electrophysiologic effects of intravenous aminophylline and inhaled metaproterenol on canine myocardium. Aminophylline produced significant decreases from baseline in the AH interval (85 +/- 6.5 [SD] to 63 +/- 4.1 ms [p less than 0.02]), Wenckebach cycle length (WCL) (226 +/- 8.7 to 182 +/- 5.8 ms [p less than 0.02]), and ventricular effective refractory period (VERP) (166 +/- 6.0 to 148 +/- 4.9 ms [p less than 0.01]). Metaproterenol produced similar results, except metaproterenol significantly decreased the atrial effective refractory period (AERP) from 152 +/- 6.6 to 130 +/- 3.2 ms (p less than 0.02), an effect not seen with aminophylline alone. Metaproterenol also produced significantly greater reductions in AH interval and WCL, as well as a greater increase in heart rate than aminophylline did. When compared with aminophylline alone, combined metaproterenol and aminophylline therapy produced significantly greater reductions in the AH interval (63 +/- 4.1 versus 48 +/- 1.2 ms for combined therapy [p less than 0.01]), HV interval (32 +/- 1.2 versus 28 +/- 2.0 ms for combined therapy [p less than 0.02]), WCL (182 +/- 5.8 versus 150 +/- 7.1 ms for combined therapy [p less than 0.02]), and VERP (148 +/- 4.9 versus 132 +/- 2.0 ms for combined therapy [p less than 0.02]). We conclude that both aminophylline and metaproterenol significantly enhance AV nodal and His-Purkinje conduction. Metaproterenol produced significant changes in both atrial and ventricular tissue refractoriness. Metaproterenol produced significantly greater changes than aminophylline alone, and inhaled metaproterenol combined with intravenous aminophylline produced greater changes in AV nodal and His-Purkinje conduction and ventricular refractoriness than did aminophylline alone in a canine model.     

Usefulness of combined propranolol and verapamil for evaluation of surgical ablation of accessory atrioventricular connections in patients without structural heart disease

Successful surgical ablation of atrioventricular (AV) accessory connections may be confirmed during postoperative electrophysiologic testing by the absence of accessory connection conduction in both the anterograde and retrograde directions. Whereas the former may be readily apparent by examination of the surface electrocardiogram during sinus rhythm or atrial pacing, assessment of the latter may be complicated by the frequent presence of enhanced retrograde AV nodal conduction in the postoperative period. Consequently, availability of interventions that selectively affect AV nodal conduction and refractoriness without concomitant effects on accessory connections may be helpful for assessing the success of the surgical procedure. In this study the effects of combined propranolol and verapamil administration on electrophysiologic properties of the AV node and the accessory AV connection were assessed both pre- and postoperatively in 17 patients (12 men and 5 women, mean age 33 years) undergoing surgical ablation of accessory connections. Preoperatively, electrophysiologic characteristics of all but 1 of the accessory AV connections were unaffected by propranolol and verapamil administration. Postoperatively, on the other hand, propranolol and verapamil significantly prolonged both the retrograde AV node effective refractory period (baseline: 272 +/- 34 ms vs after drugs: 384 +/- 70 ms [p less than 0.0001]) and the shortest cycle length maintaining 1:1 ventriculoatrial conduction (baseline: 357 +/- 99 ms vs after drugs: 485 +/- 64 ms [p less than 0.0001]). Late postoperative electrophysiologic evaluation (7 +/- 3 weeks) revealed no evidence of residual accessory AV connection conduction, and all patients remain asymptomatic at 21 +/- 10 months follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of programmed stimulation in predicting efficacy of propafenone in long-term antiarrhythmic therapy for paroxysmal supraventricular tachycardia

The electrophysiologic effects of intravenous (i.v.) and oral propafenone were evaluated in 14 patients with Wolff-Parkinson-White syndrome and in 10 patients with atrioventricular (AV) nodal reentrant tachycardia. The effective refractory periods of the right atrium and the AV node increased after both preparations. In patients with Wolff-Parkinson-White syndrome, i.v. propafenone blocked anterograde accessory pathway conduction in 2 patients and retrograde conduction in 1; during oral therapy, accessory pathway conduction block occurred in 2 additional patients. The mean cycle length of the supraventricular tachycardia (SVT) increased from 338 +/- 60 ms to 387 +/- 56 ms (p less than 0.05) after i.v. application, and from 336 +/- 65 ms to 367 +/- 65 ms (p less than 0.05) during oral propafenone. The shortest pacing interval maintaining a 1:1 AV conduction increased from 325 +/- 65 ms to 368 +/- 81 ms (p less than 0.05) after i.v. infusion, and from 333 +/- 57 ms to 369 +/- 75 ms (p less than 0.05) during oral therapy. There was no difference in the electrophysiologic effects between i.v. and oral propafenone. The induction of SVT was prevented by i.v. propafenone in 10 of 20 patients and in 4 additional patients with oral propafenone. During follow-up, 6 of 7 patients, whose SVT could not be initiated by electrophysiologic drug testing, remained free from recurrences, whereas 5 of 7 patients with inducible tachycardia had recurrences of SVT. Thus, in patients with SVT, propafenone prolonged accessory pathway and AV nodal conduction and had a beneficial effect on circus movement tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative quantitative electrophysiologic effects of adenosine triphosphate on the sinus node and atrioventricular node

A pharmacologic approach was used to characterize the sinus node (SN) and atrioventricular (AV) node responses to intravenous adenosine triphosphate (ATP) in 21 patients during electrophysiologic testing. ATP produced dose-dependent prolongation of spontaneous sinus cycle length. The mean maximal increase in sinus cycle length was 294 +/- 60 ms (n = 10). The mean dose of ATP required to produce this maximal sinus cycle length prolongation was 3.5 +/- 1.0 mg. The dose-response curve for sinus cycle length prolongation was sigmoid in shape with an EC50 of 0.39 mg derived from a median effect plot. There was a negative correlation between the control sinus cycle length and the dose of ATP required to produce the maximal prolongation of cycle length (p less than 0.05). In contrast, the mean dose of ATP producing AV block was 4.4 +/- 0.97 mg and the EC50 was 2.98 mg. There was a positive correlation between the AV nodal functional refractory period and the prolongation of the AH interval with a 2 mg dose (p less than 0.05). Consistent with the AV nodal dose-response curves, 8 mg ATP terminated paroxysmal reentrant supraventricular tachycardia at the AV node in 8 of 9 patients. Thus, SN and AV node responses to ATP have differences in their electrophysiologic correlates and EC50. These findings suggest that ATP has potentially different mechanisms of action on SN automaticity and AV nodal conduction that requires further investigation.