Electrophysiologic properties of prenalterol

We assessed the electrophysiological properties of prenalterol, a new beta-selective agonist, in 10 patients with normal and 10 patients with delayed atrioventricular (A-V) conduction times. We evaluated sinus node function, A-V conduction times, refractory periods, atrial or ventricular arrhythmias, spontaneous or induced by the single extrastimulus technique during basal conditions, 5 minutes after a first dose of 20 micrograms/kg of prenalterol, and 5, 15 and 30 minutes after a second injection of the same dose. Prenalterol increased heart rate about 20%, with statistically significant shortening of right atrial refractory periods, A-V nodal functional and effective refractory periods and A-H interval in both groups after the first dose. In the 6 patients with sick sinus syndrome, prenalterol increased heart rate significantly and decreased maximum sinus node recovery time which reached a statistically significant value (P less than 0.05) 5 and 30 minutes after the second dose. At the highest dose, prenalterol seemed to increase the number of ventricular and/or atrial arrhythmias only in those patients with the arrhythmias before treatment. Prenalterol increases heart rate and decreases A-V node conduction times. The shortening of maximum sinus node recovery time in patients with the sick sinus syndrome, especially if confirmed after oral administration, could indicate a specific use of this drug in patients with sinus bradycardia or atrial fibrillation with a slow ventricular response.     

Effects of digitalis on sinus nodal function in patients with sick sinus syndrome

The effect on sinus rhythmicity and automaticity of complete digitalization in a 24 hour period was observed in 14 patients with sick sinus syndrome. Sinus nodal function was evaluated in these patients by assessing sinus nodal recovery time and by treadmill exercise testing and 24 hour Holter monitoring, before and after digoxin administration. Corrected sinus nodal recovery times ranged from 240 to 2,065 msec (average 714) before digoxin and were shortened to 250 to 1,260 msec (average 565) after the glycoside. Further, digoxin induced accelerated infra sinus escape pacemaker activity in five patients: junctional and ventricular in one and atrial in four. Spontaneous sinus rate evaluated with Holter monitoring revealed an average of 56 beats/min (range 43 to 69) before digitalis that was unchanged (average 58 beats/min; range 48 to 74) after digoxin therapy. Similarly, the sinus nodal response to exercise was unaffected after digitalization (average 118 beats/min both before and during digitalis therapy). It is concluded that digoxin does not exert adverse effects on sinus nodal function in patients with sick sinus syndrome. The glycoside can be used safely in these patients when indicated for cardiac pump dysfunction or for control of tachyarrhythmia.     

Human Electropharmacology of Tocainide, a lidocaine congener

The electropharmacology of tocainide, an orally active congener of lidocaine, was evaluated in 10 patients with coronary artery disease. Electrophysiologic measurements including sinus nodal recovery time, sinoatrial conduction time, intraatrial conduction time, atrial, atrioventricular (A-V) nodal and ventricular refractory periods and intraventricular conduction time were obtained before and after intravenous infusion of tocainide. At blood levels shown to be effective against ventricular arrhythmias, tocainide produced no statistically significant changes in the electrophysiologic measurements, although occasional marked individual effects were observed. No side effects were observed during these studies. No adverse effects on A-V conduction were observed in patients with an intraventricular conduction disturbance or a prolonged control H-V interval. Thus, plasma tocainide concentrations effective in the therapy of ventricular arrhythmias exert no adverse effects on cardiac electrophysiologic properties in patients with coronary artery disease.     

Electrophysiologic effects of isoproterenol on cardiac conduction system in man.

The effects of isoproternol (ISOP) on the functional properties of the A-V conduction system were studied in 16 patients using His-bundle recordings and the atrial extrastimulus technique. In all patients, ISOP at an infusion rate of 1 mcg. per minute resulted in sinus acceleration and enhancement of A-V nodal conduction, but had no effect on His-Purkinje conduction time. ISOP significantly decreased both functional and effective refractory periods of the A-V node. The relative refractory period of the His-Purkinje system decreased by a small amount in five patients in whom the parameter could be compared before and after the drug.     

Electrophysiologic effects of tolamolol on atrioventricular conduction in man

The electrophysiologic effects of tolamolol (UK-6558-01), a beta-adrenergic blocking agent, were studied in 13 patients by means of intracardiac electrograms and the extrastimulus method. Tolamolol (4 to 30 mg. intravenously) resulted in : (1) prolongation of sinus cycle length (SCL) in all patients (p less than 0.01); (2) prolongation of sinus escape time (SET) in 11 of 13 patients (p less than 0.001); (3) prolongation of A-V nodal conduction time during sinus rhythm in 1i of 13 patients (p less than 0.001); (4) onset of A-V nodal Wenckebach block at longer paced cycle lengths in 10 of 11 patients (p less than 0.001); (5) prolongation of the functional refractory period (FRP) of the A-V node in 11 of 11 patients (p less than 0.001); and (6) prolongation of the effective refractory period (ERP) of the A-V node in 10 of 10 patients (P less than 0.001). Tolamolol had no effect on His-Purkinje system (HPS) conduction time in any patient, including 3 patients with abnormal H-V intervals. Because of the marked increase in A-V nodal conduction time encountered by premature atrial depolarizations, the relative and effective refractory periods of the HPS could not be determined in any patient after tolamolol. Atropine (0.5 or 1.0 mg. intravenously) significantly reversed the effects of tolamolol on: sinus cycle length (4 of 5 patients); sinus escape time (3 of 3 patients); A-V nodal conduction time (4 of 5 patients); and A-V nodal refractioriness (5 of 5 patients).     

Effect of glucagon on cardiac conduction in man

His bundle electrograms were obtained in 26 patients before and after intravenous administration of glucagon (50 μg/kg). The group consisted of 4 patients with normal conduction and 22 patients with conduction disease. The P-A interval, measured in all patients, was 35 ± 1.4 msec (mean ± standard error of the mean) before and 30 ± 1.5 msec after infusion of glucagon (P < 0.001). The mean A-H interval during sinus rhythm in all patients and during pacing at 100/min in 21 patients was, respectively, 97 ± 6.0 msec and 114 ± 6.4 msec before, and 96 ± 6.0 msec and 114 ± 6.6 msec after infusion of glucagon (not significant). The mean H-V interval in 25 patients was 48 ± 2.6 msec before and 49 ± 2.0 msec after infusion of glucagon (not significant). The mean sinus rate and sinus recovery times were, respectively, 73 ± 3.0 beats/min and 1,025 ± 42.0 msec before and 81 ± 3.0 beats/min and 919 ± 27.0 msec after infusion of glucagon (P < 0.001 and < 0.01). Functional and effective refractory periods were measured (In milliseconds) with use of the atrial extrastimulus technique. The mean atrial functional and effective refractory periods (21 patients) were, respectively, 273 ± 11.6 and 252 ± 12.0 before and 256 ± 10.0 and 238 ± 9.6 after infusion of glucagon (P < 0.001 and < 0.01). Mean atrloventricular (A-V) nodal functional refractory period (22 patients) and effective refractory period (15 patients) were 465 ± 22.0 and 404 ± 33.0 before and 457 ± 23.0 and 395 ± 32.0 after the infusion (not significant). The mean effective refractory period of the His-Purkinje system (2 patients) was 440 ± 45.0 before and 425 ± 55.0 after infusion of glucagon (not significant).In summary, glucagon increased sinus nodal automaticity, as manifested by an increase in sinus rate and decrease of sinus nodal recovery time, and improved intraatrial conduction as manifested by a reduction of the P-A interval and atrial functional and effective refractory periods. Glucagon had no effect on A-V nodal or intraventricular conduction.     

Right atrial versus left atrial echo zones: A proposed new criterion for determining the atrial site of retrograde preexcitation

In a patient whose electrocardiogram (ECG) initially (1966) showed a Type A Wolff-Parkinson-White pattern, recurrent supraventricular tachycardia (SVT) developed but never subsequently showed antegrade bypass conduction. Intracardiac pacing studies (1975) revealed that premature high right atrial (induced 250–450 msec after atrial depolarization) or coronary sinus depolarization (250–550 msec) resulted in SVT. Late coronary sinus depolarization resulted in SVT without A-H prolongation. During SVT, P wave morphology changed and the coronary sinus atrial electrogram preceded that from the low right atrium; retrograde ventriculoatrial conduction time was 240 msec. Neither pacing the high right atrium or coronary sinus up to rates of 200 beats/min nor progressive atrial premature depolarizations from the high right atrium or coronary sinus resulted in antegrade bypass conduction. Failure of antegrade bypass conduction does not preclude SVT due to retrograde pre-excitation and must be distinguished from atrioventricular (A-V) nodal reentry. Atrial effective refractory period (200 msec) was shorter than the minimal time required for an atrial impulse to return to the atrium (380 msec), suggesting concealed antegrade bypass conduction. Stimulation of the atrium linked to the A-V bypass results in earlier bypass activation and recovery and explains the differing high right atrial vs coronary sinus echo zones.     

Electrophysiologic properties of procainamide in man

The electrophysiologic properties of procainamide were studied in 16 patients and correlated with plasma levels. Procainamide caused a minimal prolongation of atrioventricular (A-V) nodal conduction in 11 of 16 patients during sinus rhythm, but His-Purkinje conduction time was significantly prolonged in 15 of 16 patients. The effective refractory period of the atrium was prolonged by procainamide in 14 of 16 patients. The effective refractory period of the A-V node decreased in 8 of 9 patients. This may have been due to (1) anticholinergic properties of procainamide, (2) production of an A-V nodal “gap” by procainamide, or (3) an apparent A-V nodal block that actually represented decremental conduction in the His bundle; procainamide then caused delay in the A-V node allowing improved intra-His conduction and ventricular depolarization. The relative refractory period of the His-Purkinje system was prolonged in 10 of 11 patients. The effective refractory period was prolonged in one patient, unchanged in a second and apparently shortened in a third. In this third patient, procainamide produced a marked delay in proximal His-Purkinje conduction allowing a distal area of refractoriness to recover, thus causing apparent shortening of the effective refractory period. Plasma levels averaged 7.1 mg/ liter at the end of the study; no toxicity was noted.     

Electrophysiologic effects of atropine on atrioventricular conduction studied by His bundle electrogram

The electrophysiologic effects of atropine were studied with His bundle recordings in 14 patients. Administration of atropine, 0.5 mg intravenously, produced a moderate degree of sinus acceleration in all patients (average increase 20 percent over control rate). Atrioventricular (A-V) nodal conduction was enhanced during both sinus rhythm and at various paced atrial rates after administration of atropine. The paced atrial rates at which the A-V nodal Wenckebach phenomenon occurred were significantly higher after administration of the drug than before. Similar effects on retrograde conduction were observed during ventricular pacing. Atropine shortened both the functional and effective refractory periods of the A-V node but appeared to have no direct effect on either His-Purkinje conduction time or refractoriness. However, aberrant ventricular conduction and block within the His-Purkinje system increased during premature atrial stimulation after atropine administration. This was the result of shortening of the functional refractory period of the A-V node by atropine, which produced significantly shorter H₁–H₂ intervals. The effect of atropine on the electrophysiologic properties of the A-V conducting system was important in interpreting the conversion of a type I gap in A-V conduction to a type II gap.     

Electrophysiologic effects of intravenous timolol

We evaluated the electrophysiologic effects and dose response of the long-acting beta-blocking drug timolol given intravenously to 12 patients during intracardiac electrophysiologic study. Electrophysiologic parameters were measured during control and immediately, 30 minutes, and 48 hours following infusion. Significant changes in electrophysiologic parameters were only observed in the five patients (Group B) who received 0.05 mg/kg and not in the seven patients who received 0.02 mg/kg (Group A). In Group B patients immediately after timolol infusion sinus cycle length increased from 840 +/- 254 msec to 1048 +/- 63 msec (P less than 0.01), A-H interval during normal sinus rhythm increased from 94 +/- 42 msec to 101 +/- 45 msec (P less than 0.05), paced cycle length to A-V nodal Wenckebach increased from 370 +/- 45 msec to 430 +/- 76 msec (P less than 0.05), and A-V nodal effective refractory period increased from 284 +/- 63 msec to 360 +/- 83 msec (P less than 0.01). Significant increases in these electrophysiologic parameters were also noted at 30 minutes following timolol infusion. Other conduction times, atrial and ventricular refractory periods, and corrected sinus node recovery. time were unaltered by timolol. All electrophysiologic parameters returned to control in 48 hours. No adverse effects were observed. We conclude that intravenous timolol in doses of 0.05 mg/kg significantly increases sinus cycle length and prolongs A-V nodal conduction and refractoriness, demonstrates peak effects immediately after intravenous administration, and is well tolerated.     

Effects of verapamil on supraventricular tachycardia in children

Thirteen patients, aged 6 weeks to 16 years, with uncontrolled recurrent Supraventricular tachycardia were given intravenous verapamil in an attempt to abolish an episode of Supraventricular tachycardia. All patients had had intracardiac electrophysiologic studies to define the mechanism of their tachycardia. In seven patients conversion to sinus rhythm occurred after administration of verapamil: Five of the seven had atrioventricular (A-V) nodal reentry as the mechanism of their supraventricular tachycardia; the other two had reentrant tachycardia involving an accessory pathway. Verapamil was effective in abolishing the Supraventricular tachycardia in these patients, probably by prolonging the A-V nodal refractory period and conduction, thus breaking the reentrant circuit. In six patients there was no conversion to sinus rhythm: Four of the six had automatic atrial ectopic tachycardia and two had automatic junctional ectopic tachycardia. Among the four patients with automatic atrial ectopic tachycardia, a junctional escape rhythm developed in one, and second degree A-V block developed in the others. The two patients with junctional ectopic tachycardia had severe symptomatic arterial hypotension after verapamil and required resuscitation with intravenous calcium chloride. In spite of the good response to intravenous verapamil in the seven patients with reentrant tachycardia, only four of the seven could be maintained successfully on long-term oral therapy. The patients who experienced conversion to sinus rhythm with an intravenous bolus dose of verapamil but in whom Supraventricular tachycardia could still be induced with programmed stimulation could not be maintained successfully on oral therapy.It is concluded that verapamil is an effective antiarrhythmic agent that can (1) abolish the acute episode of Supraventricular tachycardia only in cases due to reentrant mechanisms, and (2) be used as an oral medication to prevent recurrences of supraventricular tachycardia in patients in whom the arrhythmia cannot be induced with programmed stimulation after intravenous doses of the drug.     

Functional abnormalities of the conduction system in children with an atrial septal defect

We performed an electrophysiologic study in 40 children with an atrial septal defect and analyzed their pre- and postoperative electrocardiograms and 24-hour Holter recordings. The electrophysiologic study showed a prolonged corrected sinus node recovery time in 83% and an abnormal sinuatrial conduction time in 25% of the children. An early Wenckebach response to atrial pacing was seen in 18%. Sixteen percent had a prolonged atrial conduction time. The atrial functional refractory period was abnormal in 35%. Two children developed nonsustained supraventricular tachycardia during the electrophysiologic study. The preoperative electrocardiogram showed first-degree atrioventricular block in 15% of the children; prolonged periods of accelerated atrial rhythm were found in 35% of the preoperative 24-hour Holter recordings. The incidence of first-degree atrioventricular block and accelerated atrial rhythm decreased postoperatively. We could not find a significant correlation between age or shunt size and the presence of electrophysiologic abnormalities or arrhythmias. These results indicate that the sinus node, atrioventricular node and atrial myocardium show some degree of dysfunction in patients with an atrial septal defect. An early operation may prevent further progression of electrophysiologic abnormalities and the development of symptomatic arrhythmias.     

Canine electrophysiology of encainide, a new antiarrhythmic drug

Encainide, a new benzanillide derivative with high potency and a good therapeutic/toxic ratio, was evaluated with the use of standard His bundle recording techniques to determine its effects on the cardiac conduction system in closed chest animals. Twenty mongrel dogs weighing 18 to 29 kg were anesthetized with 4 percent chloralose and classified into groups: group 1, a control group and groups 2,3, and 4, which were given 0.3, 0.9 and 2.7 mg/kg body weight, respectively, of encalnide In an intravenous infusion over a 15 minute period. Plasma concentration, blood pressure, surface electrocardiogram and atrlal and His bundle electrograms were recorded before, during and after drug infusion for a total of 120 minutes. Heart rate, A-H and H-V intervals, the QRS complex and Q-Tc interval were measured every 5 minutes during sinus rhythm and with constant atrial pacing. In addition, sinus nodal recovery time and atrial, atrioventrlcular (A-V) nodal and left ventricular refractory periods were measured before and immediately after infusion and every 30 minutes for 2 hours. Peak plasma concentration averaged 450 ng/ml in group 2,1,300 ng/ml in group 3 and 4,000 ng/ml in group 4. Blood pressure was not altered at any dose level throughout the study. The QRS complex and H-V interval were significantly prolonged (P < 0.005) at doses of 0.9 mg/kg and greater. These effects correlated well with plasma concentration. There was no significant change in heart rate, corrected sinus nodal recovery time, A-H interval, Q-Tc Interval atrial, A-V nodal or left ventricular refractory period. It is concluded that, unlike other antiarrhythmic agents, encainide prolongs His-Purkinje system conduction without significantly affecting conduction or refractoriness of other parts of the cardiac conduction system in animals.     

Electrophysiologic effects of atropine on sinus node and atrium in patients with sinus nodal dysfunction

Electrophysiologic studies were conducted in 21 patients with sinus nodal dysfunction before and after intravenous administration of 1 to 2 mg of atropine. The mean sinus cycle length (± standard error of the mean) was 1,171 ± 35 msec before and 806 ± 29 msec after administration of atropine (P < 0.001). Mean sinus nodal recovery time determined at a paced rate of 130/min and maximal recovery time were, respectively, 1,426 ± 75 and 1,690 ± 100 msec before and 1,169 ± 90 and 1,311 ± 111 msec after atropine (P < 0.001 and < 0.001). Mean calculated sinoatrial conduction time, measured in 16 patients, was 113 ± 8 msec before and 105 ± 9.7 msec after atropine (difference not significant). Mean atrial effective refractory period, measured at an equivalent driven cycle length, was 262 ± 11.1 msec before and 256 ± 10.3 msec after atropine (not significant). Mean atrial functional refractory period was 302 ± 12.5 msec before and 295 ± 11.3 msec after atropine (not significant).

The shortening of sinus cycle length and sinus recovery time with atropine was similar to that noted in patients without sinus nodal dysfunction. In contrast, atropine had insignificant effects on sinoatrial conduction and atrial refractoriness in this group whereas it shortens both in normal subjects. This finding may reflect altered perinodal and atrial electrophysiologic properties in patients with sinus node disease.     

Electrophysiologic findings in patients with idiopathic hypertrophic subaortic stenosis

Thirteen patients with catheterization-proved idiopathic hypertrophic subaortic stenosis underwent intracardiac electrophysiologic study. There was a large incidence of arrhythmias and a strikingly large incidence of conduction system abnormalities among these patients. The P-A and A-H intervals were normal in all patients. Atrial pacing resulted in Mobitz type 1 block proximal to the His bundle at an abnormal rate (less than 140/min) in 2 of 12 patients (17 percent). H-V intervals were prolonged (greater than 50 msec) in 10 of 12 patients (83 percent) and were greater than 60 msec in 7 patients (58 percent). The atrial effective refractory period was prolonged in 3 of 12 patients and was markedly prolonged in 1 of them. Effective refractory period of the atrioventricular (A-V) node, determined in five patients, was prolonged in three. Dual responses of the A-V node to atrial extrastimuli were found in seven patients. Dual A-V nodal repsonses were evoked with propranolol in three patients and persisted in the other four patients with dual responses despite propranolol administration.     

Reversal of electrical remodeling after cardioversion of persistent atrial fibrillation

INTRODUCTION: In animals, atrial fibrillation results in reversible atrial electrical remodeling manifested as shortening of the atrial effective refractory period, slowing of intra-atrial conduction, and prolongation of sinus node recovery time. There is limited information on changes in these parameters after cardioversion in patients with persistent atrial fibrillation. METHODS AND RESULTS: Thirty-eight patients who had been in atrial fibrillation for 1 to 12 months underwent electrophysiologic testing 10 minutes and 1 hour after cardioversion. At 1 week, 19 patients still in sinus rhythm returned for repeat testing. Reverse remodeling of the effective refractory period was not uniform across the three atrial sites tested. At the lateral right atrium, there was a highly significant increase in the effective refractory period between 10 minutes and 1 hour after cardioversion (drive cycle length 400 ms: 204 +/- 17 ms vs 211 +/- 20 ms, drive cycle length 550 ms: 213 +/- 18 ms vs 219 +/- 23 ms, P < 0.001). The effective refractory period at the coronary sinus and distal coronary sinus did not change in the first hour but had increased by 1 week. The corrected sinus node recovery time did not change in the first hour but was shorter at 1 week (606 +/- 311 ms vs 408 +/- 160 ms, P = 0.009). P wave duration also was shorter at 1 week (135 +/- 18 ms vs 129 +/- 13 ms, P = 0.04) consistent with increasing atrial conduction velocity. CONCLUSION: The atrial effective refractory period increases, sinus node function improves, and atrial conduction velocity goes up in the first week after cardioversion of long-standing atrial fibrillation in humans. Reverse electrical remodeling of the effective refractory period occurs at different rates in different regions of the atrium.     

Mechanisms of cardiac arrhythmias after the Mustard operation for transposition of the great arteries

To determine the mechanisms of the cardiac arrhythmias frequently seen after the Mustard operation for transposition of the great arteries, intracardiac electrophysiologic studies were performed in 52 children 1 to 8 years after the Mustard operation. Sinus nodal automaticity as judged from the response to rapid atrial pacing was abnormal in 28 of the 52 children. Sinoatrial conduction (conduction of the sinus impulse to the atrium) was found to be abnormal in three of nine patients studied with the atrial extrastimulus method. Conduction of the sinus impulse from the high right atrium to the atrioventricular (A-V) node was abnormally delayed in only 2 of 41 subjects. The low lateral wall of the right atrium was depolarlzed late in 3 of 11 subjects (including the preceding 2). Two subjects showed delayed A-V nodal conduction and one delayed His-Purkinje conduction. The mechanism of supraventricular tachycardia induced in the laboratory was determined to be sinoatrial nodal reentry in four subjects and atrial muscle reentry in four. Two of the four with atrial muscle reentry had prolonged high right atrium to low lateral right atrium intervals during sinus rhythm.

Thus, damage to the sinus node remains the most common cause of arrhythmias after the Mustard operation. In addition, delayed atrial conduction may predispose to atrial muscle reentrant tachycardia.     

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.     

Sick sinus syndrome due to cardiac amyloidosis

In a patient suffering from cardiac amyloidosis a case of sick sinus syndrome, manifested by markedly prolonged recovery time of the sinus node, was documented by an atrial pacing study. The first A-V junctional escape interval was markedly prolonged following the termination of the atrial pacing, pointing to a coexisting A-V nodal dysfunction. The patient required a permanent artificial pacemaker implantation.     

Electrophysiologic effects of the antiarrhythmic agent disopyramide phosphate

The electrophysiologic effects of the antiarrhythmic agent disopyramide phosphate given intravenously were studied in 10 patients with cardiac disease. Studies included determinations of sinus recovery time and refractoriness of the atria, the atrioventricular (A-V) node and the His-Purkinje system. Measurements were performed at rest and 15 and 30 minutes after administration of disopyramide. Serum drug levels were measured at these times.Sinus recovery time was shortened at both 15 and 30 minutes, with an average decrease of 39.5 and 146.2 msec, respectively (P < 0.01). Atrial refractoriness was not altered significantly, but tended to be reduced; the mean effective refractory period was 289.5 msec before administration of disopyramide and 259 and 270 msec 15 and 30 minutes, respectively, after administration. The functional refractory period of the atrioventricular (A-V) node was definitely prolonged in seven patients 15 minutes after administration of disopyramide. The relative refractory period of the His-Purkinje System was not altered.Although this study does not elucidate the mechanism by which disopyramide achieves its antiarrhythmic effects, animal work has shown that it is similar to that of quinidine. In the doses used the drug does not seem to cause first, second or third degree A-V block or fascicular or bundle branch block; it did not increase the severity of first degree A-V block in the three patients with this disturbance. The drug may be particularly useful when arrhythmias are associated with slow sinus rates.