Functional Refractory Period Of Atrioventricular Node Research Articles

Arrhythmia and sudden death associated with elevated cardiac chloride channel activity

The identification and analysis of several cationic ion channels and their associated genes have greatly improved our understanding of the molecular and cellular mechanisms of cardiac arrhythmia. Our objective in this study was to examine the involvement of anionic ion channels in cardiac arrhythmia. We used a transgenic mouse model to overexpress the human cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-regulated chloride channel. We used RNase protection and in situ hybridization assays to determine the level of CFTR expression, and radiotelemetry and in vivo electrophysiological study in combination with pharmacological intervention to analyse the cardiac function. Cardiac CFTR overexpression leads to stress-related sudden death in this model. In vivo intracardiac electrophysiological studies performed in anaesthetized mice showed no significant differences in baseline conduction parameters including atrial-His bundle (AH) or His bundle-ventricular (HV) conduction intervals, atrioventricular (AV) Wenckebach or 2:1 AV block cycle length and AV nodal functional refractory period. However, following isoproterenol administration, there was marked slowing of conduction parameters, including high-grade AV block in transgenic mice, with non-sustained ventricular tachycardia easily inducible using programmed stimulation or burst pacing. Our sudden death mouse model can be a valuable tool for investigation of the role of chloride channels in arrhythmogenesis and, potentially, for future evaluation of novel anti-arrhythmic therapeutic strategies and pharmacological agents.

The assessment of autonomic function in chronic atrial fibrillation: description of a non-invasive technique based on circadian rhythm of atrioventricular nodal functional refractory periods

Heart rate variability (HRV) parameters can be used to assess autonomic function and to predict outcome, but this has been done exclusively in patients with sinus rhythm. Atrial fibrillation (AF) is the commonest sustained arrhythmia and is particularly prevalent in heart failure. We have developed a simple index to assess autonomic function in patients with chronic AF. Forty patients with chronic AF (>1 month) and symptoms of heart failure underwent ambulatory 24 h electrocardiography recording as well as evaluation of symptoms, exercise capacity (6 min walk distance), ventricular function (echocardiography and radionuclide ventriculography), and neuroendocrine activation. A number of standard HRV parameters shown to have prognostic significance in sinus rhythm were also determined. A modified in-house HRV statistical programme was used to filter labelled QRS intervals and to compute the 5th percentile RR interval in each hour. This parameter has been shown to approximate the functional refractory period (FRP) of the atrioventricular node (AVN). A cosine curve was fitted to hourly 5th percentile RR intervals for each patient and from this was estimated the diurnal change in hourly 5th percentile RR interval (approximating DeltaFRP of the AVN) and, by inference, diurnal variation in sympathovagal input to the AVN. Digoxin was the sole agent permitted for control of ventricular rate. DeltaFRP of the AVN varied and revealed a significant correlation, on multivariate analysis, with mean RR interval (P<0.001), SDARR (SD of 5-min average RR intervals during 24 h, P<0.001), and NYHA class of heart failure (classes III and IV heart failure vs. classes I and II, P=0.02). SDARR has previously been shown independently to predict mortality in patients with chronic AF and heart failure. This analysis describes a novel non-invasive method for assessing autonomic function in chronic AF. Whether DeltaFRP in chronic AF patients can independently predict adverse prognosis or sudden death requires further study.

The Effects of Dobutamine and Phenylephrine on Atrioventricular Conduction During Combined Use of Halothane and Thoracic Epidural Lidocaine

The purpose of this study was to measure cardiac sympathetic nerve activity (CSNA) and atrioventricular (AV) conduction and to test the effects of dobutamine (DOB) and phenylephrine (PHE) on AV conduction during combined use of halothane and thoracic epidural lidocaine. Cats were anesthetized with 1 % halothane and an epidural catheter was inserted through T-9 laminectomy. His bundle and atrial electrocardiograms were obtained and atrial electric stimulation was performed using quadripolar catheter electrodes. Cats underwent left thoracotomy, and CSNA was recorded directly from the left ventrolateral or ventromedial nerve. In addition to sinus cycle length (SCL) measurement during spontaneous beating, the functional refractory period (FRP) of the atrioventricular node (AV node), effective refractory period (ERP) of the atrium, atrium-His (A-H) intervals were determined just before and 10, 20, and 30 min after epidural administration of 1% lidocaine (0.2 mL/kg) in Group C. DOB 5 micrograms/kg/min (Group DOB) and PHE 0.5-1.0 micrograms/kg/min (Group PHE) were intravenously administered from 12 to 22 min after epidural lidocaine. CSNA and mean arterial pressure (MAP) were markedly decreased and SCL, FRP of AV node, ERP of atrium and A-H interval were significantly prolonged after epidural lidocaine. MAP increased to baseline level during DOB or PHE infusion. Worsening of cardiac electrophysiological variables was improved with DOB infusion, but did not change with PHE infusion. We conclude that thoracic epidural lidocaine during halothane anesthesia almost eliminates CSNA, and thereby attenuates sinus node automaticity and AV node function. DOB restored normal cardiac electrophysiological variables, and therefore is preferable to phenylephrine as a pressor drug.

Radiofrequency versus pharmacologic modification of the atrioventricular node

Although transcatheter radiofrequency modification of the atrioventricular (AV) node has been proposed as curative treatment in AV nodal reentry tachycardias, its role for the control of the ventricular rate in atrial tachyarrhythmias remains unclear. The aim of this study was to analyze the acute effect of radiofrequency current on AV nodal conduction and refractoriness, and to compare it with the effects of two antiarrhythmic drugs such as amiodarone (class III) and flecainide (class I). Twenty-one dogs were studied: (1) radiofrequency group (5 W for less than 45 seconds; 2 to 12 discharges: seven dogs); (2) amiodarone group (5 mg/kg intravenously; seven dogs); and (3) flecainide group (2 mg/kg intravenously; seven dogs). The following parameters were measured under basal conditions and after each procedure: AH interval, AV nodal functional refractory period, Wenckebach cycle length, minimum R-R interval during atrial fibrillation, and fitting of AV nodal function curve to a hyperbolic equation using its linear transformation. The AV nodal effective refractory period could not be calculated in any dog in the basal study because it was shorter than the atrial functional refractory period. After radiofrequency, the percentage increment was greater for the AH interval than for the AV nodal functional refractory period (60 ± 28% versus 29 ± 16%, p ≤ 0.05); the percentage increment in the AH interval did not correlate with that of any other interval, whereas the percentage increment of the AV nodal functional refractory period correlated with that of the Wenckebach cycle length ( r = 0.83, p ≤ 0.05) and minimum R-R interval during atrial fibrillation ( r = 0.78, p ≤ 0.05). Neither after amiodarone (62 ± 16% versus 50 ± 21%, p = NS) nor after flecainide (18 ± 7% versus 12 ± 6%, p = NS) were there significant differences between the percentage incremento in the AH interval and AV nodal functional refractory period; furthermore, unlike radiofrequency, the percentage increment in the AH interval correlated with that of the AV nodal functional refractory period after amiodarone ( r = 0.87, p ≤ 0.01) and flecainide ( r = 0.86, p ≤ 0.01). The AV nodal function curve was displaced upwards and to the right with each procedure; the ordinate axis intercept of the straight line of the hyperbolic equation significantly decreased only with amiodarone. It was concluded that: (1) Radiofrequency current, unlike antiarrhythmic drugs, induces a dissociation between conduction and refractoriness, with a predominant modification of the former. (2) The prolongation of the parameters valuable in controlling ventricular rate in atrial tachyarrhythmias (Wenckeback cycle length and minimum R-R interval during atrial fibrillation) depends on the modification of AV nodal refractoriness and not on the increase in the AH interval. (3) The prolongation of the AH interval can be a misleading end point during the ablation procedures.

Origin, domain, and dynamics of rate-induced variations of functional refractory period in rabbit atrioventricular node.

Different aspects of the intrinsic regulation of rate-induced variations of functional refractory period of atrioventricular node (FRPN) were studied in isolated rabbit heart preparations. First, the hypothesis that these variations originate from the net interaction between facilitation and fatigue was tested. For a constant fast rate, selective effects of faciliation and of steady-stage fatigue were independently shown to shorten and prolong, respectively, FRPN while their combined effects were shown to result in intermediate changes corresponding to the sum of their individual effects. Second, selective and combined effects on FRPN were shown to start for rates corresponding to the upper half of the 1:1 nodal conduction range and to reach their maximums at the fastest rate tested. Third, the time-courses of fatigue-induced prolongations in nodal conduction time and FRPN were shown to be closely linked. Facilitation effects on conduction time and FRPN were confirmed, as previously shown for in situ dog hearts, to be linked, but time-independent. Fourth, FRPN was shown not to correspond to particular limits in its subintervals, but to be, nevertheless, related to nodal refractoriness. Fifth, it was demonstrated that, in conditions of combined facilitation and transient fatigue such as those prevailing in current endocavitary investigations of nodal function, FRPN could be shortened, left unchanged or prolonged by a constant fast rate depending on its duration. In conclusion, the present study demonstrates the dual origin of rate-induced FRPN variations, their rate and time dependence, their relation to changes in nodal refractoriness, and their involvements in various nodal responses.

Electrophysiologic properties of intravenous isradipine in persons with normal sinus node and atrioventricular nodal function

Isradipine (PN 200-110) is a new dihydropyridine calcium entry blocker with powerful vasodilating properties. Plasma concentrations obtained after commonly used dosage do not decrease myocardial contractility. However, in vitro studies have demonstrated negative chronotropic action with only minor dromotropic influence. Therefore, the electrophysiologic properties of intravenous isradipine 0.3 μg/kg for 30 minutes in persons with normal sinus and atrioventricular nodal function were investigated. There were no unwanted side effects. Mean blood pressure decreased slightly, but not significantly (107 ± 19 to 100 ± 9 mm Hg). Sinus cycle length decreased from 798 ± 176 to 730 ± 163 msec (p <0.01). The atrioventricular nodal functional refractory period decreased from 418 ± 40 to 399 ± 47 (p <0.05) and the atrial His interval decreased from 95 ± 20 to 91 ± 20 (p <0.01). The His ventricle interval, corrected sinus node recovery time, Wenckebach cycle length, and QRS duration remained unchanged. The QT c was prolonged from 417 ± 39 to 427 ± 40 (p <0.01). It was concluded that isradipine has no depressant effect on normal sinus and atrioventricular node function in humans and is well tolerated. The electrophysiologic effects seem to be the results of enhanced sympathetic tone provoked by peripheral vasodilatation.

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 EC 50 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 < 0.05). In contrast, the mean dose of ATP producing AV block was 4.4 ±0.97 mg and the EC 50 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 < 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 EC 50. These findings suggest that ATP has potentially different mechanisms of action on SN automaticity and AV nodal conduction that requires further investigation.

Atrioventricular nodal function in the immature canine heart [corrected and republished article orginally printed in Pediatr Res 1987 Nov;22(5):616-20

Previous studies have suggested that the atrioventricular nodal functional refractory period in the neonate is equal to or shorter than that of the ventricle, providing little or no protection to the ventricle against rapid atrial rates and allowing closely coupled atrial beats to fall within the ventricular vulnerable period. We evaluated atrioventricular node function in 21 mongrel neonatal puppies, 3-15 days old, and 15 adult dogs utilizing intracardiac His bundle recording and stimulation techniques. The mean atrioventricular nodal functional refractory period (173.1 +/- 20.0 ms) exceeded both the ventricular effective refractory period (139.5 +/- 14.3) and ventricular functional refractory period (163.3 +/- 14.5) in the neonates. Furthermore, the atrioventricular node was the site of limiting antegrade conduction in all neonates. No ventricular arrhythmias were induced by atrial extrastimulation in any of the neonates. The site of conduction delay during atrial extrastimulation was confined to the atrioventricular node in 15/16 neonates (94%) while 1/16 (6%) had combined nodal and infranodal delay. The neonates developed Wenckebach, at significantly faster heart rates than the adults, but both groups developed Wenckebach at approximately twice the resting heart rate. Retrograde conduction was a consistent finding in the neonates. However, antegrade Wenckebach occurred at a significantly faster heart rate than retrograde Wenckebach suggesting different functional properties. Our data suggest that in the neonatal canine, the atrioventricular node functional refractory period is longer than both the ventricular effective refractory period and ventricular functional refractory period. Furthermore, the degree of protection offered by the neonatal atrioventricular node to the ventricle appears to be comparable to that of the adult.

Kinetics of electrophysiologic changes during oral loading of amiodarone and after withdrawal of amiodarone in the unsedated dog.

We examined the temporal kinetics of onset and offset of the cardiac electrophysiologic effects of orally administered amiodarone in chronically instrumented, unsedated adult dogs (n = 8). Right atrial (RA), atrioventricular nodal (AVN), and right ventricular (RV) effective refractory period (ERP), and AVN functional refractory period (FRP), were determined daily for 21 days during amiodarone loading (24 mg/kg/day) and for 21 days after cessation of amiodarone. Left ventricular (LV) ERP was assessed in four of eight animals. Group mean RA-ERP peaked and plateaued early during amiodarone loading (time to reach one-half observed peak change [t1/2 onset] = 1.2 +/- 0.5 days) and rapidly returned toward baseline after cessation of drug (decay time to one-half peak value [t1/2 offset] = 2.0 +/- 1.7 days). Group mean RV-ERP rose in a linear manner throughout the loading period (t1/2 onset = 9.3 +/- 2.1 days) and remained elevated after cessation of drug (t1/2 offset greater than 21.0 days). Group mean AVN-ERP and FRP exhibited temporal kinetics intermediate between those of the RA-ERP and RV-ERP, both during amiodarone loading and after cessation of the drug. Group mean LV-ERP onset kinetics (assessed in a limited number of animals, n = 4) appeared to differ from RV-ERP onset kinetics (t1/2 onset = 2.5 +/- 2.5 days), whereas LV-ERP and RV-ERP offset kinetics appeared similar (t1/2 offset greater than 21 days). In summary, our findings demonstrate that during oral loading, the temporal sequence of onset of amiodarone-induced electrophysiologic effects is site dependent. Similarly, after cessation of amiodarone, the persistence of drug-induced electrophysiologic effects is both variable and site dependent.

Amrinone: Acute electrophysiologic and hemodynamic effects in patients with congestive heart failure

Amrinone is an effective inotropic agent, but its electrophysiologic effects in humans have not been previously determined. Fifteen patients with congestive heart failure (CHF) New York Heart Association functional class II to IV, underwent an electrophysiologic study after withdrawal of all other cardioactive drugs before and after 10 to 20 μg/kg/min of intravenous amrinone (doses that increased cardiac index and decreased pulmonary capillary wedge pressure and systemic vascular resistance, p < 0.002). Amrinone caused no change in PR, QRS, QTc, AH or HV intervals or maximal corrected sinus node recovery time and had no significant effect on the ventricular effective refractory periods. Amrinone decreased the atrial effective refractory period from 256 ± 40 to 240 ± 38 ms (p = 0.015), and the atrioventricular (AV) nodal functional refractory period from 374 ± 65 to 356 ± 64 ms (p < 0.05), and enhanced maximal 1:1 AV nodal conduction from 371 ± 46 to 334 ± 47 ms (p = 0.006). Nine patients had baseline HV prolongation; this was not affected by amrinone. The frequency of inducible ventricular tachycardia was not significantly affected by amrinone. Holter recordings (24 to 48 hours) were obtained from 10 patients before and after acute oral amrinone dosing (75 to 150 mg every 8 hours). There was no change in the number of ventricular premature contractions per 24 hours (2,197 ± 3,305 vs 2,616 ± 2,436) or number of runs of ventricular tachycardia per 24 hours (10 ± 12 vs 12 ± 13); however, the number of ventricular couplets per 24 hours increased from 22 ± 34 to 52 ± 55 (p = 0.054). Thus, amrinone is safe to use in patients with intraventricular conduction disturbances. It shortens the atrial effective and AV nodal functional refractory period and enhances AV nodal conduction, and it has minimal effects on ventricular arrhythmogenesis during acute drug administration.

Enhanced atrioventricular nodal conduction in man: electrophysiologic effects of pharmacologic autonomic blockade.

Enhanced atrioventricular nodal conduction (EAVC) comprises a portion of the spectrum of atrioventricular node electrophysiology in which physiologic slowing of atrioventricular conduction is diminished. To evaluate the basis of EAVC in humans, we compared the effect of pharmacologic autonomic blockade on electrophysiologic characteristics of atrioventricular nodal conduction and refractoriness in 10 patients with EAVC and 12 patients without EAVC (non-EAVC). The effects of autonomic blockade (0.2 mg/kg iv propranolol and 0.04 mg/kg iv atropine) on sinus cycle length and atrial refractory period were similar in both EAVC and non-EAVC patients. After autonomic blockade, minimum atrial paced cycle length with 1:1 atrioventricular conduction lengthened in EAVC patients (control, 268 +/- 25 msec; blockade, 307 +/- 34 msec; p less than .01), but remained unchanged in non-EAVC patients (control, 392 +/- 69 msec; blockade, 382 +/- 49 msec; p = NS). Similarly, atrioventricular nodal functional refractory periods tended to lengthen in EAVC patients, while remaining unchanged or shortening in non-EAVC patients. Furthermore, although autonomic blockade reduced differences between EAVC and non-EAVC patients, both minimum cycle length with 1:1 atrioventricular conduction and atrioventricular functional refractory period remained shorter in EAVC than in non-EAVC patients (p less than .02). Thus, baseline differences in autonomic atrioventricular nodal control differ in EAVC and non-EAVC patients, but do not fully account for differences in atrioventricular nodal electrophysiologic properties in these patients. Consequently, underlying structural functional factors may play an important role in determining the range of atrioventricular nodal electrophysiologic characteristics in man.

Electrophysiologic and hemodynamic effects of propafenone, a new antiarrhythmic agent, on the anesthetized, closed-chest dog: Comparative study with lidocaine

The relative hemodynamic and electrophysiologic effects of a new antiarrhythmic drug, propafenone, and lidocaine were evaluated in eight closed-chest, anesthetized dogs. Propafenone (4 mg/kg intravenously) significantly ( p < 0.05) lowered aortic and pulmonary systolic pressures and caused a rise in heart rate ( p < 0.05). Cardiac output decreased from 4.5 ± 1 to 3.8 ± 0.7 L/min ( p < 0.05) during atrial pacing at 400 msec cycle length. Propafenone had no effect on pulmonary and aortic diastolic pressures. Lidocaine (5 mg/kg intravenously) caused a significant ( p < 0.05) decrease in aortic systolic pressure and a rise in heart rate. Lidocaine had no significant effect on the other measured hemodynamic parameters. Propafenone, unlike lidocaine, significantly ( p < 0.05) increased atrioventricular nodal functional refractory period and right ventricular endocardial (apex) cathodal (0.5 ± 0.1 mA to 1.9 ± 0.3 mA) and bipolar (1.4 ± 0.3 to 2.2 ± 0.4 mA) diastolic excitability threshold. Propafenone, unlike lidocaine, also caused a significant ( p = 0.05) intraatrial conduction delay; however, neither drug caused conduction slowing in the His-Purkinje system. Both drugs had no effect on sinus nodal recovery time and on the effective refractory period of the right ventricular endocardium (apex). Mean plasma propafenone levels during hemodynamic and electrophysiologic measurement ranged between 3.2 ± 1.8 μg/ml and 1.7 ± 1.1 μg/ml. All of the propafenone-induced effects were reversible within 90 minutes. We conclude that propafenone differs from lidocaine in its atrial, AV nodal, and ventricular electrophysiologic properties, and thus these may explain propafenone's greater efficacy over lidocaine against both certain atrial and ventricular arrhythmias. Propafenone's negative inotropic effects, however, should necessitate caution in its use.

Electrophysiological effects of sotalol--just another beta blocker?

The electrophysiological effects of intravenous sotalol hydrochloride (0.4 mg/kg) were assessed in 24 patients, including 13 with the Wolff-Parkinson-White syndrome, undergoing routine electrophysiological study. Fifteen to 30 minutes after sotalol administration there was a significant increase in sinus cycle length and in sinus node recovery time. There was a small increase in the AH interval, but the HV interval was unchanged. The QT and JT intervals, measured during sinus rhythm, were both increased. The atrial, ventricular, and atrioventricular nodal effective refractory periods were all prolonged, as was the atrioventricular nodal functional refractory period. In 13 patients with ventricular pre-excitation there was an increase of the accessory pathway anterograde and retrograde effective refractory periods. In 12 of these 13 sotalol was given during atrioventricular re-entrant tachycardia, resulting in termination in five. Tachycardia cycle length increased in all patients, with the major effect being in the atrioventricular direction. Though some of the effects seen in these patients are consistent with the beta adrenergic antagonist properties of sotalol, the effect on atrial, ventricular, and accessory pathway effective refractory periods and on ventricular repolarisation is not typical of that observed with other beta blockers but may be the result of lengthening of the action potential duration. These findings suggest that sotalol may be a more versatile antiarrhythmic agent than other beta receptor antagonists.

Short time constant for rate-dependent changes of atrioventricular conduction in dogs.

The number of short cardiac cycles necessary to induce, and normal cycles to dissipate, a rate-dependent shortening in atrioventricular (AV) nodal functional refractory period (FRP) and conduction time (CT) was determined in six anesthetized dogs. For the induction study, the periodic premature stimulation procedure was performed at control and repeated six times while 1, ..., 6 conditioning short prepremature cycles (PPC) were introduced between the last basic cycle and the premature cycle. In all dogs, FRP was maximally shortened and the recovery curve was maximally shifted to the left when the premature cycle was preceded by 1 PPC. Adding 2, ..., 6 PPC resulted in slightly fewer but persistent shortenings of both FRP and CT. The dissipation of the FRP and CT shortenings produced by 2 and 6 PPC was studied subsequently in the same dogs by introducing 1, ..., 6 normal basic cycles between the last PPC and the test premature cycle. The FRP and CT shortenings induced by 2 or 6 PPC were almost completely dissipated after one normal basic cycle. Thus, one short cycle produces a maximum shortening in AV nodal FRP and CT, and one normal basic cycle is sufficient to dissipate these effects.

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 μg/ml). NAPA decreased blood pressure (p <0.005), increased corrected Q-T interval (p <0.01) and increased the atrial and ventricular effective refractory periods from 267 ± 40 to 307 ± 41 ms (p <0.01) and from 278 ± 37 to 301 ± 32.8 ms (p <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 μg/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 Properties of Methyldopa in Man

There is little information on the effects of methyldopa on the human conduction system. His bundle ECGs were obtained in 11 patients before and after the intravenous infusion of 100 mg of methyldopa. Antegrade refractory periods were obtained with the extrastimulus method. The significant results were as follows: the sinus rate was 71 +/- 4 beats per minute before, and 65 +/- 3 beats per minute after methyldopa (P less than 0.01). The mean A-H interval at a paced rate of 120 beats per minute was 113 +/- 14 msec before, and 135 +/- 18 msec after, methyldopa (P less than 0.05). The mean atrioventricular nodal functional refractory period was 430 +/- 23 msec before and 452 +/- 24 msec after methyldopa administration (P less than 0.001). The mean effective refractory period was 385 +/- 29 msec before, and 388 +/- 27 msec after methyldopa (P less than 0.01). The sinus node recovery time in the control state was 989 +/- 55 msec and 1102 +/- 66 msec after methyldopa infusion (P less than 0.05). Thus, methyldopa can impair conduction through the atrioventricular node and depress the sinus node.

Influence of plasma drug level and the presence of conduction disease on the electrophysiologic effects of procainamide

Electrophysiologic measurements were made in 16 patients before and after the intravenous administration of procainamide. The drug was administered at two different dose levels. The lower plasma procainamide level (6 to 7 μg/ml) caused small decreases in cycle length (848 ± 13 versus 799 ± 42 msec), sinus nodal recovery time (1,166 ± 81 versus 1,024 ± 90 msec at a paced rate of 120 beats/min) and sinoatrial conduction time (105 ± 11 to 90 ± 9 msec). Sinus or atrial echo zones, whether or not they caused supraventricular tachyarrhythmia, were abolished by procainamide in 11 of 13 instances. The higher plasma level of procainamide (10 to 11 μg/ml) generally caused greater changes in electrophysiologic measurements. Atrial refractory periods tended to increase but changed significantly only at higher plasma levels. The latter effect was blunted in patients with a prolonged sinoatrial conduction time. The A-H interval and atrioventricular nodal functional refractory period tended to decrease at higher plasma levels, but not significantly. The H-V interval increased slightly from 48 ± 2 to 52 ± 2 msec; this effect was blunted in patients with bundle branch block. It is concluded that procainamide could be useful in managing supraventricular tachyarrhythmia because it abolishes atrial and sinus echo zones that trigger supraventricular tachyarrhythmia and because its widespread effects make it capable of blocking reentry at several sites. The electrophysiologic effects or procainamide are less predictable in patients with conduction disease, and some effects occur only at high plasma levels.

The relationship between atrioventricular nodal refractoriness and the functional refractory period in the dog.

We studied the relationship between the atrioventricular nodal functional refractory period (FRP) and refractoriness by mathematical analysis and by measurement during antegrade Wenckebach cycles in 16 dogs. The FRP relates directly to the conduction time of the control beat, and inversely to the coordinates of the point on the A'-H' vs. A-A refractory curve where the slope is -1. The FRP can vary without any change in refractoriness as measured by the effective refractory period (ERP) or the refractory curve. In 16 dogs the ERP and the FRP were measured during 4:3 Wenckebach cycles. Because of changes in the control conduction times, the FRP declined and did not reflect the progressive increase in refractoriness recorded during Wenckebach cycles. The FRP is a complex parameter and does not reliably measure refractoriness.