Atrioventricular Nodal Effective Refractory Period Research Articles

Evidence that cocaine slows cardiac conduction by an action on both AV nodal and His-Purkinje tissue in the dog

The effects of intravenous cocaine (2 mg/kg) were tested on several indices of cardiac electrical activity in sedated dogs. These included sinus rate, PR, AH, and HV intervals; AV nodal effective refractory period (AVNERP); ventricular effective refractory period; QRS duration; and the QT interval. Cocaine induced significant changes in six control animals with an intact-functioning autonomic nervous systems. After pharmacologic autonomic blockade with propranolol plus propantheline, cocaine increased the PR interval (+11 ± 4.0 ms, p < 0.05), primarily by slowing conduction at the AV nodal level. However, with constant atrial pacing at a rate above the sinus cycle length, prolongation of both the AH and the HV intervals (+15 ± 2.5 and + 6.7 ± 1.7 ms, respectively) occurred. There was also a significant increase in the AVNERP (+ 29 ± 5.9 ms, p < 0.05). Consistent with the observed rate-dependent HV prolongation, cocaine decreased the rate of rise of phase 0 of the transmembrane action potential of Purkinje fibers. These data indicate that cocaine impairs cardiac conduction by direct actions on AV nodal and His-Purkinje cells.

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.

Electrophysiologic Effects and Antiarrhythmic Efficacy of Recainam in Patients with Supraventricular Tachycardia

Recainam is a new antiarrhythmic agent with class Ic properties. To evaluate its electrophysiologic effects and antiarrhythmic efficacy in patients with recurrent supraventricular tachycardia (SVT), programmed electrical stimulation was performed in 10 patients before and after intravenous recainam (loading dose 0.8 mg/kg, infusion 1 mg/kg/h), and in four patients on oral recainam 1,200 mg/day. Five patients had atrioventricular (AV) node reentrant tachycardia; five had AV-reciprocating tachycardia. There were no significant changes in electrocardiographic and intracardiac intervals after either intravenous or oral recainam. After intravenous recainam, the ventricular effective refractory period (ERP) shortened (231 +/- 14-219 +/- 9 ms, p less than 0.05). The antegrade ERP of all three bidirectional accessory pathway markedly prolonged, but the effect on retrograde accessory pathway and AV node ERPs was unremarkable. SVT induction was prevented in three of 10 patients and SVT cycle length increased modestly in seven (357 +/- 44-374 +/- 42 ms, p = 0.07). On oral recainam, an increase in the frequency of spontaneous SVT occurred in two patients. At the doses given, recainam caused less electrophysiologic change than expected, had modest antiarrhythmic efficacy, and might have significant arrhythmogenic potential.

A Reappraisal of Atrioventricular Nodal Excitability During Functional 2:1 Block: What Should be the Gauge?*

By using extrastimulation technique the effective refractory period (ERP) of the atrioventricular (AV) node is conventionally defined as the longest A1A2 interval at which conduction of A2 is blocked within the node. With the prolongation of the AV nodal transit time that is associated with this technique, the delayed AV nodal arrival of the A1 impulse will cause an overestimation of the true interval if the A1A2 interval is used as the gauge. Under this condition, the conventional approach will not accurately delineate the ERP of the AV node. However, this prolongation of the nodal transit time can be calculated by subtracting the basal conduction time from the conducted A-H interval. By subtracting out the prolongation from the longest A1A2 at which A2 impulse is blocked, not only an interval more indicative of the true AV nodal ERP can be obtained, but also the apparent discrepancies between the in vitro and human AV nodal recovery curves disappear.

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 < 0.0001]) and the shortest cycle length maintaining 1:1 ventriculoatrial conduction (baseline: 357 ± 99 ms vs after drugs: 485 ± 64 ms [p < 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. Thus, thecombined administration of propranolol and verapamil may prove helpful for differentiating between retrograde AV nodal and residual accessory connection conduction during early postoperative assessment of patients undergoing surgery for accessory AV connection ablation.

Modification of human atrioventricular nodal function by selective atrioventricular nodal artery catheterization.

The hypothesis that human atrioventricular (AV) nodal function can be modulated selectively with a new technique of AV nodal artery catheterization was tested in eight subjects referred for diagnostic cardiac catheterization or electrophysiological studies. Three patients had no history of arrhythmias. Three patients had supraventricular tachycardia (SVT) due to reentry confined to the AV node (AVNRT). One patient had SVT due to reentry over a concealed AV bypass tract (AVRT-CBT), and one patient had nonsustained ventricular tachycardia. In each subject, sinus cycle length, AH interval, HV interval, AV nodal effective refractory period (AVN-ERP), and Wenckebach paced cycle length were measured in a control state. A flexible infusion catheter was then positioned selectively in the AV nodal artery of each subject. Through this catheter, a constant infusion of 0.1 mg/min procainamide at a flow rate of 0.125 ml/min (n = 1) or 50 micrograms/min acetylcholine at a flow rate of 0.25 ml/min (n = 4) was administered. Electrophysiological parameters were determined again during selective AV nodal artery drug infusion and during infusion of saline at identical rates. Two subjects developed transient AV nodal block during selective AV nodal catheterization alone and did not receive an infusion of drug or saline. A stable position of the AV nodal artery catheter could not be achieved in one other subject, who also received no drug or saline. In the other five subjects, drug infusion caused an increase in AVN-ERP from a control value of 312 +/- 52 msec to a value of 543 +/- 228 msec (p less than 0.05) and an increase in Wenckebach paced cycle length from a control value of 360 +/- 47 msec to a value of 572 +/- 217 msec (p less than 0.05). These parameters were unchanged from control during selective saline infusion. In two patients with AVNRT, drug infusion abolished SVT by causing complete blockade of ventriculoatrial conduction as well as lengthening of anterograde AVN-ERP. In the patient with AVRT-CBT, drug infusion abolished SVT by preventing repetitive anterograde AV conduction. Saline had no effect on SVT inducibility. Selective AV nodal artery catheterization enables AV nodal function to be modulated exclusively. Delivery of ablative agents to the AV node by this technique may be useful in patients with refractory SVT.

Quantification of human concealed atrioventricular nodal conduction: Relation to ventricular response during atrial fibrillation

We studied the relation between a new quantitative index of concealed atrioventricular nodal (AVN) conduction and the variability of ventricular response during atrial fibrillation in 12 patients without preexcitation. The second atrial extrastimulus (A 3) was introduced following the first extrastimulus (A 2), which was fixed at a coupling interval 20 to 40 msec longer than the AVN effective refractory period (ERP) during a basic atrial drive (A 1) cycle length of 400 to 750 msec. The AVNERP of conducted A 2 defined as the longest A 2A 3 interval at which A 3 was not conducted to the His bundle was determined. This pacing sequence was repeated, whereas A 2 was fixed at a coupling interval 20 to 40 msec shorter than the AVNERP, which means A 2 was concealed within the AVN. Thus AVNERP of blocked A 2, defined as the longest A 2A 3 interval at which A 3 was not conducted to the His bundle, was measured. Concealment index (AVNERP of blocked A 2/AVNERP of conducted A 2) was developed to quantitate the magnitude of concealed penetration into the AVN by A 2. During atrial fibrillation induced by premature or rapid atrial stimulation, the coefficient of variation (SD/mean) of R-R intervals and the maximum R-R/minimum R-R interval were significantly correlated with the concealment index ( r = 0.838, p < 0.001; r = 0.678, p < 0.05). However, neither of these parameters was correlated with AVNERP. Both the minimum R-R and the mean R-R interval were related to the AVNERP ( r = 0.946, r = 0.823, p < 0.001). The maximum R-R interval was not related to the AVNERP ( r = 0.567, p = NS). We conclude that the concealment index may be a useful predictor of the magnitude of concealed AVN conduction, which may have an important role in determining irregularity of the ventricular response to atrial fibrillation.

Modification of Atrioventricular Conduction by Selective AV Nodal Artery Catheterization

The effects of selective AV nodal artery embolization on AV nodal function was investigated in six closed-chest adult dogs. Programmed atrial stimulation was performed to determine control values for AV nodal effective refractory period (AVN-ERP) and the paced cycle length at which AV nodal Wenckebach conduction occurred (WCL). Using standard percutaneous femoral techniques of coronary artery catheterization, a flexible infusion catheter was positioned selectively in the AV nodal artery. Proper positioning of the catheter was confirmed angiographically and by selective acetylcholine (ACH) infusion into the AV nodal artery, which caused transient complete AV nodal block in three dogs, and for the group, caused lengthening of both AVN-ERP and WCL. Following cessation of ACH infusion and autonomic blockade with atropine 0.04 mg/kg and propranolol 0.2 mg/kg, denervated recontrol values for AVN-ERP and WCL were 192 msec and 243 msec, respectively. The AV nodal artery was then embolized with a suspension of cross-linked collagen fibrils in either normal saline or absolute ethanol. Successful embolization of the AV nodal artery, confirmed angiographically, caused an acute increase in AVN-ERP (243 msec, P less than 0.05 compared to denervated control) and WCL (287 msec, P = 0.058 compared to denervated control). However, at a mean follow-up of 37 days, only one animal exhibited a chronic increase in AVN-ERP and WCL. Selective AV nodal artery catheterization can be performed using standard percutaneous catheterization techniques. Selective administration of agents with direct cidal effects on the AV node using this technique may provide an alternative to conventional methods of catheter ablation of AV conduction in patients with drug-resistant supraventricular arrhythmias.

Low energy partial ablation of the atrioventricular node junction in the dog using a suction-ablation catheter

A suction electrode catheter was used for low energy, partial ablation of the atrioventricular (AV) node junction in 12 dogs. In 10 dogs, partial injury of the AV node was induced. In six dogs, delivered energy was measured precisely with use of a specially designed electronic circuit. The total energy required for partial ablation was 225 ± 91 J. The increase in PR (p < 0.0001) and AH (p < 0.001) intervals was proportional to the energy delivered. After ablation, the PR interval increased from 98 ± 10 to 154 ± 33 ms (p < 0.004) and the AH interval from 59 ± 8 to 102 ± 16 ms (p < 0.004). There was no significant change in QRS, QTc, HV or RR intervals. AH and PR intervals were significantly prolonged at 3, 7 and 14 days after ablation (p < 0.05).Anterograde conduction was significantly altered in 10 dogs. Anterograde AV node effective refractory period increased from 157 ± 14 to 214 ± 45 ms (p < 0.005). Anterograde AV node Wenckebach cycle length increased from 196 ± 30 to 244 ± 44 ms (p < 0.002). Retrograde conduction was assessed in three dogs. Retrograde AV node effective refractory period increased from 156 ± 21 to 260 ms in two dogs, with complete retrograde block in the third. These changes persisted for up to 2 weeks. Pathologic changes were limited to the region of the AV node. In four dogs adherent thrombus without pulmonary emboli was noted.Partial focal injury to the AV node is feasible in the canine model. A similar technique may be applicable for treatment of reentrant AV node tachycardias in humans.

Electrophysiologic studies of the heart in patients with rheumatoid arthritis

We investigated the electrophysiological properties of the heart in patients with definite or classical rheumatoid arthritis using programmed electrical stimulation techniques. Twelve patients with rheumatoid arthritis and without evidence of organic heart disease or arrhythmia detectable with serial electrocardiograms and 24-hour ambulatory electrocardiographic monitoring were compared with 12 control subjects. Stimulation was performed from the high right atrium and right ventricular apex at a drive cycle length of 600 msec and the recording sites included high right atrium, atrioventricular junction and distal coronary sinus. There was no statistically significant difference in the corrected sinus node recovery time between the study and control group of patients. Similarly, no differences from normal were found in the AH and HV intervals or in the atrial and ventricular refractoriness, whereas the atrioventricular nodal effective refractory period was higher in patients with rheumatoid arthritis, compared with the control group (338 ± 38 vs 286 ± 29, P < 0.02). The atrial conduction time during basic cycle length had a tendency to increase from high right atrium to atrioventricular junction in the study group and reached statistical significance from high right atrium to coronary sinus (92 ± 15 vs 74 ± 14, P < 0.05). Electrophysiologic differences between the study and control patients also included a greater increase in maximal intraatrial (40 ± 13 vs 27 ± 16, P < 0.05) and interatrial conduction delay (54 ± 16 vs 31 ± 12, P < 0.01) of early premature stimuli in patients with rheumatoid arthritis. In addition atrial arrhythmias were induced in 3 patients with rheumatoid arthritis but in no control patient. The clinical importance of these findings is uncertain. Nevertheless, our data suggest that abnormalities in atrial conduction time may be present in patients with rheumatoid arthritis and predispose to the initiation of atrial tachyarrhythmias.

Electrophysiological effects of intravenous sotalol in acute myocardial infarction: A double-blind placebo-controlled study

Controlled studies of the electrophysiological effects of beta-blockade in acute myocardial infarction have not previously been published. In this controlled, double-blind study 20 patients were randomized to treatment with placebo or sotalol administered as a continuous infusion for 12 h. Programmed electrical stimulation was performed from the right atrium. After 60 min of infusion in the sotalol-treated patients (n = 10) there was a significant prolongation of sinus cycle length (+15%) and sinus node recovery time (+28%). The AV nodal effective refractory period was prolonged by 15% after 45 min of infusion. Variables reflecting myocardial repolarization, atrial effective refractory period and QT interval, were increased by 20% and 10%, respectively. In the placebo group, except at 12 h, there was a general pattern of slightly diminishing values for all measured variables. The electrophysiological changes in the sotalol-treated group could be explained by the combined Class II and III activities of this drug. The infusion of sotalol was well tolerated, and the anticipated electrophysiological and Class II and III antiarrhythmic effects were observed, despite the acute myocardial infarction.

Electrophysiologic effects of intravenous dipyridamole

We evaluated the electrophysiologic effects of dipyridamole given intravenously to 24 patients during intracardiac electrophysiologic study. Electrophysiologic parameters were measured before and 5 minutes following infusion of 0.5 mg/kg of dipyridamole. The drug significantly shortened the sinus cycle length by 26 per cent ( P < 0.001), sinuatrial conduction time by 15 per cent ( P < 0.01), maximal sinus node recovery time by 21 per cent ( P < 0.001), atrial and atrioventricular nodal effective refractory period by 8 and by 11 per cent, respectively (both P < 0.01), ventricular effective refractory period by 4 per cent ( P < 0.001), paced cycle length to atrioventricular nodal Mobitz type II block by 5 per cent ( P = 0.046), and QT interval during sinus rhythm by 10 per cent ( P < 0.01). After dipyridamole, the PA interval increased by 16 per cent ( P < 0.001), the AH interval by 11 per cent ( P < 0.01), and the corrected QT interval by 5 per cent ( P < 0.01). During retrograde conduction we observed a shortening of the ventriculoatrial interval by 6 per cent ( P = 0.036), retrograde atrioventricular nodal effective refractory period by 5 per cent ( P < 0.001), paced cycle length to atrioventricular nodal Wenckebach and atrioventricular nodal Mobitz type II block both by 8 per cent ( P < 0.01). We conclude that intravenous dipyridamole increases sinus node automaticity and reduces atrial, atrioventricular nodal and ventricular refractory periods, prolongs intra-atrial and atrioventricular nodal conduction, but does not produce any changes in His-Purkinje system conduction times. Paced cycle length to atrioventricular nodal Wenckebach and Mobitz type II block decreased after dipyridamole during antegrade as well as retrograde conduction.

Cardiac conduction abnormalities during percutaneous balloon mitral or aortic valvotomy.

To evaluate the electrophysiologic changes in the cardiac conduction system that occur during percutaneous mitral or aortic balloon valvotomy, we prospectively studied the conduction system in 19 patients (10 mitral, 8 aortic, and 1 both) undergoing this procedure. A His bundle electrogram was recorded in all patients, and when sinus rhythm was present, the atrioventricular (AV) node effective refractory period was measured. Holter monitoring was performed during and for 24 hours after the procedure. Follow-up electrocardiograms (ECG) were available in 11 patients 2.3 +/- 1.5 months after the procedure. The AV node effective refractory period before (276 +/- 86 msec) and after valvotomy (298 +/- 85 msec) were not significantly different. The maximum His-Purkinje conduction time (HV interval) observed during valvotomy (66 +/- 20 msec) was significantly longer (p less than 0.01) than that measured before (57 +/- 10 msec) or after (60 +/- 18 msec) valvotomy. The mean HV intervals before and after valvotomy were not significantly different. The mean QRS complex duration increased from 95 +/- 28 to 112 +/- 28 msec during valvotomy and remained significantly prolonged (109 +/- 26 msec) 24 hours after the procedure (p less than 0.01). A new intraventricular conduction defect (QRS complex duration greater than 100 msec) or bundle branch block occurred in five of 13 patients who had normal QRS duration before the procedure. The change in HV interval did not correlate with the change in QRS complex duration. In four patients, the newly acquired intraventricular conduction defect was still present on follow-up ECG tracing. Complete heart block was not observed in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hypoxia on atrioventricular node of adult and neonatal rabbit hearts.

We used an isolated perfused heart model to assess the effects of graded hypoxia (95, 45, 20, 10, or 0% O2, exposure for 5 min) on the adult and neonatal (0-3 days) rabbit atrioventricular (AV) node. The AV nodal function was assessed by measuring the A-H interval at a constant atrial pacing cycle length, the longest pacing cycle length resulting in Wenckebach periodicity [Wenckebach cycle length (WCL)] and the AV nodal effective refractory period (AVNERP). The A-H intervals remained stable in neonatal hearts until O2 saturation was decreased to 10%. On the other hand, the A-H intervals began to increase in adult rabbit hearts at 20% O2. In 95% O2, the AV nodal WCL was longer in adult hearts than in the neonatal hearts (165 +/- 8 ms vs. 142 +/- 7 ms). The effect of hypoxia on the AV nodal WCL was significantly greater in adult hearts than in neonatal hearts when the O2 saturation was decreased to 20% (a 54% increase in adults vs. a 14% increase in neonates, P = 0.02). The difference was greater at lower levels of O2. In 95% O2 at comparable basis driving cycle length (240 ms), the A-H intervals were equal in neonatal and adult hearts (43 +/- 3 vs. 43 +/- 7 ms), but the AVNERP of the neonates was significantly longer than that of the adults (133 +/- 21 vs. 97 +/- 19 ms, P = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy, safety, and tolerance of d-sotalol in patients with refractory supraventricular tachyarrhythmias

The efficacy, safety, and electrophysiologic effects of intravenous and oral d-sotalol, an investigational class III antiarrhythmic agent, are not yet well characterized. We evaluated the electrophysiologic, antiarrhythmic, and hemodynamic effects of d-sotalol infusion (1.5 to 2.75 mg/kg) and of chronic oral therapy (200 to 400 mg bid) in 10 patients with chronic, paroxysmal supraventricular tachyarrhythmias refractory to 5 ± 2 standard agents. Four patients had paroxysmal supraventricular tachycardia (PSVT), four had paroxysmal atrial fibrillation, two had atrial flutter, and one had nonparoxysmal reciprocating junctional tachycardia (NPRJT). PSVT was inducible or spontaneously present in 4 of 4 before d-sotalol. After intravenous d-sotalol PSVT was noninducible in three patients and slowed by 40% in one. Atrial fibrillation was inducible or spontaneously present in 4 of 4 before therapy. After intravenous d-sotalol, one became noninducible, and three achieved rate-slowing (the mean falling from 69 to 61 bpm). In one patient, atrial flutter became noninducible; in another, d-sotalol slowed the rate of atrial flutter by 28%. D-sotalol restored sinus rhythm in the patient with NPRJT. Intravenous d-sotalol increased the sinus cycle length; the QTc, PR, and AH intervals; and the AV nodal functional refractory period, the AV nodal effective refractory period; and the right ventricular effective refractory period significantly. The atrial effective refractory period, sinoatrial conduction time, and corrected sinus recovery time tended to increase, but did not reach statistical significance. The QRS, PA, and HV intervals did not change. Mean BP fell 13.4 ± 9.2% after intravenous d-sotalol, but no adverse symptoms developed. Oral d-sotalol caused hypotension (predrug 120/80, post-sotalol 80/60) and had to be discontinued in one patient. Sustained benefit during chronic therapy was noted in 9 of 10 patients (mean followup, 7.4 ± 5.1 months), with no adverse effects other than mild light intolerance in one patient and fatigue (which responded to dose reduction) in another. The electrocardiogram and electrophysiologic parameters measured an oral d-sotalol were not different than those produced by intravenous d-sotalol. Thus, d-sotalol is usually effective and well-tolerated in patients with refractory PSVT. Also, intravenous testing appears predictive of chronic oral efficacy.

Atrioventricular Nodal Conduction and Refractoriness Following Abrupt Changes in Cycle Length

The properties of the atrioventricular (AV) nodal conduction and effective refractory period in man are generally evaluated at a constant basic cycle length (CL) and, in most cases, they demonstrate an inverse relationship to the drive cycle. The response of AV node to abrupt change in CL is less defined. We therefore studied the effects of abrupt changes in CL on AV nodal conduction time and refractoriness in 18 patients. AV nodal conduction time, and effective and functional refractory periods were measured during: (1) a constant long CL, (2) a constant short CL, and (3) after an abrupt increase in CL just prior to the introduction of extrastimuli. In 10 of the 18 patients a constant long CL of 600 ms, a constant short CL of 400 ms and a sudden short-to-long change in CL (400 to 600 ms) were tested. AV nodal conduction times (A2H2) were measured at the shortest and longest comparable A1A2 intervals. The mean value of the shortest A2H2 intervals for constant CL of 600 ms was 144 +/- 18 ms; for a constant CL of 400 ms it was 162 +/- 17 ms; after a sudden short-to-long change in CL (400 to 600 ms) it was 142 +/- 14 ms. The mean value of the longest A2H2 intervals at a constant CL of 600 ms was 185 +/- 18 ms; at a constant CL of 400 ms it was 236 +/- 26 ms (p less than 0.01) and after a short-to-long change in CL (400 to 600 ms) 199 +/- 21 ms. AV nodal effective refractory periods measured at the same three CLs had mean values of 279 +/- 13 ms; 300 +/- 15 ms and 294 +/- 13 ms, respectively. Similar results were obtained when other CLs such as 700 to 900, 500 to 900, and 400 to 700 ms were tested. The data suggest that after abrupt short-to-long changes in CL, AV nodal function curves shift from long constant CL toward short constant CL as the coupling intervals decrease, indicating a cumulative pattern. Although the return to baseline conduction time after the fast basic rate is known to be slow, the limitation of this effect to the very early premature beat in the human has not been reported previously.

Biphasic dose-response relationship observed with Bay k 8644 on atrioventricular nodal conduction inhibited by verapamil

The effects of a calcium channel blocker, verapamil, on the atrioventricular (AV) node, are antagonized by calcium, intravenously infused, so long as plasma calcium concentration does not reach 5.0 or 5.5 mmol.l-1, as previously shown. Beyond this, the antagonistic effects decrease progressively, so that there is a bell-shaped relationship between dose (or concentration) and response. The purpose of the present experiments has been to investigate a possible similar dose-response curve with a calcium channel activator, Bay k 8644. The study was carried out in anaesthetized, atropinized dogs, with cardiac pacing. The His bundle potentials were recorded by endocavitary electrodes and the AV nodal effective refractory period was measured by the extrastimulus method. Verapamil impaired AV nodal conduction and additional infusion of Bay k 8644 at a rate of 1 microgram.kg-1.min-1 partly antagonized this effect. Increasing the infusion rate of Bay k 8644 to 5 micrograms.kg-1.min-1 did not further increase but reduced the antagonism. In other experiments where infusion of calcium had partly antagonized the effect of verapamil, Bay k 8644 infused after cessation of calcium infusion did not further antagonize the effect of verapamil which even became again increasingly marked. Consequently, in the AV node depressed by a calcium channel blocker, Bay k 8644 gives rise to a bell-shaped dose-response relationship of its verapamil-antagonistic action and the reversal of this action by high doses of Bay k 8644 can be observed after both administration of either calcium or Bay k 8644 in moderate doses.

Beat-to-beat changes in atrioventricular nodal excitability and its modulation by concealed conduction during functional 2:1 block in man.

An atrial pacing model of functional 2:1 block was used in 10 patients to investigate for the first time the electrophysiologic properties of the human atrioventricular node during intermittent conduction. By varying the terminal portion of the 2:1 atrial train and using the extrastimulus technique, we characterized atrioventricular nodal (AVN) conduction and refractoriness after five different methods of AVN activation: a conducted beat (method I), a conducted beat with omission of the prior blocked beat (method II), a blocked beat (method III), a blocked beat "converted" to one that conducts by omission of the prior conducted beat (method IV), and finally, 1:1 conduction at twice the cycle length of the 2:1 train (control method V). Observed AVN conduction times obeyed the following relationship: method I greater than method II greater than method V, indicating a cumulative effect of concealed penetration by the blocked beats. During 2:1 block, the AVN effective refractory period (ERP) alternated with a mean beat-to-beat difference of at least 100 msec, due mostly to marked ERP abbreviation during AVN activation by method III (vs both 2:1 train cycle length and activation by method V). Concealed penetration by the blocked beat prolonged AVN ERP for the propagated beat (vs that with methods II and V), but to a lesser extent than conduction time was increased. Moreover, the AVN recovery curve with method I was displaced upward and to the right compared with that with methods II to V.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian variations in the electrical properties of the human heart assessed by sequential bedside electrophysiologic testing

To assess the variability of the currently used electrophysiologic parameters and their possible circadian rhythm, sequential bedside electrophysiologic testing was performed during a 24-hour period, at intervals of 1 to 2 hours, in 12 patients who had normal atrioventricular (AV) conduction times and normal sinus node function. The coefficients of variation during the 24-hour period were: ± 10.4% for the R-R interval, ± 10.6% for the sinus node recovery time (SRT) at atrial pacing of 100 bpm, ± 32.5% for the corrected SRT, ± 15.1% for the ventriculoatrial (VA) effective refractory period (ERP), ± 8.3% for the AV nodal ERP, ± 5.7% for the AH interval, ± 5.2% for the HV interval, ± 5.5% for the atrial ERP, ± 3.3% for the right ventricular ERP, ± 2.8% for the QT interval, ± 4% for the VA interval, and ± 3.4% for the retrograde Kent bundle ERP. Between 12:00 midnight and 7:00 am, there was significant lengthening of: the sinus node rate ( p < 0.0005), the SRT at atrial paced rates of 100 and 120 bpm ( p < 0.025), the QT interval duration ( p < 0.025), and the ERP of the atria ( p < 0.025), AV node ( p < 0.01), and right ventricle ( p < 0.05). Thus conventional electrophysiologic parameters are subject to daily variability and, like sinus node function, AV nodal and myocardial refractoriness follow a circadian rhythm with an acrophase between 12:00 midnight and 7:00 am. In addition, prolonged bedside recording of the His bundle potential can be reliably obtained.

Acute electrophysiologic effects of pirmenol in normal subjects and in patients with Wolff-Parkinson-White syndrome

The acute electrophysiologic effects of pirmenol are reported in 8 normal subjects and in 8 patients with Wolff-Parkinson-White (WPW) syndrome. Standard electrophysiologic testing was performed before and after a 50-mg intravenous bolus and a 60-minute infusion of 150 mg of pirmenol. After pirmenol administration, AH interval, atrial refractory period, atrioventricular (AV) nodal functional refractory period and Wenckebach cycle length did not change; however, sinus cycle length decreased from 743 ±169 to 650 ± 133 ms (p < 0.001), sinoatrial conduction time from 103 ± 35 to 78 ± 37 ms (p < 0.05) and AV nodal effective refractory period from 308 ± 51 to 272 ± 23 ms (p < 0.01). Pirmenol increased the HV interval from 43 ± 5 to 48 ± 6 ms (p < 0.05) and ventricular functional refractory period from 247 ± 21 to 260 ± 21 ms (p < 0.005). Anterograde effective refractory period of the accessory AV pathway increased in 4 of 6 patients with ventricular preexcitation and retrograde effective refractory period increased in all patients. Pirmenol treatment prolonged the shortest preexcited RR interval from 253 ± 38 to 459 ± 19 ms (p < 0.05) and the average RR interval from 354 ± 26 to 421 ± 60 ms (p < 0.01) during atrial fibrillation in all 6 patients with preexcitation. Pirmenol did not influence the inducibility or cycle length of AV reciprocating tachycardia in the patients with WPW syndrome. The pirmenol infusions were well tolerated. Thus, pirmenol therapy has a direct depressant effect and an indirect vagolytic action on electrophysiologic measurements, a clinically beneficial effect in slowing the ventricular response to atrial fibrillation in WPW syndrome and little effect on reciprocating AV tachycardia.