Nodal Effective Refractory Period Research Articles

Characterization of Atrioventricular Nodal Behavior and Ventricular Response During Atrial Fibrillation Before and After a Selective Slow-Pathway Ablation

The presence of atrioventricular nodal dual-pathway physiology in patients with atrioventricular nodal reentrant tachycardia (AVNRT) provides an opportunity to characterize the effect of a selective slow-pathway ablation on the ventricular rate during atrial fibrillation (AF). This may have important clinical implications for the nonpharmacological management of AF with a rapid ventricular rate. Selective radiofrequency catheter ablation of the atrioventricular nodal slow pathway was performed with a stepwise approach in patients with documented sustained AVNRT. The AV nodal conduction properties and refractoriness and the ventricular rate during induced AF were assessed at baseline and under autonomic blockade before and after a selective slow-pathway ablation in 18 patients (mean age, 34 +/- 8 years). Sustained AVNRT was induced with a mean cycle length of 339 +/- 58 ms. A slow-pathway ablation was successfully achieved with 5 +/- 4 applications of radiofrequency energy. The shortest cycle length of 1:1 AV conduction and the AV nodal effective refractory period significantly prolonged after ablation (367 +/- 53 versus 403 +/- 55 ms, P < .0001, and 258 +/- 55 versus 292 +/- 74 ms, P < .05, respectively). Selective slow-pathway ablation significantly prolonged the mean (526 +/- 93 versus 612 +/- 107 ms, P < .0001), the shortest (378 +/- 59 versus 423 +/- 73 ms, P < .0001), and the longest (826 +/- 150 versus 969 +/- 226 ms, P < .01) cycle lengths of the ventricular response to AF. Significant slowing of the ventricular rate during AF occurred in 13 patients (72%), including all eight patients in whom AV nodal dual-pathway physiology was abolished. Five patients did not have a significant change in the ventricular rate during AF; a persistent dual AV nodal pathway physiology was demonstrable in four of these patients. Loss of dual-pathway physiology after ablation had a sensitivity of 77%, specificity of 80%, and positive predictive value of 91% for slowing the ventricular rate during AF. In patients undergoing a slow-pathway ablation for control of AVNRT, selective slow-pathway ablation may cause a significant decrease in the ventricular rate during AF. These effects are primarily due to the prolongation of AV nodal conduction properties and refractory period of the residual AV nodal transmission system. These findings may have important therapeutic implications for the nonpharmacological treatment of AF, particularly in patients with underlying dual AV nodal physiology.

991-71 Electrophysiologic Findings in Patients with Obstructive Sleep Apnea Associated Ventricular Asystole

Fourteen patients (47 ± 11 years) with ventricular asystole of 5.6 ± 2.7 sec (range: 3.1–13.6 sec) due to complete atrioventricular (AV) block (n = 8), sinoatrial (SA) block or sinus node (SN) arrest (n = 5) or both (n = 1) occurring exclusively during sleep apnea episodes as documented by cardiorespiratory polysomnography underwent conventional electrophysiologic study: evaluation of sinus node function included rate corrected SN recovery time (CSNRT), sinoatrial conduction time (SACT, Narula method), and sinus rate (SR) response to atropine (0.02 mg/kg). CSNRT of &lt;550 ms, SACT of &lt;125 ms, and SR increase after atropin to &gt;90 bpm were considered to be normal. Assessment of AV-conduction included AH- and HV-intervals. AV-Wenckebach periods, and AV nodal effective refractory periods (ERPs) before and after atropine. None of the 14 pts received digitalis, beta-blockers or verapamil during polysomnography or EP study. 6 pts (42%) had hypertensive heart disease, 1 pt (8%) had coronary disease, and 7 pts (50%) showed no evidence of structural heart disease. SN function was normal in 12 of 14 pts (86%). Two pts had slightly prolonged SACTs (160 and 165 ms respectively). CSNRT and SR response to atropine was normal in all pts. AV nodal function was normal in 8 of 14 pts (57%) and abnormal in 4 pts (43%): 2 pts had prolonged AH-intervals of 135 and 143 ms, and 2 pts had AV-Wenckebach points at 520 and 730 ms and AV nodal ERPs of 500 and 700 ms respectively. AV-nodal function normalized after administration of atropine in all 4 pts. His-Purkinje system function was normal in 8 pts (57%), and 6 pts (43%) had slightly prolonged HV-Intervals (range: 59–63 ms). Intra- or infra His block was not observed in any pt. In conclusion , normal or only slightly abnormal electrophysiologic findings in most patients with sleep apnea associated ventricular asystole support the hypothesis that ventricular asystole is due to a neurally mediated cardioinhibitory reflex. However, it remains unsolved, why sleep apnea associated prolonged ventricular asystole does occur in some pts and does not occur in other pts despite severe obstructive sleep apnea.

Effect of site, summation and asynchronism of inputs on atrioventricular nodal conduction and refractoriness.

The impulses coming from the sinus node synchronically penetrate the AV node via the crista terminalis and inter-atrial septum. Studies in superfused rabbit AV preparations suggest that the crista terminalis is a more effective input than the inter-atrial septum, and that the summation of both inputs facilitates AV nodal conduction. The aim of this study was to verify the hypothesis in a more physiological model, such as the whole rabbit heart perfused by a Langendorff system. Fifteen rabbit hearts were studied in a Langendorff perfusion system with six bipolar extracellular electrodes: two for stimulating (crista terminalis and inter-atrial septum) and four for recording (crista terminalis, inter-atrial septum, His bundle electrogram and right ventricle). Seven hearts (Group I) were consecutively paced at the crista terminalis, inter-atrial septum and both sites simultaneously, to determine the AV nodal Wenckebach cycle length and effective refractory period under basal conditions and after acetylcholine (0.75 x 10(-6) M). In eight hearts under 0.75 x 10(-6) M acetylcholine (Group II), the crista terminalis and inter-atrial septum were simultaneously (delay = 0 ms) or sequentially (delay = 2, 4, 6, 8, 10, 12, 14, and 16 ms) stimulated to calculate the AV nodal effective refractory period and the AH interval at an atrial coupling interval 5 ms longer than the AV nodal effective refractory period, for each delay tested.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized comparative study of the electrophysiological and electrocardiographic effects of isradipine vs verapamil

Isradipine is a new dihydropyridine calcium antagonist reported to have minimal effects on cardiac electrophysiology. Of 19 patients with normal cardiac electrophysiological profiles, 11 received isradipine intravenously at doses of 0.0010, 0.0020, 0.0040 and 0.0080 mg.kg-1 (0.0150 mg.kg-1 total dose), and eight received verapamil intravenously at 0.0125, 0.0250, 0.0500 and 0.1000 mg.kg-1 (0.1875 mg.kg-1 total dose). One patient experienced hypotension several minutes after receiving the third isradipine dose. With isradipine, systolic blood pressure (BP) decreased from 154 +/- 24 to 151 +/- 22, 143 +/- 25, 133 +/- 19 and 124 +/- 17 mmHg, respectively. Diastolic BP decreased from 83 +/- 10 (baseline) to 80 +/- 12, 76 +/- 10, 74 +/- 7 and 68 +/- 9 mmHg, respectively. With verapamil, systolic BP changed from 132 +/- 20 (baseline) to 135 +/- 29, 132 +/- 24, 130 +/- 25 and 115 +/- 17 mmHg, respectively, and diastolic BP changed from 80 +/- 14 to 84 +/- 14, 81 +/- 9, 78 +/- 6 and 73 +/- 5 mmHg, respectively. Isradipine had no significant effect on the PR, QRS, QT and QTc intervals, nor were there changes in the atrial-His (AH) and His-ventricle (HV) intervals, atrioventricular nodal effective refractory period. Wenckebach cycle length or sinus node recovery time. Similarly, verapamil at the doses studied did not significantly affect PR, QRS, QT, QTc, AH or HV intervals. However, with verapamil, the Wenckebach cycle length changed significantly from 394 +/- 82 (baseline) to 448 +/- 93 ms. Despite the significant fall in BP with isradipine, heart rate did not change significantly. These results support the electrophysiological neutrality of isradipine on the cardiac conduction system.

Effects of diltiazem on concealed atrioventricular nodal conduction in relation to ventricular response during atrial fibrillation in anesthetized dogs

By means of a new quantitative index for concealed conduction, we evaluated the effects of diltiazem on atrioventricular (AV) node concealment and correlated this index with the variability of the ventricular response during atrial fibrillation in 16 anesthetized mongrel dogs. After determination of the atrial effective refractory period (ERP), AV nodal ERP (AVNERP), concealment zone, and concealment index (AVNERP of blocked atrial extrasystole/AVNERP of conducted atrial extrasystole), the R-R intervals during atrial fibrillation induced by electrical stimulation were measured. Both low (0.1 mg/kg) and medium (0.2 to 0.4 mg/kg) doses of diltiazem prolonged the AVNERP and increased the mean R-R interval during atrial fibrillation. Only medium doses of diltiazem increased the degree of concealed conduction in the AV node and accentuated the variability of R-R intervals. There was a good positive correlation between the variability of the ventricular response during atrial fibrillation and the concealment index. In conclusion, medium doses of diltiazem are more effective in reducing heart rate during atrial fibrillation than a low dose. However, medium doses also increase the degree of concealed conduction in the AV node and enhance the irregularity of the ventricular response during atrial fibrillation. Measurement of the concealment index is useful for quantitating the degree of concealed conduction in the AV node, which is actually an important determinant of the ventricular response during atrial fibrillation.

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.

Acute conversion of paroxysmal supraventricular tachycardia with intravenous diltiazem

Diltiazem has electrophysiologic effects similar to those of verapamil. Its efficacy and safety in 4 doses for treatment of induced supraventricular tachycardia (SVT) were examined and compared with those of placebo in 87 patients (25 with atrioventricular [AV] nodal reentry tachycardia, 60 with AV reentry associated with an accessory AV connection, and 2 with atrial tachycardia). Conversion to sinus rhythm occurred in 4 of 14 patients (29%) with 0.05 mg/kg of diltiazem, 16 of 19 (84%) with 0.15 mg/kg, 13 of 13 (100%) with 0.25 mg/kg, and 14 of 17 (82%) with 0.45 mg/kg compared with 6 of 24 (25%) treated with placebo. Conversion rates in groups receiving doses of 0.15 to 0.45 mg/kg of diltiazem were superior to that in the placebo group (p < 0.001). Time to conversion was 3.0 ± 2.6 minutes in responding diltiazem patients compared with 5.9 ± 6.1 minutes in responding control patients. Diltiazem administration resulted in significant lengthening of SVT cycle length, AH interval, and AV nodal effective refractory period and block cycle length. The most frequent adverse response to diltiazem was hypotension (7 of 63 patients); however, only 4 patients had symptoms related to hypotension. Thus, intravenous diltiazem in doses of 0.15, 0.25 and 0.45 mg/kg is an effective and safe treatment for the acute management of SVT.

Permanent AV block or modification of AV nodal function by selective AV nodal artery ethanol infusion.

The acute and chronic effects of selective AV nodal artery ethanol infusion on AV nodal function was studied in 9 closed chest anesthetized dogs. Using standard percutaneous techniques of arterial catheterization, a 2.2 French infusion catheter was positioned in the AV nodal artery. Ten minute infusions into the AV nodal artery of 25%, 50%, or 100% ethanol in normal saline at rates of 0.5 mL/min acutely resulted in complete AV nodal block (AVB) in 5 dogs, 2:1 AV nodal block in 1 dog, and prolongation of AV nodal effective refractory period and/or Wenckebach cycle length in the remaining 3 dogs. One dog died with persistent complete AV block 1 week after the ethanol infusion. When restudied 4 weeks later, 7 of the 8 surviving dogs had persistent modification of AV nodal function, including complete AV block in 5 dogs and lengthening of AV nodal effective refractory period and/or Wenckebach cycle length without AV block in 2 dogs. Pathologic examination of the animals exhibiting chronic modification or ablation of AV nodal function revealed healing infarction of the AV node or its approaches. Distant myocardial necrosis was not observed and left ventricular function was normal. Slow infusion of low concentrations of ethanol into the AV nodal artery results in AV nodal modification or ablation due to localized necrosis in or around the AV node. This technique may have a role in AV nodal modification or ablation, particularly in patients who have failed DC shock or radiofrequency ablation.

Selective transcatheter ablation of the fast and slow pathways using radiofrequency energy in patients with atrioventricular nodal reentrant tachycardia.

The safety and efficacy of selective fast versus slow pathway ablation using radiofrequency energy and a transcatheter technique in patients with atrioventricular nodal reentrant tachycardia (AVNRT) were evaluated. Forty-nine consecutive patients with symptomatic AVNRT were included. There were 37 women and 12 men (mean age, 43 +/- 20 years). The first 16 patients underwent a fast pathway ablation with radiofrequency current applied in the anterior/superior aspect of the tricuspid annulus. The remaining 33 patients initially had their slow pathway targeted at the posterior/inferior aspect of the right interatrial septum. The fast pathway was successfully ablated in the initial 16 patients and in three additional patients after an unsuccessful slow pathway ablation. A mean of 10 +/- 8 radiofrequency pulses were delivered; the last (successful) pulse was at a power of 24 +/- 7 W for a duration of 22 +/- 15 seconds. Four of these 19 patients developed complete atrioventricular (AV) block. In the remaining 15 patients, the post-ablation atrio-His intervals prolonged from 89 +/- 30 to 138 +/- 43 msec (p less than 0.001), whereas the shortest 1:1 AV conduction and effective refractory period of the AV node remained unchanged. Ten patients lost their ventriculoatrial (VA) conduction, and the other five had a significant prolongation of the shortest cycle length of 1:1 VA conduction (280 +/- 35 versus 468 +/- 30 msec, p less than 0.0001). Slow pathway ablation was attempted initially in 33 patients and in another two who developed uncommon AVNRT after successful fast pathway ablation. Of these 35 patients, 32 had no AVNRT inducible after 6 +/- 4 radiofrequency pulses with the last (successful) pulse given at a power of 36 +/- 12 W for a duration of 35 +/- 15 seconds. After successful slow pathway ablation, the shortest cycle length of 1:1 AV conduction prolonged from 295 +/- 44 to 332 +/- 66 msec (p less than 0.0005), the AV nodal effective refractory period increased from 232 +/- 36 to 281 +/- 61 msec (p less than 0.0001), and the atrio-His interval as well as the shortest cycle length of 1:1 VA conduction remained unchanged. No patients developed AV block. Among the last 33 patients who underwent a slow pathway ablation as the initial attempt and a fast pathway ablation only when the former failed, 32 (97%) had successful AVNRT abolition with intact AV conduction. During a mean follow-up of 6.5 +/- 3.0 months, none of the 49 patients had recurrent tachycardia. Forty patients had repeat electrophysiological studies 4-8 weeks after their successful ablation, and AVNRT could not be induced in 39 patients. These data suggest that both fast and slow pathways can be selectively ablated for control of AVNRT: Slow pathway ablation, however, by obviating the risk of AV block, appears to be safer and should be considered as the first approach.

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.

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.

Determinants of Acute Hemodynamic and Electrophysiologic Effects of Verapamil in Humans: Role of Myocardial Drug Uptake

To examine the relationship between myocardial verapamil content (MVC) and acute effects in humans, coronary sinus catheterization was used in 22 patients to determine myocardial uptake of verapamil after bolus intravenous (i.v.) verapamil (4 mg) injection. Verapamil-induced effects on hemodynamic and electrophysiologic parameters were measured simultaneously and correlated with MVC per unit baseline coronary sinus blood flow (MVC:F). Myocardial uptake of verapamil was rapid: peak MVC (1.2 +/- 0.2% of injected dose) occurred at 5.4 +/- 0.4 min; at 30 min, residual MVC was 71.1 +/- 3.4% of maximum. Peak MVC:F in individual patients was inversely related to the extent of coronary artery disease (p less than 0.005) but not to left ventricular (LV) systolic function. Verapamil produced significant (p less than 0.001) early reductions in arterial pressure and systemic vascular resistance (SVR); cardiac index (CI) increased, left ventricular (LV) positive dP/dt was unchanged. Verapamil prolonged (p less than 0.01) PR and AH intervals (maximum at 12-18 min) and atrioventricular (AV) nodal effective and functional refractory periods (ERP, FRP) (maximum at 30 min). In individual patients, the extent of changes in AH intervals (r = 0.69; p less than 0.05) and LV dP/dt (r = 0.62; p less than 0.05) correlated with peak MVC:F. We conclude that after i.v. injection, verapamil uptake by the human myocardium is rapid and more extensive in patients with minor coronary artery disease. Despite the hysteresis between MVC and drug effects, MCV is a determinant of inotropic and electrophysiologic effects of verapamil.

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.

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.

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.

Electrophysiological determinants of antidromic reentry induced during atrial extrastimulation. Insights from a pacing model of Wolff-Parkinson-White syndrome.

The electrophysiology of antidromic reentry, a less common phenomenon than orthodromic reentry, remains a poorly understood aspect of the Wolff-Parkinson-White (WPW) syndrome. We used a pacing model of ventricular preexcitation in patients without WPW, so that electrophysiological events in the normal pathway during atrial extrastimulation (A1-A2 technique) could be precisely delineated without the obscuring effect of an actual accessory pathway. Ventricular preexcitation was simulated by an A1-V1 sequential basic drive with A2-V2 extrastimulation at progressively shorter A1-A2 (equal to V1-V2) coupling intervals. At each coupling interval tested within the zone of atrioventricular (A-V) nodal effective refractory period (since anterograde block of A2 was considered mandatory for manifestation of antidromic reentry), responses were assessed after A2 alone (method I), V2 alone (method II), and A2 plus V2 (method III, the complete preexcitation model). The entire pacing protocol was performed at two A-V intervals, short (50 msec) and long (150-180 msec), thereby simulating different proximities between the A pacing site and "accessory pathway" location. Of 47 consecutive unmedicated patients screened for the study protocol, 38 failed to meet minimal prerequisites for possible initiation of antidromic reentry because of failure in 18 (38% of total) to achieve anterograde A-V nodal block of A2, even though 1:1 ventriculoatrial conduction to cycle lengths less than or equal to 500 msec (less than or equal to 400 msec in 12) was present; and poor or absent ventriculoatrial conduction in the others. The nine remaining candidates underwent the full pacing protocol. Antidromic reentry (retrograde atrial response following V2 in method III) was observed in only two cases (4% of total), and both were associated with retrograde His-Purkinje system delays (documented by method II) occurring in tandem with a long A-V interval, thereby allowing for completion of retrograde A-V nodal recovery after penetration by A2. Indeed, such a prolonged recovery time prevented initiation of antidromic reentry in six of the nine patients (proven by intact ventriculoatrial conduction in method II). Retrograde A-V nodal block of V2, independent of A2, prevented an antidromic echo in one case. Findings in our model help to clarify the various factors, including specific anterograde and retrograde A-V nodal properties; anatomic relation between the accessory and normal pathways; and the retrograde His-Purkinje system delays, that must prevail in a concerted fashion to permit the initiation of antidromic reentry during the A1-A2 technique in patients with the WPW syndrome.

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)