Congenital tumor of atrioventricular node with complete heart block and sudden death. Mesothelioma or lymphangio-endothelioma of atrioventricular node.
Explore the source record for details and available documents.
Adult↗
SEARCH · Search PubMed
Results for “Atrioventricular Node”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Perinodal cryosurgery for atrioventricular node reentry tachycardia in 23 patients.
Atrioventricular node reentry tachycardia is the most common cause of paroxysmal supraventricular tachycardia. Available nonpharmacologic therapies include (1) catheter ablation or cryosurgical ablation of the His bundle and insertion of a permanent pacemaker and (2) surgical dissection around the atrioventricular node or discrete cryosurgery of the perinodal tissues, in an attempt to divide or ablate only one of the dual atrioventricular node conduction pathways responsible for the tachycardia while leaving the other intact. This report describes 23 consecutive patients who underwent the discrete cryosurgical procedure between August 13, 1982, and March 16, 1989. The first patient in this series, a 38-year-old woman, is the first patient in whom refractory atrioventricular node reentry tachycardia was cured surgically by a procedure designed to treat this arrhythmia. The ages of the 13 female and 10 male patients ranged from 12 to 56 years with an average age of 29 years. Fourteen of the 23 patients (61%) had the Wolff-Parkinson-White syndrome. Other associated arrhythmias included atrial flutter/fibrillation (n = 2), right atrial reentrant tachycardia (n = 1), junctional tachycardia (n = 1), and a Mahaim fiber (n = 1). Associated anatomic abnormalities included Ebstein's anomaly in two patients and a large right atrial aneurysm in one patient. The perinodal cryosurgical procedure was performed through a right atriotomy in the normothermic beating heart. Multiple 3 mm diameter cryolesions were placed around the borders of the triangle of Koch on the lower right atrial septum to alter the input pathways of the atrioventricular node. There were no operative deaths in this series of patients. Postoperatively, all 23 patients had normal atrioventricular conduction, and no heart block has occurred in any patients during the follow-up period. All patients have remained free of atrioventricular node reentry tachycardia (and of the Wolff-Parkinson-White syndrome) and none has required postoperative antiarrhythmic drugs for either of these arrhythmias. We consider this simple, safe, easily performed, and uniformly successful operation to be the procedure of choice for the treatment of medically refractory atrioventricular node reentry tachycardia.
Adolescent↗
High-resolution, three-dimensional fluorescent imaging reveals multilayer conduction pattern in the atrioventricular node.
BACKGROUND: The atrioventricular node (AVN) is the only normal electrical link between the upper and lower chambers of the heart. The AVN modulates transmission of impulses, thus coordinating the contraction of the atria and ventricles. METHODS AND RESULTS: Structural and functional complexity, combined with the absence of adequate experimental techniques, has complicated attempts to directly evaluate the three-dimensional electrical activity of the AVN. Thus, despite a century of research by conventional electrophysiologic and histologic methods, even the existence of conduction through AVN is still debated. CONCLUSIONS: Using a novel combination of microelectrode recordings and high resolution fluorescent imaging with voltage-sensitive dyes, we have for the first time clearly demonstrated three-dimensional conduction through the AVN.
Animals↗
Inhibition of L-type calcium current by propafenone in single myocytes isolated from the rabbit atrioventricular node.
1. The atrioventricular node (AVN) is an important part of the conduction system in the heart and is a significant site of antiarrhythmic drug action. The class 1 antiarrhythmic propafenone is effective in treating a variety of arrhythmias, including those involving the AVN. In this study, we have investigated the effects of propafenone on ionic currents in single rabbit AVN cells, focusing in particular on those on L-type calcium current (ICa,L). 2. With a standard K-based internal dialysis solution, exposure to 5 microM propafenone reduced significantly the amplitude of ICa,L. In spontaneously active AVN myocytes, action potential upstroke velocity was decreased by propafenone exposure, consistent with the observed change in ICa,L. 3. By use of a Cs-based internal dialysis solution to record ICa,L selectively, voltage clamp test pulses were applied from a holding potential of -40 mV to +10 mV (stimulation frequency 0.33 Hz). Propafenone 5 microM reduced mean ICa,L density at +10 mV from -9.58 +/- 1.05 pA/pF to -4.19 +/- 0.60 pA/pF (P < 0.002). A range of propafenone concentrations were applied which reduced ICa,L in a dose-dependent manner (IC50 1.7 microM). When test pulses were applied to a range of potentials, propafenone reduced ICa,L at each potential without significantly affecting the activation curve for this current. Thus, propafenone reduced ICa,L conductance, without affecting the voltage-dependent activation properties of the current. 4. ICa,L block by propafenone exhibited tonic-, use- and frequency-dependent characteristics. 5. In the presence of propafenone, the voltage-dependence of inactivation of ICa,L was shifted 8 mV in the hyperpolarizing direction. Also, the recovery of ICa,L from inactivation was slowed by propafenone. 6. The ICa,L blocking properties of propafenone may mediate some of the antiarrhythmic properties of this agent, particularly in regions of the heart such as the AVN in which ICa,L contributes significantly to the action potential upstroke.
Action Potentials↗
The actions of nickel on membrane currents activated by hyperpolarisation in single cells from the rabbit atrioventricular node.
1. The atrioventricular node (AVN) is vital for cardiac function as it normally provides the only conduction route for the cardiac impulse from atria to ventricles and can act as a pacemaker for the ventricles if the sinoatrial node (SAN) fails. We have shown previously that whilst 80-90% of AVN myocytes do not possess If (we have termed these type 1 cells), a small proportion (10-20%) of AVN cells (type 2) do exhibit If. 2. The present study describes the effects of the divalent cation nickel (Ni) on membrane currents activated by hyperpolarising voltage clamps from -40/mV in type 1 and type 2 cells at 35 degrees C, using the whole cell patch clamp technique. In type 2 cells 5 mM Ni enhanced the amplitude of If. At -120 mV the mean Ni-activated If was -1.85 +/- 0.28 pA/pF (mean +/- SEM; n = 5). Ni significantly enhanced If at -70 mV and at all potentials negative to this (p < 0.05 at -70, -80, -90 and -110 mV; 0.05 < p < 0.1 at -100 mV; p < 0.005 at -120 mV). 3. In type 1 cells, which exhibit a small time-independent inward current on hyperpolarisation there was no activation of If by Ni (p > 0.1 at all potentials between -40 mV and -120 mV). 4. In type 1 cells 5 mM Ni significantly reduced the time-independent inward current activated by a hyperpolarising pulse to -120 mV (p < 0.02) and had a smaller effect at -110 and -100 mV (0.05 < p < 0.1 at these potentials). With pulses to less negative potentials there was no significant alteration of the time-independent current. 5. An additional observation was that the fast sodium current activated on repolarisation of the membrane potential to -40 mV after a hyperpolarising voltage clamp appeared to be blocked by Ni. However, this apparent blockade reflected a positive shift in the activation threshold for INa, since a repolarising step to -30 mV could still elicit INa. 6. Ni is known to block sarcolemmal Na/Ca exchange in cardiac cells, and one possible mechanism for the enhancement of If by Ni in type 2 cells is increased intracellular Ca via Na/Ca exchange blockade increasing If. The reduction in end pulse current in type 1 cells is also consistent with Na/Ca exchange current blockade. A second possibility of the enhanced If in type 2 cells with Ni is a positive shift of the activation curve for If in the presence of an increased concentration of external divalent cations.
Animals↗
Actions of the digitalis analogue strophanthidin on action potentials and L-type calcium current in single cells isolated from the rabbit atrioventricular node.
1. The atrioventricular node (AVN) of the heart is vital to normal cardiac function and is a major site of antiarrhythmic drug action. This study describes the effects of the cardiac glycoside analogue strophanthidin on spontaneous action potentials and L-type calcium current recorded from single AVN cells isolated from the rabbit heart. 2. With a standard KCl-based internal dialysis solution, exposure to 50 microM strophanthidin produced a progressive depolarization of the maximum diastolic potential and a reduction in action potential amplitude and upstroke velocity. Sustained application resulted in the loss of action potentials and occurrence of spontaneous 'bell-shaped' depolarizations. 3. Cells were whole-cell voltage clamped at -40 mV and depolarizing voltage clamps applied. With a standard KCl-based internal dialysis solution, exposure to 50 microM strophanthidin caused a large reduction of ICa,L at all potentials between -30 and +40 mV (n = 4). At + 10 mV, the mean ICa,L amplitude was reduced from -232 +/- 65 pA to -48 +/- 26 pA (P < 0.05; 1 test; n = 5 cells). 4. To record ICa,L more selectively, cells were dialysed with a Cs-based pipette solution. A short strophanthidin exposure reduced ICa,L amplitude from -250 +/- 31 pA to -88 +/- 19 pA (P < 0.001; n = 8 cells). For both KCl and CsCl-based solutions it was observed that sustained exposure to strophanthidin for several minutes caused spontaneous inward fluctuations in the membrane current record similar to the 'ITI' (arrhythmogenic oscillatory transient inward) current shown for other cardiac cells. 5. When the calcium chelator BAPTA was added to the pipette solution (10 mM), the reduction in ICa,L by strophanthidin was largely eliminated (P > 0.1), and no spontaneous inward current fluctuations were observed after sustained exposure to strophanthidin (n = 8 cells). 6. When external Ca in the perfusate was replaced with Ba, strophanthidin did not significantly reduce the Ba current through L-type calcium channels (n = 5 cells). 7. We conclude that strophanthidin reduces ICa,L by an indirect action, mediated by the rise in intracellular calcium (Cai) which follows inhibition of the Na/K pump caused by cardiac glycosides. The appearance of spontaneous ITI with strophanthidin would also seem to be mediated by a rise in Cai, and may contribute to the spontaneous oscillations in membrane potential observed after prolonged strophanthidin exposure.
Action Potentials↗
Pathology of radiofrequency catheter ablation of the atrioventricular node.
Catheter ablation of the atrioventricular node is now the treatment of choice for definitive management of some supraventricular tachyarrhythmias. Radiofrequency current is used as the energy source in most centers. We describe a 67-year-old woman who had rheumatic mitral valve disease and chronic atrial fibrillation with rapid ventricular response. She underwent successful radiofrequency catheter ablation of the atrioventricular node, followed by permanent pacemaker insertion. She required mitral valve replacement 16 months later and died postoperatively of left ventricular failure. At autopsy, there were patches of organized endocardial thrombus and discrete endocardial and myocardial fibrous scar at the ablation sites, replacing most of the atrioventricular node. The long-term pathologic changes after atrioventricular node ablation with radiofrequency current, used in a clinical setting, have not been previously described and are illustrated here.
Aged↗
"Fade" of hyperpolarizing responses to vagal stimulation at the sinoatrial and atrioventricular nodes of the rabbit heart.
Previous studies have suggested that maintained vagal stimulation or acetylcholine infusion results in a fade of responses in the sinoatrial node but not in the atrioventricular node, implying different muscarinic receptor subtypes in the two regions. We investigated this hypothesis in 23 isolated rabbit atrial preparations made quiescent by continuous superfusion with verapamil (1 microgram/ml). Transmembrane potentials were recorded simultaneously from cells in the sinoatrial pacemaker region and from the "N" region of the atrioventricular node. Postganglionic vagal stimulation was achieved by the application of trains of pulses (50-150 microseconds; 10-20 V; 200 Hz). Simultaneous application of long-lasting (1-10 sec) vagal trains produced hyperpolarizations which were nearly identical for both nodal regions. Maximal hyperpolarizations (approximately or equal to 24 mV for sinoatrial node; 26 mV for atrioventricular node) were reached about 500 msec after initiation of the vagal train. Thereafter, hyperpolarizations faded, following a biphasic time course, and thus displaying two different time constants, one fast (tau fast = 580 msec for sinoatrial node; 550 msec for atrioventricular node), and one slow (tau slow = 9.2 sec for both sinoatrial and atrioventricular nodes). Hyperpolarizations during brief (200-msec) but repetitive vagal trains also faded biphasically, but approached a steady state much more rapidly than responses to long-lasting trains. Recovery from hyperpolarization decay occurred rather slowly and was linear. Our results demonstrate that the membrane potential responses to vagal stimulation in the atrioventricular node are indistinguishable from those in the sinoatrial node, and suggest that similar muscarinic receptors are operative in both regions. These phenomena may play an important role in the response of the cardiac conducting system to direct or reflexly mediated vagal input.
Animals↗
[Effect of verapamil on the electrophysiological properties of the atrioventricular node in patients with atrioventricular nodal tachycardia].
Explore the source record for details and available documents.
Adult↗
Direct identification of parameters in a mathematical model describing conduction through the atrioventricular node.
Function of the atrioventricular node is assessed during intracardiac electrophysiology study by relating the output intervals A2H2 and H1H2 to the input A1A2, where A and H are, respectively, atrial and His bundle electrograms recorded by catheter. The H1H2 curves have been previously deduced from a model describing the A2H2 curves. Because of presence in a few cases of different behaviour of A2H2 and H1H2, this study aimed to establish a more suitable model of H1H2 independently of A2H2 for the particular case of a single transmission pathway. The two models were compared by calculation of standard error of the estimate. As a first approximation, the deduced model may be sufficient. However, the standard error of the estimate was less with the direct algorithm, which is therefore the more suitable for further development, particularly for recognition and modelling of conduction over multiple pathways through the atrioventricular node.
Adult↗
[Mesothelioma in atrioventricular node. A cause of atrioventricular block and sudden death].
Explore the source record for details and available documents.
Adult↗
Localization of the origin of the atrioventricular junctional rhythm induced during selective ablation of slow-pathway conduction in patients with atrioventricular node reentrant tachycardia.
During radiofrequency catheter ablation of slow atrioventricular node pathway conduction in patients with atrioventricular node reentrant tachycardia, an atrioventricular junction rhythm is frequently observed. The origin and relation to ablation success of this junctional rhythm was examined in this study. By using standard intracardiac electrophysiology techniques, we studied the radiofrequency energy-induced atrioventricular junctional rhythm in 43 consecutive patients with atrioventricular node reentrant tachycardia undergoing selective ablation of slow-pathway conduction. The frequency of atrioventricular junctional activity was correlated with successful and unsuccessful attempts at ablation of slow-pathway conduction. Also, we compared the sequence of retrograde atrial activation of radiofrequency energy-induced atrioventricular junctional beats in a subgroup of 22 patients with the retrograde activation sequence observed during pacing from the right ventricular apex and the site of successful ablation of slow-pathway conduction. A total of 201 radiofrequency-energy applications was delivered in 43 patients with > or = 5 atrioventricular junctional beat(s) induced during 110 (55%) of 201 ablation attempts. Atrioventricular junctional activity was noted during 98% of successful ablations but only 43% of the unsuccessful attempts (sensitivity, 98%; specificity, 57%; negative predictive value, 99%). The mean time to appearance of atrioventricular junctional beats was 8.8 +/- 4.1 sec (mean +/- SD) after the onset of radiofrequency-energy application. In 22 (100%) of 22 patients in whom detailed atrial mapping was performed, the retrograde atrial activation sequence of the radiofrequency-induced atrioventricular junctional beats was earliest in the anterior atrial septum, identical to that seen during pacing from the right ventricular apex. Earliest retrograde atrial activation was at the posterior septum in all patients during pacing from the successful ablation site, a markedly different activation pattern compared with that seen during either radiofrequency ablation or ventricular pacing. Whereas the occurrence of atrioventricular junctional activity during radiofrequency ablation does not necessarily herald a successful ablation of slow atrioventricular node pathway conduction, its absence strongly suggests that the energy is being applied in an unsuccessful fashion. Furthermore, it appears that radiofrequency energy-induced atrioventricular junctional beats originate not from the endocardium in contact with the ablating catheter tip but instead appear to exit remotely from the anterior atrial septal region. This finding supports the existence of specialized tissues in the atrioventricular junction that preferentially transmit the effects of radiofrequency energy to an anterior exit site, possibly identical to the atrial exit site of the retrograde fast atrioventricular node conduction pathway.
Atrioventricular Node↗
Vagally induced hyperpolarization in atrioventricular node.
The effects of postganglionic vagal stimulation on atrioventricular nodal conduction were studied in 12 rabbit atrial-atrioventricular nodal preparations. Vagal stimulation was introduced in the sinus and atrioventricular nodes, separately or in combination, using single bursts of subthreshold stimuli. The sinus cycle length was scanned to identify the phasic effect of vagal stimulation. Action potentials from cells in the AN, N, and NH regions of the atrioventricular node were recorded by microelectrode techniques. Vagally induced hyperpolarization of cells in the atrioventricular node resulted in a phase-dependent prolongation of conduction time and reflected the level of residual hyperpolarization at the moment of arrival of the next atrial beat at the atrioventricular nodal input region. Vagally induced hyperpolarization was membrane potential dependent, although its overall time course was similar at different phases. Increased diastolic depolarization followed the maximal hyperpolarization. This "rebound" observed at certain phases was responsible for paradoxical shortening of the conduction time after vagal stimulation. The predominant effects of local vagal stimulation in the atrioventricular node were observed in cells in or near the N region. Slower rate of rise, shorter amplitude and duration, as well as step formations were among the changes in action potentials recorded from these cells. The effects of vagal stimulation were inhomogeneous between different regions of the atrioventricular node as well as within the N region, producing alternative pathways of conduction and the potential for reentry. The concomitant changes in sinus cycle length resulting from vagal stimulation in the sinus node region altered the phasic effects of vagal stimulation introduced in the atrioventricular node. This was related to a direct influence of the prolonged sinus cycle length on atrioventricular nodal refractoriness as well as an indirect effect on the degree of residual vagally induced hyperpolarization at the moment of arrival of the delayed atrial beat. These findings provide mechanistic explanations for the complex effects of vagal stimulation on atrioventricular nodal conduction.
Animals↗
A modified electrocardiographic algorithm for differentiating typical atrioventricular node re-entrant tachycardia from atrioventricular reciprocating tachycardia mediated by concealed accessory pathway.
Non-invasive prediction of tachycardia mechanism is becoming clinically important in the era of catheter ablation for curing supraventricular tachycardia. Twelve-lead electrocardiograms (ECGs) during sinus rhythm and atrioventricular node re-entrant tachycardia (AVNRT) or atrioventricular reciprocating tachycardia (AVRT) with a narrow QRS complex were obtained from 154 consecutive adult patients who had received successful radiofrequency catheter ablation. The ECGs of initial 104 patients were analysed by three observers without knowledge of the electrophysiological diagnosis. The two arrhythmias were accurately diagnosed in 68% of cases. Three criteria were found to be discriminators of tachycardia mechanism by univariable analysis. Pseudo r/Q/S waves predicated AVNRT in 92% of cases (sensitivity 71%; specificity 95%). Retrograde P wave predicated AVRT in 86% of cases (sensitivity 75%; specificity 85%), RP interval > or =100 ms in 93% (sensitivity 71%; specificity 94%) and ST-segment elevation in lead aVR in 83% (sensitivity 71%; specficity 83%). According to the initial results, we proposed a modified stepwise ECG algorithm which used pseudo r/S/Q waves, RP interval and ST-segment elevation in lead aVR during tachycardia. Two observers assessed the modified algorithm in the remaining 50 patients. The algorithm was able to correctly diagnose the tachycardia mechanism in 84% and 87%, respectively. Using the modified algorithm can improve the accuracy and simplify the differential diagnosis between typical AVNRT and AVRT via concealed accessory pathway in adult patients.
Adult↗
Transient outward current carried by potassium and sodium in quiescent atrioventricular node cells of rabbits.
Single atrioventricular node cells were dispersed by treating the rabbit heart with collagenase. In Tyrode's solution, the cells became rounded, and about 20% of them showed spontaneous activity, whereas the rest remained quiescent. When those quiescent cells were whole-cell clamped, depolarizing clamp pulses from the holding potential of -83 mV induced an outward current which decayed quickly, with a time course similar to that of the transient outward current in the Purkinje fiber. The amplitude of the current became larger when progressively more positive clamp pulses were given from a very negative holding potential. The inactivation time course of this current consisted of two exponential components. Single-channel current recordings from those cells revealed a class of channels that activated more frequently during the initial part of depolarizing pulses. Summation of those unitary currents reproduced activation and inactivation time courses of the macroscopic current well, suggesting that this channel corresponds to the transient outward current. The current-voltage relationship of the channel was linear with the slope conductance of 19.9 +/- 1.8 pS (n = 7), and the reversal potential was near the resting potential of the atrioventricular node cell with 5.4 mM potassium chloride and 134.6 mM sodium chloride in the pipette. The channel was passing mainly potassium ions, but sodium ions also seemed to carry a fraction of the current. The possible role of the transient outward current in the quiescent node cell is discussed.
Animals↗
[Comparative study of auricular stimulation by transesophageal and endocavitary approach for evaluating sinus and atrioventricular node function].
The purpose of this study was to find out whether non-invasive transoesophageal pacing could effectively replace right intra-atrial pacing for the indirect evaluation of sinus node and atrioventricular (AV) node function. In a population of 17 patients the corrected sinus node recovery time (CSRT), the atrio-sinu-atrial conduction time (ASACT) and Wenckebach's point (W) were calculated by intracavitary pacing, then by transoesophageal pacing. There was no significant difference between the two methods in pre-pacing sinus cycle. With right intra-atrial pacing, mean CSRT value was 365 +/- 54 ms (with 5 values greater than 520 ms), mean ASACT value was 229 +/- 29 ms (with 8 values greater than 220 ms), and W occurred at a mean cycle length of 425 +/- 29 ms. With transoesophageal pacing, mean CSRT value was 406 +/- 87 ms (with 5 values greater than 520 ms), mean ASACT value was 222 +/- 17 ms (with 8 values greater than 220 ms), and W occurred at a mean cycle length of 408 +/- 26 ms. The two methods correlated very closely for CSRT and W (r = 0.97) and relatively well for ASACT (r = 0.84). The number of CSRT and ASACT values regarded as prolonged was the same with the two methods; 84% of recorded (i.e. maximal) CSRT values occurred with the same length of pacing cycle. There was no statistically significant difference between the two methods in the calculation of CSRT and ASACT, but W occurred at a slightly shorter cycle (p less than 0.05) with transoesophageal pacing. Thus, transoesophageal pacins is a non-invasive, easy to perform method for indirect exploration of sinus node and AV node function in patients who do not require subnodal conduction studies.
Aged↗
Percutaneous catheter modification of the atrioventricular node. A potential cure for atrioventricular nodal reentrant tachycardia.
Our purpose was to describe a technique of atrioventricular (AV) node modification for patients with drug refractory AV nodal reentrant tachycardia (AVNRT). Nine patients (mean age, 45 +/- 20; range, 14-82) with recurrent drug refractory AVNRT (n = 8) or sudden cardiac death thought to be precipitated by AVNRT (n = 1) underwent a percutaneous catheter procedure to modify AV nodal function. The area between the electrode recording the maximal His-bundle electrogram and the ostium of the coronary sinus was divided into three zones. Perinodal direct current shocks of 100-300 J were delivered to one (n = 2), two (n = 3), or three (n = 4) zones without complications. The procedure endpoints were modification of AV conduction (either first degree AV block or complete retrograde ventriculo-atrial [VA] block) and failure to induce AVNRT before or after isoproterenol and/or atropine administration. Six of nine patients (67%) have had no inducible or spontaneous AVNRT over a mean follow-up of 12.3 +/- 4.1 months (range, 4.5-17). One of the six underwent repeat, successful modification, because AVNRT was inducible at restudy 2 days after the initial procedure. AVNRT recurred in three patients (33%), one early (3 days) and two late (3-4 months). Two of these patients underwent complete ablation of the AV junction and permanent pacemaker placement, whereas one is controlled with drug therapy. Therefore, AV nodal modification resulted in tachycardia control without antiarrhythmic drugs in six of nine (67%) and obviated the need for complete AV junctional ablation in seven of nine patients (78%). Elimination of AVNRT appears to result from either block in the retrograde fast pathway or modification of the antegrade slow pathway, such that AVNRT cannot be sustained. Additional findings suggest that an atrio-Hisian accessory connection may not be involved in AVNRT in some of these patients. Percutaneous catheter AV nodal modification appears to be a promising technique for treatment of refractory AVNRT and may obviate need for complete AV junctional ablation in a substantial number of patients with drug/pacemaker refractory AVNRT.
Adult↗
Electrophysiological effects of ibutilide on the delayed rectifier K(+) current in rabbit sinoatrial and atrioventricular node cells.
Biophysical and pharmacological characteristics of the delayed rectifier K(+) current (I(K)) of rabbit sinoatrial (SA) node and atrioventricular (AV) node cells have been studied using the whole-cell patch clamp technique together with a recently developed antiarrhythmic agent, ibutilide. Ibutilide is a potent blocker of the rapid delayed rectifier K(+) current, I(Kr). Superfusion with ibutilide (10(-7) M) caused a decrease in the spontaneous firing frequency, depolarization of the maximal diastolic potential and prolongation of the action potential duration in both SA and AV node cells. In whole cell voltage clamp experiments done on myocytes from SA node, ibutilide (10(-7) M) blocked I(K) strongly (40%) and had smaller effects on Ca(2+) current (10%) and hyperpolarization-activated inward current, I(f) (11%). In AV node cells, the corresponding reductions were I(K) (68%), I(Ca) (13%) and I(f) (10%), respectively. A 10-fold increase in the concentration of ibutilide further decreased I(K) in SA node cells (67+/-8%), and blocked I(K) almost completely in AV node cells. These results are consistent with the hypothesis that the delayed rectifier K(+) current in SA node cell is generated by both I(Kr) and I(Ks), whereas I(Kr) predominates in AV node cells. Knowledge of the differences in the distribution of I(Kr), as well as the different sensitivity to blockers of I(Kr) in nodal cells, is important for understanding modifications of the automaticity, conduction velocity, and refractoriness by class III antiarrhythmic agents.
Action Potentials↗