Atrioventricular Nodal Effective Refractory Period Research Articles

The effects of ketamine on dexmedetomidine‐induced electrophysiologic changes in children

Dexmedetomidine is an alpha2-adrenergic agonist used for sedation and analgesia in children. We previously showed that dexmedetomidine depresses sinus and AV nodal function resulting in adverse hemodynamic effects such as bradycardia and increased blood pressure. We hypothesized that these effects of dexmedetomidine might be antagonized by co-administration of ketamine, which has sympathomimetic properties. Twenty-two children (ages 5-17 years) undergoing electrophysiologic (EP) study and ablation for supraventricular tachycardia were enrolled. Patients were kept sedated with continuous infusion of propofol at a fixed rate. Hemodynamic and EP parameters were measured before and after a loading dose of dexmedetomidine (1 μg·kg(-1)). A continuous infusion of dexmedetomidine (0.7 μg·kg(-1) ·h(-1)) was initiated and a ketamine loading dose (1 mg·kg(-1)), followed by continuous infusion (1 mg·kg(-1) ·h(-1)), was given. A repeat set of hemodynamic and EP parameters were then measured at the time of projected peak tissue concentration for both drugs. A significant increase in mean arterial pressure (MAP) was seen compared with baseline after loading of dexmedetomidine. This returned to baseline after co-administration of ketamine (mean difference between baseline and after ketamine 1.8 mmHg; 95%CI, -7.8 to 4.3; P = <0.001). A decrease in heart rate was seen after dexmedetomidine followed by a return to baseline after co-administration of ketamine (mean difference between baseline and after ketamine -6.5 bpm; 95%CI, -11.2 to -1.8; P = 0.005). Sinus node recovery time was lengthened after dexmedetomidine but returned to baseline after ketamine (mean difference between baseline and after ketamine -16.2 ms; 95%CI, -63 to 30; P = 0.014). QT was prolonged after dexmedetomidine and returned to baseline after ketamine (mean difference between baseline and after ketamine -34.2 ms; 95%CI, -48.4 to -20.2; P = 0.004). AV nodal effective refractory period was also impaired after dexmedetomidine and showed weak evidence for return to baseline function after ketamine (mean difference between baseline and after ketamine -22.8 ms; 95%CI, -40.2 to -5.2; P = 0.069). The concurrent use of ketamine may mitigate the negative chronotropic effects of dexmedetomidine.

Post-ablation prolongation of atrioventricular nodal refractory period is correlated with long-term success of cryoablation for atrioventricular nodal reentrant tachycardia in the case of the persistence of a residual jump.

PurposeA residual slow pathway after successful cryoablation for atrioventricular nodal reentrant tachycardia (AVNRT) is correlated with a higher recurrence rate. We described determinants of recurrence in subjects with a residual jump.MethodsWe analyzed the data of subjects with acute successful slow pathway cryoablation for AVNRT using a 6-mm-tip cryocatheter. Success was defined as AVNRT non-inducibility. Patients with no baseline elicitable jump, no inducible AVNRT, and transient first atrioventricular (AV) block at the last site were excluded.ResultsFrom 371 patients who underwent cryoablation from May 2002 to March 2011, 303 fulfilled the entry criteria (mean age, 41 ± 16; 222 women). Baseline AV nodal effective refractory period (ERP) was 272 ± 57 ms, postprocedural 331 ± 64 (P < 0.001), and the mean of the difference (Δ ERP) 60 ± 41. At the end of the procedure, 64 patients (21 %) had a residual jump, of whom 22 with a single echo. At 12 months follow-up, the actuarial recurrence-free rate was 70.3 % in patients with a residual jump and 86 % in those without (P = 0.01). In patients with a jump, only Δ AV nodal ERP was correlated with recurrence (37 ± 41 vs. 68 ± 47 ms; P < 0.04) while a single echo was not. The actuarial rate of recurrence was 60.8 % in patients with a Δ AV nodal ERP ≤ 30 ms and 18.8 % in those with a Δ AV nodal ERP >30 ms (P < 0.01).ConclusionsSuppression of slow pathway conduction is the optimal endpoint for AVNRT cryoablation. A residual jump can be tolerated if AV nodal ERP postcryoablation is prolonged >30 ms.

Atrioventricular node functional remodeling induced by atrial fibrillation

The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF. To determine whether AVN undergoes functional remodeling during AF. AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls. Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P <.01), longer AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P <.01), an earlier transition from fast-pathway to SP conduction (at a longer prematurity, 249 ± 60 ms vs 171 ± 24 ms; P <.01), and a slower ventricular rate during simulated AF (RR interval 249 ± 42 ms vs 202 ± 12 ms; P <.01). Notably, a larger proportion of conducted beats utilized the SP in AF preparations (92% ± 12% vs 63% ± 32%; P <.05). Long-term AF in dogs resulted in a longer atrioventricular conduction time and AVN effective refractory period and a slower ventricular rate during AF compared with the controls. Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF.

Correlations between long-term results after cryoablation for atrioventricular nodal reentry tachycardia and a residual jump associated or not with a single echo

While in radiofrequency ablation for atrioventricular nodal reentry tachycardia (AVNRT) a residual jump and a single echo do not seem to substantially modify long-term results, in cryoablation procedures their effects are still under evaluation. The purpose of this study was to evaluate if a residual jump associated or not with an isolated echo is correlated with outcome. acute successful slow pathway cryoablation for slow-fast AVNRT. use of a 4 mm tip cryocatheter, no baseline elicitable jump or inducible AVNRT, and unwanted persistent first degree atrioventricular (AV) block at the end of the procedure. Cryoablation (-80°C × 4 min) was applied after successful cryomapping. Atrioventricular nodal reentry tachycardia inducibility was checked 30 min later on and off isoproterenol. Acute success was defined as AVNRT non-inducibility. Among 332 patients (pts) who had undergone cryoablation from May 2002 to March 2010 in our institutions, 245 of them fulfilled the entry criteria (173 women, mean age 41 ± 16 years, ineffective drugs 1.3 ± 1.1). A 7-Fr 6-mm tip cryocatheter (CryoCath®) was used in all cases. Baseline AV nodal effective refractory period (ERP) was 271 ± 55 ms, post-procedural ERP 331 ± 60 ms (P< 0.001), and the mean of the difference between baseline and post-procedural ERP 63 ± 38 ms. A/V ratio at successful site was 1 ± 0.4. Forty-four pts (18%) had a residual jump at the end of the procedure, and 14 of them had an associated single echo. Global cryoapplication time was 993 ± 797 s. During a follow-up of 40 ± 10 months, 43 pts (17.5%) had recurrences. At 12 months follow-up, actuarial rate of recurrence-free pts was 85% in the group without residual jump (201 pts), 63.3% with residual jump and no echo (30 pts), and 60.6% with residual jump associated with a single echo (P< 0.003 among groups). Univariate predictors of recurrences were persistence of a residual jump (P< 0.001) and total cryoapplication time (P< 0.02). In a multivariate model, only residual jump was independently correlated with recurrences (P< 0.01). In patients undergoing AVNRT cryoablation, slow-pathway suppression is correlated with a better outcome. A single echo is associated with a recurrence risk similar to residual jump without echo. It may be suggested that pursuing a procedural endpoint up to slow pathway complete suppression may improve long-term success.

The Impact of Age on the Electrophysiological Characteristics and Different Arrhythmia Patterns in Patients with Wolff-Parkinson-White Syndrome

Information about the impact of age on the electrophysiological characteristics of accessory pathways (APs) in patients with Wolff-Parkinson-White (WPW) syndrome remains limited. A total of 1,885 consecutive patients (mean age 43 ± 17 years, male 61.5%) with WPW syndrome who were referred to the tertiary center for an electrophysiological study and radiofrequency catheter ablation were investigated. The patients were divided into 4 groups based on their age (Group 1: <20; Group 2: 20-39; Group 3: 40-59; Group 4: ≧60 years old). With age, more left-sided APs (53.2%, 67.7%, 71.7%, 75.7%, P < 0.001) and a longer duration of the arrhythmia (4.3 ± 2.8 years, 10.1 ± 7.0 years, 12.4 ± 10.9 years, 14.0 ± 12.4 years, P < 0.001) were noted. The incidence of concealed APs (53.5%, 53.0%, 57.8%, 60.9%, P = 0.01), and orthodromic atrioventricular (AV) reentrant tachycardia (92.4%, 94.2%, 96.5%, 96.3%, P = 0.023) increased with age. The tachycardia cycle length, antegrade (275.5 ± 42.2 ms, 286.7 ± 62.7 ms, 302.5 ± 66.5 ms, 315.2 ± 80.2 ms, P < 0.001) and retrograde AP effective refractory periods (APERPs) (254.0 ± 42.5 ms, 263.3 ± 51.8 ms, 274.5 ± 100.5 ms, 292.7 ± 57.0 ms, P < 0.001), atrial ERP, antegrade AV node effective refractory period (AVNERP), and ventricular effective refractory period (VERP) lengthened as the age increased. The incidence of decremental APs, multiple APs, and a catecholamine response were similar. The duration of the catheter ablation, total fluoroscopy time, acute success rate, complication rate, and incidence of a secondary procedure were similar between the different age groups. The electrophysiological characteristics and pattern of the arrhythmic attack associated with the AP changed with age.

Cardiac Electrophysiological and Antiarrhythmic Effects of N-n-butyl Haloperidol Iodide

Aims: N-n-butyl haloperidol (F₂), a novel compound of quaternary ammonium salt derivatives of haloperidol, was reported to antagonize myocardial ischemia/reperfusion injuries. The antiarrhythmic potential and electrophysiological effects of F₂ on rat cardiac tissues were investigated. Methods and Results: In Langendorff-perfused rat hearts, the ventricular arrhythmias were induced by left anterior descending coronary artery of rat heart ligated for 20 min before the release of the ligature. F₂ provided some inhibitive effects against ischemia- and reperfusion-induced ventricular arrhythmias. In His bundle electrogram and epicardial ECG recordings, the drug produced bradycardia, delayed the conduction through the atrioventricular node and prolonged the Wenckebach cycle length and atrioventricular nodal effective refractory period. In whole-cell patch-clamp study, F₂ primarily inhibited the L-type Ca²⁺ current (I_Ca,L) (IC₅₀ = 0.17 µM) with tonic blocking properties and little use-dependence. And the drug also decreased the Na⁺ current (IC₅₀ = 77.5 µM), the transient outward K⁺ current (IC₅₀ = 20.4 µM), the steady-state outward K⁺ current (IC₅₀ = 56.2 µM) and the inward rectifier K⁺ current (IC₅₀ = 127.3 µM). Conclusion: F₂ may be a promising drug for the treatment of ischemic heart disease with cardiac arrhythmia.

Changes in electrophysiologic properties of the conductive system of the heart in children with atrioventricular nodal reentrant tachycardia after 2–8 years following radiofrequency catheter ablation of the slow pathway

Radiofrequency ablation of the slow pathway is an effective method of treatment in children with atrioventricular nodal reentrant tachycardia. The aim of our study was to evaluate anterograde conduction properties in children before and after radiofrequency ablation of the slow pathway and to determine the efficacy and safety of this method. Noninvasive transesophageal electrophysiological examination was performed in 30 patients at the follow-up period (mean duration, 3.24 years) after radiofrequency ablation of the slow pathway. The slow pathway function was observed in 13 patients one day after ablation, in 26 patients during the follow-up period, and in 28 patients after administration of atropine sulfate. Atrioventricular node conduction was significantly decreased the following day after ablation and at the follow-up versus the preablation (165.2 [30.2] bmp and 146.3 [28.5] bpm versus 190.9 [31.4] bpm; P<0.001). The atrioventricular node effective refractory period prolonged significantly the following day after ablation and at the follow-up versus the preablation (319.3 [55.3] ms and 351.0 [82.1] ms versus 248.3 [36.6] ms; P<0.001). Effective refractory period of the fast pathway prolonged significantly as compared with the preablation (from 408.0 [60.4] ms to 481.2 [132.9] ms; P=0.005). The prolongation of effective refractory period of the slow pathway was more significant than effective refractory period of the fast pathway at the follow-up (P<0.001). Two late recurrences occurred; one patient had atrial tachycardia. Children with atrioventricular nodal reentrant tachycardia can be effectively and safety cured by ablative therapy. The end-point during slow pathway ablation should be the abolition of tachycardia with preservation of dual atrioventricular nodal physiology.

Sequential dual chamber extrastimulation: A novel pacing maneuver to identify the presence of a slowly conducting concealed accessory pathway

Transient VA block can be created in the AV node (AVN) when an atrial extrastimulus is delivered at the AVN effective refractory period (ERP) due to anterograde concealed conduction. We hypothesized that ventricular stimulation during pacing-induced AVN refractoriness could identify concealed accessory pathways (APs) that remain hidden with standard maneuvers. Patients undergoing electrophysiological study for supraventricular tachycardia were screened for presence of an AP using standard pacing maneuvers and/or V pacing during adenosine infusion. The dual-chamber sequential extrastimulation maneuver consisted of an 8-beat drive train of simultaneous AV pacing at 600 msec, followed by an A2 delivered at AVN ERP, followed by a V2 delivered at the drive train cycle length (600 msec). Repeat drives were then performed with decrements of 10 msec for V2 until VA block was seen. Retrograde AVN and AP ERP were recorded with standard (V1, V2) and dual-chamber extrastimulation (A1/V1, A2, V2). Patients with an AP identified with standard pacing, manifest pre-excitation, or A ERP < AVN ERP were excluded. Fourteen patients with and 19 patients without an AP were studied. In all patients with an AP, exclusive VA conduction over the AP, without fusion, was seen with the described pacing maneuver. In patients without an AP, retrograde AV nodal ERP was extended by a mean of 138 +/- 46 msec (range 50 to 210 msec) with the A2. Anterograde concealed conduction into the AP was also seen in some patients who showed AP conduction during standard V1V2 pacing (mean retrograde extension of ERP 12 +/- 8 msec, range 0 to 20 msec). Dual-chamber sequential extrastimulation is a useful maneuver for identifying slowly conducting APs not revealed with standard pacing maneuvers because of an ERP and conduction time similar to the AVN. The maneuver uses anterograde concealed conduction to prolong AVN refractoriness much more than that of a concealed AP, thereby allowing the AP to become manifest with the V2.

Focal Pharmacological Modulation of Atrioventricular Nodal Conduction via Implantable Catheter

Pharmacological ventricular rate control is an acceptable atrial fibrillation (AF) therapy limited by systemic toxicity. We postulate that focal catheter-based drug delivery into the atrioventricular nodal (AVN) region may effectively control ventricular rate during AF without systemic toxicity. This study evaluated the effects of focally administered acetylcholine on AVN conduction and refractoriness during sinus rhythm and AF. Canines (n=7) were anesthetized and instrumented to assess cardiac electrophysiology and blood pressure. A custom drug delivery catheter was implanted in the AVN region. Incremental doses of acetylcholine starting at 10 microg/min were infused until complete AV block was achieved. Acetylcholine induced dose-dependent AV block. AF induction and electrophysiology measurements were performed during baseline and acetylcholine-induced first-degree and third-degree AV block. During AF, infusion of acetylcholine decreased ventricular rates from 182+/-32 to 77+/-28 and 28+/-8 bpm (first-degree and third-degree AV block, respectively; P<0.05). At the first-degree AV block dose, AVN effective refractory period increased from 186+/-37 to 282+/-33 ms, and Wenckebach cycle length increased from 271+/-29 to 378+/-58 ms (P<0.05). The first-degree AV block dose prolonged AV and AH intervals by 26% and 23% (P<0.05), whereas AA intervals and blood pressure remained unchanged, demonstrating a local effect. All effects were reversed 20 minutes after infusion was stopped. Focal acetylcholine delivery into the AVN increased AVN refractoriness and significantly decreased ventricular rate response during induced AF in a dose-related, reversible manner without systemic side effects. This may represent a novel therapy for AF whereby ventricular rate is controlled with the use of an implantable drug delivery system.

Electrophysiologic Characteristics and Radiofrequency Catheter Ablation in Children with Wolff‐Parkinson‐White Syndrome

The majority of cardiac arrhythmias in children are supraventricular tachycardia, which is mainly related to an accessory pathway (AP)-mediated reentry mechanism. The investigation for Wolff-Parkinson-White (WPW) syndrome in adults is numerous, but there is only limited information for children. This study was designed to evaluate the specific electrophysiologic characteristics and the outcome of radiofrequency (RF) catheter ablation in children with WPW syndrome. From December 1989 to August 2005, a total of 142 children and 1,219 adults with atrioventricular reentrant tachycardia (AVRT) who underwent ablation at our institution were included. We compared the clinical and electrophysiologic characteristics between children and adults with WPW syndrome. The incidence of intermittent WPW syndrome was higher in children (7% vs 3%, P=0.025). There was a higher occurrence of rapid atrial pacing needed to induce tachycardia in children (67% vs 53%, P=0.02). However, atrial fibrillation (AF) occurred more commonly in adult patients (28% vs 16%, P=0.003). The pediatric patients had a higher incidence of multiple pathways (5% vs 1%, P<0.001). Both the onset and duration of symptoms were significantly shorter in the pediatric patients. The antegrade 1:1 AP conduction pacing cycle length (CL) and antegrade AP effective refractory period (ERP) in children were much shorter than those in adults with manifest WPW syndrome. Furthermore, the retrograde 1:1 AP conduction pacing CL and retrograde AP ERP in children were also shorter than those in adults. The antegrade 1:1 atrioventricular (AV) node conduction pacing CL, AV nodal ERP, and the CL of the tachycardia were all shorter in the pediatric patients. This study demonstrated the difference in the electrophysiologic characteristics of APs and the AV node between pediatric and adult patients. RF catheter ablation was a safe and effective method to manage children with WPW syndrome.

Cryoablation in pediatric atrioventricular nodal reentry: Electrophysiologic effects on atrioventricular nodal conduction

Cryoablation for treatment of atrioventricular nodal reentrant tachycardia (AVNRT) is safe and efficacious. Information on the effects of cryoablation on atrioventricular (AV) nodal conduction is limited. The purpose of this study was to evaluate the effects of cryoablation on AV nodal conduction in pediatric patients with AVNRT. We retrospectively analyzed electrophysiologic studies before and after successful cryoablation. Patients were divided into two groups: group 1 (n = 22, age 14 +/- 3 years) had baseline discontinuous atrial-to-His interval (AH) conduction curves; and group 2 (n = 13, age 12 +/- 4 years, P = .054) had continuous curves. At baseline, group 1 had longer measurements of maximal AH with A1A2, AV nodal effective refractory period, and AV block cycle length. Postcryoablation, both group 1 and group 2 showed decreases in maximal AH with A1A2 pacing or atrial overdrive pacing and in the finding of PR > or = RR with atrial overdrive pacing (group 1: 55% vs 5%, P < .001; group 2: 69% vs 0%, P < .001). A significant increase in overall AV effective refractory period and a decrease in AV block cycle length were found in group 1 but not group 2. Fifty percent of group 1 patients had complete abolition of slow pathway conduction. Successful cryoablation for treatment of AVNRT is associated with a reduction in PR > or = RR and with decreases in maximal AH with A1A2 pacing or atrial overdrive pacing. Further study is needed to determine the usefulness of these parameters for assessment of ablation efficacy or as proxies for AVNRT inducibility.

Calmodulin kinase II activity is required for normal atrioventricular nodal conduction

Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is abundant in myocardium. CaMKII activity is augmented by catecholamine stimulation, which enhances AV nodal conduction, suggesting the hypothesis that CaMKII also contributes to AV nodal conduction properties. The purpose of this study was to test the potential role of CaMKII in regulating AV nodal conduction in heart. We developed a novel mouse with genetic CaMKII inhibition by cardiac-specific expression of autocamtide 3 inhibitory peptide (AC3-I) mimicking a conserved sequence of the CaMKII regulatory domain. We also engineered a control transgenic mouse with cardiac expression of an inactive, scrambled version of AC3-I (autocamtide 3 control peptide [AC3-C]) and performed electrophysiologic measurements in vivo and in Langendorff-perfused isolated hearts. AC3-I and AC3-C were abundantly expressed in AV nodal cells. AC3-I mice with implanted ECG telemeters showed enhanced Wenckebach-type AV conduction block after isoproterenol (present in 9/9 mice) compared with AC3-C mice (present in 1/5 mice, P = .005). Intracardiac recordings showed significant PR and AH interval prolongation in AC3-I mice at baseline and after isoproterenol compared with AC3-C mice. HV durations were not different. Langendorff-perfused AC3-I hearts had significantly prolonged Wenckebach cycle lengths and AV nodal effective refractory periods compared with AC3-C hearts, whereas sinus node recovery time and left ventricular effective refractory times were similar between these genotypes. These studies define CaMKII as a critical determinant of normal and catecholamine-stimulated AV nodal conduction responses.

Atrioventricular nodal fast pathway modification: mechanism for lack of ventricular rate slowing in atrial fibrillation.

Atrioventricular node (AVN) modification is one of the alternatives for ventricular rate control in patients with drug refractory atrial fibrillation (AF). However, the underlying mechanisms, and in particular the role of the dual pathway electrophysiology is not clear. By using a novel index, His electrogram (HE) alternans, we have previously demonstrated in rabbits that both the slow (SP) and the fast pathways (FP) are involved in AVN conduction during AF. This electrophysiological-morphological study was designed to address the role of selective FP ablation on AVN conduction during AF. In 12 rabbit AVN preparations dual pathway conduction was confirmed by HE alternans during A1A2 pacing protocol, as well as during AF. On average 48% of the conducted beats during AF utilized the FP. Selective FP ablation (n=12) guided by HE alternans resulted in only-SP conduction, with longer AVN conduction time at basic beats, but without change of AVN effective refractory period (ERP). Interestingly, despite elimination of all FP-conducted beats during AF, the selective FP ablation allowed previously concealed SP beats to be conducted, resulting in little net effect on the ventricular rate (average His-His interval 199+/-10 ms before versus 201+/-13 ms after FP ablation, p>0.05). Morphological evidence indicated that FP ablation created lesions within the transitional cells of the superior approaches at the junction between the central fibrous body and the AVN. However, extension of FP ablation lesion into the compact AVN domain resulted in non-selective AVN modification and slowing of ventricular rate during AF. Despite its longer ERP, FP is responsible for a substantial number of ventricular beats during AF. However, selective FP ablation has a minor effect on ventricular rate. The most likely mechanism for this phenomenon is that FP ablation allows previously concealed SP beats to be conducted. On the other hand, ventricular rate slowdown could be achieved if FP ablations caused collateral damage in the compact node. This study highlights the usefulness of HE alternans as a novel tool to monitor dual pathway conduction during AF and to guide AVN modification.

Autonomic blockade unmasks maturational differences in rate-dependent atrioventricular nodal conduction and facilitation in the mouse.

In large animals, rate-dependent AV nodal (AVN) properties of conduction are modulated by autonomic inputs. In this study, we investigated whether the properties of AVN conduction and facilitation are altered by autonomic blockade in the mouse and whether this effect is age dependent. Young (age 4-6 weeks; n = 11) and adult (age 8-9 months; n = 11) female mice underwent in vivo electrophysiologic testing, before and after autonomic blockade. After autonomic blockade, the adult mice had significantly longer AVN effective refractory period (AVNERP; 67 +/- 14 msec vs 56 +/- 4 msec, P = 0.05) and functional refractory period (AVNFRP; 81 +/- 10 msec vs 72 +/- 4 msec, P = 0.05). With autonomic blockade, the increase from baseline of AVN Wenckebach cycle length (deltaAVW; 1.8 +/- 8.1 msec vs 8.8 +/- 3.3 msec, P = 0.04), as well as of AVNERP (deltaAVNERP; 3.5 +/- 3.5 msec vs 21.4 +/- 12.6 msec, P = 0.002) and AVNFRP (deltaAVNFRP; 2.3 +/- 3.2 msec vs 12.8 +/- 9.0 msec, P = 0.008), was significantly larger in adult than in young mice. Compared with young mice, adult mice were less likely to exhibit AVN facilitation (44% vs 90%, P = 0.03) and had smaller maximal shortening of AVN conduction times after the "test beat" for any coupling of the "facilitating beat" (4 +/- 4 msec vs 7 +/- 3 msec, P = 0.05). Complete autonomic blockade significantly increases AVN conduction times and refractory periods in adult but not in young mice. Adult mice also exhibit less AVN facilitation. Our results confirm that, like in larger animals, rate-dependent murine AVN properties of conduction are under autonomic regulation. Adult mice have higher sympathetic AVN inputs at baseline, leading to slower conduction after autonomic blockade.

Conduction Properties of Accessory Atrioventricular pathways: Importance of the Accessory Pathway Location and Normal Atrioventricular Conduction

Objective—The objective of this study was to determine the conduction properties of the nOlmal atrioventricular (AV) conduction system in relation to accessory pathway (AP) location in patients with symptomatic Wolff–Parkinson–White syndrome.Design—The conduction properties of the AP and the AV node were studied in 356 patients with single manifest AP who underwent successful ablation.Results—Sixty-three percent of the APs were located on the left free wall (226) and the remaining 37% were posteroseptal, anteroseptal and right free wall. AV block (PR ≥ 220 ms) was observed in 15 patients, 8 cases being associated with the right free wall (15%) compared with 7 on the left free wall (3%, p = 0.002) and none on the anteroseptal (p = 0.02) or posteroseptal (P = 0.007). The PR (182 ± 30ms) and AH (102 ± 25 ms) intervals associated with right free wall AP Were longer than left free wall (166 ± 23, 88 ± 21 ms, p < 0.000 I, respectively), anteroseptal (155 ± 11 , 79 ± 12 ms, p < 0.0001) and posteroseptal AP (ISS ± 16,79 ± 13 ms, p < 0.0001), whereas the PR and AH intervals associated with posteroseptal and anteroseptal AP were shorter than left free wall AP (p < 0.05). When patients with A V block were excluded from the analysis, the PR intervals in patients with right free wall AP were still longer than in those with left free Wall (p < 0.005), anteroseptal (p < 0.001) and posteroseptal AP (p < 0.0001), as were the PR intervals associated with left free wall AP compared with data of posteroseptal (p < 0.01) and anteroseptal AP (p < 0.05). Significant differences in AV nodal effective refractory period, anterograde and retrograde AV block cycle length were also observed in relation to AP location.Conclution—The conduction properties of the normal AV conduction system are associated with specific AP location in patients with Wolff–Parkinson–White syndrome.

The effects of aging on AV nodal recovery properties.

The purpose of this study was to assess the changes of AV nodal recovery properties with aging. Although in children and young adults it was found that there were age dependent changes in their AV nodal recovery properties, in the older population this information was not available. In 92 subjects (aged 16-92 years) without AV nodal disease or dual AV nodal pathway physiology, their AV nodal recovery curves were studied by delivering premature atrial extrastimuli coupled to basic atrial beats during cardiac electrophysiological study. Data were analyzed using linear regression and curve-fitting techniques. Patients were grouped by age, group I < 40 years (n = 33), group II 40-59 years (n = 26), and group III > 60 years (n = 33). The results showed that the AV nodal recovery curve did not change significantly in the aging process except that the AV nodal effective refractory period had a positive correlation with increasing age. The latter was significantly increased in group III when compared to group I or group II. For this parameter, when patients whose AV nodal refractory period was limited by the atrial refractory period were excluded, there was still a statistically significant increase in group III compared to group II (P < 0.05): group I (n = 27): 202+/-42 ms; group II (n = 17): 197+/-26 ms; and group III (n = 17): 224+/-46 ms. The results suggest that the AV nodal recovery curve remains unchanged once it reaches adulthood, with the exception that the nodal effective refractory period becomes slightly longer after age 60.

Effects of ajmaline on rate-dependent atrioventricular node properties: Potential role in experimental atrioventricular re-entrant tachycardia

Ajmaline is a well-known atrioventricular (AV) node depressant agent, but its effects on functional properties of the AV node and on experimental AV re-entrant tachycardia have not been explored. The aims of the present study were (1) to determine whether ajmaline administration modifies the rate-dependent properties of the AV node and (2) to correlate these changes with the actions of ajmaline on an in vitro model of AV re-entrant tachycardia. Selective stimulation protocols and mathematical formulations were used to quantify independently AV node recovery, facilitation, and fatigue in 10 isolated rabbit AV nodes. Ajmaline decreased facilitation and fatigue and had no significant effect on AV node recovery. The most important effect of ajmaline was rate-induced prolongation of AV node effective refractory period, resulting in a greater increase in tachycardia cycle length. AV re-entrant tachycardia was sustained when AV effective refractory period divided to tachycardia cycle length was less than 1, ajmaline suppressed AV re-entrant tachycardia by increasing the slope of the AV effective refractory period divided to tachycardia cycle length versus tachycardia rate relation, causing the critical ratio of 1 to be attained at a slower rate. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for changes in nodal conduction time, AV effective refractory period, tachycardia cycle length, and AV effective refractory period divided to tachycardia cycle length under all conditions. It can be concluded that (1) ajmaline increases AV conduction time, decreases AV node fatigue, and facilitation, without altering AV node recovery. (2) Ajmaline significantly prolongs AV effective refractory period in a rate-dependent manner. (3) These changes play a role in ajmaline's actions on experimental AV re-entrant tachycardia. Ajmaline's ability to terminate re-entrant supraventricular tachycardia may be due, at least in part, to its ability to amplify the rate-induced prolongation of the nodal refractory period.

Cryothermal ablation of the slow pathway for the elimination of atrioventricular nodal reentrant tachycardia.

We report the first successful slow pathway ablation using a novel catheter-based cryothermal technology for the elimination of atrioventricular nodal reentrant tachycardia (AVNRT). Eighteen patients with typical AVNRT underwent cryoablation. Reversible loss of slow pathway (SP) conduction during cryothermy (ice mapping) was demonstrated in 11 of 12 patients. Because of time constraints, only 2 sites were ice mapped in 1 patient. Seventeen of 18 patients had successful cryoablation of the SP. One patient had successful ice mapping of the SP, but inability to cool beyond -38 degrees C prevented successful cryoablation. A single radiofrequency lesion at this site eliminated SP conduction. No patient has had recurrent AVNRT over 4.9+/-1.7 months of follow-up. During cryoablation, accelerated junctional tachycardia was not seen and was therefore not available to guide lesion delivery. Adherence of the catheter tip during cryothermy (cryoadherence) allowed atrial pacing to test for SP conduction. Cryoablation in the anterior septum produced inadvertent transient PR prolongation consistent with loss of fast pathway conduction in 1 patient and transient (6.5 seconds) 2:1 AV block in another. On rewarming, the PR interval returned to normal, and the AV nodal effective refractory period was unchanged in both. Accelerated junctional tachycardia was seen on rewarming in both but not during cryothermy. Cryothermal ablation of the SP was achieved in patients with this novel technique. Successful ice mapping of both the SP and fast pathway was demonstrated. The ability to test the functionality of specific ablation sites before production of a permanent lesion may eliminate inadvertent AV block.

Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities.

Previous electrophysiologic investigations have described AV conduction disturbances in connexin40 (Cx40)-deficient mice. Because expression of Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Purkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of deficiencies in Cx40. Ten Cx40-/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40-/- mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6+/-6.4 msec vs 36.0+/-4.1 msec, P = 0.002). Not only the HV interval (14.0+/-3.0 msec vs 10.4+/-1.2 msec, P = 0.003) but also the AH interval (33.2+/-4.8 msec vs 27.1+/-3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40-/- compared with Cx40+/+ mice. Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction.

Rate-dependency of Action Potential Duration and Refractoriness in Isolated Myocytes from the Rabbit AV Node and Atrium

During atrial fibrillation, ventricular rate is determined by atrioventricular nodal (AVN) conduction, which in part is dependent upon the refractoriness of single AVN cells. The aims of this study were to investigate the rate-dependency of the action potential duration (APD) and effective refractory period (ERP) in single myocytes isolated from the AV node and atrium of rabbit hearts, using whole cell patch clamping, and to determine the contribution of the 4-aminopyridine (4-AP)-sensitive current, ITO1to these relationships in the two cell types. AVN cells had a more positive maximum diastolic potential (−60±1 v−71±2 mV), lower Vmax(8±2 v 144±17 V/s) and higher input resistance [420±46 v 65±7 MΩ (mean±s.eP<0.05n =9–33)], respectively, than atrial myocytes. Stepwise increases in rate from 75 beats/min caused activation failure and Wenckebach periodicity in AVN cells (at around 400 beats/min), but 1:1 activation in atrial cells (at up to 600 beats/min). Rate reduction from 300 to 75 beats/min shortened the ERP in both cell types (from 155±7 to 135±11 ms in AVN cells [P<0.05, n=6] and from 130±8 to 106±7 ms in atrial cells [P<0.05, n=10]). Rate increase from 300 to 480 and 600 beats/min shortened ERP in atrial cells, by 12±4% (n=8) and 26±7% (n=7), respectively (P<0.05). By contrast, AVN ERP did not shorten at rates >300 beats/min. In atrial cells, rate reduction to 75 beats/min caused marked shortening of APD50(from 51±6 to 29±6 ms, P<0.05). 4-AP (1 mm ) significantly prolonged atrial APD50at 75 beats/min (P<0.05, n=7), but not at 300 or 400 beats/min. In AVN cells, in contrast, there was less effect of rate change on APD, and 4-AP did not alter APD50at any rate. 4-AP also did not affect APD90or ERP in either cell type. In conclusion, a lack of ERP-shortening at high rates in rabbit single AVN cells may contribute to ventricular rate control. ITO1contributed to the APD50rate relation in atrial, but not AVN cells and did not contribute to the ERP rate relation in either cell type.