Atrioventricular Nodal Conduction Time Research Articles

HE EFFECT OF PROBENECID ON α-1-ADRENOCEPTOR STIMULATION INDUCED PROARRHYTHMIC CONDUCTION IN THE ATRIOVENTRICULAR NODE OF RAT HEART

Cardiac tissue contains adrenergic receptors (AR) not only of the beta type, but also of the alpha type (α-AR). Both types of ARs play signifi cant role in regulation of cardiomyocytes electrophysiology in diff erent parts of the heart, including the atrioventricular node (AVN). An augmentation of α1-AR mediated component of adrenergic signaling results in impaired conduction of excitation in the heart and onset of various rhythm disturbances including AVNassociated arrhythmias. The activation of α1-AR facilitates anionic transmembrane transport causing electrophysiological changes in myocytes. Current study is aimed to the investigation of the eff ects of anion/chloride blockade on α1-AR-mediated proarrhythmic alteration of AVN functioning. Functional characteristics of AVN including AVN conduction time, AVN refractoriness and the AVN conduction alterations were examined via recording of surface electrograms in Langendorff -perfused isolated rat heart (Wistar, 250 ± 30 g). Phenylephrine was used as α1-AR agonist. Probenecid demonstrating anion/chloride transmembrane conductance blocking activity was used to modify Phe-induced α1-AR-mediated eff ects in AVN. The activation of α1-AR by Phe results in a signifi cant increase in the duration of AV intervals (N = 10, p < 0.001) and eff ective refractory period (ERP) in the AVN (by 9.8% ± 1.2%, n = 10, p < 0.001). Also, Phe induces AV-blocks of conduction and oscillations in atrioventricular delay (N = 10) at the stimulation rates close to ERP. Probenecid signifi cantly reduces the magnitude of AVD oscillations during non-stationary conduction in the AV node. In addition, probenecid attenuates ERP prolongation caused by Phe (107 ± 4 ms, N = 6) and 114.2 ± 5.35 ms (N = 10) in presence of only Phe and Phe with probenecid, respectively, returning its values toward typical for normal conditions. In conclusion, probenecid maintains physiological mode of AVN conduction when α1-AR are stimulated. This also suggests that chloride ion channels and anion carriers may contribute to the α1-AR-mediated AVN arrhythmias.

Effectiveness of the repurposed drug isotretinoin in an experimental murine model of Chagas disease

Benznidazole and nifurtimox are the drugs currently used for the treatment of Chagas disease, however its side effects may affect patient adherence. In the search for new alternative therapies, we previously identified isotretinoin (ISO), an FDA-approved drug widely used for the treatment of severe acne through a drug repurposing strategy. ISO shows a strong activity against Trypanosoma cruzi parasites in the nanomolar range, and its mechanism of action is through the inhibition of T. cruzi polyamine and amino acid transporters from the Amino Acid/Auxin Permeases (AAAP) family. In this work, a murine model of chronic Chagas disease (C57BL/6 J mice), intraperitoneally infected with T. cruzi Nicaragua isolate (DTU TcI), were treated with different oral administrations of ISO: daily doses of 5 mg/kg/day for 30 days and weekly doses of 10 mg/kg during 13 weeks. The efficacy of the treatments was evaluated by monitoring blood parasitemia by qPCR, anti-T. cruzi antibodies by ELISA, and cardiac abnormalities by electrocardiography. No parasites were detected in blood after any of the ISO treatments. The electrocardiographic study of the untreated chronic mice showed a significant decrease in heart rate, while in the treated mice this negative chronotropic effect was not observed. Atrioventricular nodal conduction time in untreated mice was significantly longer than in treated animals. Mice treated even with ISO 10 mg/kg dose every 7 days, showed a significant reduction in anti-T. cruzi IgG levels. In conclusion, the intermittent administration of ISO 10 mg/kg would improve myocardial compromise during the chronic stage.

Genetic variation rs6795970 of the SCN10A gene is associated with PR interval in young population of Republic of Moldova

Abstract Background/Objectives The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction time. Prolongation of the PR interval increase risk of atrial fibrillation (AF) and heart block. Genome-wide association studies (GWAS) have identified association of a nonsynonymous single nucleotide polymorphism (SNP), rs6795970, in the SCN10A gene with PR interval in individuals of European and Asian ancestry. The aim of the study was to determine distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova. Methods 1380 young participants from Republic of Moldova aged between 19–25 years, were genotyped for rs6795970 in the SCN10A gene, using TaqMan SNP Genotyping Assay. Results The genotype G/G, A/G, A/A distributions of rs6795970 among participants were 37%, 48%, 15%, respectively (χ2=0.086, p=0.770). The allele frequencies for G and A, in young participants were 61% and 39%, respectively. We observed association between rs6795970_A and a prolongation of the PR interval (p=0.003). Conclusions In our study, we determined that distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova was consistent with 1000 Genomes data in the European population. Therefore, our data demonstrate that the A allele is associated with prolongation of the PR interval and at least 15% of all participants (the A/A genotype), may have an increased risk of conduction abnormalities. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National project “Study of molecular genetic polymorphism of metabolic risk factors in young population of the Republic of Moldova National project “Identification and validation of genetic and epigenetic biomarkers in chronic non-communicable diseases with major impact on public health”

Determining the Site of Accessory Pathways in Orthodromic Reciprocating Tachycardia by Using the Response to Right Ventricular Pacing

Postpacing interval (PPI) after right ventricular (RV) pacing entrainment minus tachycardia cycle length (TCL) with a correction for atrioventricular (AV) node delay (corrected PPI-TCL) was useful to differentiate atrioventricular node reentrant tachycardia (AVNRT) from orthodromic reciprocating tachycardia (ORT). However, the value of corrected PPI-TCL in determining the site of the accessory pathway (AP) in ORT has not been investigated. The purpose of this study was to assess whether the corrected PPI-TCL is useful in differentiating ORT using a left-sided AP from a right-sided AP. We studied 52 patients with ORT using a left-sided AP and 13 patients with a right-sided AP. The PPI was measured upon cessation of the RV pacing at a cycle length 10-40 ms shorter than the TCL. The corrected PPI-TCL was calculated from the subtraction of the increment in AV nodal conduction time of the first PPI from the PPI-TCL. The mean corrected PPI-TCL was 83 ± 20 ms in patients with ORT using a left-sided AP and 27 ± 19 ms in patients with a right-sided AP (P ≤ 0.001). All patients with ORT using a left-sided AP except three patients with left septal AP and none of the patients with ORT using a right-sided AP had a corrected PPI-TCL > 55 ms. The corrected PPI-TCL after the RV pacing entrainment is useful to guide differentiating ORT using a left-sided AP from a right-sided AP.

Cardiohemodynamic and electrophysiological effects of a selective EP4 receptor agonist ONO­-AE1­-329 in the halothane-anesthetized dogs

Cardiovascular effects of a highly selective prostaglandin E2 type 4 (EP4) receptor agonist ONO-AE1-329 were assessed with the halothane-anesthetized dogs (n=6). ONO-AE1-329 was intravenously infused in three escalating doses of 0.3, 1 and 3ng/kg/min for 10min with a pause of 20min between the doses. The low dose of 0.3ng/kg/min significantly increased maximum upstroke velocity of left ventricular pressure by 18% at 20min, indicating increase of ventricular contractility. The middle dose of 1ng/kg/min significantly decreased total peripheral resistance by 24% and left ventricular end-diastolic pressure by 32% at 10min, indicating dilation of arteriolar resistance vessels and venous capacitance ones, respectively; and increased cardiac output by 25% at 10min in addition to the change induced by the low dose. The high dose of 3ng/kg/min increased heart rate by 34% at 10min; decreased mean blood pressure by 14% at 10min and atrioventricular nodal conduction time by 13% at 5min; and shortened left ventricular systolic period by 8% at 10min and electromechanical coupling defined as an interval from completion of repolarization to the start of ventricular diastole by 39% at 10min in addition to the changes induced by the middle dose. No significant change was detected in a ventricular repolarization period. These results indicate that ONO-AE1-329 may possess a similar cardiovascular profile to typical phosphodiesterase 3 inhibitors as an inodilator, and suggest that EP4 receptor stimulation can become an alternative strategy for the treatment of congestive heart failure.

Mechanisms and clinical significance of adenosine-induced dormant accessory pathway conduction after catheter ablation.

Adenosine can unmask dormant pulmonary vein conduction after isolation. The role of adenosine in uncovering dormant accessory pathway (AP) conduction after AP ablation is unknown. We evaluated 109 consecutive patients (age, 41 ± 28 years; 62 [57%] men) who were administered adenosine after successful AP ablation. Dormant AP conduction was defined as adenosine-induced recurrent AP conduction, as demonstrated by recurrent preexcitation or change in retrograde ventriculoatrial activation patterns. Dormant AP conduction was identified in 13 (12%) patients. Adenosine led to transient retrograde AP conduction in 6 patients and transient anterograde AP conduction in 8 patients. In all these cases, adenosine-induced AP conduction occurred during the bradycardia phase of adenosine effect and resulted in dormant AP conduction times shorter than atrioventricular nodal conduction times before adenosine administration. On the basis of analysis of timing of occurrence of dormant AP conduction, the mechanism of adenosine-induced AP conduction was determined to be caused by AP excitability recovery in ≥ 12 (92%) cases. The presence of dormant AP conduction was a significant predictor of chronic recurrent AP conduction requiring repeat ablation (odds ratio, 8.54; 95% confidence interval, 1.09-66.9; P=0.041). Adenosine can unmask dormant AP conduction after catheter ablation. Direct effects of adenosine on the AP, possibly via AP membrane potential hyperpolarization, are the dominant mechanism of adenosine-induced AP conduction after ablation. Dormant AP conduction is associated with higher rates of recurrent AP conduction requiring repeat ablation.

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.

Genome-wide association studies of the PR interval in African Americans.

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta = 5.1 msec per minor allele, 95% CI = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans.

A Randomized Invasive Cardiac Electrophysiology Study of the Combined Ion Channel Blocker AZD1305 in Patients After Catheter Ablation of Atrial Flutter

This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305. After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion. Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals. AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.

One-Dimensional Mathematical Model of the Atrioventricular Node Including Atrio-Nodal, Nodal, and Nodal-His Cells

Mathematical models are a repository of knowledge as well as research and teaching tools. Although action potential models have been developed for most regions of the heart, there is no model for the atrioventricular node (AVN). We have developed action potential models for single atrio-nodal, nodal, and nodal-His cells. The models have the same action potential shapes and refractoriness as observed in experiments. Using these models, together with models for the sinoatrial node (SAN) and atrial muscle, we have developed a one-dimensional (1D) multicellular model including the SAN and AVN. The multicellular model has slow and fast pathways into the AVN and using it we have analyzed the rich behavior of the AVN. Under normal conditions, action potentials were initiated in the SAN center and then propagated through the atrium and AVN. The relationship between the AVN conduction time and the timing of a premature stimulus (conduction curve) is consistent with experimental data. After premature stimulation, atrioventricular nodal reentry could occur. After slow pathway ablation or block of the L-type Ca 2+ current, atrioventricular nodal reentry was abolished. During atrial fibrillation, the AVN limited the number of action potentials transmitted to the ventricle. In the absence of SAN pacemaking, the inferior nodal extension acted as the pacemaker. In conclusion, we have developed what we believe is the first detailed mathematical model of the AVN and it shows the typical physiological and pathophysiological characteristics of the tissue. The model can be used as a tool to analyze the complex structure and behavior of the AVN.

Catheter-induced modulation of the electric conductivity of the atrioventricular node by high-frequency current

A radio-frequency current was delivered via a catheter to the atrioventricular (AV) node in 13 patients with supraventricular arrhythmias (maximal heart rate 215/min). In nine patients with atrial fibrillation, three with AV nodal re-entry tachycardia and one with AV re-entry tachycardia, AV node conduction time was prolonged from 95 +/- 43 ms to 168 +/- 72 ms. In three patients the radio-frequency current had no lasting effect, necessitating AV node ablation with a direct-current shock. During a mean observation period of five months, all ten patients in whom the radio-frequency current had been successfully applied remained free of symptoms without any anti-arrhythmia treatment. There were no complications during or after treatment.

Clinical and electrophysiological characteristics of patients having atrial flutter with 1:1 atrioventricular conduction

The purpose of this retrospective study was to assess characteristics of patients who had suffered atrial flutter (AFL) with 1:1 atrioventricular (AV) conduction (1:1 AFL). Subjects were 8 patients (61 +/- 14 years) with documented 1:1 AFL, and 101 AFL patients without a history of 1:1 AFL (control patients). 1:1 AFL occurred during physical activity with a ventricular rate of 218 +/- 18 bpm. Antiarrhythmic agents were administered to all eight 1:1 AFL patients, whereas AV nodal conduction-suppressing agents were administered to four. The maximum ventricular rate at which 1:1 AV conduction occurred was significantly lower than when spontaneous 1:1 AFL occurred (164 vs. 218 bpm, P < 0.05). The 1:1 AFL patients had a significantly longer AFL cycle length (CL) (292 vs. 258 ms, P < 0.05) and more rapid AV nodal conduction time (maximum 1:1 AV conduction: 375 vs. 464 ms, P < 0.05) than did control. Arrhythmia had occurred in patients with an AFL CL > or = 250 ms and a CL of maximum 1:1 AV conduction < or = 400 ms. Clinicians should be aware of the potential for 1:1 AV conduction in AFL patients, especially in those with remarkable prolongation of the CL in addition to enhanced AV conduction.

First postpacing interval after tachycardia entrainment with correction for atrioventricular node delay: A simple maneuver for differential diagnosis of atrioventricular nodal reentrant tachycardias versus orthodromic reciprocating tachycardias

The difference between the first postpacing interval (PPI) after tachycardia entrainment from the right ventricular apex and the tachycardia cycle length (TCL) can be used as an index of proximity to the circuit. The purpose of this study was to determine whether the response to entrainment of tachycardia during ventricular stimulation with correction for AV node delay is a useful, simple maneuver for differentiating AV nodal reentrant tachycardia (AVNRT) from orthodromic reciprocating tachycardia (ORT) using a concealed accessory pathway. The study consisted of 193 consecutive patients who underwent electrophysiologic study and ablation of regular paroxysmal supraventricular tachycardia without preexcitation during sinus rhythm. Tachycardia entrainment was attempted through trains of 5 to 15 right ventricular apex pacing pulses. The increment in AV nodal conduction time in the first PPI was subtracted from the PPI-TCL difference (corrected PPI-TCL). Electrophysiologic study demonstrated ORT in 84 patients and AVNRT in 109 patients. Transient entrainment was achieved in all but 12 patients. The mean corrected PPI-TCL difference was significantly shorter in 77 patients with ORT (66 +/- 27 ms) than in 104 AVNRT patients (151 +/- 28 ms; P <.0001). Patients with septal accessory pathways had shorter corrected PPI-TCL differences than patients with free-wall accessory pathways. The presence of a corrected PPI-TCL difference <110 ms identified all but one patient with ORT, and no patients with AVNRT had such a difference. The return cycle after tachycardia entrainment by right ventricular apex stimulation with correction for AV node delay is a rapid, useful maneuver for differential diagnosis of AVNRT vs ORT in patients without preexcitation. The presence of a corrected PPI-TCL <110 ms accurately identified with high reliability those patients with ORT.

Gender Differences in Electrophysiologic Effects of Mental Stress and Autonomic Tone Inhibition:

Gender differences exist in electrophysiologic properties and the occurrence of certain arrhythmias. Mental stress may trigger serious arrhythmias, including ventricular tachycardias and ventricular fibrillation. This study investigates gender differences in the electrophysiologic effects on different levels of the cardiac conduction system elicited by mental stress and autonomic tone inhibition. Twenty-three healthy volunteers (11 male and 12 female) participated in the study. Electrophysiologic and hemodynamic variables were measured at baseline, during mental stress produced by Stroop's color word conflict test (CWT), and after autonomic tone inhibition (ATI) with propranolol (0.15 mg/kg) and atropine (0.02 mg/kg). During CWT, men showed shorter QT and JT durations, whereas women had shorter refractoriness in the atrial tissue and AV node. After ATI, no gender differences in sinus nodal properties were noted, whereas AV nodal refractoriness and conduction time became shorter in women, and QT and JT duration and the refractory period of the right ventricle were shorter in men. In women, mental stress produces a pronounced effect on the AV node and on the sinus node. Men react with a more pronounced effect on ventricular electrophysiologic properties. Certain gender differences in cardiac electrophysiologic properties seem to be intrinsic. After ATI, women have a higher heart rate and shorter AV nodal refractoriness but longer QT and JT intervals and longer effective refractory periods in the right ventricle. These differences may partly explain why certain arrhythmias occur more often in women than in men.

Effects of Acute Systemic Endothelin Receptor Blockade on Cardiac Electrophysiology In Vivo

BQ-123, a selective endothelin-A receptor antagonist, has been demonstrated to suppress arrhythmias. However, the role of physiologic levels of endogenous endothelin-1 (ET-1) with respect to electrophysiologic properties of the heart is unknown. BQ-123 (0.45, 0.9, 1.8, 3.6, 7.2, and 14.4 microg/kg/min; n = 10) or saline (control, n = 5) was administered IV for 15 minutes of continuous-rate infusion at incremental doses to anesthetized normal pigs. BQ-123 had no effect on PR and QT interval, QRS duration, intraatrial and AV nodal conduction time as well as the atrial, AV nodal, and ventricular effective refractory periods. As compared with baseline, BQ-123 at 7.2 and 14.4 microg/kg/min caused an increase in heart rate (99 +/- 17 versus 110 +/- 14 and 118 +/- 14 bpm, respectively; P < 0.05), shortened sinus node recovery time (818 +/- 165 versus 641 +/- 69 and 609 +/- 74 milliseconds, respectively; P < 0.05) and decreased mean arterial pressure at 14.4 microg/kg/min (95 +/- 18 versus 80 +/- 11 mm Hg; P < 0.05). We conclude that in the normal pig, physiologic levels of ET-1 have no effect on conduction properties of atrial, AV nodal, or Purkinje fibers. However, antagonism of ET-1 by BQ-123 unmasks the effect of ET-1 on maintenance of vasomotor tone, which in turn may affect heart rate and sinus node automaticity in the intact pig.

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.

Free radicals potentiate the negative dromotropic effect of adenosine in guinea pig isolated heart

Objective — Adenosine is released during myocardial ischaemia and delays atrioventricular nodal (AV) conduction.We hypothesized that free radicals present during reperfusion potentiate the negative dromotropic effect of adenosine on the AV node.Methods and results — Guinea pig hearts were prepared using the Langendorff technique, paced (200 beats/min), and instrumented to measure the atrium-to-His bundle (A-H) interval, an index of AV nodal conduction time. Adenosine (2 μM) prolonged the A-H interval by 5.7±0.5 ms from a control value of 35.7±1.3 ms. (n = 10, P<0.05). In the absence of adenosine, the superoxide (O2-) generator pyrogallol (20 μM) did not affect the A-H interval (0.7±0.2 ms prolongation, n = 10). However, concurrent infusion of adenosine (2 μM) and pyrogallol (20 μM) lengthened the A-H interval by 11.0±0.8 ms from control (n = 10, P<0.001). This A-H interval prolongation was reversed by cyclopentyl-1,3-dipropylxanthine (100 nM), a selective A1-adenosine receptor antagonist (P<0.001, n = 5). Similarly, A-H interval prolongation was decreased to 4.3±0.4 ms when NG-methyl-L-arginine (100 μM), a nitric oxide (NO) synthase inhibitor, was infused (n = 4).The superoxide scavenger superoxide dismutase (200 U/ml) also diminished the A-H interval prolongation to 7.1±0.6 ms (n = 4, P<0.001). Ba2+ (100 μM), a blocker of the adenosine-induced inward potassium current (IK, ADO), did not significantly affect this potentiation (13.0±0.8 and 10.8±0.7 ms greater than control A-H interval in the absence and presence of Ba2+, respectively, n = 4).Conclusions — Superoxides and adenosine delay AV nodal conduction in a synergistic manner via a NO-dependent mechanism involving an IK, ADO-independent component. This phenomenon may contribute to the genesis of reperfusion arrhythmias.

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.

Perioperative atrial tachyarrhythmias.

Perioperative atrial tachyarrhythmias.

Electrophysiologic characteristics of diverse accessory pathway locations of antidromic reciprocating tachycardia

This study assessed antidromic reciprocating tachycardia (ART) in patients with paraseptal accessory pathways (APs). Previous clinical experience suggests that paraseptal APs are unable to serve as the anterograde limb during ART. Based on the reentry wavelength concept, we hypothesized that anatomic location of a paraseptal AP may not preclude occurrence of ART. If wavelength criteria were met due to prolonged conduction time retrogradely in the atrioventricular node or anterogradely in the AP, ART may be sustained. All patients who had ART in the electrophysiologic laboratory at our institution (1991 to 1998) were studied. Based on fluoroscopically guided electrophysiologic mapping and radiofrequency ablation, AP location was classified as paraseptal, posterior, or lateral. Conduction time and refractoriness measurements were made for all components of the ART circuit. Of 24 patients with ART, 5 (21%) had ART utilizing a paraseptal AP. Anterograde conduction time through the AP and retrograde atrioventricular nodal conduction time were significantly longer in patients with paraseptal versus lateral pathways. Isoproterenol was required for ART induction in 38% of patients with a posterior AP, 36% with lateral AP location, but not in patients with a paraseptal AP. There were no significant differences in tachycardia cycle length or refractoriness of anterograde and/or retrograde components of the macroreentry circuit between the 3 pathway locations. Thus, ART can occur in patients with a paraseptal AP. Slower anterograde pathway conduction, or retrograde atrioventricular nodal conduction renders the wavelength critical for completion of the antidromic reentrant circuit.