Discrete radiofrequency lesion at the atrial insertion site of the tendon of Todaro in the perfused rabbit preparation lengthens A-H interval, mimicking fast pathway input ablation. This study attempts to define the cellular electrophysiology of the ablation region prior to and after the elimination of fast AV node conduction. In six superfused rabbit AV node preparations, the cellular electrophysiology around the region of the atrial insertion to the tendon of Todaro was recorded using standard microelectrode technique prior to and after ablation. Before ablation, the action potentials recorded in the area of proposed lesion were exclusively from atrial or AN cells. At postablation, the superior margin of the lesion was populated with atrial or AN cells. AN, N, or NH cells bordered the lower part of the lesion. Electrophysiology of surviving cells at the edges of the lesion showed no significant changes in their Vmax, APD50 or APD90 and MDP from preablation values. Fast AV node pathway input ablation in the rabbit heart can be accomplished with a singular lesion around the atrial insertion site of the tendon of Todaro, involving atrial or AN cells. The results of the studies imply that inputs to the compact node may act as a substrate for successful ablation of AV node reentry tachycardia.
Action Potentials/physiology ; Animal ; Atrioventricular Node/surgery* ; Atrioventricular Node/physiology ; Atrioventricular Node/cytology* ; Catheter Ablation/methods* ; Electrophysiology ; Rabbits ; Recovery of Function ; Tachycardia, Supraventricular/surgery ; Tachycardia, Supraventricular/physiopathology

BACKGROUND AND OBJECTIVES: In cases of radiofrequency catheter ablation (RFCA) for patients with atrioventricular nodal re-entrant tachycardia (AVNRT), complete elimination of slow pathway is not always achievable. Furthermore, in situations of the so-called modified slow pathway, the underlying mechanism of tachycardia elimination remains unclear. SUBJECTS AND METHODS: Patients who underwent RFCA for AVNRT, and showed persistence of dual atrioventricular nodal physiology but no induction of AVNRT after ablation were enrolled. We measured electrophysiologic parameters before and after the ablation procedure. RESULTS: The study subjects included 31 patients (39% men; mean age 43±19 years). The RR interval, Wenckebach cycle length of AV node, slow pathway effective refractory period, maximal AH interval of fast pathway and slow pathway showed no significant changes before and after ablation. However, fast pathway effective refractory period (360±67 vs. 304±55, p<0.001) and differences between slow pathway effective refractory period and fast pathway effective refractory period (90±49 vs. 66±35, p=0.009) were decreased after slow pathway ablation. CONCLUSION: We suggest a possible relationship between the mechanism of tachycardia elimination in AVNRT and an alteration of the re-entrant circuit by removal of the atrial tissue in Koch's triangle. This may be a critical component of providing the excitable gap for the maintenance of tachycardia rather than the electrical damage of slow pathway itself.
Atrioventricular Node* ; Catheter Ablation ; Humans ; Male ; Physiology* ; Tachycardia*

BACKGROUNDAdvances in catheter ablation procedures for the treatment of supraventricular arrhythmias have created the need to understand better the morphological and electrophysiological characteristics of the inferior nodal extension (INE) and transitional cellular band (TCB) in the atrioventricular (AV) junctional area.

METHODSFirstly, we observed the histological features of 10 rabbit AV junctional areas by serial sections under light microscopy. Then we recorded the action potentials (APs) of transitional cells (TCs) in the INE, TCBs, AV node, and ordinary right atrial myocytes from the AV junctional area of 30 rabbits using standard intracellular microeletrode techniques.

RESULTSUnder light microscopy, the INE appeared to be mostly composed of transitional cells linking upward to the AV node. Four smaller TCBs originated in the orifice of the coronary sinus, the region between the septal leaflet of the tricuspid valve and the coronary sinus, the inferior wall of the left atrium, and the superior interatrial septum, respectively, all linking to the INE or the AV node. Compared with ordinary atrial myocytes, the AP of the TCs in both the INE and the TCBs had a spontaneous phase 4 depolarization (not present in ordinary atrial myocytes), with a less negative maximum diastolic potential, a smaller amplitude, a slower maximum velocity of AP upstroke, and a longer action potential duration at 50% repolarization (APD50) and at 30% repolarization (APD30). The AP characteristics of these TCs were similar to those of the AV node, except that the velocities of the phase 4 spontaneous depolarization were slower and their action potential durations at 90% repolarization (APD90) were shorter. Moreover, APD50 and APD30 of the TCs of the TCBs were shorter than in the case of TCs of the AV node.

CONCLUSIONSThe TCs of the INE and TCBs are similar to slow response automatic cells. They provide a substrate for slow pathway conduction. In addition, repolarization heterogeneity exists in the AV junctional area.

Action Potentials ; Animals ; Atrioventricular Node ; cytology ; physiology ; Female ; Male ; Rabbits

BACKGROUNDThe morphological and electrophysiological characteristics of cardiac cells in Koch triangle are still disputed. We studied the appearance and electrical properties of these diverse myocytes to elucidate their complex electrophysiological phenomena.

METHODSExperiments were conducted using cooled charge coupling device (CCD) system and whole cell, patch clamp technique to determine the morphology, action potential and sodium current density of single viable myocytes enzymatically isolated from the Koch triangle of rabbit hearts.

RESULTSMorphologically, cardiac cells in shape of spider, tiny spindle, slender spindle, rod and strip were observed in percentage of 3.0 +/- 0.3, 35.0 +/- 5.0, 15.0 +/- 2.0, 40.0 +/- 5.0 and 6.0 +/- 0.7 respectively. The cellular dimensions and capacitance gradually increased in the above order (all P < 0.05). Electrophysiologically, action potential configurations recorded from them were similar respectively to nodal (N), atrial nodal (AN), nodal Hisian (NH), atrial (A) and Hisian like potentials obtained from the intact atrioventricular nodal preparations. Diastolic depolarization appeared in all myocytes except for rod cells. Sodium current density increased in the order of tiny spindle, strip, rod, slender spindle cell (all P < 0.05), but could not be detected in spider-shaped cells. Linear regression analysis revealed that membrane capacitance was correlated negatively to the rate of diastolic depolarization r = -0.70, P < 0.001, but positively to maximum depolarization potential, amplitude of action potential, upstroke velocity and maximum peak value of sodium current density r = 0.84, 0.80, 0.87 and 0.75, respectively; all P < 0.001.

CONCLUSIONSThe results demonstrated that spider-shaped, spindle, rod and strip cells in Koch triangle might correspond to pacemaking, transitional, atrial and Purkinje like cells, respectively. Furthermore, tiny spindle and slender spindle cells were referred to transitional cell alpha (TCalpha) and beta (TCbeta) accordingly considering their distinctive electrical properties. Different myocytes with diverse electrical properties constituted the infrastructure of sophisticated electrophysiological phenomena in Koch triangle. In view of the prominent percentage and electrical properties, tiny spindle and slender spindle cells were presumed to play important roles.

Action Potentials ; Animals ; Atrioventricular Node ; cytology ; physiology ; Female ; Male ; Myocytes, Cardiac ; cytology ; physiology ; Rabbits ; Sodium Channels ; physiology

The purpose of this study was to determine the electrophysiological effects of genistein (GST) on spontaneous activity of atrioventricular (AV) node and the underlying mechanism(s). Action potentials in AV node cells were recorded using intracellular microelectrode technique. GST not only reduced the amplitude of action potential (APA), maximal rate of depolarization (V(max)), velocity of diastolic (phase 4) depolarization (VDD), and rate of spontaneous firing (RSF), but also prolonged 90% duration of action potential (APD(90)) in a concentration-dependent manner. The effects of GST (50 micromol/L) could be blocked completely by pretreatment with Bay K8644 (0.25 micromol/L), an agonist of L-type calcium channel. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 0.5 mmol/L), a nitric oxide (NO) synthase inhibitor, did not affect the effects of GST on AV node cells. Elevation of Ca(2+) concentration (5 mmol/L) in superfusate antagonized the effects of GST (50 micromol/L). These results suggest that GST exerted a negative electrophysiological effects of spontaneous activity of AV node cells in rabbits. These effects were likely due to reduction in calcium influx, but had no association with NO release.
Action Potentials ; drug effects ; Animals ; Atrioventricular Node ; cytology ; physiology ; Calcium Channels ; drug effects ; Dose-Response Relationship, Drug ; Genistein ; pharmacology ; Male ; Phytoestrogens ; pharmacology ; Rabbits

Arrhythmia, Sinus ; physiopathology ; Arrhythmias, Cardiac ; physiopathology ; surgery ; Atrioventricular Node ; anatomy & histology ; physiology ; Catheter Ablation ; Electrophysiologic Techniques, Cardiac ; Electrophysiology ; Heart ; anatomy & histology ; physiology ; Heart Atria ; anatomy & histology ; Heart Conduction System ; physiology ; Humans ; Models, Cardiovascular ; Wolff-Parkinson-White Syndrome ; physiopathology

BACKGROUNDMutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease. This study aimed to determine the expression and localization of connexins in neonatal myocytes transfected with wild-type (WT) or mutant LMNA to elucidate how these mutations cause heart diseases.

METHODSWe studied the connexin 43 (Cx43) and connexin 40 (Cx40) expression in cultured neonatal myocytes transfected with wild-type (WT) or mutant LMNA (Glu82Lys (E82K) and Arg644Cys (R644C)) using confocal imaging and Western blotting analysis.

RESULTSCx43 protein expression was reduced by 40% in cells transfected with LMNA E82K than that in cells transfected with WT LMNA cDNA. Confocal imaging showed that the Cx43 located inside the cells by LMNA E82K. By contrast, LMNA E82K mutation had no effect on expression and localization of Cx40. LMNA R644C transfection did not show any significant effects on gap junctions at all.

CONCLUSIONSOur findings suggest that LMNA E82K significantly reduced the Cx43 expression and altered its localization which may be one of the pathological mechanisms underlying LMNA-related heart disease.

Animals ; Atrioventricular Node ; pathology ; Blotting, Western ; Cardiomyopathy, Dilated ; metabolism ; pathology ; Cells, Cultured ; Connexin 43 ; metabolism ; Connexins ; metabolism ; Fluorescent Antibody Technique ; Gap Junctions ; metabolism ; Humans ; Lamin Type A ; genetics ; physiology ; Mutation ; Rats ; Transfection

The electrophysiological effects of nitric oxide (NO) on spontaneous activity of rabbit atrioventricular (AV) node cells were examined using intracellular microelectrode technique. The results obtained are as follows. (1) NO donors sodium nitroprusside (SNP, 1~1000 micromol/L) and 3-morpholinosydnonimine (SIN-1, 100, 1000 micromol/L) decreased the amplitude of action potential (APA), rate of spontaneous firing (RSF), velocity of diastolic (phase 4) depolarization (VDD), and maximal rate of depolarization (V(max)) in a concentration-dependent manner. (2) Pretreatment with L-type calcium channel agonist Bay K8644 (0.25 micromol/L) completely reversed the effects of SNP (100 micromol/L) on AV node cells. (3) Elevation of Ca(2+) concentration (5 mmol/L) in superfusate antagonized the effects of SNP on AV node cells. (4) Perfusion with Ca(2+)-free K-H solution, completely abolished the effects of SNP on AV node cells. (5) Application of methylene blue (50 micromol/L), a guanylyl cyclase inhibitor, failed to abolish the inhibitory effects of SNP (100 micromol/L). All these results suggest that NO exerts a negative effect on spontaneous activity of AV node cells in rabbits. These effects are likely due to reduction in calcium influx via a cGMP-independent mechanism.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Action Potentials ; drug effects ; Animals ; Atrioventricular Node ; cytology ; physiology ; Calcium ; metabolism ; Calcium Channel Agonists ; pharmacology ; Calcium Channels, L-Type ; metabolism ; Depression, Chemical ; Female ; Male ; Microelectrodes ; Nitric Oxide ; physiology ; Rabbits

To study the electrophysiological effects of capsaicin on spontaneous activity of rabbit atrioventricular (AV) node cells, parameters of action potential in AV node were recorded using intracellular microelectrode technique. Capsaicin (1-30 micromol/L) not only decreased the amplitude of action potential, maximal rate of depolarization (V(max)), velocity of diastolic (phase 4) depolarization, and rate of pacemaker firing, but also prolonged the duration of 90% repolarization of action potential (APD(90)) in a concentration-dependent manner. Both application of L-type Ca(2+) channel agonist Bay K8644 (0.5 micromol/L) and elevation of calcium concentration (5 mmol/L) in superfusate antagonized the effects of capsaicin on pacemaker cells. Pretreatment with ruthenium red (10 micromol/L), a capsaicin receptor blocker, did not affect the effects of capsaicin on AV node cells. Capsaicin exerted an inhibitory action on spontaneous activity of AV node cells in rabbits. These effects were likely due to reduction in calcium influx, but were not mediated by VR1.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Action Potentials ; drug effects ; Animals ; Atrioventricular Node ; cytology ; physiology ; Calcium ; metabolism ; Calcium Channel Agonists ; pharmacology ; Calcium Channels, L-Type ; drug effects ; Capsaicin ; pharmacology ; Male ; Microelectrodes ; Rabbits ; Receptors, Drug ; antagonists & inhibitors ; Ruthenium Red ; pharmacology