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Nitric oxide synthase containing nerves in the atrioventricular node of the guinea pig heart.

Immunoelectron microscopy was performed to localize immunoreactivity for nitric oxide synthase (NOS) in the guinea-pig atrioventricular node. Many small ganglia were found in the interatrial septum near the atrioventricular node. A small number of neurons in these ganglia were immunoreactive. NOS immunoreactive axons were observed in nerve bundles near or within the node. Very thick immunoreactive axons, 8-10 microns in diameter, were found between the conductive tissue and the ordinary cardiac muscles. Electron-microscopic examination confirmed that these axons were unmyelinated. Nerve bundles in this region contained both myelinated and unmyelinated axons; however, immunoreactivity was detected exclusively in unmyelinated axons. Fine NOS-immunoreactive nerve fibers with terminal varicosities were often seen in the atrioventricular node. Close contact between NOS-immunoreactive axon varicosity and specialized cardiac muscle cell was observed. Intranodal ganglia were observed among the specialized cardiac muscles. They were surrounded by numerous axons, some of them were immunoreactive. Direct axo-somatic synapses from NOS-immunoreactive terminals to the intranodal ganglion cells were observed. The present results indicate a possibility that nitric oxide plays a role in the neural control of the conductive tissue in the heart through direct neuromuscular contact.

Amino Acid Oxidoreductases↗

Electrophysiologic actions of aprindine in rabbit atrioventricular node.

Aprindine hydrochloride is a potent antiarrhythmic agent against various atrial and ventricular tachyarrhythmias. To elucidate its pharmacological actions in the atrioventricular node, electrophysiologic experiments were conducted by applying microelectrode and voltage clamp methods to small preparations of the rabbit atrioventricular node. At a concentration 1 mumol/l, aprindine decreased the spontaneous firing frequency, maximal rate of depolarization, action potential amplitude, and take-off potential (P less than 0.05, n = 7). The spontaneous and rate-controlled action potential durations at 50 and 100% repolarization were prolonged by aprindine. Voltage-clamp experiments using the double microelectrode method revealed that aprindine blocked the slow inward current (Isi) in a voltage-dependent manner with a dissociation constant of 10 mumol/l and Hill coefficient of 0.8. The steady-state inactivation curve for Isi was shifted toward more negative potentials by 2.5 +/- 0.9 mV (P less than 0.05, n = 5) without a significant change in the slope factor. This finding suggests that aprindine has a higher affinity for inactivated slow inward (or Ca2+) channels than for resting channels. Aprindine caused use-dependent block of Isi, a result consistent with the drug's slow dissociation from inactivated Ca2+ channels. The delayed rectifying K+ current (IK) tail obtained on repolarization from +10 mV to -60 mV was significantly decreased from 15.4 +/- 2.4 to 6.8 +/- 1.4 nA (P less than 0.01, n = 6) and the deactivation time constant significantly increased by 20.7% (P less than 0.01, n = 6). The steady-state activation curve for IK was shifted in the hyperpolarized direction by 6.9 +/- 2.9 mV, suggesting a potent voltage-dependent block of this current by aprindine. The hyperpolarization-activated inward current (Ih) was decreased from 14.4 +/- 5.4 to 12.0 +/- 5.5 nA (P less than 0.05, n = 5). The transient outward and inward currents induced by 1 mumol/l acetylstrophanthidin were almost completely suppressed after the addition of 1 mumol/l aprindine. These results suggest that aprindine exerts a negative chronotropic action both by slowing deactivation of IK and by reducing Isi and Ih, and delays atrioventricular nodal conduction by reducing Isi and IK. These blocking actions of aprindine together with its inhibition of the transient outward and inward currents may explain its antiarrhythmic effects on the atrioventricular node.

Action Potentials↗

Characterisation of beta 1 and beta 2 adrenoceptor subtypes in the atrioventricular node of diabetic rat hearts by quantitative autoradiography.

STUDY OBJECT: The aim was to determine whether the changes in beta adrenoceptors might be involved in the conduction system of diabetic rat hearts. DESIGN: beta Adrenoceptors in the atrioventricular node of diabetic hearts and controls were characterised by quantitative autoradiography. EXPERIMENTAL MATERIAL: The experiments were performed in five male Wistar rats injected with streptozotocin (65 mg.kg-1) to induce diabetes and in five rats injected with vehicle alone. MEASUREMENTS AND MAIN RESULTS: 125I-iodocyanopindolol binding sites decreased by 25% in atrioventricular node of diabetic hearts compared to control hearts without a significant change in the affinity. The selective beta 1 adrenoceptor antagonist CGP20712A (100 nmol.litre-1) displaced about 30% and 50% of the total atrioventricular node binding sites in diabetic and control hearts, respectively. CONCLUSIONS: These data support the concept that a decrease in beta adrenoceptors, mainly of the beta 1 subtype, in the atrioventricular node may play an important role in the cardiac conduction disturbance of diabetic animals.

Animals↗

Cryosurgical ablation of fetal atrioventricular node: new model to treat fetal malignant tachyarrhythmias.

BACKGROUND: Sustained tachyarrhythmia resulting in fetal hydrops is often refractory to medical therapy. Fetal atrioventricular node ablation associated with epicardial fetal pacing has the potential to be an effective procedure for this morbid association. METHODS: To assess the feasibility of therapeutic fetal heart block, we developed a technique of intrauterine cryosurgical ablation of fetal atrioventricular node without the need for cardiac bypass in 8 fetal lambs. Complete heart block was obtained by applying the cryoprobe over the coronary sinus. Fetal pacing was then performed to allow fetal survival. RESULTS: Complete heart block was achieved in 100% of the fetal lambs. Postoperative evaluation revealed persistent atrioventricular block. The hearts were studied at different postoperative times. Morphologic evaluation of the area containing the cryosurgical lesion revealed varied extension of necrosis of the atrioventricular node and hemorrhage, with involvement of the His bundle and proximal right bundle branch. CONCLUSIONS: This procedure is technically feasible and offers an alternative approach to the treatment of drug-resistant, life-threatening fetal supraventricular tachyarrhythmias associated with hydrops fetalis.

Animals↗

Origin of so-called mesothelioma of the atrioventricular node. An immunohistochemical study.

To determine the origin of a mesothelioma of the atrioventricular node, immunohistochemical studies that used various antibodies, including the antibody against mesothelial cells, were performed on a mesothelioma of the atrioventricular node in a case. The lining cells of the tubules that composed the tumor were negative when tested with anti-mesothelial cell antibodies. Carcinoembryonic antigen was negative, but the secretory component was positive. Serotonin and calcitonin were positive in a few cells. We concluded that a mesothelial origin was unlikely, and it was suggested that the tumor was of an entodermal origin.

Atrioventricular Node↗

Neuroma in the region of the atrioventricular node.

A three month old infant died of apparent sudden infant death syndrome. Autopsy showed a neuroma in the region of the atrioventricular node, unassociated with neurofibromatosis. The atrioventricular node and bundle of His were normal. It was not possible to ascribe the sudden death to the neuroma.

Atrioventricular Node↗

Ventricular pacing vs dual chamber pacing in patients with persistent atrial fibrillation after atrioventricular node ablation: open randomized study.

AIM: To compare ventricular rate responsive (VVIR) pacing with dual chamber rate responsive (DDDR) pacing and antiarrhythmic drugs for the treatment of patients with persistent atrial fibrillation after atrioventricular node ablation. METHODS: One hundred two patients with persistent atrial fibrillation eligible for the atrioventricular node ablation were randomly assigned to the therapy with either VVIR pacemaker (n=52) or DDDR pacemaker and antiarrhythmic drugs (n=50). After ablation, patients in both pacing groups were assigned to take anticoagulant therapy. The primary end point was stroke or death from cardiovascular causes. RESULTS: After a mean follow-up of 26.6+/-9.5 months, there was no difference in the stroke or death rates between patients with VVIR pacing (6 or 5.2% per year) and those with DDDR pacing and antiarrhythmic drugs (6 or 5.9% per year, P=0.930). The observed rates of death from all causes, hospitalization for heart failure, and myocardial ischemia were similar in the two patient groups. There was a significantly lower rate of development of permanent atrial fibrillation in patients with DDDR pacing and antiarrhythmic drugs, with a reduction in absolute risk by 56% and relative risk by 64% (32% vs 88%; P<0.001). CONCLUSION: With respect to cardiovascular death and morbidity, VVIR pacing is not inferior to DDDR pacing and antiarrhythmic drugs for the treatment of patients with persistent atrial fibrillation after atrioventricular node ablation and may be considered as an appropriate therapy for such patients.

Atrial Fibrillation↗

Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction.

Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) < or =40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 +/- 10 years; 45 men), LVEF was 26% +/- 8% and 34% +/- 13% (p <0.001) before and after ablation, respectively. During follow-up (40 +/- 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (> or =45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.

Aged↗

[The development of the atrioventricular node and bundle of His in the human embryonic period].

To study the development of the atrioventricular specific system, together with the closely related mesenchymal tissue (from which the fibrous skeleton of the heart later develops). Thirty human embryos ranging from 3 mm to 30 mm crown-rump length (Carnegie stages 10-23) were used. The primordium of the atrioventricular specific system was observed for the first time in human embryos of 10 mm Crown-Rump length (Carnegie stage 16) as a cellular aggregate located below the inferior endocardial cushion. The primordium cells originate from the myocardium of the posterior wall of the atrioventricular canal. The primordium later forms both the atrioventricular node and the His bundle. The mesenchymal tissue which surrounds these features originates from the endocardial cushions (particularly from the inferior endocardial cushion). Todaro's tendon and the central fibrous body are later formed from the inferior endocardial cushion. The atrioventricular node and His bundle are both formed from the primordium of the atrioventricular specific system. The node is produced from the cranial-dorsal extension of the primordium while the His bundle is produced from the growth of the primordium in a ventral-caudal direction. The central fibrous body is anatomically defined in the stages post-dating morphogenesis of the atrioventricular specific system.

Atrioventricular Node↗

Limitation of tachycardia zone resulting from longitudinal dissociation of the atrioventricular node in concealed pre-excitation.

Two cases with a concealed left-sided accessory atrioventricular bypass tract are described. In both, functional longitudinal dissociation of the atrioventricular node narrowed the range of atrial premature beat coupling intervals which could initiate re-entry using the accessory pathway. In case 1 early premature atrial beats were followed by an atrioventricular nodal re-entrant echo. The atrial echo pre-empted retrograde conduction over the Kent bundle and thus limited the development of paroxysmal supraventricular tachycardia. In case 2 atrioventricular nodal conduction showed typical features ascribed to dual atrioventricular nodal pathways. In addition there was a bradycardia-related retrograde block in the concealed accessory pathway. Early premature atrial beats, because of exclusive "slow pathway" anterograde conduction, arrived at the ventricles during the period of bradycardia-dependent retrograde block and failed to initiate a macro re-entrant tachycardia. This study shows that (1) longitudinal dissociation within the atrioventricular node may limit the ability to initiate tachycardia in patients with concealed pre-excitation; and (2) discontinuous atrioventricular nodal conduction curves occasionally help to reveal bradycardia-related retrograde block in a concealed accessory pathway.

Arrhythmias, Cardiac↗

Temperature and impedance monitoring during radiofrequency catheter ablation of slow AV node pathway in patients with atrioventricular node reentrant tachycardia.

This study was designed to observe the changes of temperature and impedance and to find the role of temperature control in radiofrequency ablation of slow pathways in patients with AV node reentrant tachycardia. Power, impedance and temperature were measured during each application of radiofrequency energy while the generator was operated in the power control mode. A total of 760 applications were delivered in 76 patients. The success rate was 100% without recurrence during a follow-up period of 8 +/- 3 months. The mean catheter tip temperature associated with successful ablation was 51.3 +/- 5.4 degrees C (range 45 degrees C to 64 degrees C), and significantly higher than the unsuccessful pulses (48.7 +/- 6.2 degrees C, P < 0.05). The mean temperature was 49.8 +/- 3.1 degrees C during accelerated junctional rhythm, significantly higher than the pulses without this rhythm. The mean temperature correlated well with early decrease of impedance (r = 0.71, P < 0.001), and an early decrease of impedance more than 5 ohms had an 87% positive predictive value for adequate tissue heating. These data suggested that, if temperature monitoring was available, setting the target temperature at about 51 degrees C could achieve adequate tissue heating for successful ablation of slow pathway; if not, impedance monitoring with an early decrease of impedance < 5 ohms could predict adequate tissue heating.

Catheter Ablation↗

[Polycystic endodermal heterotopy of the atrioventricular node].

We present the two first Spanish cases about the endodermic heterotopia of the atrioventricular node. This is an infrequent and probably congenital lesion, with a not well known histogenesis and associated with heart blocks and sudden death, which affects women in most cases. The first observation attaches a 55 years-old woman with an acute leukemia who died during the first chemotherapy treatment. The second observation affects a 25 years-old woman, with previous heart blocks, who died suddenly. A complete post-mortem study was done in both cases (including cardiac conduction system) with conventional histopathological study and extensive immunohistochemical panel. Ultrastructural study of first case was done. In both cases a multicystic and tubular lesion was found in the atrioventricular node region. It was lined by two or more cubic and polyhedral cell layers. In the cystic lumina an eosinophilic material, which corresponded to acid and neutral mucosubstances was found. The maximal lesion's diameter were: 0.9 and 1.3 cm, respectively. Immunohistochemically it was detected in both cases strong positivity for cytoqueratines, EMA, CEA and focally for chromogranin A and calcitonin. The immunohistochemical results in both cases express and endodermic differentiation (with neuroendocrine fenotipe).

Adult↗

Endocardial stimulation of efferent parasympathetic nerves to the atrioventricular node in humans: optimal stimulation sites and the effects of digoxin.

UNLABELLED: The purposes of this study were to identify optimal sites of stimulation of efferent parasympathetic nerve fibers to the human atrioventricular node via an endocardial catheter and to investigate the interaction between digoxin and vagal activation at the end organ. METHODS: The ventricular rate was measured during atrial fibrillation, prior to and during parasympathetic nerve stimulation, in 8 patients taking digoxin and in 10 controls. High frequency electrical stimuli were delivered via an hexapolar or quadripolar electrode catheter, placed at the posteroseptal right atrium near the atrioventricular node (n=18 patients) or in the coronary sinus (n=12 of 18 patients). In 4 patients, stimulation was repeated after intravenous administration of 1 to 2 mg of atropine. RESULTS: Nerve stimulation prolonged the R-R interval in all patients. Stimulation close to the posteroseptal right atrium led to maximal atrioventricular nodal slowing. The mean R-R intervals at baseline and during parasympathetic nerve stimulation (60 mA) from the posteroseptal right atrium and the proximal coronary sinus were 581+/-79 ms, 2440+/-466, and 900+/-228 ms respectively (p=0.0001). The response to nerve stimulation was greater in patients taking digoxin than in patients not taking the drug (p=0.02). Junctional rhythm occurred during nerve stimulation in 8/8 patients taking digoxin and 0/10 not taking the drug (p=0.0001). The response to stimulation was eliminated after atropine (p=0.01). CONCLUSIONS: Parasympathetic nerves to the atrioventricular node were stimulated from the proximal coronary sinus as well as the posteroseptal right atrium. Stimulation at the posteroseptal right atrium resulted in the greatest response, and digoxin enhanced this response. The augmented response suggests that an interaction may exist between parasympathetic stimulation and digoxin at the end organ.

Aged↗

Plasma cell leukemia accompanied by polyclonal gammopathy and congenital tumor in the atrioventricular node.

A 32-year-old man with plasma cell leukemia and congenital tumor of the atrioventricular node is described. Although M protein could not be detected by immunoelectrophoresis, the examination of bone marrow atypical plasma cells with immunofluorescent and immunoperoxidase showed that most of these plasma cells produced IgG or IgA. Also some plasma cells possessed concomitantly both IgG and IgA. An electrocardiogram revealed complete atrioventricular block. The patient died of aspergillosis and bleeding in the lung. Postmortem examination revealed the infiltration of atypical plasma cells in the bone marrow, spleen, liver and lungs, and infiltration of mesothelial tumor cells in the atrioventricular node.

Adult↗

Properties and substrate of slow pathway exposed with a compact node targeted fast pathway ablation in rabbit atrioventricular node.

INTRODUCTION: The properties and substrates of slow and fast AV nodal pathway remain unclear. This applies particularly to the slow pathway (SP), which is largely concealed by fast pathway (FP) conduction. We designed a new FP ablation approach that exposes the SP over the entire cycle length range and allows for its independent characterization and ablation. METHODS AND RESULTS: Premature stimulation was performed before and after FP ablation with 5.4 +/- 1.9 lesions (300-microm diameter each; overall lesion size 1.4 +/- 0.5 mm) targeting the junction between perinodal and compact node tissues in seven rabbit heart preparations. The resulting SP recovery curve and control curve had the same maximum nodal conduction time (165 +/- 22 msec vs 164 +/- 24 msec; P = NS) and effective refractory period (101 +/- 10 msec vs 100 +/- 9 msec; P = NS). The two curves covered the same cycle length range. However, the SP curve was shifted up with respect to control one at intermediate and long cycle lengths and thus showed a longer minimum nodal conduction time (81 +/- 15 msec vs 66 +/- 10 msec; P < 0.01) and functional refractory period (180 +/- 11 msec vs 170 +/- 12 msec; P < 0.05). The SP curve was continuous and closely fitted by a single exponential function. Small local lesions (2 +/- 1) applied to the posterior nodal extension resulted in third-degree nodal block in all preparations. CONCLUSION: The posterior nodal extension can sustain effective atrial-His conduction at all cycle lengths and account for both the manifest and concealed portion of SP. Slow and FP conduction primarily arise from the posterior extension and compact node, respectively.

Animals↗

The spontaneous action potential of rabbit atrioventricular node cells.

The rabbit atrioventricular (A-V) node, with dimensions of approximately 5 X 3 mm was dissected into 15 small specimens (0.5 X 0.5 mm). A majority of the specimens continued to discharge spontaneous action potentials, the action potential configuration being almost identical in different specimens. The amplitude (98 mV) and the maximum rate of rise of the action potential (11 V/sec) were similar to those recorded from the intact A-V node (amplitude 98 mV, maximum rate of rise of action potential 12 V/sec). In these small specimens, the "resting membrane potential (-44 mV)" was approximately 20 mV less negative than that in the intact A-V node preparation (-62 mV) before the dissecting procedure. The spontaneous discharge in these small A-V node specimens was attributed to the low resting membrane potential. The small specimen became inexcitable under the effects of blockers of is, though TTX had no significant effect on the action potential. The after-hyperpolarization was observed after cessation of the depolarizing current pulse. It is concluded that the slow inward current and the slow kinetics of the outward current contribute to the generation of the spontaneous A-V node action potentials as in the sinoatrial node.

Action Potentials↗