Background-There is an effort to build an anatomically and biophysically detailed virtual heart, and, although there are models for the atria and ventricles, there is no model for the sinoatrial node (SAN

Abstract-During failure of the sinoatrial node, the heart can be driven by an atrioventricular (AV) junctional pacemaker.The position of the leading pacemaker site during AV junctional rhythm is debated. In this study, we present evidence from high-resolution fluorescent imaging of electrical activity in rabbit isolated atrioventricular node (AVN) preparations that, in the majority of cases (11 out of 14), the AV junctional rhythm originates in the region extending from the AVN toward the coronary sinus along the tricuspid valve (posterior nodal extension, PNE). Histological and immunohistochemical investigation showed that the PNE has the same morphology and unique pattern of expression of neurofilament160 (NF160) and connexins (Cx40, Cx43, and Cx45) as the AVN itself. Block of the pacemaker current, I f , by 2 mmol/L Cs ϩ increased the AV junctional rhythm cycle length from 611Ϯ84 to 949Ϯ120 ms (meanϮSD, nϭ6, PϽ0.001). Immunohistochemical investigation showed that the principal I f channel protein, HCN4, is abundant in the PNE. As well as the AV junctional rhythm, the PNE described in this study may also be involved in the slow pathway of conduction into the AVN as well as AVN reentry, and the predominant lack of expression of Cx43 as well as the presence of Cx45 in the PNE shown could help explain its slow conduction. Key Words: ablation Ⅲ electrophysiology Ⅲ surgery Ⅲ arrhythmia Ⅲ imaging S ince Tawara's discovery of the atrioventricular node (AVN) nearly a century ago, 1 anatomists and electrophysiologists have established that the AVN is the only conduction pathway between the atria and ventricles in the normal heart. 2 The AVN has unique slow and frequencydependent conduction properties. 2 Under normal physiological conditions, the AVN determines the appropriate frequency-dependent delay of conduction between the atria and ventricles and, during atrial fibrillation, the AVN filters high-frequency excitation, thus protecting the ventricular myocardium. 3 The AVN has dual inputs (fast and slow pathways) from the atrial myocardium and this may be the substrate for AVN reentry. 4,5 The AVN also has pacemaking ability: during failure of the sinoatrial node, the heart can be driven by an atrioventricular (AV) junctional pacemaker, although the position of the leading pacemaker site is debated. 6,7 Recent application of fluorescent imaging with voltagesensitive dyes 5,8 -12 has provided new insights into the electrophysiology of the AV junction. With fluorescent imaging, we have recently shown how the fast and slow pathways of conduction support normal conduction, 9 AVN echo, 5 and AVN reentry. 12 Application of immunohistochemical imaging has shown that the expression of ion channels 13 and gap junction channel isoforms 14,15 can explain the electrophysiology of the AVN. In particular, a lack of or a low density of Na ϩ channels in the compact node (CN) can explain the slow upstroke and low amplitude of the action potential in CN. 13 Similarly, in CN, a lack of or a low density of low impedance isoforms of gap...

Abstract-Because of its complexity, the atrioventricular node (AVN), remains 1 of the least understood regions of the heart. The aim of the study was to construct a detailed anatomic model of the AVN and relate it to AVN function. The electric activity of a rabbit AVN preparation was imaged using voltage-dependent dye. The preparation was then fixed and sectioned. Sixty-five sections at 60-to 340-m intervals were stained for histology and immunolabeled for neurofilament (marker of nodal tissue) and connexin43 (gap junction protein). This revealed multiple structures within and around the AVN, including transitional tissue, inferior nodal extension, penetrating bundle, His bundle, atrial and ventricular muscle, central fibrous body, tendon of Todaro, and valves. A 3D anatomically detailed mathematical model (Ϸ13 million element array) of the AVN and surrounding atrium and ventricle, incorporating all cell types, was constructed. Comparison of the model with electric activity recorded in experiments suggests that the inferior nodal extension forms the slow pathway, whereas the transitional tissue forms the fast pathway into the AVN. In addition, it suggests the pacemaker activity of the atrioventricular junction originates in the inferior nodal extension. Computer simulation of the propagation of the action potential through the anatomic model shows how, because of the complex structure of the AVN, reentry (slow-fast and fast-slow) can occur. In summary, a mathematical model of the anatomy of the AVN has been generated that allows AVN conduction to be explored. Figure 1A). The function of the AVN is to conduct action potentials at an appropriate conduction velocity from the atria to the ventricles. Functionally, the AVN is complex. For example, the AVN shows dual pathway conduction: the slow pathway into the AVN runs from the isthmus (between coronary sinus and tricuspid valve) to the apex of the triangle of Koch, whereas the fast pathway is more cranial ( Figure 1B). The AVN is a subsidiary pacemaker, and the leading pacemaker site has been reported to be within the slow pathway. 1 AVN reentrant tachycardia is the most common paroxysmal supraventricular tachycardia (except atrial fibrillation) in adults 2 ; prevention involves ablation of the isthmus. 2 The AVN, perhaps more than any other tissue in the heart, owes its complexity of function to its complexity of structure (ie, anatomy). To understand the structure-function relationships of the AVN, the aim of the present study was to generate an anatomic model of the AVN and relate it to function. For research and teaching, there is an effort to build a "virtual heart." 3 This requires anatomic models in the form of mathematical arrays or finite element models for each part of the heart. Such models exist for the atria, ventricles, and sinoatrial node (SAN). 3,4 Here is the first such anatomic model (mathematical array) of the AVN. The study was carried out on the rabbit, because the rabbit AVN preparation is amenable to experimentation and is widely used, an...

Background-Recent clinical electrophysiology studies and successful results of radiofrequency catheter ablation therapy suggest that high-frequency focal activity in the pulmonary veins (PVs) plays important roles in the initiation and perpetuation of atrial fibrillation, but the mechanisms underlying the focal arrhythmogenic activity are not understood. Methods and Results-Extracellular potential mapping of rabbit right atrial preparations showed that ryanodine (2 mol/L) caused a shift of the leading pacemaker from the sinoatrial node to an ectopic focus near the right PV-atrium junction. The transmembrane potential recorded from the isolated myocardial sleeve of the right PV showed typical atrial-type action potentials with a stable resting potential under control conditions. Treatment with ryanodine (0.5 to 2 mol/L) resulted in a depolarization of the resting potential and a development of pacemaker depolarization. These changes were enhanced transiently after an increase in the pacing rate: a self-terminating burst of spontaneous action potentials (duration, 33.6Ϯ5.0 s; nϭ32) was induced by a train of rapid stimuli (3. A trial fibrillation (AF) is the most common of all sustained tachyarrhythmias and is one of the major causes of stroke. The most widely accepted mechanism of AF is multiple reentrant wavelets. 1 However, recent clinical studies have shown that paroxysmal AF is initiated by bursts of premature excitations originating primarily in the pulmonary veins (PVs), and radiofrequency ablation or electrical isolation of these foci can eliminate AF. 2,3 More recently, Haïs-saguerre et al 4 reported that in patients with drug-resistant chronic AF and structural heart disease, after electrical cardioversion, the PVs are also the dominant trigger reinitiating AF. Therefore, the PVs are important not only for the initiation of AF but also for its maintenance. 5 The myocardial fibers of the left atrium wrap around the PVs entering the left atrium to form "myocardial sleeves" (MSs), 6,7 and this structure is the origin of focal activity. 8 Previous studies have suggested that PVMSs show a variety of spontaneous activities such as sinoatrial (SA) node-type automaticity, rapid spontaneous activities via early or delayed afterdepolarizations, 8 -12 and microreentry based on a marked heterogeneous tissue structure. 12,13 However, the electrophysiological properties of PVMSs have not been fully characterized.In the present study, we investigated the electrophysiological properties of rabbit PVMSs. The results show that addition of 0.5 to 2 mol/L ryanodine to PVMSs uncovers pacing-induced spontaneous activity. Ryanodine at low concentrations locks the sarcoplasmic reticulum (SR) Ca 2ϩ release channel, the ryanodine receptor (RyR), in a subconductance state, causing a Ca 2ϩ -independent Ca 2ϩ release from the SR. 14 MethodsRabbits weighing 1.5 to 2.0 kg (Chubu-Kagaku-Shizai, Nagoya, Japan) were anesthetized with pentobarbital (30 to 40 mg/kg IV), and the heart was quickly excised. The right atrium, including the SA...

The population pharmacokinetic parameters of vancomycin obtained here can be used to individualize the dosage of vancomycin in institutions with similar patient population characteristics.

The widespread distribution of HCN4 can explain the widespread location of the leading pacemaker site during sinus rhythm, the extensive region of tissue that has to be ablated to stop sinus rhythm, and the widespread distribution of ectopic foci responsible for atrial tachycardia.

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We analyzed and organized the reasons why the amorphous wire CMOS IC magneto-impedance sensor (MI sensor) has rapidly been mass-produced as the electronic compass chips for the smart phones, mobile phones, and the wrist watches. Comprehensive advantageous features regarding six terms of (1) microsizing and ultralow power consumption, (2) high linearity without any hysteresis for the magnetic field detection, (3) high sensitivity for magnetic field detection with a Pico-Tesla resolution, (4) quick response for detection of magnetic field, (5) high temperature stability, and (6) high reversibility against large disturbance magnetic field shock are based on the magneto-impedance effect in the amorphous wires. We have detected the biomagnetic field using the Pico-Tesla resolution MI sensor at the room temperature such as the magneto-cardiogram (MCG), the magneto-encephalogram (MEG), and the self-oscillatory magnetic field of guinea-pig stomach smooth muscles (in vitro) that suggest the origin of the biomagnetic field is probably pulsive flow of Ca2+through the muscle cell membrane.