Cardiac Electrophysiology

Microvolt-level T-wave alternans (TWA) is a new arrhythmia risk marker to assess subtle changes in repolarization that has been introduced for arrhythmia risk stratification. Recent experimental studies have demonstrated that it reflects a heartrate dependent increased spatial dispersion of repolarization associated with unidirectional conduction block, and reentry that may result in the occurrence of ventricular fibrillation. Clinical studies have convincingly demonstrated that TWA is closely related to arrhythmia induction in the electrophysiology (EP) laboratory as well as to the occurrence of spontaneous ventricular tachyarrhythmias in patients undergoing EP study. Subsequent studies showed that TWA-assessed noninvasively-is predictive of future arrhythmic events in patients with implanted ICDs as well as for ventricular tachyarrhythmias in patients with congestive heart failure without a prior history of arrhythmias. There is still controversy, however, about the predictive val...

Many problems in Biology and Engineering are governed by anisotropic reaction–diffusion equations with a very rapidly varying reaction term. This usually implies the use of very fine meshes and small time steps in order to accurately capture the propagating wave while avoiding the appearance of spurious oscillations in the wave front. This work develops a family of macro finite elements amenable for solving anisotropic reaction–diffusion equations with stiff reactive terms. The developed elements are incorporated on a semi-implicit algorithm based on operator splitting that includes adaptive time stepping for handling the stiff reactive term. A linear system is solved on each time step to update the transmembrane potential, whereas the remaining ordinary differential equations are solved uncoupled. The method allows solving the linear system on a coarser mesh thanks to the static condensation of the internal degrees of freedom (DOF) of the macroelements while maintaining the accuracy of the finer mesh. The method and algorithm have been implemented in parallel. The accuracy of the method has been tested on two- and three-dimensional examples demonstrating excellent behavior when compared to standard linear elements. The better performance and scalability of different macro finite elements against standard finite elements have been demonstrated in the simulation of a human heart and a heterogeneous two-dimensional problem with reentrant activity. Results have shown a reduction of up to four times in computational cost for the macro finite elements with respect to equivalent (same number of DOF) standard linear finite elements as well as good scalability properties.

Doxorubicin (DOX) is a broad spectrum anthracycline antibiotic used
to treat multiple cancers. The use of DOX is limited by significant
cardiotoxicity,  hepatotoxicity  and  nephrotoxicity.  Quercetin  is  a
dietary-flavonoid found in plants which prevents oxidant injury and
protects against lipid peroxidation. The objective of the present study
was to assess the possible protective role of quercetin on doxorubicin
induced  hepatic,  cardiac  and  renal  toxicity  in  male  Wistar  rats.
Doxorubicin  (10mg/kg  body  weight)  was  administered  twice  and
quercetin  (100mg/kg  body  weight)  was  administered  on  all  the  21
days of the experimental period. Body weight, heart weight, creatine
kinase in serum and heart, the activities of the antioxidant enzymes in
liver,  heart  and  kidney  were  decreased  in doxorubicin  administered
rats. Liver and kidney weight, liver marker enzymes in serum, liver
and  kidney,  lactate  dehyrogenase  in  serum,  liver,  heart  and  kidney,
urea and creatinine in serum, lipid peroxide content in liver, heart and
kidney were increased. All the biochemical parameters mentioned
above  were  restored  to  near  normal  levels  on  quercetin
administration with doxorubicin. Administration of doxorubicin in
rats  altered  the  biochemical  parameters  but,  did  not  cause  much
effect on the tissues such as liver, heart and kidney which is evident
with histological studies.

Cardiac arrhythmias are defined as disturbances in normal heart rhythm which vary from inconsequential to serious life threatening conditions. Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate an ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration(APD) and frequency of oscillations of the auto-rhythmic cells  in WHM2D a large variety of cardiac arrhythmias can be generated. Sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and AV conduction blocks are thereby simulated. WHM2D includes key components of the electrical conduction system of the heart like  the SA (Sino atrial) node cells, fast conducting inter-atrial pathways, slow conducting Atrivenctricular (AV) node,  bundleof His cells, Purkinje network, atrial and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundleof His cells and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias.

The shape and size of electrode's head may have a strong influence on the sensing performance, both of intra-cavitary electrodes and intra-tissue electrodes, whenever the sensed region is close enough to electrode's surface. The purpose of this paper is to discuss the performance of concave electrodes when used as sensing devices. The shape and size of a critical region of higher sensing sensitivity to the electric activity of biological tissues is studied using a mathematical model of a homogeneous and isotropic volume conductor. A formula is derived for the measured potential difference between a proximal concave electrode and a distal indifferent one, due to tissues' electrical activity.

Distribution of M Cells, introduction: M cells and transitional cells residing in the deep structures of the ventriculur free walls are distinguished by the ability of their action putentials to prolong disproportionately to those of other ventricular cells at relatively slow rates. This feature of the M cell due. at least in part, to a smaller contribution of the slowly activating component of the delayed rectifier current UK,) is thought to contrihute to the unique pharmacologic responsiveness of M cells, making them the primary targets in ventricular myocardium for agents that cau.se action potential prolongation and induce early and delayed afterdepolarizations and triggered activity. Previous studies dealt exclusively with the characteristics and distrihution of M cells in the canine right and left ventricular free wall near the ba.se of the ventricles. The present study uses standard microeiectrode techniques to define their behavior and distrihution in the apical region of the ventricular wall as well as in the endwardial structures of the ventricle, including the interventricular septum, papillar>' muscles, and traheculae. Methods and Results: Action potentials recorded from the M region (deep subepicardium) displayed similar characteristics (steep action potential duration |API)l-rate relations) in the base and apex. However, important differences were apparent in the other regions. In epicardium. the spike and dome morphology of the action potential was less accentuated and the rate dependence of APD more pronounced in the apex versus the base. In endocardium, and especially deep suhendocardium. rate dependence of APD was considerably more pronounced in tbe apex. Transmembrane recordings from tbe subsurface layers of tbe septum, trabeculae. and papillary muscles revealed M cell behavior (steep APD-rate relations) in the deep suhendocardium. Kpicardial and transitional hehavior were also observed in the deep layers ofthe.se endiKardiat structures. Conclusion: Our results indicate that M cells reside throughout the deep subepicardial layers of the free wall of the canine left ventricle as well as in the deep suhendocardial layers of the septum, papillary muscles, and trabeculae. The data also demonstrate prominent traasmural as well as apicohasal gradients of phase 1 and phase 3 repolarization. These findings may have implications relative to our understanding of the electriKardiographic J wave, T wave, U wave, and long OTU intervals.

Methods and Results: To quantify the scope of neck and back problems, we surveyed 70 interventional electrophysiologists in Canada using an electronic survey with in person and email reminders. We also surveyed an age-and gender-matched group of noninterventional cardiologists. We received responses from a total of 58 of 70 interventional electrophysiologists (response rate 82.8%). There was a significantly higher prevalence of cervical spondylosis among electrophysiologists compared to matched noninterventional cardiologists (20.7% compared to 5.5%, P = 0.033). There was a trend for increased prevalence of lumbar spondylosis (25.9% compared to 16.7%, P = 0.298). Among electrophysiologists, those with cervical spondylosis were older (49.83 ± 10.48 years compared to 44.57 ± 9.20, P = 0.092) and had worked in the specialty for longer in comparison to unaffected physicians (19.67 ± 10.06 years compared to 13.37 ± 8.97 years, P = 0.039). All other variables including gender, height, weight, BMI, type of lead, weekly average lead time, and % of time standing in electrophysiology laboratory were not different. On multivariable analysis there were no independent predictors of disease.

Purpose: The present study examined whether HRV is predictive of CAN in patients with DMII. Subjects and methods: The study group consisted of 50 patients, newly diagnosed with type 2 diabetes mellitus. The control group consisted of 50 healthy subjects. HRV was measured using a 24-hour ECG Holter monitoring system. Time domain parameters used are: SDNN, and SDANN. Results: There are significant differences between disease duration. Orthostatic hypotension was found in 14 patients and heart rate increased over 100 at rest was found in 28 patients. HRV parameters are lower in DM group but differences are significant only for SDNN. From the total group, more than half had HRV parameters below the normal range (56%). Of the asymptomatic patients, 14 (28%) had abnormal HRV parameters. Decreased HRV was found in newly diagnosed type two DM. Conclusion: HRV is decreased in newly diagnosed DM II. Heart Rate Variability (HRV) is a Powerful Predictor in the Early Diagnosis of Cardiac Autonomic Neuropathy (CAN) In Patients with Type Two Diabetes Mellitus (DM II). [Abdulhalim Salim Serafi. Heart Rate Variability (HRV) is a Powerful Predictor IN the Early Diagnosis of Cardiac Autonomic Neuropathy (CAN) In Patients with Type Two Diabetes Mellitus (DM II). Life Sci J

En este trabajo ciertos problemas de la biología de los tejidos excitables son replanteados como problemas físicos y son estudiados mediante los conceptos y los métodos de la física no lineal. Se trata de un trabajo fundamentalmente de biofísica matemática, motivado por un conjunto de problemas originados en el estudio del significado electrofisiológico de los parámetros que se suelen emplear para caracterizar las curvas intensidad umbral versus duración en los tejidos biológicos excitables .
Presentamos un análisis cualitativo de la dinámica del umbral las membranas uniformemente polarizadas y analizamos en profundidad los diferentes conceptos de umbral local de membrana.
Caracterizamos las geometrías del campo de corriente eléctrica generado por un electrodo en el conductor de volumen equivalente a los tejidos por medio de desarrollos multipolares.
Introducimos el concepto de región de influencia del electrodo sobre la fibra o el sincicio funcional blanco de la excitación, para poder efectuar un análisis modal no lineal de las ecuaciones de campo que describen la interacción entre el tejido (fibra o sincicio funcional) y el electrodo estimulador.
Introducimos el conjunto de decaimiento, la pseudo-variedad umbral y el conjunto amplificador en el espacio de configuración formado por las amplitudes de modo. Describimos la acción polarizante del electrodo mediante las proyecciones del factor de forma de la función activante para una fibra, y de la función activante generalizada para un sincicio eléctrico con anisotropía desigual. Analizamos el proceso de excitación en el espacio de configuración empleando la teoría de la estabilidad y las bifurcaciones de los sistemas dinámicos, obteniendo así ejemplos concretos y cuantitativos del concepto básico de familia de estados umbral.
Trabajando con varios modos acoplados, consideramos el bloqueo anódico por el cátodo, la excitación anódica de cierre y la excitación catódica de apertura. Explicamos la excitación anódica de cierre y la excitación catódica de apertura en términos de una desestabilización de modos al superar la correspondiente amplitud umbral (desestabilización “dura” del estado de reposo).
Fundamentamos los modelos clásicos de uno y dos factores para la excitación y esbozamos su generalización en un nuevo modelo de tres factores. La idea original de funcional de excitación  resulta fundamental en todo ese desarrollo, así como el uso de los sistemas rompientes de Vogel, la linealización de la dinámica en el conjunto de decaimiento y la aproximación de la pseudo-variedad umbral por una variedad lineal.
Obtenemos diferentes expresiones analíticas para las curvas intensidad umbral versus duración de membranas uniformemente polarizadas (capítulo III)  y para el caso tanto de fibras como de sincicios funcionales (capítulos V a VIII) polarizados en forma no uniforme. En estas fórmulas los parámetros globales del umbral utilizados en electrofisiología clínica se expresan en función de los parámetros locales utilizados en electrofisiología básica, de las dimensiones características del tejido (diámetro de la fibra, fracción de membranas y fracciones de volumen del sincicio funcional), de sus parámetros eléctricos (resistividad del citoplasma de la fibra, conductividades del continuo intracelular y del continuo intersticial del sincicio eléctrico), y de las características del campo de corriente generado por el electrodo estimulador en el conductor de volumen equivalente a los tejidos.
Además, introducimos la distinción entre excitabilidad global y excitabilidad local, y entre respuesta eléctrica activa y respuesta eléctrica pasiva.
Construimos un modelo del sistema electrodo-tejidos considerado como dipolo eléctrico (en el sentido de la teoría de circuitos) en el que relacionamos la polarizabilidad de la interfase electrodo-tejidos con su dimensión fractal, interpretando los parámetros de la impedancia de Drake.
Analizamos las curvas intensidad-duración para pulsos estimuladores de voltaje controlado. Discutimos el incremento fisiológico del umbral. Introducimos el "electrodo manzana" como electrodo representativo de los electrodos cóncavos.
Analizamos la propagación de un potencial de acción en un sincicio funcional. Empleamos una adaptación del método de Kompaneyetz y la teoría de perturbaciones singulares para tener en cuenta los procesos de activación y de recuperación en las membranas excitables.
Mediante el empleo del concepto de frente virtual relacionamos la velocidad de propagación con la curvatura media del frente, con los procesos de activación y recuperación, y con las propiedades de heterogeneidad y anisotropía (tal como aparecen expresadas en el tensor de dispersión eléctrica de las membranas), en condiciones de propagación  estable y auto-sostenida del potencia1 de acción.
Exploramos las relaciones entre la curvatura media crítica para un frente convexo y las dimensiones críticas de la región de despolarización inicial, a partir de la cual se genera el potencial de acción, conectando de esa forma la posibilidad de propagación estable con la posibilidad de generación del potencial de acción.
Discutimos la generalización de la idea de familias de estados umbral más allá de las condiciones de la estimulación de fibras y sincicios funcionales por electrodos extra-tisulares.
Obtenemos una estimación para las constantes de tiempo de fibras y sincicios funcionales despolarizados por micro-electrodos internos.
Planteamos la aplicación del-concepto de familias de estados umbral para  el estudio de la influencia, sobre el proceso de excitación en una fibra o en un sincicio funcional, de una distribución espacial arbitraria del voltaje transmembrana y de las variables de activación,  recuperación y adaptación,  originadas en una distribución espacio-temporal de acciones sinápticas, en la actividad de grupos de células marcapaso, en los potenciales de campo producidos por la interacción eléctrica entre células vecinas o a través de la acción de mediadores  químicos de acción difusa distribuidos en el espacio intersticial, en la actividad de focos ectópicos, etc.
A lo largo de todo el desarrollo y la discusión final relacionamos los resultados teóricos con los datos experimentales o de simulación digital. Generalmente ha habido buen acuerdo entre la teoría y el experimento. No obstante, la confirmación o rectificación de varios de estos resultados teóricos exige una contraparte experimental que hasta el momento parece no estar disponible. Es necesario, entonces, diseñar y llevar a cabo experimentos nuevos.
La idea de la región de influencia del electrodo y el empleo del metódo de Kompaneyetz conlleva ciertas limitaciones que, por un lado, nos condujeron a estudiar la polarización de la zona blanco justo hasta el umbral, y por el otro nos condujeron a considerar la propagación de un potencial de acción plenamente desarrollado. Queda fuera del alcance de nuestro análisis la descripción detallada de la transición entre un potencial de acción incipiente, que emerge de lo que hubiera sido una respuesta local; y un potencial de acción que se propaga ya en forma estable, en su plenitud. Este es un tema fundamental para estudiar en el futuro.
No obstante, a través del presente trabajo se han aclarado varias cuestiones electrofisiológicas que permanecieron confusas durante muchos años. Asimismo se tienen nuevas bases para el desarrollo de una teoría físico-matemática de la estimulación eléctrica de tejidos biológicos -tanto fibras como sincicios funcionales- mediante electrodos externos, posiblemente utilizable en electrofisiología clínica, en terapéutica  y en ingeniería biomédica.

Right ventricular out_ow tract (RVOT) tachycardia refers to the most common form of idiopathic ventricular tachycardia (VT). 1,2 Idiopathic VT, as its designation suggests, occurs in the absence of structural heart disease. This usually implies that no abnormalities are apparent on an exercise stress test, echocardiogram and cardiac arteriogram. In recent years, additions to the diagnostic armamentarium, such as the signal averaged ECG, gated magnetic resonance imaging (MRI) and myocardial biopsies have allowed a more precise de~nition of "idiopathic" and have identi~ed patients with occult forms of arrhythmogenic right ventricular dysplasia (ARVD) who might have been previously classi~ed as having a normal heart.

The majority of idiopathic right ventricular arrhythmias (VAs) including ventricular tachycardia/premature depolarizations (VT/ VPDs) originate in the right ventricular outflow tract (RVOT) and rarely from the inflow, near the His-bundle (HB) region, free wall or apex of the right ventricle (RV) . There are only a few reports on successful radiofrequency ablation (RFA) of idiopathic RV VAs originating from the tricuspid annulus (TA) near the HB .

The second Copenhagen AF, Aspirin, and Anticoagulation Study (AFASAK II) [1] involved randomized comparison of~xed minidose warfarin, 1.25 mg/d with or without aspirin, 300 mg/d, vs. either aspirin or adjusted-dose warfarin, INR 2.0-3.0. The Minidose Warfarin In Nonrheumatic Atrial Fibrillation Study (MWNAFS) [2] compared~xed-dose warfarin, 1.25 mg/d vs. adjusted-dose warfarin, INR 2.0-3.0. Both trials were halted after publication of the Stroke Prevention in Atrial Fibrillation (SPAF) III high-risk randomized trial data [3] which showed a clear advantage of adjusted-dose warfarin, INR 2.0-3.0 vs.~xed-dose warfarin, 1-3 mg/d, INR range 1.2-1.5, plus aspirin, 325 mg/d. Early discontinuation of AFASAK II and MWNAFS resulted in a lack of statistical power for these studies to individually assess the comparisons tested. While the AFASAK II results appear inconsistent with other reports, it should be noted that 25% of patients discontinued therapy, and as a result 5/12 primary events in the warfarin, INR 2.0-3.0, group occurred in those who had withdrawn, while only 2/24 events in the two low-dose warfarin groups and 2/10 events in the aspirin group occurred off therapy. An ef~cacy analysis was not performed, but would likely have favored adjusted warfarin. The withdrawal rate in the MWNAFS study was 16%. The rate of ischemic stroke was signi~cantly higher, 3.7% vs. 0% per year in the minidose warfarin group. Secondary analysis of primary events (ischemic stroke, peripheral embolism, cerebral or fatal hemorrhage, vascular death) in patients on treatment revealed 10 events in minidose vs. 4 events in adjusted-dose warfarin groups (7.2 vs. 3.3%/yr, p ϭ 0.01). When combined with the results of the SPAF III high risk study, the data appeared to show incomplete protection from thromboembolic events by minidose warfarin with or without aspirin ( .

A 76-year-old woman was referred to our hospital for unresponsiveness and hypotension. She had developed constipation that had led to ileus and had received 34 g of magnesium citrate (Magcolol P®) orally the day before.
She was lethargic, her blood pressure was less than 50 mmHg, and electrocardiogram (ECG) revealed sinus ar- rest with junctional escape rhythm.
Her serum concentration of magnesium (Mg) was markedly elevated (16.6 mg/dl =13.7 mEq/l). Emergency colonoscopy revealed ischemic colitis.
As her condition ameliorated, her renal function returned to normal. Hence, the present case suggests that severe hypermagnesemia can occur in the absence of pre-existing renal dysfunction in elderly patients with gastrointestinal diseases.
(Internal Medicine 44: 448–452, 2005)

Resumen: En esta primera parte, después de resumir y reformular la teoría de bidominio de la electrocardiología, se emplea un modelo matemático simplificado de la excitación del miocardio a través de electrodos de marcapaso para estudiar, justo hasta el umbral, la dinámica del sistema electrodo-miocardio. Se introduce una región de influencia del electrodo de marcapaso sobre el miocardio, para poder plantear un problema mixto, ho-mogéneo de Dirichlet y no homogéneo de Neumann a partir de las ecuaciones no lineales del modelo de bidominio, de modo de describir el efecto polarizante del electrodo. Un enfoque basado en el análisis modal no lineal se emplea para transformar las ecuaciones de campo en un sistema de ecuaciones diferenciales ordinarias no lineales en las amplitudes de modo. El valor umbral de la perturbación que causa inestabilidad se estima em-pleando una versión modificada del método de Eckhaus. Se identifican patrones espacia-les de polarización de las membranas que corresponden a una familia de estados umbral en el espacio de estados construido a partir de las amplitudes de modo. Se obtienen las formas y los tamaños de las regiones liminales (que deben ser despolarizadas por enci-ma del umbral uniforme de membrana para que pueda generarse un potencial de acción propagado). Se deducen fórmulas para curvas intensidad-duración (I-D), obtenidas me-diante pulsos catódicos de corriente controlada, incluyendo fórmulas analíticas para las constantes de tiempo (cronaxias) y reobases, en términos de parámetros geométricos y electroquímicos del electrodo, de la distancia entre el electrodo y el miocardio ventricular, de las propiedades eléctricas del conductor de volumen de los tejidos, y de la distribución local de los parámetros electrotónicos y de excitabilidad del músculo cardíaco. Se expli-can varios resultados experimentales (las regiones liminales y el comportamiento de los parámetros de las curvas I-D) y se predicen algunos fenómenos nuevos (relacionados con las regiones liminales, las familias de estados umbral y los parámetros de las curvas I-D). Este enfoque teórico-analítico mediante análisis modal no lineal se extenderá, en la Parte II de este trabajo, para tener en cuenta la anisotropía desigual y la heterogeneidad del miocardio. Palabras clave: Modelos de bidominio del miocardio. Diseño de electrodos de marcapa-so. Umbrales de excitabilidad. Análisis modal no lineal. Familias de estados umbral. Regiones liminales. Estimulación catódica de cierre. Curvas intensidad-duración.

The purpose of this investigation was to evaluate factors affecting the outcome following penetrating cardiac trauma in a developing country and to compare our results with others in developed countries. Analysis of the cause of trauma, age, sex, different tools of investigations used, concomitant organ injuries, SBP, GCS, ISS, RTS, TRISS and mortality were performed. This study included 35 patients; all were males. Mortality rate was 22.8%. It was significant with low SBP (p =0.021), GCS ˂ 9 (p =0.02), non-presentation with tamponade (p = 0.023), low ISS (p =0.02), low RTS (p =0.007), low TRISS (p = 0.003), less blood transfusion (p =0.001) and longer time before entrance to OR (p= 0.019). Meanwhile, mortality were not significant with age (p =0.33), mechanism of injury (p =0.16), other associated injuries (p =0.16) or associated intra-abdominal injuries (p= 0.16). Rapid assessment and prompt surgical intervention may reduce mortality. Even in a developing country, mortality rates could reach those in developed countries depending on clinical skills and accessible technology tools.

The goal of systems biology is to relate events at the molecular level to more integrated scales from organelle to cell, tissue, and living organism. Here, we review how normal and abnormal excitation-contraction coupling properties emerge from the protein scale, where behaviors are dominated by randomness, to the cell and tissue scales, where heart has to beat with reliable regularity for a lifetime. Beginning with the fundamental unit of excitation-contraction coupling, the couplon where L-type Ca channels in the sarcolemmal membrane adjoin ryanodine receptors in the sarcoplasmic reticulum membrane, we show how a network of couplons with 3 basic properties (random activation, refractoriness, and recruitment) produces the classic physiological properties of excitation-contraction coupling and, under pathophysiological conditions, leads to Ca alternans and Ca waves. Moving to the tissue scale, we discuss how cellular Ca alternans and Ca waves promote both reentrant and focal arrhythmias in the heart. Throughout, we emphasize the qualitatively novel properties that emerge at each new scale of integration. (Circ Res. 2011;108:98-112.)

“Atrial tachycardia” encompasses those forms of supraventricular tachycardia that do not involve the atrioventricular node as an obligate part of the tachycardia circuit. We have previously reviewed a conceptual approach for understanding the epidemiology, ...

Alterations of the β-adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of β-adrenoceptor activation on local Ca 2+ release in electrically coupled and uncoupled T-tubules in ventricular myocytes from HF rats. We employ an ultrafast random access multi-photon (RAMP) microscope to simultaneously record action potentials and Ca 2+ transients from multiple T-tubules in ventricular cardiomyocytes from a HF rat model of coronary ligation compared to sham-operated rats as a control. We confirmed that β-adrenergic stimulation increases the frequency of Ca 2+ sparks, reduces Ca 2+ transient variability, and hastens the decay of Ca 2+ transients: all these effects are similarly exerted by β-adrenergic stimulation in control and HF cardiomyocytes. Conversely, β-adrenergic stimulation in HF cells accelerates a Ca 2+ rise exclusively in the proximity of T-tubules that regularly conduct the action potential. The delayed Ca 2+ rise found at T-tubules that fail to conduct the action potential is instead not affected by β-adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to β-adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the β-adrenergic signalling may be directly caused by the lack of electrical activity.

Mantendo a regularidade anual da publicação dos registos de electrofisiologia, apresentam-se os resultados referentes ao ano de 2004. Com efeito, consideramos importante a apresentação das casuísticas globais, assim como os resultados dos centros onde esta ...

The novel antiarrhythmic drug K201 (4-[3-{1-(4-benzyl)piperidinyl}propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine monohydrochloride) is currently in development for treatment of atrial fibrillation. K201 not only controls intracellular calcium release by the ryanodine receptors, but also possesses a ventricular action that might predispose to torsade de pointes arrhythmias. The anti-and proarrhythmic effects of K201 were investigated in the anesthetized canine chronic atrioventricular block model. Two doses of K201 (0.1 and 0.3 mg/kg/2 min followed by 0.01 and 0.03 mg/kg/30 min i.v.) were tested in 4 serial experiments in dogs with normally conducted sinus rhythm (n = 10) and in torsade de pointes-susceptible dogs with chronic atrioventricular block. Susceptibility was assessed with dofetilide (0.025 mg/kg/5 min i.v.). Beat-to-beat variability of repolarization was quantified as short-term variability of left ventricular monophasic action potential duration. In dogs with normally conducted sinus rhythm, both doses of K201 prolonged ventricular repolarization whereas only the higher dose prolonged atrial repolarization. At chronic atrioventricular block, dofetilide induced torsade de pointes in 9 of 10 dogs. K201 did neither suppress nor prevent dofetilide-induced torsade de pointes. K201 dose-dependently prolonged ventricular repolarization. In contrary to the lower dose, the higher dose did increase beat-to-beat variability of repolarization (from 1.2 ± 0.3 to 2.9 ± 0.8 ms, P b 0.05) and resulted in spontaneous, repetitive torsade de pointes arrhythmias in 1 of 7 dogs; Programmed electrical stimulation resulted in torsade de pointes in 2 more dogs. In conclusion, both doses of K201 showed a class III effect. No relevant antiarrhythmic effects against dofetilide-induced torsade de pointes were seen. Only at the higher dose a proarrhythmic signal was observed.

Molecular targets for pharmacological modulation of sinoatrial (SA) pacemaking include ion channels in-volved in sinoatrial pacemaking and components of the receptor-II messenger systems that may modulate, such channels in physiological and pathological condi-tions. These ...

A case–control study (1:1) was conducted with a total of 72 patients: 36 cases (depressed LVEF) and 36 controls
(normal LVEF). Patients were matched by left atrial diameter (LAD), the presence of arterial hypertension,
and other variables that might influence the results (age, gender and paroxysmal vs. persistent AF). There
were no statistical differences in the variables used to perform the matching. Patients with depressed LVEF
had higher LV end diastolic diameter (55.6+6.2 vs. 52.4+5.5, P ¼ 0.03), higher LV end systolic diameter
(40.3+6.9 vs. 32.6+4.3, P , 0.001), lower LVEF (41.4+8.0 vs. 63.1+5.5, P , 0.001) and were more likely to
have structural heart disease. After a mean follow-up of 16+13 months, survival analysis for AF recurrences
showed no differences between patients with depressed vs. normal LVEF (50.0 vs. 55.6%, log rank ¼ 0.82). Cox
regression analysis revealed LAD to be the only variable correlated to recurrence [OR 1.11 (1.01–1.22),
P ¼ 0.03]. Analysis at 6 months showed a significant increase in LVEF (43.23+7.61 to 51.12+13.53%, P ¼ 0.01)
for the case group.

Current approaches for the ablation of atrial fibrillation are often effective, but only partially rooted in mechanistic understanding. Accordingly, they are unable to predict whether a given patient will or will not do well, or which lesions sets should or should not be performed – in any given patient. This goal would require clearer mechanistic definition of what sustains AF after it has been triggered (i.e. electrophysiological substrates). There are two schools of thought. The first proposes disorganized activity that self-sustains with no ‘driver’, and the second describes drivers that then cause disorganization. Interestingly, these mechanisms can be separated in human studies by mapping approach – proponents of the disorganized hypothesis studying small atrial areas at high resolution, and proponents of the driver model studying wide fields-of-view at varying resolutions. Focal impulse and rotor modulation (FIRM) mapping combines a wide field of view with physiologically based signal filtering and phase analysis, and has revealed that human AF is often sustained by rotors. In the CONFIRM Trial, targeting stable AF rotors/sources for ablation improved the single-procedure efficacy for paroxysmal and persistent AF over conventional ablation alone, as now confirmed by independent laboratories. FIRM mapping gives a mechanistic foundation to predict whether any selected lesions should intersect AF sources in any given patient and which mechanisms may cause recurrence. Rotors of varying characteristics have now been shown by many groups. These insights have reinvigorated interest in AF mapping, and rationalizing these findings will likely translate into improved therapy for our patients.

Records of brain electrical activity from intracranial and scalp EEG of seven patients with different types of epilepsy are analyzed to predict the epileptic seizure onset. A method based on the CSP and SVM is introduced. This is an efficient method to predict epileptic seizures: from 52 pre-seizure signals, the seizure onsets in 23 of those are predicted. Through this method, we propose a seizure prediction model which gets an accuracy rate represented by predictions / seizures of 5/20-5/5 and a pseudo-prediction rate of 1.6-10.9 per hour.

Significant advancements in imaging technology and the dramatic increase in computer power over the last few years broke the ground for the construction of anatomically realistic models of the heart at an unprecedented level of detail. To effectively make use of high-resolution imaging datasets for modeling purposes, the imaged objects have to be discretized. This procedure is trivial for structured grids. However, to develop generally applicable heart models, unstructured grids are much preferable. In this study, a novel image-based unstructured mesh generation technique is proposed. It uses the dual mesh of an octree applied directly to segmented 3-D image stacks. The method produces conformal, boundary-fitted, and hexahedra-dominant meshes. The algorithm operates fully automatically with no requirements for interactivity and generates accurate volume-preserving representations of arbitrarily complex geometries with smooth surfaces. The method is very well suited for cardiac electrophysiological simulations. In the myocardium, the algorithm minimizes variations in element size, whereas in the surrounding medium, the element size is grown larger with the distance to the myocardial surfaces to reduce the computational burden. The numerical feasibility of the approach is demonstrated by discretizing and solving the monodomain and bidomain equations

When you began computer modeling of the heart over 40 years ago, what were the factors that made progress difficultcomputing power or biology? Probably the most difficult thing was convincing the mathematicians and computer scientists that I was capable.You have to realise that at that time the idea that biologists might actually do mathematics and computing was an exceedingly rare thing. All the other users of the London University computer, Mercury, and remember, in those days there was only one computer in the whole of the university, were mathematicians, computer specialists, crystallographers and particle physicists.The idea of a biologist coming along saying 'I've got some experimental data, I've fitted some equations to it and I want to do some integrating of the differential equations' was very peculiar-they weren't really prepared to believe I could do it. And that's the reason I was given time at two o'clock in the morning. I was given the worst time as it were, from two until four o'clock in the morning. Of course, I felt very, very pleased when six months later I was able to tell them that we had a paper in Nature.There wasn't a difficulty from the point of view of the data-I'd got it in my own laboratory with my supervisor. I had the

The last two decades have witnessed a signi~cant increase in the interest of heart rate variability (HRV), which has been one of the promising developments in non-invasive electrocardiology. With the advent of appropriate signal processing techniques, HRV has provided insight into the relationship of the autonomic nervous system and into the mechanisms by which it in_uences disease progression and cardiovascular mortality.