No description available.

Atrial fibrillation (AF) is a complex, multifaceted arrhythmia. Pathogenesis of AF is associated with multiple aetiologies and the mechanisms by which it is sustained and perpetuated are similarly diverse. In particular, regional heterogeneity in the electrophysiological properties of normal and pathological tissue plays a critical role in the occurrence of AF. Understanding AF in the context of electrophysiological heterogeneity requires cell-specific ionic models of electrical activity which can then be incorporated into models on larger temporal and spatial scales. Biophysically-based models have typically dominated the study of cellular excitability providing detailed and precise descriptions in the form of complex mathematical formulations. However, such models have limited applicability in multidimensional simulations as the computational expense is too prohibitive. Simplified mathematical models of cardiac cell electrical activity are an alternative approach to these traditional biophysically-detailed models. Utilizing this approach enables the embodiment of cellular excitation characteristics at minimal computational cost such that simulations of arrhythmogensis in atrial tissue are conceivable. In this thesis, a simplified, generic mathematical model is proposed that characterizes and reproduces the action potential waveforms of individual cardiac myocytes. It incorporates three time-dependent ionic currents and an additional time-independent leakage current. The formulation of the three time-dependent ionic currents is based on 4-state Markov schemes with state transition rates expressed as nonlinear sigmoidal functions of the membrane potential. Parameters of the generic model were optimized to fit the action potential waveforms of the Beeler-Reuter model, and, experimental recordings from atrial and sinoatrial cells of rabbits. A nonlinear least-squares optimization routine was employed for the parameter fits. The model was successfully fitted to the Beeler-Reuter waveform (RMS error: 1.4999 mV) and action potentials recorded from atrial tissue (RMS error: 1.3398 mV) and cells of the peripheral (RMS error: 2.4821 mV) and central (RMS error: 2.3126 mV) sinoatrial node. Thus, the model presented here is a mathematical framework by which a wide variety of cell-specific AP morphologies can be reproduced. Such a model offers the potential for insights into possible mechanisms that contribute to heterogeneity and/or arrhythmia.

No description available.

Submitted by FABRÍCIO ELY GOSSLER null (fabricio_ely8@hotmail.com) on 2017-02-09T16:24:59Z No. of bitstreams: 1 Fabrício E. Gossler-Dissertação - Unesp - Feis-PPGEE.pdf: 5023440 bytes, checksum: b5346eb35f509f2283b503acccf22ec3 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-02-14T16:08:30Z (GMT) No. of bitstreams: 1 gossler_fe_me_ilha.pdf: 5023440 bytes, checksum: b5346eb35f509f2283b503acccf22ec3 (MD5) / Made available in DSpace on 2017-02-14T16:08:30Z (GMT). No. of bitstreams: 1 gossler_fe_me_ilha.pdf: 5023440 bytes, checksum: b5346eb35f509f2283b503acccf22ec3 (MD5) Previous issue date: 2016-12-19 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Existem diferentes tipos de funções wavelets que podem ser utilizadas na Transformada Wavelet. Na maioria das vezes, a função wavelet escolhida para a análise de um determinado sinal vai ser aquela que melhor se ajusta no domínio tempo-frequência do mesmo. Existem vários tipos de funções wavelets que podem ser escolhidas para certas aplicações, sendo que algumas destas pertencem a conjuntos específicos denominados de famílias wavelets, tais como a Haar, Daubechies, Symlets, Morlet, Meyer e Gaussianas. Nesse trabalho é apresentada uma nova família de funções wavelets geradas a partir de polinômios com coeficientes de Fibonacci (FCPs). Essa família recebe o nome de Golden, e cada membro desta é obtido por uma derivada de ordem n do quociente entre dois FCPs distintos. As Golden wavelets foram deduzidas através das observações de que, em alguns casos, a derivada de ordem n, do quociente entre dois FCPs distintos, resulta em uma função que possui as características de uma onda de duração curta. Como aplicação, algumas wavelets apresentadas no decorrer deste trabalho são utilizadas na classificação de arritmias cardíacas em sinais de eletrocardiograma, que foram extraídos da base de dados do MIT-BIH arrhythmia database. / There exist different types of wavelet functions that can be used in the Wavelet Transform. In most cases, the wavelet function chosen for the analysis of a given signal will be the one that best adjusts in the time-frequency domain of the same signal. There are many types of wavelet functions that can be chosen for certain applications, some of which belong to specific sets called wavelet families, such as Haar, Daubechies, Symlets, Morlet, Meyer, and Gaussians. In this work a new wavelet functions family generated from Fibonacci-coefficients polynomials (FCPs) is presented. This family is called Golden, and each member is obtained by the n-th derivative of the quotient between two distinct FCPs. The Golden wavelets were deduced from the observations that in some cases the n-th derivative of the quotient between two distinct FCPs results in a function that has the characteristics of a short-duration wave. As an application, some wavelets presented in the course of this work are used to cardiac arrhythmia classification in electrocardiogram signals, which were extracted from the MITBIH arrhythmia database. / CNPq: 130123/2015-3

Recent studies suggest that cardiomyocyte membrane microdomains, caveolae and transverse tubules, play a key role in cardiac arrhythmia. Mutation of caveolin-encoding genes CAV3, co-expressed with genes of caveolae ion channels, leads to a late persistent sodium currents and delayed repolarization stage, called LQT9 disease. A simplified three-current model is created to largely reduce the well-known Pandit rat ventricular myocyte model. The mathematical tractability of the three-current model allows us to conduct asymptotic analysis and efficiently estimate action potential duration. Improvement in the description of the mechanism for caveolae sodium current is incorporated into the three-current model utilizing a probability density approach for the four-state caveolae neck-channel coupling. The prolongation of action potentials and the formation of potential arrhythmia are shown to arise if caveolae neck open probability varies. A minimal model of the Ca2+ spatial distribution of CICR units illustrates the transverse tubule remodeling in failing myocyte causes dysfunction in the Ca2+ profile. With regards to discrimination of protein localization, which is widely used in biological experiments, the bagging pruned decision tree algorithm is tested to be one of the algorithms with best performance on the large data set, and it succeeds in extracting information to be highly predictive on test data. Parallel computation technique is applied to accelerate the speed of implementation in K-nearest neighbor learning algorithms on big data sets.

<p>During the last years, drugs that prolong the repolarisation phase of the myocardial action potential, due to inhibition of the rapid component of the delayed-rectifying potassium channel (I_Kr) have been in focus. In addition to arrhythmogenic potential, selective Ikr-blockers have also been shown to be embryotoxic and teratogenic in animal studies. The aim of this thesis was to investigate a theory that these developmental toxic results from pharmacologically induced episodes of embryonic cardiac arrhythmias leading to hypoxia related damage in the embryo. Almokalant (ALM) was used as a model compound for selective Ikr-blockers. ALM induced embryonic cardiac arrhythmia, and in similarity with results obtained by maternal hypoxia, ALM induced embryonic death and growth retardation in both rats, and mice. </p><p>The theory of a hypoxia-related mechanism was strengthened by the results that ALM induce phase specific external and visceral defects (e.g. cleft lip/palate, distal digital, cardiovascular, and urogenital defects), and that the skeletal defects (not shown before) showed a clear trend; the later the treatment the more caudal was the site of the defect, which is in accordance with results from maternal hypoxia induced by e.g. lowering of the O₂ content in the air. The spin trapping agent PBN decreased almokalant induced malformations, suggesting that the defects mainly are caused by reoxygenation damage after episodes of severe embryonic dysrhythmia, rather than "pure hypoxia".</p><p>Sotalol was tested in a third species, the rabbit who expresses functional I_Kr channels both in the embryo and in the adult, where it induced developmental toxicity, and indicating that the embryo is more sensitive than the adult towards arrhythmia caused by I_Kr-blockers. </p>

During the last years, drugs that prolong the repolarisation phase of the myocardial action potential, due to inhibition of the rapid component of the delayed-rectifying potassium channel (IKr) have been in focus. In addition to arrhythmogenic potential, selective Ikr-blockers have also been shown to be embryotoxic and teratogenic in animal studies. The aim of this thesis was to investigate a theory that these developmental toxic results from pharmacologically induced episodes of embryonic cardiac arrhythmias leading to hypoxia related damage in the embryo. Almokalant (ALM) was used as a model compound for selective Ikr-blockers. ALM induced embryonic cardiac arrhythmia, and in similarity with results obtained by maternal hypoxia, ALM induced embryonic death and growth retardation in both rats, and mice. The theory of a hypoxia-related mechanism was strengthened by the results that ALM induce phase specific external and visceral defects (e.g. cleft lip/palate, distal digital, cardiovascular, and urogenital defects), and that the skeletal defects (not shown before) showed a clear trend; the later the treatment the more caudal was the site of the defect, which is in accordance with results from maternal hypoxia induced by e.g. lowering of the O2 content in the air. The spin trapping agent PBN decreased almokalant induced malformations, suggesting that the defects mainly are caused by reoxygenation damage after episodes of severe embryonic dysrhythmia, rather than "pure hypoxia". Sotalol was tested in a third species, the rabbit who expresses functional IKr channels both in the embryo and in the adult, where it induced developmental toxicity, and indicating that the embryo is more sensitive than the adult towards arrhythmia caused by IKr-blockers.

Ultrasound Current Source Density Imaging (UCSDI) is a noninvasive modality for mapping electrical activities in the body (brain and heart) in 4-dimensions (space + time). Conventional cardiac mapping technologies for guiding the radiofrequency ablation procedure for treatment of cardiac arrhythmias have certain limitations. UCSDI can potentially overcome these limitations and enhance the electrophysiology mapping of the heart. UCSDI exploits the acoustoelectric (AE) effect, an interaction between ultrasound pressure and electrical resistivity. When an ultrasound beam intersects a current path in a material, the local resistivity of the material is modulated by the ultrasonic pressure, and a change in voltage signal can be detected based on Ohm's Law. The degree of modulation is determined by the AE interaction constant K. K is a fundamental property of any type of material, and directly affects the amplitude of the AE signal detected in UCSDI. UCSDI requires detecting a small AE signal associated with electrocardiogram. So sensitivity becomes a major challenge for transferring UCSDI to the clinic. This dissertation will determine the limits of sensitivity and resolution for UCSDI, balancing the tradeoff between them by finding the optimal parameters for electrical cardiac mapping, and finally test the optimized system in a realistic setting. This work begins by describing a technique for measuring K, the AE interaction constant, in ionic solution and biological tissue, and reporting the value of K in excised rabbit cardiac tissue for the first time. K was found to be strongly dependent on concentration for the divalent salt CuSO₄, but not for the monovalent salt NaCl, consistent with their different chemical properties. In the rabbit heart tissue, K was determined to be 0.041 ± 0.012 %/MPa, similar to the measurement of K in physiologic saline: 0.034 ± 0.003 %/MPa. Next, this dissertation investigates the sensitivity limit of UCSDI by quantifying the relation between the recording electrode distance and the measured AE signal amplitude in gel phantoms and excised porcine heart tissue using a clinical intracardiac catheter. Sensitivity of UCSDI with catheter was 4.7 μV/mA (R² = 0.999) in cylindrical gel (0.9% NaCl), and 3.2 μV/mA (R² = 0.92) in porcine heart tissue. The AE signal was detectable more than 25 mm away from the source in cylindrical gel (0.9% NaCl). Effect of transducer properties on UCSDI sensitivity is also investigated using simulation. The optimal ultrasound transducer parameters chosen for cardiac imaging are center frequency = 0.5 MHz and f/number = 1.4. Last but not least, this dissertation shows the result of implementing the optimized ultrasound parameters in live rabbit heart preparation, the comparison of different recording electrode configuration and multichannel UCSDI recording and reconstruction. The AE signal detected using the 0.5 MHz transducer was much stronger (2.99 μV/MPa) than the 1.0 MHz transducer (0.42 μV/MPa). The clinical lasso catheter placed on the epicardium exhibited excellent sensitivity without being too invasive. 3-dimensional cardiac activation maps of the live rabbit heart using only one pair of recording electrodes were also demonstrated for the first time. Cardiac conduction velocity for atrial (1.31 m/s) and apical (0.67 m/s) pacing were calculated based on the activation maps. The future outlook of this dissertation includes integrating UCSDI with 2-dimensional ultrasound transducer array for fast imaging, and developing a multi-modality catheter with 4-dimensional UCSDI, multi-electrode recording and echocardiography capacity.

Orientador: Francisco Villarreal Alvarado / Resumo: Existem diferentes tipos de funções wavelets que podem ser utilizadas na Transformada Wavelet. Na maioria das vezes, a função wavelet escolhida para a análise de um determinado sinal vai ser aquela que melhor se ajusta no domínio tempo-frequência do mesmo. Existem vários tipos de funções wavelets que podem ser escolhidas para certas aplicações, sendo que algumas destas pertencem a conjuntos específicos denominados de famílias wavelets, tais como a Haar, Daubechies, Symlets, Morlet, Meyer e Gaussianas. Nesse trabalho é apresentada uma nova família de funções wavelets geradas a partir de polinômios com coeficientes de Fibonacci (FCPs). Essa família recebe o nome de Golden, e cada membro desta é obtido por uma derivada de ordem n do quociente entre dois FCPs distintos. As Golden wavelets foram deduzidas através das observações de que, em alguns casos, a derivada de ordem n, do quociente entre dois FCPs distintos, resulta em uma função que possui as características de uma onda de duração curta. Como aplicação, algumas wavelets apresentadas no decorrer deste trabalho são utilizadas na classificação de arritmias cardíacas em sinais de eletrocardiograma, que foram extraídos da base de dados do MIT-BIH arrhythmia database. / Mestre

Idiopathic ventricular tachycardias, which occur in patients without structural heart disease, are a common entity, representing up to 10% of all ventricular tachycardias evaluated by cardiac electrophysiology services. Pregnancy can increase the incidence of various cardiac arrhythmias. Factors that can potentially promote arrhythmias in pregnancy include the effects of hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia, and underlying heart disease. Ventricular arrhythmias in pregnancy are repetitive monomorphic ventricular premature complexes and couplets that frequently originate at the right ventricular outflow tract. New onset symptomatic repetitive right ventricular outflow tract ventricular tachycardia during pregnancy has been inadequately reported in the literature. We present a case of symptomatic repetitive right ventricular outflow tract tachycardia that started during pregnancy and continued in the postpartum period, requiring curative treatment with electrophysiology study and radiofrequency ablation.