Publication: Caracterización electrofisiológica de la fibrilación y la insuficiencia cardiaca mediante análisis de espacio, tiempo y frecuencia de potenciales cardiacos eléctricos y ópticos
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2017-02-21
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Universidad Complutense de Madrid
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Abstract
Esta Tesis Doctoral está constituida en su mayor parte por 3 artículos publicados en los que la técnica conocida como "cartografiado óptico" tiene un papel esencial. La introducción del cartografiado óptico hace más de dos décadas permitió la caracterización de la propagación de las ondas eléctricas en el corazón con alta resolución espacial (submilimétrica) y temporal (1-3 ms). Una vez se ilumina la región a estudiar con luz cuasi-monocromática (luz de una determinada longitud de onda), una molécula sensible al voltaje previamente inyectada emite fluorescencia que se proyecta sobre una cámara de vídeo especial que es capaz de adquirir imágenes a alta velocidad. A modo de ejemplo de los hallazgos que ha facilitado el cartografiado óptico, su uso postuló a los rotores (reentradas funcionales que generan frentes de onda espirales) como potenciales “directores” de la fibrilación cardiaca en modelos animales. La generación de películas de fase identificó varios patrones de activación durante la fibrilación cardiaca, incluyendo los anteriormente citados rotores, afloramientos/focos, ondas periódicas con alta organización espacio-temporal y actividad desorganizada/rotura de frentes. El análisis espectral de los potenciales de acción ópticos registrados permitió la identificación de áreas de alta frecuencia con potencial para dirigir el proceso de fibrilación incluso en la ausencia de rotores visibles epicárdicamente. Más recientemente, la cartografía simultánea de las superficies endocárdicas y epicárdicas de las aurículas permitió la interpretación del comportamiento de las “ondas pergamino” 3D, cuya manifestación 2D endo o/y epicárdica es usualmente un rotor o un afloramiento. Por lo tanto, el cartografiado óptico puede ser considerado como una herramienta de gran relevancia para registrar los patrones de activación/repolarización durante las arritmias cardiacas, con alta resolución espacial y temporal. Sin embargo, como cualquier técnica, las estrategias actuales de mapeo óptico tienen algunas limitaciones: i) se requiere el uso de moléculas sensibles al voltaje tóxicas que impiden su uso en estudios humanos in vivo; ii) el modelo de corazón aislado utilizado en estudios de cartografiado óptico no incluye el efecto del sistema nervioso autónomo que puede tener un impacto significativo en ciertas arritmias cardíacas, y iii) la tecnología de cartografiado óptico actual no permite registros "panorámicos" endo-epicárdicos simultáneos o verdadero cartografiado intramural...
This Doctoral Thesis largely consists of 3 published articles in which the technique known as “optical mapping” has an essential role. The introduction of optical mapping over two decades ago enabled the characterization of cardiac wave propagation with high spatial (submillimeter) and temporal (1-3 ms) resolution. Upon quasi-monochromatic illumination of the mapped surface (with light of an specific wavelength), a previously injected voltage-sensitive dye emits fluorescence that is projected onto a video camera with high acquisition rate. As an example of the insights provided by this technique, the use of optical mapping postulated rotors (functional re-entries generating spiral wavefronts) as potential drivers of cardiac fibrillation in animal models. Generation of phase movies identified several patterns of activation during cardiac fibrillation, including the aforementioned rotors, but also breakthroughs/foci, spatiotemporally organized periodic waves and disorganized activity/wavebreaks. In addition, spectral analysis of the registered optical action potentials enabled the identification of highfrequency areas potentially driving the fibrillation process, even in the absence of visible epicardial rotors. More recently, simultaneous mapping of the endocardial and epicardial surfaces of the atria enabled interpretation of the 3D behavior of scroll waves, whose 2D endo and/or epicardial manifestations are usually rotors or breakthroughs. Therefore, optical mapping can be considered as a powerful tool to register activation/repolarization patterns during cardiac arrhythmias with high spatiotemporal resolution. However, like any approach, current optical mapping strategies have some limitations: i) they require the use of toxic voltage-sensitive dyes that preclude their use in in-vivo human studies; ii) the isolated heart model used in optical mapping studies does not include the effect of the autonomic nervous system which may have a significant impact on certain cardiac arrhythmias, and iii) the current optical mapping technology does not allow “panoramic” simultaneous endoepicardial or true intramural mapping...
This Doctoral Thesis largely consists of 3 published articles in which the technique known as “optical mapping” has an essential role. The introduction of optical mapping over two decades ago enabled the characterization of cardiac wave propagation with high spatial (submillimeter) and temporal (1-3 ms) resolution. Upon quasi-monochromatic illumination of the mapped surface (with light of an specific wavelength), a previously injected voltage-sensitive dye emits fluorescence that is projected onto a video camera with high acquisition rate. As an example of the insights provided by this technique, the use of optical mapping postulated rotors (functional re-entries generating spiral wavefronts) as potential drivers of cardiac fibrillation in animal models. Generation of phase movies identified several patterns of activation during cardiac fibrillation, including the aforementioned rotors, but also breakthroughs/foci, spatiotemporally organized periodic waves and disorganized activity/wavebreaks. In addition, spectral analysis of the registered optical action potentials enabled the identification of highfrequency areas potentially driving the fibrillation process, even in the absence of visible epicardial rotors. More recently, simultaneous mapping of the endocardial and epicardial surfaces of the atria enabled interpretation of the 3D behavior of scroll waves, whose 2D endo and/or epicardial manifestations are usually rotors or breakthroughs. Therefore, optical mapping can be considered as a powerful tool to register activation/repolarization patterns during cardiac arrhythmias with high spatiotemporal resolution. However, like any approach, current optical mapping strategies have some limitations: i) they require the use of toxic voltage-sensitive dyes that preclude their use in in-vivo human studies; ii) the isolated heart model used in optical mapping studies does not include the effect of the autonomic nervous system which may have a significant impact on certain cardiac arrhythmias, and iii) the current optical mapping technology does not allow “panoramic” simultaneous endoepicardial or true intramural mapping...
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Medicina, leída el 04/02/2016. Tesis formato europeo (compendio de artículos)