Efectos electrofisiológicos miocárdicos intrínsecos producidos por la inhibición del sistema de intercambio sodio-protón, en condiciones de normoxia, y tras la isquemia miocárdica regional. Estudio experimental.

RESUMEN Hemos investigado: 1) los efectos protectores del intercambiador sodio-protón (NHE), con el 5-(N-etil-N-isopropil) amiloride (EIPA), a concentración 0.4 M, sobre la inducibilidad de la fibrilación ventricular (FV), y sobre la refractariedad miocárdica ventricular, tras la oclusión arterial coronaria; 2) los efectos electrofisiológicos intrínsecos producidos por la inhibición del NHE, administrando EIPA 0.4 y 1 M, en condiciones de normal oxigenación, sobre el automatismo sinusal, la conducción sinoauricular y auriculoventricular (AV), y sobre la refractariedad auricular, ventricular, y del sistema de conducción AV; y 3) los efectos electrofisiológicos miocárdicos intrínsecos producidos por la inhibición del NHE, con EIPA 0.4 y 1 M, sobre la frecuencia dominante (FD) de la FV inducida, en condiciones de normoxia, como característica electrofisiológica estrechamente relacionada con la refractariedad ventricular. Todos los experimentos se realizaron en corazón aislado y perfundido de conejo (preparación tipo Langendorff). Para conseguir el primer objetivo aplicamos el test del extraestímulo (TEE) ventricular con uno, dos, y tres extraestímulos, para tratar de inducir la FV. La aplicación del primer extraestímulo sirvió además para establecer el periodo refractario objeto de investigación. Las determinaciones se realizaron previamente y tras la oclusión arterial coronaria circunfleja, en dos grupos de experimentos: control y tratados con EIPA 0.4 M. Para cumplimentar el segundo objetivo analizamos: a) periodos refractarios efectivo y funcional auricular y del sistema de conducción AV mediante el TEE auricular, periodos refractarios efectivo y funcional ventricular mediante el TEE ventricular; b) automatismo sinusal mediante la determinación de la longitud del ciclo sinusal y del tiempo de recuperación del nodo sinusal; y c) tiempo de conducción sinoauricular con el test de Narula, conducción AV y conducción ventriculoauricular retrógrada, mediante la medición de la longitud del ciclo de Wenckebach y la longitud del ciclo de Wenckebach retrógrado respectivamente. Finalmente, para acometer el tercer objetivo analizamos, por el método de Welch, la FD media, máxima y mínima de la FV inducida por estimulación a frecuencias crecientes. Los parámetros citados se estudiaron en situación control e inhibiendo el NHE, con EIPA. Utilizamos dos concentraciones de dicho inhibidor: 0.4 y 1 M; la primera se halla en el rango de la IC50 para el NHE y la segunda es la concentración más comúnmente usada en los estudios de protección miocárdica. La inhibición del NHE con EIPA 0.4 M protegió al miocardio isquémico, al dificultar la inducibilidad de la FV. Este efecto protector, probablemente está relacionado, al menos en parte, con el mantenimiento de la refractariedad ventricular en el miocardio isquémico, lo cual ha sido también observado en el presente trabajo. Excepto para el caso del periodo refractario efectivo del sistema de conducción AV, que aumentó ligeramente con EIPA 1 M, la inhibición del NHE con EIPA 0.4 y 1 M en condiciones de normal oxigenación, no modificó la refractariedad intrínseca ventricular, auricular, ni del sistema de conducción AV, así como tampoco la FD de la FV inducida, mientras que deprimió ligeramente el cronotropismo sinusal y la conducción AV, si bien estos últimos podrían ser efectos secundarios, relacionados con la capacidad depresora del automatismo sinusal y la conducción AV que ejerce el amiloride, precursor del EIPA. El hecho de que la inhibición del NHE, manifestara efectos electrofisiológicos antiarrítmicos intrínsecos sobre el miocardio isquémico, impidiendo la caída de la refractariedad, y no ejerciera ninguna modificación electrofisiológica, en condiciones de normal oxigenación, sobre la refractariedad y la FD de la FV, propiedades ligadas a la aparición de arritmias por reentrada, coincide con lo relatado por diversos investigadores acerca del escaso, sino nulo, papel del NHE en situación fisiológica y su importancia en circunstancias fisiopatológicas como la isquemia. __________________________________________________________________________________________________We have investigated the protective effects of the sodium-proton exchanger (NHE) inhibition using 5-(N-ethyl-N-isopropyl) amiloride (EIPA) 0.4 M, on the incidence of induced ventricular fibrillation (VF), and on intrinsic ventricular refractoriness, after circumflex coronary artery occlusion. Experiments were performed on isolated rabbit heart. To induce VF extrastimulus test with one, two and three extrastimuli, was used; the first extrastimulus application also served to determine refractory periods. Parameters were determined previously and after coronary occlusion, in both control and EIPA 0.4 M treated groups. In order to investigate whether the NHE inhibition produces some myocardial intrinsic electrophysiological effect, we have also investigated using EIPA, 0.4 and 1 M, in normoxic condition: a) the sinus cycle length and sinus node recovery time, as an automatism index; b) the sinoatrial conduction (Narulas test), and atrioventricular (AV) and ventricleatrial conduction, by anterograde and retrograde Wenckebach cycle length determination respectively; c) atrial, ventricular, and AV conduction system, effective and functional refractory periods using the extrastimulus test; and d) mean, minimum and maximum dominant frequency (DF) of VF by the Welchs method, which are properties closely related with ventricular refractoriness. NHE inhibition with 0.4 M protected the ischemic myocardium, decreasing VF inducibility, at least in part, by the maintenance of ischemic myocardium refractoriness, observed in this study. No modification on refractoriness was observed, in normoxic conditions, except an AV conduction system effective refractory period increase, with EIPA 1 M. The DF of VF was either not modified. EIPA 0.4 and 1 M also slightly depressed sinus chronotropism and AV conduction

The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity

The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to aphysical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four diVerent pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular Wbrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 ¿M), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These Wndings reveal that the myocardial electrophysiological modiWcations produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.The authors thank Carmen Rams, Ana Diaz, Pilar Navarro and Cesar Avellaneda for their excellent technical assistance. This work has been supported by grants from the Spanish Ministry of Education and Science (DEP2007-73234-C03-01) and Generalitat Valenciana (PROMETEO 2010/093). M Zarzoso was supported by a research scholarship from Generalitat Valenciana (BFPI/2008/003).Zarzoso Muñoz, M.; Such Miquel, L.; Parra Giraldo, G.; Brines Ferrando, L.; Such, L.; Chorro, F.; Guerrero, J.... (2012). The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity. European Journal of Applied Physiology. 112(6):2185-2193. https://doi.org/10.1007/s00421-011-2189-4S218521931126Armour JA, Hopkins DA (1990a) Activity of in vivo canine ventricular neurons. Am J Physiol Heart Circ Physiol 258:H326–H336. doi: 10.1152/ajpregu.00183.2004Armour JA, Hopkins DA (1990b) Activity of canine in situ left atrial ganglion neurons. Am J Physiol Heart Circ Physiol 259:H1207–H1215Armour JA (2004) Cardiac neuronal hierarchy in health and disease. 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Alteration of Ventricular Fibrillation by Flecainide, Verapamil, and Sotalol

Background—The purpose of this study was to determine whether the myocardial electrophysiological properties are useful for predicting changes in the ventricular fibrillatory pattern. Methods and Results—Thirty-two Langendorff-perfused rabbit hearts were used to record ventricular fibrillatory activity with an epicardial multiple electrode. Under control conditions and after flecainide, verapamil, or d,l-sotalol, the dominant frequency (FrD), type of activation maps, conduction velocity, functional refractory period, and wavelength (WL) of excitation were determined during ventricular fibrillation (VF). Flecainide (1.9±0.3 versus 2.4±0.6 cm, P<0.05) and sotalol (2.1±0.3 versus 2.5±0.5 cm, P<0.05) prolonged WL and diminished FrD during VF, whereas verapamil (2.0±0.2 versus 1.7±0.2 cm, P<0.001) shortened WL and increased FrD. Simple linear regression revealed an inverse relation between FrD and the functional refractory period (r=0.66, P<0.0001), a direct relation with respect to conduction velocity (r=0.33, P<0.01), and an inverse relation with respect to WL estimated during VF (r=0.49, P<0.0001). By stepwise multiple regression, the functional refractory periods were the only predictors of FrD. Flecainide and sotalol increased the circuit size of the reentrant activations, whereas verapamil decreased it. The 3 drugs significantly reduced the percentages of more complex activation maps during VF. Conclusions—The activation frequency is inversely related to WL during VF, although a closer relation is observed with the functional refractory period. Despite the diverging effects of verapamil versus flecainide and sotalol on the activation frequency, WL, and size of the reentrant circuits, all 3 drugs reduce activation pattern complexity during VF.Chorro Gasco, Francisco Javier, [email protected] ; Guerrero Martinez, Juan Francisco, [email protected] ; Sanchis Fores, Juan, [email protected] ; Such Belenguer, Luis, [email protected]

Competitiveness and overtourism: a proposal for an early warning system in Spanish urban destinations

The tourism industry is undergoing accelerated changes that pose significant challenges for both destination and business managers as well as for researchers of the tourism phenomenon. Two of these challenges that are particularly relevant are the emergence of the sharing economy and its influence on the degree of overtourism perceived in the tourist destinations. This paper addresses the subject through the use of machine learning techniques. The findings show that machine learning techniques are especially well-suited tools for dealing with these kinds of tourism issues. The findings also show that for the Spanish case, tourism competitiveness is a key predictor of overtourism

Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart

[EN] A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1 mu M), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activation complexity, as an approach to myocardial heterogeneity and stability. The VV interval was longer in the trained group than in the control group both prior to atropine (78 +/- 10 vs. 68 +/- 10 ms) and after atropine (76 +/- 8 vs. 67 +/- 10 ms). Likewise, FRPVF was longer in the trained group than in the control group both prior to and after atropine (53 +/- 8 vs. 42 +/- 7 ms and 50 +/- 6 vs. 40 +/- 6 ms, respectively), and atropine did not modify FRPVF. The CV of FRPVF was lower in the trained group than in the control group prior to atropine (12.5 +/- 1.5% vs. 15.1 +/- 3.8%) and, decreased after atropine (15.1 +/- 3.8% vs. 12.2 +/- 2.4%) in the control group. The trained group showed higher NE values before (0.40 +/- 0.04 vs. 0.36 +/- 0.05) and after atropine (0.37 +/- 0.04 vs. 0.34 +/- 0.06; p = 0.08). Training decreased the CV of NE both before (23.3 +/- 2% vs. 25.2 +/- 4%; p = 0.08) and after parasympathetic blockade (22.6 +/- 1% vs. 26.1 +/- 5%). Cholinergic blockade did not modify these parameters within the control and trained groups. Activation complexity was lower in the trained than in the control animals before atropine (34 +/- 8 vs. 41 +/- 5), and increased after atropine in the control group (41 +/- 5 vs. 48 +/- 9, respectively). Thus, training decreases the intrinsic heterogeneity of the myocardium, increases electrophysiological stability, and prevents some modifications due to muscarinic block.This research was supported by the Spanish Ministry of Education and Science, (DEP2007-73234-C03-01 to AMA), http://www.mecd.gob.es/portada-mecd/; and the Generalitat Valenciana (PROMETEO 2010/093 to FJC, and FPI/2008/003 to MZ), http://www.gva.es/va/inicio/presentacion; jsessionid=ydprbDQZTsCTz85W1Such-Miquel, L.; Brines-Ferrando, L.; Alberola, A.; Zarzoso Muñoz, M.; Chorro Gasco, FJ.; Guerrero-Martínez, JF.; Parra-Giraldo, G.... (2018). Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart. 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Análisis del efecto del ejercicio físico en la homogeneidad espacial del espectro de la señal de fibrilación ventricular

El presente trabajo estudia las modificaciones intrínsecas que el ejercicio físico produce en la respuesta cardíaca durante fibrilación ventricular (FV), tanto en condiciones de perfusión estable como cuando se produce isquemia en una zona del miocardio. Se estudiarán dichas modificaciones comparándolas con las producidas por el efecto de un fármaco (Glibenclamida) y con un grupo control. El análisis se realizará desde el punto de vista del dominio frecuencial, estudiando la homogeneidad espacial de la frecuencia dominante (ROIsaFD) y de la energía normalizada (ROIsaEN), en registros de cartografía cardíaca unipolar de corazón aislado de conejo. Se utilizarán tres grupos de conejos: control (GC: sin entrenamiento, N=18), entrenados (GE: N=9) y fármaco (GF: sin entrenamiento, con tratamiento, N=15). Se realizarán comparaciones intergrupos, teniendo en cuenta el hecho de que se realizan medidas repetidas en el tiempo, y se harán comparaciones intragrupos para estudiar el efecto del tiempo. Los resultados obtenidos sugieren que los efectos intrínsecos producidos por ejercicio físico sobre la homogeneidad espacial de la respuesta espectral de la FV son similares a los producidos por el tratamiento con Glibenclamida, especialmente cuando se tienen zonas isquémicas

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Las técnicas utilizadas en el análisis de la señal de fibrilación ventricular (FV), obtenida mediante sistemas de mapeado utilizando matrices de electrodos, extraen información del proceso a partir de parámetros calculados principalmente en el dominio del tiempo o de la frecuencia. El presente trabajo plantea la aplicación del índice de regularidad (IR), propuesto inicialmente para caracterizar la fibrilación auricular humana, a la señal de FV en un modelo experimental de corazón animal. Los resultados obtenidos muestran que el IR permite extraer información de los mapas de FV no disponible de forma directa cuando se estudian mediante los métodos clásicos en el tiempo o la frecuencia, cuantificando el grado de modificación en la morfología de las ondas de activación durante la FV

El reto de la competitividad turística a largo plazo en la era de la innovación: España como caso de estudio

This article questions whether the innovation deficit observed in the tourism sector on a global scale also characterises the world’s leading power in terms of tourism competitiveness and whether Spain is taking the right steps so as to guarantee the future leadership of its destinations. Spain’s innovative framework will be analysed in its European context, placing emphasis on the innovative intensity of the most important tourist regions. Spanish tourism companies and their capacity for innovation will also be studied in relation to those operating in other sectors. Formulas for generating tourism industries capable of assimilating and creating innovation will be proposed as a way of tackling the transformations that the sector is currently experiencing with the emergence of smart tourism destinations, the sharing economy and other disruptive changes, such as artificial intelligence. It is important to take a long-term perspective of competitiveness in which innovation and digital transformation have become the centre of political, social and corporate action in the sector. Meeting these challenges will mean the implementation of a series of more specific policies and strategies that will foster Smart Tourist Destinations and the development of a more digitalised and responsible economy in which the collaboration between citizens and tourists within the destination is the frame of reference.Este artículo cuestiona si el déficit de innovación observado en el sector turístico a escala global también caracteriza la capacidad de liderazgo en lo que respecta a competitividad turística, y también si España está dando los pasos adecuados para garantizar el liderazgo futuro de sus destinos. El marco de referencia de la innovación española será analizado en su contexto europeo, haciendo énfasis en la intensidad de innovación de las regiones turísticas más importantes. Las empresas turísticas españolas y su capacidad innovadora también serán analizadas, en relación a otras que operan en sectores distintos. Se harán propuestas para estimular la generación de industrias turísticas capaces de asimilar y crear innovación, como una manera de abordar las transformaciones que el sector está experimentando en la actualidad con la emergencia de los destinos turísticos inteligentes, la economía colaborativa y otros cambios disruptivos, como la inteligencia artificial. Es importante adoptar una perspectiva de largo plazo de la competitividad en la cual la innovación y la transformación digital se conviertan en el eje de las acciones tanto políticas como sociales y corporativas del sector. Enfrentar este desafío supondrá la implementación de una serie de políticas y estrategias más específicas que, a su vez, fomentarán los Destinos Turísticos Inteligentes y el desarrollo de una economía más digitalizada pero también más responsable en la que la colaboración entre ciudadanos y turistas dentro del destino sea el marco de referencia

EL DESARROLLO DEL TURISMO EN EL PARQUE NATURAL DEL ALTO TAJO

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Se puede entender que la economía colaborativa no es sino una continuación de la revolución tecnológica que vive el sector turístico, cuya naturaleza transversal, unida al alto volumen de demandantes, le permite ser un campo de pruebas, aplicación y desarrollo de numerosos avances tecnológicos. Sin duda se abren multitud de preguntas acerca de la regulación, el futuro o las consecuencias para los sectores tradicionales e impacto sobre el turismo. Este artículo trata de explorar el efecto de la economía colaborativa en el turismo, y de forma concreta sobre el sector del alojamiento, en cuestiones de diversificación de la oferta y competencia para los hoteles tradicionales. Para ello se llevará a cabo una revisión de la literatura sobre la influencia de AirBnB y plataformas similares y, posteriormente, se plantea un estudio empírico, valorando desde un punto de vista de ubicación, la distribución de la oferta hotelera y de viviendas de alquiler online para la ciudad de Alicante