Análisis de regularidad en fibrilación ventricular: aplicación a registros de mapeado cardíaco

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

Modifications on regularity and spectrum of ventricular fibrillation signal induced by physical training

The objective of this work is to study the modifications on cardiac response during ventricular fibrillation (VF) induced by physical training. The analysis was performed in the frequency domain of VF, and the regularity of the signal was also considered. Two sets of records were acquired: control (G1: without physical training, N=10), and trained (G2, N=9). Cardiac registers were obtained using a 240-electrodes matrix located on left ventricle of isolated rabbit heart. A Langendorff system was used to maintain the heart perfusion. VF was induced by increased frequencies. To analyze the time course of VF, records were processed in 4-second segments. For every segment and channel, Welch periodogram with Hanning window, two non-overlapped sections and zero padding, was computed. Parameters considered in frequency domain are: dominant frequency (DF) and normalized energy (NE: spectral energy in the window DF±1Hz, normalized by spectral energy in 5-35Hz band). For every segment and channel, a regularity analysis of VF was performed, obtaining the regularity index (RI), which is a measure of similarity among local activation waves present in every channel. Mean values for the parameters (DF, NE and RI) of the whole set of electrodes were computed for every segment. Obtained results show that DF is lower for trained rabbits (G1: 18.234±1, 241Hz; G2: 14.370±0, 866Hz; p<0.001). NE is greater for this group (G1: 0.140±0.006; G2: 0.263±0.017; p<0.001), suggesting a greater spectral concentration around DF. Finally, a greater regularity has been observed in the fibrillation signal for trained group (IR, G1: 0.756±0.026; G2: 0.834±0.014; p<0.001). As a summary, the results suggest that both spectral characteristics and regularity of VF signal are clearly different for G1 and G2 groups. The trained group (G2) shows greater regularity, lower DF and spectral dispersion. These factors should be interpreted as a more stable cardiac response to V

Analysis of spatial and temporal evolution of regularity maps during ventricular fibrillation

The analysis of cardiac mapping allows investigating the structure of ventricular fibrillation (VF). This work analyzes regions of interest (ROI) on cardiac maps obtained from the regularity analysis of VF records, providing information about signal regularity at each time instant and its spatial distribution. Cardiac registers were obtained using a 240- electrodes matrix located on left ventricle of isolated rabbit heart. A Langendorff system was used to maintain the heart perfusion. VF was induced by increased frequencies. Two groups of records were considered: control (G1: without physical training, N=10), and trained (G2, N=9). Records were processed in consecutive 4-second segments. Regularity index (RI) was obtained for every segment and channel. RI is a measure of similarity degree among local activation waves for every channel. A map with the RI value of each channel was computed for the 82 register segments. To analyze the spatial distribution of RI, a threshold value was determined experimentally and applied to the map in order to obtain the ROI. Two parameters were calculated: ROI spatial number (ROIsn, a measure of spatial fragmentation), and ROI spatial area (ROIsa, the percentage of area map occupied by ROI). In case of the time course of ROI, two additional parameters were computed: the number of electrodes which value had changed respect to the threshold in two consecutive maps (ROIen, which is related with the change size), and the cumulative absolute differences of RI values for the electrodes which are changed (ROIed). Obtained results for spatial analysis show that the number of ROI is lower for trained rabbits (ROIsn; G1: 4.465±1.120; G2: 2.,227±0.623; p<0.001), but ROI spatial area is greater than the control group (ROIsa; G1: 76.235±5.355%; G2: 88.163±2.885%; p<0.001). Time-course analysis shows that more electrodes change between consecutive maps in the control group (ROIen, G1: 22.455±6.702; G2: 13.877±2.485; p<0.001). No significant differences were found for ROIed (G1: 18.509±6.932; G2: 18.619±4.196; n.s.). To conclude, ROI analysis on RI maps applied to trained and no trained rabbits groups shows that VF cardiac response is more irregular and spatially fragmented in no trained group. In addition, regularity maps are more stable with time in trained group

Relación entre el espectro y la regularidad en la señal de fibrilación ventricular modificada por el ejercicio físico

El presente trabajo estudia las modificaciones intrínsecas que el ejercicio físico produce en la respuesta cardíaca durante la FV. Se han calculado dos parámetros relacionados con el espectro de la señal (FD: frecuencia dominante, y EN: energía normalizada), y otro relacionado con la regularidad de las OAL (IR: índice de regularidad), Se ha realizado un análisis de correlación entre los tres parámetros para valorar su grado de complementariedad. Se consideraron dos grupos de conejos: control (G1: sin entrenamiento, N=10) y entrenados (G2, N=9). Se utilizó un electrodo matricial de 240 canales localizado en ventrículo izquierdo de corazón aislado de conejo perfundido mediante un sistema de Langendorff. La FV se indujo por estimulación a frecuencias crecientes. Los resultados muestran que el grupo entrenado presenta una mayor regularidad de la señal (IR: G1: 0,757+-0,091; G2: 0,845+-0,084; p<0.001), así como menor FD (G1: 18.23±2.96Hz; G2: 14.13+-1.73Hz; p<0.001) y dispersión espectral (EN: G1: 0,138+-0.105; G2: 0,293+-0,176; p<0.001). El análisis de las relaciones entre parámetros muestra correlaciones significativas entre los parámetros para todos los casos excepto para IR y FD en G2, por lo que estos parámetros proporcionan información complementaria, ya que analizan aspectos diferentes de la señal como la morfología de las ondas de activación y su frecuencia. La existencia de correlación entre ambas para G1 puede ser debida a otras causas, tales como las modificaciones en ambos factores inducidas por la presencia de reentradas o colisiones entre frentes de activación.. Como conclusión, los resultados obtenidos sugieren que el entrenamiento físico produce una respuesta cardíaca más estable ante FV, debida a modificaciones intrínsecas en las características electrofisiológicas cardíacas

Analysis of the influence of parasympathetic postganglionic neurons on cardiac response in ventricular fibrillation

Physical training modifies the sympathetic-vagal balance of autonomic nervous system. Previous studies have shown that such training also produces intrinsic modifications of cardiac electrophysiological properties in isolated heart during Ventricular Fibrillation (VF). Ten NZW trained rabbits were studied to test if the modifications are related to the activity of postganglionic parasympathetic neurons. Two records per subject were acquired during VF: before (G1) and after (G2) the infusion of atropine to inhibit the activity of neurons. Mapping records were obtained using a 240-channel electrode array located in the left ventricle of isolated heart (perfused by Langendorff system). VF was induced by stimulation at increasing frequencies. To analyze the time course of fibrillation, the records were processed in 4-second consecutive segments. For each channel and segment, the following parameters were computed: 1) Dominant Frequency (DF), obtained by the Welch periodogram b) Normalized Energy (NE) in a frequency band centered at the DF; c) Regularity Index (RI), which analyzes the similarity of local activation waves in every segment and channel; d) Coefficients of Variance of DF (CVDF), NE (CVNE) and RI (CVRI). For each segment, we obtained the average value of each of the parameters analyzed for all electrodes. The results are: a) DF (G1: 13.671 ± 0.509 Hz, G2: 14.783 ± 0.455 Hz), b) NE (G1: 0.398 ± 0.014; G2: 0.380 ± 0.013); c) RI (G1: 0.855 ± 0.017; G2: 0.865 ± 0.015), d) CVDF (G1: 0.109 ± 0.009; G2: 0.098 ± 0.008), e) CVNE (G1: 0.398 ± 0.014; G2: 0.380 ± 0.013 ) f) CVRI (G1: 0.084 ± 0.009; G2: 0.078 ± 0.008). None of these parameters showed significant differences between groups. Thus, the parasympathetic postganglionic neurons seem to have no effect on the cardiac response in VF due to physical training

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis

Objective Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. Design Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. Results Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. Conclusions p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis

New clinical and toxicological scenario of gammaglutamyltranspeptidase Nueva singladura clínica y toxicológica de la gammaglutamiltranspeptidasa

After the discovery of gammaglutamyltranspeptidase in 1950 by Hanes, the significance of its increased levels in clinical practice has mainly been focused on ethanol toxicity, and also some neoplasms and biliary tract obstruction. More recently, attention has swift to the metabolic functions of this enzyme, as a neutralizer of oxygen free radicals and as a glutathione donor to the cell. High serum levels of gamma-glutamyltranspeptidase is known to occur when oxidative stress is increased, or associated with several vascular risk factors and the insulin resistance syndrome, as an early marker of diabetes. There are also a number of drugs that induce the expression of the tissue enzyme (microsomes) with the result of high serum levels without structural damage to the liver. Because it is a ubiquitous enzyme, a very high number of causes can be involved, that may be difficult to recognize. Finally, because glutathione is necessary to conjugate a number of chemical compounds, from an epidemiological and toxicological perspective, the enzyme might be useful as a biomarker of several ambient toxins. In this review we want to emphasize the increasing clinical and diagnostic significance of this enzyme discovered half a century ago.<br>Desde su descubrimiento en 1950 por Hanes, la enzima gammaglutamiltranspeptidasa, al menos en medicina clínica, se ha vinculado casi en exclusiva, al valor de su aumento en la toxicidad por etanol y, en menor medida, de la existencia de ciertas neoplasias y de bloqueo de la vía biliar. Más recientemente, menudean trabajos acerca de su papel metabólico, mediando la neutralización de radicales libres de oxígeno y aprovisionando de glutatión a las células. El nivel sérico de gammaglutamiltranspeptidasa es expresivo de estrés oxidativo aumentado y se ha asociado a diversos factores de riesgo cardiovascular y a componentes del síndrome de resistencia a la insulina, de modo que sería un biomarcador precoz para el desarrollo de diabetes. Por otro lado numerosos fármacos inducen la enzima tisular (microsomas) pudiendo dar elevaciones séricas que no suponen daño estructural a nivel hepático. Su ubicuidad anátomo-citológica hace que pueda aumentar en suero en numerosos procesos, siendo por ello en ocasiones dificultoso patentizar su origen. Finalmente, desde un ángulo epidemiológico y toxicológico, siendo que el glutatión es necesario para conjugar diversas sustancias químicas, la enzima resultaría un biomarcador, entre otros, de numerosas sustancias nocivas medioambientales. Se incide en conjunto en este ensanchamiento del significado clínico y diagnóstico de una enzima que se creía suficientemente conocida desde hace medio siglo en que se descubrió

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study

Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en Espana˜ en 2019. Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda Espana. ˜ Resultados: Se obtuvo información de 1933 pacientes procedentes de 11 Comunidades Autónomas, de 47 neurólogos o genetistas. Edad media: 53,64 anos ˜ ± 20,51 desviación estándar (DE); 938 varones (48,5%), 995 mujeres (51,5%). En 920 pacientes (47,6%) no se conoce el defecto genético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más frecuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEH recesiva más frecuente es la SPG7. Conclusiones: La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clínicos.Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials