Investigación del perfil de riesgo preoperatorio en cirugía cardiaca : validación de nuevos modelos concretos de estratificación

La presente investigación tiene como propósito la identificación de factores de riesgo preoperatorios de carácter predictivo frente a la mortalidad hospitalaria tras cirugía cardiaca en el ámbito de la Comunidad de Extremadura. Hemos logrado identificar doce variables preoperatorias de riesgo y definir un modelo de predicción (ERQUICE) de mortalidad esperada en función del perfil de riesgo de cada paciente concreto. Otro propósito de este estudio es ponderar el valor de nuestro modelo predictivo (ERQUICE) frente a otros descritos en la literatura internacional, así como explorar la aplicabilidad de estos últimos en el entorno sanitario de la comunidad extremeña. Pensamos que la herramienta descrita (el modelo ERQUICE), constituye una utilidad necesaria para acometer políticas de toma de decisiones, enmarcadas en el ámbito de mejora de la calidad asistencial de la cirugía cardiaca en Extremadur

Automatic quantification of cardiomyocyte dimensions and connexin 43 lateralization in fluorescence images

Cardiomyocytes’ geometry and connexin 43 (CX43) amount and distribution are structural features that play a pivotal role in electrical conduction. Their quantitative assessment is of high interest in the study of arrhythmias, but it is usually hampered by the lack of automatic tools. In this work, we propose a software algorithm (Myocyte Automatic Retrieval and Tissue Analyzer, MARTA) to automatically detect myocytes from fluorescent microscopy images of cardiac tissue, measure their morphological features and evaluate the expression of CX43 and its degree of lateralization. The proposed software is based on the generation of cell masks, contouring of individual cells, enclosing of cells in minimum area rectangles and splitting of these rectangles into end-to-end and middle compartments to estimate CX43 lateral-to-total ratio. Application to human ventricular tissue images shows that mean differences between automatic and manual methods in terms of cardiomyocyte length and width are below 4 µm. The percentage of lateral CX43 also agrees between automatic and manual evaluation, with the interquartile range approximately covering from 3% to 30% in both cases. MARTA is not limited by fiber orientation and has an optimized speed by using contour filtering, which makes it run hundreds of times faster than a trained expert. Developed for CX43 studies in the left ventricle, MARTA is a flexible tool applicable to morphometric and lateralization studies of other markers in any heart chamber or even skeletal muscle. This open-access software is available online.Fil: Oliver Gelabert, Antoni. Universidad de Zaragoza; EspañaFil: García Mendívil, Laura. Universidad de Zaragoza; EspañaFil: Vallejo Gil, José María. University Hospital Miguel Servet; EspañaFil: Fresneda Roldán, Pedro Carlos. University Hospital Miguel Servet; EspañaFil: Andelová, Katarína. Centre of Experimental Medicine; EslovaquiaFil: Fañanás Mastral, Javier. University Hospital Miguel Servet; EspañaFil: Vázquez Sancho, Manuel. University Hospital Miguel Servet; EspañaFil: Matamala Adell, Marta. University Hospital Miguel Servet; EspañaFil: Sorribas Berjón, Fernando. University Hospital Miguel Servet; EspañaFil: Ballester Cuenca, Carlos. University Hospital Miguel Servet; EspañaFil: Tribulova, Narcisa. Centre of Experimental Medicine; EslovaquiaFil: Ordovás, Laura. Universidad de Zaragoza; EspañaFil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pueyo, Esther. Biomedical Research Networking Center in Bioengineering; España. Universidad de Zaragoza; Españ

Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution

Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers: CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratomesliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verifed viability. Optically mapped transmembrane potentials confrmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically.Fil: Oliván Viguera, Aida. Universidad de Zaragoza; EspañaFil: Pérez Zabalza, María. Universidad de Zaragoza; EspañaFil: García Mendívil, Laura. Universidad de Zaragoza; EspañaFil: Mountris, Konstantinos A.. Universidad de Zaragoza; EspañaFil: Orós Rodrigo, Sofía. Universidad de Zaragoza; EspañaFil: Ramos Marquès, Estel. Universidad de Zaragoza; EspañaFil: Vallejo Gil, José María. University Hospital Miguel Servet; EspañaFil: Fresneda Roldán, Pedro Carlos. University Hospital Miguel Servet; EspañaFil: Fañanás Mastral, Javier. University Hospital Miguel Servet; EspañaFil: Vázquez Sancho, Manuel. University Hospital Miguel Servet; EspañaFil: Matamala Adell, Marta. University Hospital Miguel Servet; EspañaFil: Sorribas Berjón, Fernando. University Hospital Miguel Servet; EspañaFil: Bellido Morales, Javier André. University Hospital Miguel Servet; EspañaFil: Mancebón Sierra, Francisco Javier. University Hospital Miguel Servet; EspañaFil: Vaca Núñez, Alexánder Sebastián. University Hospital Miguel Servet; EspañaFil: Ballester Cuenca, Carlos. University Hospital Miguel Servet; EspañaFil: Marigil, Miguel Ángel. Hospital San Jorge; EspañaFil: Pastor, Cristina. Aragón Institute of Health Sciences; EspañaFil: Ordovás, Laura. Aragón Agency for Research and Development; España. Universidad de Zaragoza; EspañaFil: Köhler, Ralf. Aragón Institute of Health Sciences; España. Aragón Agency for Research and Development; EspañaFil: Diez, Emiliano Raúl. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Humana Normal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pueyo, Esther. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina; España. Universidad de Zaragoza; Españ

Investigación del perfil de riesgo preoperatorio en cirugía cardiaca : validación de nuevos modelos concretos de estratificación

La presente investigación tiene como propósito la identificación de factores de riesgo preoperatorios de carácter predictivo frente a la mortalidad hospitalaria tras cirugía cardiaca en el ámbito de la Comunidad de Extremadura. Hemos logrado identificar doce variables preoperatorias de riesgo y definir un modelo de predicción (ERQUICE) de mortalidad esperada en función del perfil de riesgo de cada paciente concreto. Otro propósito de este estudio es ponderar el valor de nuestro modelo predictivo (ERQUICE) frente a otros descritos en la literatura internacional, así como explorar la aplicabilidad de estos últimos en el entorno sanitario de la comunidad extremeña. Pensamos que la herramienta descrita (el modelo ERQUICE), constituye una utilidad necesaria para acometer políticas de toma de decisiones, enmarcadas en el ámbito de mejora de la calidad asistencial de la cirugía cardiaca en Extremadur

Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution

Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers: CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research