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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; España Fil: Pérez Zabalza, María. Universidad de Zaragoza; España Fil: García Mendívil, Laura. Universidad de Zaragoza; España Fil: Mountris, Konstantinos A.. Universidad de Zaragoza; España Fil: Orós Rodrigo, Sofía. Universidad de Zaragoza; España Fil: Ramos Marquès, Estel. Universidad de Zaragoza; España Fil: Vallejo Gil, José María. University Hospital Miguel Servet; España Fil: Fresneda Roldán, Pedro Carlos. University Hospital Miguel Servet; España Fil: Fañanás Mastral, Javier. University Hospital Miguel Servet; España Fil: Vázquez Sancho, Manuel. University Hospital Miguel Servet; España Fil: Matamala Adell, Marta. University Hospital Miguel Servet; España Fil: Sorribas Berjón, Fernando. University Hospital Miguel Servet; España Fil: Bellido Morales, Javier André. University Hospital Miguel Servet; España Fil: Mancebón Sierra, Francisco Javier. University Hospital Miguel Servet; España Fil: Vaca Núñez, Alexánder Sebastián. University Hospital Miguel Servet; España Fil: Ballester Cuenca, Carlos. University Hospital Miguel Servet; España Fil: Marigil, Miguel Ángel. Hospital San Jorge; España Fil: Pastor, Cristina. Aragón Institute of Health Sciences; España Fil: Ordovás, Laura. Aragón Agency for Research and Development; España. Universidad de Zaragoza; España Fil: Köhler, Ralf. Aragón Institute of Health Sciences; España. Aragón Agency for Research and Development; España Fil: 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; Argentina Fil: Pueyo, Esther. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina; España. Universidad de Zaragoza; España

Cardiomyocytes&rsquo, 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 &mu, m. 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.

ResumenObjetivoLa disección de arterias coronarias es una entidad con escasa frecuencia. Su espectro clínico puede abarcar desde la muerte súbita, el infarto agudo de miocardio o la angina de pecho. No hay un consenso acerca de la mejor opción terapéutica.MétodosSe analizan 4 casos acontecidos en los últimos años. Un varón de 56 años y una mujer de 50 años en los que se realiza cirugía de revascularización miocárdica, una mujer de 46 años en la que se implanta un stent, y una mujer de 48 años en la que se decide tratamiento médico.ResultadosDichos pacientes presentaron una evolución favorable pudiendo ser dados de alta. En seguimiento, los pacientes sometidos a cirugía no han presentado otros eventos de interés, permaneciendo estables. En el caso de la paciente sobre la que se realizó intervencionismo presentó redisección con implante de nuevo stent a los 3 años. El último caso ha permanecido estable y ha sido dado de alta recientemente.ConclusionesLa conducta a seguir es variada sin existir consenso ni estandarización. Si el paciente está estable y el vaso es pequeño puede considerarse tratamiento médico. Si el paciente está inestable hay una mayor indicación de intervencionismo. En los casos de disección del tronco coronario izquierdo y multivaso la tendencia es hacia la cirugía de bypass coronaria. Dada la escasa incidencia de la enfermedad sería interesante el estudio de series mayores de casos para la confrontación de resultados y poder determinar de una manera más eficaz el mejor tratamiento a seguir.AbstractObjectivesCoronary artery dissection is a rare clinical entity. Its clinical form of presentation has a wide spectrum from sudden death and acute myocardial infarction, to angina. There is no consensus about the best treatment.MethodsFour patients are presented: a 56 year-old male and a 50 year-old female who underwent coronary artery bypass surgery, a 46 year-old female who had percutaneous coronary artery revascularisation and a 48 year-old female who had medical treatment.ResultsThe patients who underwent surgery have been uneventful. The patient with coronary artery stenting had re-dissection and re-stenting. The woman who had medical treatment has been stable.ConclusionsAlthough the treatment of these patients is varied, there is no consensus, or standardisation. If a patient is stable and has small vessel disease, medical treatment can be a good option. If patient is unstable and has main or multi-vessel disease, coronary artery bypass surgery is preferred. Additional studies are needed to conduct a better evaluation of treatment.

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., The biological age, measured by transcriptional markers, explains better than the chronological age the transcriptional dynamics of the human aging myocardium. microRNAs that change expression in the aging left ventricle are identified. Such microRNAs potentially regulate genes with cardiac‐specific functions. Cardiac‐enriched microRNAs that increase or decrease with biological age are present in plasma. They are thus candidate biomarkers to represent the biological age of the heart.

Optical mapping (OM) allows ex vivo measurement of electrophysiological signals at high spatio-temporal resolution, but the signal-to-roise ratio is commonly low. A variety of software options have been proposed to extract relevant information from OM recordings, being ElectroMap the most advanced tool currently available. In this study, improved methods are presented for processing OM signals of cardiac transmembrane voltage. A software called OMap is developed that incorporates novel techniques into ElectroMap for improved baseline drift removal, spatiotemporal filtering and characterization of action potential duration (APD) maps. In synthetically generated signals contaminated with baseline wander, white noise and the combination of both, the errors in APD maps between noisy and clean signals are remarkably lower for OMap than for ElectroMap, particularly for high noise levels. In OM signals recorded from human ventricular tissue specimens, OMap allows to clearly characterize the APD shortening effect induced by ß-adrenergic stimulation, whereas ElectroMap renders highly overlapped APD distributions for baseline and ß-adrenergic stimulation. In conclusion, improved methods are proposed and tested to characterize human ventricular electrophysiology from noisy OM recordings. Fil: Perez Zabalza, Maria. Universidad de Zaragoza; España Fil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Rhyins, Julia. Northeastern University; Estados Unidos Fil: Mountris, Kostantinos A.. Universidad de Zaragoza; España Fil: Vallejo Gil, Jose M.. Hospital Miguel Servet; España Fil: Fresneda Roldan, Pedro C.. Hospital Miguel Servet; España Fil: Fananas-Mastral, Javier. Hospital Miguel Servet; España Fil: Matamal Adell, Marta. Hospital Miguel Servet; España Fil: Sorribas Berjon, Fernando. Hospital Miguel Servet; España Fil: Vazquez Sancho, Manuel. Hospital Miguel Servet; España Fil: Ballester Cuenca, Carlos. Hospital Miguel Servet; España Fil: Segovia Roldan, Margarita. Universidad de Zaragoza; España Fil: Olivan Viguera, Aida. Universidad de Zaragoza; España Fil: Pueyo, Esther. Universidad de Zaragoza; España