RESUMEN
One of the most vital processes of the body is the cardiovascular system's proper operation. Physiological processes in the heart are regulated by the balance of cardioprotective and pathological mechanisms. The insulin-like growth factor system (IGF system, IGF signaling pathway) plays a pivotal role in regulating growth and development of various cells and tissues. In myocardium, the IGF system provides cardioprotective effects as well as participates in pathological processes. This review summarizes recent data on the role of IGF signaling in cardioprotection and pathogenesis of various cardiovascular diseases, as well as analyzes severity of these effects in various scenarios.
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Enfermedades Cardiovasculares , Miocardio , Transducción de Señal , Humanos , Animales , Miocardio/metabolismo , Enfermedades Cardiovasculares/metabolismo , Somatomedinas/metabolismo , Corazón/fisiología , Factor I del Crecimiento Similar a la Insulina/metabolismoRESUMEN
Rationale: Regulatory processes of transcription factors (TFs) shape heart development and influence the adult heart's response to stress, contributing to cardiac disorders. Despite their significance, the precise mechanisms underpinning TF-mediated regulation remain elusive. Here, we identify that EBF1, as a TF, is highly expressed in human heart tissues. EBF1 is reported to be associated with human cardiovascular disease, but its roles are unclear in heart. In this study, we investigated EBF1 function in cardiac system. Methods: RNA-seq was utilized to profile EBF1 expression patterns. CRISPR/Cas9 was utilized to knock out EBF1 to investigate its effects. Human pluripotent stem cells (hPSCs) differentiated into cardiac lineages were used to mimic cardiac development. Cardiac function was evaluated on mouse model with Ebf1 knockout by using techniques such as echocardiography. RNA-seq was conducted to analyze transcriptional perturbations. ChIP-seq was employed to elucidate EBF1-bound genes and the underlying regulatory mechanisms. Results: EBF1 was expressed in some human and mouse cardiomyocyte. Knockout of EBF1 inhibited cardiac development. ChIP-seq indicated EBF1's binding on promoters of cardiogenic TFs pivotal to cardiac development, facilitating their transcriptional expression and promoting cardiac development. In mouse, Ebf1 depletion triggered transcriptional perturbations of genes, resulting in cardiac remodeling. Mechanistically, we found that EBF1 directly bound to upstream chromatin regions of cardiac hypertrophy-inducing genes, contributing to cardiac hypertrophy. Conclusions: We uncover the mechanisms underlying EBF1-mediated regulatory processes, shedding light on cardiac development, and the pathogenesis of cardiac remodeling. These findings emphasize EBF1's critical role in orchestrating diverse aspects of cardiac processes and provide a promising therapeutic intervention for cardiomyopathy.
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Perfilación de la Expresión Génica , Miocitos Cardíacos , Transactivadores , Animales , Humanos , Ratones , Transactivadores/genética , Transactivadores/metabolismo , Miocitos Cardíacos/metabolismo , Diferenciación Celular/genética , Corazón/fisiopatología , Ratones Noqueados , Células Madre Pluripotentes/metabolismo , Transcriptoma/genética , Sistemas CRISPR-Cas/genéticaRESUMEN
The quantification of cardiac strains as structural indices of cardiac function has a growing prevalence in clinical diagnosis. However, the highly heterogeneous four-dimensional (4D) cardiac motion challenges accurate "regional" strain quantification and leads to sizable differences in the estimated strains depending on the imaging modality and post-processing algorithm, limiting the translational potential of strains as incremental biomarkers of cardiac dysfunction. There remains a crucial need for a feasible benchmark that successfully replicates complex 4D cardiac kinematics to determine the reliability of strain calculation algorithms. In this study, we propose an in-silico heart phantom derived from finite element (FE) simulations to validate the quantification of 4D regional strains. First, as a proof-of-concept exercise, we created synthetic magnetic resonance (MR) images for a hollow thick-walled cylinder under pure torsion with an exact solution and demonstrated that "ground-truth" values can be recovered for the twist angle, which is also a key kinematic index in the heart. Next, we used mouse-specific FE simulations of cardiac kinematics to synthesize dynamic MR images by sampling various sectional planes of the left ventricle (LV). Strains were calculated using our recently developed non-rigid image registration (NRIR) framework in both problems. Moreover, we studied the effects of image quality on distorting regional strain calculations by conducting in-silico experiments for various LV configurations. Our studies offer a rigorous and feasible tool to standardize regional strain calculations to improve their clinical impact as incremental biomarkers.
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Fantasmas de Imagen , Ratones , Animales , Imagen por Resonancia Magnética/métodos , Simulación por Computador , Corazón/diagnóstico por imagen , Corazón/fisiología , Modelos Cardiovasculares , Humanos , Análisis de Elementos Finitos , AlgoritmosRESUMEN
S-Limonene (s-Lim) is a monocyclic monoterpene found in a variety of plants and has been shown to present antioxidant and cardioprotective activity in experimental models of myocardial infarction. The aim of this study was to evaluate the potential mechanism by which s-Lim exerts its antiarrhythmic effect, focusing on the blockade of ß-adrenoceptor (ß-AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the ß-adrenergic pathway, sarcomeric shortening and L-type calcium current (ICa,L). In isolated hearts, 10 µM of s-Lim did not alter the ECG profile or LVPD. s-Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50 µM and reduced heart rate at the concentrations of 30 (12.4%) and 50 µM (16.6%). s-Lim (10 µM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1 µM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s-Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker ß1-AR). In vivo, s-Lim antagonized the effect of ISO (agonists ß1-AR), presenting a similar effect to propranolol (a non-selective blocker ß-AR). In ventricular cardiomyocyte, s-Lim did not alter the voltage dependence for ICa,L activation or the ICa,L density. In addition, s-Lim did not affect changes in the ECG effect mediated by 5 µM forskolin (an activator of adenylate cyclase). In an in vivo caffeine/ISO-induced arrhythmia model, s-Lim (1 mg/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s-Lim is related to blockade of ß-AR in the heart.
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Antiarrítmicos , Limoneno , Ratas Wistar , Receptores Adrenérgicos beta , Transducción de Señal , Animales , Ratas , Antiarrítmicos/farmacología , Masculino , Receptores Adrenérgicos beta/metabolismo , Limoneno/farmacología , Transducción de Señal/efectos de los fármacos , Terpenos/farmacología , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Ciclohexenos/farmacología , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Isoproterenol/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismoRESUMEN
Introduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood. Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h. Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish. Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.
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Adhesiones Focales , Corazón , Nanopartículas del Metal , Plata , Pez Cebra , Animales , Pez Cebra/embriología , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Corazón/efectos de los fármacos , Corazón/embriología , Plata/toxicidad , Plata/química , Adhesiones Focales/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Compared to traditional unipolar radiofrequency ablation (RFA), bipolar RFA offers advantages such as more precise heat transfer and higher ablation efficiency. Clinically, myocardial baseline impedance (BI) is one of the important factors affecting the effectiveness of ablation. We aim at finding suitable ablation protocols and coping strategies by analyzing the ablation effects and myocardial impedance changes of bipolar RFA under different BIs. In this research, a three-dimensional local myocardial computer model was constructed for bipolar RFA simulation, and in vitro experimental data were used to validate accuracy. Four fixed low-power levels (20 W, 25 W, 30 W, and 35 W) and six myocardial BIs (91.02 Ω, 99.83 Ω, 111.03 Ω, 119.77 Ω, 130.03 Ω, and 135.45 Ω) were set as initial conditions, with an ablation duration of 120-s. In the context of low-power and long-duration (LPLD) ablation, the maximum TID (TIDM) decreased by 21-32 Ω, depending on the BI. In cases where steam pop did not occur, TIDM increased with the increase in power. For the same power, there was no significant difference in TIDM for the range of BIs. In cases where steam pop occurred, for every 1 Ω increase in BI, TIDM increased by 0.34-0.41 Ω. The simulation results also showed that using a higher power resulted in a smaller decrease in TIDM. This study provided appropriate ablation times and impedance decrease ranges for bipolar LPLD RFA. The combination of 25 W for 120-s offered optimal performance when considering effectiveness and safety simultaneously.
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Simulación por Computador , Impedancia Eléctrica , Ablación por Radiofrecuencia , Ablación por Radiofrecuencia/métodos , Factores de Tiempo , Humanos , CorazónRESUMEN
Engineered heart tissues (EHTs) generated from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent powerful platforms for human cardiac research, especially in drug testing and disease modeling. Here, we report a flexible, three-dimensional electronic framework that enables real-time, spatiotemporal analysis of electrophysiologic and mechanical signals in EHTs under physiological loading conditions for dynamic, noninvasive, longer-term assessments. These electromechanically monitored EHTs support multisite measurements throughout the tissue under baseline conditions and in response to stimuli. Demonstrations include uses in tracking physiological responses to pharmacologically active agents and in capturing electrophysiological characteristics of reentrant arrhythmias. This platform facilitates precise analysis of signal location and conduction velocity in human cardiomyocyte tissues, as the basis for a broad range of advanced cardiovascular studies.
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Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Ingeniería de Tejidos , Humanos , Ingeniería de Tejidos/métodos , Miocitos Cardíacos/fisiología , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/citología , Corazón/fisiología , Fenómenos ElectrofisiológicosRESUMEN
The innate immune response is triggered rapidly after injury and its spatiotemporal dynamics are critical for regeneration; however, many questions remain about its exact role. Here we show that MyD88, a key component of the innate immune response, controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. We find in cryoinjured myd88-/- ventricles a significant reduction in neutrophil and macrophage numbers and the expansion of a collagen-rich endocardial population. Further analyses reveal compromised PI3K/AKT pathway activation in the myd88-/- endocardium and increased myofibroblasts and scarring. Notably, endothelial-specific overexpression of myd88 reverses these neutrophil, fibrotic and scarring phenotypes. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a target of the MyD88 signaling pathway, and using loss-of-function and gain-of-function tools, we show that it controls neutrophil recruitment. Altogether, these findings shed light on the pivotal role of MyD88 in modulating inflammation and fibrosis during tissue regeneration.
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Fibrosis , Inmunidad Innata , Factor 88 de Diferenciación Mieloide , Regeneración , Transducción de Señal , Proteínas de Pez Cebra , Pez Cebra , Animales , Animales Modificados Genéticamente , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Endocardio/metabolismo , Endocardio/patología , Endocardio/inmunología , Corazón/fisiopatología , Inmunidad Innata/genética , Macrófagos/metabolismo , Macrófagos/inmunología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patología , Infiltración Neutrófila , Neutrófilos/metabolismo , Neutrófilos/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regeneración/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Data augmentation is a technique usually deployed to mitigate the possible performance limitation from training a neural network model on a limited dataset, especially in the medical domain. This paper presents a study on effects of applying different rotation settings to augment cardiac volumes from the Multi-modality Whole Heart Segmentation dataset, in order to improve the segmentation performance. This study presents a comparison between conventional 2D (slice-wise) rotation primarily on the axial axis, 3D (volume-wise) rotation, and our proposed rotation setting that takes into account possible cardiac alignment according to its anatomy. The study has suggested two key considerations: 2D slice-wise rotation should be avoided when using 3D data for segmentation, due to intrinsic structural correlation between subsequent slices, and that 3D rotations may help improve segmentation performance on data previously unseen to the model.
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Corazón , Imagenología Tridimensional , Humanos , Imagenología Tridimensional/métodos , Corazón/diagnóstico por imagen , Corazón/anatomía & histología , Redes Neurales de la Computación , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
High mitochondrial DNA (mtDNA) amount has been reported to be beneficial for resistance and recovery of metabolic stress, while increased mtDNA synthesis activity can drive aging signs. The intriguing contrast of these two mtDNA boosting outcomes prompted us to jointly elevate mtDNA amount and frequency of replication in mice. We report that high activity of mtDNA synthesis inhibits perinatal metabolic maturation of the heart. The offspring of the asymptomatic parental lines are born healthy but manifest dilated cardiomyopathy and cardiac collapse during the first days of life. The pathogenesis, further enhanced by mtDNA mutagenesis, involves prenatal upregulation of mitochondrial integrated stress response and the ferroptosis-inducer MESH1, leading to cardiac fibrosis and cardiomyocyte death after birth. Our evidence indicates that the tight control of mtDNA replication is critical for early cardiac homeostasis. Importantly, ferroptosis sensitivity is a potential targetable mechanism for infantile-onset cardiomyopathy, a common manifestation of mitochondrial diseases.
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Replicación del ADN , ADN Mitocondrial , Miocitos Cardíacos , Animales , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Ratones , Miocitos Cardíacos/metabolismo , Femenino , Masculino , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Ferroptosis/genética , Miocardio/metabolismo , Miocardio/patología , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/genética , Ratones Endogámicos C57BL , Animales Recién Nacidos , Humanos , Corazón/fisiopatología , FibrosisRESUMEN
Recent epidemiological studies have shown that patients with right-sided breast cancer (RBC) treated with X-ray irradiation (IR) are more susceptible to developing cardiovascular diseases, such as arrhythmias, atrial fibrillation, and conduction disturbances after radiotherapy (RT). Our aim was to investigate the mechanisms induced by low to moderate doses of IR and to evaluate changes in the cardiac sympathetic nervous system (CSNS), atrial remodeling, and calcium homeostasis involved in cardiac rhythm. To mimic the RT of the RBC, female C57Bl/6J mice were exposed to X-ray doses ranging from 0.25 to 2 Gy targeting 40% of the top of the heart. At 60 weeks after RI, Doppler ultrasound showed a significant reduction in myocardial strain, ejection fraction, and atrial function, with a significant accumulation of fibrosis in the epicardial layer and apoptosis at 0.5 mGy. Calcium transient protein expression levels, such as RYR2, NAK, Kir2.1, and SERCA2a, increased in the atrium only at 0.5 Gy and 2 Gy at 24 h, and persisted over time. Interestingly, 3D imaging of the cleaned hearts showed an early reduction of CSNS spines and dendrites in the ventricles and a late reorientation of nerve fibers, combined with a decrease in SEMA3a expression levels. Our results showed that local heart IR from 0.25 Gy induced late cardiac and atrial dysfunction and fibrosis development. After IR, ventricular CSNS and calcium transient protein expression levels were rearranged, which affected cardiac contractility. The results are very promising in terms of identifying pro-arrhythmic mechanisms and preventing arrhythmias during RT treatment in patients with RBC.
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Calcio , Ratones Endogámicos C57BL , Sistema Nervioso Simpático , Animales , Ratones , Sistema Nervioso Simpático/efectos de la radiación , Sistema Nervioso Simpático/metabolismo , Femenino , Calcio/metabolismo , Rayos X , Corazón/efectos de la radiación , Corazón/fisiopatología , Remodelación Atrial/efectos de la radiaciónRESUMEN
Cardiovascular disease (CVD) represents a significant global health challenge, remaining the leading cause of illness and mortality worldwide. The adult heart's limited regenerative capacity poses a major obstacle in repairing extensive damage caused by conditions like myocardial infarction. In response to these challenges, nanomedicine has emerged as a promising field aimed at improving treatment outcomes through innovative drug delivery strategies. Nanocarriers, such as nanoparticles (NPs), offer a revolutionary approach by facilitating targeted delivery of therapeutic agents directly to the heart. This precise delivery system holds immense potential for treating various cardiac conditions by addressing underlying mechanisms such as inflammation, oxidative stress, cell death, extracellular matrix remodeling, prosurvival signaling, and angiogenic pathways associated with ischemia-reperfusion injury. In this review, we provide a concise summary of the fundamental mechanisms involved in cardiac remodeling and regeneration. We explore how nanoparticle-based drug delivery systems can effectively target the afore-mentioned mechanisms. Furthermore, we discuss clinical trials that have utilized nanoparticle-based drug delivery systems specifically designed for cardiac applications. These trials demonstrate the potential of nanomedicine in clinical settings, paving the way for future advancements in cardiac therapeutics through precise and efficient drug delivery. Overall, nanomedicine holds promise in revolutionizing the treatment landscape of cardiovascular diseases by offering targeted and effective therapeutic strategies that address the complex pathophysiology of cardiac injuries.
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Nanomedicina , Medicina Regenerativa , Humanos , Medicina Regenerativa/métodos , Nanomedicina/métodos , Animales , Nanopartículas , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/terapia , Sistemas de Liberación de Medicamentos/métodos , Regeneración/efectos de los fármacos , Corazón/efectos de los fármacos , Corazón/fisiologíaRESUMEN
Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFß inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.
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Dioxoles , Fibrosis , Infarto del Miocardio , Piridinas , Ingeniería de Tejidos , Animales , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Infarto del Miocardio/metabolismo , Infarto del Miocardio/genética , Ratones , Humanos , Piridinas/farmacología , Piridinas/uso terapéutico , Ingeniería de Tejidos/métodos , Dioxoles/farmacología , Dioxoles/uso terapéutico , Miocardio/patología , Miocardio/metabolismo , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Benzamidas/farmacología , Benzamidas/uso terapéutico , Modelos Animales de Enfermedad , Transducción de Señal , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Remodelación Ventricular/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Corazón/fisiopatología , Corazón/efectos de los fármacos , AmidasRESUMEN
Contemporary cardiac injury models in zebrafish larvae include cryoinjury, laser ablation, pharmacological treatment and cardiac dysfunction mutations. Although effective in damaging cardiomyocytes, these models lack the important element of myocardial hypoxia, which induces critical molecular cascades within cardiac muscle. We have developed a novel, tractable, high throughput in vivo model of hypoxia-induced cardiac damage that can subsequently be used in screening cardioactive drugs and testing recovery therapies. Our potentially more realistic model for studying cardiac arrest and recovery involves larval zebrafish (Danio rerio) acutely exposed to severe hypoxia (PO2=5-7â mmHg). Such exposure induces loss of mobility quickly followed by cardiac arrest occurring within 120â min in 5â days post fertilization (dpf) and within 40â min at 10â dpf. Approximately 90% of 5â dpf larvae survive acute hypoxic exposure, but survival fell to 30% by 10â dpf. Upon return to air-saturated water, only a subset of larvae resumed heartbeat, occurring within 4â min (5â dpf) and 6-8â min (8-10â dpf). Heart rate, stroke volume and cardiac output in control larvae before hypoxic exposure were 188±5â bpm, 0.20±0.001â nL and 35.5±2.2â nL/min (n=35), respectively. After briefly falling to zero upon severe hypoxic exposure, heart rate returned to control values by 24â h of recovery. However, reflecting the severe cardiac damage induced by the hypoxic episode, stroke volume and cardiac output remained depressed by â¼50% from control values at 24â h of recovery, and full restoration of cardiac function ultimately required 72â h post-cardiac arrest. Immunohistological staining showed co-localization of Troponin C (identifying cardiomyocytes) and Capase-3 (identifying cellular apoptosis). As an alternative to models employing mechanical or pharmacological damage to the developing myocardium, the highly reproducible cardiac effects of acute hypoxia-induced cardiac arrest in the larval zebrafish represent an alternative, potentially more realistic model that mimics the cellular and molecular consequences of an infarction for studying cardiac tissue hypoxia injury and recovery of function.
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Modelos Animales de Enfermedad , Paro Cardíaco , Hipoxia , Larva , Pez Cebra , Animales , Paro Cardíaco/fisiopatología , Paro Cardíaco/etiología , Paro Cardíaco/metabolismo , Paro Cardíaco/complicaciones , Miocardio/metabolismo , Miocardio/patología , Corazón/fisiopatología , Frecuencia CardíacaRESUMEN
BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) serves as a prodromal phase of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Blunted tachycardia (BT) during postural changes indicates neurogenic orthostatic hypotension, a marker of autonomic dysfunction. We aimed to investigate whether BT is associated with cardiac sympathetic neurogenic denervation. Additionally, we conducted a preliminary short-term follow-up to examine the potential prognostic significance of BT regarding phenoconversion and mortality. METHODS: Forty-three patients with iRBD at Shiga University of Medical Science Hospital underwent active standing tests to identify BT, defined by a specific ratio of decrease in systolic blood pressure to inadequate increase in heart rate after standing, and orthostatic hypotension. 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) were performed. Participants were followed up for 3.4 ± 2.4 years for phenoconversion and 4.0 ± 2.3 years for mortality assessment, and the risk of events was analyzed using log-rank tests. RESULTS: Among the 43 participants (mean age, 72.3 ± 7.9 years; 8 female), 17 met the BT criteria. We found no significant comorbidity-related differences in hypertension or diabetes between the BT(+) and BT(-) groups. Orthostatic hypotension was more prevalent in the BT(+) group than in the BT(-) group (47.1% vs 7.7%, p = 0.003). BT(+) patients were older with a lower early and delayed MIBG uptake; however, no significant differences were observed in DAT accumulation. Phenoconversion was observed in seven (41.2%) BT(+) and seven (26.9%) BT(-) patients. Three deaths were recorded in the BT(+) group (17.6%) and three in the BT(-) group (11.5%). No significant differences were observed in the risk of phenoconversion or mortality between the groups. CONCLUSIONS: We have identified the possibility that BT reflects cardiac sympathetic neurogenic denervation in patients with iRBD. Future research is needed to elucidate the potential prognostic value of BT.
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Trastorno de la Conducta del Sueño REM , Taquicardia , Humanos , Masculino , Femenino , Anciano , Trastorno de la Conducta del Sueño REM/diagnóstico , Taquicardia/diagnóstico , Corazón/inervación , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano de 80 o más Años , Simpatectomía/métodos , 3-Yodobencilguanidina , Estudios de SeguimientoRESUMEN
Development of the heart is a very intricate and multiplex process as it involves not only the three spatial dimensions but also the fourth or time dimension. Over time, the heart of an embryo needs to adapt its function to serve the increasing complexity of differentiation and growth towards adulthood. It becomes even more perplexing by expanding time into millions of years, allocating related species in the tree of life. As the evolution of soft tissues can hardly be studied, we have to rely on comparative embryology, supported heavily by genetic and molecular approaches. These techniques provide insight into relationships, not only between species, but also between cell populations, signaling mechanisms, molecular interactions and physical factors such as hemodynamics. Heart development depends on differentiation of a mesodermal cell population that - in more derived taxa - continues in segmentation of the first and second heart field. These fields deliver not only the cardiomyocytes, forming the three-dimensionally looping cardiac tube as a basis for the chambered heart, but also the enveloping epicardium. The synchronized beating of the heart is then organized by the conduction system. In this Review, the epicardium is introduced as an important player in cardiac differentiation, including the conduction system.
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Evolución Biológica , Sistema de Conducción Cardíaco , Hemodinámica , Pericardio , Vertebrados , Animales , Pericardio/fisiología , Pericardio/embriología , Vertebrados/fisiología , Sistema de Conducción Cardíaco/fisiología , Corazón/fisiología , Corazón/embriologíaRESUMEN
In the multi-organ segmentation task of medical images, there are some challenging issues such as the complex background, blurred boundaries between organs, and the larger scale difference in volume. Due to the local receptive fields of conventional convolution operations, it is difficult to obtain desirable results by directly using them for multi-organ segmentation. While Transformer-based models have global information, there is a significant dependency on hardware because of the high computational demands. Meanwhile, the depthwise convolution with large kernel can capture global information and have less computational requirements. Therefore, to leverage the large receptive field and reduce model complexity, we propose a novel CNN-based approach, namely adjacent-scale fusion U-Net with large kernel (ASF-LKUNet) for multi-organ segmentation. We utilize a u-shaped encoder-decoder as the base architecture of ASF-LKUNet. In the encoder path, we design the large kernel residual block, which combines the large and small kernels and can simultaneously capture the global and local features. Furthermore, for the first time, we propose an adjacent-scale fusion and large kernel GRN channel attention that incorporates the low-level details with the high-level semantics by the adjacent-scale feature and then adaptively focuses on the more global and meaningful channel information. Extensive experiments and interpretability analysis are made on the Synapse multi-organ dataset (Synapse) and the ACDC cardiac multi-structure dataset (ACDC). Our proposed ASF-LKUNet achieves 88.41% and 89.45% DSC scores on the Synapse and ACDC datasets, respectively, with 17.96M parameters and 29.14 GFLOPs. These results show that our method achieves superior performance with favorable lower complexity against ten competing approaches.ASF-LKUNet is superior to various competing methods and has less model complexity. Code and the trained models have been released on GitHub.