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Introduction: Although mechanical circulatory support saved many lives during the last decade, clinical observations have shown that the continuous flow pumps are associated with a much higher incidence of gastrointestinal bleeding and kidney problems, among others, compared with the earlier generation pulsatile pumps. However, the presence of several moving mechanical components made pulsatile pumps less durable, bulky, and prone to malfunction, ultimately leading to bias in favor of continuous flow designs. Objective: The aim of the current work is to create a prototype tubular pulsatile pump and to test the timing of the pump in a left heart simulator. Methods: A left heart simulator to mimic pumping from a failing heart was created. This was used to experimentally test the output of a prototype ventricular assist device relative to a failing heart in the form of flow and pressure. The effect of pulsation timing was quantified. Results: A failing heart was simulated with an average flow rate of 1.1 L/min and a systolic pressure of 47 mm Hg. With the pump, the flow rate increases to 4.8 L/min and a systolic pressure of 110 mm Hg, in a copulsation mode, while activating for 300–400 ms. If the activation time is reduced, or increased, the pump becomes less effective. Load on the heart is reduced when the pump operates in a counterpulsation mode. Conclusion: A pulsatile pump, like the one proposed, provides adequate output for mechanical circulatory support, while minimizing the number of moving parts that could otherwise lead to tribological wear. [ABSTRACT FROM AUTHOR]

During development, the heart begins pumping as a valveless multilayered tube capable of driving blood flow throughout the embryonic vasculature. The mechanical properties and how they interface with pumping function are not well-defined at this stage. Here, we evaluate pumping patterns using a fluid–structure interaction computational model, combined with experimental data and an energetic analysis to investigate myocardial mechanical properties. Through this work, we propose that a myocardium modeled as a Neo-Hookean material with a material constant on the order of 10 kPa is necessary for the heart tube to function with an optimal pressure and cardiac output. [ABSTRACT FROM AUTHOR]

Before septation processes shape its four chambers, the embryonic heart is a straight tube that spontaneously bends and twists breaking the left-right symmetry. In particular, the heart tube is subjected to a cell remodeling inducing ventral bending and dextral torsion during the clooping phase. In this work we propose a morphomechanical model for the torsion of the heart tube that behaves as a nonlinear elastic body. We hypothesize that this spontaneous looping can be modeled as a mechanical instability due to accumulation of residual stresses induced by the geometrical frustration of tissue remodeling, which mimics the cellular rearrangement within the heart tube. Thus, we perform a linear stability analysis of the resulting nonlinear elastic boundary value problem to determine the onset of c-looping as a function of the geometry of the tube and of the internal remodeling rate. We perform numerical simulations to study the fully nonlinear morphological transition, showing that the soft tube develops a realistic self-contacting looped shape in the physiological range of geometrical parameters. [ABSTRACT FROM AUTHOR]

Early heart development depends on the coordinated participation of heterogeneous cell sources. As pioneer work from Adriana C. Gittenberger-de Groot demonstrated, characterizing these distinct cell sources helps us to understand congenital heart defects. Despite decades of research on the segregation of lineages that form the primitive heart tube, we are far from understanding its full complexity. Currently, single-cell approaches are providing an unprecedented level of detail on cellular heterogeneity, offering new opportunities to decipher its functional role. In this review, we will focus on three key aspects of early heart morphogenesis: First, the segregation of myocardial and endocardial lineages, which yields an early lineage diversification in cardiac development; second, the signaling cues driving differentiation in these progenitor cells; and third, the transcriptional heterogeneity of cardiomyocyte progenitors of the primitive heart tube. Finally, we discuss how single-cell transcriptomics and epigenomics, together with live imaging and functional analyses, will likely transform the way we delve into the complexity of cardiac development and its links with congenital defects.

During human embryonic development the early establishment of a functional heart is vital to support the growing fetus. However, forming the embryonic heart is an extremely complex process, requiring spatiotemporally controlled cell specification and differentiation, tissue organization, and coordination of cardiac function. These complexities, in concert with the early and rapid development of the embryonic heart, mean that understanding the intricate interplay between these processes that help shape the early heart remains highly challenging. In this review I focus on recent insights from animal models that have shed new light on the earliest stages of heart development. This includes specification and organization of cardiac progenitors, cell and tissue movements that make and shape the early heart tube, and the initiation of the first beat in the developing heart. In addition I highlight relevant in vitro models that could support translation of findings from animal models to human heart development. Finally I discuss challenges that are being addressed in the field, along with future considerations that together may help move us towards a deeper understanding of how our hearts are made., (Copyright © 2024. Published by Elsevier Inc.)

Cytotoxicity and inflammation‐associated toxic responses could be induced by bacterial lipopolysaccharides (LPS) in vitro and in vivo, respectively. However, the mechanism involved in LPS‐induced cardiac malformation in prenatal fetus is still unknown. In this study, we demonstrated that LPS was induced in gut microbiota imbalance mice, and next, LPS exposure during gastrulation in the chick embryo increased the incidence of cardia bifida. Gene transfection and tissue transplantation trajectory indicated that LPS exposure restricted the cell migration of cardiac progenitors to primary heart field in gastrula chick embryos. In vitro explant allograft of GFP‐labeled anterior primitive streak demonstrated that LPS treatments could inhibit cell migration. A similar observation was also obtained from the cell migration assay of scratch wounds using primary culture of cardiomyocytes or H9c2 cells. In the embryos exposed to LPS, expressions of Nkx2.5 and GATA5 were disturbed. These genes are associated with cardiomyocyte differentiation when heart tube fusion occurs. Furthermore, pHIS3, C‐caspase3 immunohistological staining indicated that cell proliferation decreased, cell apoptosis increased in the heart tube of chick embryo. Meanwhile, in vivo, pHIS3 immunohistological staining and Hochest/PI staining also draw the similar conclusions. The LPS exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. At last, we showed that LPS‐induced cardia bifida could be partially rescued through the addition of antioxidants. Together, these results reveal that excess ROS generation is involved in the LPS‐induced defects in heart tube during chick embryo development. Cytotoxicity and inflammation‐associated toxic responses could be induced by bacterial lipopolysaccharides (LPS) in vitro and in vivo, respectively. The LPS exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. [ABSTRACT FROM AUTHOR]

An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high‐salt exposure has an adverse impact on cardiogenesis. Here we report high‐salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E‐cadherin/N‐cadherin/Laminin and interfering with mesoderm formation during the epithelial‐mesenchymal transition(EMT). Furthermore, the DiI+ cell migration trajectory in vivo and scratch wound assays in vitro indicated that high‐salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7. Besides, down‐regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up‐regulation of Wnt3a/β‐catenin caused aberrant cardiomyocyte differentiation at HH7 and HH10. High‐salt exposure also inhibited cell proliferation and promoted apoptosis. Most importantly, our study revealed that excessive reactive oxygen species(ROS)generated by high salt disturbed the expression of cardiac‐related genes, detrimentally affecting the above process including EMT, cell migration, differentiation, cell proliferation and apoptosis, which is the major cause of malformation of heart tubes. [ABSTRACT FROM AUTHOR]