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"Heart - anatomy "
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The man who touched his own heart : true tales of science, surgery, and mystery
Tells the raucous, gory, mesmerizing story of the heart, from the first \"explorers\" who dug up cadavers and plumbed their hearts' chambers, through the first heart surgeries-which had to be completed in three minutes before death arrived-to heart transplants and the latest medical efforts to prolong our hearts' lives, almost defying nature in the process. Thought of as the seat of our soul, then as a mysteriously animated object, the heart is still more a mystery than it is understood. Why do most animals only get one billion beats? (And how did modern humans get to over two billion-effectively letting us live out two lives?) Why are sufferers of gingivitis more likely to have heart attacks? Why do we often undergo expensive procedures when cheaper ones are just as effective? What do Da Vinci, Mary Shelley, and contemporary Egyptian archaeologists have in common? And what does it really feel like to touch your own heart, or to have someone else's beating inside your chest? Rob Dunn's fascinating history of our hearts brings us deep inside the science, history, and stories of the four chambers we depend on most.
Book
Spatially organized cellular communities form the developing human heart
The heart, which is the first organ to develop, is highly dependent on its form to function
1
,
2
. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell–cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair.
Combining single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization reveals in detail the cellular interactions and specialization of cardiac cell types that form and remodel the human heart.
Journal Article
Breakthrough! : how three people saved \blue babies\ and changed medicine forever
\"The story of the landmark 1944 surgical procedure that repaired the heart of a child with blue baby syndrome--lack of blood oxygen caused by a congenital defect. The team that developed the procedure included a cardiologist and a surgeon, but most of the actual work was done by Vivien Thomas, an African American lab assistant who was frequently mistaken for a janitor\"-- Provided by publisher.
Book
Development of the Hearts of Lizards and Snakes and Perspectives to Cardiac Evolution
Birds and mammals both developed high performance hearts from a heart that must have been reptile-like and the hearts of extant reptiles have an unmatched variability in design. Yet, studies on cardiac development in reptiles are largely old and further studies are much needed as reptiles are starting to become used in molecular studies. We studied the growth of cardiac compartments and changes in morphology principally in the model organism corn snake (Pantherophis guttatus), but also in the genotyped anole (Anolis carolinenis and A. sagrei) and the Philippine sailfin lizard (Hydrosaurus pustulatus). Structures and chambers of the formed heart were traced back in development and annotated in interactive 3D pdfs. In the corn snake, we found that the ventricle and atria grow exponentially, whereas the myocardial volumes of the atrioventricular canal and the muscular outflow tract are stable. Ventricular development occurs, as in other amniotes, by an early growth at the outer curvature and later, and in parallel, by incorporation of the muscular outflow tract. With the exception of the late completion of the atrial septum, the adult design of the squamate heart is essentially reached halfway through development. This design strongly resembles the developing hearts of human, mouse and chicken around the time of initial ventricular septation. Subsequent to this stage, and in contrast to the squamates, hearts of endothermic vertebrates completely septate their ventricles, develop an insulating atrioventricular plane, shift and expand their atrioventricular canal toward the right and incorporate the systemic and pulmonary venous myocardium into the atria.
Journal Article
Cardiogenesis and the Complex Biology of Regenerative Cardiovascular Medicine
The heart is a complex organ system composed of a highly diverse set of muscle and nonmuscle cells. Understanding the pathways that drive the formation, migration, and assembly of these cells into the heart muscle tissue, the pacemaker and conduction system, and the coronary vasculature is a central problem in developmental biology. Efforts to unravel the biological complexity of in vivo cardiogenesis have identified a family of closely related multipotent cardiac progenitor cells. These progenitors must respond to non-cell-autonomous signaling cues to expand, differentiate, and ultimately integrate into the three-dimensional heart structures. Coupling tissue-engineering technologies with patient-specific cardiac progenitor biology holds great promise for the development of human cell models of human disease and may lay the foundation for novel approaches in regenerative cardiovascular medicine.
Journal Article
Spatially resolved multiomics of human cardiac niches
The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system
1
. The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated
FOXP2
in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug–target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG
+
and IgA
+
plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.
Single-cell and spatial transcriptomic analysis of eight human heart tissues reveals the cellular profiles and tissue architecture of niches including the cardiac conduction system, and a new tool, drug2cell, identifies drug target expression.
Journal Article
Clonally dominant cardiomyocytes direct heart morphogenesis
As vertebrate embryos develop to adulthood, their organs undergo marked changes in size and tissue architecture. The heart acquires muscle mass and matures structurally to fulfil increasing circulatory needs, a process that is incompletely understood. Here we used multicolour clonal analysis to define the contributions of individual cardiomyocytes as the zebrafish heart undergoes morphogenesis from a primitive embryonic structure into its complex adult form. We find that the single-cardiomyocyte-thick wall of the juvenile ventricle forms by lateral expansion of several dozen cardiomyocytes into muscle patches of variable sizes and shapes. As juvenile zebrafish mature into adults, this structure becomes fully enveloped by a new lineage of cortical muscle. Adult cortical muscle originates from a small number of cardiomyocytes—an average of approximately eight per animal—that display clonal dominance reminiscent of stem cell populations. Cortical cardiomyocytes initially emerge from internal myofibres that in rare events breach the juvenile ventricular wall, and then expand over the surface. Our results illuminate the dynamic proliferative behaviours that generate adult cardiac structure, revealing clonal dominance as a key mechanism that shapes a vertebrate organ.
Using a conditional multicolour tracing approach, the contributions of individual cardiomyocytes to zebrafish heart morphogenesis are defined, revealing clonal dominance as a key mechanism.
Heart development driven by cardiomyocytes
Using a conditional multicolour tracing approach, Vikas Gupta and Kenneth Poss have defined the contributions of individual cardiomyocytes to the zebrafish heart as it undergoes morphogenesis from a primitive embryonic structure to its complex adult form. They report that the early developing heart is constructed from numerous cell clones that form a primordial layer. Myocytes in the trabeculated layer arise by delamination from the primordial layer, and then a cortical layer emerges as juveniles mature to adults. Only a small number of cardiomyocytes create adult cortical muscle, displaying clonal dominance that is reminiscent of stem-cell populations.
Journal Article
Cells of the adult human heart
Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.
Single-cell and single-nucleus RNA sequencing are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease.
Journal Article
Influence of Signalment Variables on Body Weight‐Normalized Echocardiographic Measurements of Heart Size in 56 169 Adult Unsedated Normal Pure‐Bred Cats
ABSTRACT
Background
Echocardiography is widely used to breed‐screen cats for the presence of heart disease. Left‐sided cardiac dimensions are non‐linearly related to body weight (BW), but the association with signalment variables is incompletely evaluated.
Objective
To validate previously published prediction equations (PE) and 95% prediction intervals (PI) and study the effects of breed, age, sex, and neutering on BW‐normalized aortic (Ao), left atrial (LA) and ventricular (LV) dimensions.
Animals
56 169 pure‐bred adult cats.
Methods
Data from heart screens conducted between 1999 and 2023 were included. Body‐weight‐(BW)‐based PE and 95% PIs were obtained by allometric scaling including only cats considered normal. The effects of signalment variables on BW‐normalized cardiac dimensions were examined using group‐wise comparisons and uni‐ and multivariable analyses.
Results
The PE and PI changed marginally from those previously reported. The BW‐normalized measurements showed greater variation for LV systolic than diastolic measurements (p < 0.001), and LA showed greater variation than Ao measurements. All signalment variables had small but significant effects on BW‐normalized variables (p < 0.001), where the effect of breed was most prominent. None of the breeds had a variable median measurement > 10% above or below the PE, or > 10% of cats outside the PI. Signalment main effects persisted after adjusting for examiner and year of examination.
Conclusions and Clinical Relevance
Breed, age, sex, and neutering status had small and mostly clinically irrelevant effects on BW‐normalized Ao, LA, and LV linear dimensions. The PE and PI intervals are valid in adult pure‐bred cats across many breeds, different ages, sexes, and neutering status.
Journal Article
Constitutive modelling of passive myocardium: a structurally based framework for material characterization
In this paper, we first of all review the morphology and structure of the myocardium and discuss the main features of the mechanical response of passive myocardium tissue, which is an orthotropic material. Locally within the architecture of the myocardium three mutually orthogonal directions can be identified, forming planes with distinct material responses. We treat the left ventricular myocardium as a non-homogeneous, thick-walled, nonlinearly elastic and incompressible material and develop a general theoretical framework based on invariants associated with the three directions. Within this framework we review existing constitutive models and then develop a structurally based model that accounts for the muscle fibre direction and the myocyte sheet structure. The model is applied to simple shear and biaxial deformations and a specific form fitted to the existing (and somewhat limited) experimental data, emphasizing the orthotropy and the limitations of biaxial tests. The need for additional data is highlighted. A brief discussion of issues of convexity of the model and related matters concludes the paper.
Journal Article