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Sensitivity analysis of diffusion tensor MRI in simulated rat myocardium
© Springer International Publishing Switzerland 2015. A model of cardiac microstructure and diffusion MRI is presented. The results show a good correspondence between the simulated and experimental measurements. A sensitivity analysis shows that the diffusivity has the greatest effect on both the apparent diffusion coefficient and the fractional anisotropy. The cross-sectional area of the cells is the next most important factor; the aspect ratio of the cell cross-section also affects the fractional anisotropy. Neither the cell length nor the volume fraction of cells has a marked effect.
Mechano-electric interactions and their role in electrical function of the heart
© Springer-Verlag London 2013. The heart is an electrically controlled and chemically powered mechanical pump. There are complex interactions between cardiac structure and function, including electrophysiology, metabolism, and mechanics. These are based on a multitude of interdigitating regulatory loops with different inherent time-scales. This chapter will focus on the acute cross-talk between electrical and mechanical activity of the heart, and in particular its relevance for normal and abnormal heart rhythms.
Digital human modelling: A global vision and a european perspective
The Physiome is an umbrella term that refers to human modelling with mathematics and computational methods, accommodating cross-disciplinary science (chemistry, biology, physics) and a breadth of dimensional and temporal scale (sub-cellular to organs, sub-microsecond to tens-of-years). The Virtual Physiological Human is a European initiative that is intended to provide a unifying architecture for the integration and cooperation of multi-scale physiome models, thereby creating a predictive platform for the description of human beings in silico. Unlike the Genome, the challenge of the Physiome may be almost unbounded, as the desire for increased detail imposes a continuing pressure for ever-finer data granularity, and the necessary Information Technology (IT) infrastructure spawns innovations that surpass conventional solutions. It is foreseen that maturing physiome activities will increasingly influence medicine, biomedical research and commercial developments, and the central role of IT highlights the need for a specific and robust IT infrastructure. The European Commission has experience of supporting challenging technical endeavours through its Framework Programmes of research, and in the forthcoming 7th Framework Programme, it will invite researchers from within and outside Europe to unite in seeking solutions to key issues of the Physiome. The Virtual Physiological Human (VPH) investment programme will establish the necessary infrastructure and address the grand technical challenges identified by experts. This paper examines the background to the strategy and the ways in which the programme's structure has been determined. © Springer-Verlag Berlin Heidelberg 2007.
Structural and functional characterisation of cardiac fibroblasts.
Cardiac fibroblasts form one of the largest cell populations, in terms of cell numbers, in the heart. They contribute to structural, biochemical, mechanical and electrical properties of the myocardium. Nonetheless, they are often disregarded by in vivo and in vitro studies into cardiac function. This review summarizes our understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart.
Spatial regulation of intracellular pH in multicellular strands of neonatal rat cardiomyocytes.
AIMS: Intracellular pH (pHi), an important modulator of cardiac function, is normally regulated to within narrow limits (7.1-7.2). In adult ventricular cell pairs, localized cellular pHi disturbances are removed by sarcolemmal acid/base transporters, but can also be dissipated (diluted) across gap junctions, aboard mobile buffers such as CO2/HCO3- and histidine-containing dipeptides (HCDPs). In the present work, we test this model of spatial pHi regulation in multicellular strands of neonatal rat ventricular myocytes. METHODS AND RESULTS: We confocally image pHi (intracellular fluorescence emitted from the pH dye carboxy-SNARF-1) in multicellular (>500 microm long, approximately 30 microm wide) cultured strands of electrically coupled, neonatal rat ventricular myocytes. Activity of sarcolemmal Na+/H+ exchange and Na+-HCO3- co-transport resembles that in adult cells. Localized photolytic H+ uncaging from intracellular 2-nitrobenzaldehyde, in the presence of CO2/HCO3- buffer, triggers considerable passive H+ spread along a strand, thus helping to dissipate the acid load. Inhibition of gap junctions (with alpha-glycyrrhetinic acid) truncates the spread, indicating they are conduits for local intracellular H+ flux. Without CO2/HCO3- buffer, longitudinal H+ mobility is reduced by approximately 90%, indicating that intracellular and cell-to-cell H+ flux relies far less on intrinsic mobile buffers (e.g. HCDPs) in neonates than in adults. This is consistent with five-fold lower HCDP levels in neonatal, compared to adult, ventricular tissue, and also with measurements of a lower intrinsic (non-CO2/HCO3-) H+ buffering capacity in neonatal strands compared with freshly isolated adult cells. CONCLUSION: We conclude that mobile buffers and gap junctions are key spatial controllers of pHi in cardiac tissue, helping to maintain a myocardial pHi syncitium. In neonatal tissue, intracellular H+ movement is CO2/HCO3- dependent, while adult tissue relies increasingly on intrinsic dipeptides that provide additional spatial pHi control, appropriate for the developmental increase in myocyte size.
Caveolae in Rabbit Ventricular Myocytes: Distribution and Dynamic Diminution after Cell Isolation.
Caveolae are signal transduction centers, yet their subcellular distribution and preservation in cardiac myocytes after cell isolation are not well documented. Here, we quantify caveolae located within 100 nm of the outer cell surface membrane in rabbit single-ventricular cardiomyocytes over 8 h post-isolation and relate this to the presence of caveolae in intact tissue. Hearts from New Zealand white rabbits were either chemically fixed by coronary perfusion or enzymatically digested to isolate ventricular myocytes, which were subsequently fixed at 0, 3, and 8 h post-isolation. In live cells, the patch-clamp technique was used to measure whole-cell plasma membrane capacitance, and in fixed cells, caveolae were quantified by transmission electron microscopy. Changes in cell-surface topology were assessed using scanning electron microscopy. In fixed ventricular myocardium, dual-axis electron tomography was used for three-dimensional reconstruction and analysis of caveolae in situ. The presence and distribution of surface-sarcolemmal caveolae in freshly isolated cells matches that of intact myocardium. With time, the number of surface-sarcolemmal caveolae decreases in isolated cardiomyocytes. This is associated with a gradual increase in whole-cell membrane capacitance. Concurrently, there is a significant increase in area, diameter, and circularity of sub-sarcolemmal mitochondria, indicative of swelling. In addition, electron tomography data from intact heart illustrate the regular presence of caveolae not only at the surface sarcolemma, but also on transverse-tubular membranes in ventricular myocardium. Thus, caveolae are dynamic structures, present both at surface-sarcolemmal and transverse-tubular membranes. After cell isolation, the number of surface-sarcolemmal caveolae decreases significantly within a time frame relevant for single-cell research. The concurrent increase in cell capacitance suggests that membrane incorporation of surface-sarcolemmal caveolae underlies this, but internalization and/or micro-vesicle loss to the extracellular space may also contribute. Given that much of the research into cardiac caveolae-dependent signaling utilizes isolated cells, and since caveolae-dependent pathways matter for a wide range of other study targets, analysis of isolated cell data should take the time post-isolation into account.
Towards high-resolution cardiac atlases: Ventricular anatomy descriptors for a standardized reference frame
Increased resolution in cardiac Magnetic Resonance Imaging (MRI) and growing interest in the effect of small structures in electrophysiology of the heart pose new challenges for cardiac atlases. In this paper we discuss the limitations of current atlas-building models when trying to incorporate cardiac small structure and argue for the need of developing a standard coordinate system for the heart that separates this from the macro-structure common to all individual hearts, in a way analogous to the stereotactic coordinate system from brain atlases. With this goal, we propose a set of methods to obtain two descriptors of the ventricular macro-structure that can be used to build a standardized reference frame: the central curve on the Left Ventricle cavity and the smoothed internal envelope of the Right Ventricle crest (i.e. the curve in the endocardial surface marking the junction between the right ventricular free wall and the septum). © 2010 Springer-Verlag Berlin Heidelberg.