Magnetic susceptibility anisotropy of myocardium imaged by cardiovascular magnetic resonance reflects the anisotropy of myocardial filament α-helix polypeptide bonds

BACKGROUND: A key component of evaluating myocardial tissue function is the assessment of myofiber organization and structure. Studies suggest that striated muscle fibers are magnetically anisotropic, which, if measurable in the heart, may provide a tool to assess myocardial microstructure and function. METHODS: To determine whether this weak anisotropy is observable and spatially quantifiable with cardiovascular magnetic resonance (CMR), both gradient-echo and diffusion-weighted data were collected from intact mouse heart specimens at 9.4 Tesla. Susceptibility anisotropy was experimentally calculated using a voxelwise analysis of myocardial tissue susceptibility as a function of myofiber angle. A myocardial tissue simulation was developed to evaluate the role of the known diamagnetic anisotropy of the peptide bond in the observed susceptibility contrast. RESULTS: The CMR data revealed that myocardial tissue fibers that were parallel and perpendicular to the magnetic field direction appeared relatively paramagnetic and diamagnetic, respectively. A linear relationship was found between the magnetic susceptibility of the myocardial tissue and the squared sine of the myofiber angle with respect to the field direction. The multi-filament model simulation yielded susceptibility anisotropy values that reflected those found in the experimental data, and were consistent that this anisotropy decreased as the echo time increased. CONCLUSIONS: Though other sources of susceptibility anisotropy in myocardium may exist, the arrangement of peptide bonds in the myofilaments is a significant, and likely the most dominant source of susceptibility anisotropy. This anisotropy can be further exploited to probe the integrity and organization of myofibers in both healthy and diseased heart tissue

Evaluation of stimulus-effect relations in left ventricular growth using a simple multiscale model

\u3cp\u3eCardiac growth is the natural capability of the heart to change size in response to changes in blood flow demand of the growing body. Cardiac diseases can trigger the same process leading to an abnormal type of growth. Prediction of cardiac growth would be clinically valuable, but so far published models on cardiac growth differ with respect to the stimulus-effect relation and constraints used for maximum growth. In this study, we use a zero-dimensional, multiscale model of the left ventricle to evaluate cardiac growth in response to three valve diseases, aortic and mitral regurgitation along with aortic stenosis. We investigate how different combinations of stress- and strain-based stimuli affect growth in terms of cavity volume and wall volume and hemodynamic performance. All of our simulations are able to reach a converged state without any growth constraint, with the most promising results obtained while considering at least one stress-based stimulus. With this study, we demonstrate how a simple model of left ventricular mechanics can be used to have a first evaluation on a designed growth law.\u3c/p\u3

Determinants of left ventricular shear strain

Mathematical models of cardiac mechanics can potentially be used to relate abnormal cardiac deformation, as measured noninvasively by ultrasound strain rate imaging or magnetic resonance tagging (MRT), to the underlying pathology. However, with current models, the correct prediction of wall shear strain has proven to be difficult, even for the normal healthy heart. Discrepancies between simulated and measured strains have been attributed to 1) inadequate modeling of passive tissue behavior, 2) neglecting active stress development perpendicular to the myofiber direction, or 3) neglecting crossover of myofibers in between subendocardial and subepicardial layers. In this study, we used a finite-element model of left ventricular (LV) mechanics to investigate the sensitivity of midwall circumferential-radial shear strain (Ecr) to settings of parameters determining passive shear stiffness, cross-fiber active stress development, and transmural crossover of myofibers. Simulated time courses of midwall LV Ecr were compared with time courses obtained in three healthy volunteers using MRT. Ecr as measured in the volunteers during the cardiac cycle was characterized by an amplitude of ~0.1. In the simulations, a realistic amplitude of the Ecr signal could be obtained by tuning either of the three model components mentioned above. However, a realistic time course of Ecr, with virtually no change of Ecr during isovolumic contraction and a correct base-to-apex gradient of Ecr during ejection, could only be obtained by including transmural crossover of myofibers. Thus, accounting for this crossover seems to be essential for a realistic model of LV wall mechanics. Copyright © 2009 the American Physiological Society

The role of talin 1 on the passive material properties op the myocardium

Talin 1 is a cytoskeletal protein which is ubiquitously located in focal adhesions and in muscle-specific integrin complexes such as costameres, intercalated discs and myotendinous junctions. Costameres connect the actin cytoskeleton to the extracellular matrix (ECM). They provide structural integrity of the cell and transduction of mechanical forces in cardiomyocytes. In the costamere talin 1 is attached to vinculin and ß integrin. These proteins are thought to be important for force transmission and mechanotransduction as they may influence the material properties of the myocardium, and hence how forces are transmitted through the cells and tissue. The goal of the present study was to determine the influence of talin 1 on the passive mechanics of the myocardium. The passive mechanics were studied by performing passive stretch experiments on isolated papillary muscles from cardiac specific talin 1 knockout mice and their wild-type littermates. Stress strain curves were obtained and the averaged curves showed a lower compliance for the talin 1 knockout mice with contracting papillary muscles. Statistical analysis showed a significant difference for contracting papillary muscles with strain measured by local muscle deformations. This suggests that an alteration of the passive material properties was found using this method. The data presented here indicate that talin may have an effect on passive mechanics of the myocardium, but more tests are needed to make definitive statistical conclusions

Optimizing ventricular fibers : uniform strain or stress, but not ATP consumption, leads to high efficiency

The aim of this work is to investigate the influence of fiber orientation in the left ventricular (LV) wall on the ejection fraction, efficiency and the heterogeneity of the distributions of developed fiber stress, strain and ATP consumption. A finite element model of LV mechanics was used with active properties of the cardiac muscle described by the Huxley-type cross-bridge model. The computed variances of sarcomere length (VarSL), developed stress (VarDS) and ATP consumption (VarATP) have several minima at different transmural courses of helix fiber angle. We identified only one region in the used design space with high ejection fraction, high efficiency of the LV and relatively small VarSL, VarDS, and VarATP. This region corresponds to the physiological distribution of the helix fiber angle in the LV wall. Tra! nsmural fiber angle can be predicted by minimizing VarSL and VarDS, but not VarATP. If VarATP was minimized then the transverse fiber angle was considerably underestimated. The results suggest that ATP consumption distribution is not regulating the fiber orientation in the heart

Left ventricular apical torsion and architecture are not inverted in situs inversus totalis

Occasionally, individuals have a complete, mirror-image reversal of their internal organ position, called situs inversus totalis (SIT). Whereas gross anatomy is mirror-imaged in SIT, this might not be the case for the internal architecture of organs, e.g. the myofiber pattern in the left cardiac ventricle. We performed a Magnetic Resonance Tagging study in 9 controls and in 8 subjects with SIT to assess the deformation pattern in the apical half of the LV wall. It appeared that both groups had the same LV apical deformation pattern. This implies that not only the superficial LV apical layers in SIT follow a normal, not inverted pattern, but the deeper layers as well. Apparently, the embryonic L/R controlling genetic pathway does determine situs-specific gross anatomy morphogenesis but it is not the only factor regulating fiber architecture within the apical part of the LV wall. We propose that mechanical forces generated in the not-inverted molecular structure of the basic right-handed helical contractile components of the sarcomere play a role in shaping the LV apex