Analysis of Passive Filling With Fibrotic Myocardial Infarction

2015 ◽  
Author(s):  
Fulufhelo Masithulela
Keyword(s):  
Myocardial Infarction ◽  
Structural Changes ◽  
Strain Energy Function ◽  
Transversely Isotropic ◽  
Magnetic Resonance Images ◽  
Cardiac Contraction ◽  
Diastolic Filling ◽  
Element Analysis ◽  
Infarcted Heart ◽  
Longitudinal Strains

Cardiovascular diseases account for one third of all deaths worldwide, more than 33% of which are related to ischemic heart disease, involving a myocardial infarction (MI). Following myocardial infarction, the injured region and ventricle undergo structural changes which are thought to be caused by elevated stresses and reduction of strains in the infarcted wall. The fibrotic phase is defined as the period when the amount of new collagen and number of fibroblasts rapidly increase in the infarcted tissue. We studied through finite element analysis the mechanics of the infarcted and remodeling rat heart during diastolic filling. Biventricular geometries of healthy and infarcted rat hearts reconstructed from magnetic resonance images were imported in Abaqus©. The passive myocardium was modelled as a nearly incompressible, hyperelastic, transversely isotropic material represented by the strain energy function W = ½C(eQ − 1) with Q = bfE112 + bt(E222 + E332 + E322) + bfs(E122 + E212 + E132 + E312). Material parameters were obtained from literature [1]. As boundary conditions, the circumferential and longitudinal displacements at the base were set to zero. The radial displacements at the base were left free. A linearly increasing pressure from 0 to 3.80 kPa and 0.86 kPa, respectively, was applied to the endocardial surfaces of left and right ventricle. Average radial, circumferential and longitudinal strains during passive filling were −0.331, 0.135, 0.042 and −0.250, −0.078 and 0.046 for the healthy heart and the infarcted heart, respectively. The average radial, circumferential and longitudinal stresses were −1.196 kPa, 3.87 kPa in the healthy heart and 0.424 kPa and −1.90 kPa, 8.74 kPa and 1.69 kPa in the infarcted heart. The strains were considerable lower in the infarcted heart compared to the health heart whereas stresses were higher in the presence of an infarct compared to the healthy case. The results of this study indicate the feasibility of the models developed for a more comprehensive assessment of mechanics of the infarcted ventricle including extension to account for cardiac contraction.

A Simple Transversely Isotropic Hyperelastic Constitutive Model Suitable for Finite Element Analysis of Fiber Reinforced Elastomers

2011 ◽  
Vol 133 (2) ◽  
Author(s):  
Leslee W. Brown ◽  
Lorenzo M. Smith
Keyword(s):  
Finite Element Analysis ◽  
Finite Element ◽  
Energy Function ◽  
Strain Energy ◽  
Strain Energy Function ◽  
Transversely Isotropic ◽  
Material Model ◽  
Fiber Reinforced ◽  
Element Analysis ◽  
Material Tests

A transversely isotropic fiber reinforced elastomer’s hyperelasticity is characterized using a series of constitutive tests (uniaxial tension, uniaxial compression, simple shear, and constrained compression test). A suitable transversely isotropic hyperelastic invariant based strain energy function is proposed and methods for determining the material coefficients are shown. This material model is implemented in a finite element analysis by creating a user subroutine for a commercial finite element code and then used to analyze the material tests. A useful set of constitutive material data for multiple modes of deformation is given. The proposed strain energy function fits the experimental data reasonably well over the strain region of interest. Finite element analysis of the material tests reveals further insight into the materials constitutive nature. The proposed strain energy function is suitable for finite element use by the practicing engineer for small to moderate strains. The necessary material coefficients can be determined from a few simple laboratory tests.

scholarly journals Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments

2017 ◽  
Vol 114 (8) ◽  
pp. E1355-E1364 ◽  
Author(s):  
Robert W. Kensler ◽  
Roger Craig ◽  
Richard L. Moss
Keyword(s):  
Protein C ◽  
Structural Changes ◽  
Binding Protein ◽  
Cardiac Contraction ◽  
Cardiac Myosin ◽  
Cross Bridge ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Thick Filaments ◽  
Myosin Binding

Cardiac myosin binding protein C (cMyBP-C) has a key regulatory role in cardiac contraction, but the mechanism by which changes in phosphorylation of cMyBP-C accelerate cross-bridge kinetics remains unknown. In this study, we isolated thick filaments from the hearts of mice in which the three serine residues (Ser273, Ser282, and Ser302) that are phosphorylated by protein kinase A in the m-domain of cMyBP-C were replaced by either alanine or aspartic acid, mimicking the fully nonphosphorylated and the fully phosphorylated state of cMyBP-C, respectively. We found that thick filaments from the cMyBP-C phospho-deficient hearts had highly ordered cross-bridge arrays, whereas the filaments from the cMyBP-C phospho-mimetic hearts showed a strong tendency toward disorder. Our results support the hypothesis that dephosphorylation of cMyBP-C promotes or stabilizes the relaxed/superrelaxed quasi-helical ordering of the myosin heads on the filament surface, whereas phosphorylation weakens this stabilization and binding of the heads to the backbone. Such structural changes would modulate the probability of myosin binding to actin and could help explain the acceleration of cross-bridge interactions with actin when cMyBP-C is phosphorylated because of, for example, activation of β1-adrenergic receptors in myocardium.

Wrinkling of a Fiber-Reinforced Membrane

2008 ◽  
Vol 76 (1) ◽  
Author(s):  
E. Shmoylova ◽  
A. Dorfmann
Keyword(s):  
Boundary Conditions ◽  
Energy Function ◽  
Mechanical Response ◽  
Transverse Isotropy ◽  
Base Material ◽  
Strain Energy Function ◽  
Transversely Isotropic ◽  
Incompressible Material ◽  
Fiber Reinforced ◽  
Relaxed Energy

In this paper we investigate the response of fiber-reinforced cylindrical membranes subject to axisymmetric deformations. The membrane is considered as an incompressible material, and the phenomenon of wrinkling is taken into account by means of the relaxed energy function. Two cases are considered: transversely isotropic membranes, characterized by one family of fibers oriented in one direction, and orthotropic membranes, characterized by two family of fibers oriented in orthogonal directions. The strain-energy function is considered as the sum of two terms: The first term is associated with the isotropic properties of the base material, and the second term is used to introduce transverse isotropy or orthotropy in the mechanical response. We determine the mechanical response of the membrane as a function of fiber orientations for given boundary conditions. The objective is to find possible fiber orientations that make the membrane as stiff as possible for the given boundary conditions. Specifically, it is shown that for transversely isotropic membranes a unique fiber orientation exists, which does not affect the mechanical response, i.e., the overall behavior is identical to a nonreinforced membrane.

Abstract 372: The Smad3 Pathway Critically Regulates Myofibroblast Proliferation And Synthetic Activity In Healing Myocardial Infarcts

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marcin Dobaczewski ◽  
Marcin Bujak ◽  
Carlos Gonzalez ◽  
Na Li ◽  
Xiao-Fan Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Proliferative Activity ◽  
Essential Role ◽  
Cardiac Fibroblasts ◽  
Cardiac Fibroblast ◽  
Synthetic Activity ◽  
Dependent Manner ◽  
Tenascin C ◽  
Infarcted Heart

We have recently demonstrated that the Transforming Growth Factor (TGF)-β/Smad3 pathway is activated in healing infarcts and plays an essential role in the pathogenesis of cardiac remodeling. Smad3 −/− mice were protected from the development of ventricular dilation following infarction and exhibited markedly reduced fibrosis of the peri-infarct area and the remodeling non-infarcted heart. Accordingly, we hypothesized that Smad3 signaling plays an essential role in regulating cardiac fibroblast function and gene expression in myocardial infarction. Surprisingly, Smad3 −/− infarcts exhibited increased peak infiltration with myofibroblasts, associated with evidence of enhanced proliferative activity. Smad3 −/− mice had a higher density of Ki-67-positive proliferating myofibroblasts in the infarcted myocardium in comparison with wildtype (WT) animals (Smad3−/− 917±291 cells/mm 2 vs. WT 614±115 cells/mm 2 , p<0.05). In vitro experiments suggested that TGF-β inhibits murine cardiac fibroblast proliferation in a concentration-dependent manner and that the antiproliferative effects of TGF-β are abrogated in Smad3 −/− fibroblasts. On the other hand Smad3 signaling was essential for extracellular matrix protein synthesis by cardiac fibroblasts. TGF-β-mediated induction of procollagen type III and of the matricellular protein tenascin-C in cardiac fibroblasts was dependent on Smad3. In addition, TGF-β-induced Tissue Inhibitor of Metalloproteinases (TIMP)-1 and -2 upregulation was also abrogated in Smad3 −/− fibroblasts, suggesting that Smad3 signaling regulates matrix metabolism. In vivo, Smad3 −/− infarcts exhibited attenuated tenascin-C and collagen deposition in the infarct and in the remodeling non-infarcted heart. Our findings suggest that the Smad3 pathway critically regulates fibroblast function in healing myocardial infarction. In Smad3 −/− mice, the healing infarct contains abundant myofibroblasts that exhibit enhanced proliferative activity, but have markedly decreased ability to synthesize extracellular matrix proteins and to produce TIMPs. In the absence of Smad3, attenuated matrix deposition in the remodeling non-infarcted heart results in decreased dilation and ameliorated diastolic dysfunction. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).

scholarly journals The Proliferation of Dentate Gyrus Progenitors in the Ferret Hippocampus by Neonatal Exposure to Valproic Acid

2021 ◽  
Vol 15 ◽  
Author(s):  
Kazuhiko Sawada ◽  
Shiori Kamiya ◽  
Ichio Aoki
Keyword(s):  
Valproic Acid ◽  
Cerebral Cortex ◽  
Magnetic Resonance ◽  
Dentate Gyrus ◽  
Structural Changes ◽  
S100 Protein ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Magnetic Resonance Images ◽  
Neonatal Exposure

Prenatal and neonatal exposure to valproic acid (VPA) is associated with human autism spectrum disorder (ASD) and can alter the development of several brain regions, such as the cerebral cortex, cerebellum, and amygdala. Neonatal VPA exposure induces ASD-like behavioral abnormalities in a gyrencephalic mammal, ferret, but it has not been evaluated in brain regions other than the cerebral cortex in this animal. This study aimed to facilitate a comprehensive understanding of brain abnormalities induced by developmental VPA exposure in ferrets. We examined gross structural changes in the hippocampus and tracked proliferative cells by 5-bromo-2-deoxyuridine (BrdU) labeling following VPA administration to ferret infants on postnatal days (PDs) 6 and 7 at 200 μg/g of body weight. Ex vivo short repetition time/time to echo magnetic resonance imaging (MRI) with high spatial resolution at 7-T was obtained from the fixed brain of PD 20 ferrets. The hippocampal volume estimated using MRI-based volumetry was not significantly different between the two groups of ferrets, and optical comparisons on coronal magnetic resonance images revealed no differences in gross structures of the hippocampus between VPA-treated and control ferrets. BrdU-labeled cells were observed throughout the hippocampus of both two groups at PD 20. BrdU-labeled cells were immunopositive for Sox2 (&gt;70%) and almost immunonegative for NeuN, S100 protein, and glial fibrillary acidic protein. BrdU-labeled Sox2-positive progenitors were abundant, particularly in the subgranular layer of the dentate gyrus (DG), and were denser in VPA-treated ferrets. When BrdU-labeled Sox2-positive progenitors were examined at 2 h after the second VPA administration on PD 7, their density in the granular/subgranular layer and hilus of the DG was significantly greater in VPA-treated ferrets compared to controls. The findings suggest that VPA exposure to ferret infants facilitates the proliferation of DG progenitors, supplying excessive progenitors for hippocampal adult neurogenesis to the subgranular layer.

Dynamics Redesign of Marine Structures

1985 ◽  
Vol 29 (04) ◽  
pp. 285-295 ◽  
Author(s):  
Curtis J. Hoff ◽  
Michael M. Bernitsas
Keyword(s):  
Large Scale ◽  
Structural Changes ◽  
Dynamic Equilibrium ◽  
Degree Of Freedom ◽  
Attractive Alternative ◽  
Equilibrium Equations ◽  
Element Analysis ◽  
Solution Methods ◽  
Tower Model ◽  
Energy Equations

The dynamic response of a marine structure depends upon the exciting forces and the modal characteristics of the structure. Excessive vibratory response requires reduction of the exciting loads or redesign of the structure or both. In this paper the general redesign problem is formulated. It applies to large-scale structures and allows for large structural changes. Solution of the redesign problem is achieved through perturbation methods which are an attractive alternative to traditional trial-and-error methods. Perturbation solution methods are based on dynamic equilibrium equations or energy equations or both. A new method based on the energy equations which enforces the mode orthogonality conditions is developed and evaluated against all existing methods. Two test cases, a 191-degree-of-freedom two-dimensional ship model and a 810-degree-of-freedom offshore light tower model are used to compare the methods numerically. It is shown that the method developed in this paper can produce, with a single finite element analysis of the baseline system, a structure which satisfies within acceptable limits all nonconflicting design objectives.

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