Material Properties Of Myocardium Research Articles

Effect of pulmonary regurgitation on cardiac functions based on a human bi-ventricle model

Background and objective: Assessing the severity of pulmonary regurgitation (PR) and identifying optimal clinically relevant indicators for its treatment is crucial, yet standards for quantifying PR remain unclear in clinical practice. Computational modelling of the heart is in the process of providing valuable insights and information for cardiovascular physiology research. However, the advancements of finite element computational models have not been widely applied to simulate cardiac outputs in patients with PR. Furthermore, a computational model that incorporates both the left ventricle (LV) and right ventricle (RV) can be valuable in assessing the relationship between left and right ventricular morphometry and septal motion in PR patients. To enhance our understanding of the effect of PR on cardiac functions and mechanical behaviour, we developed a human bi-ventricle model to simulate five cases with varying degrees of PR severity. Methods: This bi-ventricle model was built using a patient-specific geometry and a widely used myofibre architecture. The myocardial material properties were described by a hyperelastic passive constitutive law and a modified time-varying elastance active tension model. To simulate realistic cardiac functions and the dysfunction of the pulmonary valve in PR disease cases, open-loop lumped parameter models representing systemic and pulmonary circulatory systems were designed. Results: In the baseline case, pressures in the aorta and main pulmonary artery and ejection fractions of both the LV and RV were within normal physiological ranges reported in the literature. The end-diastolic volume (EDV) of the RV under varying degrees of PR was comparable to the reported cardiac magnetic resonance imaging data. Moreover, RV dilation and interventricular septum motion from the baseline to the PR cases were clearly observed through the long-axis and short-axis views of the bi-ventricle geometry. The RV EDV in the severe PR case increased by 50.3% compared to the baseline case, while the LV EDV decreased by 18.1%. The motion of the interventricular septum was consistent with the literature. Furthermore, ejection fractions of both the LV and RV decreased as PR became severe, with LV ejection fraction decreasing from 60.5% at baseline to 56.3% in the severe case and RV ejection fraction decreasing from 51.8% to 46.8%. Additionally, the average myofibre stress of the RV wall at end-diastole significantly increased due to PR, from 2.7±12.1 kPa at baseline to 10.9±26.5 kPa in the severe case. The average myofibre stress of the LV wall at end-diastole increased from 3.7±18.1 kPa to 4.3±20.3 kPa. Conclusions: This study established a foundation for the computational modelling of PR. The simulated results showed that severe PR leads to reduced cardiac outputs in both the LV and RV, clearly observable septum motion, and a significant increase in the average myofibre stress in the RV wall. These findings demonstrate the potential of the model for further exploration of PR.

Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension.

Although pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we discriminated the contributions of RV geometric remodeling and alterations of myocardial material properties to changes in systolic and diastolic chamber function. Significant and rapid RV hypertrophic wall thickening was sufficient to stabilize ejection fraction in response to increased pulmonary arterial pressure by week 4 without significant changes in systolic myofilament activation. After week 4, RV end-diastolic pressure increased significantly with no corresponding changes in end-diastolic volume. Significant RV diastolic chamber stiffening by week 5 was not explained by RV hypertrophy. Instead, model analysis showed that the increases in RV end-diastolic chamber stiffness were entirely attributable to increased resting myocardial material stiffness that was not associated with significant myocardial fibrosis or changes in myocardial collagen content or type. These findings suggest that whereas systolic volume in this model of RV pressure overload is stabilized by early RV hypertrophy, diastolic dilation is prevented by subsequent resting myocardial stiffening.NEW & NOTEWORTHY Using a novel combination of hemodynamic and morphological measurements over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we found that compensated systolic function was almost entirely explained by RV hypertrophy, but subsequently altered RV end-diastolic mechanics were primarily explained by passive myocardial stiffening that was not associated with significant collagen extracellular matrix accumulation.

Estimating cardiomyofiber strain in vivo by solving a computational model.

Since heart contraction results from the electrically activated contraction of millions of cardiomyocytes, a measure of cardiomyocyte shortening mechanistically underlies cardiac contraction. In this work we aim to measure preferential aggregate cardiomyocyte ("myofiber") strains based on Magnetic Resonance Imaging (MRI) data acquired to measure both voxel-wise displacements through systole and myofiber orientation. In order to reduce the effect of experimental noise on the computed myofiber strains, we recast the strains calculation as the solution of a boundary value problem (BVP). This approach does not require a calibrated material model, and consequently is independent of specific myocardial material properties. The solution to this auxiliary BVP is the displacement field corresponding to assigned values of myofiber strains. The actual myofiber strains are then determined by minimizing the difference between computed and measured displacements. The approach is validated using an analytical phantom, for which the ground-truth solution is known. The method is applied to compute myofiber strains using in vivo displacement and myofiber MRI data acquired in a mid-ventricular left ventricle section in N=8 swine subjects. The proposed method shows a more physiological distribution of myofiber strains compared to standard approaches that directly differentiate the displacement field.

Comprehensive computational assessment of blood flow characteristics of left ventricle based on in-vivo MRI in presence of artificial myocardial infarction

BackgroundUnderstanding the effects of cardiac diseases on the heart's functionality which is the purpose of many biomedical researches, directly affects the diagnostic and therapeutic methods. Myocardial infarction (MI) is a common complication of cardiac ischemia, however, the impact of MI on the left ventricle (LV) flow patterns has not been widely considered by computational fluid dynamics studies thus far. MethodsIn this study, we present an insightful numerical method that creates an artificial MI on an image-based fluid-structure interactional model of normal LV to investigate its influence on the flow in comparison with the normal case. Seventeen different models were developed to evaluate the effects of location, percentage, myocardial material properties and dilation size of MI on the LV's performance, area strain, wall displacement, pressure-volume loop, wall shear stress and velocity field. ResultsThe results show that MI considerably changes blood flow features which are fully dependent on MI parameters. For the case of constant MI location, the effect of a decrease of infarcted myocardium stiffness, increase of dilation size and increase of MI percentage are mostly similar. Although the location differences of MI under other constant conditions have similar impact on the ejection fraction, they also lead to dissimilar variations in the LV flow pattern and other indicators. ConclusionsThe presented model showed a capable computational method for investigating various mechanical MI conditions with respect to cardiac flow pattern. The perspective of this model development seems to be an applicable tool for MI clinical diagnosis and prediction of complications related to MI.

Partial LVAD restores ventricular outputs and normalizes LV but not RV stress distributions in the acutely failing heart in silico.

PurposeHeart failure is a worldwide epidemic that is unlikely to change as the population ages and life expectancy increases. We sought to detail significant recent improvements to the Dassault Systèmes Living Heart Model (LHM) and use the LHM to compute left ventricular (LV) and right ventricular (RV) myofiber stress distributions under the following 4 conditions: (1) normal cardiac function; (2) acute left heart failure (ALHF); (3) ALHF treated using an LV assist device (LVAD) flow rate of 2 L/min; and (4) ALHF treated using an LVAD flow rate of 4.5 L/min.Methods and ResultsIncorporating improved systolic myocardial material properties in the LHM resulted in its ability to simulate the Frank-Starling law of the heart. We decreased myocardial contractility in the LV myocardium so that LV ejection fraction decreased from 56% to 28%. This caused mean LV end diastolic (ED) stress to increase to 508% of normal, mean LV end systolic (ES) stress to increase to 113% of normal, mean RV ED stress to decrease to 94% of normal and RV ES to increase to 570% of normal. When ALHF in the model was treated with an LVAD flow rate of 4.5 L/min, most stress results normalized. Mean LV ED stress became 85% of normal, mean LV ES stress became 109% of normal and mean RV ED stress became 95% of normal. However, mean RV ES stress improved less dramatically (to 342% of normal values).ConclusionsThese simulations strongly suggest that an LVAD is effective in normalizing LV stresses but not RV stresses that become elevated as a result of ALHF.

A Novel Method for Quantifying Smooth Regional Variations in Myocardial Contractility Within an Infarcted Human Left Ventricle Based on Delay-Enhanced Magnetic Resonance Imaging

Heart failure is increasing at an alarming rate, making it a worldwide epidemic. As the population ages and life expectancy increases, this trend is not likely to change. Myocardial infarction (MI)-induced adverse left ventricular (LV) remodeling is responsible for nearly 70% of heart failure cases. The adverse remodeling process involves an extension of the border zone (BZ) adjacent to an MI, which is normally perfused but shows myofiber contractile dysfunction. To improve patient-specific modeling of cardiac mechanics, we sought to create a finite element model of the human LV with BZ and MI morphologies integrated directly from delayed-enhancement magnetic resonance (DE-MR) images. Instead of separating the LV into discrete regions (e.g., the MI, BZ, and remote regions) with each having a homogeneous myocardial material property, we assumed a functional relation between the DE-MR image pixel intensity and myocardial stiffness and contractility--we considered a linear variation of material properties as a function of DE-MR image pixel intensity, which is known to improve the accuracy of the model's response. The finite element model was then calibrated using measurements obtained from the same patient--namely, 3D strain measurements-using complementary spatial modulation of magnetization magnetic resonance (CSPAMM-MR) images. This led to an average circumferential strain error of 8.9% across all American Heart Association (AHA) segments. We demonstrate the utility of our method for quantifying smooth regional variations in myocardial contractility using cardiac DE-MR and CSPAMM-MR images acquired from a 78-yr-old woman who experienced an MI approximately 1 yr prior. We found a remote myocardial diastolic stiffness of C(0) = 0.102 kPa, and a remote myocardial contractility of T(max) = 146.9 kPa, which are both in the range of previously published normal human values. Moreover, we found a normalized pixel intensity range of 30% for the BZ, which is consistent with the literature. Based on these regional myocardial material properties, we used our finite element model to compute patient-specific diastolic and systolic LV myofiber stress distributions, which cannot be measured directly. One of the main driving forces for adverse LV remodeling is assumed to be an abnormally high level of ventricular wall stress, and many existing and new treatments for heart failure fundamentally attempt to normalize LV wall stress. Thus, our noninvasive method for estimating smooth regional variations in myocardial contractility should be valuable for optimizing new surgical or medical strategies to limit the chronic evolution from infarction to heart failure.

Human Cardiac Function Simulator for the Optimal Design of a Novel Annuloplasty Ring with a Sub-valvular Element for Correction of Ischemic Mitral Regurgitation.

Ischemic mitral regurgitation is associated with substantial risk of death. We sought to: (1) detail significant recent improvements to the Dassault Systèmes human cardiac function simulator (HCFS); (2) use the HCFS to simulate normal cardiac function as well as pathologic function in the setting of posterior left ventricular (LV) papillary muscle infarction; and (3) debut our novel device for correction of ischemic mitral regurgitation. We synthesized two recent studies of human myocardial mechanics. The first study presented the robust and integrative finite element HCFS. Its primary limitation was its poor diastolic performance with an LV ejection fraction below 20% caused by overly stiff ex vivo porcine tissue parameters. The second study derived improved diastolic myocardial material parameters using in vivo MRI data from five normal human subjects. We combined these models to simulate ischemic mitral regurgitation by computationally infarcting an LV region including the posterior papillary muscle. Contact between our novel device and the mitral valve apparatus was simulated using Dassault Systèmes SIMULIA software. Incorporating improved cardiac geometry and diastolic myocardial material properties in the HCFS resulted in a realistic LV ejection fraction of 55%. Simulating infarction of posterior papillary muscle caused regurgitant mitral valve mechanics. Implementation of our novel device corrected valve dysfunction. Improvements in the current study to the HCFS permit increasingly accurate study of myocardial mechanics. The first application of this simulator to abnormal human cardiac function suggests that our novel annuloplasty ring with a sub-valvular element will correct ischemic mitral regurgitation.Electronic supplementary materialThe online version of this article (doi:10.1007/s13239-015-0216-z) contains supplementary material, which is available to authorized users.

Modeling the Effects of Myocardial Fiber Architecture and Material Properties on the Left Ventricle Mechanics during Rapid Filling Phase

Modeling the Effects of Myocardial Fiber Architecture and Material Properties on the Left Ventricle Mechanics during Rapid Filling Phase

Applications of Computational Modeling in Cardiac Surgery

Although computational modeling is common in many areas of science and engineering, only recently have advances in experimental techniques and medical imaging allowed this tool to be applied in cardiac surgery. Despite its infancy in cardiac surgery, computational modeling has been useful in calculating the effects of clinical devices and surgical procedures. In this review, we present several examples that demonstrate the capabilities of computational cardiac modeling in cardiac surgery. Specifically, we demonstrate its ability to simulate surgery, predict myofiber stress and pump function, and quantify changes to regional myocardial material properties. In addition, issues that would need to be resolved in order for computational modeling to play a greater role in cardiac surgery are discussed.

Afterload quantitation for evaluation of myocardial strain

Background Systolic myocardial strain is load dependent, but the CMR literature largely disregards effects of myocardial afterload on strain and strain rate. This may reflect well known limitations of conventional myocardial afterload assessment using wall stress analyses, which are based on erroneous assumptions about left ventricular(LV) geometry and/or myocardial material properties. Therefore, we compared the utility of a nongeometric afterload index (NGI) derived from LV pressure(P) volume(V) and mass, which requires no assumptions about material properties, to that of conventional noninvasive end-systolic circumferential stress(CWS) as determinants of CMR LV circumferential strain(CST), ejection fraction(EF) and strain rate(SR) in normals(NL) and patients with nonischemic dilated cardiomyopathy(CM).

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

The material properties of myocardium are an important determinant of global left ventricular function. Myocardial infarction results in a series of maladaptive geometric alterations which lead to increased stress and risk of heart failure. In vivo studies have demonstrated that material injection can mitigate these changes. More importantly, the material properties of these injectates can be tuned to minimize wall thinning and ventricular dilation. The current investigation combines experimental data and finite element modeling to correlate how injectate mechanics and volume influence myocardial wall stress. Experimentally, mechanics were characterized with biaxial testing and injected hydrogel volumes were measured with magnetic resonance imaging. Injection of hyaluronic acid hydrogel increased the stiffness of the myocardium/hydrogel composite region in an anisotropic manner, significantly increasing the modulus in the longitudinal direction compared to control myocardium. Increased stiffness, in combination with increased volume from hydrogel injection, reduced the global average fiber stress by ~14% and the transmural average by ~26% in the simulations. Additionally, stiffening in an anisotropic manner enhanced the influence of hydrogel treatment in decreasing stress. Overall, this work provides insight on how injectable biomaterials can be used to attenuate wall stress and provides tools to further optimize material properties for therapeutic applications.

A Meshfree Method for Simulating Myocardial Electrical Activity

An element-free Galerkin method (EFGM) is proposed to simulate the propagation of myocardial electrical activation without explicit mesh constraints using a monodomain model. In our framework the geometry of myocardium is first defined by a meshfree particle representation that is, a sufficient number of sample nodes without explicit connectivities are placed in and inside the surface of myocardium. Fiber orientations and other material properties of myocardium are then attached to sample nodes according to their geometrical locations, and over the meshfree particle representation spatial variation of these properties is approximated using the shape function of EFGM. After the monodomain equations are converted to their Galerkin weak form and solved using EFGM, the propagation of myocardial activation can be simulated over the meshfree particle representation. The derivation of this solution technique is presented along a series of numerical experiments and a solution of monodomain model using a FitzHugh-Nagumo (FHN) membrane model in a canine ventricular model and a human-heart model which is constructed from digitized virtual Chinese dataset.

A Method for Automatically Optimizing Medical Devices for Treating Heart Failure: Designing Polymeric Injection Patterns

Heart failure continues to present a significant medical and economic burden throughout the developed world. Novel treatments involving the injection of polymeric materials into the myocardium of the failing left ventricle (LV) are currently being developed, which may reduce elevated myofiber stresses during the cardiac cycle and act to retard the progression of heart failure. A finite element (FE) simulation-based method was developed in this study that can automatically optimize the injection pattern of the polymeric "inclusions" according to a specific objective function, using commercially available software tools. The FE preprocessor TRUEGRID((R)) was used to create a parametric axisymmetric LV mesh matched to experimentally measured end-diastole and end-systole metrics from dogs with coronary microembolization-induced heart failure. Passive and active myocardial material properties were defined by a pseudo-elastic-strain energy function and a time-varying elastance model of active contraction, respectively, that were implemented in the FE software LS-DYNA. The companion optimization software LS-OPT was used to communicate directly with TRUEGRID((R)) to determine FE model parameters, such as defining the injection pattern and inclusion characteristics. The optimization resulted in an intuitive optimal injection pattern (i.e., the one with the greatest number of inclusions) when the objective function was weighted to minimize mean end-diastolic and end-systolic myofiber stress and ignore LV stroke volume. In contrast, the optimization resulted in a nonintuitive optimal pattern (i.e., 3 inclusions longitudinallyx6 inclusions circumferentially) when both myofiber stress and stroke volume were incorporated into the objective function with different weights.

Invited Commentary

Progressive dilation of the left ventricle (LV) and deterioration of LV pump performance often occur after myocardial infarction (MI). A number of pharmacological or nonpharmacological interventions, or both, have been used to attenuate or even reverse these progressive adverse changes in LV geometry and function. However, mechanisms that contribute to these changes, especially the role of the changes in the material properties of the MI region, remain largely unexplored. In this article, Pilla and colleagues [1Pilla J.J. Gorman III, J.H. Gorman R.C. et al.Theoretical impact of infarct compliance on left ventricular function.Ann Thorac Surg. 2009; 87: 803-811Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar] describe a mathematical simulation for changes in hemodynamics and LV geometry as a function of changing the compliance (or stiffness) of a hypothesized MI region. The authors refer to the mathematical model as a “lumped parameter” simulation, which comprised of resistive, capacitive, and unidirectional flow (diode) components. This model was first used to simulate normal hemodynamics and LV geometry based on database records of normal ovine physiology. An important component of this model was the inclusion of a compensatory element that accounted for maintenance of stroke volume through a feedback input that altered total blood volume. Next, this model was used to simulate LV pressures and volumes while incorporating a noncontributing portion of the LV (the MI region) at a set compliance value for the MI region. The authors report that the simulated LV pressure-volume curves closely approximated recorded values in an ovine MI model. A significant finding from this model was the attenuation in LV dilation and oxygen consumption with a stiffer (noncompliant) infarct region. An important implication of this finding with respect to remodeling of the infarct region is that modification of the composition and content of the MI scar can provide a means to prevent the almost inevitable LV dilation and deterioration in pump function after MI. Moreover, these findings provide a mathematical basis for the attenuation in post-MI LV dilation that has been reported in prior studies where biocompatible scaffolding/matrix was injected into the MI region. However, it must be recognized that any mathematical model is built on a series of assumptions and that these conditions are even more difficult to apply to the heterogeneous “border” region between the viable myocardium and the MI region. It has been postulated that the differential stress and strain patterns at the transition between viable myocardium and the border zone, as well as the interface between the border zone and the MI region, likely exacerbate expansion of the MI region. The relative paucity of critical basic science detailing of myocardial material properties, in particular at the border region, precludes more comprehensive mathematical modeling of LV remodeling post-MI. An important consideration for any model is its clinical applicability or application of the model, or both, to better understand where and when a certain therapeutic modality may confer clinical benefit. For example, if a hypothesized intervention were known to provide a specific time-dependent effect on the material properties of the MI region, then this model could be implemented to determine long-term effects of the intervention on LV dilation post-MI. In this light, further validation from complementary in vivo studies in which the relationship between compliance and the extent of LV dilation post-MI are warranted. Nevertheless, the findings from the mathematical model developed by Pilla and colleagues [1Pilla J.J. Gorman III, J.H. Gorman R.C. et al.Theoretical impact of infarct compliance on left ventricular function.Ann Thorac Surg. 2009; 87: 803-811Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar] form an important first step to further understanding the role of changes in myocardial material properties and pathologic remodeling after MI. Theoretic Impact of Infarct Compliance on Left Ventricular FunctionThe Annals of Thoracic SurgeryVol. 87Issue 3PreviewAfter coronary occlusion, the infarct region loses contractile function immediately and then undergoes a progressive healing process. This causes complex and time-dependent changes in infarct material properties that have not been well described experimentally. We used a theoretic approach to assess how infarct compliance effects left ventricular (LV) size and function after myocardial infarction. Full-Text PDF

Strain measurement in the left ventricle during systole with deformable image registration

The objective of this study was to validate a deformable image registration technique, termed Hyperelastic Warping, for left ventricular strain measurement during systole using cine-gated, non-tagged MR images with strains measured from tagged MRI. The technique combines deformation from high resolution, non-tagged MR image data with a detailed computational model, including estimated myocardial material properties, fiber direction, and active fiber contraction, to provide a comprehensive description of myocardial contractile function. A normal volunteer (male, age 30) with no history of cardiac pathology was imaged with a 1.5 T Siemens Avanto clinical scanner using a TrueFISP imaging sequence and a 32-channel cardiac coil. Both tagged and non-tagged cine MR images were obtained. The Hyperelastic Warping solution was evolved using a series of non-tagged images in ten intermediate phases from end-diastole to end-systole. The solution may be considered as ten separate warping problems with multiple templates and targets. At each stage, an active contraction was initially applied to a finite element model, and then image-based warping penalty forces were utilized to generate the final registration. Warping results for circumferential strain (R(2)=0.75) and radial strain (R(2)=0.78) were strongly correlated with results obtained from tagged MR images analyzed with a Harmonic Phase (HARP) algorithm. Results for fiber stretch, LV twist, and transmural strain distributions were in good agreement with experimental values in the literature. In conclusion, Hyperelastic Warping provides a unique alternative for quantifying regional LV deformation during systole without the need for tags.

Method and Apparatus for Soft Tissue Material Parameter Estimation Using Tissue Tagged Magnetic Resonance Imaging

We describe an experimental method and apparatus for the estimation of constitutive parameters of soft tissue using Magnetic Resonance Imaging (MRI), in particular for the estimation of passive myocardial material properties. MRI tissue tagged images were acquired with simultaneous pressure recordings, while the tissue was cyclically deformed using a custom built reciprocating pump actuator A continuous three-dimensional (3D) displacement field was reconstructed from the imaged tag motion. Cavity volume changes and local tissue microstructure were determined from phase contrast velocity and diffusion tensor MR images, respectively. The Finite Element Method (FEM) was used to solve the finite elasticity problem and obtain the displacement field that satisfied the applied boundary conditions and a given set of material parameters. The material parameters which best fit the FEM predicted displacements to the displacements reconstructed from the tagged images were found by nonlinear optimization. The equipment and method were validated using inflation of a deformable silicon gel phantom in the shape of a cylindrical annulus. The silicon gel was well described by a neo-Hookian material law with a single material parameter C1=8.71+/-0.06kPa, estimated independently using a rotational shear apparatus. The MRI derived parameter was allowed to vary regionally and was estimated as C1 =8.80+/-0.86kPa across the model. Preliminary results from the passive inflation of an isolated arrested pig heart are also presented, demonstrating the feasibility of the apparatus and method for isolated heart preparations. FEM based models can therefore estimate constitutive parameters accurately and reliably from MRI tagging data.

Chronic beta-adrenoreceptor activation increases cardiac cavity size through chamber remodeling and not via modifications in myocardial material properties.

Chronic beta-adrenoreceptor (beta-AR) activation increases left ventricular (LV) cavity size by promoting a rightward shift in LV diastolic pressure-volume (P-V) relations in association with increases in low-tensile strength myocardial (non-cross-linked) collagen concentrations. Because diastolic P-V relations are determined by chamber remodeling as well as by myocardial material properties (indexed by myocardial stiffness), both of which are associated with modifications in myocardial collagen cross-linking, we evaluated whether chamber remodeling or alterations in myocardial material properties govern beta-AR-mediated modifications in diastolic P-V relations. The effects of chronic administration of isoproterenol (Iso; 0.04 mg.kg(-1).day(-1) from 12 to 19 mo of age) to spontaneously hypertensive rats (SHRs) on LV cavity dimensions, LV diastolic P-V relations, myocardial collagen characteristics, myocardial stiffness constants [e.g., the slope of the LV diastolic stress-strain relation (k)], and LV chamber and myocardial systolic function were assessed. SHRs at 19 mo of age had normal LV diastolic P-V relations, marked myocardial fibrosis (using a pathological score), increased myocardial cross-linked (insoluble to cyanogen bromide digestion) type I and type III collagen concentrations, and enhanced myocardial k values. Iso administration to SHRs resulted in enlarged LV cavity dimensions mediated by a rightward shift in LV diastolic P-V relations, increased volume intercept of the LV diastolic P-V relation, decreased LV relative wall thickness despite a tendency to augment LV hypertrophy, and increased non-cross-linked type I and type III myocardial collagen concentrations. Iso administration resulted in reduced pump function without modification of intrinsic myocardial systolic function. However, despite increasing myocardial non-cross-linked concentrations, Iso failed to alter myocardial k in SHRs. These results suggest that beta-AR-mediated rightward shifts in LV diastolic P-V relations, which induce decreased pump function, are mediated by chamber remodeling but not by modifications in myocardial material properties.

Ventricular mechanics in diastole: material parameter sensitivity

Models of ventricular mechanics have been developed over the last 20 years to include finite deformation theory, anisotropic and inhomogeneous material properties and an accurate representation of ventricular geometry. As computer performance and the computational efficiency of the models improve, clinical application of these heart mechanics models is becoming feasible. One such application is to estimate myocardial material properties by adjusting the constitutive parameters to match wall deformation from MRI or ultrasound measurements, together with a measurement (or estimate) of ventricular pressure. Pigs are now the principal large animal model for these studies and in this paper we present the development of a new three-dimensional finite element model of the heart based on measurements of the geometry and the fibre and sheet orientations of pig hearts. The end-diastolic deformation of the model is computed using the “pole-zero” constitutive law which we have previously used to model the mechanics of passive myocardial tissue specimens. The sensitivities of end-diastolic fibre-sheet material strains and heart shape to changes in the material parameters are computed for the parameters of the pole-zero law in order to assess the utility of the models for inverse material property determination.

Matrix metalloproteinase inhibition modifies left ventricular remodeling after myocardial infarction in pigs

Background: Global and regional shape changes that occur within the left ventricular wall after myocardial infarction have been termed infarct expansion. A potential mechanism for this postinfarction remodeling is activation of the matrix metalloproteinases. Accordingly, the present study examined the effects of matrix metalloproteinase inhibition on left ventricular global geometry after myocardial infarction in pigs. Methods: Myocardial infarction was created in pigs by means of occlusion of the first and second obtuse marginal branches of the circumflex coronary artery, resulting in a uniform left ventricular free wall infarct size of 21% ± 2%. At 5 days after infarction, the pigs were randomized to undergo broad-spectrum matrix metalloproteinase inhibition (n = 9; PD166793, 20 mg · kg−1 · d−1 by mouth) or myocardial infarction alone (n = 8). Ten pigs served as noninfarction control animals. Left ventricular end-diastolic area, determined by means of echocardiography, was measured 8 weeks after infarction. Results: Left ventricular end-diastolic area increased in both the myocardial infarction plus broad-spectrum matrix metalloproteinase inhibition and myocardial infarction only groups compared to reference control animals (3.7 ± 0.2 cm2), but was reduced with broad-spectrum matrix metalloproteinase inhibition compared to myocardial infarction alone (4.5 ± 0.2 vs 4.9 ± 0.2 cm2, respectively; P <.05). Regional radial stress within the infarct region increased in both infarction groups when compared to values obtained from reference control animals (599 ± 152 g/cm2), but was attenuated in the myocardial infarction plus broad-spectrum matrix metalloproteinase inhibition group compared to the myocardial infarction alone group (663 ± 108 vs 1242 ± 251 g/cm2, respectively; P <.05). Similarly, regional myocardial stiffness increased in both the myocardial infarction plus broad-spectrum matrix metalloproteinase inhibition and the myocardial infarction only groups compared with that observed in reference control animals (14 ± 1 rkm, P <.05) but was lower with broad-spectrum matrix metalloproteinase inhibition than with myocardial infarction alone (42 ± 6 vs 68 ± 10 rkm, respectively; P <.05). Conclusions: Matrix metalloproteinase inhibition reduced postinfarction left ventricular dilation, reduced regional myocardial wall stress, and modified myocardial material properties. These unique findings suggest that increased myocardial matrix metalloproteinase activation after infarction contributes directly to the left ventricular remodeling process.J Thorac Cardiovasc Surg 2003;125:602-10

Constitutive properties of hypertrophied myocardium: cellular contribution to changes in myocardial stiffness.

Recent studies have suggested that pressure overload hypertrophy (POH) alters the viscoelastic properties of individual cardiocytes when studied in isolation. However, whether these changes in cardiocyte properties contribute causally to changes in the material properties of the cardiac muscle as a whole is unknown. Accordingly, a selective, isolated, acute change in cardiocyte constitutive properties was imposed in an in vitro system capable of measuring the resultant effect on the material properties of the composite cardiac muscle. POH caused an increase in both myocardial elastic stiffness, from 20.5 +/- 1.3 to 28.4 +/- 1.8, and viscous damping, from 15.2 +/- 1.1 to 19.8 +/- 1.5 s (normal vs. POH, P < 0.05), respectively. Recent studies have shown that cardiocyte constitutive properties could be acutely altered by depolymerizing the microtubules with colchicine. Colchicine caused a significant decrease in the viscous damping in POH muscles (19.8 +/- 1.5 s at baseline vs. 14.7 +/- 1.3 s after colchicine, P < 0.05). Therefore, myocardial material properties can be altered by selectively changing the constitutive properties of one element within this muscle tissue, the cardiocyte. Changes in the constitutive properties of the cardiocytes themselves contribute to the abnormalities in myocardial stiffness and viscosity that develop during POH.