Properties Of Myocardial Tissue Research Articles

16 The cardiac toxicity CMR study in patients with lung cancer treated with chemo-radiotherapy: The cart study- a semi quantitative analysis of the myocardial perfusion index

Background There are limited data on the cardiac effects of radiotherapy and chemo-radiotherapy on the heart in patients with non-small cell lung cancer (NSCLC). CART is a pilot study designed to investigate change in myocardial function and tissue properties where Patients will undergo cardiac magnetic resonance (CMR) at baseline, during treatment, at 6 weeks and at 6 months after treatment completion. Here we report our preliminary findings related to temporal changes in myocardial perfusion index (MPI). Methods CMR was performed on a Siemens MAGNETOM Verio (Erlangen, Germany) 3.0 Tesla scanner. First-pass myocardial perfusion was assessed by saturation recovery prepared dynamic contrast enhanced sequence during administration of 0.1 mmol/kg of gadoterate meglumine (Dotarem). Semiquantitative analysis was performed on segmented basal and mid-LV short axis slices to derive normalised upslopes of myocardial signal intensity profiles (myocardial perfusion index, MPI). The change in MPI over time was analysed statistically using a linear mixed effects model. Results 13 patients currently have undergone CMR at baseline and during treatment (mean age 66 years, SD: 9; 71% male), 8 patients have undergone CMR at 6 weeks post treatment initiation (5 patients lost to follow-up/ died), and 6 patients have undergone CMR at 6 months from baseline (n = 2 lost to follow-up/ died). Perfusion index (Figure 1) varies significantly with time (p = 0.0015). After adjustment for multiple testing, the increase from baseline is statistically significant at 6 weeks (p = 0.014) and approaches significance at 6 months (p = 0.074) post treatment. Conclusion Change in microvascular perfusion is most pronounced 6 weeks following the completion of treatment. This finding will be used in the design of future clinical studies, where measurement of MPI will provide a robust comparison of different existing and emerging treatment protocols for NSCLC with regard to their effects on myocardial physiology. Funding Beatson Oncology Centre Fund

Dynamic and static tensile mechanical properties of myocardial tissue.

Event Abstract Back to Event Dynamic and static tensile mechanical properties of myocardial tissue. Sherif Ramadan1, 2, 3, Hani Naguib1, 2, 3 and Narinder Paul3, 4 1 University of Toronto, Mechanical and Industrial Engineering, Canada 2 University of Toronto, Smart and Adaptive Polymers Lab, Canada 3 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada 4 Toronto General Hospital, Joint Department of Medical Imaging, Canada Introduction: Heart disease is a significant cause of morbidity and mortality that affects 1.3 million Canadians annually[1]. Coronary artery disease (CAD) is a leading cause of heart disease and is due to progressive accumulation of arterial plaque resulting in occlusion of the arterial lumen and abnormal myocardial contractility[2]. Computed Tomography Coronary Angiography (CTCA) is used to exclude significant CAD in patients with low-intermediate pre-test probability[3],[4]. However, dynamic anthropomorphic CT phantom devices that realistically mimic normal and diseased cardiac tissues are required to test new imaging techniques and algorithms that target ultralow radiation dose and high resolution CTCA. This study aims to quantify the mechanical properties of myocardial tissue to allow for the fabrication of phantoms that mimic the behaviour of heart tissue under varying hemodynamic conditions. Materials and Methods: The elasticity of myocardial tissue was tested under static and dynamic conditions. Tensile testing was performed to obtain the Young’s modulus and a dynamic mechanical analyzer (DMA) induced a frequency sweep to determine the complex (dynamic) modulus. A frequency range of 0.5Hz to 3.5Hz was analyzed as these frequencies correspond to human heart rates of 30 to 210bpm. Multiple tissue samples were taken from each pig and lamb heart, these animal models were chosen as they are close human analogues and are commonly used as replacements for human tissue[5],[6].The heart tissue was tested while freshly sacrificed without any intervening freeze-thaw cycles to ensure the integrity of the muscle tissue. The tissue was placed in a balanced salt solution and tested at 37°C to simulate in vitro conditions[7]. Results and Discussion: Preliminary data (mean ± SD): The tensile and complex moduli were tested on 6 pig and lamb hearts; tensile modulus of lamb = 0.06 ±0.03 (n=15 samples) and for pig =0.04 ± 0.03 (n=11 samples); the complex modulus for lamb = 0.03Mpa at 0.5Hz to 0.06 Mpa at 3.5Hz ± 0.02 (n=15 samples) and for pig = 0.03Mpa at 0.5Hz to 0.06 Mpa at 3.5Hz ± .01 (n=15 samples) and both exhibited a linear trend. These values indicate that myocardial tissue behaves similarly to soft rubbers and stiffens under higher frequency loads. Moreover, for tensile testing there was no statistical difference between individual hearts or animals (P values of 0.235, 0.483, and 0.73 between the animals, pig hearts, and lamb hearts respectively). Conclusions: The static and dynamic moduli of myocardial tissue in pig and lamb hearts is between 0.02 and 0.1Mpa which is similar to soft, rubber-like materials. This quantitative data will inform selection and fabrication of customized biomaterials for construction of the myocardium in a dynamic anthropomorphic tissue realistic heart phantom.

MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction

Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI.

Building a better infarct: Modulation of collagen cross-linking to increase infarct stiffness and reduce left ventricular dilation post-myocardial infarction

Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood.The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9−/−; n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42). At day 7 post-MI, WT LVs displayed a 3-fold increase in end-diastolic volume, while MMP-9−/− showed only a 2-fold increase (p<0.05). Biaxial mechanical testing revealed that MMP-9−/− infarcts were stiffer than WT infarcts, as indicated by a 1.3-fold reduction in predicted in vivo circumferential stretch (p<0.05). Paradoxically, MMP-9−/− infarcts had a 1.8-fold reduction in collagen deposition (p<0.05). This apparent contradiction was explained by a 3.1-fold increase in lysyl oxidase (p<0.05) in MMP-9−/− infarcts, indicating that MMP-9 deletion increased collagen cross-linking activity. Furthermore, MMP-9 deletion led to a 3.0-fold increase in bone morphogenetic protein-1, the metalloproteinase that cleaves pro-collagen and pro-lysyl oxidase (p<0.05) and reduced fibronectin fragmentation by 49% (p<0.05) to enhance lysyl oxidase activity. We conclude that MMP-9 deletion increases infarct stiffness and prevents LV dilation by reducing collagen degradation and facilitating collagen assembly and cross-linking through preservation of the fibronectin network and activation of lysyl oxidase.

Intracardiac myocardial elastography in canines and humans in vivo.

Intracardiac echocardiography (ICE) is a useful imaging modality which is used during RF ablation procedures to identify anatomical structures. Utilizing ICE in conjunction with myocardial elastography (ME) can provide additional information on the mechanical properties of cardiac tissue and provide information on mechanical changes caused by ablation. The objective of this study was to demonstrate that ICE can be used at high frame rate using a diverging beam transmit sequence to image myocardial strain and differentiate myocardial tissue properties before, during, and after ablation for a clinical ablation procedure. In this feasibility study, three normal canines and eight patients with atrial fibrillation (AF) were studied in vivo. A 5.8-MHz ICE transducer was used to image the heart with a diverging beam transmit method achieving 1200 frames per second (fps). Cumulative axial displacement estimation was performed using 1-D cross-correlation with a window size of 2.7 mm and 95% overlap. Axial cumulative strains were estimated in the left atrium (LA) and right atrium (RA) using a least-squares estimator with a kernel of 2 mm on the axial displacements. In the canine case, radial thickening was detected in the lateral wall and in the interatrial septum during LA emptying. For AF patients, the mean absolute strain in the ablated region was lower (6.7 ± 3.1%) than before the ablation (17.4 ± 9.3%) in LA at the end of the LA emptying phase. In the cavotricuspid isthmus (CTI) region, mean absolute strain magnitude at the end of the RA emptying phase was found to be higher during ablation (43.0 ± 18.1%) compared with after ablation (33.7 ± 15.8%). Myocardial strains in the LA of an AF patient were approximately 2.6 times lower in the ablated region than before ablation. This initial feasibility indicates that ME can be used as a new imaging modality in conjunction with ICE in RF ablation guidance and lesion monitoring.

Myocardial Tissue Characterization by Magnetic Resonance Imaging

Cardiac magnetic resonance (CMR) imaging is a well-established noninvasive imaging modality in clinical cardiology. Its unsurpassed accuracy in defining cardiac morphology and function and its ability to provide tissue characterization make it well suited for the study of patients with cardiac diseases. Late gadolinium enhancement was a major advancement in the development of tissue characterization techniques, allowing the unique ability of CMR to differentiate ischemic heart disease from nonischemic cardiomyopathies. Using T2-weighted techniques, areas of edema and inflammation can be identified in the myocardium. A new generation of myocardial mapping techniques are emerging, enabling direct quantitative assessment of myocardial tissue properties in absolute terms. This review will summarize recent developments involving T1-mapping and T2-mapping techniques and focus on the clinical applications and future potential of these evolving CMR methodologies.

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome.

Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or β-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and β1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.

Chaotic Nature of Myocardial Ultrasonic Radio Frequency Signals Changes Following Anti-Hypertensive Medications

Chaotic nature of myocardial ultrasonic radio-frequency (RF) signals have been shown to reflect myocardial tissue properties in humans (1). The decreased plasma adiponectin levels or increased plasma aldosterone levels play an important role in cardiac hypertrophy and fibrosis in patients with hypertension (2)(3). Quasistatic behavior was prevalent in the RF signals in the hypertensive patients. Regression of myocardial fibrosis changed RF signals from quasistatic to chaotic nature, and restraint of myocardial hypertrophy, vice versa. I. INTRODUCTION Chaotic nature of myocardial ultrasonic radio-frequency (RF) signals reflects myocardial tissue properties; however, it is unclear whether it changes after treatment in accord with changes in myocardial properties in hypertensive patients.

Simulation of Changes in Myocardial Tissue Properties During Left Ventricular Assistance With a Rotary Blood Pump

We considered a mathematical model to investigate changes in geometric and hemodynamic indices of left ventricular function in response to changes in myofiber contractility and myocardial tissue stiffness during rotary blood pump support. Left ventricular assistance with a rotary blood pump was simulated based on a previously published biventricular model of the assisted heart and circulation. The ventricles in this model were based on the one-fiber model that relates ventricular function to myofiber contractility and myocardial tissue stiffness. The simulations showed that indices of ventricular geometry, left ventricular shortening fraction, and ejection fraction had the same response to variations in myofiber contractility and myocardial tissue stiffness. Hemodynamic measures showed an inverse relation compared with geometric measures. Particularly, pulse pressure and arterial dP/dtmax increased when myofiber contractility increased, whereas increasing myocardial tissue stiffness decreased these measures. Similarly, the lowest pump speed at which the aortic valve remained closed increased when myofiber contractility increased and decreased when myocardial tissue stiffness increased. Therefore, simultaneous monitoring of hemodynamic parameters and ventricular geometry indirectly reflects the status of the myocardial tissue. The appropriateness of this strategy will be evaluated in the future, based on in vivo studies.

Design, construction, and evaluation of a dynamic MR compatible cardiac left ventricle model

Development of magnetic resonance (MR) sequences is important to answer clinical questions and to overcome current limitations. To meet the challenges of cardiac MR, dynamic and reproducible testing conditions are required. We aimed at developing a dynamic MR-compatible cardiac left ventricle model that imitates myocardial tissue properties and simulates dynamic motion. A dynamic left ventricle silicone model was designed to match myocardial T(1) and T(2) relaxation times. Silicone mixtures were explored to replicate T(2) values of myocardial edema. A controllable piston pump was constructed to produce pulsatile flow paradigms. They were validated against flow sensors and MR data, including SSFP-based and phase-contrast-based sequences. A dedicated software interface was developed for the control. Model dimensions represented cardiac left ventricle dimensions of healthy men. The range of end diastolic volumes was 85-175 ml, depending on the driven stroke volume. Stroke volume quantification for flow paradigms of 30∕60∕90∕120 ml resulted in 29.2∕57.6∕88.8∕118.4 ml by MR volumetry, 29.6∕59.9∕89.4∕119.0 ml by phase contrast measurements, and 29.9∕60.4∕91.1∕120.9 ml by flow meter revealing consistency. The system accurately replicated physiological and pathophysiological flow paradigms. The silicon model exhibited T(1) of 1002 ± 8 ms, T(2) of 58 ± 1 ms. Signal intensities (a.u.) of the ventricle model were 128 ± 23 for FGRE (vs 138 ± 17 in vivo) and 1156 ± 37 for b-SSFP (vs 991 ± 96 in vivo). T(2) of 75 ± 2 ms was achieved for the myocardial pathology. We developed a controllable left ventricle model resembling MR signal characteristics of human myocardium, including pathological conditions, and allowing for the replication of contraction and flow paradigms.

Multi-scale computational models of familial hypertrophic cardiomyopathy: genotype to phenotype

Familial hypertrophic cardiomyopathy (FHC) is an inherited disorder affecting roughly one in 500 people. Its hallmark is abnormal thickening of the ventricular wall, leading to serious complications that include heart failure and sudden cardiac death. Treatment is complicated by variation in the severity, symptoms and risks for sudden death within the patient population. Nearly all of the genetic lesions associated with FHC occur in genes encoding sarcomeric proteins, indicating that defects in cardiac muscle contraction underlie the condition. Detailed biophysical data are increasingly available for computational analyses that could be used to predict heart phenotypes based on genotype. These models must integrate the dynamic processes occurring in cardiac cells with properties of myocardial tissue, heart geometry and haemodynamic load in order to predict strain and stress in the ventricular walls and overall pump function. Recent advances have increased the biophysical detail in these models at the myofilament level, which will allow properties of FHC-linked mutant proteins to be accurately represented in simulations of whole heart function. The short-term impact of these models will be detailed descriptions of contractile dysfunction and altered myocardial strain patterns at the earliest stages of the disease-predictions that could be validated in genetically modified animals. Long term, these multi-scale models have the potential to improve clinical management of FHC through genotype-based risk stratification and personalized therapy.

Left atrial reservoir function predicts atrial fibrillation recurrence after catheter ablation: a two-dimensional speckle strain study

Predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are not fully defined. We hypothesized that 2D left atrial (LA) regional strain maps would help identify abnormal atrial substrate that increases susceptibility to AF recurrence post-CA. Sixty-three patients (63 ± 10years, 60% male) underwent CA for symptomatic paroxysmal (75%) or persistent (25%) AF. Baseline LA mechanical function determined using speckle tracking echocardiography was compared between those with AF recurrence (AFR) and no recurrence post-CA. Bi-dimensional global and regional maps of LA wall velocity, strain, and strain rate (SR) were obtained during end ejection and early diastole. After 18 ± 12months of follow-up, 34 patients were free of AFR post-CA. There were no differences in clinical characteristics, LA and LV volumes, and Doppler estimates of LV diastolic function and filling pressures at baseline between patients with recurrent AF and those that maintained sinus rhythm. However, the LA emptying fraction (55 ± 17% vs. 64 ± 14%, p = 0.04), global and regional systolic and diastolic strains, SR, and velocities were reduced in patients with recurrent AF. There was marked attenuation of peak LA lateral wall longitudinal strain (LS; 11 ± 7% vs. 20 ± 14%, p = 0.007) and SR (0.9 ± 0.4 vs.1.3 ± 0.6s(-1), p = 0.01). Multivariate analysis revealed lateral wall LS (odds ratio = 1.15, 95% CI = 1.02-1.28, p = 0.01) as an independent predictor of AFR. Regional LA lateral wall LS is a pre-procedural determinant of AFR in patients undergoing CA, independent of LA enlargement. Characterization of atrial myocardial tissue properties by speckle tracking echo may aid the appropriate selection of adjunctive strategies and prognostication of patients undergoing CA.

Imaging electrical excitation inside the myocardial wall

Cardiac arrhythmias are often triggered by ectopic membrane depolarization originating deep inside the myocardial wall. Here we propose a new method utilizing a novel near-infrared voltage-sensitive fluorescent dye DI-4-ANBDQBS to determine the three-dimensional (3D) coordinates of the sources of such depolarization. We tested the method in live preparations of pig left and right ventricular myocardium (thickness 8-18 mm) and phantoms imitating the optical properties of myocardial tissue. The method utilizes an alternating transillumination approach that involves comparing pairs of simultaneously recorded broad-field epifluorescence and transillumination images produced at two alternating directions of illumination. Recordings were taken simultaneously by two CCD cameras facing the endocardial and epicardial surfaces of the heart at a frame rate up to 3 KHz. In live preparations, we were able to localize the origin of the depolarization wave with a precision of ±1.3mm in the transmural direction and 3 mm in the image plane. The accuracy of detection was independent of the depth of the source inside ventricular wall.

Improved quantification of T2* relaxation in magnetic resonance imaging

MRI can acquire images from which myocardial tissue properties can be derived. One such parameter is T2* relaxation. Currently there is software available that calculate T2* values and generate tissue maps. However, they do not give information of certainty and they have problems with numerical stability for low T2* values.

Small animal look-locker inversion recovery (SALLI)

Cardiac T1 mapping allows for quantitative analysis of myocardial tissue properties. Pulse sequences for human applications are not suitable for in-vivo studies in small animals.The aim of this study was to develop a single magnetic resonance imaging (MRI) approach for comprehensive assessment of cardiac function and tissue properties in small animals with high heart rates.

Sex Differences in the Mechanical Properties of Rat Myocardium After Exposure to Simulated Microgravity

Female astronauts are more likely than male astronauts to develop presyncope and orthostatic intolerance when they return to normal gravity after space-flights. The underlying mechanisms for this are unclear but could include myocardial adaptations to micro-gravity conditions. This study was designed to test whether there are sex-specific changes in the mechanical properties of myocardial tissue in rats subjected to a period of simulated microgravity. Multicellular myocardial preparations were isolated from control male and female Sprague-Dawley rats and corresponding experimental animals that were hind-limb unloaded (HLU) for 14 days. Preparations were subjected to standard mechanical tests imposed under muscle length control in solutions with pCa values ranging from 9.0 to 4.5. The rates of tension recovery (ktr) measured in pCa 4.5 solution were significantly higher (p<0.002, 2-way ANOVA) in the preparations isolated from the HLU animals than in preparations isolated from the control groups (ktr mean values ± SEM measured in pCa 4.5 were: 7.45±0.37 s−1 for female control; 9.54±0.50 s−1 female HLU; 7.70±0.46 s−1 male control and 8.42±0.37 s−1 male HLU). The relative content of slower beta-Myosin Heavy Chain decreased in both HLU groups compared to the corresponding control groups (p<0.01, 2-way ANOVA). There was no interaction for this parameter between sex and unloading condition (p=0.93, 2-way ANOVA). The heart-to-body weight ratios increased significantly in the HLU groups (p<0.0001, 2-way ANOVA) but again there was no interaction with sex (p=0.84, 2-way ANOVA). If similar mechanisms operate in humans, female astronauts may be more likely to develop presyncope after space-flights than male astronauts because their hearts contain a greater relative content of the alpha-Myosin Heavy Chain when they return to Earth.

Ultrasound Tissue Characterization of the Myocardium in Patients After Kawasaki Disease

We sought to determine if changes in myocardial physical properties, detected by ultrasound tissue characterization (UTC), are present in asymptomatic children years after an acute episode of Kawasaki disease (KD) and if such changes are related to coronary artery aneurysms (CAs). Myocardial UTC analysis was performed 4.8 + or - 3.4 years after acute KD in 22 patients, mean age 6.6 + or - 3.4 years, with or without CA, who had a normal ECG and normal left ventricular (LV) systolic and diastolic function by echocardiography. Twenty-two age-matched subjects were studied as controls. Cyclic variation of integrated backscatter (cvIBS) and calibrated integrated backscatter (cIBS) were assessed in 16 LV myocardial segments in each patient and control. We found large differences in the UTC data between patients and controls: cvIBS, 7.8 + or - 0.8 vs 8.9 + or - 0.6 dB; cIBS, 28.6 + or - 3.2 vs 25.2 + or - 1.0 dB (P\10-3 for both). The average values of cIBS and cvIBS did not differ significantly between KD patients with and patients without CA or stenosis. In conclusion, UTC analysis demonstrated significant differences in myocardial tissue properties between KD patients and controls, despite similar measures of LV function, independent of coronary artery abnormalities. UTC analysis might improve risk stratification for KD patients.

Modeling of Viscoelastic Properties of Isolated Myocardial Tissue Samples at Different Levels: Cardiomyocytes and Trabeculae

Viscoelastic properties of myocardium play an important role in a heart function. They determine the extent of filling of the heart, its subsequent stroke volume and contraction velocity. We present here the 3D model consisting of elastic springs and linear damping elements on basis of our earlier model [1] (Fig. 1A). Due to changes of geometry the model manifests nonlinear viscoelastic behavior in response to longitudinal stretch. Depending on set of input parameters, the model allows to describe quantitatively nonlinear viscoelastic behavior of both single cardiomyocytes and multicellular samples like trabeculae (Fig. 1B). Model volume stability is an essential condition for model parameter selection because in vivo a volume of cardiomyocytes is virtually unchanged. It is significant that viscoelastic parameters of structural elements of the model remain constant all over the range of investigated strains.Thus, we can describe main viscoelastic properties of myocardial tissue at different organization levels within the basis of the simple mechanical model.[1] Smoluk, L. et al. 2008. The FASEB J.22:756.9.[2] Granzier, H. and Irving, T. 1995. Biophys. J. 68:1027-1044.[3] Granzier, H. et al. 1996. Biophys. J. 70:430-442.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Vinculin Contributes to the Passive Stiffness of Myocardium

In cardiomyocytes, the costamere links the Z disc to the surrounding extracellular matrix. Proteins at these junctions include integrins, talin, and vinculin (Vin). Vin is also found in the intercalated discs. Cardiac-specific Vin knockout (VinKO) mice have a sudden death phenotype early in life (<12 weeks of age) with a progressive dilated cardiomyopathy leading to 100% mortality by 32 wks. At 7 weeks of age, systolic ventricular function is normal.We hypothesize that deletion of the costameric protein Vin leads to changes in passive stiffness prior to the onset of systolic dysfunction. Vin deletion may disrupt the normal force transmission pathways from ECM to cytoskeleton through the integrin-based costamere or cell-to-cell force transmission along the myocyte axis, which may manifest in altered passive material properties of the myocardium.To test the mechanical properties of myocardial tissue, a system was developed in which murine right ventricular papillary muscles could be passively strained in the axial direction while simultaneously measuring force. Papillary muscles from 7 week old VinKO mice and WT controls were isolated and stretched. Stress-strain analysis was used to measure passive stiffness in the direction of myocardial fibers.Stress-strain curves were significantly different between WT and VinKO papillary muscles (p<0.05). The slope of the VinKO curve was less than in the WT curve, indicating that VinKO muscles are more compliant in the fiber direction. This data suggests that Vin contributes to the passive mechanical properties of the myocardium, and disrupting the mechanical linkage between the cytoskeleton and the cell membrane reduces the overall stiffness of the myocardium.

4D cardiac strain imaging for diagnosis of chronic heart failure

Strain imaging or elastography is a well-known technique for measuring passive and active deformation of biological tissue [1,2]. Cardiac strain imaging has been assessed as a non-invasive technique for mapping the mechanical properties of myocardial tissue and monitoring cardiac diseases, such as fibrosis and infarction [2]. The introduction of real-time 3D ultrasound imaging has boosted research in 3D strain imaging. The complex heart movements and deformations require 3D+t data for accurate assessment of strain in all directions. Sub-optimal temporal resolution of 3D datasets is still a problem. In this study, BiPlane and full 3D volume imaging are used for measuring cardiac strain in 3 orthogonal directions and their application to detect chronic heart failure.