Properties Of Myocardial Tissue Research Articles

Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue

The myocardial tissue lacks significant intrinsic regenerative capability to replace the lost cells. Therefore, the heart is a major target of research within the field of tissue engineering, which aims to replace infarcted myocardium and enhance cardiac function. The primary objective of this work was to develop a biocompatible, degradable and superelastic heart patch from poly(glycerol sebacate) (PGS). PGS was synthesised at 110, 120 and 130 °C by polycondensation of glycerol and sebacic acid with a mole ratio of 1:1. The investigation was focused on the mechanical and biodegrading behaviours of the developed PGS. PGS materials synthesised at 110, 120 and 130 °C have Young's moduli of 0.056, 0.22 and 1.2 MPa, respectively, which satisfy the mechanical requirements on the materials applied for the heart patch and 3D myocardial tissue engineering construction. Degradation assessment in phosphate buffered saline and Knockout™ DMEM culture medium has demonstrated that the PGS has a wide range of degradability, from being degradable in a couple of weeks to being nearly inert. The matching of physical characteristics to those of the heart, the ability to fine tune degradation rates in biologically relevant media and initial data showing biocompatibility indicate that this material has promise for cardiac tissue engineering applications.

Effect of electrode locations and respiration in the characterization of myocardial tissue using a transcatheter impedance method

Our objective is to evaluate whether it is possible to characterize the passive electrical properties of myocardial tissue in contact with the electrocatheters used in arrhythmia diagnosis or radio frequency ablation techniques. To characterize the tissue, we propose the use of electrical impedance spectroscopy to measure the impedance between the catheter tip and an external electrode, assuming a three-electrode method. We constructed a 3D finite-element model of the thorax to estimate the impedance as measured in different situations. We defined an area on the anterior wall of the left ventricle in which we simulated three tissue states: healthy, acute ischaemic and scar. We studied the effect of the following parameters on the measured impedance spectrum: the position of the external electrode, the position and orientation of the catheter tip and the overall effect of the subject's respiration. Results show that the highest frequency phase (around 300 kHz) yields the best differentiation of tissue states and that it is less sensitive to respiration than the impedance magnitude. The phase is also less influenced by the catheter tip position (either touching the wall or floating) and the orientation of the catheter inside the left ventricle. The best position for the external electrode is on the chest; this position is less affected by breathing and is more sensitive to tissue changes. One can still distinguish between tissue states if the external electrode is placed on the back, but the effect of respiration is higher.

Ultrasonic tissue characterization for patients with Chagas' disease

This study was undertaken to test the hypothesis that ultrasonic tissue characterization, as evaluated by intensity and cardiac cyclic variation of integrated backscatter (IBS), could identify early myocardial involvement in Chagas' disease. We evaluated 69 participants, age 15 to 73 years (mean ± SD: 49 ± 12 years), who were divided as following: 19 control subjects; 13 patients with the indeterminate form of Chagas' disease; 7 patients with the digestive form; and 30 patients with the cardiac form. IBS images were obtained in parasternal short-axis (basal, papillary muscle, apical) view and analyzed in 12 left ventricular (LV) segments (anterior, lateral, posterior, and septal). The following IBS variables were evaluated: (1) the corrected coefficient (CC) of IBS, obtained by dividing IBS intensity, in each cardiac segment, by IBS intensity measured in a rubber phantom using the same equipment adjustments at the same depth; and (2) magnitude of cardiac cyclic variation (MCV) of IBS, as measured by the peak-to-peak difference between maximal and minimal values of IBS in cardiac cycle. The CC of IBS was increased ( P < .05) for patients with the cardiac form who had LV segments with normal wall motion as compared with control subjects, in 4 of 12 segments evaluated (basal anterior, midposterior and midseptal, anterior apical), whereas the remaining chagasic groups were comparable with controls subjects. The CC of IBS tended to increase with worsening of LV segmental wall motion. MCV showed a large individual variability and had a large mean value ( P < .05) in just 1 of 12 segments evaluated, when patients with the cardiac form were compared with control subjects. No correlation was observed between the magnitude of LV dysfunction and MCV of IBS. In conclusion: (1) the CC of IBS was able to provide early differentiation of cardiac involvement for patients with Chagas' disease who had LV segments with normal wall motion; (2) increase of CC of IBS with worsening of LV segmental wall motion suggests a relationship between the acoustic properties of myocardial tissue and grading of myocardial fibrosis; (3) MCV was not able to differentiate patients with Chagas' disease from control subjects; and (4) patients with the indeterminate form of Chagas' disease were not differentiated from control subjects by any of the IBS techniques evaluated in this study.

Development of an in vivo method for determining material properties of passive myocardium

Calculation of mechanical stresses and strains in the left ventricular (LV) myocardium by the finite element (FE) method relies on adequate knowledge of the material properties of myocardial tissue. In this paper, we present a model-based estimation procedure to characterize the stress-strain relationship in passive LV myocardium. A 3D FE model of the LV myocardium was used, which included morphological fiber and sheet structure and a nonlinear orthotropic constitutive law with different stiffness in the fiber, sheet, and sheet-normal directions. The estimation method was based on measured wall strains. We analyzed the method's ability to estimate the material parameters by generating a set of synthetic strain data by simulating the LV inflation phase with known material parameters. In this way we were able to verify the correctness of the solution and to analyze the effects of measurement and model error on the solution accuracy and stability. A sensitivity analysis was performed to investigate the observability of the material parameters and to determine which parameters to estimate. The results showed a high degree of coupling between the parameters governing the stiffness in each direction. Thus, only one parameter in each of the three directions was estimated. For the tested magnitudes of added noise and introduced model errors, the resulting estimated stress-strain characteristics in the fiber and sheet directions converged with good accuracy to the known relationship. The sheet-normal stress-strain relationship had a higher degree of uncertainty as more noise was added and model error was introduced.

Development of an in vivo method for determining material properties of passive myocardium

Calculation of mechanical stresses and strains in the left ventricular (LV) myocardium by the finite element (FE) method relies on adequate knowledge of the material properties of myocardial tissue. In this paper, we present a model-based estimation procedure to characterize the stress–strain relationship in passive LV myocardium. A 3D FE model of the LV myocardium was used, which included morphological fiber and sheet structure and a nonlinear orthotropic constitutive law with different stiffness in the fiber, sheet, and sheet-normal directions. The estimation method was based on measured wall strains. We analyzed the method's ability to estimate the material parameters by generating a set of synthetic strain data by simulating the LV inflation phase with known material parameters. In this way we were able to verify the correctness of the solution and to analyze the effects of measurement and model error on the solution accuracy and stability. A sensitivity analysis was performed to investigate the observability of the material parameters and to determine which parameters to estimate. The results showed a high degree of coupling between the parameters governing the stiffness in each direction. Thus, only one parameter in each of the three directions was estimated. For the tested magnitudes of added noise and introduced model errors, the resulting estimated stress–strain characteristics in the fiber and sheet directions converged with good accuracy to the known relationship. The sheet-normal stress–strain relationship had a higher degree of uncertainty as more noise was added and model error was introduced.

Modeling total heart function.

Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.

In vitro engineering of heart muscle: Artificial myocardial tissue

Introduction: Myocardial infarction followed by heart failure represents one of the major causes of morbidity and mortality, particularly in industrialized countries. Engineering and subsequent transplantation of contractile artificial myocardial tissue and, consequently, the replacement of ischemic and infarcted areas of the heart provides a potential therapeutic alternative to whole organ transplantation. Methods: Artificial myocardial tissue samples were engineered by seeding neonatal rat cardiomyocytes with a commercially available 3-dimensional collagen matrix. The cellular engraftment within the artificial myocardial tissues was examined microscopically. Force development was analyzed in spontaneously beating artificial myocardial tissues, after stretching, and after pharmacologic stimulation. Moreover, electrocardiograms were recorded. Results: Artificial myocardial tissues showed continuous, rhythmic, and synchronized contractions for up to 13 weeks. Embedded cardiomyocytes were distributed equally within the 3-dimensional matrix. Application of Ca2+ and epinephrine, as well as electrical stimulation or stretching, resulted in enhanced force development. Electrocardiographic recording was possible on spontaneously beating artificial myocardial tissue samples and revealed physiologic patterns. Conclusions: Using a clinically well-established collagen matrix, contractile myocardial tissue can be engineered in vitro successfully. Mechanical and biologic properties of artificial myocardial tissue resemble native cardiac tissue. Use of artificial myocardial tissues might be a promising approach to reconstitute degenerated or failing cardiac tissue in many disease states and therefore provide a reasonable alternative to whole organ transplantation.J Thorac Cardiovasc Surg 2002;124:63-9

Dielectrical spectroscopy of canine myocardium during acute ischemia and hypoxia at frequency spectrum from 100 kHz to 6 GHz.

We studied dielectrical properties of canine myocardium during acute ischemia and hypoxia using dielectrical spectroscopy method at frequency spectrum from 100 kHz to 6 GHz. This study was conducted on a group of six canines with acute ischemia and seven canines with hypoxia. Hypoxia (10% for 30 min) decreases myocardial resistance (rho), while the dielectrical permittivity (epsilon') of the myocardial tissue remains statistically unchanged. Acute ischemia for 2 hr causes significant frequency-dependent changes in both epsilon' and rho of myocardial tissue. Myocardial resistance increases, while the sign and amplitude of changes in the myocardial epsilon' are frequency and time dependent. These observations open up an opportunity for assessing the properties of myocardial tissue using dielectrical spectroscopy as well as noninvasively with the help of imaging methods based on electrical impedance and microwave tomography.

Studies of prevention, treatment and mechanisms of heart failure in the aging spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) is an animal model of genetic hypertension which develops heart failure with aging, similar to man. The consistent pattern of a long period of stable hypertrophy followed by a transition to failure provides a useful model to study mechanisms of heart failure with aging and test treatments at differing phases of the disease process. The transition from compensated hypertrophy to failure is accompanied by changes in cardiac function which are associated with altered active and passive mechanical properties of myocardial tissue; these events define the physiologic basis for cardiac decompensation. In examining the mechanism for myocardial tissue dysfunction, studies have demonstrated a central role for neurohormonal activation, and specifically the renin-angiotensin-aldosterone system. Pharmacologic attenuation of this system at differing points in the course of the process suggests that prevention but not reversal of myocardial tissue dysfunction is possible. The roles of the extracellular matrix, apoptosis, intracellular calcium, beta-adrenergic stimulation, microtubules, and oxygen supply-demand relationships in ultimately mediating myocardial tissue dysfunction are reviewed. Studies suggest that while considerable progress has been made in understanding and treating the transition to failure, our current state of knowledge is limited in scope and we are not yet able to define specific mechanisms responsible for tissue dysfunction. It will be necessary to integrate information on the roles of newly discovered, and as yet undiscovered, genes and pathways to provide a clearer understanding of maladaptive remodeling seen with heart failure. Understanding the mechanism for tissue dysfunction is likely to result in more effective treatments for the prevention and reversal of heart failure with aging. It is anticipated that the SHR model will assist us in reaching these important goals.

Laser induced fluorescence attenuation spectroscopy: detection of hypoxia.

The development of a new laser-induced fluorescence (LIF) spectroscopy technique for the measurement of the attenuation spectrum of tissue is described. The technique, termed laser-induced fluorescence attenuation spectroscopy (LIFAS), has been applied to study the effects of hypoxia on the in vivo optical properties of renal and myocardial tissue in the 350-600-nm band. Excimer laser (Xe-Cl) is used to excite a small volume of the tissue (rabbit model, N = 20) and induce autofluorescence. The emitted LIF is monitored fiberoptically at two locations that are unevenly displaced about the fluorescing volume. The optical attenuation of the tissue is calculated from the dual LIF measurements by assuming an exponential decay of the fluorescence with distance. The results indicate that hypoxia modulates the attenuation spectrum leading to characteristic changes in its shape. Primarily, the spectral profile becomes more concave between 455 nm and 505 nm and two spectral peaks at about 540 and 580 nm disappear leaving in their place a single peak at about 555 nm. The attenuation spectra of normoxic and hypoxic tissue are used to train partial least squares multivariate model for spectral classification. The model detected acute renal and myocardial hypoxia with an accuracy greater than 90% (range: 90%-96%) and 74% (range: 74%-90%), respectively.

Ventricular fibrillation in the neonate: elusive or illusive?

Ventricular fibrillation (VF) in mature large mammals is usually a terminal event. It constitutes the most common mode of exitus and the main cause of sudden cardiac death in humans. In neonates, VF is of particular interest because it often reverse spontaneously and promptly to potentially become a non-lethal event. Accordingly, the study of VF and spontaneous defibrillation (SDF) in the neonate is key for the understanding of the developmental anatomical and functional characteristics enabling mammalian myocardium to initiate and sustain this lethal arrhythmia. Such characteristics may include age-related changes of myocardial tissue properties, mass and geometry, autonomic cardiac innervation and myocardial perfusion/hydration. In the human neonate, VF/SDF could provide a plausible framework for explaining and directing the search for the elusive evidence underlying the mechanism and age distribution of the sudden infant death syndrome.

Quantitative modeling of the anisotropy of ultrasonic backscatter from canine myocardium

Reports extensions and new results of the First Time Domain Born approximation model used by Mottley and Miller (1982) to describe the anisotropy of ultrasonic backscatter measured in canine myocardium. The interaction of an ultrasonic plane wave impulse with a single cylindrical scatterer using time and frequency domain approaches is reviewed. Myocardial tissue is modeled as a suspension of aligned cylindrically shaped scatterers uniformly distributed in a homogeneous medium. The authors propose extensions to this model to deal with nonideal scatterer orientation, by introducing axial distribution functions and scatterer size distributions based on histology, modeled as a uniform distribution. The backscatter coefficient in the range 2.0-8.0 MHz is calculated. An algorithm to compute the average differential scattering cross section is presented. Ultrasonic elastic properties of myocardial tissue are discussed. Results of the anisotropy of the numerically computed backscatter parameters for model media having nominal mechanical and acoustic properties of canine myocardial tissue are presented and compared to available experimental data along with discussion of possible conclusions. >

Normal ultrasonic myocardial reflectivity in athletes with increased left ventricular mass. A tissue characterization study.

Ultrasonic integrated backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content. The integrated backscatter is also increased in hypertrophic cardiomyopathy, probably because of fiber disarray. The purpose of this study was to investigate myocardial tissue reflectivity in subjects with physiological hypertrophy caused by intense physical training and to assess the relation between the acoustic properties of myocardial tissue and left ventricular wall thickness assessed by conventional two-dimensional echocardiography. Twenty-four young male athletes (14 professional cyclists and 10 weight lifters, all in full agonistic activity) were studied together with 10 normal age-matched controls with sedentary life. By means of a commercially available two-dimensional echocardiograph, standard measurements were obtained according to the recommendations of the American Society of Echocardiography. With a prototype implemented in our Institute, an on-line radiofrequency analysis of ultrasound signals was also performed to obtain quantitative operator-independent measurements of the integrated backscatter of the myocardial walls. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent integrated backscatter (%IB). Compared with control subjects, athletes showed greater thickness values of septum (controls, 9 +/- 1; cyclists, 14 +/- 2; weight lifters, 15 +/- 1 mm, mean +/- SD; p less than 0.01) and posterior wall (9 +/- 1, 12 +/- 2, and 12 +/- 1 mm, respectively; p less than 0.01) but similar values of %IB for both septum (23 +/- 4%, 21 +/- 7%, and 23 +/- 8%, p = NS) and posterior wall (10 +/- 2%, 9 +/- 2%, and 11 +/- 2%, p = NS). In athletes, no correlation was found between septal and posterior wall thickness and the corresponding regional myocardial reflectivity (r = 0.23, p = NS and r = 0.01, p = NS, respectively). Furthermore, we compared the quantitative ultrasonic data between two subsets of 10 athletes and 10 patients with hypertrophic cardiomyopathy and similar degrees of septal thickness (16 +/- 1 versus 17 +/- 1 mm, respectively, p = NS). Septal and posterior wall %IB results were significantly higher in patients with hypertrophic cardiomyopathy (53 +/- 13% and 36 +/- 9%, respectively) than in athletes (21 +/- 7% and 10 +/- 3%, respectively; p less than 0.01 for both). We conclude that 1) endurance athletes show a normal pattern of quantitatively assessed ultrasonic backscatter despite of a marked left ventricular hypertrophy and 2) athletes and patients with hypertrophic cardiomyopathy and similar degrees of myocardial wall thickness can be differentiated on the basis of quantitative analysis of backscattered signal.

Involvement of vitamin D3 with cardiovascular function. III. Effects on physical and morphological properties

We have previously shown that depletion of vitamin D3 in rats results in a large increase in the contractile function of isolated hearts (R. E. Weishaar, J. Clin. Invest. 79: 1706-1712, 1987). To characterize the mechanism responsible for this increase, the effect of vitamin D3 depletion on key physical and morphological properties of cardiac muscle was examined. Depletion of vitamin D3 increased the heart weight/body weight ratio. This increase could neither be blocked by limiting hypocalcemia nor reversed by restoring increasing serum calcium levels. The cardiomegaly observed 9 wk after vitamin D3 depletion was not accompanied by an increase in myocardial water content or leakage of myocardial creatine phosphokinase and was not caused by myocardial cell hypertrophy. Histological examination of ventricular muscle from vitamin D3-deficient rats revealed a significant decrease in myofibrillar area and a significant increase in extracellular space. The increase in extracellular space was accompanied by a significant increase in myocardial collagen. Prevention of hypocalcemia in the vitamin D3-deficient rats did not prevent the increase in myocardial collagen. Such alterations in the physical and morphological properties of myocardial tissue might represent the basis for the change in myocardial contractile function that accompanies lengthy periods of vitamin D3 deficiency.

Quantification of the mechanical properties of noncontracting canine myocardium under simultaneous biaxial loading

Detailed understanding of cardiac mechanics depends upon accurate and complete characterization of the three-dimensional properties of both normal and diseased myocardial tissue. This, however, can only be obtained by performing multiaxial tests on cardiac tissue. In this study we subjected thin sheets of passive canine left ventricular myocardium to various combinations of simultaneous biaxial stretching. During each stretch the ratio of the orthogonal strains was kept constant and the corresponding stresses remained proportional. We fitted the biaxial stress-strain data both with exponential strain-energy functions with quadratic powers of strains as well as with an alternative function with nonintegral powers of strains. We used our recently developed nonparametric method to assess the reliability of the coefficients for each of these functions. The quadratic strain-energy functions resulted in wide intra- and interspecimen variability in the coefficients. Moreover, both their absolute and relative values demonstrated marked load history dependence such that interpretation of the direction of anisotropy was difficult. Fitting the data with the alternative nonintegral strain-energy function seemed to alleviate these problems. This alternative strain-energy function may provide more self-consistent results than the more commonly used quadratic strain-energy functions.

Quantitative Echocardiographic Image Texture: Normal Contraction-Related Variability

Myocardial tissue characterization using ultrasound is a growing area of investigation which attempts to evaluate the structure of the myocardium by analysis of ultrasound signals. Our laboratory has been exploring the use of texture analysis for the determination of myocardial tissue properties from two-dimensional echocardiographic images. In the present study, we tested the hypothesis that echocardiographic image texture varies with cardiac contraction in normal human subjects. In 17 subjects, we obtained long-and short-axis images at end diastole and end systole. Echo image texture was assessed using three classes of quantitative texture measures: run length, gray level difference, and busyness statistics. These statistics measure various attributes of image texture. We found significant contraction-related changes in image texture for the left ventricular posterior wall. This observation is important in that future applications of texture analysis to echocardiographic image data will require that texture be measured at a consistent point in the cardiac cycle. Moreover, it is possible that alteration in the normal variation of texture with cardiac contraction may be a sensitive indicator of abnormal myocardium.

Cardiac wall mechanics and torsion of the canine left ventricle during ejection

Mathematical modeling is a common approach to study the mechanics of the wall of the left ventricle. In designing such a model generally symplifying assumptions are proposed on left ventricular geometry, myocardial tissue properties and stress or strain distribution across the wall. Common assumptions on geometry are a spherical (6, 8), a cylindrical (2) or ellipsoidal (7,10,12) shape of the left ventricle. Generally myocardial tissue is considered to be isotropic despite its obviously anisotropic properties. We developed a cylindrical, thick-walled model (1,2) which differs from other models by considering anisotropy of myocardial tissue and torsion of the left ventricle. Torsion reflects rotation of the apex with respect to the base around the long axis of the left ventricle, and is associated with shear deformation of the outer surface (epicardium) of the left ventricle when using a cylindrical coordinate system.

A study of the rheological properties of myocardial tissue

A study of the rheological properties of myocardial tissue

Evidence for mechanisms of ultrasonic attenuation in tissue derived from measurements on myocardium

Although reports have suggested that protein content, especially collagen content, may be a significant determinant of the acoustic properties of soft tissue, the responsible mechanisms have not been established. Two classes of mechanisms have been considered: (1) structural, conformational, or chemical relaxations of the macromolecular constituents, and (2) processes arising from the inhomogeneous nature of tissue, such as viscous relative motion. As an approach toward identifying the mechanisms, the present investigations address quantitatively the relationship between the ultrasonic attenuation and certain physical properties of myocardial tissue. Myocardial infarction provides a method for investigating the relationship between collagen content and the ultrasonic attenuation, since increased concentration of collagen has been reported in areas of infarct. Collagen concentration was determined quantitatively using an assay for hydroxyproline. Measurements were conducted in vitro on approximately 900 sites from 60 dogs. The dependence of the ultrasonic attenuation on frequency and temperature, as well as on collagen concentration, was investigated to provide evidence of the mechanisms responsible for the attenuation.