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Sample records for cardiac tissue depth

  1. Evaluation of optical imaging and spectroscopy approaches for cardiac tissue depth assessment

    SciTech Connect

    Lin, B; Matthews, D; Chernomordik, V; Gandjbakhche, A; Lane, S; Demos, S G

    2008-02-13

    NIR light scattering from ex vivo porcine cardiac tissue was investigated to understand how imaging or point measurement approaches may assist development of methods for tissue depth assessment. Our results indicate an increase of average image intensity as thickness increases up to approximately 2 mm. In a dual fiber spectroscopy configuration, sensitivity up to approximately 3 mm with an increase to 6 mm when spectral ratio between selected wavelengths was obtained. Preliminary Monte Carlo results provided reasonable fit to the experimental data.

  2. Functional cardiac tissue engineering

    PubMed Central

    Liau, Brian; Zhang, Donghui; Bursac, Nenad

    2013-01-01

    Heart attack remains the leading cause of death in both men and women worldwide. Stem cell-based therapies, including the use of engineered cardiac tissues, have the potential to treat the massive cell loss and pathological remodeling resulting from heart attack. Specifically, embryonic and induced pluripotent stem cells are a promising source for generation of therapeutically relevant numbers of functional cardiomyocytes and engineering of cardiac tissues in vitro. This review will describe methodologies for successful differentiation of pluripotent stem cells towards the cardiovascular cell lineages as they pertain to the field of cardiac tissue engineering. The emphasis will be placed on comparing the functional maturation in engineered cardiac tissues and developing heart and on methods to quantify cardiac electrical and mechanical function at different spatial scales. PMID:22397609

  3. Bioactive scaffolds for engineering vascularized cardiac tissues

    PubMed Central

    Chiu, Loraine; Radisic, Milica; Vunjak-Novakovic, Gordana

    2013-01-01

    Functional vascularization is a key requirement for the development and function of most tissues, and most critically cardiac muscle. Rapid and irreversible loss of cardiomyocytes during cardiac infarction directly results from the lack of blood supply. Contractile cardiac grafts, engineered using cardiovascular cells in conjunction with biomaterial scaffolds, are an actively studied method for cardiac repair. In this article, we focus on biomaterial scaffolds designed to mediate the development and maturation of vascular networks, by immobilized growth factors. The interactive effects of multiple vasculogenic factors are discussed in the context of cardiac tissue engineering. PMID:20857391

  4. Cardiac Conduction through Engineered Tissue

    PubMed Central

    Choi, Yeong-Hoon; Stamm, Christof; Hammer, Peter E.; Kwaku, Kevin F.; Marler, Jennifer J.; Friehs, Ingeborg; Jones, Mara; Rader, Christine M.; Roy, Nathalie; Eddy, Mau-Thek; Triedman, John K.; Walsh, Edward P.; McGowan, Francis X.; del Nido, Pedro J.; Cowan, Douglas B.

    2006-01-01

    In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal’s natural life. Perfusion of hearts with fluorescently labeled lectin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding recipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy. PMID:16816362

  5. Biomimetic materials design for cardiac tissue regeneration.

    PubMed

    Dunn, David A; Hodge, Alexander J; Lipke, Elizabeth A

    2014-01-01

    Cardiovascular disease is the leading cause of death worldwide. In the absence of sufficient numbers of organs for heart transplant, alternate approaches for healing or replacing diseased heart tissue are under investigation. Designing biomimetic materials to support these approaches will be essential to their overall success. Strategies for cardiac tissue engineering include injection of cells, implantation of three-dimensional tissue constructs or patches, injection of acellular materials, and replacement of valves. To replicate physiological function and facilitate engraftment into native tissue, materials used in these approaches should have properties that mimic those of the natural cardiac environment. Multiple aspects of the cardiac microenvironment have been emulated using biomimetic materials including delivery of bioactive factors, presentation of cell-specific adhesion sites, design of surface topography to guide tissue alignment and dictate cell shape, modulation of mechanical stiffness and electrical conductivity, and fabrication of three-dimensional structures to guide tissue formation and function. Biomaterials can be engineered to assist in stem cell expansion and differentiation, to protect cells during injection and facilitate their retention and survival in vivo, and to provide mechanical support and guidance for engineered tissue formation. Numerous studies have investigated the use of biomimetic materials for cardiac regeneration. Biomimetic material design will continue to exploit advances in nanotechnology to better recreate the cellular environment and advance cardiac regeneration. Overall, biomimetic materials are moving the field of cardiac regenerative medicine forward and promise to deliver new therapies in combating heart disease.

  6. Electrical stimulation systems for cardiac tissue engineering

    PubMed Central

    Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

    2009-01-01

    We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures. PMID:19180087

  7. Electrical stimulation systems for cardiac tissue engineering.

    PubMed

    Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

    2009-01-01

    We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures.

  8. Towards Depth-Resolved Optical Imaging of Cardiac Electrical Activity.

    PubMed

    Walton, Richard D; Bernus, Olivier

    2015-01-01

    The spatiotemporal dynamics of arrhythmias are likely to be complex three-dimensional phenomena. Yet, the lack of high-resolution three-dimensional imaging techniques, both in the clinic and the experimental lab, limits our ability to better understand the mechanisms of such arrhythmias. Optical mapping using voltage-sensitive dyes is a widely used tool in experimental electrophysiology. It has been known for decades that even in its most basic application, epi-fluorescence, the optical signal contains information from within a certain intramural volume. Understanding of this fundamental property of optical signals has paved the way towards novel three-dimensional optical imaging techniques. Here, we review our current understanding of the three-dimensional nature of optical signals; how penetration depths of cardiac optical imaging can be improved by using novel imaging modalities and finally, we highlight new techniques inspired from optical tomography and aiming at full depth-resolved optical mapping of cardiac electrical activity. PMID:26238062

  9. Cardiac tissue engineering using perfusion bioreactor systems

    PubMed Central

    Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

    2009-01-01

    This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955

  10. Propagating unstable wavelets in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Boyle, Patrick M.; Madhavan, Adarsh; Reid, Matthew P.; Vigmond, Edward J.

    2012-01-01

    Solitonlike propagating modes have been proposed for excitable tissue, but have never been measured in cardiac tissue. In this study, we simulate an experimental protocol to elicit these propagating unstable wavelets (PUWs) in a detailed three-dimensional ventricular wedge preparation. PUWs appear as fixed-shape wavelets that propagate only in the direction of cardiac fibers, with conduction velocity approximately 40% slower than normal action potential excitation. We investigate their properties, demonstrating that PUWs are not true solitons. The range of stimuli for which PUWs were elicited was very narrow (several orders of magnitude lower than the stimulus strength itself), but increased with reduced sodium conductance and reduced coupling in nonlongitudinal directions. We show that the phenomenon does not depend on the particular membrane representation used or the shape of the stimulating electrode.

  11. Distilling complexity to advance cardiac tissue engineering.

    PubMed

    Ogle, Brenda M; Bursac, Nenad; Domian, Ibrahim; Huang, Ngan F; Menasché, Philippe; Murry, Charles E; Pruitt, Beth; Radisic, Milica; Wu, Joseph C; Wu, Sean M; Zhang, Jianyi; Zimmermann, Wolfram-Hubertus; Vunjak-Novakovic, Gordana

    2016-06-01

    The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of a healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or "big questions" were articulated that, if addressed, could substantially advance the current state of the art in modeling heart disease and realizing heart repair. PMID:27280684

  12. Capillary force lithography for cardiac tissue engineering.

    PubMed

    Macadangdang, Jesse; Lee, Hyun Jung; Carson, Daniel; Jiao, Alex; Fugate, James; Pabon, Lil; Regnier, Michael; Murry, Charles; Kim, Deok-Ho

    2014-06-10

    Cardiovascular disease remains the leading cause of death worldwide(1). Cardiac tissue engineering holds much promise to deliver groundbreaking medical discoveries with the aims of developing functional tissues for cardiac regeneration as well as in vitro screening assays. However, the ability to create high-fidelity models of heart tissue has proven difficult. The heart's extracellular matrix (ECM) is a complex structure consisting of both biochemical and biomechanical signals ranging from the micro- to the nanometer scale(2). Local mechanical loading conditions and cell-ECM interactions have recently been recognized as vital components in cardiac tissue engineering(3-5). A large portion of the cardiac ECM is composed of aligned collagen fibers with nano-scale diameters that significantly influences tissue architecture and electromechanical coupling(2). Unfortunately, few methods have been able to mimic the organization of ECM fibers down to the nanometer scale. Recent advancements in nanofabrication techniques, however, have enabled the design and fabrication of scalable scaffolds that mimic the in vivo structural and substrate stiffness cues of the ECM in the heart(6-9). Here we present the development of two reproducible, cost-effective, and scalable nanopatterning processes for the functional alignment of cardiac cells using the biocompatible polymer poly(lactide-co-glycolide) (PLGA)(8) and a polyurethane (PU) based polymer. These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function(10-14). Using a nanopatterned (NP) silicon master as a template, a polyurethane acrylate (PUA) mold is fabricated. This PUA mold is then used to pattern the PU or PLGA hydrogel via UV-assisted or solvent-mediated capillary force lithography (CFL), respectively(15,16). Briefly, PU or PLGA pre-polymer is drop dispensed onto a glass coverslip

  13. Capillary Force Lithography for Cardiac Tissue Engineering

    PubMed Central

    Macadangdang, Jesse; Lee, Hyun Jung; Carson, Daniel; Jiao, Alex; Fugate, James; Pabon, Lil; Regnier, Michael; Murry, Charles; Kim, Deok-Ho

    2014-01-01

    Cardiovascular disease remains the leading cause of death worldwide1. Cardiac tissue engineering holds much promise to deliver groundbreaking medical discoveries with the aims of developing functional tissues for cardiac regeneration as well as in vitro screening assays. However, the ability to create high-fidelity models of heart tissue has proven difficult. The heart’s extracellular matrix (ECM) is a complex structure consisting of both biochemical and biomechanical signals ranging from the micro- to the nanometer scale2. Local mechanical loading conditions and cell-ECM interactions have recently been recognized as vital components in cardiac tissue engineering3-5. A large portion of the cardiac ECM is composed of aligned collagen fibers with nano-scale diameters that significantly influences tissue architecture and electromechanical coupling2. Unfortunately, few methods have been able to mimic the organization of ECM fibers down to the nanometer scale. Recent advancements in nanofabrication techniques, however, have enabled the design and fabrication of scalable scaffolds that mimic the in vivo structural and substrate stiffness cues of the ECM in the heart6-9. Here we present the development of two reproducible, cost-effective, and scalable nanopatterning processes for the functional alignment of cardiac cells using the biocompatible polymer poly(lactide-co-glycolide) (PLGA)8 and a polyurethane (PU) based polymer. These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function10-14. Using a nanopatterned (NP) silicon master as a template, a polyurethane acrylate (PUA) mold is fabricated. This PUA mold is then used to pattern the PU or PLGA hydrogel via UV-assisted or solvent-mediated capillary force lithography (CFL), respectively15,16. Briefly, PU or PLGA pre-polymer is drop dispensed onto a glass coverslip and the PUA

  14. Optimization of Electrical Stimulation Parameters for Cardiac Tissue Engineering

    PubMed Central

    Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

    2010-01-01

    In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile cardiac tissue constrcuts. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation, to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, and were thus used in tissue engineering studies. Cardiac tissues stimulated at 3V/cm amplitude and 3Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43, and the best developed contractile behavior. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. PMID:21604379

  15. Optimization of electrical stimulation parameters for cardiac tissue engineering.

    PubMed

    Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

    2011-06-01

    In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile engineered cardiac tissues. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, were thus used in tissue engineering studies. Engineered cardiac tissues stimulated at 3 V/cm amplitude and 3 Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43 and the best-developed contractile behaviour. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering.

  16. Distilling complexity to advance cardiac tissue engineering

    PubMed Central

    Ogle, Brenda M.; Bursac, Nenad; Domian, Ibrahim; Huang, Ngan F; Menasché, Philippe; Murry, Charles; Pruitt, Beth; Radisic, Milica; Wu, Joseph C; Wu, Sean M; Zhang, Jianyi; Zimmermann, Wolfram-Hubertus; Vunjak-Novakovic, Gordana

    2016-01-01

    The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or “big questions” were articulated that, if addressed, could substantially advance the current state-of-the-art in modeling heart disease and realizing heart repair. PMID:27280684

  17. Cardiac image modelling: Breadth and depth in heart disease.

    PubMed

    Suinesiaputra, Avan; McCulloch, Andrew D; Nash, Martyn P; Pontre, Beau; Young, Alistair A

    2016-10-01

    With the advent of large-scale imaging studies and big health data, and the corresponding growth in analytics, machine learning and computational image analysis methods, there are now exciting opportunities for deepening our understanding of the mechanisms and characteristics of heart disease. Two emerging fields are computational analysis of cardiac remodelling (shape and motion changes due to disease) and computational analysis of physiology and mechanics to estimate biophysical properties from non-invasive imaging. Many large cohort studies now underway around the world have been specifically designed based on non-invasive imaging technologies in order to gain new information about the development of heart disease from asymptomatic to clinical manifestations. These give an unprecedented breadth to the quantification of population variation and disease development. Also, for the individual patient, it is now possible to determine biophysical properties of myocardial tissue in health and disease by interpreting detailed imaging data using computational modelling. For these population and patient-specific computational modelling methods to develop further, we need open benchmarks for algorithm comparison and validation, open sharing of data and algorithms, and demonstration of clinical efficacy in patient management and care. The combination of population and patient-specific modelling will give new insights into the mechanisms of cardiac disease, in particular the development of heart failure, congenital heart disease, myocardial infarction, contractile dysfunction and diastolic dysfunction.

  18. Spatially Extended Memory Models of Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Fox, Jeffrey; Riccio, Mark; Hua, Fei; Bodenschatz, Eberhard; Gilmour, Robert

    2002-03-01

    Beat-to-beat alternation of cardiac electrical properties (alternans) commonly occurs during rapid periodic pacing. Although alternans is generally associated with a resititution curve with slope >=1, recent studies by Gauthier and co-workers reported the absence of alternans in frog heart tissue with a restitution curve of slope >=1. These experimental findings were understood in terms of a memory model in which the duration D of an action potential depends on the preceding rest interval I as well as a memory variable M that accumulates during D and dissipates during I. We study the spatiotemporal dynamics of a spatially extended 1-d fiber using an ionic model that exhibits memory effects. We find that while a single cell can have a restitution slope >=1 and not show alternans (because of memory), the spatially extended system exhibits alternans. To understand the dynamical mechanism of this behavior, we study a coupled maps memory model both numerically and analytically. These results illustrate that spatial effects and memory effects can play a significant role in determining the dynamics of wave propagation in cardiac tissue.

  19. Antibodies to cardiac conducting tissue and abnormalities of cardiac conduction in rheumatoid arthritis.

    PubMed Central

    Villecco, A S; de Liberali, E; Bianchi, F B; Pisi, E

    1983-01-01

    The prevalence of antibodies to cardiac conducting tissue and cardiac conduction electrocardiographic abnormalities were studied in 60 patients with rheumatoid arthritis (RA). Complete or incomplete right bundle branch block (RBBB) was found in 21 patients (35%). Antibodies to cardiac conducting tissue were found in 16 (76%) of the 21 with RBBB and in eight (21%) of the 39 without RBBB. Cardiac conducting tissue antibodies (CCTA) were found only in one of 42 patients with RBBB unrelated to RA and in two out of 60 normal subjects. This newly documented immunological abnormality is thus correlated with disorder of conducting tissue. PMID:6352096

  20. Depth-resolved fluorescence of human ectocervical tissue

    NASA Astrophysics Data System (ADS)

    Wu, Yicong; Xi, Peng; Cheung, Tak-Hong; Yim, So Fan; Yu, Mei-Yung; Qu, Jianan Y.

    2005-04-01

    The depth-resolved autofluorescence of normal and dysplastic human ectocervical tissue within 120um depth were investigated utilizing a portable confocal fluorescence spectroscopy with the excitations at 355nm and 457nm. From the topmost keratinizing layer of all ectocervical tissue samples, strong keratin fluorescence with the spectral characteristics similar to collagen was observed, which created serious interference in seeking the correlation between tissue fluorescence and tissue pathology. While from the underlying non-keratinizing epithelial layer, the measured NADH fluorescence induced by 355nm excitation and FAD fluorescence induced by 457nm excitation were strongly correlated to the tissue pathology. The ratios between NADH over FAD fluorescence increased statistically in the CIN epithelial relative to the normal and HPV epithelia, which indicated increased metabolic activity in precancerous tissue. This study demonstrates that the depth-resolved fluorescence spectroscopy can reveal fine structural information on epithelial tissue and potentially provide more accurate diagnostic information for determining tissue pathology.

  1. Enabling microscale and nanoscale approaches for bioengineered cardiac tissue.

    PubMed

    Chan, Vincent; Raman, Ritu; Cvetkovic, Caroline; Bashir, Rashid

    2013-03-26

    In this issue of ACS Nano, Shin et al. present their finding that the addition of carbon nanotubes (CNT) in gelatin methacrylate (GelMA) results in improved functionality of bioengineered cardiac tissue. These CNT-GelMA hybrid materials demonstrate cardiac tissue with enhanced electrophysiological performance; improved mechanical integrity; better cell adhesion, viability, uniformity, and organization; increased beating rate and lowered excitation threshold; and protective effects against cardio-inhibitory and cardio-toxic drugs. In this Perspective, we outline recent progress in cardiac tissue engineering and prospects for future development. Bioengineered cardiac tissues can be used to build "heart-on-a-chip" devices for drug safety and efficacy testing, fabricate bioactuators for biointegrated robotics and reverse-engineered life forms, treat abnormal cardiac rhythms, and perhaps one day cure heart disease with tissue and organ transplants.

  2. Biomaterial based cardiac tissue engineering and its applications

    PubMed Central

    Huyer, Locke Davenport; Montgomery, Miles; Zhao, Yimu; Xiao, Yun; Conant, Genevieve; Korolj, Anastasia; Radisic, Milica

    2015-01-01

    Cardiovascular disease is a leading cause of death worldwide, necessitating the development of effective treatment strategies. A myocardial infarction involves the blockage of a coronary artery leading to depletion of nutrient and oxygen supply to cardiomyocytes and massive cell death in a region of the myocardium. Cardiac tissue engineering is the growth of functional cardiac tissue in vitro on biomaterial scaffolds for regenerative medicine application. This strategy relies on the optimization of the complex relationship between cell networks and biomaterial properties. In this review, we discuss important biomaterial properties for cardiac tissue engineering applications, such as elasticity, degradation, and induced host response, and their relationship to engineered cardiac cell environments. With these properties in mind, we also emphasize in vitro use of cardiac tissues for high-throughput drug screening and disease modelling. PMID:25989939

  3. Bioactive polymers for cardiac tissue engineering

    NASA Astrophysics Data System (ADS)

    Wall, Samuel Thomas

    2007-05-01

    Prevalent in the US and worldwide, acute myocardial infarctions (AMI) can cause ischemic injuries to the heart that persist and lead to progressive degradation of the organ. Tissue engineering techniques exploiting biomaterials present a hopeful means of treating these injuries, either by mechanically stabilizing the injured ventricle, or by fostering cell growth to replace myocytes lost to damage. This thesis describes the development and testing of a synthetic extracellular matrix for cardiac tissue engineering applications. The first stage of this process was using an advanced finite element model of an injured ovine left ventricle to evaluate the potential benefits of injecting synthetic materials into the heart. These simulations indicated that addition of small amounts non-contractile material (on the order of 1--5% total wall volume) to infarct border zone regions reduced pathological systolic fiber stress to levels near those found in normal remote regions. Simulations also determined that direct addition to the infarct itself caused increases in ventricle ejection fraction while the underlying performance of the pump, ascertained by the Starling relation, was not improved. From these theoretical results, biomaterials were developed specifically for injection into the injured myocardium, and were characterized and tested for their mechanical properties and ability to sustain the proliferation of a stem cell population suitable for transplantation. Thermoresponsive synthetic copolymer hydrogels consisting of N-isopropylacrylamide and acrylic acid, p(NIPAAm-co-AAc), crosslinked with protease degradable amino acid sequences and modified with integrin binding ligands were synthesized, characterized in vitro, and used for myocardial implantation. These injectable materials could maintain a population of bone marrow derived mesenchymal stem cells in both two dimensional and three dimensional culture, and when tested in vivo in a murine infarct model they

  4. Micromolded Gelatin Hydrogels for Extended Culture of Engineered Cardiac Tissues

    PubMed Central

    McCain, Megan L.; Agarwal, Ashutosh; Nesmith, Haley W.; Nesmith, Alexander P.; Parker, Kevin Kit

    2014-01-01

    Defining the chronic cardiotoxic effects of drugs during preclinical screening is hindered by the relatively short lifetime of functional cardiac tissues in vitro, which are traditionally cultured on synthetic materials that do not recapitulate the cardiac microenvironment. Because collagen is the primary extracellular matrix protein in the heart, we hypothesized that micromolded gelatin hydrogel substrates tuned to mimic the elastic modulus of the heart would extend the lifetime of engineered cardiac tissues by better matching the native chemical and mechanical microenvironment. To measure tissue stress, we used tape casting, micromolding, and laser engraving to fabricate gelatin hydrogel muscular thin film cantilevers. Neonatal rat cardiac myocytes adhered to gelatin hydrogels and formed aligned tissues as defined by the microgrooves. Cardiac tissues could be cultured for over three weeks without declines in contractile stress. Myocytes on gelatin had higher spare respiratory capacity compared to those on fibronectin-coated PDMS, suggesting that improved metabolic function could be contributing to extended culture lifetime. Lastly, human induced pluripotent stem cell-derived cardiac myocytes adhered to micromolded gelatin surfaces and formed aligned tissues that remained functional for four weeks, highlighting their potential for human-relevant chronic studies. PMID:24731714

  5. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

    PubMed

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

    Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

  6. Real time assessment of RF cardiac tissue ablation with optical spectroscopy

    SciTech Connect

    Demos, S G; Sharareh, S

    2008-03-20

    An optical spectroscopy approach is demonstrated allowing for critical parameters during RF ablation of cardiac tissue to be evaluated in real time. The method is based on incorporating in a typical ablation catheter transmitting and receiving fibers that terminate at the tip of the catheter. By analyzing the spectral characteristics of the NIR diffusely reflected light, information is obtained on such parameters as, catheter-tissue proximity, lesion formation, depth of penetration of the lesion, formation of char during the ablation, formation of coagulum around the ablation site, differentiation of ablated from healthy tissue, and recognition of micro-bubble formation in the tissue.

  7. Living cardiac tissue slices: an organotypic pseudo two-dimensional model for cardiac biophysics research.

    PubMed

    Wang, Ken; Terrar, Derek; Gavaghan, David J; Mu-U-Min, Razik; Kohl, Peter; Bollensdorff, Christian

    2014-08-01

    Living cardiac tissue slices, a pseudo two-dimensional (2D) preparation, have received less attention than isolated single cells, cell cultures, or Langendorff-perfused hearts in cardiac biophysics research. This is, in part, due to difficulties associated with sectioning cardiac tissue to obtain live slices. With moderate complexity, native cell-types, and well-preserved cell-cell electrical and mechanical interconnections, cardiac tissue slices have several advantages for studying cardiac electrophysiology. The trans-membrane potential (Vm) has, thus far, mainly been explored using multi-electrode arrays. Here, we combine tissue slices with optical mapping to monitor Vm and intracellular Ca(2+) concentration ([Ca(2+)]i). This combination opens up the possibility of studying the effects of experimental interventions upon action potential (AP) and calcium transient (CaT) dynamics in 2D, and with relatively high spatio-temporal resolution. As an intervention, we conducted proof-of-principle application of stretch. Mechanical stimulation of cardiac preparations is well-established for membrane patches, single cells and whole heart preparations. For cardiac tissue slices, it is possible to apply stretch perpendicular or parallel to the dominant orientation of cells, while keeping the preparation in a constant focal plane for fluorescent imaging of in-slice functional dynamics. Slice-to-slice comparison furthermore allows one to assess transmural differences in ventricular tissue responses to mechanical challenges. We developed and tested application of axial stretch to cardiac tissue slices, using a manually-controlled stretching device, and recorded Vm and [Ca(2+)]i by optical mapping before, during, and after application of stretch. Living cardiac tissue slices, exposed to axial stretch, show an initial shortening in both AP and CaT duration upon stretch application, followed in most cases by a gradual prolongation of AP and CaT duration during stretch maintained

  8. Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions.

    PubMed

    Seidel, Thomas; Edelmann, J-C; Sachse, Frank B

    2016-05-01

    Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 µm. This allowed extensive analyzes revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control vs. infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale. PMID:26399990

  9. Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions.

    PubMed

    Seidel, Thomas; Edelmann, J-C; Sachse, Frank B

    2016-05-01

    Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 µm. This allowed extensive analyzes revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control vs. infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale.

  10. Multiple spiral patterns in a cardiac tissue

    NASA Astrophysics Data System (ADS)

    Bai, Zhanguo; Li, Xia

    2009-11-01

    Ventricular fibrillation (VF) is the major cause of sudden cardiac death, the leading cause of death in the industrialized world. However, the mechanisms for its onset are still not well understood. Recent experiments indicate that VF is induced by transitions of cardiac electric propagationg waves from a single spiral wave to multiple waves. To further understand the underlying mechanism of VF, we investigated the interaction between two waves in a two-dimensional excitable media. Three types of multiple spirals including multi-arm spirals have been found depending on the rotation direction and the distance among spiral waves.

  11. Depth sensitive oblique polarized reflectance spectroscopy of oral epithelial tissue

    NASA Astrophysics Data System (ADS)

    Jimenez, Maria K.; Lam, Sylvia; Poh, Catherine; Sokolov, Konstantin

    2014-05-01

    Identifying depth-dependent alterations associated with epithelial cancerous lesions can be challenging in the oral cavity where variable epithelial thicknesses and troublesome keratin growths are prominent. Spectroscopic methods with enhanced depth resolution would immensely aid in isolating optical properties associated with malignant transformation. Combining multiple beveled fibers, oblique collection geometry, and polarization gating, oblique polarized reflectance spectroscopy (OPRS) achieves depth sensitive detection. We report promising results from a clinical trial of patients with oral lesions suspected of dysplasia or carcinoma demonstrating the potential of OPRS for the analysis of morphological and architectural changes in the context of multilayer, epithelial oral tissue.

  12. Albumin fiber scaffolds for engineering functional cardiac tissues.

    PubMed

    Fleischer, Sharon; Shapira, Assaf; Regev, Omri; Nseir, Nora; Zussman, Eyal; Dvir, Tal

    2014-06-01

    In recent years attempts to engineer contracting cardiac patches were focused on recapitulation of the myocardium extracellular microenvironment. We report here on our work, where for the first time, a three-dimensional cardiac patch was fabricated from albumin fibers. We hypothesized that since albumin fibers' mechanical properties resemble those of cardiac tissue extracellular matrix (ECM) and their biochemical character enables their use as protein carriers, they can support the assembly of cardiac tissues capable of generating strong contraction forces. Here, we have fabricated aligned and randomly oriented electrospun albumin fibers and investigated their structure, mechanical properties, and chemical nature. Our measurements showed that the scaffolds have improved elasticity as compared to synthetic electrospun PCL fibers, and that they are capable of adsorbing serum proteins, such as laminin leading to strong cell-matrix interactions. Moreover, due to the functional groups on their backbone, the fibers can be chemically modified with essential biomolecules. When seeded with rat neonatal cardiac cells the engineered scaffolds induced the assembly of aligned cardiac tissues with high aspect ratio cardiomyocytes and massive actinin striation. Compared to synthetic fibrous scaffolds, cardiac cells cultured within aligned or randomly oriented scaffolds formed functional tissues, exhibiting significantly improved function already on Day 3, including higher beating rate (P = 0.0002 and P < 0.0001, respectively), and higher contraction amplitude (P = 0.009 and P = 0.003, respectively). Collectively, our results suggest that albumin electrospun scaffolds can play a key role in contributing to the ex vivo formation of a contracting cardiac muscle tissue.

  13. Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction

    PubMed Central

    Khattab, Ahmad; Islam, Mohammad Ariful; Hweij, Khaled Abou; Zeitouny, Joya; Waters, Renae; Sayegh, Malek; Hossain, Md Monowar; Paul, Arghya

    2016-01-01

    Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI. PMID:27668147

  14. Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction

    PubMed Central

    Khattab, Ahmad; Islam, Mohammad Ariful; Hweij, Khaled Abou; Zeitouny, Joya; Waters, Renae; Sayegh, Malek; Hossain, Md Monowar; Paul, Arghya

    2015-01-01

    Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI. PMID:27668147

  15. Role of adipose tissue in the pathogenesis of cardiac arrhythmias.

    PubMed

    Samanta, Rahul; Pouliopoulos, Jim; Thiagalingam, Aravinda; Kovoor, Pramesh

    2016-01-01

    Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms.

  16. Characterization of electrical stimulation electrodes for cardiac tissue engineering.

    PubMed

    Tandon, Nina; Cannizzaro, Chris; Figallo, Elisa; Voldman, Joel; Vunjak-Novakovic, Gordana

    2006-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. The goal of this study was to assess the conditions of electrical stimulation with respect to the electrode geometry, material properties and charge-transfer characteristics at the electrode-electrolyte interface. We compared various biocompatible materials, including nanoporous carbon, stainless steel, titanium and titanium nitride, for use in cardiac tissue engineering bioreactors. The faradaic and non-faradaic charge transfer mechanisms were assessed by electrochemical impedance spectroscopy (EIS), studying current injection characteristics, and examining surface properties of electrodes with scanning electron microscopy. Carbon electrodes were found to have the best current injection characteristics. However, these electrodes require careful handling because of their limited mechanical strength. The efficacy of various electrodes for use in 2-D and 3-D cardiac tissue engineering systems with neonatal rat cardiomyocytes is being determined by assessing cell viability, amplitude of contractions, excitation thresholds, maximum capture rate, and tissue morphology.

  17. Novel anisotropic engineered cardiac tissues: studies of electrical propagation

    PubMed Central

    Bursac, Nenad; Loo, Yihua; Leong, Kam; Tung, Leslie

    2007-01-01

    The goal of this study was to engineer cardiac tissue constructs with uniformly anisotropic architecture, and to evaluate their electrical function using multi-site optical mapping of cell membrane potentials. Anisotropic polymer scaffolds made by leaching of aligned sucrose templates were seeded with neonatal rat cardiac cells and cultured in rotating bioreactors for 6-14 days. Cells aligned and interconnected inside the scaffolds and when stimulated by a point electrode, supported macroscopically continuous, anisotropic impulse propagation. By culture day 14, the ratio of conduction velocities along vs. across cardiac fibers reached a value of 2, similar to that in native neonatal ventricles, while action potential duration and maximum capture rate respectively decreased to 120 ms and increased to ~5 Hz. The shorter culture time and larger scaffold thickness were associated with increased incidence of sustained reentrant arrhythmias. In summary, this study is the first successful attempt to engineer a cm2-size, functional anisotropic cardiac tissue patch. PMID:17689494

  18. Electrical and mechanical stimulation of cardiac cells and tissue constructs.

    PubMed

    Stoppel, Whitney L; Kaplan, David L; Black, Lauren D

    2016-01-15

    The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro.

  19. The affect of tissue depth variation on craniofacial reconstructions.

    PubMed

    Starbuck, John M; Ward, Richard E

    2007-10-25

    We examined the affect of tissue depth variation on the reconstruction of facial form, through the application of the American method, utilizing published tissue depth measurements for emaciated, normal, and obese faces. In this preliminary study, three reconstructions were created on reproductions of the same skull for each set of tissue depth measurements. The resulting morphological variation was measured quantitatively using the anthropometric craniofacial variability index (CVI). This method employs 16 standard craniofacial anthropometric measurements and the results reflect "pattern variation" or facial harmony. We report no appreciable variation in the quantitative measure of the pattern facial form obtained from the three different sets of tissue depths. Facial similarity was assessed qualitatively utilizing surveys of photographs of the three reconstructions. Surveys indicated that subjects frequently perceived the reconstructions as representing different individuals. This disagreement indicates that size of the face may blind observers to similarities in facial form. This research is significant because it illustrates the confounding effect that normal human variation contributes in the successful recognition of individuals from a representational three-dimensional facial reconstruction. Research results suggest that successful identification could be increased if multiple reconstructions were created which reflect a wide range of possible outcomes for facial form. The creation of multiple facial images, from a single skull, will be facilitated as computerized versions of facial reconstruction are further developed and refined. PMID:17353107

  20. Anisotropic Silk Biomaterials Containing Cardiac Extracellular Matrix for Cardiac Tissue Engineering

    PubMed Central

    Stoppel, Whitney L.; Hu, Dongjian; Domian, Ibrahim J.; Kaplan, David L.; Black, Lauren D.

    2015-01-01

    Cardiac malformations and disease are the leading causes of death in the United States in live-born infants and adults, respectively. In both of these cases, a decrease in the number of functional cardiomyocytes often results in improper growth of heart tissue, wound healing complications, and poor tissue repair. The field of cardiac tissue engineering seeks to address these concerns by developing cardiac patches created from a variety of biomaterial scaffolds to be used in surgical repair of the heart. These scaffolds should be fully degradable biomaterial systems with tunable properties such that the materials can be altered to meet the needs of both in vitro culture (e.g., disease modeling) and in vivo application (e.g., cardiac patch). Current platforms do not utilize both structural anisotropy and proper cell-matrix contacts to promote functional cardiac phenotypes and thus there is still a need for critically sized scaffolds that mimic both the structural and adhesive properties of native tissue. To address this need, we have developed a silk-based scaffold platform containing cardiac tissue-derived extracellular matrix (cECM). These silk-cECM composite scaffolds have tunable architectures, degradation rates, and mechanical properties. Subcutaneous implantation in rats demonstrated that addition of the cECM to aligned silk scaffold led to 99% endogenous cell infiltration and promoted vascularization of a critically sized scaffold (10 mm × 5 mm × 2.5 mm) after 4 weeks in vivo. In vitro, silk-cECM scaffolds maintained the HL-1 atrial cardiomyocytes and human embryonic stem cell-derived cardiomyocytes and promoted a more functional phenotype in both cell types. This class of hybrid silk-cECM anisotropic scaffolds offers new opportunities for developing more physiologically relevant tissues for cardiac repair and disease modeling. PMID:25826196

  1. Anisotropic silk biomaterials containing cardiac extracellular matrix for cardiac tissue engineering.

    PubMed

    Stoppel, Whitney L; Hu, Dongjian; Domian, Ibrahim J; Kaplan, David L; Black, Lauren D

    2015-06-01

    Cardiac malformations and disease are the leading causes of death in the United States in live-born infants and adults, respectively. In both of these cases, a decrease in the number of functional cardiomyocytes often results in improper growth of heart tissue, wound healing complications, and poor tissue repair. The field of cardiac tissue engineering seeks to address these concerns by developing cardiac patches created from a variety of biomaterial scaffolds to be used in surgical repair of the heart. These scaffolds should be fully degradable biomaterial systems with tunable properties such that the materials can be altered to meet the needs of both in vitro culture (e.g. disease modeling) and in vivo application (e.g. cardiac patch). Current platforms do not utilize both structural anisotropy and proper cell-matrix contacts to promote functional cardiac phenotypes and thus there is still a need for critically sized scaffolds that mimic both the structural and adhesive properties of native tissue. To address this need, we have developed a silk-based scaffold platform containing cardiac tissue-derived extracellular matrix (cECM). These silk-cECM composite scaffolds have tunable architectures, degradation rates, and mechanical properties. Subcutaneous implantation in rats demonstrated that addition of the cECM to aligned silk scaffold led to 99% endogenous cell infiltration and promoted vascularization of a critically sized scaffold (10 × 5 × 2.5 mm) after 4 weeks in vivo. In vitro, silk-cECM scaffolds maintained the HL-1 atrial cardiomyocytes and human embryonic stem cell-derived cardiomyocytes and promoted a more functional phenotype in both cell types. This class of hybrid silk-cECM anisotropic scaffolds offers new opportunities for developing more physiologically relevant tissues for cardiac repair and disease modeling. PMID:25826196

  2. Design of electrical stimulation bioreactors for cardiac tissue engineering.

    PubMed

    Tandon, N; Marsano, A; Cannizzaro, C; Voldman, J; Vunjak-Novakovic, G

    2008-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.

  3. Design of Electrical Stimulation Bioreactors for Cardiac Tissue Engineering

    PubMed Central

    Tandon, N.; Marsano, A.; Cannizzaro, C.; Voldman, J.; Vunjak-Novakovic, G.

    2009-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering. PMID:19163486

  4. Depth-resolved monitoring of analytes diffusion in ocular tissues

    NASA Astrophysics Data System (ADS)

    Larin, Kirill V.; Ghosn, Mohamad G.; Tuchin, Valery V.

    2007-02-01

    Optical coherence tomography (OCT) is a noninvasive imaging technique with high in-depth resolution. We employed OCT technique for monitoring and quantification of analyte and drug diffusion in cornea and sclera of rabbit eyes in vitro. Different analytes and drugs such as metronidazole, dexamethasone, ciprofloxacin, mannitol, and glucose solution were studied and whose permeability coefficients were calculated. Drug diffusion monitoring was performed as a function of time and as a function of depth. Obtained results suggest that OCT technique might be used for analyte diffusion studies in connective and epithelial tissues.

  5. Controlling the Structural and Functional Anisotropy of Engineered Cardiac Tissues

    PubMed Central

    Bursac, N

    2014-01-01

    The ability to control the degree of structural and functional anisotropy in 3D engineered cardiac tissues would have high utility for both in vitro studies of cardiac muscle physiology and pathology as well as potential tissue engineering therapies for myocardial infarction. Here, we applied a high aspect ratio soft lithography technique to generate network-like tissue patches seeded with neonatal rat cardiomyocytes. Fabricating longer elliptical pores within the patch networks increased the overall cardiomyocyte and extracellular matrix (ECM) alignment within the patch. Improved uniformity of cell and matrix alignment yielded an increase in anisotropy of action potential propagation and faster longitudinal conduction velocity (LCV). Cardiac tissue patches with a higher degree of cardiomyocyte alignment and electrical anisotropy also demonstrated greater isometric twitch forces. After two weeks of culture, specific measures of electrical and contractile function (LCV = 26.8 ± 0.8 cm/s, specific twitch force = 8.9 ± 1.1 mN/mm2 for the longest pores studied) were comparable to those of neonatal rat myocardium. We have thus described methodology for engineering of highly functional 3D engineered cardiac tissues with controllable degree of anisotropy. PMID:24717534

  6. Spring-like fibers for cardiac tissue engineering.

    PubMed

    Fleischer, Sharon; Feiner, Ron; Shapira, Assaf; Ji, Jing; Sui, Xiaomeng; Daniel Wagner, H; Dvir, Tal

    2013-11-01

    Recapitulation of the cellular microenvironment of the heart, which promotes cell contraction, remains a key challenge in cardiac tissue engineering. We report here on our work, where for the first time, a 3-dimensional (3D) spring-like fiber scaffold was fabricated, successfully mimicking the coiled perimysial fibers of the heart. We hypothesized that since in vivo straightening and re-coiling of these fibers allow stretching and contraction of the myocardium in the direction of the cardiomyocytes, such a scaffold can support the assembly of a functional cardiac tissue capable of generating a strong contraction force. In this study, the mechanical properties of both spring-like single fibers and 3D scaffolds composed of them were investigated. The measurements showed that they have increased elasticity and extensibility compared to corresponding straight fibers and straight fiber scaffolds. We have also shown that cardiac cells cultivated on single spring-like fibers formed cell-fiber interactions that induced fiber stretching in the direction of contraction. Moreover, cardiac cells engineered within 3D thick spring-like fiber scaffolds formed a functional tissue exhibiting significantly improved function, including stronger contraction force (p = 0.002), higher beating rate (p < 0.0001) and lower excitation threshold (p = 0.02), compared to straight fiber scaffolds. Collectively, our results suggest that spring-like fibers can play a key role in contributing to the ex vivo formation of a contracting cardiac muscle tissue. We envision that cardiac tissues engineered within these spring-like fiber scaffolds can be used to improve heart function after infarction.

  7. Polycaprolactone/oligomer compound scaffolds for cardiac tissue engineering.

    PubMed

    Reddy, Chaganti Srinivasa; Venugopal, Jayarama Reddy; Ramakrishna, Seeram; Zussman, Eyal

    2014-10-01

    Polycaprolactone (PCL), a synthetic biocompatible and biodegradable polymer generally used as a scaffold material for tissue engineering applications. The high stiffness and hydrophobicity of the PCL fiber mesh does not provide significant cell attachment and proliferation in cardiac tissue engineering. Towards this goal, the study focused on a compound of PCL and oligomer hydrogel [Bisphenol A ethoxylated dimethacrylate (BPAEDMA)] processed into electrospun nanofibrous scaffolds. The composition, morphology and mechanical properties of the compound scaffolds, composed of varying ratios of PCL and hydrogel were characterized by scanning electron microscopy, infrared spectroscopy and dynamic mechanical analyzer. The elastic modulus of PCL/BPAEDMA nanofibrous scaffolds was shown to be varying the BPAEDMA weight fraction and was decreased by increasing the BPAEDMA weight fraction. Compound fiber meshes containing 75 wt % BPAEDMA oligomer hydrogel exhibited lower modulus (3.55 MPa) and contact angle of 25(o) . Rabbit cardiac cells cultured for 10 days on these PCL/BPAEDMA compound nanofibrous scaffolds remained viable and expressed cardiac troponin and alpha-actinin proteins for the normal functioning of myocardium. Cell adhesion and proliferations were significantly increased on compound fiber meshes containing 75 wt % BPAEDMA, when compared with other nanofibrous scaffolds. The results observed that the produced PCL/BPAEDMA compound nanofibrous scaffolds promote cell adhesion, proliferation and normal functioning of cardiac cells to clinically beneficial levels, relevant for cardiac tissue engineering. PMID:24288184

  8. Facial tissue depths in children with cleft lip and palate.

    PubMed

    Starbuck, John M; Ghoneima, Ahmed; Kula, Katherine

    2015-03-01

    Cleft lip and palate (CLP) is a craniofacial malformation affecting more than seven million people worldwide that results in defects of the hard palate, teeth, maxilla, nasal spine and floor, and maxillodental asymmetry. CLP facial soft-tissue depth (FSTD) values have never been published. The purpose of this research is to report CLP FSTD values and compare them to previously published FSTD values for normal children. Thirty-eight FSTDs were measured on cone beam computed tomography images of CLP children (n = 86; 7-17 years). MANOVA and ANOVA tests determined whether cleft type, age, sex, and bone graft surgical status affect tissue depths. Both cleft type (unilateral/bilateral) and age influence FSTDs. CLP FSTDs exhibit patterns of variation that differ from normal children, particularly around the oronasal regions of the face. These differences should be taken into account when facial reconstructions of children with CLP are created. PMID:25442980

  9. Depth-encoded synthetic aperture optical coherence tomography of biological tissues with extended focal depth.

    PubMed

    Mo, Jianhua; de Groot, Mattijs; de Boer, Johannes F

    2015-02-23

    Optical coherence tomography (OCT) has proven to be able to provide three-dimensional (3D) volumetric images of scattering biological tissues for in vivo medical diagnostics. Unlike conventional optical microscopy, its depth-resolving ability (axial resolution) is exclusively determined by the laser source and therefore invariant over the full imaging depth. In contrast, its transverse resolution is determined by the objective's numerical aperture and the wavelength which is only approximately maintained over twice the Rayleigh range. However, the prevailing laser sources for OCT allow image depths of more than 5 mm which is considerably longer than the Rayleigh range. This limits high transverse resolution imaging with OCT. Previously, we reported a novel method to extend the depth-of-focus (DOF) of OCT imaging in Mo et al.Opt. Express 21, 10048 (2013)]. The approach is to create three different optical apertures via pupil segmentation with an annular phase plate. These three optical apertures produce three OCT images from the same sample, which are encoded to different depth positions in a single OCT B-scan. This allows for correcting the defocus-induced curvature of wave front in the pupil so as to improve the focus. As a consequence, the three images originating from those three optical apertures can be used to reconstruct a new image with an extended DOF. In this study, we successfully applied this method for the first time to both an artificial phantom and biological tissues over a four times larger depth range. The results demonstrate a significant DOF improvement, paving the way for 3D high resolution OCT imaging beyond the conventional Rayleigh range. PMID:25836528

  10. Cardiac tissue characterization using near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Singh Moon, Rajinder; Hendon, Christine P.

    2014-03-01

    Cardiac tissue from swine and canine hearts were assessed using diffuse reflectance near-infrared spectroscopy (NIRS) ex vivo. Slope measured between 800-880 nm reflectance was found to reveal differences between epicardial fat and normal myocardium tissue. This parameter was observed to increase monotonically from measurements obtained from the onset of radiofrequency ablation (RFA). A sheathe-style fiber optic catheter was then developed to allow real-time sampling of the zone of resistive heating during RFA treatment. A model was developed and used to extract changes in tissue absorption and reduced scattering based on the steady-state diffusion approximation. It was found that key changes in tissue optical properties occur during application of RF energy and can be monitored using NIRS. These results encourage the development of NIRS integrated catheters for real-time guidance of the cardiac ablation treatment.

  11. Mechanical bidomain model of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Puwal, Steffan; Roth, Bradley J.

    2010-10-01

    Intracellular and extracellular spaces are separately considered in an electrical bidomain model of tissue. We propose a mechanical bidomain model separately considering the intracellular and extracellular spaces, coupled through a linear restoring force proportional to the displacement difference of the two spaces. We consider a mechanically passive model of heart fibers (no tension) with an action potential, and an electrically passive model (no action potential) in tissue with an ischemic boundary. We find the pressure and displacement fields arising from our consideration of a bidomain instead of a monodomain and note interesting characteristics evident only with a bidomain approach.

  12. Connective tissue growth factor induces cardiac hypertrophy through Akt signaling

    SciTech Connect

    Hayata, Nozomi; Fujio, Yasushi; Yamamoto, Yasuhiro; Iwakura, Tomohiko; Obana, Masanori; Takai, Mika; Mohri, Tomomi; Nonen, Shinpei; Maeda, Makiko; Azuma, Junichi

    2008-05-30

    In the process of cardiac remodeling, connective tissue growth factor (CTGF/CCN2) is secreted from cardiac myocytes. Though CTGF is well known to promote fibroblast proliferation, its pathophysiological effects in cardiac myocytes remain to be elucidated. In this study, we examined the biological effects of CTGF in rat neonatal cardiomyocytes. Cardiac myocytes stimulated with full length CTGF and its C-terminal region peptide showed the increase in cell surface area. Similar to hypertrophic ligands for G-protein coupled receptors, such as endothelin-1, CTGF activated amino acid uptake; however, CTGF-induced hypertrophy is not associated with the increased expression of skeletal actin or BNP, analyzed by Northern-blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy. These findings indicate that CTGF is a novel hypertrophic factor in cardiac myocytes.

  13. Biomimetic Polymers for Cardiac Tissue Engineering

    PubMed Central

    2016-01-01

    Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform. PMID:27073119

  14. Electroactive 3D materials for cardiac tissue engineering

    NASA Astrophysics Data System (ADS)

    Gelmi, Amy; Zhang, Jiabin; Cieslar-Pobuda, Artur; Ljunngren, Monika K.; Los, Marek Jan; Rafat, Mehrdad; Jager, Edwin W. H.

    2015-04-01

    By-pass surgery and heart transplantation are traditionally used to restore the heart's functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

  15. Cardiac tissue engineering and regeneration using cell-based therapy

    PubMed Central

    Alrefai, Mohammad T; Murali, Divya; Paul, Arghya; Ridwan, Khalid M; Connell, John M; Shum-Tim, Dominique

    2015-01-01

    Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. PMID:25999743

  16. Histology validation of mapping depth-resolved cardiac fiber orientation in fresh mouse heart using optical polarization tractography

    PubMed Central

    Wang, Y.; Zhang, K.; Wasala, N. B.; Yao, X.; Duan, D.; Yao, G.

    2014-01-01

    Myofiber organization in cardiac muscle plays an important role in achieving normal mechanical and electrical heart functions. An imaging tool that can reveal microstructural details of myofiber organization is valuable for both basic research and clinical applications. A high-resolution optical polarization tractography (OPT) was recently developed based on Jones matrix optical coherence tomography (JMOCT). In this study, we validated the accuracy of using OPT for measuring depth-resolved fiber orientation in fresh heart samples by comparing directly with histology images. Systematic image processing algorithms were developed to register OPT with histology images. The pixel-wise differences between the two tractographic results were analyzed in details. The results indicate that OPT can accurately image depth-resolved fiber orientation in fresh heart tissues and reveal microstructural details at the histological level. PMID:25136507

  17. Electrospun biocomposite nanofibrous patch for cardiac tissue engineering.

    PubMed

    Prabhakaran, Molamma P; Kai, Dan; Ghasemi-Mobarakeh, Laleh; Ramakrishna, Seeram

    2011-10-01

    A bioengineered construct that matches the chemical, mechanical, biological properties and extracellular matrix morphology of native tissue could be suitable as a cardiac patch for supporting the heart after myocardial infarction. The potential of utilizing a composite nanofibrous scaffold of poly(dl-lactide-co-glycolide)/gelatin (PLGA/Gel) as a biomimetic cardiac patch is studied by culturing a population of cardiomyocyte containing cells on the electrospun scaffolds. The chemical characterization and mechanical properties of the electrospun PLGA and PLGA/Gel nanofibers were studied by Fourier transform infrared spectroscopy, scanning electron microscopy and tensile measurements. The biocompatibility of the scaffolds was also studied and the cardiomyocytes seeded on PLGA/Gel nanofibers were found to express the typical functional cardiac proteins such as alpha-actinin and troponin I, showing the easy integration of cardiomyocytes on PLGA/Gel scaffolds. Our studies strengthen the application of electrospun PLGA/Gel nanofibers as a bio-mechanical support for injured myocardium and as a potential substrate for induction of endogenous cardiomyocyte proliferation, ultimately reducing the cardiac dysfunction and improving cardiac remodeling. PMID:21813957

  18. Nuclear Morphology and Deformation in Engineered Cardiac Myocytes and Tissues

    PubMed Central

    Bray, Mark-Anthony; Adams, William J.; Geisse, Nicholas A.; Feinberg, Adam W.; Sheehy, Sean P.; Parker, Kevin Kit

    2010-01-01

    Cardiac tissue engineering requires finely-tuned manipulation of the extracellular matrix (ECM) microenvironment to optimize internal myocardial organization. The myocyte nucleus is mechanically connected to the cell membrane via cytoskeletal elements, making it a target for the cellular response to perturbation of the ECM. However, the role of ECM spatial configuration and myocyte shape on nuclear location and morphology is unknown. In this study, printed ECM proteins were used to configure the geometry of cultured neonatal rat ventricular myocytes. Engineered one- and two-dimensional tissue constructs and single-myocyte islands were assayed using live fluorescence imaging to examine nuclear position, morphology and motion as a function of the imposed ECM geometry during diastolic relaxation and systolic contraction. Image analysis showed that anisotropic tissue constructs cultured on microfabricated ECM lines possessed a high degree of nuclear alignment similar to that found in vivo; nuclei in isotropic tissues were polymorphic in shape with an apparently random orientation. Nuclear eccentricity was also increased for the anisotropic tissues, suggesting that intracellular forces deform the nucleus as the cell is spatially confined. During systole, nuclei experienced increasing spatial confinement in magnitude and direction of displacement as tissue anisotropy increased, yielding anisotropic deformation. Thus, the nature of nuclear displacement and deformation during systole appears to rely on a combination of the passive myofibril spatial organization and the active stress fields induced by contraction. Such findings have implications in understanding the genomic consequences and functional response of cardiac myocytes to their ECM surroundings under conditions of disease. PMID:20382423

  19. Optical control of excitation waves in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Burton, Rebecca A. B.; Klimas, Aleksandra; Ambrosi, Christina M.; Tomek, Jakub; Corbett, Alex; Entcheva, Emilia; Bub, Gil

    2015-12-01

    In nature, macroscopic excitation waves are found in a diverse range of settings including chemical reactions, metal rust, yeast, amoeba and the heart and brain. In the case of living biological tissue, the spatiotemporal patterns formed by these excitation waves are different in healthy and diseased states. Current electrical and pharmacological methods for wave modulation lack the spatiotemporal precision needed to control these patterns. Optical methods have the potential to overcome these limitations, but to date have only been demonstrated in simple systems, such as the Belousov-Zhabotinsky chemical reaction. Here, we combine dye-free optical imaging with optogenetic actuation to achieve dynamic control of cardiac excitation waves. Illumination with patterned light is demonstrated to optically control the direction, speed and spiral chirality of such waves in cardiac tissue. This all-optical approach offers a new experimental platform for the study and control of pattern formation in complex biological excitable systems.

  20. Wave emission on interacting heterogeneities in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Hörning, Marcel; Takagi, Seiji; Yoshikawa, Kenichi

    2010-08-01

    Cardiac arrhythmias, a precursor of fibrillationlike states in the beating heart, are associated with spiral waves, which are likely to become pinned to heterogeneities. Far-field pacing (FFP) is a promising method for terminating such waves by using heterogeneities in the tissue as internal pacing sites. In this study we investigated the role of multiple obstacles and their interaction during FFP. We show that a secondary nearby obstacle can significantly modulate the minimum electrical field in FFP. Further, we show that essentially the same effect can be observed in cardiac tissue culture, which is a powerful experimental model to simulate heart activity. Here, an isotropic cell distribution leads to domain formation of locally distributed depolarization sites. Both secondary obstacles and domain formation of local depolarization sites can modulate energy requirements to originate wave propagation on obstacles. Our theoretical result was confirmed by experiments with cardiomyocyte monolayers. This result may be useful for the future application of FFP to a real beating heart.

  1. Approximate analytical solutions for excitation and propagation in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Greene, D'Artagnan; Shiferaw, Yohannes

    2015-04-01

    It is well known that a variety of cardiac arrhythmias are initiated by a focal excitation in heart tissue. At the single cell level these currents are typically induced by intracellular processes such as spontaneous calcium release (SCR). However, it is not understood how the size and morphology of these focal excitations are related to the electrophysiological properties of cardiac cells. In this paper a detailed physiologically based ionic model is analyzed by projecting the excitation dynamics to a reduced one-dimensional parameter space. Based on this analysis we show that the inward current required for an excitation to occur is largely dictated by the voltage dependence of the inward rectifier potassium current (IK 1) , and is insensitive to the detailed properties of the sodium current. We derive an analytical expression relating the size of a stimulus and the critical current required to induce a propagating action potential (AP), and argue that this relationship determines the necessary number of cells that must undergo SCR in order to induce ectopic activity in cardiac tissue. Finally, we show that, once a focal excitation begins to propagate, its propagation characteristics, such as the conduction velocity and the critical radius for propagation, are largely determined by the sodium and gap junction currents with a substantially lesser effect due to repolarizing potassium currents. These results reveal the relationship between ion channel properties and important tissue scale processes such as excitation and propagation.

  2. Cardiac tissue ablation with catheter-based microwave heating.

    PubMed

    Rappaport, C

    2004-11-01

    The common condition of atrial fibrillation is often treated by cutting diseased cardiac tissue to disrupt abnormal electrical conduction pathways. Heating abnormal tissue with electromagnetic power provides a minimally invasive surgical alternative to treat these cardiac arrhythmias. Radio frequency ablation has become the method of choice of many physicians. Recently, microwave power has also been shown to have great therapeutic benefit in medical treatment requiring precise heating of biological tissue. Since microwave power tends to be deposited throughout the volume of biological media, microwave heating offers advantages over other heating modalities that tend to heat primarily the contacting surface. It is also possible to heat a deeper volume of tissue with more precise control using microwaves than with purely thermal conduction or RF electrode heating. Microwave Cardiac Ablation (MCA) is used to treat heart tissue that allows abnormal electrical conduction by heating it to the point of inactivation. Microwave antennas that fit within catheter systems can be positioned close to diseased tissue. Specialized antenna designs that unfurl from the catheter within the heart can then radiate specifically shaped fields, which overcome problems such as excessive surface heating at the contact point. The state of the art in MCA is reviewed in this paper and a novel catheter-based unfurling wide aperture antenna is described. This antenna consists of the centre conductor of a coaxial line, shaped into a spiral and insulated from blood and tissue by a non-conductive fluid filled balloon. Initially stretched straight inside a catheter for transluminal guiding, once in place at the cardiac target, the coiled spiral antenna is advanced into the inflated balloon. Power is applied in the range of 50-150 W at the reserved industrial, scientific and medical (ISM) frequency of 915 MHz for 30-90 s to create an irreversible lesion. The antenna is then retracted back into the

  3. Exercise at depth alters bradycardia and incidence of cardiac anomalies in deep-diving marine mammals.

    PubMed

    Williams, Terrie M; Fuiman, Lee A; Kendall, Traci; Berry, Patrick; Richter, Beau; Noren, Shawn R; Thometz, Nicole; Shattock, Michael J; Farrell, Edward; Stamper, Andy M; Davis, Randall W

    2015-01-16

    Unlike their terrestrial ancestors, marine mammals routinely confront extreme physiological and physical challenges while breath-holding and pursuing prey at depth. To determine how cetaceans and pinnipeds accomplish deep-sea chases, we deployed animal-borne instruments that recorded high-resolution electrocardiograms, behaviour and flipper accelerations of bottlenose dolphins (Tursiops truncatus) and Weddell seals (Leptonychotes weddellii) diving from the surface to >200 m. Here we report that both exercise and depth alter the bradycardia associated with the dive response, with the greatest impacts at depths inducing lung collapse. Unexpectedly, cardiac arrhythmias occurred in >73% of deep, aerobic dives, which we attribute to the interplay between sympathetic and parasympathetic drivers for exercise and diving, respectively. Such marked cardiac variability alters the common view of a stereotypic 'dive reflex' in diving mammals. It also suggests the persistence of ancestral terrestrial traits in cardiac function that may help explain the unique sensitivity of some deep-diving marine mammals to anthropogenic disturbances.

  4. Exercise at depth alters bradycardia and incidence of cardiac anomalies in deep-diving marine mammals.

    PubMed

    Williams, Terrie M; Fuiman, Lee A; Kendall, Traci; Berry, Patrick; Richter, Beau; Noren, Shawn R; Thometz, Nicole; Shattock, Michael J; Farrell, Edward; Stamper, Andy M; Davis, Randall W

    2015-01-01

    Unlike their terrestrial ancestors, marine mammals routinely confront extreme physiological and physical challenges while breath-holding and pursuing prey at depth. To determine how cetaceans and pinnipeds accomplish deep-sea chases, we deployed animal-borne instruments that recorded high-resolution electrocardiograms, behaviour and flipper accelerations of bottlenose dolphins (Tursiops truncatus) and Weddell seals (Leptonychotes weddellii) diving from the surface to >200 m. Here we report that both exercise and depth alter the bradycardia associated with the dive response, with the greatest impacts at depths inducing lung collapse. Unexpectedly, cardiac arrhythmias occurred in >73% of deep, aerobic dives, which we attribute to the interplay between sympathetic and parasympathetic drivers for exercise and diving, respectively. Such marked cardiac variability alters the common view of a stereotypic 'dive reflex' in diving mammals. It also suggests the persistence of ancestral terrestrial traits in cardiac function that may help explain the unique sensitivity of some deep-diving marine mammals to anthropogenic disturbances. PMID:25592286

  5. Bimodal biophotonic imaging of the structure-function relationship in cardiac tissue

    PubMed Central

    Hucker, William J.; Ripplinger, Crystal M.; Fleming, Christine P.; Fedorov, Vadim V.; Rollins, Andrew M.; Efimov, Igor R.

    2009-01-01

    The development of systems physiology is hampered by the limited ability to relate tissue structure and function in intact organs in vivo or in vitro. Here, we show the application of a bimodal biophotonic imaging approach that employs optical coherence tomography and fluorescent imaging to investigate the structure-function relationship at the tissue level in the heart. Reconstruction of cardiac excitation and structure was limited by the depth penetration of bimodal imaging to ∼2 mm in atrial tissue, and ∼1 mm in ventricular myocardium. The subcellular resolution of optical coherence tomography clearly demonstrated that microscopic fiber orientation governs the pattern of wave propagation in functionally characterized rabbit sinoatrial and atrioventricular nodal preparations and revealed structural heterogeneities contributing to ventricular arrhythmias. The combination of this bimodal biophotonic imaging approach with histology and/or immunohistochemistry can span multiple scales of resolution for the investigation of the molecular and structural determinants of intact tissue physiology. PMID:19021392

  6. Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

    PubMed Central

    Annabi, Nasim; Tsang, Kelly; Mithieux, Suzanne M.; Nikkhah, Mehdi; Ameri, Afshin

    2013-01-01

    Heart failure is a major international health issue. Myocardial mass loss and lack of contractility are precursors to heart failure. Surgical demand for effective myocardial repair is tempered by a paucity of appropriate biological materials. These materials should conveniently replicate natural human tissue components, convey persistent elasticity, promote cell attachment, growth and conformability to direct cell orientation and functional performance. Here, microfabrication techniques are applied to recombinant human tropoelastin, the resilience-imparting protein found in all elastic human tissues, to generate photocrosslinked biological materials containing well-defined micropatterns. These highly elastic substrates are then used to engineer biomimetic cardiac tissue constructs. The micropatterned hydrogels, produced through photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment, spreading, alignment, function, and intercellular communication of cardiomyocytes by providing an elastic mechanical support that mimics their dynamic mechanical properties in vivo. The fabricated MeTro hydrogels also support the synchronous beating of cardiomyocytes in response to electrical field stimulation. These novel engineered micropatterned elastic gels are designed to be amenable to 3D modular assembly and establish a versatile, adaptable foundation for the modeling and regeneration of functional cardiac tissue with potential for application to other elastic tissues. PMID:24319406

  7. Practical aspects of cardiac tissue engineering with electrical stimulation.

    PubMed

    Cannizzaro, Christopher; Tandon, Nina; Figallo, Elisa; Park, Hyoungshin; Gerecht, Sharon; Radisic, Milica; Elvassore, Nicola; Vunjak-Novakovic, Gordana

    2007-01-01

    Heart disease is a leading cause of death in western society. Despite the success of heart transplantation, a chronic shortage of donor organs, along with the associated immunological complications of this approach, demands that alternative treatments be found. One such option is to repair, rather than replace, the heart with engineered cardiac tissue. Multiple studies have shown that to attain functional tissue, assembly signaling cues must be recapitulated in vitro. In their native environment, cardiomyocytes are directed to beat in synchrony by propagation of pacing current through the tissue. Recently, we have shown that electrical stimulation directs neonatal cardiomyocytes to assemble into native-like tissue in vitro. This chapter provides detailed methods we have employed in taking this "biomimetic" approach. After an initial discussion on how electric field stimulation can influence cell behavior, we examine the practical aspects of cardiac tissue engineering with electrical stimulation, such as electrode selection and cell seeding protocols, and conclude with what we feel are the remaining challenges to be overcome.

  8. Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization.

    PubMed

    Carrier, R L; Papadaki, M; Rupnick, M; Schoen, F J; Bursac, N; Langer, R; Freed, L E; Vunjak-Novakovic, G

    1999-09-01

    Cardiac tissue engineering has been motivated by the need to create functional tissue equivalents for scientific studies and cardiac tissue repair. We previously demonstrated that contractile cardiac cell-polymer constructs can be cultivated using isolated cells, 3-dimensional scaffolds, and bioreactors. In the present work, we examined the effects of (1) cell source (neonatal rat or embryonic chick), (2) initial cell seeding density, (3) cell seeding vessel, and (4) tissue culture vessel on the structure and composition of engineered cardiac muscle. Constructs seeded under well-mixed conditions with rat heart cells at a high initial density ((6-8) x 10(6) cells/polymer scaffold) maintained structural integrity and contained macroscopic contractile areas (approximately 20 mm(2)). Seeding in rotating vessels (laminar flow) rather than mixed flasks (turbulent flow) resulted in 23% higher seeding efficiency and 20% less cell damage as assessed by medium lactate dehydrogenase levels (p < 0.05). Advantages of culturing constructs under mixed rather than static conditions included the maintenance of metabolic parameters in physiological ranges, 2-4 times higher construct cellularity (p &le 0.0001), more aerobic cell metabolism, and a more physiological, elongated cell shape. Cultivations in rotating bioreactors, in which flow patterns are laminar and dynamic, yielded constructs with a more active, aerobic metabolism as compared to constructs cultured in mixed or static flasks. After 1-2 weeks of cultivation, tissue constructs expressed cardiac specific proteins and ultrastructural features and had approximately 2-6 times lower cellularity (p < 0.05) but similar metabolic activity per unit cell when compared to native cardiac tissue.

  9. Cardiac tissue slices: preparation, handling, and successful optical mapping

    PubMed Central

    Wang, Ken; Lee, Peter; Mirams, Gary R.; Sarathchandra, Padmini; Borg, Thomas K.; Gavaghan, David J.; Kohl, Peter

    2015-01-01

    Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and optical mapping of transmembrane potential and intracellular free calcium concentration transients (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in the epicardium-tangential plane contained well-aligned in-slice myocardial cell strands (“fibers”) in subepicardial and midmyocardial sections. Cut with a high-precision slow-advancing microtome at a thickness of 350 to 400 μm, tissue slices preserved essential action potential (AP) properties of the precutting Langendorff-perfused heart. We identified the need for a postcutting recovery period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady-state values for AP duration (APD) (identified by exponential fitting). There was no significant difference between the postcutting recovery dynamics in slices obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical uncouplers during the cutting process. A rapid increase in APD, seen after cutting, was caused by exposure to ice-cold solution during the slicing procedure, not by tissue injury, differences in uncouplers, or pH-buffers (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and conduction, a combination of multipoint and field stimulation should be used to avoid misinterpretation based on source-sink effects. In summary, we describe in detail the preparation, mapping, and data analysis approaches for reproducible cardiac tissue slice-based investigations into AP and CaT dynamics. PMID:25595366

  10. Optical Imaging of Voltage and Calcium in Cardiac Cells & Tissues

    PubMed Central

    Herron, Todd J.; Lee, Peter; Jalife, José

    2012-01-01

    Cardiac optical mapping has proven to be a powerful technology for studying cardiovascular function and disease. The development and scientific impact of this methodology are well documented. Because of its relevance in cardiac research, this imaging technology advances at a rapid pace. Here we review technological and scientific developments during the past several years and look also towards the future. First we explore key components of a modern optical mapping setup, focusing on 1) new camera technologies, 2) powerful light-emitting-diodes (from ultraviolet to red) for illumination, 3) improved optical filter technology, 4) new synthetic and optogenetic fluorescent probes, 5) optical mapping with motion and contraction, 6) new multi-parametric optical mapping techniques and 7) photon scattering effects in thick tissue preparations. We then look at recent optical mapping studies in single cells, cardiomyocyte monolayers, atria and whole hearts. Finally, we briefly look into the possible future roles of optical mapping in the development of regenerative cardiac research, cardiac cell therapies, and molecular genetic advances. PMID:22343556

  11. [Investigation of light penetration depth and distribution inside citrus tissue].

    PubMed

    Wu, Chen-Kai; Zhang, Liang; Shen, Huang-Tong; Fu, Xia-Ping

    2014-03-01

    Experiment was carried out to explore the light intensity change inside citrus samples in the present study. An experimental platform was set up, including a light box, a spectrometer, a sample stage, an optic fiber probe, light sources, etc. The sample stage is adjustable in three dimensions. The optic fiber probe was used to measure the light changes by observing the light attenuation and intensity variation within the citrus tissues. A 632 nm laser source and a 50 W tungsten halogen lamp light source were used. Light intensity and transmittance were investigated at different positions within the citrus fruit. The band with most significant intensity difference was selected to analyze the light intensity and transmittance trends in different positions inside the citrus fruit In order to examine the influence significance of the sample factor on test results, SPSS software was used to do the analysis of variation (ANOVA) of different samples. The results showed that light intensity and transmittance have a positive correlation with puncture depth, while citrus peel and stone have a more obvious attenuation effect than citrus flesh, and the influence of the sample factor on the test results is not significant. Further research can be carried out by improving the experimental device. The method used and results obtained in this study are valuable for studies on light transmission properties inside fruit tissue, not only for citrus but also for other kinds of fruits.

  12. Effects of depth and chest volume on cardiac function during breath-hold diving.

    PubMed

    Marabotti, Claudio; Scalzini, Alessandro; Cialoni, Danilo; Passera, Mirko; Ripoli, Andrea; L'Abbate, Antonio; Bedini, Remo

    2009-07-01

    Cardiac response to breath-hold diving in human beings is primarily characterized by the reduction of both heart rate and stroke volume. By underwater Doppler-echocardiography we observed a "restrictive/constrictive" left ventricular filling pattern compatible with the idea of chest squeeze and heart compression during diving. We hypothesized that underwater re-expansion of the chest would release heart constriction and normalize cardiac function. To this aim, 10 healthy male subjects (age 34.2 +/- 10.4) were evaluated by Doppler-echocardiography during breath-hold immersion at a depth of 10 m, before and after a single maximal inspiration from a SCUBA device. During the same session, all subjects were also studied at surface (full-body immersion) and at 5-m depth in order to better characterize the relationship of echo-Doppler pattern with depth. In comparison to surface immersion, 5-m deep diving was sufficient to reduce cardiac output (P = 0.042) and increase transmitral E-peak velocity (P < 0.001). These changes remained unaltered at a 10-m depth. Chest expansion at 10 m decreased left ventricular end-systolic volume (P = 0.024) and increased left ventricular stroke volume (P = 0.024). In addition, it decreased transmitral E-peak velocity (P = 0.012) and increased deceleration time of E-peak (P = 0.021). In conclusion the diving response, already evident during shallow diving (5 m) did not progress during deeper dives (10 m). The rapid improvement in systolic and diastolic function observed after lung volume expansion is congruous with the idea of a constrictive effect on the heart exerted by chest squeeze.

  13. Biologically improved nanofibrous scaffolds for cardiac tissue engineering.

    PubMed

    Bhaarathy, V; Venugopal, J; Gandhimathi, C; Ponpandian, N; Mangalaraj, D; Ramakrishna, S

    2014-11-01

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(l-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. PMID:25280706

  14. Analysis of cardiac tissue by gold cluster ion bombardment

    NASA Astrophysics Data System (ADS)

    Aranyosiova, M.; Chorvatova, A.; Chorvat, D.; Biro, Cs.; Velic, D.

    2006-07-01

    Specific molecules in cardiac tissue of spontaneously hypertensive rats are studied by using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The investigation determines phospholipids, cholesterol, fatty acids and their fragments in the cardiac tissue, with special focus on cardiolipin. Cardiolipin is a unique phospholipid typical for cardiomyocyte mitochondrial membrane and its decrease is involved in pathologic conditions. In the positive polarity, the fragments of phosphatydilcholine are observed in the mass region of 700-850 u. Peaks over mass 1400 u correspond to intact and cationized molecules of cardiolipin. In animal tissue, cardiolipin contains of almost exclusively 18 carbon fatty acids, mostly linoleic acid. Linoleic acid at 279 u, other fatty acids, and phosphatidylglycerol fragments, as precursors of cardiolipin synthesis, are identified in the negative polarity. These data demonstrate that SIMS technique along with Au 3+ cluster primary ion beam is a good tool for detection of higher mass biomolecules providing approximately 10 times higher yield in comparison with Au +.

  15. Examination of Optical Depth Effects on Fluorescence Imaging of Cardiac Propagation

    PubMed Central

    Bray, Mark-Anthony; Wikswo, John P.

    2003-01-01

    Optical mapping with voltage-sensitive dyes provides a high-resolution technique to observe cardiac electrodynamic behavior. Although most studies assume that the fluorescent signal is emitted from the surface layer of cells, the effects of signal attenuation with depth on signal interpretation are still unclear. This simulation study examines the effects of a depth-weighted signal on epicardial activation patterns and filament localization. We simulated filament behavior using a detailed cardiac model, and compared the signal obtained from the top (epicardial) layer of the spatial domain with the calculated weighted signal. General observations included a prolongation of the action upstroke duration, early upstroke initiation, and reduction in signal amplitude in the weighted signal. A shallow filament was found to produce a dual-humped action potential morphology consistent with previously reported observations. Simulated scroll wave breakup exhibited effects such as the false appearance of graded potentials, apparent supramaximal conduction velocities, and a spatially blurred signal with the local amplitude dependent upon the immediate subepicardial activity; the combination of these effects produced a corresponding change in the accuracy of filament localization. Our results indicate that the depth-dependent optical signal has significant consequences on the interpretation of epicardial activation dynamics. PMID:14645100

  16. Three-dimensional cardiac tissue fabrication based on cell sheet technology.

    PubMed

    Masuda, Shinako; Shimizu, Tatsuya

    2016-01-15

    Cardiac tissue engineering is a promising therapeutic strategy for severe heart failure. However, conventional tissue engineering methods by seeding cells into biodegradable scaffolds have intrinsic limitations such as inflammatory responses and fibrosis arising from the degradation of scaffolds. On the other hand, we have developed cell sheet engineering as a scaffold-free approach for cardiac tissue engineering. Confluent cultured cells are harvested as an intact cell sheet using a temperature-responsive culture surface. By layering cardiac cell sheets, it is possible to form electrically communicative three-dimensional cardiac constructs. Cell sheet transplantation onto damaged hearts in several animal models has revealed improvements in heart functions. Because of the lack of vasculature, the thickness of viable cardiac cell sheet-layered tissues is limited to three layers. Pre-vascularized structure formation within cardiac tissue and multi-step transplantation methods has enabled the formation of thick vascularized tissues in vivo. Furthermore, development of original bioreactor systems with vascular beds has allowed reconstruction of three-dimensional cardiac tissues with a functional vascular structure in vitro. Large-scale culture systems to generate pluripotent stem cell-derived cardiac cells can create large numbers of cardiac cell sheets. Three-dimensional cardiac tissues fabricated by cell sheet engineering may be applied to treat heart disease and tissue model construction.

  17. Cardiac dysfunction among soft tissue sarcoma patients in Denmark

    PubMed Central

    Shantakumar, Sumitra; Olsen, Morten; Vo, Thao T; Nørgaard, Mette; Pedersen, Lars

    2016-01-01

    Purpose Soft tissue sarcoma (STS) patients may experience post-treatment cardiotoxicity, yet no population-based data exist. We examined the incidence of left ventricular ejection fraction (LVEF) decline, heart failure, and cardiac death following STS diagnosis among adults, using Danish patient registries and medical record review. Patients and methods LVEF decline was examined in a regional cohort of STS patients diagnosed during 1997–2011 in Western Denmark for whom cardiac imaging data were available. LVEF decline was defined as an absolute decline from baseline to follow-up of 10% or more, or, where baseline imaging was not available, a decline below the lower limit of normal (or 40%) for a follow-up LVEF. Heart failure and cardiac death were investigated in a national Danish cohort of all STS patients diagnosed from 2000 to 2009. We followed patients from STS diagnosis until heart failure, cardiac death, emigration or December 31, 2012 (whichever occurred first). Results The incidence rate of LVEF decline for the regional cohort with follow-up data (N=100, five events) or baseline and follow-up measurements (N=75, 19 events) was 16.8 (95% confidence interval [CI]: 7.0–40.3) and 108 (95% CI: 69–170), respectively, per 1,000 person-years. In the national cohort (N=1,187), the incidence of heart failure (40 events) and cardiac death (15 events) was 7.3 (95% CI: 5.4–10.0) and 2.7 (95% CI: 1.6–4.5), respectively, per 1,000 person-years. The strongest predictors of heart failure were doxorubicin treatment (hazard ratio [HR] =2.2, 95% CI: 0.5–10.2) and pre-existing cardiovascular disease (HR=6.3, 95% CI: 0.98–40.6). Conclusion LVEF decline occurred more frequently compared to heart failure or cardiac death in a nationally representative cohort of Danish STS patients. PMID:27186077

  18. Morphometric study of cardiac muscle: the problem of tissue shrinkage

    SciTech Connect

    Gerdes, A.M.; Kriseman, J.; Bishop, S.P.

    1982-03-01

    Comparison of data from morphometric studies dealing with the heart is complicated by the fact that little information dealing with cell size changes during tissue processing is available. To investigate these changes, isolated cardiac myocytes were adhered to glass cover slips of Sykes Moore chambers and photographed after each step of processing for transmission electron microscopy. Six different experiments with a minimum of 10 cells each were followed through the entire procedure after fixation with isoosmolar glutaraldehyde. Cellular dimension changes were determined by tracing individual isolated myocytes after each step of the procedure with a sonic digitizer. Significant cell volume changes occurred after osmium (16 per cent swelling), postosmium wash (10 per cent swelling), and uranyl acetate (25 per cent shrinkage). Hypertonic aldehyde solutions resulted in cellular shrinkage during fixation not found with isotonic solutions. Changes in cell cross-sectional area rather than length were largely responsible for altered cell volumes during any given phase of processing. The results indicate that, although cell volume changes occur during processing, final cell dimensions of embedded cells were not different from unfixed cells. In whole tissue blocks, inclusion of propylene oxide in the procedure resulted in tissue shrinkage which was not observed in isolated myocytes, suggesting that different tissue components react in a variable manner to propylene oxide. After each of the other steps in processing, tissue blocks reacted in a similar manner to the isolated myocytes.

  19. Morphometric study of cardiac muscle: the problem of tissue shrinkage.

    PubMed

    Gerdes, A M; Kriseman, J; Bishop, S P

    1982-03-01

    Comparison of data from morphometric studies dealing with the heart is complicated by the fact that little information dealing with cell size changes during tissue processing is available. To investigate these changes, isolated cardiac myocytes were adhered to glass cover slips of Sykes Moore chambers and photographed after each step of processing for transmission electron microscopy. Six different experiments with a minimum of 10 cells each were followed through the entire procedure after fixation with isoosmolar glutaraldehyde. Cellular dimension changes were determined by tracing individual isolated myocytes after each step of the procedure with a sonic digitizer. Significant cell volume changes occurred after osmium (16 per cent swelling), postosmium wash (10 per cent swelling), and uranyl acetate (25 per cent shrinkage). Hypertonic aldehyde solutions resulted in cellular shrinkage during fixation not found with isotonic solutions. Changes in cell cross-sectional area rather than length were largely responsible for altered cell volumes during any given phase of processing. The results indicate that, although cell volume changes occur during processing, final cell dimensions of embedded cells were not different from unfixed cells. In whole tissue blocks, inclusion of propylene oxide in the procedure resulted in tissue shrinkage which was not observed in isolated myocytes, suggesting that different tissue components react in a variable manner to propylene oxide. After each of the other steps in processing, tissue blocks reacted in a similar manner to the isolated myocytes.

  20. Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents.

    PubMed

    Bayes-Genis, Antoni; Soler-Botija, Carolina; Farré, Jordi; Sepúlveda, Pilar; Raya, Angel; Roura, Santiago; Prat-Vidal, Cristina; Gálvez-Montón, Carolina; Montero, José Anastasio; Büscher, Dirk; Izpisúa Belmonte, Juan Carlos

    2010-11-01

    Myocardial infarction caused by vascular occlusion results in the formation of nonfunctional fibrous tissue. Cumulative evidence indicates that cell therapy modestly improves cardiac function; thus, novel cell sources with the potential to repair injured tissue are actively sought. Here, we identify and characterize a cell population of cardiac adipose tissue-derived progenitor cells (ATDPCs) from biopsies of human adult cardiac adipose tissue. Cardiac ATDPCs express a mesenchymal stem cell-like marker profile (strongly positive for CD105, CD44, CD166, CD29 and CD90) and have immunosuppressive capacity. Moreover, cardiac ATDPCs have an inherent cardiac-like phenotype and were able to express de novo myocardial and endothelial markers in vitro but not to differentiate into adipocytes. In addition, when cardiac ATDPCs were transplanted into injured myocardium in mouse and rat models of myocardial infarction, the engrafted cells expressed cardiac (troponin I, sarcomeric α-actinin) and endothelial (CD31) markers, vascularization increased, and infarct size was reduced in mice and rats. Moreover, significant differences between control and cell-treated groups were found in fractional shortening and ejection fraction, and the anterior wall remained significantly thicker 30days after cardiac delivery of ATDPCs. Finally, cardiac ATDPCs secreted proangiogenic factors under in vitro hypoxic conditions, suggesting a paracrine effect to promote local vascularization. Our results indicate that the population of progenitor cells isolated from human cardiac adipose tissue (cardiac ATDPCs) may be valid candidates for future use in cell therapy to regenerate injured myocardium. PMID:20713059

  1. Electrical Pacing of Cardiac Tissue Including Potassium Inward Rectification.

    PubMed

    Galappaththige, Suran; Roth, Bradley J

    2015-01-01

    In this study cardiac tissue is stimulated electrically through a small unipolar electrode. Numerical simulations predict that around an electrode are adjacent regions of depolarization and hyperpolarization. Experiments have shown that during pacing of resting cardiac tissue the hyperpolarization is often inhibited. Our goal is to determine if the inward rectifying potassium current (IK1) causes the inhibition of hyperpolarization. Numerical simulations were carried out using the bidomain model with potassium dynamics specified to be inward rectifying. In the simulations, adjacent regions of depolarization and hyperpolarization were observed surrounding the electrode. For cathodal currents the virtual anode produces a hyperpolarization that decreases over time. For long duration pulses the current-voltage curve is non-linear, with very small hyperpolarization compared to depolarization. For short pulses, the hyperpolarization is more prominent. Without the inward potassium rectification, the current voltage curve is linear and the hyperpolarization is evident for both long and short pulses. In conclusion, the inward rectification of the potassium current explains the inhibition of hyperpolarization for long duration stimulus pulses, but not for short duration pulses.

  2. Depth-selective fiber-optic probe for characterization of superficial tissue at a constant physical depth

    PubMed Central

    Fang, Can; Brokl, David; Brand, Randall E.; Liu, Yang

    2011-01-01

    The in vivo assessment of superficial tissue has shown great promise in many biomedical applications. Significant efforts have been expended in designing compact fiber-optic probes with short tissue penetration depth targeting the superficial epithelium. In this paper, we present a compact and simple two-channel fiber-optic probe with superior depth selectivity for the superficial tissue. This probe employs a high-index ball-lens with an optimized illumination area and the maximal overlap between light illumination and collection spots, while maintaining sufficient light collection efficiency with minimized specular reflection. Importantly, we show that this probe allows the selection of a constant and shallow physical penetration depth, insensitive to a wide range of tissue-relevant scattering coefficients and anisotropy factors. We demonstrate the capability of this depth-selective fiber-optic probe to accurately quantify the absorber concentration in superficial tissue without the distortion of tissue scattering properties; and characterize the optical properties of superficial skin tissue. PMID:21483607

  3. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    NASA Astrophysics Data System (ADS)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  4. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    PubMed Central

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-01-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

  5. Curvature-dependent excitation propagation in cultured cardiac tissue

    NASA Astrophysics Data System (ADS)

    Kadota, S.; Kay, M. W.; Magome, N.; Agladze, K.

    2012-02-01

    The geometry of excitation wave front may play an important role on the propagation block and spiral wave formation. The wave front which is bent over the critical value due to interaction with the obstacles may partially cease to propagate and appearing wave breaks evolve into rotating waves or reentry. This scenario may explain how reentry spontaneously originates in a heart. We studied highly curved excitation wave fronts in the cardiac tissue culture and found that in the conditions of normal, non-inhibited excitability the curvature effects do not play essential role in the propagation. Neither narrow isthmuses nor sharp corners of the obstacles, being classical objects for production of extremely curved wave front, affect non-inhibited wave propagation. The curvature-related phenomena of the propagation block and wave detachment from the obstacle boundary were observed only after partial suppression of the sodium channels with Lidocaine. Computer simulations confirmed the experimental observations. The explanation of the observed phenomena refers to the fact that the heart tissue is made of finite size cells so that curvature radii smaller than the cardiomyocyte size loses sense, and in non-inhibited tissue the single cell is capable to transmit excitation to its neighbors.

  6. Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

    PubMed

    Hasan, Anwarul; Waters, Renae; Roula, Boustany; Dana, Rahbani; Yara, Seif; Alexandre, Toubia; Paul, Arghya

    2016-07-01

    Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field. PMID:26953627

  7. Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration.

    PubMed

    Masumoto, Hidetoshi; Ikuno, Takeshi; Takeda, Masafumi; Fukushima, Hiroyuki; Marui, Akira; Katayama, Shiori; Shimizu, Tatsuya; Ikeda, Tadashi; Okano, Teruo; Sakata, Ryuzo; Yamashita, Jun K

    2014-01-01

    To realize cardiac regeneration using human induced pluripotent stem cells (hiPSCs), strategies for cell preparation, tissue engineering and transplantation must be explored. Here we report a new protocol for the simultaneous induction of cardiomyocytes (CMs) and vascular cells [endothelial cells (ECs)/vascular mural cells (MCs)], and generate entirely hiPSC-engineered cardiovascular cell sheets, which showed advantageous therapeutic effects in infarcted hearts. The protocol adds to a previous differentiation protocol of CMs by using stage-specific supplementation of vascular endothelial cell growth factor for the additional induction of vascular cells. Using this cell sheet technology, we successfully generated physically integrated cardiac tissue sheets (hiPSC-CTSs). HiPSC-CTS transplantation to rat infarcted hearts significantly improved cardiac function. In addition to neovascularization, we confirmed that engrafted human cells mainly consisted of CMs in >40% of transplanted rats four weeks after transplantation. Thus, our HiPSC-CTSs show promise for cardiac regenerative therapy.

  8. Ablation of cardiac myosin–binding protein-C accelerates contractile kinetics in engineered cardiac tissue

    PubMed Central

    de Lange, Willem J.; Grimes, Adrian C.; Hegge, Laura F.

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) caused by mutations in cardiac myosin–binding protein-C (cMyBP-C) is a heterogenous disease in which the phenotypic presentation is influenced by genetic, environmental, and developmental factors. Though mouse models have been used extensively to study the contractile effects of cMyBP-C ablation, early postnatal hypertrophic and dilatory remodeling may overshadow primary contractile defects. The use of a murine engineered cardiac tissue (mECT) model of cMyBP-C ablation in the present study permits delineation of the primary contractile kinetic abnormalities in an intact tissue model under mechanical loading conditions in the absence of confounding remodeling events. We generated mechanically integrated mECT using isolated postnatal day 1 mouse cardiac cells from both wild-type (WT) and cMyBP-C–null hearts. After culturing for 1 wk to establish coordinated spontaneous contraction, we measured twitch force and Ca2+ transients at 37°C during pacing at 6 and 9 Hz, with and without dobutamine. Compared with WT, the cMyBP-C–null mECT demonstrated faster late contraction kinetics and significantly faster early relaxation kinetics with no difference in Ca2+ transient kinetics. Strikingly, the ability of cMyBP-C–null mECT to increase contractile kinetics in response to adrenergic stimulation and increased pacing frequency were severely impaired. We conclude that cMyBP-C ablation results in constitutively accelerated contractile kinetics with preserved peak force with minimal contractile kinetic reserve. These functional abnormalities precede the development of the hypertrophic phenotype and do not result from alterations in Ca2+ transient kinetics, suggesting that alterations in contractile velocity may serve as the primary functional trigger for the development of hypertrophy in this model of HCM. Our findings strongly support a mechanism in which cMyBP-C functions as a physiological brake on contraction by positioning myosin

  9. Quantitative imaging of intact cardiac tissue using remote focusing microscopy

    NASA Astrophysics Data System (ADS)

    Corbett, A. D.; Burton, R. A. B.; Bub, G.; Wilson, T.

    2015-03-01

    Remote focussing microscopy offers many advantages when acquiring volumetric data from living tissue. The all-optical means of refocussing does not agitate the specimen by moving either the stage or imaging objective. Aberrationcompensated imaging extends over volumes as large as 450 μm x 450 μm x 200 μm (X, Y and Z) allowing data to be collected from hundreds of cells. The speed with which refocussing can be achieved is limited only by the mechanical movement of a small (2 mm diameter) mirror. Using a pair of oblique imaging planes to rapidly acquire (<200ms) depth information temporally freezes residual tissue motion in the arrested heart. This paper discusses the progress of remote focussing microscopy from a novel imaging technique to a reliable tool in the life sciences. Specifically, we describe recent efforts to achieve the accurate calibration of both distance and orientation within the imaging volume. Using a laser machined fluorescent specimen it is possible to identify, with high sensitivity, small (<1%) depth-dependent magnification changes which are a linear function of axial misalignment of the imaging objective. The sensitivity of the calibration procedure limits distortion to <1 μm over the entire imaging volume. This work finds direct application in identifying the microscopic effects of chronic disease in the living heart.

  10. Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.

    PubMed

    Dilley, Rodney J; Morrison, Wayne A

    2014-11-01

    Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation.

  11. Role of tissue thickness on depth of morphologic skin damage

    NASA Astrophysics Data System (ADS)

    RajaMahmood, T. L. I.; Mat Jafri, M. Z.; Omar, Khalid M.

    2013-05-01

    Different zonal areas of the skins have different thickness and different adnexal composition. For this reason, the power density and exposure duration have to be adjusted to the area that being treated. The effects of laser expose to the different area of the skin has been studied by using the power density of 20.31 W/cm2 and the times when the cracking sound heard is the explosive duration recorded for each area of the skins. As a result, the histologic sections revealed that the explosive duration varied significantly with the difference in thickness of the skin tissue. Also, the expanding spaces between hair follicles and its surrounding tissue as well as denaturation of collagen fiberswere shownin each skin section and were mainly affected by the photothermal effect produced from the CO2 laser-skin tissue interaction.

  12. Depth

    PubMed Central

    Koenderink, Jan J; van Doorn, Andrea J; Wagemans, Johan

    2011-01-01

    Depth is the feeling of remoteness, or separateness, that accompanies awareness in human modalities like vision and audition. In specific cases depths can be graded on an ordinal scale, or even measured quantitatively on an interval scale. In the case of pictorial vision this is complicated by the fact that human observers often appear to apply mental transformations that involve depths in distinct visual directions. This implies that a comparison of empirically determined depths between observers involves pictorial space as an integral entity, whereas comparing pictorial depths as such is meaningless. We describe the formal structure of pictorial space purely in the phenomenological domain, without taking recourse to the theories of optics which properly apply to physical space—a distinct ontological domain. We introduce a number of general ways to design and implement methods of geodesy in pictorial space, and discuss some basic problems associated with such measurements. We deal mainly with conceptual issues. PMID:23145244

  13. Depth.

    PubMed

    Koenderink, Jan J; van Doorn, Andrea J; Wagemans, Johan

    2011-01-01

    Depth is the feeling of remoteness, or separateness, that accompanies awareness in human modalities like vision and audition. In specific cases depths can be graded on an ordinal scale, or even measured quantitatively on an interval scale. In the case of pictorial vision this is complicated by the fact that human observers often appear to apply mental transformations that involve depths in distinct visual directions. This implies that a comparison of empirically determined depths between observers involves pictorial space as an integral entity, whereas comparing pictorial depths as such is meaningless. We describe the formal structure of pictorial space purely in the phenomenological domain, without taking recourse to the theories of optics which properly apply to physical space-a distinct ontological domain. We introduce a number of general ways to design and implement methods of geodesy in pictorial space, and discuss some basic problems associated with such measurements. We deal mainly with conceptual issues.

  14. Probing elastic modulus and depth of bottom-supported inclusions in model tissues using piezoelectric cantilevers.

    PubMed

    Yegingil, Hakki; Shih, Wan Y; Shih, Wei-Heng

    2007-11-01

    We have experimentally investigated the depth sensitivity limit of a piezoelectric cantilever tissue elastic modulus sensor and simultaneously determined the elastic modulus and the depth of a tumor directly. Using model tissues consisting of bottom-supported modeling clay inclusions of various depths in a gelatin matrix, we empirically determined that the depth sensitivity limit of a piezoelectric cantilever sensor was twice the linear dimension of the indentation area (or the cantilever width). Knowing the depth sensitivity limit of the individual cantilever sensor as input and treating a model tissue that has the gelatin matrix on top and the modeling clay inclusion at the bottom as two springs in series, we showed that the elastic moduli and depths of the hard inclusions could be simultaneously determined with the elastic modulus profiles measured by two cantilevers with different widths as input.

  15. Reentry Near the Percolation Threshold in a Heterogeneous Discrete Model for Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Alonso, Sergio; Bär, Markus

    2013-04-01

    Arrhythmias in cardiac tissue are related to irregular electrical wave propagation in the heart. Cardiac tissue is formed by a discrete cell network, which is often heterogeneous. A localized region with a fraction of nonconducting links surrounded by homogeneous conducting tissue can become a source of reentry and ectopic beats. Extensive simulations in a discrete model of cardiac tissue show that a wave crossing a heterogeneous region of cardiac tissue can disintegrate into irregular patterns, provided the fraction of nonconducting links is close to the percolation threshold of the cell network. The dependence of the reentry probability on this fraction, the system size, and the degree of excitability can be inferred from the size distribution of nonconducting clusters near the percolation threshold.

  16. Increasing the penetration depth for ultrafast laser tissue ablation using glycerol based optical clearing

    NASA Astrophysics Data System (ADS)

    Gabay, Ilan; Subramanian, Kaushik G.; Martin, Chris; Yildirim, Murat; Tuchin, Valery V.; Ben-Yakar, Adela

    2016-03-01

    Background: Deep tissue ablation is the next challenge in ultrafast laser microsurgery. By focusing ultrafast pulses below the tissue surface one can create an ablation void confined to the focal volume. However, as the ablation depth increases in a scattering tissue, increase in the required power can trigger undesired nonlinear phenomena out of focus that restricts our ability to ablate beyond a maximum ablation depth of few scattering lengths. Optical clearing (OC) might reduce the intensity and increase the maximal ablation depth by lowering the refractive index mismatch, and therefore reducing scattering. Some efforts to ablate deeper showed out of focus damage, while others used brutal mechanical methods for clearing. Our clinical goal is to create voids in the scarred vocal folds and inject a biomaterial to bring back the tissue elasticity and restore phonation. Materials and methods: Fresh porcine vocal folds were excised and applied a biocompatible OC agent (75% glycerol). Collimated transmittance was monitored. The tissue was optically cleared and put under the microscope for ablation threshold measurements at different depths. Results: The time after which the tissue was optically cleared was roughly two hours. Fitting the threshold measurements to an exponential decay graph indicated that the scattering length of the tissue increased to 83+/-16 μm, which is more than doubling the known scattering length for normal tissue. Conclusion: Optical clearing with Glycerol increases the tissue scattering length and therefore reduces the energy for ablation and increases the maximal ablation depth. This technique can potentially improve clinical microsurgery.

  17. Coiled fiber scaffolds embedded with gold nanoparticles improve the performance of engineered cardiac tissues

    NASA Astrophysics Data System (ADS)

    Fleischer, Sharon; Shevach, Michal; Feiner, Ron; Dvir, Tal

    2014-07-01

    Coiled perimysial fibers within the heart muscle provide it with the ability to contract and relax efficiently. Here, we report on a new nanocomposite scaffold for cardiac tissue engineering, integrating coiled electrospun fibers with gold nanoparticles. Cultivation of cardiac cells within the hybrid scaffolds promoted cell organization into elongated and aligned tissues generating a strong contraction force, high contraction rate and low excitation threshold.Coiled perimysial fibers within the heart muscle provide it with the ability to contract and relax efficiently. Here, we report on a new nanocomposite scaffold for cardiac tissue engineering, integrating coiled electrospun fibers with gold nanoparticles. Cultivation of cardiac cells within the hybrid scaffolds promoted cell organization into elongated and aligned tissues generating a strong contraction force, high contraction rate and low excitation threshold. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00300d

  18. Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues.

    PubMed

    Feric, Nicole T; Radisic, Milica

    2016-01-15

    Engineering functional human cardiac tissue that mimics the native adult morphological and functional phenotype has been a long held objective. In the last 5 years, the field of cardiac tissue engineering has transitioned from cardiac tissues derived from various animal species to the production of the first generation of human engineered cardiac tissues (hECTs), due to recent advances in human stem cell biology. Despite this progress, the hECTs generated to date remain immature relative to the native adult myocardium. In this review, we focus on the maturation challenge in the context of hECTs, the present state of the art, and future perspectives in terms of regenerative medicine, drug discovery, preclinical safety testing and pathophysiological studies.

  19. Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis

    PubMed Central

    Burchfield, Jana S; Dimmeler, Stefanie

    2008-01-01

    A new era has begun in the treatment of ischemic disease and heart failure. With the discovery that stem cells from diverse organs and tissues, including bone marrow, adipose tissue, umbilical cord blood, and vessel wall, have the potential to improve cardiac function beyond that of conventional pharmacological therapy comes a new field of research aiming at understanding the precise mechanisms of stem cell-mediated cardiac repair. Not only will it be important to determine the most efficacious cell population for cardiac repair, but also whether overlapping, common mechanisms exist. Increasing evidence suggests that one mechanism of action by which cells provide tissue protection and repair may involve paracrine factors, including cytokines and growth factors, released from transplanted stem cells into the surrounding tissue. These paracrine factors have the potential to directly modify the healing process in the heart, including neovascularization, cardiac myocyte apoptosis, inflammation, fibrosis, contractility, bioenergetics, and endogenous repair. PMID:19014650

  20. Evolution of the complex permittivity of biological tissue at microwaves ranges: correlation study with burn depth.

    PubMed

    Matthieu, Brusson; Jerome, Rossignol; Stephane, Binczak; Gabriel, Laurent

    2014-01-01

    The evolution of the muscle tissue's complex permittivity represents a growing interest in terms of characterization in medicine and biology. The influence of a burned part on the permittivity is not very developed. In this work, an estimation of the complex permittivity of biological tissues is performed as a function of the depth of burn tissues. The sensor, an open-ended coaxial probe, is placed directly against each sample. The evolution of the complex permittivity is studied for two measurements conditions (in the air and in a physiological solution). A correlation study is attempted with the depth of burn tissue.

  1. Non-Linear Dynamics of Cardiac Alternans: Subcellular to Tissue-Level Mechanisms of Arrhythmia

    PubMed Central

    Gaeta, Stephen A.; Christini, David J.

    2012-01-01

    Cardiac repolarization alternans is a rhythm disturbance of the heart in which rapid stimulation elicits a beat-to-beat alternation in the duration of action potentials and magnitude of intracellular calcium transients in individual cardiac myocytes. Although this phenomenon has been identified as a potential precursor to dangerous reentrant arrhythmias and sudden cardiac death, significant uncertainty remains regarding its mechanism and no clinically practical means of halting its occurrence or progression currently exists. Cardiac alternans has well-characterized tissue, cellular, and subcellular manifestations, the mechanisms and interplay of which are an active area of research. PMID:22783195

  2. The role of tissue engineering and biomaterials in cardiac regenerative medicine

    PubMed Central

    Zhao, Yimu; Feric, Nicole T.; Thavandiran, Nimalan; Nunes, Sara S.; Radisic, Milica

    2014-01-01

    In recent years, the development of three-dimensional engineered heart tissue (EHT) has made large strides forward due to advances in stem cell biology, materials science, pre-vascularization strategies and nanotechnology. As a result, the role of tissue engineering in cardiac regenerative medicine has become multi-faceted as new applications become feasible. Cardiac tissue engineering has long been established to have the potential to partially or fully restore cardiac function following cardiac injury. However, EHTs may also serve as surrogate human cardiac tissue for drug-related toxicity screening. Cardiotoxicity remains a major cause of drug withdrawal in the pharmaceutical industry. Unsafe drugs reach the market because pre-clinical evaluation is insufficient to weed out cardiotoxic drugs in all their forms. Bioengineering methods could provide functional and mature human myocardial tissues, i.e. physiologically relevant platforms, for screening the cardiotoxic effects of pharmaceutical agents and facilitate the discovery of new therapeutic agents. Finally, advances in induced pluripotent stem cells have made patient-specific EHTs possible, which opens up the possibility of personalized medicine. Herein, we give an overview of the present state of the art in cardiac tissue engineering, the challenges to the field and future perspectives. PMID:25442432

  3. The role of tissue engineering and biomaterials in cardiac regenerative medicine.

    PubMed

    Zhao, Yimu; Feric, Nicole T; Thavandiran, Nimalan; Nunes, Sara S; Radisic, Milica

    2014-11-01

    In recent years, the development of 3-dimensional engineered heart tissue (EHT) has made large strides forward because of advances in stem cell biology, materials science, prevascularization strategies, and nanotechnology. As a result, the role of tissue engineering in cardiac regenerative medicine has become multifaceted as new applications become feasible. Cardiac tissue engineering has long been established to have the potential to partially or fully restore cardiac function after cardiac injury. However, EHTs may also serve as surrogate human cardiac tissue for drug-related toxicity screening. Cardiotoxicity remains a major cause of drug withdrawal in the pharmaceutical industry. Unsafe drugs reach the market because preclinical evaluation is insufficient to weed out cardiotoxic drugs in all their forms. Bioengineering methods could provide functional and mature human myocardial tissues, ie, physiologically relevant platforms, for screening the cardiotoxic effects of pharmaceutical agents and facilitate the discovery of new therapeutic agents. Finally, advances in induced pluripotent stem cells have made patient-specific EHTs possible, which opens up the possibility of personalized medicine. Herein, we give an overview of the present state of the art in cardiac tissue engineering, the challenges to the field, and future perspectives. PMID:25442432

  4. 3D engineered cardiac tissue models of human heart disease: learning more from our mice.

    PubMed

    Ralphe, J Carter; de Lange, Willem J

    2013-02-01

    Mouse engineered cardiac tissue constructs (mECTs) are a new tool available to study human forms of genetic heart disease within the laboratory. The cultured strips of cardiac cells generate physiologic calcium transients and twitch force, and respond to electrical pacing and adrenergic stimulation. The mECT can be made using cells from existing mouse models of cardiac disease, providing a robust readout of contractile performance and allowing a rapid assessment of genotype-phenotype correlations and responses to therapies. mECT represents an efficient and economical extension to the existing tools for studying cardiac physiology. Human ECTs generated from iPSCMs represent the next logical step for this technology and offer significant promise of an integrated, fully human, cardiac tissue model.

  5. Functional Analysis of the Engineered Cardiac Tissue Grown on Recombinant Spidroin Fiber Meshes

    PubMed Central

    Teplenin, Alexander; Krasheninnikova, Anna; Agladze, Nadezhda; Sidoruk, Konstantin; Agapova, Olga; Agapov, Igor; Bogush, Vladimir; Agladze, Konstantin

    2015-01-01

    In the present study, we examined the ability of the recombinant spidroin to serve as a substrate for the cardiac tissue engineering. For this purpose, isolated neonatal rat cardiomyocytes were seeded on the electrospun spidroin fiber matrices and cultured to form the confluent cardiac monolayers. Besides the adhesion assay and immunostaining analysis, we tested the ability of the cultured cardiomyocytes to form a functional cardiac syncytium by studying excitation propagation in the cultured tissue with the aid of optical mapping. It was demonstrated that recombinant spidroin fiber meshes are directly suitable for the adherence and growth of the cardiomyocytes without additional coating with the attachment factors, such as fibronectin. PMID:25799394

  6. Electrical stimulation of cardiac adipose tissue-derived progenitor cells modulates cell phenotype and genetic machinery.

    PubMed

    Llucià-Valldeperas, A; Sanchez, B; Soler-Botija, C; Gálvez-Montón, C; Prat-Vidal, C; Roura, S; Rosell-Ferrer, J; Bragos, R; Bayes-Genis, A

    2015-11-01

    A major challenge of cardiac tissue engineering is directing cells to establish the physiological structure and function of the myocardium being replaced. Our aim was to examine the effect of electrical stimulation on the cardiodifferentiation potential of cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs). Three different electrical stimulation protocols were tested; the selected protocol consisted of 2 ms monophasic square-wave pulses of 50 mV/cm at 1 Hz over 14 days. Cardiac and subcutaneous ATDPCs were grown on biocompatible patterned surfaces. Cardiomyogenic differentiation was examined by real-time PCR and immunocytofluorescence. In cardiac ATDPCs, MEF2A and GATA-4 were significantly upregulated at day 14 after stimulation, while subcutaneous ATDPCs only exhibited increased Cx43 expression. In response to electrical stimulation, cardiac ATDPCs elongated, and both cardiac and subcutaneous ATDPCs became aligned following the linear surface pattern of the construct. Cardiac ATDPC length increased by 11.3%, while subcutaneous ATDPC length diminished by 11.2% (p = 0.013 and p = 0.030 vs unstimulated controls, respectively). Compared to controls, electrostimulated cells became aligned better to the patterned surfaces when the pattern was perpendicular to the electric field (89.71 ± 28.47º for cardiac ATDPCs and 92.15 ± 15.21º for subcutaneous ATDPCs). Electrical stimulation of cardiac ATDPCs caused changes in cell phenotype and genetic machinery, making them more suitable for cardiac regeneration approaches. Thus, it seems advisable to use electrical cell training before delivery as a cell suspension or within engineered tissue.

  7. Human Cardiac Tissue Engineering: From Pluripotent Stem Cells to Heart Repair

    PubMed Central

    Jackman, Christopher P.; Shadrin, Ilya Y.; Carlson, Aaron L.; Bursac, Nenad

    2014-01-01

    Engineered cardiac tissues hold great promise for use in drug and toxicology screening, in vitro studies of human physiology and disease, and as transplantable tissue grafts for myocardial repair. In this review, we discuss recent progress in cell-based therapy and functional tissue engineering using pluripotent stem cell-derived cardiomyocytes and we describe methods for delivery of cells into the injured heart. While significant hurdles remain, notable advances have been made in the methods to derive large numbers of pure human cardiomyocytes, mature their phenotype, and produce and implant functional cardiac tissues, bringing the field a step closer to widespread in vitro and in vivo applications. PMID:25599018

  8. Fabrication of omentum-based matrix for engineering vascularized cardiac tissues.

    PubMed

    Shevach, Michal; Soffer-Tsur, Neta; Fleischer, Sharon; Shapira, Assaf; Dvir, Tal

    2014-06-01

    Fabricating three-dimensional, biocompatible microenvironments to support functional tissue assembly remains a key challenge in cardiac tissue engineering. We hypothesized that since the omentum can be removed from patients by minimally invasive procedures, the obtained underlying matrices can be manipulated to serve as autologous scaffolds for cardiac patches. Here we initially characterized the structural, biochemical and mechanical properties of the obtained matrix, and demonstrated that cardiac cells cultivated within assembled into elongated and aligned tissues, generating a strong contraction force. Co-culture with endothelial cells resulted in the formation of blood vessel networks in the patch without affecting its function. Finally, we have validated that omental scaffolds can support mesenchymal and induced pluripotent stem cells culture, thus may serve as a platform for engineering completely autologous tissues. We envision that this approach may be suitable for treating the infarcted heart and may open up new opportunities in the broader field of tissue engineering and personalized regenerative medicine.

  9. Multifractality in depth dependent tissue refractive index variations probed via low-coherence back scattering spectroscopy

    NASA Astrophysics Data System (ADS)

    Dey, Rajib; Das, Nandan K.; Chakraborty, Semanti; Muvva, Sri B.; Ghosh, Nirmalya

    2016-04-01

    We have analyzed here low coherence spectroscopic data by multifractal analysis for obtaining tissue multifratality in depth wise index distribution. Essentially, in this method, a spectral domain interference pattern is recorded in a common path interferometer with a broad band source operated in back scattering mode. The recorded interference spectrum is subjected to Fourier domain processing to compute depth wise index distribution with a resolution of the order of one micron. The experimental set-up was validated, initially, by verifying depths of mica sheet layers and diameter of polystyrene microspheres and later, it was used for assessment of depth wise index (RI) distribution of cervical tissue slices. The structures of cervical tissues at different stages of cancer change rapidly which are manifested in the RI distribution and in turn, are encoded as multi-resolution information. This information can, effectively, be extracted by using multifractal detrended fluctuation analysis (MFDFA), where, multifractal parameters such as Hurst exponent h(q = 2) and width of singularity spectrum (Δα) show definitive change as cancer progresses from grade I to grade II. Moreover, the depth distribution of RI exhibited stronger multifractality (increased Δα) and considerably weakened correlations (decreased h(q = 2)) for tissues with higher pathological grades. Therefore, the technique of low coherence back-scattered (LCBS) interferometry bears a promise of using depth distribution of tissue refractive index and MFDFA analysis appears as a label free biomarker to detect cancer at early.

  10. Cardiac elastography: detecting pathological changes in myocardium tissues

    NASA Astrophysics Data System (ADS)

    Konofagou, Elisa E.; Harrigan, Timothy; Solomon, Scott

    2003-05-01

    Estimation of the mechanical properties of the cardiac muscle has been shown to play a crucial role in the detection of cardiovascular disease. Elastography was recently shown feasible on RF cardiac data in vivo. In this paper, the role of elastography in the detection of ischemia/infarct is explored with simulations and in vivo experiments. In finite-element simulations of a portion of the cardiac muscle containing an infarcted region, the cardiac cycle was simulated with successive compressive and tensile strains ranging between -30% and 20%. The incremental elastic modulus was also mapped uisng adaptive methods. We then demonstrated this technique utilizing envelope-detected sonographic data (Hewlett-Packard Sonos 5500) in a patient with a known myocardial infarction. In cine-loop and M-Mode elastograms from both normal and infarcted regions in simulations and experiments, the infarcted region was identifed by the up to one order of magnitude lower incremental axial displacements and strains, and higher modulus. Information on motion, deformation and mechanical property should constitute a unique tool for noninvasive cardiac diagnosis.

  11. Gold nanoparticle-decellularized matrix hybrids for cardiac tissue engineering.

    PubMed

    Shevach, Michal; Fleischer, Sharon; Shapira, Assaf; Dvir, Tal

    2014-10-01

    Decellularized matrices are valuable scaffolds for engineering functional cardiac patches for treating myocardial infarction. However, the lack of quick and efficient electrical coupling between adjacent cells may jeopardize the success of the treatment. To address this issue, we have deposited gold nanoparticles on fibrous decellularized omental matrices and investigated their morphology, conductivity, and degradation. We have shown that cardiac cells engineered within the hybrid scaffolds exhibited elongated and aligned morphology, massive striation, and organized connexin 43 electrical coupling proteins. Finally, we have shown that the hybrid patches demonstrated superior function as compared to pristine patches, including a stronger contraction force, lower excitation threshold, and faster calcium transients.

  12. [Epicardial adipose tissue and its role in cardiac physiology and disease].

    PubMed

    Toczyłowski, Kacper; Gruca, Michał; Baranowski, Marcin

    2013-06-20

    Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT) has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype) leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  13. Oblique polarized reflectance spectroscopy for depth sensitive measurements in the epithelial tissue

    NASA Astrophysics Data System (ADS)

    Jimenez, Maria K.; Fradkin, Leonid; Nieman, Linda T.; Lam, Sylvia; Poh, Catherine; Sokolov, Konstantin

    2013-02-01

    Optical spectroscopy has shown potential as a tool for precancer detection by discriminating alterations in the optical properties within epithelial tissues. Identifying depth-dependent alterations associated with the progression of epithelial cancerous lesions can be especially challenging in the oral cavity due to the variable thickness of the epithelium and the presence of keratinization. Optical spectroscopy of epithelial tissue with improved depth resolution would greatly assist in the isolation of optical properties associated with cancer progression. Here, we report a fiber optic probe for oblique polarized reflectance spectroscopy (OPRS) that is capable of depth sensitive detection by combining the following three approaches: multiple beveled fibers, oblique collection geometry, and polarization gating. We analyze how probe design parameters are related to improvements in collection efficiency of scattered photons from superficial tissue layers and to increased depth discrimination within epithelium. We have demonstrated that obliquely-oriented collection fibers increase both depth selectivity and collection efficiency of scattering signal. Currently, we evaluate this technology in a clinical trial of patients presenting lesions suspicious for dysplasia or carcinoma in the oral cavity. We use depth sensitive spectroscopic data to develop automated algorithms for analysis of morphological and architectural changes in the context of the multilayer oral epithelial tissue. Our initial results show that OPRS has the potential to improve the detection and monitoring of epithelial precancers in the oral cavity.

  14. Tissue and Animal Models of Sudden Cardiac Death

    PubMed Central

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

    2015-01-01

    Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

  15. Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.

    PubMed

    Koshman, Yevgeniya E; Sternlicht, Mark D; Kim, Taehoon; O'Hara, Christopher P; Koczor, Christopher A; Lewis, William; Seeley, Todd W; Lipson, Kenneth E; Samarel, Allen M

    2015-12-01

    Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective tissue growth factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. Our aim was to test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cε (PKCε) mouse model of DCM. Transgenic mice expressing constitutively active PKCε in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to cardiac fibrosis, heart failure, and increased mortality. Beginning at 3 months of age, PKCε mice were treated with a neutralizing monoclonal antibody to CTGF (FG-3149) for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic functions in PKCε mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling was elevated in PKCε mice, but significantly decreased by CTGF inhibition. However total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCε mice suggests that CTGF inhibition may benefit patients with DCM. Additional studies to explore this potential are warranted.

  16. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  17. Verification of cardiac tissue electrophysiology simulators using an N-version benchmark

    PubMed Central

    Niederer, Steven A.; Kerfoot, Eric; Benson, Alan P.; Bernabeu, Miguel O.; Bernus, Olivier; Bradley, Chris; Cherry, Elizabeth M.; Clayton, Richard; Fenton, Flavio H.; Garny, Alan; Heidenreich, Elvio; Land, Sander; Maleckar, Mary; Pathmanathan, Pras; Plank, Gernot; Rodríguez, José F.; Roy, Ishani; Sachse, Frank B.; Seemann, Gunnar; Skavhaug, Ola; Smith, Nic P.

    2011-01-01

    Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future. PMID:21969679

  18. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

    PubMed Central

    Finosh, G.T.; Jayabalan, Muthu

    2012-01-01

    Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

  19. Controlling spiral waves and turbulent states in cardiac tissue by traveling wave perturbations

    NASA Astrophysics Data System (ADS)

    Wang, Peng-Ye; Xie, Ping

    2000-03-01

    We propose a traveling wave perturbation method to control the spatiotemporal dynamics in cardiac tissue. With a two-variable model we demonstrate that the method can successfully suppress the wave instability (alternans in action potential duration) in the one-dimensional case and convert spiral waves and turbulent states to the normal traveling wave state in the two-dimensional case. An experimental scheme is suggested which may provide a new design for a cardiac defibrillator.

  20. Cone-shell Raman spectroscopy (CSRS) for depth-sensitive measurements in layered tissue.

    PubMed

    Khan, Khan Mohammad; Majumder, Shovan Kumar; Gupta, Pradeep Kumar

    2015-11-01

    We report the development of a depth-sensitive Raman spectroscopy system using the configuration of cone-shell excitation and cone detection. The system uses a 785 nm diode laser and three identical axicons for Raman excitation of the target sample in the form of a hollow conic section. The Raman scattered light from the sample, passed through the same (but solid) conic section, is collected for detection. Apart from its ability of probing larger depths (~ few mm), an important attraction of the system is that the probing depths can be varied by simply varying the separation between axicons in the excitation arm. Furthermore, no adjustment is required in the sample arm, which is a significant advantage for noncontact, depth-sensitive measurement. Evaluation of the performance of the developed setup on nonbiological phantom and biological tissue sample demonstrated its ability to recover Raman spectra of layers located at depths of ~2-3 mm beneath the surface.

  1. Effect of Cardiac Tissue Anisotropy on Three-Dimensional Electrical Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    He, Zhi Zhu; Liu, Jing

    A three-dimensional (3D) electrical action potential propagation model is developed to characterize the integrated effect of cardiac tissue structure using a homogenous function with a spatial inhomogeneity. This method may be more effective for bridging the gap between computational models and experimental data for cardiac tissue anisotropy. A generalized 3D eikonal relation considering anisotropy and a self-similar evolution solution of such a relation are derived to identify the effect of anisotropy and predict the anisotropy-induced electrical wave propagation instabilities. Furthermore, the phase field equation is introduced to obtain the complex three-dimensional numerical solution of the new correlation. The present results are expected to be valuable for better understanding the physiological behavior of cardiac tissues.

  2. Age-related changes in tissue macrophages precede cardiac functional impairment.

    PubMed

    Pinto, Alexander R; Godwin, James W; Chandran, Anjana; Hersey, Lucy; Ilinykh, Alexei; Debuque, Ryan; Wang, Lina; Rosenthal, Nadia A

    2014-05-01

    Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using theCx3cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1-GFP(hi) and Mrc1+GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1+GFP(lo), comprises ~50% of total Mrc1+ cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1+ cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1+ subsets also reveal that Mrc1+GFP(lo) cTMs have a decreased number of immune response genes (Cx3cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgfβr1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis. PMID:24861132

  3. Reduced Graphene Oxide-GelMA Hybrid Hydrogels as Scaffolds for Cardiac Tissue Engineering.

    PubMed

    Shin, Su Ryon; Zihlmann, Claudio; Akbari, Mohsen; Assawes, Pribpandao; Cheung, Louis; Zhang, Kaizhen; Manoharan, Vijayan; Zhang, Yu Shrike; Yüksekkaya, Mehmet; Wan, Kai-Tak; Nikkhah, Mehdi; Dokmeci, Mehmet R; Tang, Xiaowu Shirley; Khademhosseini, Ali

    2016-07-01

    Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cell behavior. Here, the myocardial tissue constructs are engineered based on reduced graphene oxide (rGO)-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhances the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibit better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes show stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial designs to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro. PMID:27254107

  4. Reduced Graphene Oxide-GelMA Hybrid Hydrogels as Scaffolds for Cardiac Tissue Engineering.

    PubMed

    Shin, Su Ryon; Zihlmann, Claudio; Akbari, Mohsen; Assawes, Pribpandao; Cheung, Louis; Zhang, Kaizhen; Manoharan, Vijayan; Zhang, Yu Shrike; Yüksekkaya, Mehmet; Wan, Kai-Tak; Nikkhah, Mehdi; Dokmeci, Mehmet R; Tang, Xiaowu Shirley; Khademhosseini, Ali

    2016-07-01

    Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cell behavior. Here, the myocardial tissue constructs are engineered based on reduced graphene oxide (rGO)-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhances the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibit better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes show stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial designs to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro.

  5. Chronic intracortical microelectrode arrays induce non-uniform, depth-related tissue responses

    NASA Astrophysics Data System (ADS)

    Woolley, Andrew J.; Desai, Himanshi A.; Otto, Kevin J.

    2013-04-01

    Objective. Brain-implanted microelectrode arrays show promise as future clinical devices. However, biological responses to various designs, compositions and locations of these implants have not been fully characterized, and may impact the long-term functionality of these devices. In order to improve our understanding of the tissue conditions at the interface of chronic brain-implanted microdevices, we proposed utilizing advanced histology and microscopy techniques to image implanted devices and surrounding tissue intact within brain slices. We then proposed utilizing these methods to examine whether depth within the cerebral cortex affected tissue conditions around implants. Approach. Histological data was collected from rodent brain slices containing intact, intracortical microdevices four weeks after implantation surgery. Thick tissue sections containing the chronic implants were processed with fluorescent antibody labels, and imaged in an optical clearing solution using laser confocal microscopy. Main Results. Tissue surrounding microdevices exhibited two major depth-related phenomena: a non-uniform microglial coating along the device length and a dense mass of cells surrounding the implant in cerebral cortical layers I and II. Detailed views of the monocyte-derived immune cells improve our understanding of the close and complex association that immune cells have with chronic brain implants, and illuminated a possible relationship between cortical depth and the intensity of a chronic monocyte response around penetrating microdevices. The dense mass of cells contained vimentin, a protein not typically expressed highly in CNS cells, evidence that non-CNS cells likely descended down the face of the penetrating devices from the pial surface. Significance. Image data of highly non-uniform and depth-dependent biological responses along a device provides novel insight into the complexity of the tissue response to penetrating brain-implanted microdevices. The presented

  6. Effect of a Plunge Electrode During Field Stimulation of Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Wikswo, J.; Woods, M.; Sidorov, V.; Langrill, D.; Roth, B.

    2003-03-01

    The response of cardiac tissue to strong electric fields is determined by 3-D cable properties, bidomain anisotropy, nonlinearities, and, most importantly, heterogeneities. Langrill and Roth (IEEE Trans. BME. 48:1207 (2001)) numerically studied the effect of a plunge electrode and found alternating regions of hyperpolarization and depolarization around the electrode in response to field shock. We sought to experimentally verify their results by using field stimulation and optical imaging of di-4-ANEPPS stained rabbit right ventricles with an insulated needle serving as a plunge electrode/heterogeneity. The experimental and numerical results agree qualitatively. The key discrepancy is the larger spatial extent of the polarization in the experimental data. The combination of transmural fiber rotation and fluorescence averaging over depth may cause the spatial scale to be larger than was predicted numerically. Because adjacent regions of opposite polarization are potential sources of wave front generation, our results suggest that plunge electrodes or similar-sized heterogeneities may play a role in far-field stimulation.

  7. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

    PubMed

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  8. Cardiac-induced physiologic noise in tissue is a direct observation of cardiac-induced fluctuations.

    PubMed

    Bhattacharyya, Pallab K; Lowe, Mark J

    2004-01-01

    Recent studies have shown that in certain cases, cardiac and respiratory rate fluctuations in BOLD-weighted MRI time courses may be an artifact unique to rapid sampled acquisitions and may not be present in longer repetition-time acquisitions. The implication of this is that, in these cases, cardiac and respiratory rate fluctuations are not aliased into data that undersample these effects and do not affect the resulting time course measurements. In this study, we show that these cases are specific to regions of large cerebrospinal fluid content and are not generally true for gray matter regions of the brain. We demonstrate that in many brain regions of interest, these fluctuations are directly observed as BOLD fluctuations and thus will affect measurements that undersample these effects.

  9. Multispectral upconversion luminescence intensity ratios for ascertaining the tissue imaging depth

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Wang, Yu; Kong, Xianggui; Liu, Xiaomin; Zhang, Youlin; Tu, Langping; Ding, Yadan; Aalders, Maurice C. G.; Buma, Wybren Jan; Zhang, Hong

    2014-07-01

    Upconversion nanoparticles (UCNPs) have in recent years emerged as excellent contrast agents for in vivo luminescence imaging of deep tissues. But information abstracted from these images is in most cases restricted to 2-dimensions, without the depth information. In this work, a simple method has been developed to accurately ascertain the tissue imaging depth based on the relative luminescence intensity ratio of multispectral NaYF4:Yb3+,Er3+ UCNPs. A theoretical mode was set up, where the parameters in the quantitative relation between the relative intensities of the upconversion luminescence spectra and the depth of the UCNPs were determined using tissue mimicking liquid phantoms. The 540 nm and 650 nm luminescence intensity ratios (G/R ratio) of NaYF4:Yb3+,Er3+ UCNPs were monitored following excitation path (Ex mode) and emission path (Em mode) schemes, respectively. The model was validated by embedding NaYF4:Yb3+,Er3+ UCNPs in layered pork muscles, which demonstrated a very high accuracy of measurement in the thickness up to centimeter. This approach shall promote significantly the power of nanotechnology in medical optical imaging by expanding the imaging information from 2-dimensional to real 3-dimensional.Upconversion nanoparticles (UCNPs) have in recent years emerged as excellent contrast agents for in vivo luminescence imaging of deep tissues. But information abstracted from these images is in most cases restricted to 2-dimensions, without the depth information. In this work, a simple method has been developed to accurately ascertain the tissue imaging depth based on the relative luminescence intensity ratio of multispectral NaYF4:Yb3+,Er3+ UCNPs. A theoretical mode was set up, where the parameters in the quantitative relation between the relative intensities of the upconversion luminescence spectra and the depth of the UCNPs were determined using tissue mimicking liquid phantoms. The 540 nm and 650 nm luminescence intensity ratios (G/R ratio) of NaYF4:Yb3

  10. Mathematical Models Based on Transfer Functions to Estimate Tissue Temperature During RF Cardiac Ablation in Real Time

    PubMed Central

    Alba-Martínez, Jose; Trujillo, Macarena; Blasco-Gimenez, Ramon; Berjano, Enrique

    2012-01-01

    Radiofrequency cardiac ablation (RFCA) has been used to treat certain types of cardiac arrhythmias by producing a thermal lesion. Even though a tissue temperature higher than 50ºC is required to destroy the target, thermal mapping is not currently used during RFCA. Our aim was thus to develop mathematical models capable of estimating tissue temperature from tissue characteristics acquired or estimated at the beginning of the procedure (electrical conductivity, thermal conductivity, specific heat and density) and the applied voltage at any time. Biological tissue was considered as a system with an input (applied voltage) and output (tissue temperature), and so the mathematical models were based on transfer functions relating these variables. We used theoretical models based on finite element method to verify the mathematical models. Firstly, we solved finite element models to identify the transfer functions between the temperature at a depth of 4 mm and a constant applied voltage using a 7Fr and 4 mm electrode. The results showed that the relationships can be expressed as first-order transfer functions. Changes in electrical conductivity only affected the static gain of the system, while specific heat variations produced a change in the dynamic system response. In contrast, variations in thermal conductivity modified both the static gain and the dynamic system response. Finally, to assess the performance of the transfer functions obtained, we conducted a new set of computer simulations using a controlled temperature protocol and considering the temperature dependence of the thermal and electrical conductivities, i.e. conditions closer to those found in clinical use. The results showed that the difference between the values estimated from transfer functions and the temperatures obtained from finite element models was less than 4ºC, which suggests that the proposed method could be used to estimate tissue temperature in real time. PMID:22715345

  11. Combined Technologies for Microfabricating Elastomeric Cardiac Tissue Engineering Scaffolds

    PubMed Central

    Guillemette, Maxime D.; Park, Hyoungshin; Hsiao, James C.; Jain, Saloni R.; Larson, Benjamin L.; Langer, Robert; Freed, Lisa E.

    2012-01-01

    Polymer scaffolds that direct elongation and orientation of cultured cells can enable tissue engineered muscle to act as a mechanically functional unit. We combined micromolding and microablation technologies to create muscle tissue engineering scaffolds from the biodegradable elastomer poly(glycerol sebacate). These scaffolds exhibited well defined surface patterns and pores and robust elastomeric tensile mechanical properties. Cultured C2C12 muscle cells penetrated the pores to form spatially controlled engineered tissues. Scanning electron and confocal microscopy revealed muscle cell orientation in a preferential direction, parallel to micromolded gratings and long axes of microablated anisotropic pores, with significant individual and interactive effects of gratings and pore design. PMID:20718054

  12. PGS:Gelatin nanofibrous scaffolds with tunable mechanical and structural properties for engineering cardiac tissues.

    PubMed

    Kharaziha, Mahshid; Nikkhah, Mehdi; Shin, Su-Ryon; Annabi, Nasim; Masoumi, Nafiseh; Gaharwar, Akhilesh K; Camci-Unal, Gulden; Khademhosseini, Ali

    2013-09-01

    A significant challenge in cardiac tissue engineering is the development of biomimetic grafts that can potentially promote myocardial repair and regeneration. A number of approaches have used engineered scaffolds to mimic the architecture of the native myocardium tissue and precisely regulate cardiac cell functions. However, previous attempts have not been able to simultaneously recapitulate chemical, mechanical, and structural properties of the myocardial extracellular matrix (ECM). In this study, we utilized an electrospinning approach to fabricate elastomeric biodegradable poly(glycerol sebacate) (PGS):gelatin nanofibrous scaffolds with a wide range of chemical composition, stiffness and anisotropy. Our findings demonstrated that through incorporation of PGS, it is possible to create nanofibrous scaffolds with well-defined anisotropy that mimic the left ventricular myocardium architecture. Furthermore, we studied attachment, proliferation, differentiation and alignment of neonatal rat cardiac fibroblast cells (CFs) as well as protein expression, alignment, and contractile function of cardiomyocyte (CMs) on PGS:gelatin scaffolds with variable amount of PGS. Notably, aligned nanofibrous scaffold, consisting of 33 wt. % PGS, induced optimal synchronous contractions of CMs while significantly enhanced cellular alignment. Overall, our study suggests that the aligned nanofibrous PGS:gelatin scaffold support cardiac cell organization, phenotype and contraction and could potentially be used to develop clinically relevant constructs for cardiac tissue engineering.

  13. Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation.

    PubMed Central

    Wikswo, J P; Lin, S F; Abbas, R A

    1995-01-01

    Traditional cable analyses cannot explain complex patterns of excitation in cardiac tissue with unipolar, extracellular anodal, or cathodal stimuli. Epifluorescence imaging of the transmembrane potential during and after stimulation of both refractory and excitable tissue shows distinctive regions of simultaneous depolarization and hyperpolarization during stimulation that act as virtual cathodes and anodes. The results confirm bidomain model predictions that the onset (make) of a stimulus induces propagation from the virtual cathode, whereas stimulus termination (break) induces it from the virtual anode. In make stimulation, the virtual anode can delay activation of the underlying tissue, whereas in break stimulation this occurs under the virtual cathode. Thus make and break stimulations in cardiac tissue have a common mechanism that is the result of differences in the electrical anisotropy of the intracellular and extracellular spaces and provides clear proof of the validity of the bidomain model. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 PMID:8599628

  14. Ultra-rapid manufacturing of engineered epicardial substitute to regenerate cardiac tissue following acute ischemic injury.

    PubMed

    Serpooshan, Vahid; Ruiz-Lozano, Pilar

    2014-01-01

    Considering the impaired regenerative capacity of adult mammalian heart tissue, cardiovascular tissue engineering aims to create functional substitutes that can restore the structure and function of the damaged cardiac tissue. The success of cardiac regenerative therapies has been limited mainly due to poor control on the structure and properties of the tissue substitute, lack of vascularization, and immunogenicity. In this study we introduce a new approach to rapidly engineer dense biomimetic scaffolds consisting of type I collagen, to protect the heart against severe ischemic injury. Scaffold biomechanical properties are adjusted to mimic embryonic epicardium which is shown to be optimal to support cardiomyocyte contractile work. Moreover, the designed patch can serve as a delivery device for targeted, controlled release of cells or therapeutic macromolecules into the lesion area.

  15. Engineered heart tissue enables study of residual undifferentiated embryonic stem cell activity in a cardiac environment.

    PubMed

    Dengler, Jana; Song, Hannah; Thavandiran, Nimalan; Massé, Stéphane; Wood, Geoffrey A; Nanthakumar, Kumaraswamy; Zandstra, Peter W; Radisic, Milica

    2011-03-01

    Embryonic stem cell (ESC) derivatives are a promising cell source for cardiac cell therapy. Mechanistic studies upon cell injection in conventional animal models are limited by inefficient delivery and poor cell survival. As an alternative, we have used an engineered heart tissue (EHT) based on neonatal rat cardiomyocytes (CMs) cultivated with electrical field stimulation as an in vitro model to study cell injection. We injected (0.001, 0.01, and 0.1 million) and tracked (by qPCR and histology) undifferentiated yellow-fluorescent protein transgenic mouse ESCs and Flk1 + /PDGFRα+ cardiac progenitor (CPs) cells, to investigate the effect of the cardiac environment on cell differentiation, as well as to test whether our in vitro model system could recapitulate the formation of teratoma-like structures commonly observed upon in vivo ESC injection. By 8 days post-injection, ESCs were spatially segregated from the cardiac cell population; however, ESC injection increased survival of CMs. The presence of ESCs blocked electrical conduction through the tissue, resulting in a 46% increase in the excitation threshold. Expression of mouse cardiac troponin I, was markedly increased in CP injected constructs compared to ESC injected constructs at all time points and cell doses tested. As early as 2 weeks, epithelial and ganglion-like structures were observed in ESC injected constructs. By 4 weeks of ESC injection, teratoma-like structures containing neural, epithelial, and connective tissue were observed in the constructs. Non-cardiac structures were observed in the CP injected constructs only after extended culture (4 weeks) and only at high cell doses, suggesting that these cells require further enrichment or differentiation prior to transplantation. Our data indicate that the cardiac environment of host tissue and electrical field stimulation did not preferentially guide the differentiation of ESCs towards the cardiac lineage. In the same environment, injection of CP

  16. Scaffold-Free Human Cardiac Tissue Patch Created from Embryonic Stem Cells

    PubMed Central

    Stevens, Kelly R.; Pabon, Lil; Muskheli, Veronica

    2009-01-01

    Progress in cardiac tissue engineering has been limited by (1) unfavorable cell and host responses to biomaterial scaffolds, (2) lack of suitable human cardiomyocyte sources, and (3) lack of fabrication techniques for scalable production of engineered tissue constructs. Here we report a novel and scalable method to generate scaffold-free human cardiac tissue patches. Human embryonic stem cells were differentiated to cardiomyocytes using activin A and BMP4 and placed into suspension on a rotating orbital shaker. Cells aggregated to form macroscopic disc-shaped patches of beating tissue after 2 days. Patch diameter was directly proportional to input cell number (approximately 11 mm with 12 million cells), and patches were 300–600 μm thick. Cardiomyocytes were concentrated around the patch edges and exhibited increased purity and maturation with time, comprising approximately 80% of total cells after 11 days. Noncardiac cell elements, primarily epithelium, were present at day 2 but were diminished markedly at later time points. Cardiomyocyte proliferation occurred throughout the patches at day 2 but declined by day 8. Patches exhibited automaticity and synchronous calcium transients, indicating electromechanical coupling. These novel scaffold-free human myocardial patches address critical challenges related to human cell sourcing and tissue fabrication that previously inhibited progress in cardiac tissue engineering. PMID:19063661

  17. Portable bioreactor for perfusion and electrical stimulation of engineered cardiac tissue

    PubMed Central

    Tandon, Nina; Taubman, Alanna; Cimetta, Elisa; Saccenti, Laetitia; Vunjak-Novakovic, Gordana

    2015-01-01

    Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Although bioreactors have facilitated the engineering of cardiac patches of clinically relevant size in vitro, a major drawback remains the transportation of the engineered tissues from a production facility to a medical operation facility while maintaining tissue viability and preventing contamination. Furthermore, after implantation, most of the cells are endangered by hypoxic conditions that exist before vascular flow is established. We developed a portable device that provides the perfusion and electrical stimulation necessary to engineer cardiac tissue in vitro, and to transport it to the site where it will be implantated. The micropump-powered perfusion apparatus may additionally function as an extracorporeal active pumping system providing nutrients and oxygen supply to the graft post-implantation. Such a system, through perfusion of oxygenated media and bioactive molecules (e.g. growth factors), could transiently support the tissue construct until it connects to the host vasculature and heart muscle, after which it could be taken away or let biodegrade. PMID:24111161

  18. Two-photon induced collagen cross-linking in bioartificial cardiac tissue

    NASA Astrophysics Data System (ADS)

    Kuetemeyer, Kai; Kensah, George; Heidrich, Marko; Meyer, Heiko; Martin, Ulrich; Gruh, Ina; Heisterkamp, Alexander

    2011-08-01

    Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs for transplantation. Besides contractile function, the stiffness of tissue engineered constructs is crucial to generate transplantable tissue surrogates with sufficient mechanical stability to withstand the high pressure present in the heart. Although several collagen cross-linking techniques have proven to be efficient in stabilizing biomaterials, they cannot be applied to cardiac tissue engineering, as cell death occurs in the treated area. Here, we present a novel method using femtosecond (fs) laser pulses to increase the stiffness of collagen-based tissue constructs without impairing cell viability. Raster scanning of the fs laser beam over riboflavin-treated tissue induced collagen cross-linking by two-photon photosensitized singlet oxygen production. One day post-irradiation, stress-strain measurements revealed increased tissue stiffness by around 40% being dependent on the fibroblast content in the tissue. At the same time, cells remained viable and fully functional as demonstrated by fluorescence imaging of cardiomyocyte mitochondrial activity and preservation of active contraction force. Our results indicate that two-photon induced collagen cross-linking has great potential for studying and improving artificially engineered tissue for regenerative therapies.

  19. The Transfer Functions of Cardiac Tissue during Stochastic Pacing

    PubMed Central

    de Lange, Enno; Kucera, Jan P.

    2009-01-01

    Abstract The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K+]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction. PMID:19134481

  20. Depth Evaluation of Soft Tissue Mimicking Phantoms Using Surface Acoustic Waves

    NASA Astrophysics Data System (ADS)

    Li, C.; Li, S.; Wei, C.; Wang, R. K.; Huang, Z.

    Surface acoustic wave (SAW) shows advantages in revealing skin mechanical properties. In this paper, we evaluates the elasticity of tissue mimicking phantoms by inversion of SAWs phase velocity to Young's Modulus, the estimated SAWs evaluating depth is determined based on the assumption of that SAWs penetration approximately equals one wavelength. The tissue mimicking phantoms are made of agar with concentration of 1%, 2% and 3%. Their elasticity tested from our system is 13.3 kPa, 53.4 kPa and 257.9 kPa respectively, with expected gradient. The evaluation depth is then estimated as 0.542 mm to 3.403 mm underneath the phantom surface, which indicates that this method is suitable to measure elasticity in dermis layer of skin.

  1. From Cardiac Tissue Engineering to Heart-on-a-Chip: Beating Challenges

    PubMed Central

    Zhang, Yu Shrike; Aleman, Julio; Arneri, Andrea; Bersini, Simone; Piraino, Francesco; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

    2015-01-01

    The heart is one of the most vital organs in the human body, which actively pumps the blood through the vascular network to supply nutrients to as well as to extract wastes from all other organs, maintaining the homeostasis of the biological system. Over the past few decades, tremendous efforts have been exerted in engineering functional cardiac tissues for heart regeneration via biomimetic approaches. More recently, progresses have been achieved towards the transformation of knowledge obtained from cardiac tissue engineering to building physiologically relevant microfluidic human heart models (i.e. heart-on-chips) for applications in drug discovery. The advancement in the stem cell technologies further provides the opportunity to create personalized in vitro models from cells derived from patients. Here starting from the heart biology, we review recent advances in engineering cardiac tissues and heart-on-a-chip platforms for their use in heart regeneration and cardiotoxic/cardiotherapeutic drug screening, and then briefly conclude with characterization techniques and personalization potential of the cardiac models. PMID:26065674

  2. Fourier transform infrared spectroscopic imaging of cardiac tissue to detect collagen deposition after myocardial infarction

    NASA Astrophysics Data System (ADS)

    Cheheltani, Rabee; Rosano, Jenna M.; Wang, Bin; Sabri, Abdel Karim; Pleshko, Nancy; Kiani, Mohammad F.

    2012-05-01

    Myocardial infarction often leads to an increase in deposition of fibrillar collagen. Detection and characterization of this cardiac fibrosis is of great interest to investigators and clinicians. Motivated by the significant limitations of conventional staining techniques to visualize collagen deposition in cardiac tissue sections, we have developed a Fourier transform infrared imaging spectroscopy (FT-IRIS) methodology for collagen assessment. The infrared absorbance band centered at 1338 cm-1, which arises from collagen amino acid side chain vibrations, was used to map collagen deposition across heart tissue sections of a rat model of myocardial infarction, and was compared to conventional staining techniques. Comparison of the size of the collagen scar in heart tissue sections as measured with this methodology and that of trichrome staining showed a strong correlation (R=0.93). A Pearson correlation model between local intensity values in FT-IRIS and immuno-histochemical staining of collagen type I also showed a strong correlation (R=0.86). We demonstrate that FT-IRIS methodology can be utilized to visualize cardiac collagen deposition. In addition, given that vibrational spectroscopic data on proteins reflect molecular features, it also has the potential to provide additional information about the molecular structure of cardiac extracellular matrix proteins and their alterations.

  3. TRPV-1-mediated elimination of residual iPS cells in bioengineered cardiac cell sheet tissues

    PubMed Central

    Matsuura, Katsuhisa; Seta, Hiroyoshi; Haraguchi, Yuji; Alsayegh, Khaled; Sekine, Hidekazu; Shimizu, Tatsuya; Hagiwara, Nobuhisa; Yamazaki, Kenji; Okano, Teruo

    2016-01-01

    The development of a suitable strategy for eliminating remaining undifferentiated cells is indispensable for the use of human-induced pluripotent stem (iPS) cell-derived cells in regenerative medicine. Here, we show for the first time that TRPV-1 activation through transient culture at 42 °C in combination with agonists is a simple and useful strategy to eliminate iPS cells from bioengineered cardiac cell sheet tissues. When human iPS cells were cultured at 42 °C, almost all cells disappeared by 48 hours through apoptosis. However, iPS cell-derived cardiomyocytes and fibroblasts maintained transcriptional and protein expression levels, and cardiac cell sheets were fabricated after reducing the temperature. TRPV-1 expression in iPS cells was upregulated at 42 °C, and iPS cell death at 42 °C was TRPV-1-dependent. Furthermore, TRPV-1 activation through thermal or agonist treatment eliminated iPS cells in cardiac tissues for a final concentration of 0.4% iPS cell contamination. These findings suggest that the difference in tolerance to TRPV-1 activation between iPS cells and iPS cell-derived cardiac cells could be exploited to eliminate remaining iPS cells in bioengineered cell sheet tissues, which will further reduce the risk of tumour formation. PMID:26888607

  4. From cardiac tissue engineering to heart-on-a-chip: beating challenges.

    PubMed

    Zhang, Yu Shrike; Aleman, Julio; Arneri, Andrea; Bersini, Simone; Piraino, Francesco; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

    2015-06-01

    The heart is one of the most vital organs in the human body, which actively pumps the blood through the vascular network to supply nutrients to as well as to extract wastes from all other organs, maintaining the homeostasis of the biological system. Over the past few decades, tremendous efforts have been exerted in engineering functional cardiac tissues for heart regeneration via biomimetic approaches. More recently, progress has been made toward the transformation of knowledge obtained from cardiac tissue engineering to building physiologically relevant microfluidic human heart models (i.e. heart-on-chips) for applications in drug discovery. The advancement in stem cell technologies further provides the opportunity to create personalized in vitro models from cells derived from patients. Here, starting from heart biology, we review recent advances in engineering cardiac tissues and heart-on-a-chip platforms for their use in heart regeneration and cardiotoxic/cardiotherapeutic drug screening, and then briefly conclude with characterization techniques and personalization potential of the cardiac models.

  5. Cardiac Meets Skeletal: What's New in Microfluidic Models for Muscle Tissue Engineering.

    PubMed

    Visone, Roberta; Gilardi, Mara; Marsano, Anna; Rasponi, Marco; Bersini, Simone; Moretti, Matteo

    2016-01-01

    In the last few years microfluidics and microfabrication technique principles have been extensively exploited for biomedical applications. In this framework, organs-on-a-chip represent promising tools to reproduce key features of functional tissue units within microscale culture chambers. These systems offer the possibility to investigate the effects of biochemical, mechanical, and electrical stimulations, which are usually applied to enhance the functionality of the engineered tissues. Since the functionality of muscle tissues relies on the 3D organization and on the perfect coupling between electrochemical stimulation and mechanical contraction, great efforts have been devoted to generate biomimetic skeletal and cardiac systems to allow high-throughput pathophysiological studies and drug screening. This review critically analyzes microfluidic platforms that were designed for skeletal and cardiac muscle tissue engineering. Our aim is to highlight which specific features of the engineered systems promoted a typical reorganization of the engineered construct and to discuss how promising design solutions exploited for skeletal muscle models could be applied to improve cardiac tissue models and vice versa. PMID:27571058

  6. MEMS scanner enabled real-time depth sensitive hyperspectral imaging of biological tissue

    PubMed Central

    Wang, Youmin; Bish, Sheldon; Tunnell, James W; Zhang, Xiaojing

    2010-01-01

    We demonstrate a hyperspectral and depth sensitive diffuse optical imaging microsystem, where fast scanning is provided by a CMOS compatible 2-axis MEMS mirror. By using lissajous scanning patterns, large field-of-view (FOV) of 1.2cm x 1.2cm images with lateral resolution of 100µm can be taken at 1.3 frames-per-second (fps). Hyperspectral and depth-sensitive images were acquired on tissue simulating phantom samples containing quantum dots (QDs) patterned at various depths in Polydimethylsiloxane (PDMS). Device performance delivers 6 nm spectral resolution and 0.43 wavelengths per second acquisition speed. A sample of porcine epithelium with subcutaneously placed QDs was also imaged. Images of the biological sample were processed by spectral unmixing in order to qualitatively separate chromophores in the final images and demonstrate spectral performance of the imaging system. PMID:21164757

  7. MEMS scanner enabled real-time depth sensitive hyperspectral imaging of biological tissue.

    PubMed

    Wang, Youmin; Bish, Sheldon; Tunnell, James W; Zhang, Xiaojing

    2010-11-01

    We demonstrate a hyperspectral and depth sensitive diffuse optical imaging microsystem, where fast scanning is provided by a CMOS compatible 2-axis MEMS mirror. By using lissajous scanning patterns, large field-of-view (FOV) of 1.2 cmx1.2 cm images with lateral resolution of 100 µm can be taken at 1.3 frames-per-second (fps). Hyperspectral and depth-sensitive images were acquired on tissue simulating phantom samples containing quantum dots (QDs) patterned at various depths in Polydimethylsiloxane (PDMS). Device performance delivers 6 nm spectral resolution and 0.43 wavelengths per second acquisition speed. A sample of porcine epithelium with subcutaneously placed QDs was also imaged. Images of the biological sample were processed by spectral unmixing in order to qualitatively separate chromophores in the final images and demonstrate spectral performance of the imaging system. PMID:21164757

  8. Determination of agar tissue phantoms depth profiles with pulsed photothermal radiometry

    NASA Astrophysics Data System (ADS)

    Milanič, Matija; Majaron, Boris; Nelson, J. Stuart

    2007-07-01

    Pulsed photothermal radiometry (PPTR) can be used for non-invasive depth profiling of skin vascular lesions (e.g., port wine stain birthmarks), aimed towards optimizing laser therapy on an individual patient basis. Optimal configuration of the experimental setup must be found and its performance characterized on samples with well defined structure, before introducing the technique into clinical practice. The aim of our study is to determine how sample structure and width of spectruml acquisition band affect the accuracy of measured depth profiles. We have constructed tissue phantoms composed of multiple layers of agar and of thin absorbing layers between the agar layers. Three phantoms had a single absorber layer at various depths between 100 and 500 μm, and one phantom had two absorber layers. In each sample we induced a non-homogeneous temperature profile with a 585 nm pulsed laser and acquired the resulting radiometric signal with a fast InSb infrared camera. We tested two configurations of the acquisition system, one using the customary 3-5 um spectruml band and one with a custom 4.5 μm cut-on filter. The laser-induced temperature depth profiles were reconstructed from measured PPTR signals using a custom algorithm and compared with sample structure as determined by histology and optical coherent tomography (OCT). PPTR determined temperature profiles correlate well with sample structure in all samples. Determination of the absorbing layer depth shows good repeatability with spatial resolution decreasing with depth. Spectruml filtering improved the accuracy of reconstructed profiles for shallow absorption layers (100-200 μm). PPTR technique enables reliable determination of structure in tissue phantoms with thin absorbing layers. Narrowing of the spectruml acquisition band (to 4.5 - 5.3 μm) improves reconstruction of objects near the surface.

  9. Functional interaction between charged nanoparticles and cardiac tissue: a new paradigm for cardiac arrhythmia?

    PubMed Central

    Ruenraroengsak, Pakatip; Shevchuk, Andrew I; Korchev, Yuri E; Lab, Max J; Tetley, Teresa D; Gorelik, Julia

    2016-01-01

    Aim To investigate the effect of surface charge of therapeutic nanoparticles on sarcolemmal ionic homeostasis and the initiation of arrhythmias. Materials & methods Cultured neonatal rat myocytes were exposed to 50 nm-charged polystyrene latex nanoparticles and examined using a combination of hopping probe scanning ion conductance microscopy, optical recording of action potential characteristics and patch clamp. Results Positively charged, amine-modified polystyrene latex nanoparticles showed cytotoxic effects and induced large-scale damage to cardiomyocyte membranes leading to calcium alternans and cell death. By contrast, negatively charged, carboxyl-modified polystyrene latex nanoparticles (NegNPs) were not overtly cytotoxic but triggered formation of 50–250-nm nanopores in the membrane. Cells exposed to NegNPs revealed pro-arrhythmic events, such as delayed afterdepolarizations, reduction in conduction velocity and pathological increment of action potential duration together with an increase in ionic current throughout the membrane, carried by the nanopores. Conclusion The utilization of charged nanoparticles is a novel concept for targeting cardiac excitability. However, this unique nanoscopic investigation reveals an altered electrophysiological substrate, which sensitized the heart cells towards arrhythmias. PMID:23140503

  10. Virtual sectioning of cardiac tissue relative to fiber orientation.

    PubMed

    Sands, Gregory B; Smaill, Bruce H; LeGrice, Ian J

    2008-01-01

    Ventricular myocardium is composed of muscle fibers organised into a complex, branching, laminar (sheet-like) structure. The fibers run approximately parallel to the epicardial wall, but their orientation relative to the circumferential axis varies transmurally, rotating from around -70 degrees at the epicardium to +70 degrees at the endocardium. This ensures that any flat transmural imaging plane or histological section contains only a partial description of myocardial architecture, as fibers intersect with the image plane at a variety of angles depending on transmural depth. We have developed a new way of viewing microstructure that accounts for this variation. Extended-volume confocal 3-D images of normal rat left-ventricular wall have previously been acquired, with an approximate size of 4x1x1 mm3. The transmural fiber rotation is measured on planes parallel to the epicardium, and used to define a curvilinear coordinate system with a transmural axis, and a second axis defined relative to the local fiber orientation. Images extracted from the image volume on curvilinear planes derived from these axes reveal a consistent view of myocardial architecture.

  11. Textile-templated electrospun anisotropic scaffolds for regenerative cardiac tissue engineering.

    PubMed

    Şenel Ayaz, H Gözde; Perets, Anat; Ayaz, Hasan; Gilroy, Kyle D; Govindaraj, Muthu; Brookstein, David; Lelkes, Peter I

    2014-10-01

    For patients with end-stage heart disease, the access to heart transplantation is limited due to the shortage of donor organs and to the potential for rejection of the donated organ. Therefore, current studies focus on bioengineering approaches for creating biomimetic cardiac patches that will assist in restoring cardiac function, by repairing and/or regenerating the intrinsically anisotropic myocardium. In this paper we present a simplified, straightforward approach for creating bioactive anisotropic cardiac patches, based on a combination of bioengineering and textile-manufacturing techniques in concert with nano-biotechnology based tissue-engineering stratagems. Using knitted conventional textiles, made of cotton or polyester yarns as template targets, we successfully electrospun anisotropic three-dimensional scaffolds from poly(lactic-co-glycolic) acid (PLGA), and thermoplastic polycarbonate-urethane (PCU, Bionate(®)). The surface topography and mechanical properties of textile-templated anisotropic scaffolds significantly differed from those of scaffolds electrospun from the same materials onto conventional 2-D flat-target electrospun scaffolds. Anisotropic textile-templated scaffolds electrospun from both PLGA and PCU, supported the adhesion and proliferation of H9C2 cardiac myoblasts cell line, and guided the cardiac tissue-like anisotropic organization of these cells in vitro. All cell-seeded PCU scaffolds exhibited mechanical properties comparable to those of a human heart, but only the cells on the polyester-templated scaffolds exhibited prolonged spontaneous synchronous contractility on the entire engineered construct for 10 days in vitro at a near physiologic frequency of ∼120 bpm. Taken together, the methods described here take advantage of straightforward established textile manufacturing strategies as an efficient and cost-effective approach to engineering 3D anisotropic, elastomeric PCU scaffolds that can serve as a cardiac patch.

  12. The role of Wnt regulation in heart development, cardiac repair and disease: A tissue engineering perspective.

    PubMed

    Pahnke, Aric; Conant, Genna; Huyer, Locke Davenport; Zhao, Yimu; Feric, Nicole; Radisic, Milica

    2016-05-01

    Wingless-related integration site (Wnt) signaling has proven to be a fundamental mechanism in cardiovascular development as well as disease. Understanding its particular role in heart formation has helped to develop pluripotent stem cell differentiation protocols that produce relatively pure cardiomyocyte populations. The resultant cardiomyocytes have been used to generate heart tissue for pharmaceutical testing, and to study physiological and disease states. Such protocols in combination with induced pluripotent stem cell technology have yielded patient-derived cardiomyocytes that exhibit some of the hallmarks of cardiovascular disease and are therefore being used to model disease states. While FDA approval of new treatments typically requires animal experiments, the burgeoning field of tissue engineering could act as a replacement. This would necessitate the generation of reproducible three-dimensional cardiac tissues in a well-controlled environment, which exhibit native heart properties, such as cellular density, composition, extracellular matrix composition, and structure-function. Such tissues could also enable the further study of Wnt signaling. Furthermore, as Wnt signaling has been found to have a mechanistic role in cardiac pathophysiology, e.g. heart attack, hypertrophy, atherosclerosis, and aortic stenosis, its strategic manipulation could provide a means of generating reproducible and specific, physiological and pathological cardiac models. PMID:26626076

  13. Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

    PubMed

    Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

    2013-09-01

    Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

  14. Myocardial Scaffold-based Cardiac Tissue Engineering: Application of Coordinated Mechanical and Electrical Stimulations

    PubMed Central

    Wang, Bo; Wang, Guangjun; To, Filip; Butler, J. Ryan; Claude, Andrew; McLaughlin, Ronald M.; Williams, Lakiesha N.; de Jongh Curry, Amy L.; Liao, Jun

    2013-01-01

    Recently, we have developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserved natural extracellular matrix structure, mechanical anisotropy, and vasculature templates, and also showed good cell recellularization and differentiation potential. In this study, a multi-stimulation bioreactor was built to provide coordinated mechanical and electrical stimulations for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (106 cells/ml) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that, after 2-day culture with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed cardiomyocyte-like phenotype, by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2-day bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2-day and 4-day tissue constructs were comparable to the tissue constructs produced by stirring reseeding followed by 2-week static culture, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development, but also for patients by reducing the waiting time in future clinical scenarios. PMID:23923967

  15. Human induced pluripotent stem cell-derived beating cardiac tissues on paper.

    PubMed

    Wang, Li; Xu, Cong; Zhu, Yujuan; Yu, Yue; Sun, Ning; Zhang, Xiaoqing; Feng, Ke; Qin, Jianhua

    2015-11-21

    There is a growing interest in using paper as a biomaterial scaffold for cell-based applications. In this study, we made the first attempt to fabricate a paper-based array for the culture, proliferation, and direct differentiation of human induced pluripotent stem cells (hiPSCs) into functional beating cardiac tissues and create "a beating heart on paper." This array was simply constructed by binding a cured multi-well polydimethylsiloxane (PDMS) mold with common, commercially available paper substrates. Three types of paper material (print paper, chromatography paper and nitrocellulose membrane) were tested for adhesion, proliferation and differentiation of human-derived iPSCs. We found that hiPSCs grew well on these paper substrates, presenting a three-dimensional (3D)-like morphology with a pluripotent property. The direct differentiation of human iPSCs into functional cardiac tissues on paper was also achieved using our modified differentiation approach. The cardiac tissue retained its functional activities on the coated print paper and chromatography paper with a beating frequency of 40-70 beats per min for up to three months. Interestingly, human iPSCs could be differentiated into retinal pigment epithelium on nitrocellulose membrane under the conditions of cardiac-specific induction, indicating the potential roles of material properties and mechanical cues that are involved in regulating stem cell differentiation. Taken together, these results suggest that different grades of paper could offer great opportunities as bioactive, low-cost, and 3D in vitro platforms for stem cell-based high-throughput drug testing at the tissue/organ level and for tissue engineering applications.

  16. Isolation, characterization and cardiac differentiation of human thymus tissue derived mesenchymal stromal cells.

    PubMed

    Lin, Ze Bang; Qian, Bo; Yang, Yu Zhong; Zhou, Kai; Sun, Jian; Mo, Xu Ming; Wu, Kai Hong

    2015-07-01

    Mesenchymal stromal cells (MSCs) are promising candidate donor cells for replacement of cardiomyocyte loss during ischemia and in vitro generation of myocardial tissue. We have successfully isolated MSCs from the discarded neonatal thymus gland during cardiac surgery. The thymus MSCs were characterized by cell-surface antigen expression. These cells have high ability for proliferation and are able to differentiate into osteoblasts and adipocytes in vitro. For cardiac differentiation, the cells were divided into 3 groups: untreated control; 5-azacytidine group and sequential exposure to 5-azacytidine, bone morphogenetic protein 4, and basic fibroblast growth factor. Thymus MSCs showed a fibrolast-like morphology and some differentiated cells increased in size, formed a ball-like appearance over time and spontaneously contracting cells were observed in sequential exposure group. Immunostaining studies, cardiac specific genes/protein expression confirmed the cardiomyocyte phenotype of the differentiated cells. These results demonstrate that thymus MSCs can be a promising cellular source for cardiac cell therapy and tissue engineering.

  17. In vivo facial tissue depth for Canadian Mi'kmaq adults: a case study from Nova Scotia, Canada.

    PubMed

    Peckmann, Tanya R; Harris, Mikkel; Huculak, Meaghan; Pringle, Ashleigh; Fournier, Michel

    2015-01-01

    This study examines facial tissue depth in Canadian Mi'kmaq adults. Using ultrasound, measurements were taken at 19 landmarks on the faces of 152 individuals aged 18-75 years old. The relationships between tissue thickness, age, and sex were investigated. A positive linear trend exists between tissue thickness and age for Mi'kmaq males and females at multiple landmarks. Seven landmarks show significant differences in facial tissue depth between males and females aged 18-34 years old; no landmarks show significant differences in facial tissue depth between males and females aged 35-45 years old and 46-55 years old. Significant differences were shown in facial tissue depth between Mi'kmaq and White Americans and Mi'kmaq and African Americans. These data can assist in 3-D facial reconstructions and aid in establishing the identity of unknown Mi'kmaq individuals.

  18. Sudden cardiac death in hemodialysis patients: an in-depth review.

    PubMed

    Green, Darren; Roberts, Paul R; New, David I; Kalra, Philip A

    2011-06-01

    Sudden cardiac death (SCD) is the leading cause of death in hemodialysis patients, accounting for death in up to one-quarter of this population. Unlike in the general population, coronary artery disease and heart failure often are not the underlying pathologic processes for SCD; accordingly, current risk stratification tools are inadequate when assessing these patients. Factors assuming greater importance in hemodialysis patients may include left ventricular hypertrophy, electrolyte shift, and vascular calcification. Knowledge regarding SCD in hemodialysis patients is insufficient, in part reflecting the lack of an agreed-on definition of SCD in this population, although epidemiologic studies suggest the most common times for SCD to occur are toward the end of the long 72-hour weekend interval between dialysis sessions and in the 12 hours immediately after hemodialysis. Accordingly, it is hypothesized that the dialysis procedure itself may have important implications for SCD. Supporting this is recognition that hemodialysis is associated with both ventricular arrhythmias and dynamic electrocardiographic changes. Importantly, echocardiography and electrocardiography may show changes that are modifiable by alterations to dialysis prescription. The most effective preventative strategy in the general population, implanted cardioverter-defibrillator devices, are less effective in the presence of chronic kidney disease and have not been studied adequately in dialysis patients. Last, many dialysis patients experience SCD despite not fulfilling current criteria for implantation, making appropriate allocation of defibrillators uncertain.

  19. Strategies for tissue engineering cardiac constructs to affect functional repair following myocardial infarction.

    PubMed

    Ye, Kathy Yuan; Black, Lauren Deems

    2011-10-01

    Tissue-engineered cardiac constructs are a high potential therapy for treating myocardial infarction. These therapies have the ability to regenerate or recreate functional myocardium following the infarction, restoring some of the lost function of the heart and thereby preventing congestive heart failure. Three key factors to consider when developing engineered myocardial tissue include the cell source, the choice of scaffold, and the use of biomimetic culture conditions. This review details the various biomaterials and scaffold types that have been used to generate engineered myocardial tissues as well as a number of different methods used for the fabrication and culture of these constructs. Specific bioreactor design considerations for creating myocardial tissue equivalents in vitro, such as oxygen and nutrient delivery as well as physical stimulation, are also discussed. Lastly, a brief overview of some of the in vivo studies that have been conducted to date and their assessment of the functional benefit in repairing the injured heart with engineered myocardial tissue is provided.

  20. Three-dimensional cardiac tissue engineering using a thermoresponsive artificial extracellular matrix.

    PubMed

    Naito, Hiroshi; Takewa, Yoshiaki; Mizuno, Toshihide; Ohya, Shoji; Nakayama, Yasuhide; Tatsumi, Eisuke; Kitamura, Soichiro; Takano, Hisateru; Taniguchi, Shigeki; Taenaka, Yoshiyuki

    2004-01-01

    The purpose of this study was to try to reconstitute three-dimensional cardiac tissue using a thermoresponsive artificial extracellular matrix, poly (N-isopropylacrylamide)-grafted gelatin (PNIPAM-gelatin), as the scaffold. PNIPAM-gelatin solution gels almost immediately when heated above 34 degrees C. We thought this property could become advantageous as scaffolding for reconstituting three-dimensional tissue. Because PNIPAM-gelatin solution gels so quickly, all seeded cells in PNIPAM-gelatin solution would become entrapped and uniformly distributed toward three dimensions. Thus it would be possible to reconstitute three-dimensional tissue by a very simple method of mixing cells and PNIPAM-gelatin solution. Fetal rat cardiac cells were mixed with PNIPAM-gelatin solution, incubated at 37 degrees C to allow the mixture to gel, and cultured in vitro. To define suitable culture conditions the following parameters were tested: (1) PNIPAM-gelatin concentration, 0.04 approximately 0.125 mg/ml; (2) cell seeding density, 1 approximately 50 x 10(6) cells/ml; and (3) addition or not of hyaluronic acid. With a PNIPAM-gelatin concentration of 0.05 mg/ml, a cell seeding density of 50 x 10(6) cells/ml, and the addition of hyaluronic acid, tissue was reconstituted and it contracted synchronously. After hematoxylin and eosin staining, the cells reconstituted three-dimensional tissue, and the tissue cross-section was approximately 60 microm thick.

  1. Simulation of a plane wavefront propagating in cardiac tissue using a cellular automata model.

    PubMed

    Barbosa, Carlos R Hall

    2003-12-21

    We present a detailed description of a cellular automata model for the propagation of action potential in a planar cardiac tissue, which is very fast and easy to use. The model incorporates anisotropy in the electrical conductivity and a spatial variation of the refractory time. The transmembrane potential distribution is directly derived from the cell states, and the intracellular and extracellular potential distributions are calculated for the particular case of a plane wavefront. Once the potential distributions are known, the associated current densities are calculated by Ohm's law, and the magnetic field is determined at a plane parallel to the cardiac tissue by applying the law of Biot and Savart. The results obtained for propagation speed and for magnetic field amplitude with the cellular automata model are compared with values predicted by the bidomain formulation, for various angles between wavefront propagation and fibre direction, characterizing excellent agreement between the models.

  2. The effects of depth on the cardiac and behavioural responses of double-crested cormorants (Phalacrocorax auritus) during voluntary diving.

    PubMed

    Enstipp, M R; Andrews, R D; Jones, D R

    2001-12-01

    Heart rate and dive behaviour were monitored in double-crested cormorants (Phalacrocorax auritus) during shallow (1 m) and deep diving (12 m), after breathing different gas mixtures, to investigate the role of depth and the accompanying changes in blood gas levels in cardiac and behavioural control during voluntary diving. Pre-dive heart rate in both shallow- and deep-diving birds was approximately three times the resting heart rate (137.9+/-17.5 beats min(-1); mean +/- S.D., N=5), falling abruptly upon submersion to around 200-250 beats min(-1). During shallow diving, the initial reduction in heart rate was followed by a secondary, more gradual decline, to around the resting level. In contrast, during deep diving, heart rate stabilised at 200-250 beats min(-1). In dives of similar duration, mean dive heart rate was significantly lower during shallow diving (163.2+/-14.0 beats min(-1)) than during deep diving (216.4+/-7.7 beats min(-1)), but in both cases was significantly above the resting value. The difference in cardiac response is probably due to an increase in arterial oxygen tension (Pa(O(2))) during the descent phase of deep dives (compression hyperoxia). Exposure to a hyperoxic gas mixture before shallow diving significantly increased mean dive heart rate, while exposure to a hypoxic gas mixture in both the shallow and deep dive tanks significantly reduced mean dive heart rate. In contrast, breathing hypercapnic gas before diving had no significant effect on dive heart rate. We suggest that the cardiac response to voluntary diving in double-crested cormorants is strongly influenced by changes in blood oxygen levels throughout the dive. Dive duration was unaffected by alterations in inspired gas composition, but surface interval duration decreased during hyperoxic gas exposure and increased during hypoxic gas exposure. The most efficient dive pattern (highest dive/pause ratio) was observed after hyperoxic exposure. Our study suggests that blood oxygen level

  3. Effect of Head Position on Facial Soft Tissue Depth Measurements Obtained Using Computed Tomography.

    PubMed

    Caple, Jodi M; Stephan, Carl N; Gregory, Laura S; MacGregor, Donna M

    2016-01-01

    Facial soft tissue depth (FSTD) studies employing clinical computed tomography (CT) data frequently rely on depth measurements from raw 2D orthoslices. However, the position of each patient's head was not standardized in this method, potentially decreasing measurement reliability and accuracy. This study measured FSTDs along the original orthoslice plane and compared these measurements to those standardized by the Frankfurt horizontal (FH). Subadult cranial CT scans (n = 115) were used to measure FSTDs at 18 landmarks. Significant differences were observed between the methods at eight of these landmarks (p < 0.05), demonstrating that high-quality data are not generated simply by employing modern imaging modalities such as CT. Proper technique is crucial to useful results, and maintaining control over head position during FSTD data collection is important. This is easily and most readily achieved in CT techniques by rotating the head to the FH plane after constructing a 3D rendering of the data.

  4. Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators

    NASA Technical Reports Server (NTRS)

    Belaguli, N. S.; Sepulveda, J. L.; Nigam, V.; Charron, F.; Nemer, M.; Schwartz, R. J.

    2000-01-01

    Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts. In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal alpha-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRF-dependent gene expression.

  5. Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture

    PubMed Central

    Feinberg, Adam W.; Alford, Patrick W.; Jin, Hongwei; Ripplinger, Crystal M.; Werdich, Andreas A.; Sheehy, Sean P.; Grosberg, Anna; Parker, Kevin Kit

    2014-01-01

    The heart is a muscular organ with a wrapping, laminar structure embedded with neural and vascular networks, collagen fibrils, fibroblasts, and cardiac myocytes that facilitate contraction. We hypothesized that these non-muscle components may have functional benefit, serving as important structural alignment cues in inter- and intra-cellular organization of cardiac myocytes. Previous studies have demonstrated that alignment of engineered myocardium enhances calcium handling, but how this impacts actual force generation remains unclear. Quantitative assays are needed to determine the effect of alignment on contractile function and muscle physiology. To test this, micropatterned surfaces were used to build 2-dimensional myocardium from neonatal rat ventricular myocytes with distinct architectures: confluent isotropic (serving as the unaligned control), confluent anisotropic, and 20 μm spaced, parallel arrays of multicellular myocardial fibers. We combined image analysis of sarcomere orientation with muscular thin film contractile force assays in order to calculate the peak sarcomere-generated stress as a function of tissue architecture. Here we report that increasing peak systolic stress in engineered cardiac tissues corresponds with increasing sarcomere alignment. This change is larger than would be anticipated from enhanced calcium handling and increased uniaxial alignment alone. These results suggest that boundary conditions (heterogeneities) encoded in the extracellular space can regulate muscle tissue function, and that structural organization and cytoskeletal alignment are critically important for maximizing peak force generation. PMID:22594976

  6. Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture.

    PubMed

    Feinberg, Adam W; Alford, Patrick W; Jin, Hongwei; Ripplinger, Crystal M; Werdich, Andreas A; Sheehy, Sean P; Grosberg, Anna; Parker, Kevin Kit

    2012-08-01

    The heart is a muscular organ with a wrapping, laminar structure embedded with neural and vascular networks, collagen fibrils, fibroblasts, and cardiac myocytes that facilitate contraction. We hypothesized that these non-muscle components may have functional benefit, serving as important structural alignment cues in inter- and intra-cellular organization of cardiac myocytes. Previous studies have demonstrated that alignment of engineered myocardium enhances calcium handling, but how this impacts actual force generation remains unclear. Quantitative assays are needed to determine the effect of alignment on contractile function and muscle physiology. To test this, micropatterned surfaces were used to build 2-dimensional myocardium from neonatal rat ventricular myocytes with distinct architectures: confluent isotropic (serving as the unaligned control), confluent anisotropic, and 20 μm spaced, parallel arrays of multicellular myocardial fibers. We combined image analysis of sarcomere orientation with muscular thin film contractile force assays in order to calculate the peak sarcomere-generated stress as a function of tissue architecture. Here we report that increasing peak systolic stress in engineered cardiac tissues corresponds with increasing sarcomere alignment. This change is larger than would be anticipated from enhanced calcium handling and increased uniaxial alignment alone. These results suggest that boundary conditions (heterogeneities) encoded in the extracellular space can regulate muscle tissue function, and that structural organization and cytoskeletal alignment are critically important for maximizing peak force generation.

  7. Cardiac adipose tissue and its relationship to diabetes mellitus and cardiovascular disease

    PubMed Central

    Noyes, Adam M; Dua, Kirandeep; Devadoss, Ramprakash; Chhabra, Lovely

    2014-01-01

    Type-2 diabetes mellitus (T2DM) plays a central role in the development of cardiovascular disease (CVD). However, its relationship to epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) in particular is important in the pathophysiology of coronary artery disease. Owing to its close proximity to the heart and coronary vasculature, EAT exerts a direct metabolic impact by secreting proinflammatory adipokines and free fatty acids, which promote CVD locally. In this review, we have discussed the relationship between T2DM and cardiac fat deposits, particularly EAT and PAT, which together exert a big impact on the cardiovascular health. PMID:25512789

  8. Wheat Germ Agglutinin Staining as a Suitable Method for Detection and Quantification of Fibrosis in Cardiac Tissue after Myocardial Infarction

    PubMed Central

    Emde, B.; Heinen, A.; Gödecke, A.; Bottermann, K.

    2014-01-01

    The quantification of fibrotic tissue is an important task in the analysis of cardiac remodeling. The use of established fibrosis staining techniques is limited on frozen cardiac tissue sections due to a reduced color contrast compared to paraffin embedded sections. We therefore used FITC-labeled wheat germ agglutinin (WGA), which marks fibrotic tissue in comparable quality as the established picrosirius red (SR) staining, for the staining of post myocardial infarction scar tissue. The fibrosis amount was quantified in a histogram-based approach using the non-commercial image processing program ImageJ. Our results clearly demonstrate that WGA-FITC is a suitable marker for cardiac fibrosis in frozen tissue sections. In combination with the histogram-based analysis, this new quantification approach is i) easy and fast to perform; ii) suitable for raw frozen tissue sections; and iii) allows the use of additional antibodies in co-immunostaining. PMID:25578975

  9. Evidence for a Border-Collision Bifurcation in Paced Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Berger, Carolyn

    2005-11-01

    Bifurcations in the electrical response of cardiac tissue can destabilize spatial-temporal waves of electrical activity in the heart, leading to tachycardia or even fibrillation. Therefore, it is important to characterize the types of bifurcations occurring in cardiac tissue. Our goal is to classify the bifurcation that occurs in cardiac cells when a change in pacing rate induces a transition from 1:1 to 2:2 phase-locked behavior. Current mathematical models predict that the bifurcation mediating the transition is a supercritical pitchfork type. For such a bifurcation, small random noise is predicted to be amplified by greater amounts as the bifurcation is approached (Weisenfeld). However, our experimental observations of paced bullfrog myocardium driven by small beat-to-beat alternations in the pacing rate (rather than driven by noise) displays de-amplification as the bifurcation is approached. To explain this surprising result, we hypothesize that the transition to 2:2 behavior is mediated by border-collision bifurcation, which is predicted to show little noise amplification. Wiesenfeld, K. Phys. Rev. A 32, 1744 (1985).

  10. The induction of reentry in cardiac tissue. The missing link: How electric fields alter transmembrane potential

    NASA Astrophysics Data System (ADS)

    Roth, Bradley J.; Krassowska, Wanda

    1998-03-01

    This review examines the initiation of reentry in cardiac muscle by strong electric shocks. Specifically, it concentrates on the mechanisms by which electric shocks change the transmembrane potential of the cardiac membrane and create the physiological substrate required by the critical point theory for the initiation of rotors. The mechanisms examined include (1) direct polarization of the tissue by the stimulating current, as described by the one-dimensional cable model and its two- and three-dimensional extensions, (2) the presence of virtual anodes and cathodes, as described by the bidomain model with unequal anisotropy ratios of the intra- and extracellular spaces, (3) polarization of the tissue due to changing orientation of cardiac fibers, and (4) polarization of individual cells or groups of cells by the electric field ("sawtooth potential"). The importance of these mechanisms in the initiation of reentry is examined in two case studies: the induction of rotors using successive stimulation with a unipolar electrode, and the induction of rotors using cross-field stimulation. These cases reveal that the mechanism by which a unipolar stimulation induces arrhythmias can be explained in the framework of the bidomain model with unequal anisotropy ratios. In contrast, none of the examined mechanisms provide an adequate explanation for the induction of rotors by cross-field stimulation. Hence, this study emphasizes the need for further experimental and theoretical work directed toward explaining the mechanism of field stimulation.

  11. Time Dependence of Anodal and Cathodal Refractory Periods in Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Bennett, Jonathan A.; Roth, Bradley J.

    1997-11-01

    Cathodal and anodal make and break excitation have been observed in cardiac tissue. Make excitation occurs when a stimulus pulse is turned on and has a lower threshold than break excitation, which occurs when a stimulus pulse is turned off. Mehra et al. (PACE 3:526) observed that over time the anodal refractory period (RP) becomes longer than the cathodal RP. After implantation, damaged tissue accumulates around the electrode, thereby increasing its effective surface area. We investigate this time-dependent change numerically by stimulating cardiac tissue using small and large electrodes. The tissue is represented as a bidomain with a Beeler-Reuter membrane. Like Mehra et al., we define the RP to be the threshold interval at a strength of 8 mA. The anodal RP is longer than the cathodal RP for the large electrode, whereas it is shorter for the small electrode. However, anode break threshold for the small electrode is less than 8 mA, but for the large electrode it is greater than 8 mA. The lengthening of the anodal RP is caused by excluding the anode break excitation with the larger electrode. This result is consistent with Mehra et al., and suggests that their observation resulted from their definition of RP.

  12. In vivo measurement of levofloxacin penetration into lung tissue after cardiac surgery.

    PubMed

    Hutschala, Doris; Skhirtladze, Keso; Zuckermann, Andreas; Wisser, Wilfried; Jaksch, Peter; Mayer-Helm, Bernhard Xaver; Burgmann, Heinz; Wolner, Ernst; Müller, Markus; Tschernko, Edda M

    2005-12-01

    Nosocomial pneumonia is a severe complication after cardiac surgery (CS). Levofloxacin, a fluoroquinolone, qualifies for the therapy of postoperative pneumonia. However, penetration properties of levofloxacin into the lung tissue could be substantially affected by CS: atelectasis, low cardiac output after CS, high volume loads, and inflammatory capillary leak potentially influence drug distribution. The aim of our study was to gain information on interstitial antibiotic concentrations in lung tissue in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Therefore, six patients undergoing elective CS participated in this prospective study. A dose of 500 mg of levofloxacin was administered intravenously in addition to standard antibiotic prophylaxis immediately after the end of surgery. Time versus concentration profiles of levofloxacin in the interstitial lung tissue and plasma were determined. A microdialysis technique was used for lung interstitial concentration measurements. The microdialysis procedure was well tolerated in all patients and no adverse events were observed. The median area under the concentration curve (AUC) of levofloxacin in interstitial lung fluid was 18.6 microg.h/ml (range, 10.1 to 33.6). The median AUC for tissue (AUC(tissue)) of unbound levofloxacin/AUC(total) in plasma was 0.6 (range, 0.4 to 0.9). The median unbound AUC(tissue)/MIC was 2.4 (range, 1.3 to 4.2) for Pseudomonas aeruginosa. Our study demonstrated the feasibility and safety of microdialysis in human lung tissue in vivo after CS. The unbound AUC/MIC ratio revealed that levofloxacin used in the described manner was borderline sufficient for the treatment of nosocomial pneumonia caused by Klebsiella pneumoniae and insufficient for the treatment of pneumonia caused by Pseudomonas aeruginosa, because the breakpoint of 30 to 40 for AUC/MIC could not be reached by the conventionally used dosage schema in our post-CS setting. Penetration was lower than in

  13. A generalized activating function for predicting virtual electrodes in cardiac tissue.

    PubMed Central

    Sobie, E A; Susil, R C; Tung, L

    1997-01-01

    To fully understand the mechanisms of defibrillation, it is critical to know how a given electrical stimulus causes membrane polarizations in cardiac tissue. We have extended the concept of the activating function, originally used to describe neuronal stimulation, to derive a new expression that identifies the sources that drive changes in transmembrane potential. Source terms, or virtual electrodes, consist of either second derivatives of extracellular potential weighted by intracellular conductivity or extracellular potential gradients weighted by derivatives of intracellular conductivity. The full response of passive tissue can be considered, in simple cases, to be a convolution of this "generalized activating function" with the impulse response of the tissue. Computer simulations of a two-dimensional sheet of passive myocardium under steady-state conditions demonstrate that this source term is useful for estimating the effects of applied electrical stimuli. The generalized activating function predicts oppositely polarized regions of tissue when unequally anisotropic tissue is point stimulated and a monopolar response when a point stimulus is applied to isotropic tissue. In the bulk of the myocardium, this new expression is helpful for understanding mechanisms by which virtual electrodes can be produced, such as the hypothetical "sawtooth" pattern of polarization, as well as polarization owing to regions of depressed conductivity, missing cells or clefts, changes in fiber diameter, or fiber curvature. In comparing solutions obtained with an assumed extracellular potential distribution to those with fully coupled intra- and extracellular domains, we find that the former provides a reliable estimate of the total solution. Thus the generalized activating function that we have derived provides a useful way of understanding virtual electrode effects in cardiac tissue. Images FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 6 PMID:9284308

  14. Effect of Twisted Fiber Anisotropy in Cardiac Tissue on Ablation with Pulsed Electric Fields

    PubMed Central

    Xie, Fei; Zemlin, Christian W.

    2016-01-01

    Background Ablation of cardiac tissue with pulsed electric fields is a promising alternative to current thermal ablation methods, and it critically depends on the electric field distribution in the heart. Methods We developed a model that incorporates the twisted anisotropy of cardiac tissue and computed the electric field distribution in the tissue. We also performed experiments in rabbit ventricles to validate our model. We find that the model agrees well with the experimentally determined ablation volume if we assume that all tissue that is exposed to a field greater than 3 kV/cm is ablated. In our numerical analysis, we considered how tissue thickness, degree of anisotropy, and electrode configuration affect the geometry of the ablated volume. We considered two electrode configurations: two parallel needles inserted into the myocardium (“penetrating needles” configuration) and one circular electrode each on epi- and endocardium, opposing each other (“epi-endo” configuration). Results For thick tissues (10 mm) and moderate anisotropy ratio (a = 2), we find that the geometry of the ablated volume is almost unaffected by twisted anisotropy, i.e. it is approximately translationally symmetric from epi- to endocardium, for both electrode configurations. Higher anisotropy ratio (a = 10) leads to substantial variation in ablation width across the wall; these variations were more pronounced for the penetrating needle configuration than for the epi-endo configuration. For thinner tissues (4 mm, typical for human atria) and higher anisotropy ratio (a = 10), the epi-endo configuration yielded approximately translationally symmetric ablation volumes, while the penetrating electrodes configuration was much more sensitive to fiber twist. Conclusions These results suggest that the epi-endo configuration will be reliable for ablation of atrial fibrillation, independently of fiber orientation, while the penetrating electrode configuration may experience problems when the

  15. Unidirectional Pinning and Hysteresis of Spatially Discordant Alternans in Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Skardal, Per Sebastian; Karma, Alain; Restrepo, Juan G.

    2012-03-01

    Spatially discordant alternans is a widely observed pattern of voltage and calcium signals in cardiac tissue that can precipitate lethal cardiac arrhythmia. Using spatially coupled iterative maps of the beat-to-beat dynamics, we explore this pattern’s dynamics in the regime of a calcium-dominated period-doubling instability at the single-cell level. We find a novel nonlinear bifurcation associated with the formation of a discontinuous jump in the amplitude of calcium alternans at nodes separating discordant regions. We show that this jump unidirectionally pins nodes by preventing their motion away from the pacing site following a pacing rate decrease but permitting motion towards this site following a rate increase. This unidirectional pinning leads to strongly history-dependent node motion that is strongly arrhythmogenic.

  16. Wave trains induced by circularly polarized electric fields in cardiac tissues.

    PubMed

    Feng, Xia; Gao, Xiang; Tang, Juan-Mei; Pan, Jun-Ting; Zhang, Hong

    2015-01-01

    Clinically, cardiac fibrillation caused by spiral and turbulent waves can be terminated by globally resetting electric activity in cardiac tissues with a single high-voltage electric shock, but it is usually associated with severe side effects. Presently, a promising alternative uses wave emission from heterogeneities induced by a sequence of low-voltage uniform electric field pulses. Nevertheless, this method can only emit waves locally near obstacles in turbulent waves and thereby requires multiple obstacles to globally synchronize myocardium and thus to terminate fibrillation. Here we propose a new approach using wave emission from heterogeneities induced by a low-voltage circularly polarized electric field (i.e., a rotating uniform electric field). We find that, this approach can generate circular wave trains near obstacles and they propagate outwardly. We study the characteristics of such circular wave trains and further find that, the higher-frequency circular wave trains can effectively suppress spiral turbulence.

  17. Wave trains induced by circularly polarized electric fields in cardiac tissues

    PubMed Central

    Feng, Xia; Gao, Xiang; Tang, Juan-Mei; Pan, Jun-Ting; Zhang, Hong

    2015-01-01

    Clinically, cardiac fibrillation caused by spiral and turbulent waves can be terminated by globally resetting electric activity in cardiac tissues with a single high-voltage electric shock, but it is usually associated with severe side effects. Presently, a promising alternative uses wave emission from heterogeneities induced by a sequence of low-voltage uniform electric field pulses. Nevertheless, this method can only emit waves locally near obstacles in turbulent waves and thereby requires multiple obstacles to globally synchronize myocardium and thus to terminate fibrillation. Here we propose a new approach using wave emission from heterogeneities induced by a low-voltage circularly polarized electric field (i.e., a rotating uniform electric field). We find that, this approach can generate circular wave trains near obstacles and they propagate outwardly. We study the characteristics of such circular wave trains and further find that, the higher-frequency circular wave trains can effectively suppress spiral turbulence. PMID:26302781

  18. Fibroblast–myocyte electrotonic coupling: Does it occur in native cardiac tissue?☆

    PubMed Central

    Kohl, Peter; Gourdie, Robert G.

    2014-01-01

    Heterocellular electrotonic coupling between cardiac myocytes and non-excitable connective tissue cells has been a long-established and well-researched fact in vitro. Whether or not such coupling exists in vivo has been a matter of considerable debate. This paper reviews the development of experimental insight and conceptual views on this topic, describes evidence in favour of and against the presence of such coupling in native myocardium, and identifies directions for further study needed to resolve the riddle, perhaps less so in terms of principal presence which has been demonstrated, but undoubtedly in terms of extent, regulation, patho-physiological context, and actual relevance of cardiac myocyte–non-myocyte coupling in vivo. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium." PMID:24412581

  19. Vascularization strategies of engineered tissues and their application in cardiac regeneration.

    PubMed

    Sun, Xuetao; Altalhi, Wafa; Nunes, Sara S

    2016-01-15

    The primary function of vascular networks is to transport blood and deliver oxygen and nutrients to tissues, which occurs at the interface of the microvasculature. Therefore, the formation of the vessels at the microcirculatory level, or angiogenesis, is critical for tissue regeneration and repair. Current strategies for vascularization of engineered tissues have incorporated multi-disciplinary approaches including engineered biomaterials, cells and angiogenic factors. Pre-vascularization of scaffolds composed of native matrix, synthetic polymers, or other biological materials can be achieved through the use of single cells in mono or co-culture, in combination or not with angiogenic factors or by the use of isolated vessels. The advance of these methods, together with a growing understanding of the biology behind vascularization, has facilitated the development of vascularization strategies for engineered tissues with therapeutic potential for tissue regeneration and repair. Here, we review the different cell-based strategies utilized to pre-vascularize engineered tissues and in making more complex vascularized cardiac tissues for regenerative medicine applications.

  20. Ensembles of engineered cardiac tissues for physiological and pharmacological study: Heart on a chip†‡

    PubMed Central

    Grosberg, Anna; Alford, Patrick W.; McCain, Megan L.; Parker, Kevin Kit

    2014-01-01

    Traditionally, muscle physiology experiments require multiple tissue samples to obtain morphometric, electrophysiological, and contractility data. Furthermore, these experiments are commonly completed one at a time on cover slips of single cells, isotropic monolayers, or in isolated muscle strips. In all of these cases, variability of the samples hinders quantitative comparisons among experimental groups. Here, we report the design of a “heart on a chip” that exploits muscular thin film technology – biohybrid constructs of an engineered, anisotropic ventricular myocardium on an elastomeric thin film – to measure contractility, combined with a quantification of action potential propagation, and cytoskeletal architecture in multiple tissues in the same experiment. We report techniques for real-time data collection and analysis during pharmacological intervention. The chip is an efficient means of measuring structure-function relationships in constructs that replicate the hierarchical tissue architectures of laminar cardiac muscle. PMID:22072288

  1. "The state of the heart": Recent advances in engineering human cardiac tissue from pluripotent stem cells.

    PubMed

    Sirabella, Dario; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2015-08-01

    The pressing need for effective cell therapy for the heart has led to the investigation of suitable cell sources for tissue replacement. In recent years, human pluripotent stem cell research expanded tremendously, in particular since the derivation of human-induced pluripotent stem cells. In parallel, bioengineering technologies have led to novel approaches for in vitro cell culture. The combination of these two fields holds potential for in vitro generation of high-fidelity heart tissue, both for basic research and for therapeutic applications. However, this new multidisciplinary science is still at an early stage. Many questions need to be answered and improvements need to be made before clinical applications become a reality. Here we discuss the current status of human stem cell differentiation into cardiomyocytes and the combined use of bioengineering approaches for cardiac tissue formation and maturation in developmental studies, disease modeling, drug testing, and regenerative medicine.

  2. Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip.

    PubMed

    Grosberg, Anna; Alford, Patrick W; McCain, Megan L; Parker, Kevin Kit

    2011-12-21

    Traditionally, muscle physiology experiments require multiple tissue samples to obtain morphometric, electrophysiological, and contractility data. Furthermore, these experiments are commonly completed one at a time on cover slips of single cells, isotropic monolayers, or in isolated muscle strips. In all of these cases, variability of the samples hinders quantitative comparisons among experimental groups. Here, we report the design of a "heart on a chip" that exploits muscular thin film technology--biohybrid constructs of an engineered, anisotropic ventricular myocardium on an elastomeric thin film--to measure contractility, combined with a quantification of action potential propagation, and cytoskeletal architecture in multiple tissues in the same experiment. We report techniques for real-time data collection and analysis during pharmacological intervention. The chip is an efficient means of measuring structure-function relationships in constructs that replicate the hierarchical tissue architectures of laminar cardiac muscle.

  3. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    PubMed Central

    Lasher, Richard A; Pahnke, Aric Q; Johnson, Jeffrey M; Sachse, Frank B

    2012-01-01

    Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06) but less than half of the native postnatal day 12 (0.90 ± 0.06) and adult (0.91 ± 0.04) myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal that the

  4. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

    PubMed

    Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease. PMID:26808149

  5. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

    PubMed

    Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

  6. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy

    PubMed Central

    Huang, Chao; Sachse, Frank B.; Hitchcock, Robert W.; Kaza, Aditya K.

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2±0.3% and 98.0±0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2±0.3% and 94.0±2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease. PMID:26808149

  7. Pushing the envelope in tissue engineering: ex vivo production of thick vascularized cardiac extracellular matrix constructs.

    PubMed

    Sarig, Udi; Nguyen, Evelyne Bao-Vi; Wang, Yao; Ting, Sherwin; Bronshtein, Tomer; Sarig, Hadar; Dahan, Nitsan; Gvirtz, Maskit; Reuveny, Shaul; Oh, Steve K W; Scheper, Thomas; Boey, Yin Chiang Freddy; Venkatraman, Subbu S; Machluf, Marcelle

    2015-05-01

    Functional vascularization is a prerequisite for cardiac tissue engineering of constructs with physiological thicknesses. We previously reported the successful preservation of main vascular conduits in isolated thick acellular porcine cardiac ventricular ECM (pcECM). We now unveil this scaffold's potential in supporting human cardiomyocytes and promoting new blood vessel development ex vivo, providing long-term cell support in the construct bulk. A custom-designed perfusion bioreactor was developed to remodel such vascularization ex vivo, demonstrating, for the first time, functional angiogenesis in vitro with various stages of vessel maturation supporting up to 1.7 mm thick constructs. A robust methodology was developed to assess the pcECM maximal cell capacity, which resembled the human heart cell density. Taken together these results demonstrate feasibility of producing physiological-like constructs such as the thick pcECM suggested here as a prospective treatment for end-stage heart failure. Methodologies reported herein may also benefit other tissues, offering a valuable in vitro setting for "thick-tissue" engineering strategies toward large animal in vivo studies.

  8. Update: Innovation in cardiology (IV). Cardiac tissue engineering and the bioartificial heart.

    PubMed

    Gálvez-Montón, Carolina; Prat-Vidal, Cristina; Roura, Santiago; Soler-Botija, Carolina; Bayes-Genis, Antoni

    2013-05-01

    Heart failure is the end-stage of many cardiovascular diseases-such as acute myocardial infarction-and remains one of the most appealing challenges for regenerative medicine because of its high incidence and prevalence. Over the last 20 years, cardiomyoplasty, based on the isolated administration of cells with regenerative capacity, has been the focal point of most studies aimed at regenerating the heart. Although this therapy has proved feasible in the clinical setting, the degree of infarcted myocardium regenerated and of improved cardiac function are at best modest. Hence, tissue engineering has emerged as a novel technology using cells with regenerative capacity, biological and/or synthetic materials, growth, proangiogenic and differentiation factors, and online registry systems, to induce the regeneration of whole organs or locally damaged tissue. The next step, seen recently in pioneering animal studies, is de novo generation of bioartificial hearts by decellularization and preservation of supporting structures for their subsequent repopulation with new contractile, vascular muscle tissue. Ultimately, this new approach would entail transplantation of the "rebuilt" heart, reestablishing cardiac function in the recipient.

  9. Controlling activation site density by low-energy far-field stimulation in cardiac tissue.

    PubMed

    Hörning, Marcel; Takagi, Seiji; Yoshikawa, Kenichi

    2012-06-01

    Tachycardia and fibrillation are potentially fatal arrhythmias associated with the formation of rotating spiral waves in the heart. Presently, the termination of these types of arrhythmia is achieved by use of antitachycardia pacing or cardioversion. However, these techniques have serious drawbacks, in that they either have limited application or produce undesirable side effects. Low-energy far-field stimulation has recently been proposed as a superior therapy. This proposed therapeutic method would exploit the phenomenon in which the application of low-energy far-field shocks induces a large number of activation sites ("virtual electrodes") in tissue. It has been found that the formation of such sites can lead to the termination of undesired states in the heart and the restoration of normal beating. In this study we investigate a particular aspect of this method. Here we seek to determine how the activation site density depends on the applied electric field through in vitro experiments carried out on neonatal rat cardiac tissue cultures. The results indicate that the activation site density increases exponentially as a function of the intracellular conductivity and the level of cell isotropy. Additionally, we report numerical results obtained from bidomain simulations of the Beeler-Reuter model that are quantitatively consistent with our experimental results. Also, we derive an intuitive analytical framework that describes the activation site density and provides useful information for determining the ratio of longitudinal to transverse conductivity in a cardiac tissue culture. The results obtained here should be useful in the development of an actual therapeutic method based on low-energy far-field pacing. In addition, they provide a deeper understanding of the intrinsic properties of cardiac cells.

  10. Controlling activation site density by low-energy far-field stimulation in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Hörning, Marcel; Takagi, Seiji; Yoshikawa, Kenichi

    2012-06-01

    Tachycardia and fibrillation are potentially fatal arrhythmias associated with the formation of rotating spiral waves in the heart. Presently, the termination of these types of arrhythmia is achieved by use of antitachycardia pacing or cardioversion. However, these techniques have serious drawbacks, in that they either have limited application or produce undesirable side effects. Low-energy far-field stimulation has recently been proposed as a superior therapy. This proposed therapeutic method would exploit the phenomenon in which the application of low-energy far-field shocks induces a large number of activation sites (“virtual electrodes”) in tissue. It has been found that the formation of such sites can lead to the termination of undesired states in the heart and the restoration of normal beating. In this study we investigate a particular aspect of this method. Here we seek to determine how the activation site density depends on the applied electric field through in vitro experiments carried out on neonatal rat cardiac tissue cultures. The results indicate that the activation site density increases exponentially as a function of the intracellular conductivity and the level of cell isotropy. Additionally, we report numerical results obtained from bidomain simulations of the Beeler-Reuter model that are quantitatively consistent with our experimental results. Also, we derive an intuitive analytical framework that describes the activation site density and provides useful information for determining the ratio of longitudinal to transverse conductivity in a cardiac tissue culture. The results obtained here should be useful in the development of an actual therapeutic method based on low-energy far-field pacing. In addition, they provide a deeper understanding of the intrinsic properties of cardiac cells.

  11. Correlation-based discrimination between cardiac tissue and blood for segmentation of 3D echocardiographic images

    NASA Astrophysics Data System (ADS)

    Saris, Anne E. C. M.; Nillesen, Maartje M.; Lopata, Richard G. P.; de Korte, Chris L.

    2013-03-01

    Automated segmentation of 3D echocardiographic images in patients with congenital heart disease is challenging, because the boundary between blood and cardiac tissue is poorly defined in some regions. Cardiologists mentally incorporate movement of the heart, using temporal coherence of structures to resolve ambiguities. Therefore, we investigated the merit of temporal cross-correlation for automated segmentation over the entire cardiac cycle. Optimal settings for maximum cross-correlation (MCC) calculation, based on a 3D cross-correlation based displacement estimation algorithm, were determined to obtain the best contrast between blood and myocardial tissue over the entire cardiac cycle. Resulting envelope-based as well as RF-based MCC values were used as additional external force in a deformable model approach, to segment the left-ventricular cavity in entire systolic phase. MCC values were tested against, and combined with, adaptive filtered, demodulated RF-data. Segmentation results were compared with manually segmented volumes using a 3D Dice Similarity Index (3DSI). Results in 3D pediatric echocardiographic images sequences (n = 4) demonstrate that incorporation of temporal information improves segmentation. The use of MCC values, either alone or in combination with adaptive filtered, demodulated RF-data, resulted in an increase of the 3DSI in 75% of the cases (average 3DSI increase: 0.71 to 0.82). Results might be further improved by optimizing MCC-contrast locally, in regions with low blood-tissue contrast. Reducing underestimation of the endocardial volume due to MCC processing scheme (choice of window size) and consequential border-misalignment, could also lead to more accurate segmentations. Furthermore, increasing the frame rate will also increase MCC-contrast and thus improve segmentation.

  12. Unpinning of rotating spiral waves in cardiac tissues by circularly polarized electric fields

    NASA Astrophysics Data System (ADS)

    Feng, Xia; Gao, Xiang; Pan, De-Bei; Li, Bing-Wei; Zhang, Hong

    2014-04-01

    Spiral waves anchored to obstacles in cardiac tissues may cause lethal arrhythmia. To unpin these anchored spirals, comparing to high-voltage side-effect traditional therapies, wave emission from heterogeneities (WEH) induced by the uniform electric field (UEF) has provided a low-voltage alternative. Here we provide a new approach using WEH induced by the circularly polarized electric field (CPEF), which has higher success rate and larger application scope than UEF, even with a lower voltage. And we also study the distribution of the membrane potential near an obstacle induced by CPEF to analyze its mechanism of unpinning. We hope this promising approach may provide a better alternative to terminate arrhythmia.

  13. Burn Depth Estimation Based on Infrared Imaging of Thermally Excited Tissue

    SciTech Connect

    Dickey, F.M.; Hoswade, S.C.; Yee, M.L.

    1999-03-05

    Accurate estimation of the depth of partial-thickness burns and the early prediction of a need for surgical intervention are difficult. A non-invasive technique utilizing the difference in thermal relaxation time between burned and normal skin may be useful in this regard. In practice, a thermal camera would record the skin's response to heating or cooling by a small amount-roughly 5 C for a short duration. The thermal stimulus would be provided by a heat lamp, hot or cold air, or other means. Processing of the thermal transients would reveal areas that returned to equilibrium at different rates, which should correspond to different burn depths. In deeper thickness burns, the outside layer of skin is further removed from the constant-temperature region maintained through blood flow. Deeper thickness areas should thus return to equilibrium more slowly than other areas. Since the technique only records changes in the skin's temperature, it is not sensitive to room temperature, the burn's location, or the state of the patient. Preliminary results are presented for analysis of a simulated burn, formed by applying a patch of biosynthetic wound dressing on top of normal skin tissue.

  14. The Multi-Domain Fibroblast/Myocyte Coupling in the Cardiac Tissue: A Theoretical Study.

    PubMed

    Greisas, Ariel; Zlochiver, Sharon

    2016-09-01

    Cardiac fibroblast proliferation and concomitant collagenous matrix accumulation (fibrosis) develop during multiple cardiac pathologies. Recent studies have demonstrated direct electrical coupling between myocytes and fibroblasts in vitro, and assessed the electrophysiological implications of such coupling. However, in the living tissues, such coupling has not been demonstrated, and only indirect coupling via the extracellular space is likely to exist. In this study we employed a multi-domain model to assess the modulation of the cardiac electrophysiological properties by neighboring fibroblasts assuming only indirect coupling. Numerical simulations in 1D and 2D human atrial models showed that extracellular coupling sustains a significant impact on conduction velocity (CV) and a less significant effect on the action potential duration. Both CV and the slope of the CV restitution increased with increasing fibroblast density. This effect was more substantial for lower extracellular conductance. In 2D, spiral waves exhibited reduced frequency with increasing fibroblast density, and the propensity of wavebreaks and complex dynamics at high pacing rates significantly increased. PMID:27150222

  15. Induction of Virtual Electrodes in Cardiac Tissue by Unipolar Stimulation Using a Three-Dimensional Bidomain Model with Rotational Anisotropy

    NASA Astrophysics Data System (ADS)

    Zhou, Yin; Jung, Peter

    2000-03-01

    Virtual electrodes play an important role in the defibrillation of cardiac tissue. Bidomain modeling of cardiac tissue must be used to simulate the formation of virtual electrodes. But inhibited by the fact that the inversion of a large matrix is required at every timestep, most of the previous bidomain studies do not deal with realistic three-dimensional cases. In this paper, a three-dimensional bidomain with effective ionic channels is used to investigate the initiation of reentry in cardiac tissue by strong unipolar electric shocks. A slab of tissue with unequal anisotropy and fiber rotation is considered,and the evolving extra-cellular potentials and transmembrane potentials are computed using a semi-implicit method to allow for a large timestep. The numerical efficiency achieved allows us to simulate the wave propagation for a reasonable long time to visualize and observe the formation of the three-dimensional virtual electrode.

  16. Local anesthetic anchoring to cardiac sodium channels. Implications into tissue-selective drug targeting.

    PubMed

    Li, R A; Tsushima, R G; Himmeldirk, K; Dime, D S; Backx, P H

    1999-07-01

    Local anesthetics inhibit Na+ channels in a variety of tissues, leading to potentially serious side effects when used clinically. We have created a series of novel local anesthetics by connecting benzocaine (BZ) to the sulfhydryl-reactive group methanethiosulfonate (MTS) via variable-length polyethylether linkers (L) (MTS-LX-BZ [X represents 0, 3, 6, or 9]). The application of MTS-LX-BZ agents modified native rat cardiac as well as heterologously expressed human heart (hH1) and rat skeletal muscle (rSkM1) Na+ channels in a manner resembling that of free BZ. Like BZ, the effects of MTS-LX-BZ on rSkM1 channels were completely reversible. In contrast, MTS-LX-BZ modification of heart and mutant rSkM1 channels, containing a pore cysteine at the equivalent location as cardiac Na+ channels (ie, Y401C), persisted after drug washout unless treated with DTT, which suggests anchoring to the pore via a disulfide bond. Anchored MTS-LX-BZ competitively reduced the affinity of cardiac Na+ channels for lidocaine but had minimal effects on mutant channels with disrupted local anesthetic modification properties. These results establish that anchored MTS-LX-BZ compounds interact with the local anesthetic binding site (LABS). Variation in the linker length altered the potency of channel modification by the anchored drugs, thus providing information on the spatial relationship between the anchoring site and the LABS. Our observations demonstrate that local anesthetics can be anchored to the extracellular pore cysteine in cardiac Na+ channels and dynamically interact with the intracellular LABS. These results suggest that nonselective agents, such as local anesthetics, might be made more selective by linking these agents to target-specific anchors.

  17. The stimulation of the cardiac differentiation of mesenchymal stem cells in tissue constructs that mimic myocardium structure and biomechanics.

    PubMed

    Guan, Jianjun; Wang, Feng; Li, Zhenqing; Chen, Joseph; Guo, Xiaolei; Liao, Jun; Moldovan, Nicanor I

    2011-08-01

    We investigated whether tissue constructs resembling structural and mechanical properties of the myocardium would induce mesenchymal stem cells (MSCs) to differentiate into a cardiac lineage, and whether further mimicking the 3-D cell alignment of myocardium would enhance cardiac differentiation. The tissue constructs were generated by integrating MSCs with elastic polyurethane nanofibers in an electrical field. Control of processing parameters resulted in tissue constructs recapitulating the fibrous and anisotropic structure, and typical stress-strain response of native porcine myocardium. MSCs proliferated in the tissue constructs when cultured dynamically, but retained a round morphology. mRNA expression demonstrated that cardiac differentiation was significantly stimulated. Enhanced cardiac differentiation was achieved by 3-D alignment of MSCs within the tissue constructs. Cell alignment was attained by statically stretching tissue constructs during culture. Increasing stretching strain from 25% to 75% increased the degree of 3-D cell alignment. Real time RT-PCR results showed that when cells assuming a high degree of alignment (with application of 75% strain), their expression of cardiac markers (GATA4, Nkx2.5 and MEF2C) remarkably increased. The differentiated cells also developed calcium channels, which are required to have electrophysiological properties. This report to some extent explains the outcome of many in vivo studies, where only a limited amount of the injected MSCs differentiated into cardiomyocytes. It is possible that the strain of the heartbeat (∼20%) cannot allow the MSCs to have an alignment high enough for a remarkable cardiac differentiation. This work suggests that pre-differentiation of MSCs into cardiomyocytes prior to injection may result in a greater degree of cardiac regeneration than simply injecting un-differentiated MSCs into heart.

  18. Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering.

    PubMed

    Wu, Yujing; Shi, Xiaoli; Li, Yi; Tian, Lei; Bai, Rui; Wei, Yujie; Han, Dong; Liu, Huiliang; Xu, Jianxun

    2016-12-01

    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE. PMID:27263018

  19. Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Wu, Yujing; Shi, Xiaoli; Li, Yi; Tian, Lei; Bai, Rui; Wei, Yujie; Han, Dong; Liu, Huiliang; Xu, Jianxun

    2016-06-01

    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE.

  20. The Dip in the Anodal Strength-Interval Curve in Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Kandel, Sunil; Roth, Bradley J.

    2012-10-01

    Heart disease -- specifically ventricular fibrillation -- is the leading cause of death in the United States. The most common treatment for this lethal arrhythmia is defibrillation: application of a strong electrical shock that resets the heart to its normal rhythm. The goal of this project is to obtain a better understanding of how anodal (hyperpolarizing) shocks affect the heart by using numerical simulations. To accomplish this goal, we will test four hypotheses to find the response of refractory tissue to an anodal shock. We will use bidomain model; the state-of-the-art mathematical description of how cardiac tissue responds to an electric shock. The innovative feature of this proposal is to integrate the bidomain model with an ion channel model (Luo-Rudy model, 1994) that includes intracellular calcium dynamics to get a detailed calculation of the mechanism of the excitation and to understand the electrical behavior of the heart, which is important for pacing and defibrillation.

  1. Action potential duration dispersion and alternans in simulated heterogeneous cardiac tissue with a structural barrier.

    PubMed

    Krogh-Madsen, Trine; Christini, David J

    2007-02-15

    Structural barriers to wave propagation in cardiac tissue are associated with a decreased threshold for repolarization alternans both experimentally and clinically. Using computer simulations, we investigated the effects of a structural barrier on the onset of spatially concordant and discordant alternans. We used two-dimensional tissue geometry with heterogeneity in selected potassium conductances to mimic known apex-base gradients. Although we found that the actual onset of alternans was similar with and without the structural barrier, the increase in alternans magnitude with faster pacing was steeper with the barrier--giving the appearance of an earlier alternans onset in its presence. This is consistent with both experimental structural barrier findings and the clinical observation of T-wave alternans occurring at slower pacing rates in patients with structural heart disease. In ionically homogeneous tissue, discordant alternans induced by the presence of the structural barrier arose at intermediate pacing rates due to a source-sink mismatch behind the barrier. In heterogeneous tissue, discordant alternans occurred during fast pacing due to a barrier-induced decoupling of tissue with different restitution properties. Our results demonstrate a causal relationship between the presence of a structural barrier and increased alternans magnitude and action potential duration dispersion, which may contribute to why patients with structural heart disease are at higher risk for ventricular tachyarrhythmias.

  2. Cardiac protein changes in ischaemic and dilated cardiomyopathy: a proteomic study of human left ventricular tissue

    PubMed Central

    Roselló-Lletí, Esther; Alonso, Jana; Cortés, Raquel; Almenar, Luis; Martínez-Dolz, Luis; Sánchez-Lázaro, Ignacio; Lago, Francisca; Azorín, Inmaculada; Juanatey, Jose R González; Portolés, Manuel; Rivera, Miguel

    2012-01-01

    The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. Previous works on proteomic analysis in cardiac tissue from patients with HF remain scant. The purpose of our study was to use a proteomic approach to investigate variations in protein expression of left ventricle tissue from patients with ischaemic (ICM) and dilated cardiomyopathy (DCM). Twenty-four explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and six non-diseased donor hearts (CNT) were analysed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence. We encountered 35 differentially regulated spots in the comparison CNT versus ICM, 33 in CNT versus DCM, and 34 in ICM versus DCM. We identified glyceraldehyde 3-phophate dehydrogenase up-regulation in both ICM and DCM, and alpha-crystallin B down-regulation in both ICM and DCM. Heat shock 70 protein 1 was up-regulated only in ICM. Ten of the eleven differentially regulated proteins common to both aetiologies are interconnected as a part of a same network. In summary, we have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of eleven proteins common to both ischaemic and dilated aetiology, we also observed different proteins altered in both groups. Furthermore, we obtained that seven of these eleven proteins are involved in cell death and apoptosis processes, and therefore in HF progression. PMID:22435364

  3. High-frequency ultrasound M-mode monitoring of HIFU ablation in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Kumon, R. E.; Gudur, M. S. R.; Zhou, Y.; Deng, C. X.

    2012-10-01

    Effective real-time HIFU lesion detection is important for expanded use of HIFU in interventional electrophysiology (e.g., epicardial ablation of cardiac arrhythmia). The goal of this study was to investigate rapid, high-frequency M-mode ultrasound imaging for monitoring spatiotemporal changes in tissue during HIFU application. The HIFU application (4.33 MHz, 1000 Hz PRF, 50% duty cycle, 1 s exposure, 6100 W/cm2) was perpendicularly applied to porcine cardiac tissue with a high-frequency imaging system (Visualsonics Vevo 770, 55 MHz, 4.5 mm focal distance) confocally aligned. Radiofrequency (RF) M-mode data (1 kHz PRF, 4 s × 7 mm) was acquired before, during, and after HIFU treatment. Gross lesions were compared with M-mode data to correlate lesion and cavity formation. Integrated backscatter, echo-decorrelation parameters, and their cumulative extrema over time were analyzed for automatically identifying lesion width and bubble formation. Cumulative maximum integrated backscatter showed the best results for identifying the final lesion width, and a criterion based on line-to-line decorrelation was proposed for identification of transient bubble activity.

  4. Feasibility of a nanomaterial-tissue patch for vascular and cardiac reconstruction.

    PubMed

    Ostdiek, Allison M; Ivey, Jan R; Hansen, Sarah A; Gopaldas, Raja; Grant, Sheila A

    2016-04-01

    Vascular and cardiac reconstruction involves the use of biological patches to treat trauma and defects. An in vivo study was performed to determine the remodeling and biologic effects of novel nanostructured vascular patches with and without gold nanoparticles. Porcine vascular tissue was decellularized and conjugated with gold nanoparticles to evaluate if integration would occur while avoiding rupture and stenosis. Swine underwent a bilateral patch angioplasty of the carotid arteries with experimental patches on the right and control patches of bovine pericardium on the left. Animals were sacrificed after surgery and at 3 and 9 weeks. Ultrasound was performed during surgery, every 3 weeks, and before euthanasia. Endothelial regeneration was examined using Evans Blue dye and histology using Trichrome and H&E. There was a 100% success rate of implantation with 0% mortality. All patches were patent on ultrasound. At 3 weeks, experimental patches had regenerating endothelial cell growth and normal healing responses. At 9 weeks, the experimental patches demonstrated excellent integration. Histology demonstrated cellular in-growth into the experimental patches and no major immune reactions. This is one of the first studies to demonstrate the feasibility of nanomaterial-tissue patches for vascular and cardiac reconstruction.

  5. Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering.

    PubMed

    Gelmi, Amy; Cieslar-Pobuda, Artur; de Muinck, Ebo; Los, Marek; Rafat, Mehrdad; Jager, Edwin W H

    2016-06-01

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

  6. Optical recording of calcium currents during impulse conduction in cardiac tissue

    PubMed Central

    Jousset, Florian; Rohr, Stephan

    2015-01-01

    Abstract. We explore the feasibility of obtaining a spatially resolved picture of Ca2+ inward currents (ICa) in multicellular cardiac tissue by differentiating optically recorded Ca2+ transients that accompany propagating action potentials. Patterned growth strands of neonatal rat ventricular cardiomyocytes were stained with the Ca2+ indicators Fluo-4 or Fluo-4FF. Preparations were stimulated at 1 Hz, and Ca2+ transients were recorded with high spatiotemporal resolution (50  μm, 2 kHz analog bandwidth) with a photodiode array. Signals were differentiated after appropriate digital filtering. Differentiation of Ca2+ transients resulted in optically recorded calcium currents (ORCCs) that carried the temporal and pharmacological signatures of L-type Ca2+ inward currents: the time to peak amounted to ∼2.1  ms (Fluo-4FF) and ∼2.4  ms (Fluo-4), full-width at half-maximum was ∼8  ms, and ORCCs were completely suppressed by 50  μmol/L CdCl2. Also, and as reported before from patch-clamp studies, caffeine reversibly depressed the amplitude of ORCCs. The results demonstrate that the differentiation of Ca2+ transients can be used to obtain a spatially resolved picture of the initial phase of ICa in cardiac tissue and to assess relative changes of activation/fast inactivation of ICa following pharmacological interventions. PMID:26158001

  7. Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics.

    PubMed

    Manohara, S R; Hanagodimath, S M; Gerward, L

    2011-11-15

    Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary, testis, soft tissue, and soft tissue (4-component), for the photon energy range 0.015-15 MeV and for penetration depths up to 40 mfp (mean free path). The chemical composition of human organs and tissues is seen to influence the energy absorption buildup factors. It is also found that the buildup factor of human organs and tissues changes significantly with the change of incident photon energy and effective atomic number, Z(eff). These changes are due to the dominance of different photon interaction processes in different energy regions and different chemical compositions of human organs and tissues. With the proper knowledge of buildup factors of human organs and tissues, energy absorption in the human body can be carefully controlled. The present results will help in estimating safe dose levels for radiotherapy patients and also useful in diagnostics and dosimetry. The tissue-equivalent materials for skeletal muscle, adipose tissue, cortical bone, and lung tissue are also discussed. It is observed that water and MS20 are good tissue equivalent materials for skeletal muscle in the extended energy range.

  8. Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering.

    PubMed

    Sakaguchi, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

    2015-05-10

    Construction of three-dimensional (3D) tissues with pre-isolated cells is a promising achievement for novel medicine and drug-discovery research. Our laboratory constructs 3D tissues with an innovative and unique method for layering multiple cell sheets. Cell sheets maintain a high-efficiently regenerating function, because of the higher cell density and higher transplantation efficiency, compared to other cell-delivery methods. Cell sheets have already been applied in clinical applications for regenerative medicine in treating patients with various diseases. Therefore, in our search to develop a more efficient treatment with cell sheets, we are constructing 3D tissues by layering cell sheets. Native animal tissues and organs have an abundance of capillaries to supply oxygen and nutrients, and to remove waste molecules. In our investigation of vascularized cardiac cell sheets, we have found that endothelial cells within cell sheets spontaneously form blood vessel networks as in vivo capillaries. To construct even thicker 3D tissues by layering multiple cell sheets, it is critical to have a medium or blood flow within the vascular networks of the cell sheets. Therefore, to perfuse medium or blood in the cell sheet vascular network to maintain the viability of all cells, we developed two types of vascular beds; (1) a femoral muscle-based vascular bed, and (2) a synthetic collagen gel-based vascular bed. Both vascular beds successfully provide the critical flow of culture medium, which allows 12-layer cell sheets to survive. Such bioreactor systems, when combined with cell sheet engineering techniques, have produced functional vascularized 3D tissues. Here we explain and discuss the various processes to obtain vascular networks by properly connecting cell sheets and the engineering of 3D tissues.

  9. Influence of different fixation protocols on the preservation and dimensions of cardiac tissue.

    PubMed

    Hołda, Mateusz K; Klimek-Piotrowska, Wiesława; Koziej, Mateusz; Piątek, Katarzyna; Hołda, Jakub

    2016-08-01

    Recent extensive progress in invasive cardiac procedures has triggered a wave of dozens of heart morphometric anatomical studies that are carried out largely using autopsied samples fixed in formaldehyde solution prior to observations and measurements. In reality, very little is known about changes in heart tissue dimensions during fixation. The aim of this study was therefore to investigate how fixation affects the dimensions of cardiac tissue, and if different types and concentrations of reagents affect this phenomenon. A total of 40 pig heart samples were investigated, and seven different measuring sites were permanently marked in every heart prior to fixation. Four study groups (n = 10 each) were assembled that differed only in concentration and the type of fixative: (i) 2% formaldehyde solution; (ii) 4% formaldehyde solution (formalin); (iii) 10% formaldehyde solution; (iv) alcoholic formalin. The samples were measured before and after fixation at the following time points: 24 h, 72 h and 168 h. It was found that different fixatives significantly affected different parameters. Almost all of the heart dimensions that were measured stabilized after 24 h; later changes were statistically insignificant in the point-to-point comparison. Change in the length of the interatrial septum surface was not altered significantly in any of the fixatives after 24 h of preservation. It was found that 10% formaldehyde increased the thickness of muscular tissue only after 24 h; this thickening was reduced after 72 h and was insignificant at 168 h. Other heart parameters in this group do not present significant changes over the entire fixation time duration. In conclusion, the 10% formaldehyde phosphate-buffered solution appeared to be the best fixative among the fixatives that were studied for cardiac morphometric purposes; this solution caused the smallest changes in tissue dimensions. Measurements should be obtained at least after 1 week of preservation

  10. Reentry produced by small-scale heterogeneities in a discrete model of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Alonso, Sergio; Bär, Markus

    2016-06-01

    Reentries are reexcitations of cardiac tissue after the passing of an excitation wave which can cause dangerous arrhythmias like tachycardia or life-threatening heart failures like fibrillation. The heart is formed by a network of cells connected by gap junctions. Under ischemic conditions some of the cells lose their connections, because gap junctions are blocked and the excitability is decreased. We model a circular region of the tissue where a fraction of connections among individual cells are removed and substituted by non-conducting material in a two-dimensional (2D) discrete model of a heterogeneous excitable medium with local kinetics based on electrophysiology. Thus, two neighbouring cells are connected (disconnected) with a probability ϕ (1 – ϕ). Such a region is assumed to be surrounded by homogeneous tissue. The circular heterogeneous area is shown to act as a source of new waves which reenter into the tissue and reexcitate the whole domain. We employ the Fenton-Karma equations to model the action potential for the local kinetics of the discrete nodes to study the statistics of the reentries in two dimensional networks with different topologies. We conclude that the probability of reentry is determined by the proximity of the fraction of disrupted connections between neighboring nodes (“cells”) in the heterogeneous region to the percolation threshold.

  11. Reentry produced by small-scale heterogeneities in a discrete model of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Alonso, Sergio; Bär, Markus

    2016-06-01

    Reentries are reexcitations of cardiac tissue after the passing of an excitation wave which can cause dangerous arrhythmias like tachycardia or life-threatening heart failures like fibrillation. The heart is formed by a network of cells connected by gap junctions. Under ischemic conditions some of the cells lose their connections, because gap junctions are blocked and the excitability is decreased. We model a circular region of the tissue where a fraction of connections among individual cells are removed and substituted by non-conducting material in a two-dimensional (2D) discrete model of a heterogeneous excitable medium with local kinetics based on electrophysiology. Thus, two neighbouring cells are connected (disconnected) with a probability ϕ (1 - ϕ). Such a region is assumed to be surrounded by homogeneous tissue. The circular heterogeneous area is shown to act as a source of new waves which reenter into the tissue and reexcitate the whole domain. We employ the Fenton-Karma equations to model the action potential for the local kinetics of the discrete nodes to study the statistics of the reentries in two dimensional networks with different topologies. We conclude that the probability of reentry is determined by the proximity of the fraction of disrupted connections between neighboring nodes (“cells”) in the heterogeneous region to the percolation threshold.

  12. Development of stable peri-implant soft tissue and mentolabial sulcus depth with an implant-retained soft tissue conformer after osteocutaneous flap reconstruction.

    PubMed

    Dhima, Matilda; Rieck, Kevin L; Arce, Kevin; Salinas, Thomas J

    2013-01-01

    Excessive soft tissue bulk, movement, chronic inflammation, and hypertrophy in periimplant areas pose challenges for long-term management of peri-implant soft tissues surrounding osteocutaneous flap reconstructions. A case history report is presented on the predictable establishment of stable peri-implant soft tissue and improved mentolabial sulcus depth in a patient treated for high-grade osteosarcoma of the mandible. Following surgical resection, reconstruction with osteocutaneous fibula free flap, and endosseous implant placement, a combined surgical and prosthetic approach was used through a lip switch vestibuloplasty and an implant-retained soft tissue conformer.

  13. Development and characterization of novel electrically conductive PANI-PGS composites for cardiac tissue engineering applications.

    PubMed

    Qazi, Taimoor H; Rai, Ranjana; Dippold, Dirk; Roether, Judith E; Schubert, Dirk W; Rosellini, Elisabetta; Barbani, Niccoletta; Boccaccini, Aldo R

    2014-06-01

    Cardiovascular diseases, especially myocardial infarction, are the leading cause of morbidity and mortality in the world, also resulting in huge economic burdens on national economies. A cardiac patch strategy aims at regenerating an infarcted heart by providing healthy functional cells to the injured region via a carrier substrate, and providing mechanical support, thereby preventing deleterious ventricular remodeling. In the present work, polyaniline (PANI) was doped with camphorsulfonic acid and blended with poly(glycerol-sebacate) at ratios of 10, 20 and 30vol.% PANI content to produce electrically conductive composite cardiac patches via the solvent casting method. The composites were characterized in terms of their electrical, mechanical and physicochemical properties. The in vitro biodegradability of the composites was also evaluated. Electrical conductivity increased from 0Scm(-1) for pure PGS to 0.018Scm(-1) for 30vol.% PANI-PGS samples. Moreover, the conductivities were preserved for at least 100h post fabrication. Tensile tests revealed an improvement in the elastic modulus, tensile strength and elasticity with increasing PANI content. The degradation products caused a local drop in pH, which was higher in all composite samples compared with pure PGS, hinting at a buffering effect due to the presence of PANI. Finally, the cytocompatibility of the composites was confirmed when C2C12 cells attached and proliferated on samples with varying PANI content. Furthermore, leaching of acid dopants from the developed composites did not have any deleterious effect on the viability of C2C12 cells. Taken together, these results confirm the potential of PANI-PGS composites for use as substrates to modulate cellular behavior via electrical stimulation, and as biocompatible scaffolds for cardiac tissue engineering applications.

  14. Tissue-nonspecific alkaline phosphatase as a target of sFRP2 in cardiac fibroblasts

    PubMed Central

    Martin, Sean; Lin, Huey; Ejimadu, Chukwuemeka

    2015-01-01

    Recent studies of myocardial infarction in secreted Frizzled-related protein 2 (sFRP2) knockout mice and our hamster heart failure therapy based on sFRP2 blockade have established sFRP2 as a key profibrotic cytokine in the heart. The failing hamster heart is marked by prominent fibrosis and calcification with elevated expression of sFRP2. Noting the involvement of tissue-nonspecific alkaline phosphatase (TNAP) in bone mineralization and vascular calcification, we determined whether sFRP2 might be an upstream regulator of TNAP. Biochemical assays revealed an approximately twofold increase in the activity of TNAP and elevated levels of inorganic phosphate (Pi) in the failing heart compared with the normal heart. Neither was this change detected in the liver or hamstring muscle nor was it associated with systemic hyperphosphatemia. TNAP was readily cloned from the hamster heart and upon overexpression increased the level of extracellular but not intracellular Pi, which is consistent with the cell surface location of the ectoenzyme. In line with the previous demonstration that sFRP2 blockade attenuated fibrosis, we show here that the therapy downregulated TNAP. This in vivo finding is corroborated by the in vitro study showing that cultured cardiac fibroblasts treated with recombinant sFRP2 protein exhibited progressive increase in the expression and activity of TNAP, which was completely abrogated by cycloheximide or tunicamycin. Induction of TNAP by sFRP2 is restricted to cardiac fibroblasts among the multiple cell types examined, and was not observed with sFRP4. The current work indicates that sFRP2 may promote cardiac fibrocalcification through coordinate activation of tolloid-like metalloproteinases and TNAP. PMID:25972450

  15. Finite element analysis of an accordion-like honeycomb scaffold for cardiac tissue engineering.

    PubMed

    Jean, Aurélie; Engelmayr, George C

    2010-11-16

    Optimizing the function of tissue engineered cardiac muscle is becoming more feasible with the development of microfabricated scaffolds amenable to mathematical modeling. In the current study, the elastic behavior of a recently developed poly(glycerol sebacate) (PGS) accordion-like honeycomb (ALH) scaffold [Engelmayr et al., 2008. Nature Materials 7 (12), 1003-1010] was analyzed. Specifically, 2D finite element (FE) models of the ALH unit cell (periodic boundary conditions) and tessellations (kinematic uniform boundary conditions) were utilized to determine a representative volume element (RVE) and to retrospectively predict the elastic effective stiffnesses. An RVE of 90 ALH unit cells (≃3.18×4.03mm) was found, indicating that previous experimental uni-axial test samples were mechanically representative. For ALH scaffolds microfabricated from PGS cured 7.5h at 160°C, FE predicted effective stiffnesses in the two orthogonal material directions (0.081±0.012 and 0.033±0.005MPa) matched published experimental data (0.083±0.004 and 0.031±0.002MPa) within 2.4% and 6.4%. Of potential use as a design criterion, model predicted global strain amplifications were lower in ALH (0.54 and 0.34) versus rectangular honeycomb (1.19 and 0.74) scaffolds, appearing to be inversely correlated with previously measured strains-to-failure. Important in matching the anisotropic mechanical properties of native cardiac muscle, FE predicted ALH scaffolds with 50μm wide PGS struts to be maximally anisotropic. The FE model will thus be useful in designing future variants of the ALH pore geometry that simultaneously provide proper cardiac anisotropy and reduced stiffness to enhance heart cell-mediated contractility.

  16. Utilization of laser Doppler flowmetry and tissue spectrophotometry for burn depth assessment using a miniature swine model.

    PubMed

    Lotter, Oliver; Held, Manuel; Schiefer, Jennifer; Werner, Ole; Medved, Fabian; Schaller, Hans-Eberhard; Rahmanian-Schwarz, Afshin; Jaminet, Patrick; Rothenberger, Jens

    2015-01-01

    Currently, the diagnosis of burn depth is primarily based on a visual assessment and can be dependent on the surgeons' experience. The goal of this study was to determine the ability of laser Doppler flowmeter combined with a tissue spectrophotometer to discriminate burn depth in a miniature swine burn model. Burn injuries of varying depth, including superficial-partial, deep-partial, and full thickness, were created in seven Göttingen minipigs using an aluminium bar (100 °C), which was applied to the abdominal skin for periods of 1, 3, 6, 12, 30, and 60 seconds with gravity alone. The depth of injury was evaluated histologically using hematoxylin and eosin staining. All burns were assessed 3 hours after injury using a device that combines a laser light and a white light to determine blood flow, hemoglobin oxygenation, and relative amount of hemoglobin. The blood flow (41 vs. 124 arbitrary units [AU]) and relative amount of hemoglobin (32 vs. 52 AU) were significantly lower in full thickness compared with superficial-partial thickness burns. However, no significant differences in hemoglobin oxygenation were observed between these depths of burns (61 vs. 60%). These results show the ability of laser Doppler flowmeter and tissue spectrophotometer in combination to discriminate between various depths of injury in the minipig model, suggesting that this device may offer a valuable tool for burn depth assessment influencing burn management.

  17. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

    PubMed

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

    2015-07-01

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

  18. A new three-variable mathematical model of action potential propagation in cardiac tissue.

    NASA Astrophysics Data System (ADS)

    Fenton, Flavio; Karma, Alain

    1996-03-01

    Modeling the electrical activity of the heart, and the complex signaling patterns which underly dangerous arrhythmias such as tachycardia and fibrillation, requires a quantitative model of action potential (AP) propagation. At present, there exist detailed ionic models of the Hodgkin-Huxley form that accurately reproduce dynamical features of the AP at a single cell level (e.g. Luo-Rudy, 1994). However, such models are not computationally tractable to study propagation in two and three-dimensional tissues of many resistively coupled cells. At the other extreme, there exists generic models of excitable media, such as the well-known FitzHugh-Nagumo model, which are only qualitative and do not reproduce essential dynamical features of cardiac AP. A new three-variable model is introduced which bridges the gap between these two types of models. It reproduces quantitatively important `mesoscopic' dynamical properties which are specific to cardiac AP, namely restitution and dispersion. At the same time, it remains computationally tractable and makes it possible to study the effect of these properties on the initiation, dynamics, and stability of complex reentrant excitations in two and three dimensions. Preliminary numerical results of the effect of restitution and dispersion on two-dimensional reentry (i.e. spiral waves) are presented.

  19. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

    PubMed Central

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R.

    2015-01-01

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed. PMID:26109634

  20. Unpinning of rotating spiral waves in cardiac tissues by circularly polarized electric fields

    PubMed Central

    Feng, Xia; Gao, Xiang; Pan, De-Bei; Li, Bing-Wei; Zhang, Hong

    2014-01-01

    Spiral waves anchored to obstacles in cardiac tissues may cause lethal arrhythmia. To unpin these anchored spirals, comparing to high-voltage side-effect traditional therapies, wave emission from heterogeneities (WEH) induced by the uniform electric field (UEF) has provided a low-voltage alternative. Here we provide a new approach using WEH induced by the circularly polarized electric field (CPEF), which has higher success rate and larger application scope than UEF, even with a lower voltage. And we also study the distribution of the membrane potential near an obstacle induced by CPEF to analyze its mechanism of unpinning. We hope this promising approach may provide a better alternative to terminate arrhythmia. PMID:24777360

  1. Unstable spiral waves and local Euclidean symmetry in a model of cardiac tissue.

    PubMed

    Marcotte, Christopher D; Grigoriev, Roman O

    2015-06-01

    This paper investigates the properties of unstable single-spiral wave solutions arising in the Karma model of two-dimensional cardiac tissue. In particular, we discuss how such solutions can be computed numerically on domains of arbitrary shape and study how their stability, rotational frequency, and spatial drift depend on the size of the domain as well as the position of the spiral core with respect to the boundaries. We also discuss how the breaking of local Euclidean symmetry due to finite size effects as well as the spatial discretization of the model is reflected in the structure and dynamics of spiral waves. This analysis allows identification of a self-sustaining process responsible for maintaining the state of spiral chaos featuring multiple interacting spirals. PMID:26117110

  2. Unstable spiral waves and local Euclidean symmetry in a model of cardiac tissue

    SciTech Connect

    Marcotte, Christopher D.; Grigoriev, Roman O.

    2015-06-15

    This paper investigates the properties of unstable single-spiral wave solutions arising in the Karma model of two-dimensional cardiac tissue. In particular, we discuss how such solutions can be computed numerically on domains of arbitrary shape and study how their stability, rotational frequency, and spatial drift depend on the size of the domain as well as the position of the spiral core with respect to the boundaries. We also discuss how the breaking of local Euclidean symmetry due to finite size effects as well as the spatial discretization of the model is reflected in the structure and dynamics of spiral waves. This analysis allows identification of a self-sustaining process responsible for maintaining the state of spiral chaos featuring multiple interacting spirals.

  3. Covariant stringlike dynamics of scroll wave filaments in anisotropic cardiac tissue.

    PubMed

    Verschelde, Henri; Dierckx, Hans; Bernus, Olivier

    2007-10-19

    It has been hypothesized that stationary scroll wave filaments in cardiac tissue describe a geodesic in a curved space whose metric is the inverse diffusion tensor. Several numerical studies support this hypothesis, but no analytical proof has been provided yet for general anisotropy. In this Letter, we derive dynamic equations for the filament in the case of general anisotropy. These equations are covariant under general spatial coordinate transformations and describe the motion of a stringlike object in a curved space whose metric tensor is the inverse diffusion tensor. Therefore the behavior of scroll wave filaments in excitable media with anisotropy is similar to the one of cosmic strings in a curved universe. Our dynamic equations are valid for thin filaments and for general anisotropy. We show that stationary filaments obey the geodesic equation. PMID:17995301

  4. Design of Electrospun Hydrogel Fibers Containing Multivalent Peptide Conjugates for Cardiac Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Rode, Nikhil Ajit

    A novel material was designed using biomimetic engineering principles to recreate the chemical and physical environment of the extracellular matrix for cardiac tissue engineering applications. In order to control the chemical and specific bioactive signals provided by the material, a multivalent conjugate of a RGD-containing cell-binding peptide with hyaluronic acid was synthesized. These conjugates were characterized using in-line size exclusion chromatography with static multi-angle light scattering, UV absorbance, and differential refractive index measurements (SEC-MALS-UV-RI) to determine their molecular weight and valency, as well as the distributions of each. These conjugates were electrospun with poly(ethylene glycol) and poly(ethylene glycol) diacrylate to create a nanofibrous hydrogel material embedded with bioinstructive macromolecules. This electrospinning process was explored and optimized to create well-formed nanofibers. The diameter and orientation of the fibers was controlled to closely mimic the nanostructure of the extracellular matrix of the myocardium. Further characterization of the material was performed to ensure that its mechanical properties resemble those found in the myocardium. The availability of the peptides embedded in the hydrogel material was confirmed by measuring peptides released by trypsin incubation and was found to be sufficient to cause cell adhesion. This material was capable of supporting cell culture, maintaining the viability of cultured fibroblasts and cardiomyocytes, and preserving cardiomyocyte functionality. In this way, this material shows promise of serving as a biomimetic in vitro scaffold for generation of functional myocardial tissue, with possible applications as an in vivo cardiac patch for repair of the damage myocardium post-myocardial infarction.

  5. A Quantitative Comparison of the Behavior of Human Ventricular Cardiac Electrophysiology Models in Tissue

    PubMed Central

    Elshrif, Mohamed M.; Cherry, Elizabeth M.

    2014-01-01

    Numerical integration of mathematical models of heart cell electrophysiology provides an important computational tool for studying cardiac arrhythmias, but the abundance of available models complicates selecting an appropriate model. We study the behavior of two recently published models of human ventricular action potentials, the Grandi-Pasqualini-Bers (GPB) and the O'Hara-Virág-Varró-Rudy (OVVR) models, and compare the results with four previously published models and with available experimental and clinical data. We find the shapes and durations of action potentials and calcium transients differ between the GPB and OVVR models, as do the magnitudes and rate-dependent properties of transmembrane currents and the calcium transient. Differences also occur in the steady-state and S1–S2 action potential duration and conduction velocity restitution curves, including a maximum conduction velocity for the OVVR model roughly half that of the GPB model and well below clinical values. Between single cells and tissue, both models exhibit differences in properties, including maximum upstroke velocity, action potential amplitude, and minimum diastolic interval. Compared to experimental data, action potential durations for the GPB and OVVR models agree fairly well (although OVVR epicardial action potentials are shorter), but maximum slopes of steady-state restitution curves are smaller. Although studies show alternans in normal hearts, it occurs only in the OVVR model, and only for a narrow range of cycle lengths. We find initiated spiral waves do not progress to sustained breakup for either model. The dominant spiral wave period of the GPB model falls within clinically relevant values for ventricular tachycardia (VT), but for the OVVR model, the dominant period is longer than periods associated with VT. Our results should facilitate choosing a model to match properties of interest in human cardiac tissue and to replicate arrhythmia behavior more closely. Furthermore, by

  6. Epicardial Adipose Tissue Is Associated with Plaque Burden and Composition and Provides Incremental Value for the Prediction of Cardiac Outcome. A Clinical Cardiac Computed Tomography Angiography Study

    PubMed Central

    Gitsioudis, Gitsios; Schmahl, Christina; Missiou, Anna; Voss, Andreas; Schüssler, Alena; Abdel-Aty, Hassan; Buss, Sebastian J.; Mueller, Dirk; Vembar, Mani; Bryant, Mark; Kauczor, Hans-Ulrich; Giannitsis, Evangelos; Katus, Hugo A.; Korosoglou, Grigorios

    2016-01-01

    Objectives We sought to investigate the association of epicardial adipose tissue (eCAT) volume with plaque burden, circulating biomarkers and cardiac outcomes in patients with intermediate risk for coronary artery disease (CAD). Methods and Results 177 consecutive outpatients at intermediate risk for CAD and completed biomarker analysis including high-sensitive Troponin T (hs-TnT) and hs-CRP underwent 256-slice cardiac computed tomography angiography (CCTA) between June 2008 and October 2011. Patients with lumen narrowing ≥50% exhibited significantly higher eCAT volume than patients without any CAD or lumen narrowing <50% (median (interquartile range, IQR): 108 (73–167) cm3 vs. 119 (82–196) cm3, p = 0.04). Multivariate regression analysis demonstrated an independent association eCAT volume with plaque burden by number of lesions (R2 = 0.22, rpartial = 0.29, p = 0.026) and CAD severity by lumen narrowing (R2 = 0.22, rpartial = 0.23, p = 0.038) after adjustment for age, diabetes mellitus, hyperlidipemia, body-mass-index (BMI), hs-CRP and hs-TnT. Univariate Cox proportional hazards regression analysis identified a significant association for both increased eCAT volume and maximal lumen narrowing with all cardiac events. Multivariate Cox proportional hazards regression analysis revealed an independent association of increased eCAT volume with all cardiac events after adjustment for age, >3 risk factors, presence of CAD, hs-CRP and hs-TnT. Conclusion Epicardial adipose tissue volume is independently associated with plaque burden and maximum luminal narrowing by CCTA and may serve as an independent predictor for cardiac outcomes in patients at intermediate risk for CAD. PMID:27187590

  7. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes.

    PubMed

    Pilarczyk, Götz; Raulf, Alexandra; Gunkel, Manuel; Fleischmann, Bernd K; Lemor, Robert; Hausmann, Michael

    2016-01-01

    The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds. PMID:26751484

  8. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

    PubMed Central

    Pilarczyk, Götz; Raulf, Alexandra; Gunkel, Manuel; Fleischmann, Bernd K.; Lemor, Robert; Hausmann, Michael

    2016-01-01

    The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds. PMID:26751484

  9. Phantom validation of Monte Carlo modeling for noncontact depth sensitive fluorescence measurements in an epithelial tissue model.

    PubMed

    Ong, Yi Hong; Zhu, Caigang; Liu, Quan

    2014-08-01

    Experimental investigation and optimization of various optical parameters in the design of depth sensitive optical measurements in layered tissues would require a huge amount of time and resources. A computational method to model light transport in layered tissues using Monte Carlo simulations has been developed for decades to reduce the cost incurred during this process. In this work, we employed the Monte Carlo method to investigate the depth sensitivity achieved by various illumination and detection configurations including both the traditional cone configurations and new cone shell configurations, which are implemented by convex or axicon lenses. Phantom experiments have been carried out to validate the Monte Carlo modeling of fluorescence in a two-layered turbid, epithelial tissue model. The measured fluorescence and depth sensitivity of different illumination–detection configurations were compared with each other. The results indicate excellent agreement between the experimental and simulation results in the trends of fluorescence intensity and depth sensitivity. The findings of this study and the development of the Monte Carlo method for noncontact setups provide useful insight and assistance in the planning and optimization of optical designs for depth sensitive fluorescence measurements.

  10. Modeling the response of normal and ischemic cardiac tissue to electrical stimulation

    NASA Astrophysics Data System (ADS)

    Kandel, Sunil Mani

    Heart disease, the leading cause of death worldwide, is often caused by ventricular fibrillation. A common treatment for this lethal arrhythmia is defibrillation: a strong electrical shock that resets the heart to its normal rhythm. To design better defibrillators, we need a better understanding of both fibrillation and defibrillation. Fundamental mysteries remain regarding the mechanism of how the heart responds to a shock, particularly anodal shocks and the resultant hyperpolarization. Virtual anodes play critical roles in defibrillation, and one cannot build better defibrillators until these mechanisms are understood. We are using mathematical modeling to numerically simulate observed phenomena, and are exploring fundamental mechanisms responsible for the heart's electrical behavior. Such simulations clarify mechanisms and identify key parameters. We investigate how systolic tissue responds to an anodal shock and how refractory tissue reacts to hyperpolarization by studying the dip in the anodal strength-interval curve. This dip is due to electrotonic interaction between regions of depolarization and hyperpolarization following a shock. The dominance of the electrotonic mechanism over calcium interactions implies the importance of the spatial distribution of virtual electrodes. We also investigate the response of localized ischemic tissue to an anodal shock by modeling a regional elevation of extracellular potassium concentration. This heterogeneity leads to action potential instability, 2:1 conduction block (alternans), and reflection-like reentry at the boarder of the normal and ischemic regions. This kind of reflection (reentry) occurs due to the delay between proximal and distal segments to re-excite the proximal segment. Our numerical simulations are based on the bidomain model, the state-of-the-art mathematical description of how cardiac tissue responds to shocks. The dynamic LuoRudy model describes the active properties of the membrane. To model ischemia

  11. Depth-resolved imaging and detection of micro-retroreflectors within biological tissue using Optical Coherence Tomography

    PubMed Central

    Ivers, Steven N.; Baranov, Stephan A.; Sherlock, Tim; Kourentzi, Katerina; Ruchhoeft, Paul; Willson, Richard; Larin, Kirill V.

    2010-01-01

    A new approach to in vivo biosensor design is introduced, based on the use of an implantable micron-sized retroreflector-based platform and non-invasive imaging of its surface reflectivity by Optical Coherence Tomography (OCT). The possibility of using OCT for the depth-resolved imaging and detection of micro-retroreflectors in highly turbid media, including tissue, is demonstrated. The maximum imaging depth for the detection of the micro-retroreflector-based platform within the surrounding media was found to be 0.91 mm for porcine tissue and 1.65 mm for whole milk. With further development, it may be possible to utilize OCT and micro-retroreflectors as a tool for continuous monitoring of analytes in the subcutaneous tissue. PMID:21258473

  12. Real-time optical monitoring of permanent lesion progression in radiofrequency ablated cardiac tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Singh-Moon, Rajinder P.; Hendon, Christine P.

    2016-02-01

    Despite considerable advances in guidance of radiofrequency ablation (RFA) therapies for atrial fibrillation, success rates have been hampered by an inability to intraoperatively characterize the extent of permanent injury. Insufficient lesions can elusively create transient conduction blockages that eventually reconduct. Prior studies suggest significantly greater met-myoglobin (Mmb) concentrations in the lesion core than those in the healthy myocardium and may serve as a marker for irreversible tissue damage. In this work, we present real-time monitoring of permanent injury through spectroscopic assessment of Mmb concentrations at the catheter tip. Atrial wedges (n=6) were excised from four fresh swine hearts and submerged under pulsatile flow of warm (37oC) phosphate buffered saline. A commercial RFA catheter inserted into a fiber optic sheath allowed for simultaneous measurement of tissue diffuse reflectance (DR) spectra (500-650nm) during application of RF energy. Optical measurements were continuously acquired before, during, and post-ablation, in addition to healthy neighboring tissue. Met-myoglobin, oxy-myoglobin, and deoxy-myoglobin concentrations were extracted from each spectrum using an inverse Monte Carlo method. Tissue injury was validated with Masson's trichrome and hematoxylin and eosin staining. Time courses revealed a rapid increase in tissue Mmb concentrations at the onset of RFA treatment and a gradual plateauing thereafter. Extracted Mmb concentrations were significantly greater post-ablation (p<0.0001) as compared to healthy tissue and correlated well with histological assessment of severe thermal tissue destruction. On going studies are aimed at integrating these findings with prior work on near infrared spectroscopic lesion depth assessment. These results support the use of spectroscopy-facilitated guidance of RFA therapies for real-time permanent injury estimation.

  13. Development and Implementation of Discrete Polymeric Microstructural Cues for Applications in Cardiac Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Pinney, James Richardson

    Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. Despite care in the acute setting of MI, subsequent development of scar tissue and a lack of treatments for this maladaptive response lead to a poor prognosis. This has increased burdens on the cost of healthcare due to chronic disability. Here a novel therapeutic strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructural cues to attenuate the fibrotic response and improve functional outcomes is presented. Additionally, applications of integrated chemical functionalizations into discrete, micro-scale polymer structures are discussed in the realm of tissue engineering in order to impart enhancements in in vivo localization, three-dimensional manipulation and drug delivery. Polymeric microstructures, termed "microrods" and "microcubes", were fabricated using photolithographic techniques and studied in three-dimensional culture models of the fibrotic environment and by direct injection into the infarct zone of adult Sprague-Dawley rats. In vitro gene expression and functional and histological results were analyzed, showing a dose-dependent down-regulation fibrotic indicators and improvement in cardiac function. Furthermore, iron oxide nanoparticles and functionalized fluorocarbons were incorporated into the polymeric microdevices to promote in situ visualization by magnetic resonance imaging as well as to facilitate the manipulation and alignment of microstructural cues in a tissue-realistic environment. Lastly, successful encapsulation of native MGF peptide within microrods is demonstrated with release over two weeks as a proof of concept in the ability to locally deliver myogenic or supportive pharmacotherapeutics to the injured myocardium. This work demonstrates the efficacy and versatility of discrete microtopographical cues to attenuate the fibrotic response after MI and suggests a novel

  14. [The morphological changes in the myocardial tissue after sudden cardiac death from alcoholic cardiomyopathy].

    PubMed

    Sokolova, O V

    2016-01-01

    This paper was designed to report the results of the retrospective analysis of the protocols of 180 forensic medical autopsy sections stored in the archives of Sankt-Petersburg Bureau of Forensic Medical Expertise and the data of the histological studies of myocardial tissues obtained after sudden cardiac death from alcoholic cardiomyopathy. The study revealed the following most pathognomonic histological criteria for alcoholic heart lesions: the alternation of hypertrophic and atrophic cardiomyocytes in the state of severe parenchymatous degeneration, pronounced mesenchymal fatty dystrophy in combination with pathological changes of the vascular walls (vascular wall plasmatization), sub-endothelial accumulation of the PAS-positive tissue compounds, microcirculatory disorders in the form of erythrocyte stasis with the manifestations of the blood "sludge" phenomenon, and precapillary fibrosis. The signs of severe parenchymatous and stromal vascular dystrophy of the myocardial histohematic barrier (HHB) are supposed to reflect the toxic effects of ethanol and its metabolites that are directly involved in the mechanisms underlying the disturbances of intracellular metabolism and dyscirculatory events leading to the development of heart muscle hypoxia.

  15. Alginate-polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering.

    PubMed

    Thankam, Finosh G; Muthu, Jayabalan

    2015-11-01

    The physiochemical and biological responses of tissue engineering hydrogels are crucial in determining their desired performance. A hybrid comacromer was synthesized by copolymerizing alginate and poly(mannitol fumarate-co-sebacate) (pFMSA). Three bimodal hydrogels pFMSA-AA, pFMSA-MA and pFMSA-NMBA were synthesized by crosslinking with Ca(2+) and vinyl monomers acrylic acid (AA), methacrylic acid (MA) and N,N'-methylene bisacrylamide (NMBA), respectively. Though all the hydrogels were cytocompatible and exhibited a normal cell cycle profile, pFMSA-AA exhibited superior physiochemical properties viz non-freezable water content (58.34%) and water absorption per unit mass (0.97 g water/g gel) and pore length (19.92±3.91 μm) in comparing with other two hydrogels. The increased non-freezable water content and water absorption of pFMSA-AA hydrogels greatly influenced its biological performance, which was evident from long-term viability assay and cell cycle proliferation. The physiochemical and biological favorability of pFMSA-AA hydrogels signifies its suitability for cardiac tissue engineering.

  16. Minimally invasive injectable short nanofibers of poly(glycerol sebacate) for cardiac tissue engineering

    NASA Astrophysics Data System (ADS)

    Ravichandran, Rajeswari; Reddy Venugopal, Jayarama; Sundarrajan, Subramanian; Mukherjee, Shayanti; Sridhar, Radhakrishnan; Ramakrishna, Seeram

    2012-09-01

    Myocardial tissue lacks the ability to appreciably regenerate itself following myocardial infarction (MI) which ultimately results in heart failure. Current therapies can only retard the progression of disease and hence tissue engineering strategies are required to facilitate the engineering of a suitable biomaterial to repair MI. The aim of this study was to investigate the in vitro properties of an injectable biomaterial for the regeneration of infarcted myocardium. Fabrication of core/shell fibers was by co-axial electrospinning, with poly(glycerol sebacate) (PGS) as core material and poly-l-lactic acid (PLLA) as shell material. The PLLA was removed by treatment of the PGS/PLLA core/shell fibers with DCM:hexane (2:1) to obtain PGS short fibers. These PGS short fibers offer the advantage of providing a minimally invasive injectable technique for the regeneration of infarcted myocardium. The scaffolds were characterized by SEM, FTIR and contact angle and cell-scaffold interactions using cardiomyocytes. The results showed that the cardiac marker proteins actinin, troponin, myosin heavy chain and connexin 43 were expressed more on short PGS fibers compared to PLLA nanofibers. We hypothesized that the injection of cells along with short PGS fibers would increase cell transplant retention and survival within the infarct, compared to the standard cell injection system.

  17. The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

    PubMed

    Albawardi, Alia; Almarzooqi, Saeeda; Saraswathiamma, Dhanya; Abdul-Kader, Hidaya Mohammed; Souid, Abdul-Kader; Alfazari, Ali S

    2015-01-01

    The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus-rapamycin, tacrolimus, and cyclosporine) on cellular respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/ threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 μM) inhibited renal (22%, P=0.002), hepatic (39%, P<0.001), and cardiac (42%, P=0.005) cellular respiration. Tacrolimus and cyclosporine had no or minimum effects on cellular respiration in these tissues. Thus, these results clearly demonstrate that impaired cellular respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.

  18. Adipose Tissue Lipolysis Promotes Exercise-induced Cardiac Hypertrophy Involving the Lipokine C16:1n7-Palmitoleate*

    PubMed Central

    Foryst-Ludwig, Anna; Kreissl, Michael C.; Benz, Verena; Brix, Sarah; Smeir, Elia; Ban, Zsofia; Januszewicz, Elżbieta; Salatzki, Janek; Grune, Jana; Schwanstecher, Anne-Kathrin; Blumrich, Annelie; Schirbel, Andreas; Klopfleisch, Robert; Rothe, Michael; Blume, Katharina; Halle, Martin; Wolfarth, Bernd; Kershaw, Erin E.; Kintscher, Ulrich

    2015-01-01

    Endurance exercise training induces substantial adaptive cardiac modifications such as left ventricular hypertrophy (LVH). Simultaneously to the development of LVH, adipose tissue (AT) lipolysis becomes elevated upon endurance training to cope with enhanced energy demands. In this study, we investigated the impact of adipose tissue lipolysis on the development of exercise-induced cardiac hypertrophy. Mice deficient for adipose triglyceride lipase (Atgl) in AT (atATGL-KO) were challenged with chronic treadmill running. Exercise-induced AT lipolytic activity was significantly reduced in atATGL-KO mice accompanied by the absence of a plasma fatty acid (FA) increase. These processes were directly associated with a prominent attenuation of myocardial FA uptake in atATGL-KO and a significant reduction of the cardiac hypertrophic response to exercise. FA serum profiling revealed palmitoleic acid (C16:1n7) as a new molecular co-mediator of exercise-induced cardiac hypertrophy by inducing nonproliferative cardiomyocyte growth. In parallel, serum FA analysis and echocardiography were performed in 25 endurance athletes. In consonance, the serum C16:1n7 palmitoleate level exhibited a significantly positive correlation with diastolic interventricular septum thickness in those athletes. No correlation existed between linoleic acid (18:2n6) and diastolic interventricular septum thickness. Collectively, our data provide the first evidence that adipose tissue lipolysis directly promotes the development of exercise-induced cardiac hypertrophy involving the lipokine C16:1n7 palmitoleate as a molecular co-mediator. The identification of a lipokine involved in physiological cardiac growth may help to develop future lipid-based therapies for pathological LVH or heart failure. PMID:26260790

  19. Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease

    PubMed Central

    Avolio, Elisa; Rodriguez-Arabaolaza, Iker; Spencer, Helen L; Riu, Federica; Mangialardi, Giuseppe; Slater, Sadie C; Rowlinson, Jonathan; Alvino, Valeria V; Idowu, Oluwasomidotun O; Soyombo, Stephanie; Oikawa, Atsuhiko; Swim, Megan M; Kong, Cherrie H T; Cheng, Hongwei; Jia, Huidong; Ghorbel, Mohamed T; Hancox, Jules C; Orchard, Clive H; Angelini, Gianni; Emanueli, Costanza; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    Background Living grafts produced by combining autologous heart-resident stem/progenitor cells and tissue engineering could provide a new therapeutic option for definitive correction of congenital heart disease. The aim of the study was to investigate the antigenic profile, expansion/differentiation capacity, paracrine activity, and pro-angiogenic potential of cardiac pericytes and to assess their engrafting capacity in clinically certified prosthetic grafts. Methods and Results CD34pos cells, negative for the endothelial markers CD31 and CD146, were identified by immunohistochemistry in cardiac leftovers from infants and children undergoing palliative repair of congenital cardiac defects. Following isolation by immunomagnetic bead-sorting and culture on plastic in EGM-2 medium supplemented with growth factors and serum, CD34pos/CD31neg cells gave rise to a clonogenic, highly proliferative (>20 million at P5), spindle-shape cell population. The following populations were shown to expresses pericyte/mesenchymal and stemness markers. After exposure to differentiation media, the expanded cardiac pericytes acquired markers of vascular smooth muscle cells, but failed to differentiate into endothelial cells or cardiomyocytes. However, in Matrigel, cardiac pericytes form networks and enhance the network capacity of endothelial cells. Moreover, they produce collagen-1 and release chemo-attractants that stimulate the migration of c-Kitpos cardiac stem cells. Cardiac pericytes were then seeded onto clinically approved xenograft scaffolds and cultured in a bioreactor. After 3 weeks, fluorescent microscopy showed that cardiac pericytes had penetrated into and colonized the graft. Conclusions These findings open new avenues for cellular functionalization of prosthetic grafts to be applied in reconstructive surgery of congenital heart disease. PMID:26080813

  20. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    PubMed Central

    Fattouh, Aya M; El-Shabrawi, Mortada H; Mahmoud, Enas H; Ahmed, Wafaa O

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue Doppler imaging. Results: Patients’ mean ages were 7.66 ± 4.16 years (vs. 6.88 ± 3.04 years for the controls). The study included 27 males and 25 females (28 and 25 respectively for the controls). Patients had larger left atrium and right ventricle (RV) (P value 0.05) and increased LV posterior wall thickness than controls (P value 0.04). They had higher late atrial diastolic filling velocity (A) of tricuspid valve (TV) inflow (0.59 ± 0.17 vs. 0.5 ± 0.1 m/s, P < 0.001) and lower ratios between the early diastolic filling velocity (E) and A wave velocity (E/A) of both mitral valve and TV inflow (1.7 ± 0.35 vs. 1.87 ± 0.34 and 1.3 ± 0.3 vs. 1.5 ± 0.3, P < 0.005 and 0.0008, respectively). Patients had significantly longer isovolumic relaxation time of LV (45.5 ± 11.1 vs. 40.5 ± 7.7 ms P 0.008), higher late diastolic peak myocardial velocity (A’) (11.8 ± 3.6 vs. 9.5 ± 2.7 ms, P 0.0003) and systolic velocity (S’) of the RV (14.5 ± 2.7 vs. 13.2 ± 2.9, P 0.01) and significantly higher myocardial performance index of both LV and RV (P 0.001 and 0.01). BNP levels were significantly higher in cases than controls (5.25 ng/l vs. 3.75 ng/l, P < 0.04) and was correlated with the E wave velocity of the TV (r 0.004) and the E/E’ ratio of the RV (r 0.001). None of the clinical or laboratory data were correlated with the BNP level. Conclusion Cirrhotic children have cardiac dysfunction mainly in the form of diastolic dysfunction. There is a need that CCM be more accurately

  1. Super-resolution fluorescence imaging to study cardiac biophysics: α-actinin distribution and Z-disk topologies in optically thick cardiac tissue slices.

    PubMed

    Hou, Yufeng; Crossman, David J; Rajagopal, Vijay; Baddeley, David; Jayasinghe, Isuru; Soeller, Christian

    2014-08-01

    A major motivation for the use of super-resolution imaging methods in the investigation of cardiac biophysics has been the insight from biophysical considerations and detailed mathematical modeling that the spatial structure and protein organisation at the scale of nanometres can have enormous implications for calcium signalling in cardiac muscle. We illustrate the use of dSTORM based super-resolution in optically thick (∼10 μm) tissue slices of rat ventricular tissue to visualize proteins at the cardiac Z-disk and compare those images with confocal (diffraction-limited) as well as electron microscopy (EM) data which still provides a benchmark in terms of resolution. α-actinin is an abundant protein target that effectively defines the Z-disk in striated muscle and provides a reference structure for other proteins at the Z-line and the transverse tubules. Using super-resolution imaging α-actinin labelling provides very detailed outlines of the contractile machinery which we have used to study the properties of Z-disks and the distribution of α-actinin itself. We determined the local diameters of the myo-fibrillar and non-myofibrillar space using α-actinin labelling. Comparison between confocal and super-resolution based myofibrillar masks suggested that super-resolution data was able to segment myofibrils accurately while confocal approaches were not always able to distinguish neighbouring myofibrillar bundles which resulted in overestimated diameters. The increased resolution of super-resolution methods provides qualitatively new information to improve our understanding of cardiac biophysics. Nevertheless, conventional diffraction-limited imaging still has an important role to play which we illustrate with correlative confocal and super-resolution data.

  2. Enhancing the depth of tissue microscope imaging using two-photon excitation of the second singlet state of fluorescent agents

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Shi, Lingyan; Pratavieira, Sebastião.; Alfano, R. R.

    2014-03-01

    Increasing the depth to image inside tissue is critical in biomedicine. Two-photon (2P) excitation of the second singlet (S2) state of a group of fluorescent agents with near infrared emission, Chlorophyll a (Chl a) and Indocyanine green (ICG), is used to extend the optical imaging regime of 2PM into "tissue optical window" for deep tissue penetration. The fast nonradiative from S2 to S1 yields both emission and absorption wavelengths in the therapeutic window. The salient feature is to place both the 2P excitation and emission wavelengths of the imaging agents falling into the "tissue optical window". As a first step to achieve deeper optical imaging, Chl a and ICG are investigated and demonstrated as imaging agents for 2P S2 excitation microscope image.

  3. Chronic hindlimb suspension unloading markedly decreases turnover rates of skeletal and cardiac muscle proteins and adipose tissue triglycerides.

    PubMed

    Bederman, Ilya R; Lai, Nicola; Shuster, Jeffrey; Henderson, Leigh; Ewart, Steven; Cabrera, Marco E

    2015-07-01

    We previously showed that a single bolus of "doubly-labeled" water ((2)H2 (18)O) can be used to simultaneously determine energy expenditure and turnover rates (synthesis and degradation) of tissue-specific lipids and proteins by modeling labeling patterns of protein-bound alanine and triglyceride-bound glycerol (Bederman IR, Dufner DA, Alexander JC, Previs SF. Am J Physiol Endocrinol Metab 290: E1048-E1056, 2006). Using this novel method, we quantified changes in the whole body and tissue-specific energy balance in a rat model of simulated "microgravity" induced by hindlimb suspension unloading (HSU). After chronic HSU (3 wk), rats exhibited marked atrophy of skeletal and cardiac muscles and significant decrease in adipose tissue mass. For example, soleus muscle mass progressively decreased 11, 43, and 52%. We found similar energy expenditure between control (90 ± 3 kcal · kg(-1)· day(-1)) and hindlimb suspended (81 ± 6 kcal/kg day) animals. By comparing food intake (∼ 112 kcal · kg(-1) · day(-1)) and expenditure, we found that animals maintained positive calorie balance proportional to their body weight. From multicompartmental fitting of (2)H-labeling patterns, we found significantly (P < 0.005) decreased rates of synthesis (percent decrease from control: cardiac, 25.5%; soleus, 70.3%; extensor digitorum longus, 44.9%; gastrocnemius, 52.5%; and adipose tissue, 39.5%) and rates of degradation (muscles: cardiac, 9.7%; soleus, 52.0%; extensor digitorum longus, 27.8%; gastrocnemius, 37.4%; and adipose tissue, 50.2%). Overall, HSU affected growth of young rats by decreasing the turnover rates of proteins in skeletal and cardiac muscles and adipose tissue triglycerides. Specifically, we found that synthesis rates of skeletal and cardiac muscle proteins were affected to a much greater degree compared with the decrease in degradation rates, resulting in large negative balance and significant tissue loss. In contrast, we found a small decrease in adipose tissue

  4. MRI-based morphological modeling, synthesis and characterization of cardiac tissue-mimicking materials.

    PubMed

    Kossivas, Fotis; Angeli, S; Kafouris, D; Patrickios, C S; Tzagarakis, V; Constantinides, C

    2012-06-01

    This study uses standard synthetic methodologies to produce tissue-mimicking materials that match the morphology and emulate the in vivo murine and human cardiac mechanical and imaging characteristics, with dynamic mechanical analysis, atomic force microscopy (AFM), scanning electron microscopy (SEM) and magnetic resonance imaging. In accordance with such aims, poly(glycerol sebacate) (PGS) elastomeric materials were synthesized (at two different glycerol (G)-sebacic (S) acid molar ratios; the first was synthesized using a G:S molar ratio of 2:2, while the second from a 2:5 G:S molar ratio, resulting in PGS2:2 and PGS2:5 elastomers, respectively). Unlike the synthesized PGS2:2 elastomers, the PGS2:5 materials were characterized by an overall mechanical instability in their loading behavior under the three successive loading conditions tested. An oscillatory response in the mechanical properties of the synthesized elastomers was observed throughout the loading cycles, with measured increased storage modulus values at the first loading cycle, stabilizing to lower values at subsequent cycles. These elastomers were characterized at 4 °C and were found to have storage modulus values of 850 and 1430 kPa at the third loading cycle, respectively, in agreement with previously reported values of the rat and human myocardium. SEM of surface topology indicated minor degradation of synthesized materials at 10 and 20 d post-immersion in the PBS buffer solution, with a noted cluster formation on the PGS2:5 elastomers. AFM nanoindentation experiments were also conducted for the measurement of the Young modulus of the sample surface (no bulk contribution). Correspondingly, the PGS2:2 elastomer indicated significantly decreased surface Young's modulus values 20 d post-PBS immersion, compared to dry conditions (Young's modulus = 1160 ± 290 kPa (dry) and 200 ± 120 kPa (20 d)). In addition to the two-dimensional (2D) elastomers, an integrative platform for accurate construction of

  5. Waveguide and articulated arm for Er:YAG laser system: shape and depth of laser cavity in hard dental tissues

    NASA Astrophysics Data System (ADS)

    Jelinkova, Helena; Dostalova, Tatjana; Miyagi, Mitsunobu; Wang, You; Shi, Yi-Wei; Dolezalova, Libuse; Hamal, Karel; Krejsa, Otakar; Kubelka, Jiri; Prochazka, Stanislav

    1998-04-01

    The aim of our study was to verify the efficiency of delivery systems for Er:YAG laser radiation which could be used in dentistry. The influence of increasing energy and number of pulses on a profile and depth of drilled holes was investigated. Er:YAG laser was operating in a free-running mode, generating a length of pulses 200 microsecond with a maximum energy of 500 mJ. The delivery systems investigated were an articulated arm and a fluorocarbon polymer-coated silver hollow glass waveguide. The prepared hard tissues were a sliced part of enamel, dentine and ivory. The laser radiation was directed on them by focusing optics (CaF2 lens) together with the cooling water to ensure that the tissues will not be burned. For the evaluation of shapes, depth and profiles of the prepared cavities the metallographic microscope, x-ray microtomograph and scanning electron microscope were used. From the results it was observed that the profile and depth of the cavities prepared by the laser radiation delivered by the various systems (waveguide or articulated arm) are not the same. The laser radiation delivered by waveguide produces a larger diameter cavity with a lower depth. The holes are smoother and without side effects.

  6. Facial soft tissue depths in craniofacial identification (part II): An analytical review of the published sub-adult data.

    PubMed

    Stephan, Carl N; Simpson, Ellie K

    2008-11-01

    Prior research indicates that while statistically significant differences exist between subcategories of the adult soft tissue depth data, magnitudes of difference are small and possess little practical meaning when measurement errors and variations between measurement methods are considered. These findings raise questions as to what variables may or may not hold meaning for the sub-adult data. Of primary interest is the effect of age, as these differences have the potential to surpass the magnitude of measurement error. Data from the five studies in the literature on sub-adults which describe values for single integer age groups were pooled and differences across the ages examined. From 1 to 18 years, most soft tissue depth measurements increased by less than 3 mm. These results suggest that dividing the data for children into more than two age groups is unlikely to hold many advantages. Data were therefore split into two groups with the division point corresponding to the mid-point of the observed trends and main data density (0-11 and 12-18 years; division point = 11.5 years). Published sub-adult data for seven further studies which reported broader age groups were pooled with the data above to produce the final tallied soft tissue depth tables. These tables hold the advantages of increased sample sizes (pogonion has greater than 1770 individuals for either age group) and increased levels of certainty (as random and opposing systematic errors specific to each independent study should average out when the data are combined).

  7. Exact coherent structures and chaotic dynamics in a model of cardiac tissue.

    PubMed

    Byrne, Greg; Marcotte, Christopher D; Grigoriev, Roman O

    2015-03-01

    Unstable nonchaotic solutions embedded in the chaotic attractor can provide significant new insight into chaotic dynamics of both low- and high-dimensional systems. In particular, in turbulent fluid flows, such unstable solutions are referred to as exact coherent structures (ECS) and play an important role in both initiating and sustaining turbulence. The nature of ECS and their role in organizing spatiotemporally chaotic dynamics, however, is reasonably well understood only for systems on relatively small spatial domains lacking continuous Euclidean symmetries. Construction of ECS on large domains and in the presence of continuous translational and/or rotational symmetries remains a challenge. This is especially true for models of excitable media which display spiral turbulence and for which the standard approach to computing ECS completely breaks down. This paper uses the Karma model of cardiac tissue to illustrate a potential approach that could allow computing a new class of ECS on large domains of arbitrary shape by decomposing them into a patchwork of solutions on smaller domains, or tiles, which retain Euclidean symmetries locally. PMID:25833430

  8. Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration.

    PubMed

    Emmert, Maximilian Y; Hitchcock, Robert W; Hoerstrup, Simon P

    2014-04-01

    Ischemic Heart Disease (IHD) still represents the "Number One Killer" worldwide accounting for the death of numerous patients. However the capacity for self-regeneration of the adult heart is very limited and the loss of cardiomyocytes in the infarcted heart leads to continuous adverse cardiac-remodeling which often leads to heart-failure (HF). The concept of regenerative medicine comprising cell-based therapies, bio-engineering technologies and hybrid solutions has been proposed as a promising next-generation approach to address IHD and HF. Numerous strategies are under investigation evaluating the potential of regenerative medicine on the failing myocardium including classical cell-therapy concepts, three-dimensional culture techniques and tissue-engineering approaches. While most of these regenerative strategies have shown great potential in experimental studies, the translation into a clinical setting has either been limited or too rapid leaving many key questions unanswered. This review summarizes the current state-of-the-art, important challenges and future research directions as to regenerative approaches addressing IHD and resulting HF.

  9. Exact coherent structures and chaotic dynamics in a model of cardiac tissue

    SciTech Connect

    Byrne, Greg; Marcotte, Christopher D.; Grigoriev, Roman O.

    2015-03-15

    Unstable nonchaotic solutions embedded in the chaotic attractor can provide significant new insight into chaotic dynamics of both low- and high-dimensional systems. In particular, in turbulent fluid flows, such unstable solutions are referred to as exact coherent structures (ECS) and play an important role in both initiating and sustaining turbulence. The nature of ECS and their role in organizing spatiotemporally chaotic dynamics, however, is reasonably well understood only for systems on relatively small spatial domains lacking continuous Euclidean symmetries. Construction of ECS on large domains and in the presence of continuous translational and/or rotational symmetries remains a challenge. This is especially true for models of excitable media which display spiral turbulence and for which the standard approach to computing ECS completely breaks down. This paper uses the Karma model of cardiac tissue to illustrate a potential approach that could allow computing a new class of ECS on large domains of arbitrary shape by decomposing them into a patchwork of solutions on smaller domains, or tiles, which retain Euclidean symmetries locally.

  10. Improved cardiac motion detection from ultrasound images using TDIOF: a combined B-mode/ tissue Doppler approach

    NASA Astrophysics Data System (ADS)

    Tavakoli, Vahid; Stoddard, Marcus F.; Amini, Amir A.

    2013-03-01

    Quantitative motion analysis of echocardiographic images helps clinicians with the diagnosis and therapy of patients suffering from cardiac disease. Quantitative analysis is usually based on TDI (Tissue Doppler Imaging) or speckle tracking. These methods are based on two independent techniques - the Doppler Effect and image registration, respectively. In order to increase the accuracy of the speckle tracking technique and cope with the angle dependency of TDI, herein, a combined approach dubbed TDIOF (Tissue Doppler Imaging Optical Flow) is proposed. TDIOF is formulated based on the combination of B-mode and Doppler energy terms in an optical flow framework and minimized using algebraic equations. In this paper, we report on validations with simulated, physical cardiac phantom, and in-vivo patient data. It is shown that the additional Doppler term is able to increase the accuracy of speckle tracking, the basis for several commercially available echocardiography analysis techniques.

  11. Development of Electrically Conductive Double-Network Hydrogels via One-Step Facile Strategy for Cardiac Tissue Engineering.

    PubMed

    Yang, Boguang; Yao, Fanglian; Hao, Tong; Fang, Wancai; Ye, Lei; Zhang, Yabin; Wang, Yan; Li, Junjie; Wang, Changyong

    2016-02-18

    Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of electrical conductivity of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one-step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chemical crosslinked poly(thiophene-3-acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo-crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mechanical, and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its conductivity (≈10(-4) S cm(-1)) falls in the range of reported conductivities for native myocardium tissue. To assess their biological activity, the brown adipose-derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without electrical stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, electrical stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.

  12. Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

    PubMed Central

    Danoviz, Maria E.; Nakamuta, Juliana S.; Marques, Fabio L. N.; dos Santos, Leonardo; Alvarenga, Erica C.; dos Santos, Alexandra A.; Antonio, Ednei L.; Schettert, Isolmar T.; Tucci, Paulo J.; Krieger, Jose E.

    2010-01-01

    Background Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers. PMID:20711471

  13. Increased interstitial loading reduces the effect of microstructural variations in cardiac tissue.

    PubMed

    Hubbard, Marjorie Letitia; Henriquez, Craig S

    2010-04-01

    Electrical propagation in diseased and aging hearts is strongly influenced by structural changes that occur in both the intracellular and interstitial spaces of cardiac tissue; however, very few studies have investigated how interactions between the two spaces affect propagation at the microscale. In this study, we used one-dimensional microstructural computer models of interconnected ventricular myocytes to systematically investigate how increasing the effective interstitial resistivity (rho(oeff)) influences action potential propagation in fibers with variations in intracellular properties such as cell coupling and cell length. Changes in rho(oeff) were incorporated into a monodomain model using a correction to the intracellular properties that was based on bidomain simulations. The results showed that increasing rho(oeff) in poorly coupled one-dimensional fibers alters the distribution of electrical load at the microscale and causes propagation to become more continuous. In the poorly coupled fiber, this continuous state is characterized by decreased gap junction delay, sustained conduction velocity, increased sodium current, reduced maximum upstroke velocity, and increased safety factor. Long, poorly coupled cells experience greater loading effects than short cells and show the greatest initial response to changes in rho(oeff). In inhomogeneous fibers with adjacent well-coupled and poorly coupled regions, increasing rho(oeff) in the poorly coupled region also reduces source-load mismatch, which delays the onset of conduction block and reduces the dispersion of repolarization at the transition between the two regions. Increasing the rho(oeff) minimizes the effect of cell-to-cell variations and may influence the pattern of activation in critical regimes characterized by low intercellular coupling, microstructural heterogeneity, and reduced or abnormal membrane excitability. PMID:20097772

  14. Laser speckle contrast imaging with extended depth of field for in-vivo tissue imaging

    PubMed Central

    Sigal, Iliya; Gad, Raanan; Caravaca-Aguirre, Antonio M.; Atchia, Yaaseen; Conkey, Donald B.; Piestun, Rafael; Levi, Ofer

    2013-01-01

    This work presents, to our knowledge, the first demonstration of the Laser Speckle Contrast Imaging (LSCI) technique with extended depth of field (DOF). We employ wavefront coding on the detected beam to gain quantitative information on flow speeds through a DOF extended two-fold compared to the traditional system. We characterize the system in-vitro using controlled microfluidic experiments, and apply it in-vivo to imaging the somatosensory cortex of a rat, showing improved ability to image flow in a larger number of vessels simultaneously. PMID:24466481

  15. Single-molecule RNA detection at depth by hybridization chain reaction and tissue hydrogel embedding and clearing

    PubMed Central

    Shah, Sheel; Lubeck, Eric; Schwarzkopf, Maayan; He, Ting-Fang; Greenbaum, Alon; Sohn, Chang Ho; Lignell, Antti; Choi, Harry M. T.; Gradinaru, Viviana; Pierce, Niles A.

    2016-01-01

    Accurate and robust detection of mRNA molecules in thick tissue samples can reveal gene expression patterns in single cells within their native environment. Preserving spatial relationships while accessing the transcriptome of selected cells is a crucial feature for advancing many biological areas – from developmental biology to neuroscience. However, because of the high autofluorescence background of many tissue samples, it is difficult to detect single-molecule fluorescence in situ hybridization (smFISH) signals robustly in opaque thick samples. Here, we draw on principles from the emerging discipline of dynamic nucleic acid nanotechnology to develop a robust method for multi-color, multi-RNA imaging in deep tissues using single-molecule hybridization chain reaction (smHCR). Using this approach, single transcripts can be imaged using epifluorescence, confocal or selective plane illumination microscopy (SPIM) depending on the imaging depth required. We show that smHCR has high sensitivity in detecting mRNAs in cell culture and whole-mount zebrafish embryos, and that combined with SPIM and PACT (passive CLARITY technique) tissue hydrogel embedding and clearing, smHCR can detect single mRNAs deep within thick (0.5 mm) brain slices. By simultaneously achieving ∼20-fold signal amplification and diffraction-limited spatial resolution, smHCR offers a robust and versatile approach for detecting single mRNAs in situ, including in thick tissues where high background undermines the performance of unamplified smFISH. PMID:27342713

  16. Single-molecule RNA detection at depth by hybridization chain reaction and tissue hydrogel embedding and clearing.

    PubMed

    Shah, Sheel; Lubeck, Eric; Schwarzkopf, Maayan; He, Ting-Fang; Greenbaum, Alon; Sohn, Chang Ho; Lignell, Antti; Choi, Harry M T; Gradinaru, Viviana; Pierce, Niles A; Cai, Long

    2016-08-01

    Accurate and robust detection of mRNA molecules in thick tissue samples can reveal gene expression patterns in single cells within their native environment. Preserving spatial relationships while accessing the transcriptome of selected cells is a crucial feature for advancing many biological areas - from developmental biology to neuroscience. However, because of the high autofluorescence background of many tissue samples, it is difficult to detect single-molecule fluorescence in situ hybridization (smFISH) signals robustly in opaque thick samples. Here, we draw on principles from the emerging discipline of dynamic nucleic acid nanotechnology to develop a robust method for multi-color, multi-RNA imaging in deep tissues using single-molecule hybridization chain reaction (smHCR). Using this approach, single transcripts can be imaged using epifluorescence, confocal or selective plane illumination microscopy (SPIM) depending on the imaging depth required. We show that smHCR has high sensitivity in detecting mRNAs in cell culture and whole-mount zebrafish embryos, and that combined with SPIM and PACT (passive CLARITY technique) tissue hydrogel embedding and clearing, smHCR can detect single mRNAs deep within thick (0.5 mm) brain slices. By simultaneously achieving ∼20-fold signal amplification and diffraction-limited spatial resolution, smHCR offers a robust and versatile approach for detecting single mRNAs in situ, including in thick tissues where high background undermines the performance of unamplified smFISH. PMID:27342713

  17. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy.

    PubMed

    Cashman, Timothy J; Josowitz, Rebecca; Johnson, Bryce V; Gelb, Bruce D; Costa, Kevin D

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death that often goes undetected in the general population. HCM is also prevalent in patients with cardio-facio-cutaneous syndrome (CFCS), which is a genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade. Understanding the mechanisms of HCM development in such RASopathies may lead to novel therapeutic strategies, but relevant experimental models of the human condition are lacking. Therefore, the objective of this study was to develop the first 3D human engineered cardiac tissue (hECT) model of HCM. The hECTs were created using human cardiomyocytes obtained by directed differentiation of induced pluripotent stem cells derived from a patient with CFCS due to an activating BRAF mutation. The mutant myocytes were directly conjugated at a 3:1 ratio with a stromal cell population to create a tissue of defined composition. Compared to healthy patient control hECTs, BRAF-hECTs displayed a hypertrophic phenotype by culture day 6, with significantly increased tissue size, twitch force, and atrial natriuretic peptide (ANP) gene expression. Twitch characteristics reflected increased contraction and relaxation rates and shorter twitch duration in BRAF-hECTs, which also had a significantly higher maximum capture rate and lower excitation threshold during electrical pacing, consistent with a more arrhythmogenic substrate. By culture day 11, twitch force was no longer different between BRAF and wild-type hECTs, revealing a temporal aspect of disease modeling with tissue engineering. Principal component analysis identified diastolic force as a key factor that changed from day 6 to day 11, supported by a higher passive stiffness in day 11 BRAF-hECTs. In summary, human engineered cardiac tissues created from BRAF mutant cells recapitulated, for the first time, key aspects of the HCM phenotype, offering a new in vitro model for studying intrinsic mechanisms and screening new

  18. Cardiac troponin I is abnormally expressed in non-small cell lung cancer tissues and human cancer cells.

    PubMed

    Chen, Chao; Liu, Jia-Bao; Bian, Zhi-Ping; Xu, Jin-Dan; Wu, Heng-Fang; Gu, Chun-Rong; Shi, Yi; Zhang, Ji-Nan; Chen, Xiang-Jian; Yang, Di

    2014-01-01

    Cardiac troponin I (cTnI) is the only sarcomeric protein identified to date that is expressed exclusively in cardiac muscle. Its expression in cancer tissues has not been reported. Herein, we examined cTnI expression in non-small cell lung cancer (NSCLC) tissues, human adenocarcinoma cells SPCA-1 (lung) and BGC 823 (gastric) by immunohistochemistry, western blot analysis and real-time PCR. Immunopositivity for cTnI was demonstrated in 69.4% (34/49) NSCLC tissues evaluated, and was strong intensity in 35.3% (6/17) lung squamous cell carcinoma cases. The non-cancer-bearing lung tissues except tuberculosis (9/9, 100%) showed negative staining for cTnI. Seven monoclonal antibodies (mAbs) against human cTnI were applied in immunofluorescence. The result showed that the staining pattern within SPCA-1 and BGC 823 was dependent on the epitope of the cTnI mAbs. The membrane and nucleus of cancer cells were stained by mAbs against N-terminal peptides of cTnI, and cytoplasm was stained by mAbs against the middle and C-terminal peptides of cTnI. A ~25 kD band was identified by anti-cTnI mAb in SPCA-1 and BGC 823 extracts by western blot, as well as in cardiomyocyte extracts. The cTnI mRNA expressions in SPCA-1 and BGC 823 cells were about ten thousand times less than that in cardiomyocytes. Our study shows for the first time that cTnI protein and mRNA were abnormally expressed in NSCLC tissues, SPCA-1 and BGC 823 cells. These findings challenge the conventional view of cTnI as a cardiac-specific protein, enabling the potential use of cTnI as a diagnostic marker or targeted therapy for cancer.

  19. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy

    PubMed Central

    Johnson, Bryce V.; Gelb, Bruce D.; Costa, Kevin D.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death that often goes undetected in the general population. HCM is also prevalent in patients with cardio-facio-cutaneous syndrome (CFCS), which is a genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade. Understanding the mechanisms of HCM development in such RASopathies may lead to novel therapeutic strategies, but relevant experimental models of the human condition are lacking. Therefore, the objective of this study was to develop the first 3D human engineered cardiac tissue (hECT) model of HCM. The hECTs were created using human cardiomyocytes obtained by directed differentiation of induced pluripotent stem cells derived from a patient with CFCS due to an activating BRAF mutation. The mutant myocytes were directly conjugated at a 3:1 ratio with a stromal cell population to create a tissue of defined composition. Compared to healthy patient control hECTs, BRAF-hECTs displayed a hypertrophic phenotype by culture day 6, with significantly increased tissue size, twitch force, and atrial natriuretic peptide (ANP) gene expression. Twitch characteristics reflected increased contraction and relaxation rates and shorter twitch duration in BRAF-hECTs, which also had a significantly higher maximum capture rate and lower excitation threshold during electrical pacing, consistent with a more arrhythmogenic substrate. By culture day 11, twitch force was no longer different between BRAF and wild-type hECTs, revealing a temporal aspect of disease modeling with tissue engineering. Principal component analysis identified diastolic force as a key factor that changed from day 6 to day 11, supported by a higher passive stiffness in day 11 BRAF-hECTs. In summary, human engineered cardiac tissues created from BRAF mutant cells recapitulated, for the first time, key aspects of the HCM phenotype, offering a new in vitro model for studying intrinsic mechanisms and screening new

  20. A mathematical model for analyzing the elasticity, viscosity, and failure of soft tissue: comparison of native and decellularized porcine cardiac extracellular matrix for tissue engineering.

    PubMed

    Bronshtein, Tomer; Au-Yeung, Gigi Chi Ting; Sarig, Udi; Nguyen, Evelyne Bao-Vi; Mhaisalkar, Priyadarshini S; Boey, Freddy Yin Chiang; Venkatraman, Subbu S; Machluf, Marcelle

    2013-08-01

    The clinical success of tissue-engineered constructs commonly requires mechanical properties that closely mimic those of the human tissue. Determining the viscoelastic properties of such biomaterials and the factors governing their failure profiles, however, has proven challenging, although collecting extensive data regarding their tensile behavior is straightforward. The easily calculated Young's modulus remains the most reported mechanical measure, regardless of its limitations, even though single-relaxation-time (SRT) models can provide much more information, which remain scarce due to a lack of manageable tools for implementing these models. We developed an easy-to-use algorithm for applying the Zener SRT model and determining the elastic moduli, viscosity, and failure profiles of materials under different mechanical tests in a user-independent manner. The algorithm was validated on the data resulting from tensile tests on native and decellularized porcine cardiac tissue, previously suggested as a promising scaffold material for cardiac tissue engineering. This analysis yields new and more accurate measurements such as the elastic moduli and viscosity, the model's relaxation time, and information on the factors governing the materials' failure profiles. These measurements indicate that the viscoelasticity and strength of the decellularized acellular extracellular matrix (ECM) are similar to those of native tissue, although its elasticity and apparent viscosity are higher. Nonetheless, reseeding and culturing the ECM with mesenchymal stem cells was shown to partially restore the mechanical properties lost after decellularization. We propose this algorithm as a platform for soft-tissue analysis that can provide comparable and unbiased measures for characterizing viscoelastic biomaterials commonly used in tissue engineering.

  1. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

    PubMed

    Patel, Vaibhav B; Mori, Jun; McLean, Brent A; Basu, Ratnadeep; Das, Subhash K; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M; Grant, Maria B; Lopaschuk, Gary D; Oudit, Gavin Y

    2016-01-01

    Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance.

  2. Cardiac mitochondrial function and tissue remodelling are improved by a non-antihypertensive dose of enalapril in spontaneously hypertensive rats.

    PubMed

    Piotrkowski, Barbara; Koch, Osvaldo R; De Cavanagh, Elena M V; Fraga, César G

    2009-04-01

    Renal and cardiac benefits of renin-angiotensin system inhibition exceed blood pressure (BP) reduction and seem to involve mitochondrial function. It has been shown that RAS inhibition prevented mitochondrial dysfunction in spontaneously hypertensive rats (SHR) kidneys. Here, it is investigated whether a non-antihypertensive enalapril dose protects cardiac tissue and mitochondria function. Three-month-old SHR received water containing enalapril (10 mg/kg/day, SHR+Enal) or no additions (SHR-C) for 5 months. Wistar-Kyoto rats (WKY) were normotensive controls. At month 5, BP was similar in SHR+Enal and SHR-C. In SHR+Enal and WKY, heart weight and myocardial fibrosis were lower than in SHR-C. Matrix metalloprotease-2 activity was lower in SHR+Enal with respect to SHR-C and WKY. In SHR+Enal and WKY, NADH/cytochrome c oxidoreductase activity, eNOS protein and activity and mtNOS activity were higher and Mn-SOD activity was lower than in SHR-C. In summary, enalapril at a non-antihypertensive dose prevented cardiac hypertrophy and modifies parameters of cardiac mitochondrial dysfunction in SHR. PMID:19296328

  3. Penetration depth in tissue-mimicking phantoms from hyperspectral imaging in SWIR in transmission and reflection geometry

    NASA Astrophysics Data System (ADS)

    Zhang, Hairong; Salo, Daniel; Kim, David M.; Berezin, Mikhail Y.

    2016-03-01

    We explored the depth penetration in tissue-mimicking intralipid-based phantoms in SWIR (800-1650 nm) using a hyperspectral imaging system composed from a 2D CCD camera coupled to a microscope. Hyperspectral images in transmission and reflection geometries were collected with a spectral resolution of 5.27 nm and a total acquisition time of 3 minutes or less that minimized artifacts from sample drying. Michelson spatial contrast was used as a metric to evaluate light penetration. Results from both transmission and reflection geometries consistently revealed the highest spatial contrast in the wavelength range of 1300 to 1350 nm.

  4. Correlation-based discrimination between cardiac tissue and blood for segmentation of the left ventricle in 3-D echocardiographic images.

    PubMed

    Saris, Anne E C M; Nillesen, Maartje M; Lopata, Richard G P; de Korte, Chris L

    2014-03-01

    For automated segmentation of 3-D echocardiographic images, incorporation of temporal information may be helpful. In this study, optimal settings for calculation of temporal cross-correlations between subsequent time frames were determined, to obtain the maximum cross-correlation (MCC) values that provided the best contrast between blood and cardiac tissue over the entire cardiac cycle. Both contrast and boundary gradient quality measures were assessed to optimize MCC values with respect to signal choice (radiofrequency or envelope data) and axial window size. Optimal MCC values were incorporated into a deformable model to automatically segment the left ventricular cavity. MCC values were tested against, and combined with, filtered, demodulated radiofrequency data. Results reveal that using envelope data in combination with a relatively small axial window (0.7-1.25 mm) at fine scale results in optimal contrast and boundary gradient between the two tissues over the entire cardiac cycle. Preliminary segmentation results indicate that incorporation of MCC values has additional value for automated segmentation of the left ventricle. PMID:24412178

  5. ACE2/Ang 1-7 axis: A critical regulator of epicardial adipose tissue inflammation and cardiac dysfunction in obesity.

    PubMed

    Patel, Vaibhav B; Basu, Ratnadeep; Oudit, Gavin Y

    2016-01-01

    Obesity is characterized by an excessive fat accumulation in adipose tissues leading to weight gain and is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; activated RAS and angiotensin (Ang) II production results in worsening of cardiovascular diseases and angiotensin converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. ACE2 is expressed in the adipocytes and its expression is upregulated in response to high fat diet induced obesity in mice. Loss of ACE2 results in heart failure with preserved ejection fraction which is mediated in part by epicardial adipose tissue inflammation. Angiotensin 1-7 reduces the obesity associated cardiac dysfunction predominantly via its role in adiponectin expression and attenuation of epicardial adipose tissue inflammation. Human heart disease is also linked with inflammed epicardial adipose tissue. Here, we discuss the important interpretation of the novel of ACE2/Ang 1-7 pathway in obesity associated cardiac dysfunction. PMID:27617176

  6. Relative capacities of time-gated versus continuous-wave imaging to localize tissue embedded vessels with increasing depth

    NASA Astrophysics Data System (ADS)

    Patel, Nimit L.; Lin, Zi-Jing; Rathore, Yajuvendra; Livingston, Edward H.; Liu, Hanli; Alexandrakis, George

    2010-01-01

    Surgeons often cannot see major vessels embedded in adipose tissue and inadvertently injure them. One such example occurs during surgical removal of the gallbladder, where injury of the nearby common bile duct leads to life-threatening complications. Near-infrared imaging of the intraoperative field may help surgeons localize such critical tissue-embedded vessels. We have investigated how continuous-wave (CW) imaging performs relative to time-gated wide-field imaging, presently a rather costly technology, under broad Gaussian beam-illumination conditions. We have studied the simplified case of an isolated cylinder having bile-duct optical properties, embedded at different depths within a 2-cm slab of adipose tissue. Monte Carlo simulations were preformed for both reflectance and transillumination geometries. The relative performance of CW versus time-gated imaging was compared in terms of spatial resolution and contrast-to-background ratio in the resulting simulated images. It was found that time-gated imaging offers superior spatial resolution and vessel-detection sensitivity in most cases, though CW transillumination measurements may also offer satisfactory performance for this tissue geometry at lower cost. Experiments were performed in reflectance geometry to validate simulation results, and potential challenges in the translation of this technology to the clinic are discussed.

  7. Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping.

    PubMed

    Rutherford, Elaine; Talle, Mohammed A; Mangion, Kenneth; Bell, Elizabeth; Rauhalammi, Samuli M; Roditi, Giles; McComb, Christie; Radjenovic, Aleksandra; Welsh, Paul; Woodward, Rosemary; Struthers, Allan D; Jardine, Alan G; Patel, Rajan K; Berry, Colin; Mark, Patrick B

    2016-10-01

    Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking-derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

  8. Dietary Salt Restriction Improves Cardiac and Adipose Tissue Pathology Independently of Obesity in a Rat Model of Metabolic Syndrome

    PubMed Central

    Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

    2014-01-01

    Background Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. Methods and Results We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z‐Leprfa/Leprfa (DS/obese) rats, which are derived from a cross between Dahl salt‐sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal‐salt (0.36% NaCl in chow) or low‐salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z‐Lepr+/Lepr+, or DS/lean rats). DS/obese rats fed the normal‐salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin–angiotensin–aldosterone system genes were increased in DS/obese rats fed the normal‐salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Conclusions Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. PMID:25468654

  9. Depth-resolved measurement of ocular fundus pulsations by low-coherence tissue interferometry

    NASA Astrophysics Data System (ADS)

    Dragostinoff, Nikolaus; Werkmeister, René M.; Gröschl, Martin; Schmetterer, Leopold

    2009-09-01

    A device that allows for the measurement of ocular fundus pulsations at preselected axial positions of a subject's eye is presented. Unlike previously presented systems, which only allow for observation of the strongest reflecting retinal layer, our system enables the measurement of fundus pulsations at a preselected ocular layer. For this purpose the sample is illuminated by light of low temporal coherence. The layer is then selected by positioning one mirror of a Michelson interferometer according to the depth of the layer. The device contains a length measurement system based on partial coherence interferometry and a line scan charge-coupled device camera for recording and online inspection of the fringe system. In-vivo measurements in healthy humans are performed as proof of principle. The algorithms used for enhancing the recorded images are briefly introduced. The contrast of the observed interference pattern is evaluated for different positions of the measurement mirror and at various distances from the front surface of the cornea. The applications of such a system may be wide, including assessment of eye elongation during myopia development and blood-flow-related changes in intraocular volume.

  10. In-depth proteomic analysis of whole testis tissue from the adult rhesus macaque.

    PubMed

    Wang, Jing; Xia, Yankai; Wang, Gaigai; Zhou, Tao; Guo, Yueshuai; Zhang, Chao; An, Xia; Sun, Yujie; Guo, Xuejiang; Zhou, Zuomin; Sha, Jiahao

    2014-06-01

    The rhesus macaque is similar to humans both anatomically and physiologically as a primate, and has therefore been used extensively in medical and biological research, including reproductive physiology. Despite sequencing of the macaque genome, limited postgenomic studies have been performed to date. In studies aimed at characterizing spermatogenesis, we successfully identified 9078 macaque testis proteins corresponding to 8662 genes, using advanced MS and an optimized proteomics platform, indicative of complex protein compositions during macaque spermatogenesis. Immunohistochemistry analysis further revealed the presence of proteins from different types of testicular cells, including Sertoli cells, Leydig cells, and various stages of germ cells. Our data provide expression evidence at protein level of 3010 protein-coding genes in 8662 identified testis genes for the first time. We further identified 421 homologous genes from the proteome already known to be essential for male infertility in mouse. Comparative analysis of the proteome showed high similarity with the published human testis proteome, implying that macaque and human may use similar proteins to regulate spermatogenesis. Our in-depth analysis of macaque spermatogenesis provides a rich resource for further studies, and supports the utility of macaque as a suitable model for the study of human reproduction.

  11. Correlation between average tissue depth data and quantitative accuracy of forensic craniofacial reconstructions measured by geometric surface comparison method.

    PubMed

    Lee, Won-Joon; Wilkinson, Caroline M; Hwang, Hyeon-Shik; Lee, Sang-Mi

    2015-05-01

    Accuracy is the most important factor supporting the reliability of forensic facial reconstruction (FFR) comparing to the corresponding actual face. A number of methods have been employed to evaluate objective accuracy of FFR. Recently, it has been attempted that the degree of resemblance between computer-generated FFR and actual face is measured by geometric surface comparison method. In this study, three FFRs were produced employing live adult Korean subjects and three-dimensional computerized modeling software. The deviations of the facial surfaces between the FFR and the head scan CT of the corresponding subject were analyzed in reverse modeling software. The results were compared with those from a previous study which applied the same methodology as this study except average facial soft tissue depth dataset. Three FFRs of this study that applied updated dataset demonstrated lesser deviation errors between the facial surfaces of the FFR and corresponding subject than those from the previous study. The results proposed that appropriate average tissue depth data are important to increase quantitative accuracy of FFR. PMID:25739646

  12. Correlation between average tissue depth data and quantitative accuracy of forensic craniofacial reconstructions measured by geometric surface comparison method.

    PubMed

    Lee, Won-Joon; Wilkinson, Caroline M; Hwang, Hyeon-Shik; Lee, Sang-Mi

    2015-05-01

    Accuracy is the most important factor supporting the reliability of forensic facial reconstruction (FFR) comparing to the corresponding actual face. A number of methods have been employed to evaluate objective accuracy of FFR. Recently, it has been attempted that the degree of resemblance between computer-generated FFR and actual face is measured by geometric surface comparison method. In this study, three FFRs were produced employing live adult Korean subjects and three-dimensional computerized modeling software. The deviations of the facial surfaces between the FFR and the head scan CT of the corresponding subject were analyzed in reverse modeling software. The results were compared with those from a previous study which applied the same methodology as this study except average facial soft tissue depth dataset. Three FFRs of this study that applied updated dataset demonstrated lesser deviation errors between the facial surfaces of the FFR and corresponding subject than those from the previous study. The results proposed that appropriate average tissue depth data are important to increase quantitative accuracy of FFR.

  13. A multistep procedure to prepare pre-vascularized cardiac tissue constructs using adult stem sells, dynamic cell cultures, and porous scaffolds

    PubMed Central

    Pagliari, Stefania; Tirella, Annalisa; Ahluwalia, Arti; Duim, Sjoerd; Goumans, Marie-Josè; Aoyagi, Takao; Forte, Giancarlo

    2014-01-01

    The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D) cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In the first step of the procedure, human mesenchymal stem cells (hMSCs) are seeded onto gelatin scaffolds to provide interconnected vessel-like structures, while human cardiomyocyte progenitor cells (hCMPCs) are stimulated in vitro to obtain their commitment toward the cardiac phenotype. The use of a modular bioreactor allows the perfusion of the whole scaffold, providing superior performance in terms of cardiac tissue maturation and cell survival. Both the cell culture on natural-derived polymers and the continuous medium perfusion of the scaffold led to the formation of a densely packaged proto-tissue composed of vascular-like and cardiac-like cells, which might complete maturation process and interconnect with native tissue upon in vivo implantation. In conclusion, the data obtained through the approach here proposed highlight the importance to provide stem cells with complementary signals in vitro able to resemble the complexity of cardiac microenvironment. PMID:24917827

  14. Biphasic Electrical Field Stimulation Aids in Tissue Engineering of Multicell-Type Cardiac Organoids

    PubMed Central

    Chiu, Loraine L.Y.; Iyer, Rohin K.; King, John-Paul

    2011-01-01

    The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple cell types. Organoids resembling cardiac myofibers were cultivated in Matrigel-coated microchannels fabricated of poly(ethylene glycol)-diacrylate. We found that field stimulation using symmetric biphasic square pulses at 2.5 V/cm, 1 Hz, 1 ms (per pulse phase) was an improved stimulation protocol, as compared to no stimulation and stimulation using monophasic square pulses of identical total amplitude and duration (5 V/cm, 1 Hz, 2 ms). This was supported by the highest success rate for synchronous contractions, low excitation threshold, the highest cell density, and the highest expression of Connexin-43 in the biphasic group. Subsequently, enriched CM were seeded on the networks of (1) cardiac fibroblasts (FB), (2) D4T endothelial cells (EC), or (3) a mixture of FB and EC that were precultured for 2 days prior to the addition of enriched CM. Biphasic field stimulation was also effective at improving electrical excitability of these cardiac organoids by improving the three-dimensional organization of the cells, increasing cellular elongation and enhancing Connexin-43 presence. PMID:18783322

  15. Biphasic electrical field stimulation aids in tissue engineering of multicell-type cardiac organoids.

    PubMed

    Chiu, Loraine L Y; Iyer, Rohin K; King, John-Paul; Radisic, Milica

    2011-06-01

    The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple cell types. Organoids resembling cardiac myofibers were cultivated in Matrigel-coated microchannels fabricated of poly(ethylene glycol)-diacrylate. We found that field stimulation using symmetric biphasic square pulses at 2.5 V/cm, 1 Hz, 1 ms (per pulse phase) was an improved stimulation protocol, as compared to no stimulation and stimulation using monophasic square pulses of identical total amplitude and duration (5 V/cm, 1 Hz, 2 ms). This was supported by the highest success rate for synchronous contractions, low excitation threshold, the highest cell density, and the highest expression of Connexin-43 in the biphasic group. Subsequently, enriched CM were seeded on the networks of (1) cardiac fibroblasts (FB), (2) D4T endothelial cells (EC), or (3) a mixture of FB and EC that were precultured for 2 days prior to the addition of enriched CM. Biphasic field stimulation was also effective at improving electrical excitability of these cardiac organoids by improving the three-dimensional organization of the cells, increasing cellular elongation and enhancing Connexin-43 presence.

  16. Ancestry and BMI Influences on Facial Soft Tissue Depths for A Cohort of Chinese and Caucasoid Women in Dunedin, New Zealand.

    PubMed

    Baillie, Louisa J; Mirijali, Seyed Ali; Niven, Brian E; Blyth, Phil; Dias, George J

    2015-09-01

    This study measured and assessed facial soft tissue depths (FSTDs) in adult female Chinese and New Zealand (NZ) Europeans (Caucasoids). Ultrasound was used to obtain depths at nine landmarks on 108 healthy subjects (51 Chinese, 57 NZ European), erect positioned, of same age group (18-29 years). Height and weight were also recorded. Statistical analysis focused on comparison of tissue depth between the two ancestry groups and the influence of Body Mass Index (BMI) (kg/m2). Results showed mean depth differences at Supra M2 and Infra M2 landmarks significantly greater for Chinese than Caucasoid women for all three BMI Classes (BMI<20, 20≤BMI<25, 25≤BMI<30), even BMI<20. For both groups BMI positively correlated with FSTD values at all landmarks except Labrale superius. This study enabled ancestry and BMI influence on FSTDs to be observed and compared for two distinct groups. Results add to knowledge about facial tissue depth variation.

  17. An empirical formula to obtain tissue-phantom ratios from percentage depth-dose curves for small fields.

    PubMed

    Ding, George X; Krauss, Rob

    2013-07-21

    For small photon fields, accurate values of a tissue-phantom ratio (TPR) are difficult to obtain either by direct measurement or by the conventional method of converting from measured percentage depth doses (%dd). This study aims to develop an empirical method to accurately obtain TPRs from %dd curves for small radiosurgery beams. The Monte Carlo simulation codes BEAMnrc/DOSXYZnrc were used to simulate the accelerator head and small, collimated fields including the circular cone accessory. The Monte Carlo directly calculated TPR values as a function of depth were compared with TPRs converted from %dd curves in a water phantom for field sizes ranging from 4 mm diameter to 10 × 10 cm(2) fields. Direct measurements of TPRs were performed with the detector remaining fixed at a SAD of 100 cm and increasing the detector depth by adding water. The %dd curves were measured at 100 cm SSD in a 50 × 50 × 50 cm(3) water tank. Using the Monte Carlo values, we developed an empirical formula to obtain TPRs from %dd and validated its accuracy. The conventional method of obtaining TPRs from %dd underestimate TPR by 3.4% and 0.6% at a depth 1.5 cm and overestimate TPR by 6.4% and 1.7% at a depth of 25 cm for 4 mm and 30 mm diameter circular fields, respectively. The empirical formula is derived from realistic Monte Carlo simulations using field sizes ranging from 4 to 30 mm and depth ranging from 1.5 to 25 cm. TPRs calculated using this function deviate from TPRs directly calculated from Monte Carlo by less than 0.5%. The accuracy of this empirical formula is validated against the directly measured TPRs in water. The developed empirical method has the potential to greatly simply the work in obtaining TPRs from measured %dd curves for small fields. By using this developed empirical formula the uncertainties between directly measured TPRs and converted TPRs from measured %dd curves are within 1%.

  18. An empirical formula to obtain tissue-phantom ratios from percentage depth-dose curves for small fields

    NASA Astrophysics Data System (ADS)

    Ding, George X.; Krauss, Rob

    2013-07-01

    For small photon fields, accurate values of a tissue-phantom ratio (TPR) are difficult to obtain either by direct measurement or by the conventional method of converting from measured percentage depth doses (%dd). This study aims to develop an empirical method to accurately obtain TPRs from %dd curves for small radiosurgery beams. The Monte Carlo simulation codes BEAMnrc/DOSXYZnrc were used to simulate the accelerator head and small, collimated fields including the circular cone accessory. The Monte Carlo directly calculated TPR values as a function of depth were compared with TPRs converted from %dd curves in a water phantom for field sizes ranging from 4 mm diameter to 10 × 10 cm2 fields. Direct measurements of TPRs were performed with the detector remaining fixed at a SAD of 100 cm and increasing the detector depth by adding water. The %dd curves were measured at 100 cm SSD in a 50 × 50 × 50 cm3 water tank. Using the Monte Carlo values, we developed an empirical formula to obtain TPRs from %dd and validated its accuracy. The conventional method of obtaining TPRs from %dd underestimate TPR by 3.4% and 0.6% at a depth 1.5 cm and overestimate TPR by 6.4% and 1.7% at a depth of 25 cm for 4 mm and 30 mm diameter circular fields, respectively. The empirical formula is derived from realistic Monte Carlo simulations using field sizes ranging from 4 to 30 mm and depth ranging from 1.5 to 25 cm. TPRs calculated using this function deviate from TPRs directly calculated from Monte Carlo by less than 0.5%. The accuracy of this empirical formula is validated against the directly measured TPRs in water. The developed empirical method has the potential to greatly simply the work in obtaining TPRs from measured %dd curves for small fields. By using this developed empirical formula the uncertainties between directly measured TPRs and converted TPRs from measured %dd curves are within 1%.

  19. Advanced computer techniques for inverse modeling of electric current in cardiac tissue

    SciTech Connect

    Hutchinson, S.A.; Romero, L.A.; Diegert, C.F.

    1996-08-01

    For many years, ECG`s and vector cardiograms have been the tools of choice for non-invasive diagnosis of cardiac conduction problems, such as found in reentrant tachycardia or Wolff-Parkinson-White (WPW) syndrome. Through skillful analysis of these skin-surface measurements of cardiac generated electric currents, a physician can deduce the general location of heart conduction irregularities. Using a combination of high-fidelity geometry modeling, advanced mathematical algorithms and massively parallel computing, Sandia`s approach would provide much more accurate information and thus allow the physician to pinpoint the source of an arrhythmia or abnormal conduction pathway.

  20. Relative capacities of time-gated versus CW imaging to localize tissue embedded vessels with increasing depth

    NASA Astrophysics Data System (ADS)

    Alexandrakis, George; Patel, Nimit L.; Lin, Zi-Jing; Livingston, Edward H.; Liu, Hanli

    2009-02-01

    The clinical motivation for our work was to help surgeons see vessels through non-translucent intraoperative tissues during laparoscopic removal of the gallbladder. Our main focus was to answer the question of how CW imaging performs relative to ICCD (Intensified Charge-Coupled Device) based time-gated imaging, which is a lot more costly, under broad Gaussian beam illumination conditions. We have studied the simplified case of an isolated bile duct embedded at different depths within a 2 cm slab of adipose tissue. Monte Carlo simulations were preformed for both reflectance and trans-illumination geometries. The relative performance of CW versus time-gated imaging was compared in terms of spatial resolution and vessel detection sensitivity in the resulting simulated images. Experiments were performed in reflectance geometry to validate simulation results. It was found that time-gated imaging offers superior spatial resolution and vessel detection sensitivity in all cases though CW trans-illumination measurements may also offer satisfactory performance for this tissue geometry at a lower cost.

  1. An Inverse Finite Element Method for Determining the Tissue Compressibility of Human Left Ventricular Wall during the Cardiac Cycle

    PubMed Central

    Hassaballah, Abdallah I.; Hassan, Mohsen A.; Mardi, Azizi N.; Hamdi, Mohd

    2013-01-01

    The determination of the myocardium’s tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle. PMID:24367544

  2. Highly purified eicosapentaenoic acid ameliorates cardiac injury and adipose tissue inflammation in a rat model of metabolic syndrome

    PubMed Central

    Ito, S.; Sano, Y.; Nagasawa, K.; Matsuura, N.; Yamada, Y.; Uchinaka, A.; Murohara, T.

    2016-01-01

    Summary Introduction n‐3 Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), which are abundant in fish oil, have been shown to delay the onset of cardiovascular events. We previously established DahlS.Z‐Lepr fa/Lepr fa (DS/obese) rats, which are derived from a cross between Dahl salt‐sensitive and Zucker rats, as a model of metabolic syndrome. This study has now explored the influence of highly purified EPA on cardiac and adipose tissue pathophysiology in this animal model. Materials and methods DS/obese rats were administered EPA (300 or 1,000 mg kg−1 d−1, per os) or vehicle from age 9 to 13 weeks. Homozygous lean (DahlS.Z‐Lepr +/Lepr +, or DS/lean) littermates were studied as controls. Results Whereas EPA had no effect on body weight, food intake or systolic blood pressure in DS/obese rats, it attenuated cardiac fibrosis, diastolic dysfunction, oxidative stress and inflammation in these animals. In addition, EPA did not affect insulin resistance but reduced adipocyte hypertrophy and inflammation in visceral fat of DS/obese rats. Moreover, EPA increased circulating levels of adiponectin as well as attenuated both the down‐regulation of AMP‐activated protein kinase phosphorylation and the up‐regulation of phosphorylation of the p65 subunit of nuclear factor‐kB in the heart of DS/obese rats. Conclusions Treatment of DS/obese rats with EPA did not affect hypertension but reduced cardiac fibrosis and diastolic dysfunction, with the latter effects being accompanied by AMP‐activated protein kinase activation and inactivation of nuclear factor‐kB signalling in the heart, possibly as a result of an increase in adiponectin secretion. EPA may be suitable for the treatment of cardiac injury associated with metabolic syndrome.

  3. Cardiomyocyte Circadian Oscillations Are Cell-Autonomous, Amplified by β-Adrenergic Signaling, and Synchronized in Cardiac Ventricle Tissue

    PubMed Central

    Welsh, David K.

    2016-01-01

    Circadian clocks impact vital cardiac parameters such as blood pressure and heart rate, and adverse cardiac events such as myocardial infarction and sudden cardiac death. In mammals, the central circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, synchronizes cellular circadian clocks in the heart and many other tissues throughout the body. Cardiac ventricle explants maintain autonomous contractions and robust circadian oscillations of clock gene expression in culture. In the present study, we examined the relationship between intrinsic myocardial function and circadian rhythms in cultures from mouse heart. We cultured ventricular explants or dispersed cardiomyocytes from neonatal mice expressing a PER2::LUC bioluminescent reporter of circadian clock gene expression. We found that isoproterenol, a β-adrenoceptor agonist known to increase heart rate and contractility, also amplifies PER2 circadian rhythms in ventricular explants. We found robust, cell-autonomous PER2 circadian rhythms in dispersed cardiomyocytes. Single-cell rhythms were initially synchronized in ventricular explants but desynchronized in dispersed cells. In addition, we developed a method for long-term, simultaneous monitoring of clock gene expression, contraction rate, and basal intracellular Ca2+ level in cardiomyocytes using PER2::LUC in combination with GCaMP3, a genetically encoded fluorescent Ca2+ reporter. In contrast to robust PER2 circadian rhythms in cardiomyocytes, we detected no rhythms in contraction rate and only weak rhythms in basal Ca2+ level. In summary, we found that PER2 circadian rhythms of cardiomyocytes are cell-autonomous, amplified by adrenergic signaling, and synchronized by intercellular communication in ventricle explants, but we detected no robust circadian rhythms in contraction rate or basal Ca2+. PMID:27459195

  4. Highly purified eicosapentaenoic acid ameliorates cardiac injury and adipose tissue inflammation in a rat model of metabolic syndrome

    PubMed Central

    Ito, S.; Sano, Y.; Nagasawa, K.; Matsuura, N.; Yamada, Y.; Uchinaka, A.; Murohara, T.

    2016-01-01

    Summary Introduction n‐3 Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), which are abundant in fish oil, have been shown to delay the onset of cardiovascular events. We previously established DahlS.Z‐Lepr fa/Lepr fa (DS/obese) rats, which are derived from a cross between Dahl salt‐sensitive and Zucker rats, as a model of metabolic syndrome. This study has now explored the influence of highly purified EPA on cardiac and adipose tissue pathophysiology in this animal model. Materials and methods DS/obese rats were administered EPA (300 or 1,000 mg kg−1 d−1, per os) or vehicle from age 9 to 13 weeks. Homozygous lean (DahlS.Z‐Lepr +/Lepr +, or DS/lean) littermates were studied as controls. Results Whereas EPA had no effect on body weight, food intake or systolic blood pressure in DS/obese rats, it attenuated cardiac fibrosis, diastolic dysfunction, oxidative stress and inflammation in these animals. In addition, EPA did not affect insulin resistance but reduced adipocyte hypertrophy and inflammation in visceral fat of DS/obese rats. Moreover, EPA increased circulating levels of adiponectin as well as attenuated both the down‐regulation of AMP‐activated protein kinase phosphorylation and the up‐regulation of phosphorylation of the p65 subunit of nuclear factor‐kB in the heart of DS/obese rats. Conclusions Treatment of DS/obese rats with EPA did not affect hypertension but reduced cardiac fibrosis and diastolic dysfunction, with the latter effects being accompanied by AMP‐activated protein kinase activation and inactivation of nuclear factor‐kB signalling in the heart, possibly as a result of an increase in adiponectin secretion. EPA may be suitable for the treatment of cardiac injury associated with metabolic syndrome. PMID:27708849

  5. A pharmacological investigation of the venom extract of the Australian box jellyfish, Chironex fleckeri, in cardiac and vascular tissues.

    PubMed

    Hughes, Richard J A; Angus, James A; Winkel, Kenneth D; Wright, Christine E

    2012-02-25

    The pharmacology of Australian box jellyfish, Chironex fleckeri, unpurified (crude) nematocyst venom extract (CVE) was investigated in rat isolated cardiac and vascular tissues and in anaesthetised rats. In small mesenteric arteries CVE (0.01-30 μg/ml) caused contractions (EC(50) 1.15±0.19 μg/ml) that were unaffected by prazosin (0.1 μM), bosentan (10 μM), CGRP(8-37) (1 μM) or tetrodotoxin (1 μM). Box jellyfish antivenom (5-92.6 units/ml) caused rightward shifts of the CVE concentration-response curve with no change in the maximum. In the presence of l-NAME (100 μM) the sensitivity and maximum response to CVE were increased, whilst MgSO(4) (6 mM) decreased both parameters. CVE (1-10 μg/ml) caused inhibition of the contractile response to electrical sympathetic nerve stimulation. Left atrial responses to CVE (0.001-30 μg/ml) were bi-phasic, composed of an initial positive inotropy followed by a marked negative inotropy and atrial standstill. CVE (0.3 μg/ml) elicited a marked decrease in right atrial rate followed by atrial standstill at 3 μg/ml. These responses were unaffected by 1 μM of propranolol, atropine or CGRP(8-37). Antivenom (54 and 73 units/ml) caused rightward shifts of the CVE concentration-response curve and prevented atrial standstill in left and right atria. The effects of CVE do not appear to involve autonomic nerves, post-synaptic α(1)- or β(1)-adrenoceptors, or muscarinic, endothelin or CGRP receptors, but may occur through direct effects on the cardiac and vascular muscle. Box jellyfish antivenom was effective in attenuating CVE-induced responses in isolated cardiac and vascular tissues. PMID:22154831

  6. Troponin I Assessment of Cardiac Involvement in Patients With Connective Tissue Disease and an Elevated Creatine Kinase MB Isoform Report of Four Cases and Review of the Literature.

    PubMed

    Badsha, H; Gunes, B; Grossman, J; Brahn, E

    1997-06-01

    Levels of creatine kinase MB isoform (CKMB) can be elevated in patients with myopathy, neuropathy, skeletal muscle injury, or renal failure in the absence of myocardial injury. These elevated CKMB levels make it difficult to identify cardiac involvement in conditions that can be associated with a variety of cardiac abnormalities or with symptoms that mimic them. Cardiac troponin I (cTnI), a myocardial regulatory protein, has a high specificity for cardiac muscle and can be used to clarify the etiology of CKMB elevations in such patients. In this report, four patients with diverse causes for increased CKMB levels are discussed with respect to cill.The first three patients, with tentative diagnoses of mixed connective tissue disease, amyotrophic lateral sclerosis, and polymyositis presented with increasing shortness of breath, tachycardia, nonspecific electrocardiogram changes, high creative kinase, and CKMB levels. A normal cTnI helped exclude a diagnosis of a cardiac cause of their symptoms. Patient 4 had a scleroderma variant and experienced sudden, fatal, cardiac decompensation caused by a dilated cardiomyopathy, accompanied by an increased cTnl.The cTnI is a reliable, specific, and quick wav of excluding or determining cardiac involvement in patients with connective tissue disease. As this test is inexpensive and becoming increasingly available, it could become the test of choice, especially in scenarios in which urgent management decisions are needed.

  7. Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue

    PubMed Central

    Maher, Jason R.; Chuchuen, Oranat; Henderson, Marcus H.; Kim, Sanghoon; Rinehart, Matthew T.; Kashuba, Angela D. M.; Wax, Adam; Katz, David F.

    2015-01-01

    We report the development of a combined confocal Raman spectroscopy (CRS) and optical coherence tomography (OCT) instrument (CRS-OCT) capable of measuring analytes in targeted biological tissues with sub-100-micron spatial resolution. The OCT subsystem was used to measure depth-resolved tissue morphology and guide the acquisition of chemically-specific Raman spectra. To demonstrate its utility, the instrument was used to accurately measure depth-resolved, physiologically-relevant concentrations of Tenofovir, a microbicide drug used to prevent the sexual transmission of HIV, in ex vivo tissue samples. PMID:26114026

  8. Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media.

    PubMed

    Pan, De-Bei; Gao, Xiang; Feng, Xia; Pan, Jun-Ting; Zhang, Hong

    2016-02-24

    Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves.

  9. Tissue engineering the cardiac microenvironment: Multicellular microphysiological systems for drug screening☆

    PubMed Central

    Kurokawa, Yosuke K.; George, Steven C.

    2016-01-01

    The ability to accurately detect cardiotoxicity has become increasingly important in the development of new drugs. Since the advent of human pluripotent stem cell-derived cardiomyocytes, researchers have explored their use in creating an in vitro drug screening platform. Recently, there has been increasing interest in creating 3D microphysiological models of the heart as a tool to detect cardiotoxic compounds. By recapitulating the complex microenvironment that exists in the native heart, cardiac microphysiological systems have the potential to provide a more accurate pharmacological response compared to current standards in preclinical drug screening. This review aims to provide an overview on the progress made in creating advanced models of the human heart, including the significance and contributions of the various cellular and extracellular components to cardiac function. PMID:26212156

  10. Tissue engineering the cardiac microenvironment: Multicellular microphysiological systems for drug screening.

    PubMed

    Kurokawa, Yosuke K; George, Steven C

    2016-01-15

    The ability to accurately detect cardiotoxicity has become increasingly important in the development of new drugs. Since the advent of human pluripotent stem cell-derived cardiomyocytes, researchers have explored their use in creating an in vitro drug screening platform. Recently, there has been increasing interest in creating 3D microphysiological models of the heart as a tool to detect cardiotoxic compounds. By recapitulating the complex microenvironment that exists in the native heart, cardiac microphysiological systems have the potential to provide a more accurate pharmacological response compared to current standards in preclinical drug screening. This review aims to provide an overview on the progress made in creating advanced models of the human heart, including the significance and contributions of the various cellular and extracellular components to cardiac function.

  11. Physiological response of cardiac tissue to bisphenol a: alterations in ventricular pressure and contractility

    PubMed Central

    Brooks, Daina; Chandra, Akhil; Jaimes, Rafael; Sarvazyan, Narine; Kay, Matthew

    2015-01-01

    Biomonitoring studies have indicated that humans are routinely exposed to bisphenol A (BPA), a chemical that is commonly used in the production of polycarbonate plastics and epoxy resins. Epidemiological studies have shown that BPA exposure in humans is associated with cardiovascular disease; however, the direct effects of BPA on cardiac physiology are largely unknown. Previously, we have shown that BPA exposure slows atrioventricular electrical conduction, decreases epicardial conduction velocity, and prolongs action potential duration in excised rat hearts. In the present study, we tested if BPA exposure also adversely affects cardiac contractile performance. We examined the impact of BPA exposure level, sex, and pacing rate on cardiac contractile function in excised rat hearts. Hearts were retrogradely perfused at constant pressure and exposed to 10−9-10−4 M BPA. Left ventricular developed pressure and contractility were measured during sinus rhythm and during pacing (5, 6.5, and 9 Hz). Ca2+ transients were imaged from whole hearts and from neonatal rat cardiomyocyte layers. During sinus rhythm in female hearts, BPA exposure decreased left ventricular developed pressure and inotropy in a dose-dependent manner. The reduced contractile performance was exacerbated at higher pacing rates. BPA-induced effects on contractile performance were also observed in male hearts, albeit to a lesser extent. Exposure to BPA altered Ca2+ handling within whole hearts (reduced diastolic and systolic Ca2+ transient potentiation) and neonatal cardiomyocytes (reduced Ca2+ transient amplitude and prolonged Ca2+ transient release time). In conclusion, BPA exposure significantly impaired cardiac performance in a dose-dependent manner, having a major negative impact upon electrical conduction, intracellular Ca2+ handing, and ventricular contractility. PMID:25980024

  12. Simultaneous measurement of cerebral and muscle tissue parameters during cardiac arrest and cardiopulmonary resuscitation

    NASA Astrophysics Data System (ADS)

    Nosrati, Reyhaneh; Ramadeen, Andrew; Hu, Xudong; Woldemichael, Ermias; Kim, Siwook; Dorian, Paul; Toronov, Vladislav

    2015-03-01

    In this series of animal experiments on resuscitation after cardiac arrest we had a unique opportunity to measure hyperspectral near-infrared spectroscopy (hNIRS) parameters directly on the brain dura, or on the brain through the intact pig skull, and simultaneously the muscle hNIRS parameters. Simultaneously the arterial blood pressure and carotid and femoral blood flow were recorded in real time using invasive sensors. We used a novel hyperspectral signalprocessing algorithm to extract time-dependent concentrations of water, hemoglobin, and redox state of cytochrome c oxidase during cardiac arrest and resuscitation. In addition in order to assess the validity of the non-invasive brain measurements the obtained results from the open brain was compared to the results acquired through the skull. The comparison of hNIRS data acquired on brain surface and through the adult pig skull shows that in both cases the hemoglobin and the redox state cytochrome c oxidase changed in similar ways in similar situations and in agreement with blood pressure and flow changes. The comparison of simultaneously measured brain and muscle changes showed expected differences. Overall the results show feasibility of transcranial hNIRS measurements cerebral parameters including the redox state of cytochrome oxidase in human cardiac arrest patients.

  13. Apolipoprotein A-I Mimetic Peptide D-4F Reduces Cardiac Hypertrophy and Improves Apolipoprotein A-I-Mediated Reverse Cholesterol Transport From Cardiac Tissue in LDL Receptor-null Mice Fed a Western Diet.

    PubMed

    Han, Jie; Zhang, Song; Ye, Ping; Liu, Yong-Xue; Qin, Yan-Wen; Miao, Dong-Mei

    2016-05-01

    Epidemiological studies have suggested that hypercholesterolemia is an independent determinant of increased left ventricular (LV) mass. Because high-density lipoprotein and its major protein apolipoprotein A-I (apoA-I) mediate reverse cholesterol transport (RCT) and have cardiac protective effects, we hypothesized that the apoA-I mimetic peptide D-4F could promote RCT in cardiac tissue and decrease cardiac hypertrophy induced by hypercholesterolemia. Low-density lipoprotein receptor-null mice were fed by a Western diet for 18 weeks and then randomized to receive water, or D-4F 0.3 mg/mL, or D-4F 0.5 mg/mL added to drinking water for 6 weeks. After D-4F administration, an increase in high-density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol, total cholesterol, and triglyceride in a trend toward dose-responsivity were found in cardiac tissue. Ultrasound biomicroscopy revealed a reduction in LV posterior wall end-diastolic dimension, and an increase in mitral valve E/A ratio and LV ejection fraction. Hematoxylin-eosin staining showed reduced LV wall thickness and myocardial cell diameter. The protein levels of ABCA1 and LXRα were elevated in cardiac tissue of D-4F treated mice compared with the controls (P < 0.05). These results demonstrated that D-4F treatment reduced cardiac hypertrophy, and improved cardiac performance in low-density lipoprotein receptor-null mice fed a Western diet, presumably through the LXRα-ABCA1 pathway associated with enhanced myocardial RCT.

  14. Pre-treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves engineered heart tissue.

    PubMed

    Radisic, Milica; Park, Hyoungshin; Martens, Timothy P; Salazar-Lazaro, Johanna E; Geng, Wenliang; Wang, Yadong; Langer, Robert; Freed, Lisa E; Vunjak-Novakovic, Gordana

    2008-09-01

    Native myocardium consists of several cell types, of which approximately one-third are myocytes and most of the nonmyocytes are fibroblasts. By analogy with monolayer culture in which fibroblasts were removed to prevent overgrowth, early attempts to engineer myocardium utilized cell populations enriched for cardiac myocytes (CMs; approximately 80-90% of total cells). We hypothesized that the pre-treatment of synthetic elastomeric scaffolds with cardiac fibroblasts (CFs) will enhance the functional assembly of the engineered cardiac constructs by creating an environment supportive of cardiomyocyte attachment and function. Cells isolated from neonatal rat ventricles were prepared to form three distinct populations: rapidly plating cells identified as CFs, slowly plating cells identified as CMs, and unseparated initial population of cells (US). The cell fractions (3 x 10(6) cells total) were seeded into poly(glycerol sebacate) scaffolds (highly porous discs, 5 mm in diameter x 2-mm thick) using Matrigeltrade mark, either separately (CM or CF), concurrently (US), or sequentially (CF pre-treatment followed by CM culture, CF + CM), and cultured in spinner flasks. The CF + CM group had the highest amplitude of contraction and the lowest excitation threshold, superior DNA content, and higher glucose consumption rate. The CF + CM group exhibited compact 100- to 200-mum thick layers of elongated myocytes aligned in parallel over layers of collagen-producing fibroblasts, while US and CM groups exhibited scattered and poorly elongated myocytes. The sequential co-culture of CF and CM on a synthetic elastomer scaffold thus created an environment supportive of cardiomyocyte attachment, differentiation, and contractile function, presumably due to scaffold conditioning by cultured fibroblasts. When implanted over the infarcted myocardium in a nude rat model, cell-free poly(glycerol sebacate) remained at the ventricular wall after 2 weeks of in vivo, and was vascularized. PMID

  15. Cardiac tissue inhibitor of matrix metalloprotease 4 dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to therapy☆

    PubMed Central

    Chaturvedi, Pankaj; Kalani, Anuradha; Familtseva, Anastasia; Kamat, Pradip Kumar; Metreveli, Naira; Tyagi, Suresh C.

    2015-01-01

    Background TIMP4 (Tissue Inhibitors of Matrix Metalloprotease 4), goes down in failing hearts and mice lacking TIMP4 show poor regeneration capacity after myocardial infarction (MI). This study is based on our previous observation that administration of cardiac inhibitor of metalloproteinase (~TIMP4) attenuates oxidative stress and remodeling in failing hearts. Therefore, we hypothesize that TIMP4 helps in cardiac regeneration by augmenting contractility and inducing the differentiation of cardiac progenitor cells into cardiomyocytes. Methods To validate this hypothesis, we transfected mouse cardiomyocytes with TIMP4 and TIMP4-siRNA and performed contractility studies in the TIMP4 transfected cardiomyocytes as compared to siRNA-TIMP4 transfected cardiomyocytes. We evaluated the calcium channel gene serca2a (sarcoplasmic reticulum calcium ATPase2a) and mir122a which tightly regulates serca2a to explain the changes in contractility. We treated mouse embryonic stem cells with cardiac extract and cardiac extract minus TIMP4 (using TIMP4 monoclonal antibody) to examine the effect of TIMP4 on differentiation of cardiac progenitor cells. Results Contractility was augmented in the TIMP4 transfected cardiomyocytes as compared to siRNA-TIMP4 transfected cardiomyocytes. There was elevated expression of serca2a in the TIMP4 transformed myocytes and down regulation of mir122a. The cells treated with cardiac extract containing TIMP4 showed cardiac phenotype in terms of Ckit+, GATA4+ and Nkx2.5 expression. Conclusion This is a novel report suggesting that TIMP4 augments contractility and induces differentiation of progenitor cells into cardiac phenotype. In view of the failure of MMP9 inhibitors for cardiac therapy, TIMP4 provides an alternative approach, being an indigenous molecule and a natural inhibitor of MMP9. PMID:25745981

  16. Pathological pigmentation in cardiac tissues of Atlantic salmon (Salmo salar L.) with cardiomyopathy syndrome

    PubMed Central

    2013-01-01

    It is widely accepted that melanin formation may play an immunologic role in invertebrates and ectothermic vertebrates. In farmed Atlantic salmon, cardiomyopathy syndrome (CMS) is a common viral disease associated with severe cardiac inflammation that may be accompanied by heavy melanisation of the heart. By the use of histology, laser capture microdissection and transcription analysis of tyrosinase genes, we here show that this melanisation is linked to de novo melanogenesis by melanomacrophages, suggesting an active part in the inflammatory reaction. No general systemic activation of the extracutaneous pigmentary system in response to viral infections with affinity to the heart was observed. PMID:24219276

  17. In vitro chick pre-cardiac explant tissue differentiation during spaceflight on SpaceHab-02

    NASA Technical Reports Server (NTRS)

    van Twest, J. S.; Paulsen, A.; Spooner, B. S.

    1995-01-01

    Chick precardiac tissue explants were cultured on the 8-day mission of STS-60, space shuttle Discovery. Development of in vitro cultures of precardiac chick tissue from embryo stages 5 though 8 (H-H) were initiated during orbit and were terminated after approximately fifteen hours of 37 degree C culture. Transmission electron microscopy and tritiated thymidine studies were performed postflight. No significant differences in cell proliferation were observed between flight and ground controls. Electron-microscopic studies revealed stage 8 explants were capable of differentiation during flight in a pattern which matched ground control tissues. As anticipated, stage 7 explant tissues had differentiated to a lesser extent compared to stage 8 tissues. Interestingly, stage 7 precardiac explant flight tissue differentiation was less than ground control tissue. This difference in differentiation between flight and ground cultures was enhanced in stage 6 tissues, as high levels of myofibril organization were only seen in ground controls. Other cellular components such as Golgi apparatus, junctional complexes, and mitochondria were present and appeared normal and healthy.

  18. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

    PubMed Central

    Kim, Junhwan; Perales Villarroel, José Paul; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W.; Becker, Lance B.

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest. PMID:26770657

  19. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    PubMed

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  20. A spatially-dense regression study of facial form and tissue depth: towards an interactive tool for craniofacial reconstruction.

    PubMed

    Shrimpton, Sarah; Daniels, Katleen; de Greef, Sven; Tilotta, Francoise; Willems, Guy; Vandermeulen, Dirk; Suetens, Paul; Claes, Peter

    2014-01-01

    Forensic Craniofacial Reconstruction (CFR) is an investigative technique used to illicit recognition of a deceased person by reconstructing the most likely face starting from the skull. A key component in most CFR methods are estimates of facial soft tissue depths (TD) at particular points (landmarks) on the skull based on averages from databases of TD recordings. These databases vary in their method of extraction, number and position of landmarks (usually sparse <100), condition of the body, population studied, and sub-categorization of the data. In this work a new dataset is presented in a novel manner based on 156 CT scans using a spatially-dense set (∼7500) of TD recordings to allow for a complete understanding of TD variation interpolating between typical landmarks. Furthermore, to unravel the interplay between soft-tissue layers, skull and facial morphology, TD and Facial Form (FF) are investigated both separately and combined. Using a partial least squares regression (PLSR) analysis, which allows for working with multivariate and spatially-dense data, on metadata of Sex, Age and BMI, different significant patterns on TD and FF variation were found. A similar, but with TD and FF combined, PLSR generated a model useful to report on both, in function of Sex, Age and BMI. In contrast to other datasets and due to the continuous nature of the regression there is no need for data sub-categorization. In further contrast, previous datasets have been presented in tabulated form, which is impractical for spatially-dense data. Instead an interactive tool was built to visualize the regression model in an accessible way for CFR practitioners as well as anatomists. The tool is free to the community and forms a base for data contributions to augment the model and its future use in practice. PMID:24378309

  1. A spatially-dense regression study of facial form and tissue depth: towards an interactive tool for craniofacial reconstruction.

    PubMed

    Shrimpton, Sarah; Daniels, Katleen; de Greef, Sven; Tilotta, Francoise; Willems, Guy; Vandermeulen, Dirk; Suetens, Paul; Claes, Peter

    2014-01-01

    Forensic Craniofacial Reconstruction (CFR) is an investigative technique used to illicit recognition of a deceased person by reconstructing the most likely face starting from the skull. A key component in most CFR methods are estimates of facial soft tissue depths (TD) at particular points (landmarks) on the skull based on averages from databases of TD recordings. These databases vary in their method of extraction, number and position of landmarks (usually sparse <100), condition of the body, population studied, and sub-categorization of the data. In this work a new dataset is presented in a novel manner based on 156 CT scans using a spatially-dense set (∼7500) of TD recordings to allow for a complete understanding of TD variation interpolating between typical landmarks. Furthermore, to unravel the interplay between soft-tissue layers, skull and facial morphology, TD and Facial Form (FF) are investigated both separately and combined. Using a partial least squares regression (PLSR) analysis, which allows for working with multivariate and spatially-dense data, on metadata of Sex, Age and BMI, different significant patterns on TD and FF variation were found. A similar, but with TD and FF combined, PLSR generated a model useful to report on both, in function of Sex, Age and BMI. In contrast to other datasets and due to the continuous nature of the regression there is no need for data sub-categorization. In further contrast, previous datasets have been presented in tabulated form, which is impractical for spatially-dense data. Instead an interactive tool was built to visualize the regression model in an accessible way for CFR practitioners as well as anatomists. The tool is free to the community and forms a base for data contributions to augment the model and its future use in practice.

  2. Estimation of cardiac conductivities in ventricular tissue by a variational approach

    NASA Astrophysics Data System (ADS)

    Yang, Huanhuan; Veneziani, Alessandro

    2015-11-01

    The bidomain model is the current standard model to simulate cardiac potential propagation. The numerical solution of this system of partial differential equations strongly depends on the model parameters and in particular on the cardiac conductivities. Unfortunately, it is quite problematic to measure these parameters in vivo and even more so in clinical practice, resulting in no common agreement in the literature. In this paper we consider a variational data assimilation approach to estimating those parameters. We consider the parameters as control variables to minimize the mismatch between the computed and the measured potentials under the constraint of the bidomain system. The existence of a minimizer of the misfit function is proved with the phenomenological Rogers-McCulloch ionic model, that completes the bidomain system. We significantly improve the numerical approaches in the literature by resorting to a derivative-based optimization method with settlement of some challenges due to discontinuity. The improvement in computational efficiency is confirmed by a 2D test as a direct comparison with approaches in the literature. The core of our numerical results is in 3D, on both idealized and real geometries, with the minimal ionic model. We demonstrate the reliability and the stability of the conductivity estimation approach in the presence of noise and with an imperfect knowledge of other model parameters.

  3. Spread of excitation in 3-D models of the anisotropic cardiac tissue. II. Effects of fiber architecture and ventricular geometry.

    PubMed

    Franzone, P C; Guerri, L; Pennacchio, M; Taccardi, B

    1998-01-15

    We investigate a three-dimensional macroscopic model of wave-front propagation related to the excitation process in the left ventricular wall represented by an anisotropic bidomain. The whole left ventricle is modeled, whereas, in a previous paper, only a flat slab of myocardial tissue was considered. The direction of cardiac fibers, which affects the anisotropic conductivity of the myocardium, rotates from the epi- to the endocardium. If the ventricular wall is conceived as a set of packed surfaces, the fibers may be tangent to them or more generally may cross them obliquely; the latter case is described by an "imbrication angle." The effect of a simplified Purkinje network also is investigated. The cardiac excitation process, more particularly the depolarization phase, is modeled by a nonlinear elliptic equation, called an eikonal equation, in the activation time. The numerical solution of this equation is obtained by means of the finite element method, which includes an upwind treatment of the Hamiltonian part of the equation. By means of numerical simulations in an idealized model of the left ventricle, we try to establish whether the eikonal approach contains the essential basic elements for predicting the features of the activation patterns experimentally observed. We discuss and compare these results with those obtained in our previous papers for a flat part of myocardium. The general rules governing the spread of excitation after local stimulations, previously delineated for the flat geometry, are extended to the present, more realistic monoventricular model.

  4. Intracellular pH in Gastric and Rectal Tissue Post Cardiac Arrest

    NASA Astrophysics Data System (ADS)

    Fisher, Elaine M.; Steiner, Richard P.; LaManna, Joseph C.

    We directly measured pHi using the pH sensitive dye, neutral red. We defined pHi for rectal and gastric tissue in whole tissue and by layer under control and arrest conditions. Fifteen minutes of arrest was not sufficient time to alter the pHi at the rectal or gastric site. On initial inspection, the stomach may be more sensitive to ischemic changes than the rectum. Understanding the mechanism by which PCO2 generation is used to track clinical changes is vital to the early detection of tissue dysoxia in order to effectively treat and manage critically ill patients.

  5. Multistability of reentrant rhythms in an ionic model of a two-dimensional annulus of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Comtois, Philippe; Vinet, Alain

    2005-11-01

    The dynamics of reentry in a model of a two-dimensional annulus of homogeneous cardiac tissue, with a Beeler-Reuter type formulation of the membrane ionic currents, is examined. The bifurcation structure of the sustained propagated solutions is described as a function of Rin and Rout , the inner and outer radii of the annulus. The transition from periodic to quasiperiodic reentry occurs at a critical Rin , which first diminishes and then saturates as Rout is increased. The reduction of the critical Rin is a consequence of the increase of the wave-front curvature. There is a range of Rin below the critical radius in which two distinct quasiperiodic solutions coexist. Each of these solutions disappears at its own specific value of Rin , and their annihilation is preceded by a new type of bifurcation leading to a regime of propagation with transient successive detachments of the wave front from the inner border of the annulus.

  6. Cardiac physiologic and tissue metabolic changes following chronic low-level cadmium and cadmium plus lead ingestion in the rat.

    PubMed

    Kopp, S J; Perry, H M; Perry, E F; Erlanger, M

    1983-06-15

    Female Long-Evans hooded rats received Schroeder's rye-based diet and 0 or 1 microgram/ml cadmium, or cadmium plus lead in mineral fortified drinking water from weaning to 18 months. The heavy metal-fed rats were normal with respect to control, including growth rates and final body weights. Rats receiving added cadmium and cadmium plus lead in the diet were characterized by a persistent hypertension which was evident after 2 months. Cardiac conduction system excitability was depressed preferentially in cadmium-(atrioventricular nodal region) and cadmium plus lead-(His-Purkinje system) fed rats. Although heart rates were comparable to control, myocardial contractile activity (peak active tension and dT/dt) was significantly decreased in intact perfused heart preparations from both heavy metal-treated groups. In conjunction with the observed physiologic changes, various tissue-specific metabolic alterations were detected in heart, kidney, and liver. Generally, prolonged heavy-metal ingestion at these levels resulted in impaired energy metabolism (e.g., decreased ATP, PCr; increased Pj, ADP concentrations) and altered essential mineral composition (e.g., calcium, magnesium, zinc, and to a lesser extent, sodium and potassium; copper levels were unaffected) that varied in severity according to the tissue. The addition of lead to the cadmium diet had little additive effect on the cardiovascular system; however, renal and hepatic tissues did exhibit apparent additive effects further suggesting that cadmium and lead actions and interactions may be tissue dependent. These experimental findings and the biologic inferences derived are consonant with the hypothesis that chronic, life-long cadmium exposure approximating environmental levels may have significant adverse effects on mammalian systems, that include effects on cardiovascular tissues.

  7. Synchrotron infrared imaging of advanced glycation endproducts (AGEs) in cardiac tissue from mice fed high glycemic diets

    PubMed Central

    Birarda, Giovanni; Holman, Elizabeth A.; Fu, Shang; Weikel, Karen; Hu, Ping; Blankenberg, Francis G.; Holman, Hoi-Ying; Taylor, Allen

    2015-01-01

    Recent research findings correlate an increased risk for dieases such as diabetes, macular degeneration and cardiovascular disease (CVD) with diets that rapidly raise the blood sugar levels; these diets are known as high glycemic index (GI) diets which include white breads, sodas and sweet deserts. Lower glycemia diets are usually rich in fruits, non-starchy vegetables and whole grain products. The goal of our study was to compare and contrast the effects of a low vs. high glycemic diet using the biochemical composition and microstructure of the heart. The improved spatial resolution and signal-to-noise for SR-FTIR obtained through the coupling of the bright synchrotron infrared photon source to an infrared spectral microscope enabled the molecular-level observation of diet-related changes within unfixed fresh frozen histologic sections of mouse cardiac tissue. High and low glycemic index (GI) diets were started at the age of five-months and continued for one year, with the diets only differing in their starch distribution (high GI diet = 100% amylopectin versus low GI diet = 30% amylopectin/70% amylose). Serial cryosections of cardiac tissue for SR-FTIR imaging alternated with adjacent hematoxylin and eosin (H&E) stained sections allowed not only fine-scale chemical analyses of glycogen and glycolipid accumulation along a vein as well as protein glycation hotspots co-localizing with collagen cold spots but also the tracking of morphological differences occurring in tandem with these chemical changes. As a result of the bright synchrotron infrared photon source coupling, we were able to provide significant molecular evidence for a positive correlation between protein glycation and collagen degradation in our mouse model. Our results bring a new insight not only to the effects of long-term GI dietary practices of the public but also to the molecular and chemical foundation behind the cardiovascular disease pathogenesis commonly seen in diabetic patients. PMID

  8. Sorbin and SH3 Domain‐Containing Protein 2 Is Released From Infarcted Heart in the Very Early Phase: Proteomic Analysis of Cardiac Tissues From Patients

    PubMed Central

    Kakimoto, Yu; Ito, Shinji; Abiru, Hitoshi; Kotani, Hirokazu; Ozeki, Munetaka; Tamaki, Keiji; Tsuruyama, Tatsuaki

    2013-01-01

    Background Few proteomic studies have examined human cardiac tissue following acute lethal infarction. Here, we applied a novel proteomic approach to formalin‐fixed, paraffin‐embedded human tissue and aimed to reveal the molecular changes in the very early phase of acute myocardial infarction. Methods and Results Heart tissue samples were collected from 5 patients who died within 7 hours of myocardial infarction and from 5 age‐ and sex‐matched control cases. Infarcted and control myocardia were histopathologically diagnosed and captured using laser microdissection. Proteins were extracted using an originally established method and analyzed using liquid chromatography–tandem mass spectrometry. The label‐free quantification demonstrated that the levels of 21 proteins differed significantly between patients and controls. In addition to known biomarkers, the sarcoplasmic protein sorbin and SH3 domain‐containing protein 2 (SORBS2) was greatly reduced in infarcted myocardia. Immunohistochemical analysis of cardiac tissues confirmed the decrease, and Western blot analysis showed a significant increase in serum sorbin and SH3 domain‐containing protein 2 in acute myocardial infarction patients (n=10) compared with control cases (n=11). Conclusions Our advanced comprehensive analysis using patient tissues and serums indicated that sarcoplasmic sorbin and SH3 domain‐containing protein 2 is released from damaged cardiac tissue into the bloodstream upon lethal acute myocardial infarction. The proteomic strategy presented here is based on precise microscopic findings and is quite useful for candidate biomarker discovery using human tissue samples stored in depositories. PMID:24342996

  9. Identification of thioredoxin target protein networks in cardiac tissues of a transgenic mouse

    PubMed Central

    Fu, Cexiong; Liu, Tong; Parrott, Andrew M.; Li, Hong

    2015-01-01

    The advent of sensitive and robust quantitative proteomics techniques has been emerging as a vital tool for deciphering complex biological puzzles that would have been challenging to conventional molecular biology methods. The method here describes the use of two isotope labeling techniques – isobaric tags for relative and absolute quantification (iTRAQ) and redox isotope-coded affinity tags (ICAT), to elucidate the cardiovascular redox-proteome changes and thioredoxin 1 (Trx1)-regulated protein network in cardiac-specific Trx1 transgenic mouse models. The strategy involves the use of an amine-labeling iTRAQ technique, gauging the global proteome changes in Trx1 transgenic mice at the protein level, while ICAT, labeling redox-sensitive cysteines, reveals the redox-status of cysteine residues. Collectively, these two quantitative proteomics techniques not only can quantify global changes of the cardiovascular proteome, but also pinpoint specific redox sensitive cysteine sites that are subjected to Trx1-catalzyed reduction. PMID:23606258

  10. Myocardial fat as a part of cardiac visceral adipose tissue: physiological and pathophysiological view.

    PubMed

    Selthofer-Relatić, K; Bošnjak, I

    2015-09-01

    Thoracic fat includes extra-pericardial (outside the visceral pericardium) and intra-pericardial (inside the visceral pericardium) adipose tissue. It is called ectopic adipose tissue although it is a normal anatomical structure. Intra-pericardial adipose tissue, which is predominantly composed of epicardial and pericoronary adipose tissue, has a significant role in cardiovascular system function. It provides metabolic-mechanical support to the heart and blood vessels in physiological conditions, while it represents metabolic-cardiovascular risk in case of qualitative and quantitative structural changes in the tissue: it correlates with coronary atherosclerotic disease, left ventricular mass, left atrium enlargement and atrial fibrillation presence. In the last decade there has been mounting evidence of fat cells presence in the myocardium of healthy (non-diseased) persons as well as in persons with both cardiovascular and non-cardiovascular diseases. Thus, it is necessary to clarify the incidence, aetiology, physiological role of fat cells in the myocardium, as well as the clinical significance of pathological fatty infiltration of the myocardium.

  11. Putative population of adipose-derived stem cells isolated from mediastinal tissue during cardiac surgery.

    PubMed

    Patel, Amit N; Yockman, James; Vargas, Vanessa; Bull, David A

    2013-01-01

    Mesenchymal stem cells have been isolated from various adult human tissues and are valuable for not only therapeutic applications but for the study of tissue homeostasis and disease progression. Subcutaneous adipose depots have been shown to contain large amounts of stem cells. There is little information that has been reported to date describing the isolation and characterization of mesenchymal stem cells from visceral adipose tissue. In this study, we describe a mesenchymal stem cell population isolated from mediastinal adipose depots. The cells express CD44, CD105, CD166, and CD90 and are negative for hematopoietic markers CD34, CD45, and HLA-DR. In addition, the cells have a multilineage potential, with the ability to differentiate into adipogenic, osteogenic, and chondrogenic cell types. The biological function of visceral adipose tissue remains largely unknown and uncharacterized. However, the proximity of adipose tissue to the heart suggests a potential role in the pathogenesis of cardiovascular disease in obesity. In addition, with the ability of fat to regulate metabolic activity in humans, this novel stem cell source may be useful to further study the mechanisms involved in metabolic disorders.

  12. Depth-resolved monitoring of diffusion of hyperosmotic agents in normal and malignant human esophagus tissues using optical coherence tomography in-vitro

    SciTech Connect

    Zhao Qingliang; Guo Zhouyi; Wei Huajiang; Yang Hongqin; Xie Shusen

    2011-10-31

    Depth-resolved monitoring with differentiation and quantification of glucose diffusion in healthy and abnormal esophagus tissues has been studied in vitro. Experiments have been performed using human normal esophagus and esophageal squamous cell carcinoma (ESCC) tissues by the optical coherence tomography (OCT). The images have been continuously acquired for 120 min in the experiments, and the depth-resolved and average permeability coefficients of the 40 % glucose solution have been calculated by the OCT amplitude (OCTA) method. We demonstrate the capability of the OCT technique for depth-resolved monitoring, differentiation, and quantifying of glucose diffusion in normal esophagus and ESCC tissues. It is found that the permeability coefficients of the 40 % glucose solution are not uniform throughout the normal esophagus and ESCC tissues and increase from (3.30 {+-} 0.09) Multiplication-Sign 10{sup -6} and (1.57 {+-} 0.05) Multiplication-Sign 10{sup -5} cm s{sup -1} at the mucous membrane of normal esophagus and ESCC tissues to (1.82 {+-} 0.04) Multiplication-Sign 10{sup -5} and (3.53 {+-} 0.09) Multiplication-Sign 10{sup -5} cm s{sup -1} at the submucous layer approximately 742 {mu}m away from the epithelial surface of normal esophagus and ESCC tissues, respectively. (optical coherence tomography)

  13. Depth-resolved monitoring of diffusion of hyperosmotic agents in normal and malignant human esophagus tissues using optical coherence tomography in-vitro

    NASA Astrophysics Data System (ADS)

    Zhao, Qingliang; Guo, Zhouyi; Wei, Huajiang; Yang, Hongqin; Xie, Shusen

    2011-10-01

    Depth-resolved monitoring with differentiation and quantification of glucose diffusion in healthy and abnormal esophagus tissues has been studied in vitro. Experiments have been performed using human normal esophagus and esophageal squamous cell carcinoma (ESCC) tissues by the optical coherence tomography (OCT). The images have been continuously acquired for 120 min in the experiments, and the depth-resolved and average permeability coefficients of the 40 % glucose solution have been calculated by the OCT amplitude (OCTA) method. We demonstrate the capability of the OCT technique for depth-resolved monitoring, differentiation, and quantifying of glucose diffusion in normal esophagus and ESCC tissues. It is found that the permeability coefficients of the 40 % glucose solution are not uniform throughout the normal esophagus and ESCC tissues and increase from (3.30 ± 0.09) × 10-6 and (1.57 ± 0.05) × 10-5 cm s-1 at the mucous membrane of normal esophagus and ESCC tissues to (1.82 ± 0.04) × 10-5 and (3.53 ± 0.09) × 10-5 cm s-1 at the submucous layer approximately 742 μm away from the epithelial surface of normal esophagus and ESCC tissues, respectively.

  14. Craniofacial reconstruction using a combined statistical model of face shape and soft tissue depths: methodology and validation.

    PubMed

    Claes, Peter; Vandermeulen, Dirk; De Greef, Sven; Willems, Guy; Suetens, Paul

    2006-05-15

    Forensic facial reconstruction aims at estimating the facial outlook associated with an unidentified skull specimen. Estimation is generally based on tabulated average values of soft tissue thicknesses measured at a sparse set of landmarks on the skull. Traditional 'plastic' methods apply modeling clay or plasticine on a cast of the skull, approximating the estimated tissue depths at the landmarks and interpolating in between. Current computerized techniques mimic this landmark interpolation procedure using a single static facial surface template. However, the resulting reconstruction is biased by the specific choice of the template and no face-specific regularization is used during the interpolation process. We reduce the template bias by using a flexible statistical model of a dense set of facial surface points, combined with an associated sparse set of skull-based landmarks. This statistical model is constructed from a facial database of (N = 118) individuals and limits the reconstructions to statistically plausible outlooks. The actual reconstruction is obtained by fitting the skull-based landmarks of the template model to the corresponding landmarks indicated on a digital copy of the skull to be reconstructed. The fitting process changes the face-specific statistical model parameters in a regularized way and interpolates the remaining landmark fit error using a minimal bending thin-plate spline (TPS)-based deformation. Furthermore, estimated properties of the skull specimen (BMI, age and gender, e.g.) can be incorporated as conditions on the reconstruction by removing property-related shape variation from the statistical model description before the fitting process. The proposed statistical method is validated, both in terms of accuracy and identification success rate, based on leave-one-out cross-validation tests applied on the facial database. Accuracy results are obtained by statistically analyzing the local 3D facial surface differences of the

  15. Craniofacial reconstruction using a combined statistical model of face shape and soft tissue depths: methodology and validation.

    PubMed

    Claes, Peter; Vandermeulen, Dirk; De Greef, Sven; Willems, Guy; Suetens, Paul

    2006-05-15

    Forensic facial reconstruction aims at estimating the facial outlook associated with an unidentified skull specimen. Estimation is generally based on tabulated average values of soft tissue thicknesses measured at a sparse set of landmarks on the skull. Traditional 'plastic' methods apply modeling clay or plasticine on a cast of the skull, approximating the estimated tissue depths at the landmarks and interpolating in between. Current computerized techniques mimic this landmark interpolation procedure using a single static facial surface template. However, the resulting reconstruction is biased by the specific choice of the template and no face-specific regularization is used during the interpolation process. We reduce the template bias by using a flexible statistical model of a dense set of facial surface points, combined with an associated sparse set of skull-based landmarks. This statistical model is constructed from a facial database of (N = 118) individuals and limits the reconstructions to statistically plausible outlooks. The actual reconstruction is obtained by fitting the skull-based landmarks of the template model to the corresponding landmarks indicated on a digital copy of the skull to be reconstructed. The fitting process changes the face-specific statistical model parameters in a regularized way and interpolates the remaining landmark fit error using a minimal bending thin-plate spline (TPS)-based deformation. Furthermore, estimated properties of the skull specimen (BMI, age and gender, e.g.) can be incorporated as conditions on the reconstruction by removing property-related shape variation from the statistical model description before the fitting process. The proposed statistical method is validated, both in terms of accuracy and identification success rate, based on leave-one-out cross-validation tests applied on the facial database. Accuracy results are obtained by statistically analyzing the local 3D facial surface differences of the

  16. All-near-infrared multiphoton microscopy interrogates intact tissues at deeper imaging depths than conventional single- and two-photon near-infrared excitation microscopes.

    PubMed

    Sarder, Pinaki; Yazdanfar, Siavash; Akers, Walter J; Tang, Rui; Sudlow, Gail P; Egbulefu, Christopher; Achilefu, Samuel

    2013-10-01

    The era of molecular medicine has ushered in the development of microscopic methods that can report molecular processes in thick tissues with high spatial resolution. A commonality in deep-tissue microscopy is the use of near-infrared (NIR) lasers with single- or multiphoton excitations. However, the relationship between different NIR excitation microscopic techniques and the imaging depths in tissue has not been established. We compared such depth limits for three NIR excitation techniques: NIR single-photon confocal microscopy (NIR SPCM), NIR multiphoton excitation with visible detection (NIR/VIS MPM), and all-NIR multiphoton excitation with NIR detection (NIR/NIR MPM). Homologous cyanine dyes provided the fluorescence. Intact kidneys were harvested after administration of kidney-clearing cyanine dyes in mice. NIR SPCM and NIR/VIS MPM achieved similar maximum imaging depth of ∼100 μm. The NIR/NIR MPM enabled greater than fivefold imaging depth (>500 μm) using the harvested kidneys. Although the NIR/NIR MPM used 1550-nm excitation where water absorption is relatively high, cell viability and histology studies demonstrate that the laser did not induce photothermal damage at the low laser powers used for the kidney imaging. This study provides guidance on the imaging depth capabilities of NIR excitation-based microscopic techniques and reveals the potential to multiplex information using these platforms.

  17. Magnetic Imaging of Applied and Propagating Action Currents in Cardiac Tissue Slices: Determination of Anisotropic Electrical Conductivities in a Two-Dimensional Bidomain.

    NASA Astrophysics Data System (ADS)

    Staton, Daniel Joseph

    We describe the first, high-resolution magnetic images of applied currents and propagating action currents in slices of canine cardiac tissue. This tissue was maintained in vitro at 37^circC. Our main conclusions are summarized as follows: the action currents produce magnetic fields which are measurable; during the initial stages of the propagating action potential, small, expanding, quatrefoil loops of current develop; the magnetic fields produced by repolarization currents are larger than previously anticipated. Most of the current associated with the propagating action potential is confined within the wavefront and should be magnetically silent; however, differences in the intracellular and extracellular electrical conductivities, in both the longitudinal and transverse fiber directions, are great enough that expanding quatrefoil current densities are associated with the wavefront and produce measurable magnetic fields. Since action currents are affected by the electrical conductivities, it is of interest to determine their values, which depend not only upon the tissue characteristics, but also on the mathematical model used to interpret the measured data. In our analysis of current injection, we use the anisotropic bidomain model which incorporates a passive, linear membrane. We introduce theoretical techniques to calculate the anisotropic conductivities of a two-dimensional bidomain. To apply these techniques to magnetic fields resulting from current injection into cardiac tissue slices, we need to improve the higher spatial frequency content of our present measurements. This may be done by measuring the magnetic field closer to the cardiac slice (presently 2.5 mm), decreasing the sampling interval of the measurement, and increasing the sampling area of the field. Magnetic fields are produced by propagating action currents, which are in turn the result of the propagating action potential. From the magnetic field, we directly image isochronal transmembrane

  18. Cardiac catheterization

    MedlinePlus

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; Heart failure - ...

  19. Efficient generation of human embryonic stem cell-derived cardiac progenitors based on tissue-specific enhanced green fluorescence protein expression.

    PubMed

    Szebényi, Kornélia; Péntek, Adrienn; Erdei, Zsuzsa; Várady, György; Orbán, Tamás I; Sarkadi, Balázs; Apáti, Ágota

    2015-01-01

    Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain their proliferative capacity before becoming quiescent mature cardiomyocytes (CMs). In medical therapy and research, the use of human pluripotent stem cell-derived CPCs would have several advantages compared with mature CMs, as the progenitors show better engraftment into existing heart tissues, and provide unique potential for cardiovascular developmental as well as for pharmacological studies. Here, we demonstrate that the CAG promoter-driven enhanced green fluorescence protein (EGFP) reporter system enables the identification and isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during differentiation confirmed up-regulation of surface markers, previously described to identify cardiac precursors and early CMs. Isolated CPCs express cardiac lineage-specific transcripts, still have proliferating capacity, and can be re-aggregated into embryoid body-like structures (CAG-EGFP(high) rEBs). Expression of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG-EGFP(high) rEBs, in which more than 90% of the cells become Troponin I positive mature CMs. Moreover, about one third of the CAG-EGFP(high) rEBs show spontaneous contractions. The method described here provides a powerful tool to generate expandable cultures of pure human CPCs that can be used for exploring early markers of the cardiac lineage, as well as for drug screening or tissue engineering applications.

  20. Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP

    PubMed Central

    Spengler, Ryan M.; Zhang, Xiaoming; Cheng, Congsheng; McLendon, Jared M.; Skeie, Jessica M.; Johnson, Frances L.; Davidson, Beverly L.; Boudreau, Ryan L.

    2016-01-01

    MicroRNAs (miRs) have emerged as key biological effectors in human health and disease. These small noncoding RNAs are incorporated into Argonaute (Ago) proteins, where they direct post-transcriptional gene silencing via base-pairing with target transcripts. Although miRs have become intriguing biological entities and attractive therapeutic targets, the translational impacts of miR research remain limited by a paucity of empirical miR targeting data, particularly in human primary tissues. Here, to improve our understanding of the diverse roles miRs play in cardiovascular function and disease, we applied high-throughput methods to globally profile miR:target interactions in human heart tissues. We deciphered Ago2:RNA interactions using crosslinking immunoprecipitation coupled with high-throughput sequencing (HITS-CLIP) to generate the first transcriptome-wide map of miR targeting events in human myocardium, detecting 4000 cardiac Ago2 binding sites across >2200 target transcripts. Our initial exploration of this interactome revealed an abundance of miR target sites in gene coding regions, including several sites pointing to new miR-29 functions in regulating cardiomyocyte calcium, growth and metabolism. Also, we uncovered several clinically-relevant interactions involving common genetic variants that alter miR targeting events in cardiomyopathy-associated genes. Overall, these data provide a critical resource for bolstering translational miR research in heart, and likely beyond. PMID:27418678

  1. Gene expression profiling in the fetal cardiac tissue after folate and low dose trichloroethylene exposure

    PubMed Central

    Caldwell, Patricia T.; Manziello, Ann; Howard, Jamie; Palbykin, Brittany; Runyan, Raymond B.; Selmin, Ornella

    2014-01-01

    Background Previous studies show gene expression alterations in rat embryo hearts and cell lines that correspond to the cardio-teratogenic effects of trichloroethylene (TCE) in animal models. One potential mechanism of TCE teratogenicity may be through altered regulation of calcium homeostatic genes with a corresponding inhibition of cardiac function. It has been suggested that TCE may interfere with the folic acid/methylation pathway in liver and kidney and alter gene regulation by epigenetic mechanisms. According to this hypothesis, folate supplementation in the maternal diet should counteract TCE effects on gene expression in the embryonic heart. Approach To identify transcriptional targets altered in the embryonic heart after exposure to TCE, and possible protective effects of folate, we used DNA microarray technology to profile gene expression in embryonic mouse hearts with maternal TCE exposure and dietary changes in maternal folate. Results Exposure to low doses of TCE (10ppb) caused extensive alterations in transcripts encoding proteins involved in transport, ion channel, transcription, differentiation, cytoskeleton, cell cycle and apoptosis. Exogenous folate did not offset the effects of TCE exposure on normal gene expression and both high and low levels of folate produced additional significant changes in gene expression. Conclusions A mechanism where TCE induces a folate deficiency does not explain altered gene expression patterns in the embryonic mouse heart. The data further suggest that use of folate supplementation, in the presence of this toxin, may be detrimental and non-protective of the developing embryo. PMID:19813261

  2. Robust image-based estimation of cardiac tissue parameters and their uncertainty from noisy data.

    PubMed

    Neumann, Dominik; Mansi, Tommaso; Georgescu, Bogdan; Kamen, Ali; Kayvanpour, Elham; Amr, Ali; Sedaghat-Hamedani, Farbod; Haas, Jan; Katus, Hugo; Meder, Benjamin; Hornegger, Joachim; Comaniciu, Dorin

    2014-01-01

    Clinical applications of computational cardiac models require precise personalization, i.e. fitting model parameters to capture patient's physiology. However, due to parameter non-identifiability, limited data, uncertainty in the clinical measurements, and modeling assumptions, various combinations of parameter values may exist that yield the same quality of fit. Hence, there is a need for quantifying the uncertainty in estimated parameters and to ascertain the uniqueness of the found solution. This paper presents a stochastic method to estimate the parameters of an image-based electromechanical model of the heart and their uncertainty due to noise in measurements. First, Bayesian inference is applied to fully estimate the posterior probability density function (PDF) of the model. To that end, Markov Chain Monte Carlo sampling is used, which is made computationally tractable by employing a fast surrogate model based on Polynomial Chaos Expansion, instead of the true forward model. Then, we use the mean-shift algorithm to automatically find the modes of the PDF and select the most likely one while being robust to noise. The approach is used to estimate global active stress and passive stiffness from invasive pressure and image-based volume quantification. Experiments on eight patients showed that not only our approach yielded goodness of fits equivalent to a well-established deterministic method, but we could also demonstrate the non-uniqueness of the problem and report uncertainty estimates, crucial information for subsequent clinical assessments of the personalized models. PMID:25485357

  3. Poly(Glycerol Sebacate)/Poly(Butylene Succinate-Butylene Dilinoleate) Fibrous Scaffolds for Cardiac Tissue Engineering

    PubMed Central

    Tallawi, Marwa; Zebrowski, David C.; Rai, Ranjana; Roether, Judith A.; Schubert, Dirk W.; El Fray, Miroslawa; Aifantis, Katerina E.

    2015-01-01

    The present article investigates the use of a novel electrospun fibrous blend of poly(glycerol sebacate) (PGS) and poly(butylene succinate-butylene dilinoleate) (PBS-DLA) as a candidate for cardiac tissue engineering. Random electrospun fibers with various PGS/PBS-DLA compositions (70/30, 60/40, 50/50, and 0/100) were fabricated. To examine the suitability of these fiber blends for heart patches, their morphology, as well as their physical, chemical, and mechanical properties were measured before examining their biocompatibility through cell adhesion. The fabricated fibers were bead-free and exhibited a relatively narrow diameter distribution. The addition of PBS-DLA to PGS resulted in an increase of the average fiber diameter, whereas increasing the amount of PBS-DLA decreased the hydrophilicity and the water uptake of the nanofibrous scaffolds to values that approached those of neat PBS-DLA nanofibers. Moreover, the addition of PBS-DLA significantly increased the elastic modulus. Initial toxicity studies with C2C12 myoblast cells up to 72 h confirmed nontoxic behavior of the blends. Immunofluorescence analyses and scanning electron microscopy analyses confirmed that C2C12 cells showed better cell attachment and proliferation on electrospun mats with higher PBS-DLA content. However, immunofluorescence analyses of the 3-day-old rat cardiomyocytes cultured for 2 and 5 days demonstrated better attachment on the 70/30 fibers containing well-aligned sarcomeres and expressing high amounts of connexin 43 in cellular junctions indicating efficient cell-to-cell communication. It can be concluded, therefore, that fibrous PGS/PBS-DLA scaffolds exhibit promising characteristics as a biomaterial for cardiac patch applications. PMID:25439964

  4. Poly(glycerol sebacate)/poly(butylene succinate-butylene dilinoleate) fibrous scaffolds for cardiac tissue engineering.

    PubMed

    Tallawi, Marwa; Zebrowski, David C; Rai, Ranjana; Roether, Judith A; Schubert, Dirk W; El Fray, Miroslawa; Engel, Felix B; Aifantis, Katerina E; Boccaccini, Aldo R

    2015-06-01

    The present article investigates the use of a novel electrospun fibrous blend of poly(glycerol sebacate) (PGS) and poly(butylene succinate-butylene dilinoleate) (PBS-DLA) as a candidate for cardiac tissue engineering. Random electrospun fibers with various PGS/PBS-DLA compositions (70/30, 60/40, 50/50, and 0/100) were fabricated. To examine the suitability of these fiber blends for heart patches, their morphology, as well as their physical, chemical, and mechanical properties were measured before examining their biocompatibility through cell adhesion. The fabricated fibers were bead-free and exhibited a relatively narrow diameter distribution. The addition of PBS-DLA to PGS resulted in an increase of the average fiber diameter, whereas increasing the amount of PBS-DLA decreased the hydrophilicity and the water uptake of the nanofibrous scaffolds to values that approached those of neat PBS-DLA nanofibers. Moreover, the addition of PBS-DLA significantly increased the elastic modulus. Initial toxicity studies with C2C12 myoblast cells up to 72 h confirmed nontoxic behavior of the blends. Immunofluorescence analyses and scanning electron microscopy analyses confirmed that C2C12 cells showed better cell attachment and proliferation on electrospun mats with higher PBS-DLA content. However, immunofluorescence analyses of the 3-day-old rat cardiomyocytes cultured for 2 and 5 days demonstrated better attachment on the 70/30 fibers containing well-aligned sarcomeres and expressing high amounts of connexin 43 in cellular junctions indicating efficient cell-to-cell communication. It can be concluded, therefore, that fibrous PGS/PBS-DLA scaffolds exhibit promising characteristics as a biomaterial for cardiac patch applications.

  5. Phase-2 reentry in cardiac tissue: Role of the slow calcium pulse

    NASA Astrophysics Data System (ADS)

    Cantalapiedra, Inma R.; Peñaranda, Angelina; Echebarria, Blas; Bragard, Jean

    2010-07-01

    Phase-2 re-entry is thought to underlie many causes of idiopathic ventricular arrhythmias as, for instance, those occurring in Brugada syndrome. In this paper, we study under which circumstances a region of depolarized tissue can re-excite adjacent regions that exhibit shorter action potential duration (APD), eventually inducing reentry. For this purpose, we use a simplified ionic model that reproduces well the ventricular action potential. With the help of this model, we analyze the conditions that lead to very short action potentials (APs), as well as possible mechanisms for re-excitation in a cable. We then study the induction of re-entrant waves (spiral waves) in simulations of AP propagation in the heart ventricles. We show that re-excitation takes place via a slow pulse produced by calcium current that propagates into the region of short APs until it encounters excitable tissue. We calculate analytically the speed of the slow pulse, and also give an estimate of the minimal tissue size necessary for allowing reexcitation to take place.

  6. Specific Uncoupling of Excitation and Contraction in Mammalian Cardiac Tissue by Lanthanum

    PubMed Central

    Sanborn, W. G.; Langer, G. A.

    1970-01-01

    Arterially cannulated rabbit interventricular septal tissue was exposed to 5–40 µM La in 2.5 mM Ca perfusate. Immediately following perfusion with La two concurrent events were consistently observed: (a) a rapid decline of active tension to a lesser steady-state value, and (b) an abrupt, release of short duration of tissue-bound Ca. The magnitude of both events was directly related to the [La]o. If the duration of exposure to La was brief, contractility returned toward normal upon return to the La-free perfusate. Elevation of [Ca]o during exposure to La counteracted its effect and induced a concurrent displacement of tissue-bound La. Cellular action potentials recorded during brief perfusion with La demonstrated that essentially normal regenerative depolarization was maintained. Analysis of the quantities of 45Ca released following exposure to 10 µM La indicated that this La-susceptible Ca was being displaced from a homogeneous pool—the one previously shown by Langer to represent contractile dependent Ca. These data led to the following conclusions: During perfusion with 2.5 mM Ca contractile dependent Ca was derived primarily from "superficially" located sites. La effected the release of contractile dependent Ca by modifying the normal permselectivity of this "superficial" membrane for activator Ca. These and other data infer that contractile dependent Ca is derived primarily from superficially located sites. PMID:5433467

  7. Stereoselective binding in cardiac tissue of the enatiomers of benzetimide, and antimuscarinic drug.

    PubMed Central

    Gray, J A; Lüllmann, H; Mitchelson, F; Reil, G H

    1976-01-01

    1 Benzetimide, possessing two stable enantiomers, dexetimide and levetimide, has been investigated in guinea-pig atria with respect to its atropine-like action and its tissue distribution. 2 The antagonistic potency of dexetimide was found to be over 6000 times higher than that of levetimide, the pA2 values being 9.82 and 6.0 respectively. 3 The tissue accumulation was investigated for both isomers in the concentration range from 1.5 X 10(-9) M to 10(-6) M yielding tissue to medium ratios (T/M) of between approximately 50 and 10. The highest values were found for the lowest concentrations. At any concentration investigated, dexetimide exhibited a higher uptake than the levoisomer. 4 The rate of uptake and washout of dexetimide was extremely slow, that of levetimide being considerably faster at equimolar concentrations. The same pattern held true for the onset and decline of the antagonistic action. 5 The high accumulation was found to be almost entirely due to unspecific binding. Even in the case of dexetimide the relative size of the receptor compartment could not be determined. The unspecific binding sites displayed a certain stereoselectivity but to a much lesser extent than the specific receptor binding sites. PMID:1260229

  8. Microwave Treatment for Cardiac Arrhythmias

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey (Inventor); Carl, James R. (Inventor); Raffoul, George W. (Inventor); Pacifico, Antonio (Inventor)

    1999-01-01

    Method and apparatus are provided for propagating microwave energy into heart tissues to produce a desired temperature profile therein at tissue depths sufficient for thermally ablating arrhythmogenic cardiac tissue to treat ventricular tachycardia and other arrhythmias while preventing excessive heating of surrounding tissues, organs, and blood. A wide bandwidth double-disk antenna is effective for this purpose over a bandwidth of about six gigahertz. A computer simulation provides initial screening capabilities for an antenna such as antenna, frequency, power level, and power application duration. The simulation also allows optimization of techniques for specific patients or conditions. In operation, microwave energy between about 1 Gigahertz and 12 Gigahertz is applied to monopole microwave radiator having a surface wave limiter. A test setup provides physical testing of microwave radiators to determine the temperature profile created in actual heart tissue or ersatz heart tissue. Saline solution pumped over the heart tissue with a peristaltic pump simulates blood flow. Optical temperature sensors disposed at various tissue depths within the heart tissue detect the temperature profile without creating any electromagnetic interference. The method may be used to produce a desired temperature profile in other body tissues reachable by catheter such as tumors and the like.

  9. Nonlinear behaviour of conduction and block in cardiac tissue with heterogeneous expression of connexin 43.

    PubMed

    Prudat, Yann; Kucera, Jan P

    2014-11-01

    Altered gap junctional coupling potentiates slow conduction and arrhythmias. To better understand how heterogeneous connexin expression affects conduction at the cellular scale, we investigated conduction in tissue consisting of two cardiomyocyte populations expressing different connexin levels. Conduction was mapped using microelectrode arrays in cultured strands of foetal murine ventricular myocytes with predefined contents of connexin 43 knockout (Cx43KO) cells. Corresponding computer simulations were run in randomly generated two-dimensional tissues mimicking the cellular architecture of the strands. In the cultures, the relationship between conduction velocity (CV) and Cx43KO cell content was nonlinear. CV first decreased significantly when Cx43KO content was increased from 0 to 50%. When the Cx43KO content was ≥60%, CV became comparable to that in 100% Cx43KO strands. Co-culturing Cx43KO and wild-type cells also resulted in significantly more heterogeneous conduction patterns and in frequent conduction blocks. The simulations replicated this behaviour of conduction. For Cx43KO contents of 10-50%, conduction was slowed due to wavefront meandering between Cx43KO cells. For Cx43KO contents ≥60%, clusters of remaining wild-type cells acted as electrical loads that impaired conduction. For Cx43KO contents of 40-60%, conduction exhibited fractal characteristics, was prone to block, and was more sensitive to changes in ion currents compared to homogeneous tissue. In conclusion, conduction velocity and stability behave in a nonlinear manner when cardiomyocytes expressing different connexin amounts are combined. This behaviour results from heterogeneous current-to-load relationships at the cellular level. Such behaviour is likely to be arrhythmogenic in various clinical contexts in which gap junctional coupling is heterogeneous.

  10. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations.

    PubMed

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P; Sawle, Philip; Pollitt, Rebecca C; Holder, Susan E; Wakeling, Emma; Moat, Neil; Pope, F Michael

    2014-02-01

    Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart disease and associated with tissue fragility. The diagnosis of a type I collagen disorder was confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was investigated with electrophoresis of collagens from cultured skin fibroblasts, showing structurally abnormal collagen type I, skin biopsy showed unusual histology and abnormal collagen fibril ultra-structure at electron microscopy. The combined clinical, surgical, histological, ultra-structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease. The degree of tissue fragility experienced at cardiac surgery in these individuals, also reported in a small number of similar case reports, suggests that patients with OI type I need careful pre-operative assessment and consideration of the risks and benefits of cardiac surgery.

  11. Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations.

    PubMed

    Vandersteen, Anthony M; Lund, Allan M; Ferguson, David J P; Sawle, Philip; Pollitt, Rebecca C; Holder, Susan E; Wakeling, Emma; Moat, Neil; Pope, F Michael

    2014-02-01

    Osteogenesis imperfecta (OI) type I is a hereditary disorder of connective tissue (HDCT) characterized by blue or gray sclerae, variable short stature, dentinogenesis imperfecta, hearing loss, and recurrent fractures from infancy. We present four examples of OI type I complicated by valvular heart disease and associated with tissue fragility. The diagnosis of a type I collagen disorder was confirmed by abnormal COL1A1 or COL1A2 gene sequencing. One patient was investigated with electrophoresis of collagens from cultured skin fibroblasts, showing structurally abnormal collagen type I, skin biopsy showed unusual histology and abnormal collagen fibril ultra-structure at electron microscopy. The combined clinical, surgical, histological, ultra-structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease. The degree of tissue fragility experienced at cardiac surgery in these individuals, also reported in a small number of similar case reports, suggests that patients with OI type I need careful pre-operative assessment and consideration of the risks and benefits of cardiac surgery. PMID:24311407

  12. Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

    NASA Technical Reports Server (NTRS)

    Verbanck, S.; Larsson, H.; Linnarsson, D.; Prisk, G. K.; West, J. B.; Paiva, M.

    1997-01-01

    In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

  13. Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model

    PubMed Central

    2012-01-01

    Background Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model. Methods 100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%. Results At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93). Conclusions Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels. PMID:22361346

  14. Cardiomyocytes In Vitro Adhesion Is Actively Influenced by Biomimetic Synthetic Peptides for Cardiac Tissue Engineering

    PubMed Central

    Huerta-Cantillo, Rocio; Comisso, Marina; Danesin, Roberta; Ghezzo, Francesca; Naso, Filippo; Gastaldello, Alessandra; Schittullo, Eleonora; Buratto, Edward; Spina, Michele; Gerosa, Gino; Dettin, Monica

    2012-01-01

    Scaffolds for tissue engineering must be designed to direct desired events such as cell attachment, growth, and differentiation. The incorporation of extracellular matrix-derived peptides into biomaterials has been proposed to mimic biochemical signals. In this study, three synthetic fragments of fibronectin, vitronectin, and stromal-derived factor-1 were investigated for the first time as potential adhesive sequences for cardiomyocytes (CMs) compared to smooth muscle cells. CMs are responsive to all peptides to differing degrees, demonstrating the existence of diverse adhesion mechanisms. The pretreatment of nontissue culture well surfaces with the (Arginine-Glycine-Aspartic Acid) RGD sequence anticipated the appearance of CMs' contractility compared to the control (fibronectin-coated well) and doubled the length of cell viability. Future prospects are the inclusion of these sequences into biomaterial formulation with the improvement in cell adhesion that could play an important role in cell retention during dynamic cell seeding. PMID:22011064

  15. Mediastinitis after cardiac surgery: improvement of bacteriological diagnosis by use of multiple tissue samples and strain typing.

    PubMed

    Tammelin, Ann; Hambraeus, Anna; Ståhle, Elisabeth

    2002-08-01

    The diagnosis of postsurgical mediastinitis (PSM) among patients with sternal wound complication (SWC) after cardiac surgery is sometimes difficult, as fever, elevated C-reactive protein levels, and chest pain can be caused by a general inflammatory reaction to the operative trauma and/or sternal dehiscence without infection. The definitions of PSM usually used emphasize clinical signs and symptoms easily observed by the surgeon. The aim of the study was to investigate whether the use of standardized multiple tissue sampling, optimal culturing methods, and strain typing, together with a microbiological criterion for infection, could identify more infected patients than clinical assessment alone. Patients reexplored due to SWC after cardiac artery bypass grafting (CABG) or heart valve replacement (HVR) with or without CABG performed at the Department for Cardio-Thoracic Surgery at the Uppsala University Hospital between 10 March 1998 and 9 September 2000 were investigated prospectively. Tissue samples were taken from the sternum or adjacent mediastinal tissue, preferably before the administration of antibiotics. Culturing was performed both directly (on agar plates) and using enrichment broth. Species identification was performed by standard methods, and strain typing was performed by pulsed-field gel electrophoresis. A total of 41 cases with at least five tissue samples each were included in the study group. Of these patients, 32 were infected according to the microbiological criterion (i.e., the same strain was found in >/=50% of the samples). Staphylococcus epidermidis was the primary pathogen in 38% of the cases (12/32), S. aureus was the primary pathogen in 31% (10/32), P. acnes was the primary pathogen in 25% (8/32), and S. simulans and S. haemolyticus were the primary pathogens in 3% (1/32) each. All cases of S. aureus infection and 86% (12/14) of coagulase-negative staphylococcus (CoNS) infections were identified from primary cultures. All cases fulfilling

  16. Quantifying the effect of tissue deformation on diffusion-weighted MRI: a mathematical model and an efficient simulation framework applied to cardiac diffusion imaging

    NASA Astrophysics Data System (ADS)

    Mekkaoui, Imen; Moulin, Kevin; Croisille, Pierre; Pousin, Jerome; Viallon, Magalie

    2016-08-01

    Cardiac motion presents a major challenge in diffusion weighted MRI, often leading to large signal losses that necessitate repeated measurements. The diffusion process in the myocardium is difficult to investigate because of the unqualified sensitivity of diffusion measurements to cardiac motion. A rigorous mathematical formalism is introduced to quantify the effect of tissue motion in diffusion imaging. The presented mathematical model, based on the Bloch-Torrey equations, takes into account deformations according to the laws of continuum mechanics. Approximating this mathematical model by using finite elements method, numerical simulations can predict the sensitivity of the diffusion signal to cardiac motion. Different diffusion encoding schemes are considered and the diffusion weighted MR signals, computed numerically, are compared to available results in literature. Our numerical model can identify the existence of two time points in the cardiac cycle, at which the diffusion is unaffected by myocardial strain and cardiac motion. Of course, these time points depend on the type of diffusion encoding scheme. Our numerical results also show that the motion sensitivity of the diffusion sequence can be reduced by using either spin echo technique with acceleration motion compensation diffusion gradients or stimulated echo acquisition mode with unipolar and bipolar diffusion gradients.

  17. Quantifying the effect of tissue deformation on diffusion-weighted MRI: a mathematical model and an efficient simulation framework applied to cardiac diffusion imaging

    NASA Astrophysics Data System (ADS)

    Mekkaoui, Imen; Moulin, Kevin; Croisille, Pierre; Pousin, Jerome; Viallon, Magalie

    2016-08-01

    Cardiac motion presents a major challenge in diffusion weighted MRI, often leading to large signal losses that necessitate repeated measurements. The diffusion process in the myocardium is difficult to investigate because of the unqualified sensitivity of diffusion measurements to cardiac motion. A rigorous mathematical formalism is introduced to quantify the effect of tissue motion in diffusion imaging. The presented mathematical model, based on the Bloch–Torrey equations, takes into account deformations according to the laws of continuum mechanics. Approximating this mathematical model by using finite elements method, numerical simulations can predict the sensitivity of the diffusion signal to cardiac motion. Different diffusion encoding schemes are considered and the diffusion weighted MR signals, computed numerically, are compared to available results in literature. Our numerical model can identify the existence of two time points in the cardiac cycle, at which the diffusion is unaffected by myocardial strain and cardiac motion. Of course, these time points depend on the type of diffusion encoding scheme. Our numerical results also show that the motion sensitivity of the diffusion sequence can be reduced by using either spin echo technique with acceleration motion compensation diffusion gradients or stimulated echo acquisition mode with unipolar and bipolar diffusion gradients.

  18. Quantifying the effect of tissue deformation on diffusion-weighted MRI: a mathematical model and an efficient simulation framework applied to cardiac diffusion imaging.

    PubMed

    Mekkaoui, Imen; Moulin, Kevin; Croisille, Pierre; Pousin, Jerome; Viallon, Magalie

    2016-08-01

    Cardiac motion presents a major challenge in diffusion weighted MRI, often leading to large signal losses that necessitate repeated measurements. The diffusion process in the myocardium is difficult to investigate because of the unqualified sensitivity of diffusion measurements to cardiac motion. A rigorous mathematical formalism is introduced to quantify the effect of tissue motion in diffusion imaging. The presented mathematical model, based on the Bloch-Torrey equations, takes into account deformations according to the laws of continuum mechanics. Approximating this mathematical model by using finite elements method, numerical simulations can predict the sensitivity of the diffusion signal to cardiac motion. Different diffusion encoding schemes are considered and the diffusion weighted MR signals, computed numerically, are compared to available results in literature. Our numerical model can identify the existence of two time points in the cardiac cycle, at which the diffusion is unaffected by myocardial strain and cardiac motion. Of course, these time points depend on the type of diffusion encoding scheme. Our numerical results also show that the motion sensitivity of the diffusion sequence can be reduced by using either spin echo technique with acceleration motion compensation diffusion gradients or stimulated echo acquisition mode with unipolar and bipolar diffusion gradients. PMID:27385441

  19. Preparation of a porous conductive scaffold from aniline pentamer-modified polyurethane/PCL blend for cardiac tissue engineering.

    PubMed

    Baheiraei, Nafiseh; Yeganeh, Hamid; Ai, Jafar; Gharibi, Reza; Ebrahimi-Barough, Somayeh; Azami, Mahmoud; Vahdat, Sadaf; Baharvand, Hossein

    2015-10-01

    A novel biodegradable electroactive polyurethane containing aniline pentamer (AP) was blended with polycaprolactone (PCL). The prepared blend (PB) and PCL were further fabricated in to scaffolds using a mixture of poly(ethylene glycol) and salt particles in a double porogen particulate leaching and compression molding methodology. Scaffolds held open and interconnected pores having pore size ranging from several μm to 150 µm. PB scaffolds had compression modulus and strength of 4.1 and 1.3 MPa, respectively. The conductivity of the scaffold was measured as 10(-5) ± 0.09 S .cm(-1) and preserved for at least 100 h post fabrication. Scaffolds supported neonatal cardiomyocytes adhesion and growth with PB showing more extensive effect on the expression of the cardiac genes involved in muscle contraction and relaxation (troponin-T) and cytoskeleton alignment (actinin-4). Our results highlight the potential of incorporation of AP as an electroactive moiety for induction of cardiomyocyte proliferation and repair of damaged heart tissue. PMID:25765879

  20. MALDI Mass Spectrometric Imaging of Cardiac Tissue Following Myocardial Infarction in a Rat Coronary Artery Ligation Model

    PubMed Central

    Menger, Robert F.; Stutts, Whitney L.; Anbukumar, Dhanam S.; Bowden, John A.; Ford, David A.; Yost, Richard A.

    2011-01-01

    Although acute myocardial infarction (MI) is consistently among the top causes of death in the United States, the spatial distribution of lipids and metabolites following MI remains to be elucidated. This work presents the investigation of an in vivo rat model of MI using mass spectrometric imaging (MSI) and multivariate data analysis. MSI was conducted on cardiac tissue following a 24-hour left anterior descending coronary artery ligation in order to analyze multiple compound classes. First, the spatial distribution of a small metabolite, creatine, was used to identify areas of infarcted myocardium. Second, multivariate data analysis and tandem mass spectrometry were used to identify phospholipid (PL) markers of MI. A number of lysophospholipids demonstrated increased ion signal in areas of infarction. In contrast, select intact PLs demonstrated decreased ion signal in the area of infarction. The complementary nature of these two lipid classes suggest increased activity of phospholipase A2, an enzyme that has been implicated in coronary heart disease and inflammation. PMID:22141424

  1. Preparation of a porous conductive scaffold from aniline pentamer-modified polyurethane/PCL blend for cardiac tissue engineering.

    PubMed

    Baheiraei, Nafiseh; Yeganeh, Hamid; Ai, Jafar; Gharibi, Reza; Ebrahimi-Barough, Somayeh; Azami, Mahmoud; Vahdat, Sadaf; Baharvand, Hossein

    2015-10-01

    A novel biodegradable electroactive polyurethane containing aniline pentamer (AP) was blended with polycaprolactone (PCL). The prepared blend (PB) and PCL were further fabricated in to scaffolds using a mixture of poly(ethylene glycol) and salt particles in a double porogen particulate leaching and compression molding methodology. Scaffolds held open and interconnected pores having pore size ranging from several μm to 150 µm. PB scaffolds had compression modulus and strength of 4.1 and 1.3 MPa, respectively. The conductivity of the scaffold was measured as 10(-5) ± 0.09 S .cm(-1) and preserved for at least 100 h post fabrication. Scaffolds supported neonatal cardiomyocytes adhesion and growth with PB showing more extensive effect on the expression of the cardiac genes involved in muscle contraction and relaxation (troponin-T) and cytoskeleton alignment (actinin-4). Our results highlight the potential of incorporation of AP as an electroactive moiety for induction of cardiomyocyte proliferation and repair of damaged heart tissue.

  2. Spreading of excitation in 3-D models of the anisotropic cardiac tissue. I. Validation of the eikonal model.

    PubMed

    Franzone, P C; Guerri, L

    1993-02-01

    In this work we investigate, by means of numerical simulations, the performance of two mathematical models describing the spread of excitation in a three dimensional block representing anisotropic cardiac tissue. The first model is characterized by a reaction-diffusion system in the transmembrane and extracellular potentials v and u. The second model is derived from the first by means of a perturbation technique. It is characterized by an eikonal equation, nonlinear and elliptic in the activation time psi(x). The level surfaces psi(x) = t represent the wave-front positions. The numerical procedures based on the two models were applied to test functions and to excitation processes elicited by local stimulations in a relatively small block. The results are in excellent agreement, and for the same problem the computation time required by the eikonal equation is a small fraction of that needed for the reaction-diffusion system. Thus we have strong evidence that the eikonal equation provides a reliable and numerically efficient model of the excitation process. Moreover, numerical simulations have been performed to validate an approximate model for the extracellular potential based on knowledge of the excitation sequence. The features of the extracellular potential distribution affected by the anisotropic conductivity of the medium were investigated.

  3. Isoform- and tissue-specific regulation of the Ca(2+)-sensitive transcription factor NFAT in cardiac myocytes and heart failure.

    PubMed

    Rinne, Andreas; Kapur, Nidhi; Molkentin, Jeffery D; Pogwizd, Steven M; Bers, Donald M; Banach, Kathrin; Blatter, Lothar A

    2010-06-01

    Nuclear factors of activated T cells (NFATs) are Ca(2+)-sensitive transcription factors that have been implicated in hypertrophy, heart failure (HF), and arrhythmias. Cytosolic NFAT is activated by dephosphorylation by the Ca(2+)-sensitive phosphatase calcineurin, resulting in translocation to the nucleus, which is opposed by kinase activity, rephosphorylation, and nuclear export. Four different NFAT isoforms are expressed in the heart. The activation and regulation of NFAT in adult cardiac myocytes, which may depend on the NFAT isoform and cell type, are not fully understood. This study compared basal localization, import, and export of NFATc1 and NFATc3 in adult atrial and ventricular myocytes to identify isoform- and tissue-specific regulatory mechanisms of NFAT activation under physiological conditions and in HF. NFAT-green fluorescent protein fusion proteins and NFAT immunocytochemistry were used to analyze NFAT regulation in adult cat and rabbit myocytes. NFATc1 displayed basal nuclear localization in atrial and ventricular myocytes, an effect that was attenuated by reducing intracellular Ca(2+) concentration and inhibiting calcineurin, and enhanced by the inhibition of nuclear export. In contrast, NFATc3 was localized to the cytoplasm but could be driven to the nucleus by angiotensin II and endothelin-1 stimulation in atrial, but not ventricular, cells. Inhibition of nuclear export (by leptomycin B) facilitated nuclear localization in both cell types. Ventricular myocytes from HF rabbits showed increased basal nuclear localization of endogenous NFATc3 and reduced responsiveness of NFAT translocation to phenylephrine stimulation. In control myocytes, Ca(2+) overload, leading to spontaneous Ca(2+) waves, induced substantial translocation of NFATc3 to the nucleus. We conclude that the activation of NFAT in adult cardiomyocytes is isoform and tissue specific and is tightly controlled by nuclear export. NFAT is activated in myocytes from HF animals and may be

  4. Functional, Anatomical, and Molecular Investigation of the Cardiac Conduction System and Arrhythmogenic Atrioventricular Ring Tissue in the Rat Heart

    PubMed Central

    Atkinson, Andrew J.; Logantha, Sunil Jit R. J.; Hao, Guoliang; Yanni, Joseph; Fedorenko, Olga; Sinha, Aditi; Gilbert, Stephen H.; Benson, Alan P.; Buckley, David L.; Anderson, Robert H.; Boyett, Mark R.; Dobrzynski, Halina

    2013-01-01

    Background The cardiac conduction system consists of the sinus node, nodal extensions, atrioventricular (AV) node, penetrating bundle, bundle branches, and Purkinje fibers. Node‐like AV ring tissue also exists at the AV junctions, and the right and left rings unite at the retroaortic node. The study aims were to (1) construct a 3‐dimensional anatomical model of the AV rings and retroaortic node, (2) map electrical activation in the right ring and study its action potential characteristics, and (3) examine gene expression in the right ring and retroaortic node. Methods and Results Three‐dimensional reconstruction (based on magnetic resonance imaging, histology, and immunohistochemistry) showed the extent and organization of the specialized tissues (eg, how the AV rings form the right and left nodal extensions into the AV node). Multiextracellular electrode array and microelectrode mapping of isolated right ring preparations revealed robust spontaneous activity with characteristic diastolic depolarization. Using laser microdissection gene expression measured at the mRNA level (using quantitative PCR) and protein level (using immunohistochemistry and Western blotting) showed that the right ring and retroaortic node, like the sinus node and AV node but, unlike ventricular muscle, had statistically significant higher expression of key transcription factors (including Tbx3, Msx2, and Id2) and ion channels (including HCN4, Cav3.1, Cav3.2, Kv1.5, SK1, Kir3.1, and Kir3.4) and lower expression of other key ion channels (Nav1.5 and Kir2.1). Conclusions The AV rings and retroaortic node possess gene expression profiles similar to that of the AV node. Ion channel expression and electrophysiological recordings show the AV rings could act as ectopic pacemakers and a source of atrial tachycardia. PMID:24356527

  5. Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke.

    PubMed

    Al-Attas, Omar S; Hussain, Tajamul; Ahmed, Mukhtar; Al-Daghri, Nasser; Mohammed, Arif A; De Rosas, Edgard; Gambhir, Dikshit; Sumague, Terrance S

    2015-07-01

    Incense smoke exposure has recently been linked to cardiovascular disease risk, heart rate variability, and endothelial dysfunction. To test the possible underlying mechanisms, oxidative stress, and inflammatory markers, gene expressions of cardiac hypertrophic and xenobiotic-metabolizing enzymes and ultrastructural changes were measured, respectively, using standard, ELISA-based, real-time PCR, and transmission electron microscope procedures in heart tissues of Wistar rats after chronically exposing to Arabian incense. Malondialdehyde, tumor necrosis alpha (TNF)-α, and IL-4 levels were significantly increased, while catalase and glutathione levels were significantly declined in incense smoke-exposed rats. Incense smoke exposure also resulted in a significant increase in atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain, CYP1A1 and CYP1A2 messenger RNAs (mRNAs). Rats exposed to incense smoke displayed marked ultrastructural changes in heart muscle with distinct cardiac hypertrophy, which correlated with the augmented hypertrophic gene expression as well as markers of cardiac damage including creatine kinase-myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Increased oxidative stress, inflammation, altered cardiac hypertrophic gene expression, tissue damage, and architectural changes in the heart may collectively contribute to increased cardiovascular disease risk in individuals exposed to incense smoke. Increased gene expressions of CYP1A1 and CYP1A2 may be instrumental in the incense smoke-induced oxidative stress and inflammation. Thus, incense smoke can be considered as a potential environmental pollutant and its long-term exposure may negatively impact human health.

  6. Surface chemical immobilization of bioactive peptides on synthetic polymers for cardiac tissue engineering.

    PubMed

    Rosellini, Elisabetta; Cristallini, Caterina; Guerra, Giulio D; Barbani, Niccoletta

    2015-01-01

    The aim of this work was the development of new synthetic polymeric systems, functionalized by surface chemical modification with bioactive peptides, for myocardial tissue engineering. Polycaprolactone and a poly(ester-ether-ester) block copolymer synthesized in our lab, polycaprolactone-poly(ethylene oxide)-polycaprolactone (PCL-PEO-PCL), were used as the substrates to be modified. Two pentapeptides, H-Gly-Arg-Gly-Asp-Ser-OH (GRGDS) from fibronectin and H-Tyr-Ile-Gly-Ser-Arg-OH (YIGSR) from laminin, were used for the functionalization. Polymeric membranes were obtained by casting from solutions and then functionalized by means of alkaline hydrolysis and subsequent coupling of the bioactive molecules through 1-(3-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride/N-hydroxysuccinimide chemistry. The hydrolysis conditions, in terms of hydrolysis time, temperature, and sodium hydroxide concentration, were optimized for the two materials. The occurrence of the coupling reaction was demonstrated by infrared spectroscopy, as the presence on the functionalized materials of the absorption peaks typical of the two peptides. The peptide surface density was determined by chromatographic analysis and the distribution was studied by infrared chemical imaging. The results showed a nearly homogeneous peptide distribution, with a density above the minimum value necessary to promote cell adhesion. Preliminary in vitro cell culture studies demonstrated that the introduction of the bioactive molecules had a positive effect on improving C2C12 myoblasts growth on the synthetic materials.

  7. Efficient simulation of three-dimensional anisotropic cardiac tissue using an adaptive mesh refinement method.

    PubMed

    Cherry, Elizabeth M; Greenside, Henry S; Henriquez, Craig S

    2003-09-01

    A recently developed space-time adaptive mesh refinement algorithm (AMRA) for simulating isotropic one- and two-dimensional excitable media is generalized to simulate three-dimensional anisotropic media. The accuracy and efficiency of the algorithm is investigated for anisotropic and inhomogeneous 2D and 3D domains using the Luo-Rudy 1 (LR1) and FitzHugh-Nagumo models. For a propagating wave in a 3D slab of tissue with LR1 membrane kinetics and rotational anisotropy comparable to that found in the human heart, factors of 50 and 30 are found, respectively, for the speedup and for the savings in memory compared to an algorithm using a uniform space-time mesh at the finest resolution of the AMRA method. For anisotropic 2D and 3D media, we find no reduction in accuracy compared to a uniform space-time mesh. These results suggest that the AMRA will be able to simulate the 3D electrical dynamics of canine ventricles quantitatively for 1 s using 32 1-GHz Alpha processors in approximately 9 h.

  8. Quantitative assessment of brain tissue oxygenation in porcine models of cardiac arrest and cardiopulmonary resuscitation using hyperspectral near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Lotfabadi, Shahin S.; Toronov, Vladislav; Ramadeen, Andrew; Hu, Xudong; Kim, Siwook; Dorian, Paul; Hare, Gregory M. T.

    2014-03-01

    Near-infrared spectroscopy (NIRS) is a non-invasive tool to measure real-time tissue oxygenation in the brain. In an invasive animal experiment we were able to directly compare non-invasive NIRS measurements on the skull with invasive measurements directly on the brain dura matter. We used a broad-band, continuous-wave hyper-spectral approach to measure tissue oxygenation in the brain of pigs under the conditions of cardiac arrest, cardiopulmonary resuscitation (CPR), and defibrillation. An additional purpose of this research was to find a correlation between mortality due to cardiac arrest and inadequacy of the tissue perfusion during attempts at resuscitation. Using this technique we measured the changes in concentrations of oxy-hemoglobin [HbO2] and deoxy-hemoglobin [HHb] to quantify the tissue oxygenation in the brain. We also extracted cytochrome c oxidase changes Δ[Cyt-Ox] under the same conditions to determine increase or decrease in cerebral oxygen delivery. In this paper we proved that applying CPR, [HbO2] concentration and tissue oxygenation in the brain increase while [HHb] concentration decreases which was not possible using other measurement techniques. We also discovered a similar trend in changes of both [Cyt-Ox] concentration and tissue oxygen saturation (StO2). Both invasive and non-invasive measurements showed similar results.

  9. The comparison of methods to identify the presence of fibrocytes in formalin-fixed, paraffin-embedded archival cardiac tissue with coronary heart disease.

    PubMed

    Lei, Pu-Ping; Shuai, Qun; Wang, Shang-Wen; Tao, Si-Ming; Qu, Yong-Qiang; Wang, Dian-Hua

    2014-12-01

    The purpose of this study was to find the optimal technical approach to identify the presence of fibrocytes in formalin-fixed, paraffin-embedded archival cardiac tissue with CHD (coronary heart disease). Using the coexpression markers CD45 and αSMA, the presence of fibrocytes was examined by three different methods, including double immunohistochemistry staining, combination labeling of immunohistochemistry and immunofluorescence and double immunofluorescence labeling. Double immunohistochemistry staining was very difficult to identify the CD45(+)/αSMA(+) fibrocytes. Although combination staining of immunohistochemistry and immunofluorescence has made it possible to evaluate the co-localization of CD45 and αSMA in the fibrocytes, this method was prone to produce many false positive cells. In contrast, CD45(+)/αSMA(+) fibrocytes could be clearly recognized by double immunofluorescence labeling. In conclusion, double immunofluorescence labeling is the optimal technical approach to identify the presence of fibrocytes in routinely processed cardiac tissue with CHD.

  10. Pulsed Intra-Arterial Drug Injection during Diastolic Phase of Cardiac Function Increases Drug Efficacy by Enhancing Pharmacological Exposure of Targeted Tissues.

    PubMed

    Rismanchi, M

    2016-06-01

    Diastolic phase of cardiac function is associated with lower arterial flow and hence higher concentration of intra arterially injected drug is achieved at the site of injection. It is herein postulated that drugs show higher efficacy when injected during the diastolic phase of cardiac function. It is also postulated that this benefit cannot be achieved when the drug is injected with higher rates thus producing the same high concentration at the site of injection. Pulsed intra arterial injection also benefits from the delayed therapeutic effect of the decaying drug before the next shot of injection resaturates the targeted tissue. Altogether, it is estimated that diastolic time-locked pulsed intra arterial injection will increase the drug efficacy up to 1.9 times the efficacy of injected drug with conventional methods. This is significant for drugs with limited dose of administration due to their disastrous side effects like tissue plasminogen activator or chemotherapeutic drugs. PMID:27672631

  11. Pulsed Intra-Arterial Drug Injection during Diastolic Phase of Cardiac Function Increases Drug Efficacy by Enhancing Pharmacological Exposure of Targeted Tissues

    PubMed Central

    Rismanchi, M.

    2016-01-01

    Diastolic phase of cardiac function is associated with lower arterial flow and hence higher concentration of intra arterially injected drug is achieved at the site of injection. It is herein postulated that drugs show higher efficacy when injected during the diastolic phase of cardiac function. It is also postulated that this benefit cannot be achieved when the drug is injected with higher rates thus producing the same high concentration at the site of injection. Pulsed intra arterial injection also benefits from the delayed therapeutic effect of the decaying drug before the next shot of injection resaturates the targeted tissue. Altogether, it is estimated that diastolic time-locked pulsed intra arterial injection will increase the drug efficacy up to 1.9 times the efficacy of injected drug with conventional methods. This is significant for drugs with limited dose of administration due to their disastrous side effects like tissue plasminogen activator or chemotherapeutic drugs. PMID:27672631

  12. Attenuation of cold stress-induced exacerbation of cardiac and adipose tissue pathology and metabolic disorders in a rat model of metabolic syndrome by the glucocorticoid receptor antagonist RU486

    PubMed Central

    Nagasawa, K; Matsuura, N; Takeshita, Y; Ito, S; Sano, Y; Yamada, Y; Uchinaka, A; Murohara, T; Nagata, K

    2016-01-01

    Objectives: Chronic stress affects the central nervous system as well as endocrine, metabolic and immune systems. However, the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We have now investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology as well as on metabolic parameters in this model. Methods: DS/obese rats were exposed to cold stress (immersion in ice-cold water to a depth of 1–2 cm for 2 h per day) with or without subcutaneous injection of the GR antagonist RU486 (2 mg kg−1day−1) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr+/Lepr+) littermates served as a control. Results: Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction in DS/obese rats in a manner sensitive to RU486 treatment. Cold stress with or without RU486 did not affect body weight or fat mass. In contrast, cold stress further increased cardiac oxidative stress as well as macrophage infiltration and proinflammatory gene expression in LV and visceral fat tissue, with all of these effects being attenuated by RU486. Cold stress also further increased GR and 11β-hydroxysteroid dehydrogenase type 1 mRNA and protein abundance in LV and visceral adipose tissue, and these effects were again inhibited by RU486. In addition, RU486 ameliorated the stress-induced aggravation of dyslipidemia, glucose intolerance and insulin resistance in DS/obese rats. Conclusions: Our results implicate GR signaling in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as of abnormal glucose and lipid metabolism in a rat model of MetS. PMID:27110688

  13. 2-Oxoglutarate dehydrogenase is a more significant source of O2(·-)/H2O2 than pyruvate dehydrogenase in cardiac and liver tissue.

    PubMed

    Mailloux, Ryan J; Gardiner, Danielle; O'Brien, Marisa

    2016-08-01

    Pyruvate dehydrogenase (Pdh) and 2-oxoglutarate dehydrogenase (Ogdh) are vital for Krebs cycle metabolism and sources of reactive oxygen species (ROS). O2(·-)/H2O2 formation by Pdh and Ogdh from porcine heart were compared when operating under forward or reverse electron transfer conditions. Comparisons were also conducted with liver and cardiac mitochondria. During reverse electron transfer (RET) from NADH, purified Ogdh generated ~3-3.5× more O2(·-)/H2O2 in comparison to Pdh when metabolizing 0.5-10µM NADH. Under forward electron transfer (FET) conditions Ogdh generated ~2-4× more O2(·-)/H2O2 than Pdh. In both liver and cardiac mitochondria, Ogdh displayed significantly higher rates of ROS formation when compared to Pdh. Ogdh was also a significant source of ROS in liver mitochondria metabolizing 50µM and 500µM pyruvate or succinate. Finally, we also observed that DTT directly stimulated O2(·-)/H2O2 formation by purified Pdh and Ogdh and in cardiac or liver mitochondria in the absence of substrates and cofactors. Taken together, Ogdh is a more potent source of ROS than Pdh in liver and cardiac tissue. Ogdh is also an important ROS generator regardless of whether pyruvate or succinate serve as the sole source of carbon. Our observations provide insight into the ROS generating capacity of either complex in cardiac and liver tissue. The evidence presented herein also indicates DTT, a reductant that is routinely added to biological samples, should be avoided when assessing mitochondrial O2(·-)/H2O2 production. PMID:27394173

  14. Syngeneic Cardiac and Bone Marrow Stromal Cells Display Tissue-Specific microRNA Signatures and microRNA Subsets Restricted to Diverse Differentiation Processes

    PubMed Central

    Meraviglia, Viviana; Azzimato, Valerio; Piacentini, Luca; Chiesa, Mattia; Kesharwani, Rupesh K.; Frati, Caterina; Capogrossi, Maurizio C.; Gaetano, Carlo; Pompilio, Giulio

    2014-01-01

    MicroRNAs are key modulators at molecular level in different biological processes, including determination of cell fate and differentiation. Herein, microRNA expression profiling experiments were performed on syngeneic cardiac (CStC) and bone marrow (BMStC) mesenchymal stromal cells cultured in standard growth medium and then in vitro exposed to adipogenic, osteogenic, cardiomyogenic and endothelial differentiation media. Analysis identified a tissue-specific microRNA signature composed of 16 microRNAs that univocally discriminated cell type of origin and that were completely unaffected by in vitro differentiation media: 4 microRNAs were over-expressed in cardiac stromal cells, and 12 were overexpressed or present only in bone marrow stromal cells. Further, results revealed microRNA subsets specifically modulated by each differentiation medium, irrespective of the cell type of origin, and a subset of 7 microRNAs that were down-regulated by all media with respect to growth medium. Finally, we identified 16 microRNAs that were differentially modulated by the media when comparing the two tissues of origin. The existence of a tissue-specific microRNA signature surviving to any differentiation stimuli, strongly support the role if microRNAs determining cell identity related to tissue origin. Moreover, we identified microRNA subsets modulated by different culture conditions in a tissue-specific manner, pointing out their importance during differentiation processes. PMID:25232725

  15. Mechanical and electrophysiological studies on the positive inotropic effect of 2-phenyl-4-oxo-hydroquinoline in rat cardiac tissues.

    PubMed Central

    Su, M. J.; Chang, G. J.; Kuo, S. C.

    1993-01-01

    1. The pharmacological and electrophysiological effect of 2-phenyl-4-oxo-hydroquinoline (YT-1), a new synthetic agent, were determined in rat isolated cardiac tissues and ventricular myocytes. 2. YT-1 was found to have a positive inotropic effect in both atria and ventricular muscles but did not cause significant increases in the spontaneously beating rate of right atria. 3. The positive inotropic effect of YT-1 was antagonized neither by beta-nor by alpha-adrenoceptor antagonists but was partially antagonized by a Ca2+ channel blocker (verapamil) and a K+ channel blocker (4-AP). 4. The action potential duration and amplitude of ventricular cells were progressively increased as the concentration of YT-1 was increased from 3 to 30 microM. 5. A voltage clamp study revealed that the prolongation of action potential duration by YT-1 was associated with a prominent inhibition of 4-AP-sensitive transient outward current (I(to)). At potentials negative to the reversal potential of K1-channels, the inward current through these channels was partially reduced by YT-1. At potentials positive to the reversal potential, the outward current through these channels was affected very little. 6. Although YT-1 blocked the amplitude of I(to), the voltage-dependence of the steady-state inactivation of I(to), was unaffected. 7. Apart from the inhibition of K+ currents, YT-1 also inhibited the sodium inward current. 8. The evidence suggests that YT-1 increases the slow inward Ca2+ current (ICa) significantly. 9. It is concluded that the positive inotropic effect of YT-1 is due predominantly to the increase of ICa and inhibition of I(to).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8106106

  16. Cardiac ion channels

    PubMed Central

    Priest, Birgit T; McDermott, Jeff S

    2015-01-01

    Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

  17. Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction.

    PubMed

    Lichtenauer, Michael; Mildner, Michael; Baumgartner, Andrea; Hasun, Matthias; Werba, Gregor; Beer, Lucian; Altmann, Patrick; Roth, Georg; Gyöngyösi, Mariann; Podesser, Bruno Karl; Ankersmit, Hendrik Jan

    2011-06-01

    Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was performed to analyse the cellular infiltrate in the ischaemic myocardium. Cardiac function was quantified by echocardiography. Planimetry of the infarcted hearts showed a significant reduction of infarction size and an improvement of post AMI remodelling in rats treated with suspensions of apoptotic PBMC (injected either intravenously or intramoycardially). Moreover, these hearts evidenced enhanced homing of macrophages and cells staining positive for c-kit, FLK-1, IGF-I and FGF-2 as compared to controls. A major finding in this study further was that the ratio of elastic and collagenous fibres within the scar tissue was altered in a favourable fashion in rats injected with apoptotic cells. Intravenous or intramyocardial injection of apoptotic cell suspensions results in attenuation of myocardial remodelling after experimental AMI, preserves left ventricular function, increases homing of regenerative cells and alters the composition of cardiac scar tissue. The higher expression of elastic fibres provides passive energy to the cardiac scar tissue and results in prevention of ventricular remodelling.

  18. Insulin-like Growth Factor-I and Slow, Bi-directional Perfusion Enhance the Formation of Tissue-Engineered Cardiac Grafts

    PubMed Central

    Cheng, Mingyu; Moretti, Matteo; Engelmayr, George C.

    2009-01-01

    Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p < 0.01), cellular viability (p < 0.01), contractile amplitude (p < 0.01), and excitation threshold (p < 0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p < 0.01), connexin-43 (p < 0.05), and total protein (p < 0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p < 0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility. PMID:18759675

  19. Micromorphological changes in cardiac tissue of drug-related deaths with emphasis on chronic illicit opioid abuse

    PubMed Central

    Seltenhammer, Monika H; Marchart, Katharina; Paula, Pia; Kordina, Nicole; Klupp, Nikolaus; Schneider, Barbara; Fitzl, Christine; Risser, Daniele U

    2013-01-01

    Aims The main intention of this retrospective study was to investigate whether chronic illicit drug abuse, especially the intravenous use of opioids (heroin), could potentially trigger the development of myocardial fibrosis in drug addicts. Design A retrospective case–control study was performed using myocardial tissue samples from both drug-related deaths (DRD) with verifiable opioid abuse and non-drug-related deaths in the same age group. Setting Department of Forensic Medicine, Medical University of Vienna, Austria (1993–94). Participants Myocardial specimens were retrieved from 76 deceased intravenous opioid users and compared to those of 23 deceased non-drug users. Measurements Drug quantification was carried out using the enzyme-multiplied immunoassay technique (EMIT), followed by [gas chromatography–mass spectrometry (GC–MS), MAT 112®], and analysed using the Integrator 3390A by Hewlett Packard® and LABCOM.1 computer (MSS-G.G.). The amount of fibrous connective tissue (FCT) in the myocardium was determined by using the morphometric software LUCIA Net version 1.16.2©, Laboratory Imaging, with NIS Elements 3.0®. Findings Drug analysis revealed that 67.11% were polydrug users and the same proportion was classified as heroin addicts (6-monoacetylmorphine, 6-MAM)—32.89% were users of pure heroin. In 76.32% of DRD cases, codeine was detected. Only 2.63% consumed cocaine. The mean morphine concentrations were 389.03 ng/g in the cerebellum and 275.52 ng/g in the medulla oblongata, respectively. Morphometric analysis exhibited a strong correlation between DRD and myocardial fibrosis. The mean proportion of FCT content in the drug group was 7.6 ± 2.9% (females: 6.30 ± 2.19%; males: 7.91 ± 3.01%) in contrast to 5.2 ± 1.7% (females: 4.45 ± 1.23%; males: 5.50 ± 1.78%) in the control group, indicating a significant difference (P = 0.0012), and a significant difference in the amount of FCT between females and males (P = 0.0383). There was no significant

  20. Postmortem mRNA Expression Patterns in Left Ventricular Myocardial Tissues and Their Implications for Forensic Diagnosis of Sudden Cardiac Death

    PubMed Central

    Son, Gi Hoon; Park, Seong Hwan; Kim, Yunmi; Kim, Ji Yeon; Kim, Jin Wook; Chung, Sooyoung; Kim, Yu-Hoon; Kim, Hyun; Hwang, Juck-Joon; Seo, Joong-Seok

    2014-01-01

    Sudden cardiac death (SCD), which is primarily caused by lethal heart disorders resulting in structural and arrhythmogenic abnormalities, is one of the prevalent modes of death in most developed countries. Myocardial ischemia, mainly due to coronary artery disease, is the most common type of heart disease leading to SCD. However, postmortem diagnosis of SCD is frequently complicated by obscure histological evidence. Here, we show that certain mRNA species, namely those encoding hemoglobin A1/2 and B (Hba1/2 and Hbb, respectively) as well as pyruvate dehydrogenase kinase 4 (Pdk4), exhibit distinct postmortem expression patterns in the left ventricular free wall of SCD subjects when compared with their expression patterns in the corresponding tissues from control subjects with non-cardiac causes of death. Hba1/2 and Hbb mRNA expression levels were higher in ischemic SCD cases with acute myocardial infarction or ischemic heart disease without recent infarction, and even in cardiac death subjects without apparent pathological signs of heart injuries, than control subjects. By contrast, Pdk4 mRNA was expressed at lower levels in SCD subjects. In conclusion, we found that altered myocardial Hba1/2, Hbb, and Pdk4 mRNA expression patterns can be employed as molecular signatures of fatal cardiac dysfunction to forensically implicate SCD as the primary cause of death. PMID:24642708

  1. Engineered 3D bioimplants using elastomeric scaffold, self-assembling peptide hydrogel, and adipose tissue-derived progenitor cells for cardiac regeneration

    PubMed Central

    Soler-Botija, Carolina; Bagó, Juli R; Llucià-Valldeperas, Aida; Vallés-Lluch, Ana; Castells-Sala, Cristina; Martínez-Ramos, Cristina; Fernández-Muiños, Teresa; Chachques, Juan Carlos; Pradas, Manuel Monleón; Semino, Carlos E; Bayes-Genis, Antoni

    2014-01-01

    Contractile restoration of myocardial scars remains a challenge with important clinical implications. Here, a combination of porous elastomeric membrane, peptide hydrogel, and subcutaneous adipose tissue-derived progenitor cells (subATDPCs) was designed and evaluated as a bioimplant for cardiac regeneration in a mouse model of myocardial infarction. SubATDPCs were doubly transduced with lentiviral vectors to express bioluminescent-fluorescent reporters driven by constitutively active, cardiac tissue-specific promoters. Cells were seeded into an engineered bioimplant consisting of a scaffold (polycaprolactone methacryloyloxyethyl ester) filled with a peptide hydrogel (PuraMatrix™), and transplanted to cover injured myocardium. Bioluminescence and fluorescence quantifications showed de novo and progressive increases in promoter expression in bioactive implant-treated animals. The bioactive implant was well adapted to the heart, and fully functional vessels traversed the myocardium-bioactive implant interface. Treatment translated into a detectable positive effect on cardiac function, as revealed by echocardiography. Thus, this novel implant is a promising construct for supporting myocardial regeneration. PMID:24936221

  2. Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells

    PubMed Central

    Matsuo, Takehiko; Masumoto, Hidetoshi; Tajima, Shuhei; Ikuno, Takeshi; Katayama, Shiori; Minakata, Kenji; Ikeda, Tadashi; Yamamizu, Kohei; Tabata, Yasuhiko; Sakata, Ryuzo; Yamashita, Jun K.

    2015-01-01

    Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1 mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2 × 106 of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8 mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart. PMID:26585309

  3. IFATS collection: Human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function.

    PubMed

    Cai, Liying; Johnstone, Brian H; Cook, Todd G; Tan, Jian; Fishbein, Michael C; Chen, Peng-Sheng; March, Keith L

    2009-01-01

    The administration of therapeutic cell types, such as stem and progenitor cells, has gained much interest for the limitation or repair of tissue damage caused by a variety of insults. However, it is still uncertain whether the morphological and functional benefits are mediated predominantly via cell differentiation or paracrine mechanisms. Here, we assessed the extent and mechanisms of adipose-derived stromal/stem cells (ASC)-dependent tissue repair in the context of acute myocardial infarction. Human ASCs in saline or saline alone was injected into the peri-infarct region in athymic rats following left anterior descending (LAD) coronary artery ligation. Cardiac function and structure were evaluated by serial echocardiography and histology. ASC-treated rats consistently exhibited better cardiac function, by all measures, than control rats 1 month following LAD occlusion. Left ventricular (LV) ejection fraction and fractional shortening were improved in the ASC group, whereas LV remodeling and dilation were limited in the ASC group compared with the saline control group. Anterior wall thinning was also attenuated by ASC treatment, and post-mortem histological analysis demonstrated reduced fibrosis in ASC-treated hearts, as well as increased peri-infarct density of both arterioles and nerve sprouts. Human ASCs were persistent at 1 month in the peri-infarct region, but they were not observed to exhibit significant cardiomyocyte differentiation. Human ASCs preserve heart function and augment local angiogenesis and cardiac nerve sprouting following myocardial infarction predominantly by the provision of beneficial trophic factors. PMID:18772313

  4. Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells.

    PubMed

    Matsuo, Takehiko; Masumoto, Hidetoshi; Tajima, Shuhei; Ikuno, Takeshi; Katayama, Shiori; Minakata, Kenji; Ikeda, Tadashi; Yamamizu, Kohei; Tabata, Yasuhiko; Sakata, Ryuzo; Yamashita, Jun K

    2015-11-20

    Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1 mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2 × 10(6) of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8 mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart.

  5. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages

    PubMed Central

    Masumoto, Hidetoshi; Nakane, Takeichiro; Tinney, Joseph P.; Yuan, Fangping; Ye, Fei; Kowalski, William J.; Minakata, Kenji; Sakata, Ryuzo; Yamashita, Jun K.; Keller, Bradley B.

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation. PMID:27435115

  6. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.

    PubMed

    Masumoto, Hidetoshi; Nakane, Takeichiro; Tinney, Joseph P; Yuan, Fangping; Ye, Fei; Kowalski, William J; Minakata, Kenji; Sakata, Ryuzo; Yamashita, Jun K; Keller, Bradley B

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation. PMID:27435115

  7. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages

    PubMed Central

    Masumoto, Hidetoshi; Nakane, Takeichiro; Tinney, Joseph P.; Yuan, Fangping; Ye, Fei; Kowalski, William J.; Minakata, Kenji; Sakata, Ryuzo; Yamashita, Jun K.; Keller, Bradley B.

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation. PMID:27435115

  8. High-resolution cellular MRI: gadolinium and iron oxide nanoparticles for in-depth dual-cell imaging of engineered tissue constructs.

    PubMed

    Di Corato, Riccardo; Gazeau, Florence; Le Visage, Catherine; Fayol, Delphine; Levitz, Pierre; Lux, François; Letourneur, Didier; Luciani, Nathalie; Tillement, Olivier; Wilhelm, Claire

    2013-09-24

    Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components.

  9. High-resolution cellular MRI: gadolinium and iron oxide nanoparticles for in-depth dual-cell imaging of engineered tissue constructs.

    PubMed

    Di Corato, Riccardo; Gazeau, Florence; Le Visage, Catherine; Fayol, Delphine; Levitz, Pierre; Lux, François; Letourneur, Didier; Luciani, Nathalie; Tillement, Olivier; Wilhelm, Claire

    2013-09-24

    Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components. PMID:23924160

  10. Effect of Broccoli (Brassica oleracea) Tissue, Incorporated at Different Depths in a Soil Column, on Meloidogyne incognita

    PubMed Central

    Roubtsova, Tatiana; López-Péŕez, Jose-Antonio; Edwards, Scott; Ploeg, Antoon

    2007-01-01

    Brassicas have been used frequently for biofumigation, a pest-management strategy based on the release of biocidal volatiles during decomposition of soil-incorporated tissue. However, the role of such volatiles in control of plant-parasitic nematodes is unclear. The goal of this study was to determine the direct localized and indirect volatile effects of amending soil with broccoli tissue on root-knot nematode populations. Meloidogyne incognita-infested soil in 50-cm-long tubes was amended with broccoli tissue, which was mixed throughout the tube or concentrated in a 10-cm layer. After three weeks at 28°C, M. incognita populations in the amended tubes were 57 to 80% smaller than in non-amended tubes. Mixing broccoli throughout the tubes reduced M. incognita more than concentrating broccoli in a 10-cm layer. Amending a 10-cm layer reduced M. incognita in the non-amended layers of those tubes by 31 to 71%, probably due to a nematicidal effect of released volatiles. However, the localized direct effect was much stronger than the indirect effect of volatiles. The strong direct effect may have resulted from the release of non-volatile nematicidal compounds. Therefore, when using biofumigation with broccoli to control M. incognita, the tissue should be thoroughly and evenly mixed through the soil layer(s) where the target nematodes occur. Effects on saprophytic nematodes were the reverse. Amended soil layers had much greater numbers of saprophytic nematodes than non-amended layers, and there was no indirect effect of amendments on saprophytic nematodes in adjacent non-amended layers. PMID:19259479

  11. Periaortic Fat Tissue: A Predictor of Cardiac Valvular Calcification, Malnutrition, Inflammation, and Atherosclerosis Components in Hemodialysis Patients.

    PubMed

    Genctoy, Gultekin; Eldem, Olcay; Ergun, Tarkan; Arikan, Serap

    2015-09-01

    Cardiac valvular calcification (CVC) in end-stage renal disease is shown to be a component of malnutrition, inflammation, atherosclerosis, calcification (MIAC) syndrome. Thoracic periaortic fat tissue (T-PAFT) is shown to be increased in patients with end-stage renal disease (ESRD), and has positive correlation with MIAC. Negative correlation between CVC and vitamin D is shown in hemodialysis (HD) patients. In this study, we investigated a relationship between body composition, T-PAFT, metabolic and inflammatory parameters, and CVC in HD patients. Seventy-six HD patients (49M) were included. CVC is defined as bright echoes of >1 mm on one or more cusps on echocardiography. Results were expressed as the number of calcified valves (0,1,2). Calcium, phosphorus, parathyroid hormone (PTH), C-reactive protein (CRP), albumin and 25-hydroxy vitamin D levels were studied from predialysis blood samples. T-PAFT was calculated using a method with manual definition of borders on images from multislice computed tomography. Basal metabolic rate, muscle mass, total and truncal fat mass were measured by bioimpedance analysis. There were 65.8% of patients who had CVC. Patients with CVC were older (63.5 ± 14.6 ± 17, P = 0.02). T-PAFT (1599 ± 596, 739.7 ± 179 mm(2) , P = 0.001) and CRP (15.8 ± 11; 11.1 ± 13.2 mg/dL; P = 0.04) were higher in the group with CVC. T-PAFT had positive correlations with CRP, MIAC, body mass index (BMI) and number of calcified valves, negative correlation with left ventricular ejection fraction, and no correlation with albumin, calcium, phosphorus, and PTH. The logistic regression analysis revealed that T-PAFT was a significant predictor of CVC. In this study, T-PAFT showed a positive correlation with inflammation, CVC, and MIAC score in HD patients. T-PAFT was a significant predictor of CVC.

  12. Minocycline attenuates brain tissue levels of TNF-α produced by neurons after prolonged hypothermic cardiac arrest in rats

    PubMed Central

    Drabek, Tomas; Janata, Andreas; Wilson, Caleb D.; Stezoski, Jason; Janesko-Feldman, Keri; Tisherman, Samuel A.; Foley, Lesley M.; Verrier, Jonathan; Kochanek, Patrick M.

    2014-01-01

    Neuro-cognitive disabilities are a well-recognized complication of hypothermic circulatory arrest. We and others have reported that prolonged cardiac arrest (CA) produces neuronal death and microglial proliferation and activation that are only partially mitigated by hypothermia. Microglia, and possibly other cells, are suggested to elaborate tumor necrosis factor alpha (TNF-α) which can trigger neuronal death cascades and exacerbate edema after CNS insults. Minocycline is neuroprotective in some brain ischemia models in part by blunting the microglial response. We tested the hypothesis that minocycline would attenuate neuroinflammation as reflected by brain tissue levels of TNF-α after hypothermic CA in rats. Rats were subjected to rapid exsanguination, followed by a 6 min normothermic CA. Hypothermia (30 °C) was then induced by an aortic saline flush. After a total of 20 min CA, resuscitation was achieved via cardiopulmonary bypass (CPB). After 5 min reperfusion, minocycline (90 mg/kg; n=6) or vehicle (PBS; n=6) were given. Hypothermia (34 °C) was maintained for 6 h. Rats were sacrificed at 6 or 24 h. TNF-α was quantified (ELISA) in four brain regions (cerebellum, CEREB; cortex, CTX; hippocampus, HIP; striatum, STRI). Naïve rats (n=6) and rats subjected to the same anesthesia and CPB but no CA served as controls (n=6). Immunocytochemistry was used to localize TNF-α. Naïve rats and CPB controls had no detectable TNF-α in any brain region. CA markedly increased brain TNF-α. Regional differences were seen, with the highest TNF-α levels in striatum in CA groups (10-fold higher, P<0.05 vs. all other brain regions). TNF-α was undetectable at 24 h. Minocycline attenuated TNF-α levels in CTX, HIP and STRI (P<0.05). TNF-α showed unique co-localization with neurons. In conclusion, we report region-dependent early increases in brain TNF-α levels after prolonged hypothermic CA, with maximal increases in striatum. Surprisingly, TNF-α co-localized in neurons and

  13. Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool for monitoring myocardial tissue renewal?

    PubMed

    Giannoni, Alberto; Giovannini, Stefania; Clerico, Aldo

    2009-01-01

    The increased analytical sensitivity of the new generation of methods for cardiac troponin I (cTnI) and T (cTnT) has demonstrated that measurable troponin is present in the blood of healthy adult subjects. These data are not in accordance with the prevailing opinion that any reliably detected increase in cardiac troponins should be considered abnormal and potentially caused by cardiac necrosis. The goal of the present review is to discuss the hypothesis that cardiac troponins can be released from cardiomyocytes, even in healthy adult subjects as a result of a process related to "physiological renewal" of the human myocardium and possibly enhanced by physical exercise or aging. The latest generation of high-sensitive cTnI and cTnT immunoassays are characterized by detection limits (DLs) as low as a few picograms. This clearly represents a greater increase in discrimination than that obtained by the most sophisticated cardiac imaging techniques that are commercially available at present. However, the critical question is whether high-sensitive troponin assays are clinically useful and in particular, whether some specific laboratory biomarkers (such as cTnI and cTnT) yield better diagnostic (or prognostic) accuracy and cost-effectiveness when compared with echocardiography in patients with cardiovascular disease. Only specific and well-designed clinical trials will answer this important question.

  14. Effect of Irradiation on Tissue Penetration Depth of Doxorubicin after Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) in a Novel Ex-Vivo Model

    PubMed Central

    Khosrawipour, Veria; Giger-Pabst, Urs; Khosrawipour, Tanja; Pour, Yousef Hedayat; Diaz-Carballo, David; Förster, Eckart; Böse-Ribeiro, Hugo; Adamietz, Irenäus Anton; Zieren, Jürgen; Fakhrian, Khashayar

    2016-01-01

    Background: This study was performed to assess the impact of irradiation on the tissue penetration depth of doxorubicin delivered during Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC). Methods: Fresh post mortem swine peritoneum was cut into 10 proportional sections. Except for 2 control samples, all received irradiation with 1, 2, 7 and 14 Gy, respectively. Four samples received PIPAC 15 minutes after irradiation and 4 other after 24 hours. Doxorubicin was aerosolized in an ex-vivo PIPAC model at 12 mmHg/36°C. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. Results: Doxorubicin penetration after PIPAC (15 minutes after irradiation) was 476 ± 74 µm for the control sample, 450 ± 45µm after 1 Gy (p > 0.05), 438 ± 29 µm after 2 Gy (p > 0.05), 396 ± 32 µm after 7 Gy (p = 0.005) and 284 ± 57 after 14 Gy irradiation (p < 0.001). The doxorubicin penetration after PIPAC (24 hours after irradiation) was 428 ± 77 µm for the control sample, 393 ± 41 µm after 1 Gy (p > 0.05), 379 ± 56 µm after 2 Gy (p > 0.05), 352 ± 53 µm after 7 Gy (p = 0.008) and 345 ± 53 after 14 Gy irradiation (p = 0.001). Conclusions: Higher (fractional) radiation dose might reduce the tissue penetration depth of doxorubicin in our ex-vivo model. However, irradiation with lower (fractional) radiation dose does not affect the tissue penetration negatively. Further studies are warranted to investigate if irradiation can be used safely as chemopotenting agent for patients with peritoneal metastases treated with PIPAC. PMID:27313780

  15. Early Prediction of Cancer Progression by Depth-Resolved Nanoscale Mapping of Nuclear Architecture from Unstained Tissue Specimens.

    PubMed

    Uttam, Shikhar; Pham, Hoa V; LaFace, Justin; Leibowitz, Brian; Yu, Jian; Brand, Randall E; Hartman, Douglas J; Liu, Yang

    2015-11-15

    Early cancer detection currently relies on screening the entire at-risk population, as with colonoscopy and mammography. Therefore, frequent, invasive surveillance of patients at risk for developing cancer carries financial, physical, and emotional burdens because clinicians lack tools to accurately predict which patients will actually progress into malignancy. Here, we present a new method to predict cancer progression risk via nanoscale nuclear architecture mapping (nanoNAM) of unstained tissue sections based on the intrinsic density alteration of nuclear structure rather than the amount of stain uptake. We demonstrate that nanoNAM detects a gradual increase in the density alteration of nuclear architecture during malignant transformation in animal models of colon carcinogenesis and in human patients with ulcerative colitis, even in tissue that appears histologically normal according to pathologists. We evaluated the ability of nanoNAM to predict "future" cancer progression in patients with ulcerative colitis who did and did not develop colon cancer up to 13 years after their initial colonoscopy. NanoNAM of the initial biopsies correctly classified 12 of 15 patients who eventually developed colon cancer and 15 of 18 who did not, with an overall accuracy of 85%. Taken together, our findings demonstrate great potential for nanoNAM in predicting cancer progression risk and suggest that further validation in a multicenter study with larger cohorts may eventually advance this method to become a routine clinical test. PMID:26383164

  16. Early Prediction of Cancer Progression by Depth-Resolved Nanoscale Mapping of Nuclear Architecture from Unstained Tissue Specimens.

    PubMed

    Uttam, Shikhar; Pham, Hoa V; LaFace, Justin; Leibowitz, Brian; Yu, Jian; Brand, Randall E; Hartman, Douglas J; Liu, Yang

    2015-11-15

    Early cancer detection currently relies on screening the entire at-risk population, as with colonoscopy and mammography. Therefore, frequent, invasive surveillance of patients at risk for developing cancer carries financial, physical, and emotional burdens because clinicians lack tools to accurately predict which patients will actually progress into malignancy. Here, we present a new method to predict cancer progression risk via nanoscale nuclear architecture mapping (nanoNAM) of unstained tissue sections based on the intrinsic density alteration of nuclear structure rather than the amount of stain uptake. We demonstrate that nanoNAM detects a gradual increase in the density alteration of nuclear architecture during malignant transformation in animal models of colon carcinogenesis and in human patients with ulcerative colitis, even in tissue that appears histologically normal according to pathologists. We evaluated the ability of nanoNAM to predict "future" cancer progression in patients with ulcerative colitis who did and did not develop colon cancer up to 13 years after their initial colonoscopy. NanoNAM of the initial biopsies correctly classified 12 of 15 patients who eventually developed colon cancer and 15 of 18 who did not, with an overall accuracy of 85%. Taken together, our findings demonstrate great potential for nanoNAM in predicting cancer progression risk and suggest that further validation in a multicenter study with larger cohorts may eventually advance this method to become a routine clinical test.

  17. Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage.

    PubMed

    Medeiros, Gabriela A; Silvério, Jaline C; Marino, Ana Paula M P; Roffê, Ester; Vieira, Valeska; Kroll-Palhares, Karina; Carvalho, Cristiano E; Silva, Andréa Alice; Teixeira, Mauro M; Lannes-Vieira, Joseli

    2009-02-01

    The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.

  18. Synthesis and tissue biodistribution of [{omega}-{sup 11}C]palmitic acid. A novel PET imagining agent for cardiac fatty acid metabolism

    SciTech Connect

    Buckman, B.O.; VanBrocklin, H.F.; Katzenellenbogen, J.A.; Dence, C.S.; Bergmann, S.R.; Welch, M.J.

    1994-12-31

    In order to diagnose patients with medium-chain acyl-CoA dehydrogenase deficiency with a noninvasive diagnostic technique such as positron emission tomography, they have developed a synthesis of [{omega}-{sup 11}C]palmitic acid. The radiochemical synthesis was achieved by coupling an alkylfuran Grignard reagent (7) with [{sup 11}C]methyl iodide, followed by rapid oxidative cleavage of the furan ring to the carboxylate using ruthenium tetraoxide. Tissue biodistribution studies in rags comparing [{omega}-{sup 11}C]palmitic acid and [1-{sup 11}C]palmitic acid show that the %ID/g and %ID/organ in the heart tissue after administration of [{omega}-{sup 11}C]palmitic acid is approximately 50% greater than after administration of [1-{sup 11}C]palmitic acid, due to the diminished metabolism of the [{omega}-{sup 11}C]palmitic acid. These studies show as well, low uptake in nontarget tissues (blood, lung, kidney, and muscle). PET images of a dog heart obtained after administration of [{omega}-{sup 11}C]- and [1-{sup 11}C]palmitic acid show virtually identical uptake and distribution in the myocardium. The differing cardiac washout of labeled palmitates measured by dynamic PET studies may allow diagnosis of disorders in cardiac fatty acid metabolism.

  19. In-depth Physiological Analysis of Defined Cell Populations in Acute Tissue Slices of the Mouse Vomeronasal Organ.

    PubMed

    Ackels, Tobias; Drose, Daniela R; Spehr, Marc

    2016-01-01

    In most mammals, the vomeronasal organ (VNO) is a chemosensory structure that detects both hetero- and conspecific social cues. Vomeronasal sensory neurons (VSNs) express a specific type of G protein-coupled receptor (GPCR) from at least three different chemoreceptor gene families allowing sensitive and specific detection of chemosensory cues. These families comprise the V1r and V2r gene families as well as the formyl peptide receptor (FPR)-related sequence (Fpr-rs) family of putative chemoreceptor genes. In order to understand the physiology of vomeronasal receptor-ligand interactions and downstream signaling, it is essential to identify the biophysical properties inherent to each specific class of VSNs. The physiological approach described here allows identification and in-depth analysis of a defined population of sensory neurons using a transgenic mouse line (Fpr-rs3-i-Venus). The use of this protocol, however, is not restricted to this specific line and thus can easily be extended to other genetically modified lines or wild type animals. PMID:27684435

  20. Accuracies of facial soft tissue depth means for estimating ground truth skin surfaces in forensic craniofacial identification.

    PubMed

    Stephan, Carl N

    2015-07-01

    Facial soft tissue thickness means have long been used as a proxy to estimate the soft tissue envelope, over the skull, in craniofacial identification. However, estimation errors of these statistics are not well understood, making casework selection of the best performing estimation models impossible and overarching method accuracies controversial. To redress this situation, residuals between predicted and ground truth values were calculated in two experiments: (1) for 27 suites of means drawn from 10 recently published studies, all examining the same 10 landmarks (N ≥ 3051), and tested against six independent raw datasets of contemporary living adults (N = 797); and (2) pairwise tests of the above six, and five other, raw datasets (N = 1063). In total, 380 out-of-sample tests of 416 arithmetic means were conducted across 11 independent samples. Experiment 1 produced an overarching mean absolute percentage error (MAE) of 29% and a standard error of the estimate (S(est)) of 2.7 mm. Experiment 2 yielded MAE of 32% and S(est) of 2.8 mm. In any instance, MAE was always ≥20% of the ground truth value. The overarching 95% limits of the error, for contemporary samples, was large (11.4 mm). CT-derived means from South Korean males and Black South African females routinely performed well across the test samples and produced the smallest errors of any tests (but did so for Black American male reference samples). Sample-specific statistics thereby performed poorly despite discipline esteem. These results—and the practice of publishing means without prior model validation—demand major reforms in the field. PMID:25394746

  1. Accuracies of facial soft tissue depth means for estimating ground truth skin surfaces in forensic craniofacial identification.

    PubMed

    Stephan, Carl N

    2015-07-01

    Facial soft tissue thickness means have long been used as a proxy to estimate the soft tissue envelope, over the skull, in craniofacial identification. However, estimation errors of these statistics are not well understood, making casework selection of the best performing estimation models impossible and overarching method accuracies controversial. To redress this situation, residuals between predicted and ground truth values were calculated in two experiments: (1) for 27 suites of means drawn from 10 recently published studies, all examining the same 10 landmarks (N ≥ 3051), and tested against six independent raw datasets of contemporary living adults (N = 797); and (2) pairwise tests of the above six, and five other, raw datasets (N = 1063). In total, 380 out-of-sample tests of 416 arithmetic means were conducted across 11 independent samples. Experiment 1 produced an overarching mean absolute percentage error (MAE) of 29% and a standard error of the estimate (S(est)) of 2.7 mm. Experiment 2 yielded MAE of 32% and S(est) of 2.8 mm. In any instance, MAE was always ≥20% of the ground truth value. The overarching 95% limits of the error, for contemporary samples, was large (11.4 mm). CT-derived means from South Korean males and Black South African females routinely performed well across the test samples and produced the smallest errors of any tests (but did so for Black American male reference samples). Sample-specific statistics thereby performed poorly despite discipline esteem. These results—and the practice of publishing means without prior model validation—demand major reforms in the field.

  2. Assessing the mechanical properties of tissue-mimicking phantoms at different depths as an approach to measure biomechanical gradient of crystalline lens

    PubMed Central

    Wang, Shang; Aglyamov, Salavat; Karpiouk, Andrei; Li, Jiasong; Emelianov, Stanislav; Manns, Fabrice; Larin, Kirill V.

    2013-01-01

    We demonstrate the feasibility of using the dominant frequency of the sample surface response to a mechanical stimulation as an effective indicator for sensing the depthwise distribution of elastic properties in transparent layered phantom samples simulating the cortex and nucleus of the crystalline lens. Focused ultrasound waves are used to noninvasively interrogate the sample surface. A phase-sensitive optical coherence tomography system is utilized to capture the surface dynamics over time with nanometer scale sensitivity. Spectral analysis is performed on the sample surface response to ultrasound stimulation and the dominant frequency is calculated under particular loading parameters. Pilot experiments were conducted on homogeneous and layered tissue-mimicking phantoms. Results indicate that the mechanical layers located at different depths introduce different frequencies to the sample surface response, which are correlated with the depth-dependent elasticity of the sample. The duration and the frequency of the ultrasound excitation are also investigated for their influences on this spectrum-based detection. This noninvasive method may be potentially applied for localized and rapid assessment of the depth dependence of the mechanical properties of the crystalline lens. PMID:24409379

  3. Quantitative Analysis of Cardiac Tissue Including Fibroblasts Using Three-Dimensional Confocal Microscopy and Image Reconstruction: Towards a Basis for Electrophysiological Modeling

    PubMed Central

    Schwab, Bettina C.; Seemann, Gunnar; Lasher, Richard A.; Torres, Natalia S.; Wülfers, Eike M.; Arp, Maren; Carruth, Eric D.; Bridge, John H. B.; Sachse, Frank B.

    2014-01-01

    Electrophysiological modeling of cardiac tissue is commonly based on functional and structural properties measured in experiments. Our knowledge of these properties is incomplete, in particular their remodeling in disease. Here, we introduce a methodology for quantitative tissue characterization based on fluorescent labeling, 3-D scanning confocal microscopy, image processing and reconstruction of tissue micro-structure at sub-micrometer resolution. We applied this methodology to normal rabbit ventricular tissue and tissue from hearts with myocardial infarction. Our analysis revealed that the volume fraction of fibroblasts increased from 4.83 ± 0.42% (mean ± standard deviation) in normal tissue up to 6.51 ± 0.38% in myocardium from infarcted hearts. The myocyte volume fraction decreased from 76.20 ± 9.89% in normal to 73.48 ± 8.02% adjacent to the infarct. Numerical field calculations on 3-D reconstructions of the extracellular space yielded an extracellular longitudinal conductivity of 0.264 ± 0.082 S/m with an anisotropy ratio of 2.095 ± 1.11 in normal tissue. Adjacent to the infarct, the longitudinal conductivity increased up to 0.400 ± 0.051 S/m, but the anisotropy ratio decreased to 1.295 ± 0.09. Our study indicates an increased density of gap junctions proximal to both fibroblasts and myocytes in infarcted versus normal tissue, supporting previous hypotheses of electrical coupling of fibroblasts and myocytes in infarcted hearts. We suggest that the presented methodology provides an important contribution to modeling normal and diseased tissue. Applications of the methodology include the clinical characterization of disease-associated remodeling. PMID:23340590

  4. NOTE: Spectra from 2.5-15 µm of tissue phantom materials, optical clearing agents and ex vivo human skin: implications for depth profiling of human skin

    NASA Astrophysics Data System (ADS)

    Viator, John A.; Choi, Bernard; Peavy, George M.; Kimel, Sol; Nelson, J. Stuart

    2003-01-01

    Infrared measurements have been used to profile or image biological tissue, including human skin. Usually, analysis of such measurements has assumed that infrared absorption is due to water and collagen. Such an assumption may be reasonable for soft tissue, but introduction of exogenous agents into skin or the measurement of tissue phantoms has raised the question of their infrared absorption spectrum. We used Fourier transform infrared spectroscopy in attenuated total reflection mode to measure the infrared absorption spectra, in the range of 2-15 µm, of water, polyacrylamide, Intralipid, collagen gels, four hyperosmotic clearing agents (glycerol, 1,3-butylene glycol, trimethylolpropane, TopicareTM), and ex vivo human stratum corneum and dermis. The absorption spectra of the phantom materials were similar to that of water, although additional structure was noted in the range of 6-10 µm. The absorption spectra of the clearing agents were more complex, with molecular absorption bands dominating between 6 and 12 µm. Dermis was similar to water, with collagen structure evident in the 6-10 µm range. Stratum corneum had a significantly lower absorption than dermis due to a lower content of water. These results suggest that the assumption of water-dominated absorption in the 2.5-6 µm range is valid. At longer wavelengths, clearing agent absorption spectra differ significantly from the water spectrum. This spectral information can be used in pulsed photothermal radiometry or utilized in the interpretation of reconstructions in which a constant μir is used. In such cases, overestimating μir will underestimate chromophore depth and vice versa, although the effect is dependent on actual chromophore depth.

  5. Cardiac Time Intervals by Tissue Doppler Imaging M-Mode: Normal Values and Association with Established Echocardiographic and Invasive Measures of Systolic and Diastolic Function

    PubMed Central

    Mogelvang, Rasmus; de Knegt, Martina Chantal; Olsen, Flemming Javier; Galatius, Søren; Jensen, Jan Skov

    2016-01-01

    Purpose To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function. Methods In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the MV. IVCT/ET, IVRT/ET and the MPI ((IVRT+IVCT)/ET) were calculated. We also included a validation population (n = 44) of patients who underwent left heart catheterization and had the MPITDI and MPIConv measured. Results IVRT, IVRT/ET and MPI all increased significantly with increasing age in both genders (p<0.001 for all). IVCT, ET, IVRT/ET, and MPI differed significantly between males and females, displaying that women, in general exhibit better cardiac function. MPITDI was significantly associated with invasive (dP/dt max) and echocardiographic measures of systolic (LVEF, global longitudinal strain and global strainrate s) and diastolic function (e’, global strainrate e)(p<0.05 for all), whereas MPIConv was significantly associated with LVEF, e’ and global strainrate e (p<0.05 for all). Conclusion Normal values of cardiac time intervals differed between genders and deteriorated with increasing age. The MPITDI (but not MPIConv) is associated with most invasive and established echocardiographic measures of systolic and diastolic function. PMID:27093636

  6. Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected Dogs

    PubMed Central

    de Paula Costa, Guilherme; Lopes, Laís Roquete; Horta, Aline Luciano; Pontes, Washington Martins; Milanezi, Cristiane M.; Guedes, Paulo Marcos da Mata; de Lima, Wanderson Geraldo; Schulz, Richard

    2016-01-01

    Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain of T. cruzi and grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. After 14 months of infection, hearts were excised and processed for qPCR analysis of Th1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), Th2 (CCL1, CCL17, CCL24, and CCL26), Th17 (CCL20) CKs, Th1 (CCR5, CCR6, and CXCR3), and Th2/Th17 (CCR3, CCR4, and CCR8) CKR, as well as IL-17. T. cruzi infection increases CCL1, CCL2, CCL4, CCL5, CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6, and CXCR3. Our data reveal an immune modulatory effect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection. PMID:27688600

  7. Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected Dogs

    PubMed Central

    de Paula Costa, Guilherme; Lopes, Laís Roquete; Horta, Aline Luciano; Pontes, Washington Martins; Milanezi, Cristiane M.; Guedes, Paulo Marcos da Mata; de Lima, Wanderson Geraldo; Schulz, Richard

    2016-01-01

    Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain of T. cruzi and grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. After 14 months of infection, hearts were excised and processed for qPCR analysis of Th1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), Th2 (CCL1, CCL17, CCL24, and CCL26), Th17 (CCL20) CKs, Th1 (CCR5, CCR6, and CXCR3), and Th2/Th17 (CCR3, CCR4, and CCR8) CKR, as well as IL-17. T. cruzi infection increases CCL1, CCL2, CCL4, CCL5, CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6, and CXCR3. Our data reveal an immune modulatory effect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection.

  8. Cardiac Rehabilitation

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Rehabilitation? Cardiac rehabilitation (rehab) is a medically supervised program ... be designed to meet your needs. The Cardiac Rehabilitation Team Cardiac rehab involves a long-term commitment ...

  9. Bioaccumulation and Tissue Distribution of Arsenic, Cadmium, Copper and Zinc in Crassostrea virginica Grown at Two Different Depths in Jamaica Bay, New York.

    PubMed

    Rodney, Eric; Herrera, Pedro; Luxama, Juan; Boykin, Mark; Crawford, Alisa; Carroll, Margaret A; Catapane, Edward J

    2007-01-01

    Historically, Jamaica Bay was a site of extensive oyster beds and shellfish culture leases that supported a significant oyster fishery in the New York area. The industrial and urban expansion of the early 1900's led to over-harvesting and a deterioration in water and bay sediment quality that coincided with shellfish decline and the ultimate disappearance of oysters from the bay. Over the past 50 years, efforts to arrest and reverse the pollution problems of Jamaica Bay have been undertaken but the area still contains metals and other pollutants at levels higher than NYS Water Quality Standards. Previous we showed that Crassostrea virginica seed transplanted to the bay had excellent growth and survival despite the bay's pollution problems. In this study we measured the one-year bioaccumulation and tissue distribution of four metals in C. virginica seed that were transplanted to the bay at two different depths: one foot from the surface and one foot above the sediment. Tissues of C. virginica were dissected, dried and digested in nitric acid. Arsenic, cadmium, copper and zinc levels were measured using electrothermal vaporization with deuterium lamp background correction in an atomic absorption spectrophotometer fitted with a THGA graphite furnace. Metals were distributed in the various tissues in μg/g dry weight amounts, which correlate well with published values for whole oysters grown in other polluted areas. Metal distributions were not homogeneous throughout the animals and in most of the tissues tested, oysters grown near the surface accumulated more metal than those positioned near bay sediment. PMID:21841973

  10. Bioaccumulation and Tissue Distribution of Arsenic, Cadmium, Copper and Zinc in Crassostrea virginica Grown at Two Different Depths in Jamaica Bay, New York

    PubMed Central

    Rodney, Eric; Herrera, Pedro; Luxama, Juan; Boykin, Mark; Crawford, Alisa; Carroll, Margaret A.; Catapane, Edward J.

    2011-01-01

    Historically, Jamaica Bay was a site of extensive oyster beds and shellfish culture leases that supported a significant oyster fishery in the New York area. The industrial and urban expansion of the early 1900’s led to over-harvesting and a deterioration in water and bay sediment quality that coincided with shellfish decline and the ultimate disappearance of oysters from the bay. Over the past 50 years, efforts to arrest and reverse the pollution problems of Jamaica Bay have been undertaken but the area still contains metals and other pollutants at levels higher than NYS Water Quality Standards. Previous we showed that Crassostrea virginica seed transplanted to the bay had excellent growth and survival despite the bay’s pollution problems. In this study we measured the one-year bioaccumulation and tissue distribution of four metals in C. virginica seed that were transplanted to the bay at two different depths: one foot from the surface and one foot above the sediment. Tissues of C. virginica were dissected, dried and digested in nitric acid. Arsenic, cadmium, copper and zinc levels were measured using electrothermal vaporization with deuterium lamp background correction in an atomic absorption spectrophotometer fitted with a THGA graphite furnace. Metals were distributed in the various tissues in μg/g dry weight amounts, which correlate well with published values for whole oysters grown in other polluted areas. Metal distributions were not homogeneous throughout the animals and in most of the tissues tested, oysters grown near the surface accumulated more metal than those positioned near bay sediment. PMID:21841973

  11. Cardiac Mitochondrial Respiratory Dysfunction and Tissue Damage in Chronic Hyperglycemia Correlate with Reduced Aldehyde Dehydrogenase-2 Activity

    PubMed Central

    Deshpande, Mandar; Thandavarayan, Rajarajan A.; Xu, Jiang; Yang, Xiao-Ping; Palaniyandi, Suresh S.

    2016-01-01

    Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7–11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts. Increase in the cardiomyocyte cross sectional area (446 ± 32 μm2 Vs 221 ± 10 μm2; p<0.0001) indicated cardiac hypertrophy in DM rats. Both diastolic and systolic dysfunctions were observed with DM rats compared to controls. Most importantly, myocardial ALDH2 activity and levels were reduced, and immunostaining for 4HNE protein adducts was increased in DM hearts compared to controls. The mitochondrial oxygen consumption rate (OCR), an index of mitochondrial respiration, was decreased in mitochondria isolated from DM hearts compared to controls (p<0.0001). Furthermore, the rate of mitochondrial respiration and the increase in carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-induced maximal respiration were also decreased with chronic hyperglycemia. Chronic hyperglycemia reduced mitochondrial OXPHOS proteins. Reduced ALDH2 activity was correlated with mitochondrial dysfunction, pathological remodeling and cardiac dysfunction, respectively. Our results suggest that chronic hyperglycemia reduces ALDH2 activity, leading to mitochondrial respiratory dysfunction and consequently cardiac damage and dysfunction. PMID:27736868

  12. Determination of zero-field size percent depth doses and tissue maximum ratios for stereotactic radiosurgery and IMRT dosimetry: comparison between experimental measurements and Monte Carlo simulation.

    PubMed

    Cheng, Chee-Wai; Cho, Sang Hyun; Taylor, Michael; Das, Indra J

    2007-08-01

    In this study, zero-field percent depth dose (PDD) and tissue maximum ratio (TMR) for 6 MV x rays have been determined by extrapolation from dosimetric measurements over the field size range 1 x 1-10 x 10 cm2. The key to small field dosimetry is the selection of a proper dosimeter for the measurements, as well as the alignment of the detector with the central axis (CAX) of beam. The measured PDD results are compared with those obtained from Monte Carlo (MC) simulation to examine the consistency and integrity of the measured data from which the zero-field PDD is extrapolated. Of the six most commonly used dosimeters in the clinic, the stereotactic diode field detector (SFD), the PTW Pinpoint, and the Exradin A14 are the most consistent and produce results within 2% of each other over the entire field size range 1 x 1-40 x 40 cm2. Although the diamond detector has the smallest sensitive volume, it is the least stable and tends to disagree with all other dosimeters by more than 10%. The zero-field PDD data extrapolated from larger field measurements obtained with the SFD are in good agreement with the MC results. The extrapolated and MC data agree within 2.5% over the clinical depth range (dmax-30 cm), when the MC data for the zero field are derived from a 1 X 1 cm2 field simulation using a miniphantom (1 x 1 x 48 cm3). The agreement between the measured PDD and the MC data based on a full phantom (48 x 48 x 48 cm3) simulation is fairly good within 1% at shallow depths to approximately 5% at 30 cm. Our results seem to indicate that zero-field TMR can be accurately calculated from PDD measurements with a proper choice of detector and a careful alignment of detector axis with the CAX. PMID:17879776

  13. Transcriptome of the Deep-Sea Black Scabbardfish, Aphanopus carbo (Perciformes: Trichiuridae): Tissue-Specific Expression Patterns and Candidate Genes Associated to Depth Adaptation

    PubMed Central

    Stefanni, Sergio; Bettencourt, Raul; Pinheiro, Miguel; Moro, Gianluca De; Bongiorni, Lucia; Pallavicini, Alberto

    2014-01-01

    Deep-sea fishes provide a unique opportunity to study the physiology and evolutionary adaptation to extreme environments. We carried out a high throughput sequencing analysis on a 454 GS-FLX titanium plate using unnormalized cDNA libraries from six tissues of A. carbo. Assemblage and annotations were performed by Newbler and InterPro/Pfam analyses, respectively. The assembly of 544,491 high quality reads provided 8,319 contigs, 55.6% of which retrieved blast hits against the NCBI nonredundant database or were annotated with ESTscan. Comparison of functional genes at both the protein sequences and protein stability levels, associated with adaptations to depth, revealed similarities between A. carbo and other bathypelagic fishes. A selection of putative genes was standardized to evaluate the correlation between number of contigs and their normalized expression, as determined by qPCR amplification. The screening of the libraries contributed to the identification of new EST simple-sequence repeats (SSRs) and to the design of primer pairs suitable for population genetic studies as well as for tagging and mapping of genes. The characterization of the deep-sea fish A. carbo first transcriptome is expected to provide abundant resources for genetic, evolutionary, and ecological studies of this species and the basis for further investigation of depth-related adaptation processes in fishes. PMID:25309900

  14. Differential effects of propofol and isoflurane on the relationship between EEG Narcotrend index and clinical stages of anaesthetic depth in sheep undergoing experimental cardiac surgery.

    PubMed

    Otto, Klaus A

    2016-02-01

    The electroencephalogram (EEG) Narcotrend index (NI) has been shown to improve anaesthetic depth monitoring in isoflurane-anaesthetised sheep. Data obtained from 13 anaesthetised juvenile female sheep were analysed retrospectively in order to assess the relationship between clinical stages of anaesthesia (CS) and NI during both propofol and isoflurane anaesthesia. Polynomial regression analysis revealed no significant association between CS and NI for propofol (R = 0.374, R(2) = 0.140, P = 0.403) but for isoflurane anaesthesia (R = 0.548, R(2) = 0.301, P = 0.010) there was a significant relationship. Furthermore, a strong correlation existed between end-tidal isoflurane concentration (ISOET) and CS (r = -0.463, P = 0.008). A combination of assessment of clinical signs and analogous EEG patterns is recommended during propofol anaesthesia.

  15. miR-17 targets tissue inhibitor of metalloproteinase 1 and 2 to modulate cardiac matrix remodeling.

    PubMed

    Li, Shu-Hong; Guo, Jian; Wu, Jun; Sun, Zhuo; Han, Mihan; Shan, Sze Wan; Deng, Zhaoqun; Yang, Burton B; Weisel, Richard D; Li, Ren-Ke

    2013-10-01

    We aimed to investigate the role of miR-17 in cardiac matrix remodeling following myocardial infarction (MI). Using real-time PCR, we quantified endogenous miR-17 in infarcted mouse hearts. Compared with related microRNAs, miR-17 was up-regulated most dramatically: 3.7-fold and 2.4-fold in the infarct region 3 and 7 d post-MI, respectively, and 2.4-fold in the border zone at d 3 compared to sham control (P<0.01). Chimeric luciferase reporter constructs were cloned for miR-17 target validation. miR-17 targeted the 3'-UTR of TIMP2 and the protein coding region of TIMP1. The miR-17 mimic decreased TIMP2 (P<0.01) and TIMP1 (P<0.05) protein expression compared with the scrambled control. Inhibition of endogenous miR-17 by in vivo antagomir delivery enhanced TIMP2 (P<0.01) and TIMP1 (P<0.05) protein expression compared to the mismatch group, decreased MMP9 activity (P<0.05), reduced infarct size as early as 7 d post-MI (P<0.05), and improved cardiac function (fractional shortening and fractional area contraction, P<0.05) at d 21 and 28 post-MI. Transgenic mice overexpressing miR-17 in the heart confirmed the deleterious role of miR-17 in matrix modulation. Our study suggests that miR-17 participates in the regulation of cardiac matrix remodeling and provides a novel therapeutic approach using miR-17 inhibitors to prevent remodeling and heart failure after MI.

  16. Microwave Treatment for Cardiac Arrhythmias

    NASA Technical Reports Server (NTRS)

    Hernandez-Moya, Sonia

    2009-01-01

    NASA seeks to transfer the NASA developed microwave ablation technology, designed for the treatment of ventricular tachycardia (irregular heart beat), to industry. After a heart attack, many cells surrounding the resulting scar continue to live but are abnormal electrically; they may conduct impulses unusually slowly or fire when they would typically be silent. These diseased areas might disturb smooth signaling by forming a reentrant circuit in the muscle. The objective of microwave ablation is to heat and kill these diseased cells to restore appropriate electrical activity in the heart. This technology is a method and apparatus that provides for propagating microwave energy into heart tissues to produce a desired temperature profile therein at tissue depths sufficient for thermally ablating arrhythmogenic cardiac tissue while preventing excessive heating of surrounding tissues, organs, and blood. A wide bandwidth double-disk antenna is effective for this purpose over a bandwidth of about six gigahertz. A computer simulation provides initial screening capabilities for an antenna such as antenna, frequency, power level, and power application duration. The simulation also allows optimization of techniques for specific patients or conditions. In comparison with other methods that involve direct-current pulses or radio frequencies below 1 GHz, this method may prove more effective in treating ventricular tachycardia. This is because the present method provides for greater control of the location, cross-sectional area, and depth of a lesion via selection of the location and design of the antenna and the choice of microwave power and frequency.

  17. Application of stochastic phenomenological modelling to cell-to-cell and beat-to-beat electrophysiological variability in cardiac tissue.

    PubMed

    Walmsley, John; Mirams, Gary R; Pitt-Francis, Joe; Rodriguez, Blanca; Burrage, Kevin

    2015-01-21

    Variability in the action potential of isolated myocytes and tissue samples is observed in experimental studies. Variability is manifested as both differences in the action potential (AP) morphology between cells (extrinsic variability), and also 'intrinsic' or beat-to-beat variability of repolarization (BVR) in the AP duration of each cell. We studied the relative contributions of experimentally recorded intrinsic and extrinsic variability to dispersion of repolarization in tissue. We developed four cell-specific parameterizations of a phenomenological stochastic differential equation AP model exhibiting intrinsic variability using APs recorded from isolated guinea pig ventricular myocytes exhibiting BVR. We performed simulations in tissue using the four different model parameterizations in the presence and the absence of both intrinsic and extrinsic variability. We altered the coupling of the tissue to determine how inter-cellular coupling affected the dispersion of the AP duration in tissue. Both intrinsic and extrinsic variability were gradually revealed by reduction of tissue coupling. However, the recorded extrinsic variability between individual myocytes produced a greater degree of dispersion in repolarization in tissue than the intrinsic variability of each myocyte.

  18. Reverse Genetic Morpholino Approach Using Cardiac Ventricular Injection to Transfect Multiple Difficult-to-target Tissues in the Zebrafish Larva

    PubMed Central

    Konantz, Judith; Antos, Christopher L.

    2014-01-01

    The zebrafish is an important model to understand the cell and molecular biology of organ and appendage regeneration. However, molecular strategies to employ reverse genetics have not yet been adequately developed to assess gene function in regeneration or tissue homeostasis during larval stages after zebrafish embryogenesis, and several tissues within the zebrafish larva are difficult to target. Intraventricular injections of gene-specific morpholinos offer an alternative method for the current inability to genomically target zebrafish genes in a temporally controlled manner at these stages. This method allows for complete dispersion and subsequent incorporation of the morpholino into various tissues throughout the body, including structures that were formerly impossible to reach such as those in the larval caudal fin, a structure often used to noninvasively research tissue regeneration. Several genes activated during larval finfold regeneration are also present in regenerating adult vertebrate tissues, so the larva is a useful model to understand regeneration in adults. This morpholino dispersion method allows for the quick and easy identification of genes required for the regeneration of larval tissues as well as other physiological phenomena regulating tissue homeostasis after embryogenesis. Therefore, this delivery method provides a currently needed strategy for temporal control to the evaluation of gene function after embryogenesis.  PMID:24961304

  19. Reverse genetic morpholino approach using cardiac ventricular injection to transfect multiple difficult-to-target tissues in the zebrafish larva.

    PubMed

    Konantz, Judith; Antos, Christopher L

    2014-01-01

    The zebrafish is an important model to understand the cell and molecular biology of organ and appendage regeneration. However, molecular strategies to employ reverse genetics have not yet been adequately developed to assess gene function in regeneration or tissue homeostasis during larval stages after zebrafish embryogenesis, and several tissues within the zebrafish larva are difficult to target. Intraventricular injections of gene-specific morpholinos offer an alternative method for the current inability to genomically target zebrafish genes in a temporally controlled manner at these stages. This method allows for complete dispersion and subsequent incorporation of the morpholino into various tissues throughout the body, including structures that were formerly impossible to reach such as those in the larval caudal fin, a structure often used to noninvasively research tissue regeneration. Several genes activated during larval finfold regeneration are also present in regenerating adult vertebrate tissues, so the larva is a useful model to understand regeneration in adults. This morpholino dispersion method allows for the quick and easy identification of genes required for the regeneration of larval tissues as well as other physiological phenomena regulating tissue homeostasis after embryogenesis. Therefore, this delivery method provides a currently needed strategy for temporal control to the evaluation of gene function after embryogenesis. 

  20. The study of simulated microgravity effects on cardiac myocytes using a 3D heart tissue-equivalent model encapsulated in alginate microbeads

    NASA Astrophysics Data System (ADS)

    Li, Yu; Tian, Weiming; Zheng, Hongxia; Yu, Lei; Zhang, Yao; Han, Fengtong

    Long duration spaceflight may increase the risk and occurrence of potentially life-threatening heart rhythm disturbances associated with alterations of cardiac myocytes, myocyte connec-tivity, and extracellular matrix resulting from prolonged exposure to zero-or low-gravity. For understanding of the effects of microgravity, either traditional 2-dimensional (2D) cell cultures of adherent cell populations or animal models were typically used. The 2D in vitro systems do not allow assessment of the dynamic effects of intercellular interactions within tissues, whereas potentially confounding factors tend to be overlooked in animal models. Therefore novel cell culture model representative of the cellular interactions and with extracellular matrix present in tissues needs to be used. In this study, 3D multi-cellular heart tissue-equivalent model was constructed by culturing neonatal rat myocardial cells in alginate microbeads for one week. With this model we studied the simulated microgravity effects on myocardiocytes by incubat-ing the microbeads in NASA rotary cell culture system with a rate of 15rpm. Cytoskeletal changes, mitochondrial membrane potential and reactive oxygen production were studied after incubating for 24h, 48h and 72h respectively. Compared with 3D ground-culture group, sig-nificant cytoskeleton depolymerization characterized by pseudo-feet disappearance, significant increase of mitochondrial membrane potential, and greater reactive oxygen production were observed in after incubating 24h, 48h, and 72h, in NASA system. The beating rate of 3D heart tissue-equivalent decreased significantly at 24h, and all the samples stopped beating after 48h incubation while the beating rate of control group did not change. This study indicated that mi-crogravity affects both the structure and function of myocardial cells. Our results suggest that a 3D heart tissue-equivalent model maybe better for attempting to elucidate the microgravity effects on myocardiocytes in

  1. Rat Cytomegalovirus Gene Expression in Cardiac Allograft Recipients Is Tissue Specific and Does Not Parallel the Profiles Detected In Vitro▿

    PubMed Central

    Streblow, Daniel N.; van Cleef, Koen W. R.; Kreklywich, Craig N.; Meyer, Christine; Smith, Patricia; Defilippis, Victor; Grey, Finn; Früh, Klaus; Searles, Robert; Bruggeman, Cathrien; Vink, Cornelis; Nelson, Jay A.; Orloff, Susan L.

    2007-01-01

    Rat cytomegalovirus (RCMV) is a β-herpesvirus with a 230-kbp genome containing over 167 open reading frames (ORFs). RCMV gene expression is tightly regulated in cultured cells, occurring in three distinct kinetic classes (immediate early, early, and late). However, the extent of viral-gene expression in vivo and its relationship to the in vitro expression are unknown. In this study, we used RCMV-specific DNA microarrays to investigate the viral transcriptional profiles in cultured, RCMV-infected endothelial cells, fibroblasts, and aortic smooth muscle cells and to compare these profiles to those found in tissues from RCMV-infected rat heart transplant recipients. In cultured cells, RCMV expresses approximately 95% of the known viral ORFs with few differences between cell types. By contrast, in vivo viral-gene expression in tissues from rat heart allograft recipients is highly restricted. In the tissues studied, a total of 80 viral genes expressing levels twice above background (5,000 to 10,000 copies per μg total RNA) were detected. In each tissue type, there were a number of genes expressed exclusively in that tissue. Although viral mRNA and genomic DNA levels were lower in the spleen than in submandibular glands, the number of individual viral genes expressed was higher in the spleen (60 versus 41). This finding suggests that the number of viral genes expressed is specific to a given tissue and is not dependent upon the viral load or viral mRNA levels. Our results demonstrate that the profiles, as well as the amplitude, of viral-gene expression are tissue specific and are dramatically different from those in infected cultured cells, indicating that RCMV gene expression in vitro does not reflect viral-gene expression in vivo. PMID:17251289

  2. Effect of tissue fat and water content on nuclear magnetic resonance relaxation times of cardiac and skeletal muscle.

    PubMed

    Scholz, T D; Fleagle, S R; Parrish, F C; Breon, T; Skorton, D J

    1990-01-01

    Understanding tissue determinants that affect the nuclear magnetic resonance (NMR) properties of myocardium would improve noninvasive characterization of myocardial tissue. To determine if NMR relaxation times would reflect changes in tissue fat content, two experimental models were investigated. First, an idealized model using mixtures of beef skeletal muscle and beef fat was studied to investigate the effects of a wide range of tissue fat content. Second, myocardium with varying fat content from hogs raised to have varying degrees of ponderosity was analyzed. Tissue fat and water contents and spin-lattice (T1) and spin-spin (T2) relaxation times at 20 MHz were measured. The skeletal muscle/fat mixtures ranged in fat content from 35% to 95% with water content variations from 50% to 75%. Water content decreased as fat content increased. A significant inverse linear relationship was found between T1 and sample fat content (r = -0.997). Spin-spin relaxation times showed a significant positive curvilinear relationship with fat content (r2 = 0.96). In the animal experiments, 18 hogs were studied with samples obtained from both right and left ventricular (LV) free walls, with care taken to avoid epicardial fat. Myocardial fat content ranged from 3% to 25%. A significant correlation was found between LV fat content and corrected LV mass (r = 0.62), which suggested that the increase in LV mass could be explained, at least in part, by changes in myocardial fat content. Similar to the muscle/fat mixture model, a significant positive curvilinear relationship was found between myocardial T2 and tissue fat content (r2 = 0.67) for all the myocardial samples.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Cardiac rehabilitation

    MedlinePlus

    ... Coronary artery disease - cardiac rehab; Angina - cardiac rehab; Heart failure - cardiac rehab ... have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery ...

  4. Avenanthramides are bioavailable and accumulate in hepatic, cardiac, and skeletal muscle tissue following oral gavage in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avenanthramides (AVA), polyphenols found exclusively in oats (Avena sativa L.), may play a role in the anti-inflammatory and anti-atherogenic activity of oats. The bioavailability of AVA has been demonstrated previously, but its distribution at the organ and tissue level and the extent of conjugati...

  5. Generation of bioartificial heart tissue by combining a three-dimensional gel-based cardiac construct with decellularized small intestinal submucosa.

    PubMed

    Vukadinovic-Nikolic, Zlata; Andrée, Birgit; Dorfman, Suzanne E; Pflaum, Michael; Horvath, Tibor; Lux, Marco; Venturini, Letizia; Bär, Antonia; Kensah, George; Lara, Angelica Roa; Tudorache, Igor; Cebotari, Serghei; Hilfiker-Kleiner, Denise; Haverich, Axel; Hilfiker, Andres

    2014-02-01

    The in vitro generation of a bioartificial cardiac construct (CC) represents a promising tool for the repair of ischemic heart tissue. Several approaches to engineer cardiac tissue in vitro have been conducted. The main drawback of these studies is the insufficient size of the resulting construct for clinical applications. The focus of this study was the generation of an artificial three-dimensional (3D), contractile, and suturable myocardial patch by combining a gel-based CC with decellularized porcine small intestinal submucosa (SIS), thereby engineering an artificial tissue of 11 cm² in size. The alignment and morphology of rat neonatal cardiomyocytes (rCMs) in SIS-CC complexes were investigated as well as the re-organization of primary endothelial cells which were co-isolated in the rCM preparation. The ability of a rat heart endothelial cell line (RHE-A) to re-cellularize pre-existing vessel structures within the SIS or a biological vascularized matrix (BioVaM) was determined. SIS-CC contracted spontaneously, uniformly, and rhythmically with an average rate of 200 beats/min in contrast to undirected contractions observed in CC without SIS support. rCM exhibited an elongated morphology with well-defined sarcomeric structures oriented along the longitudinal axis in the SIS-CC, whereas round-shaped and random-arranged rCM were observed in CC. Electric coupling of rCM was demonstrated by microelectrode array measurements. A dense network of CD31⁺/eNOS⁺ cells was detected as permeating the whole construct. Superficial supplementation of RHE-A cells to SIS-CC led to the migration of these cells through the CC, resulting in the re-population of pre-existing vessel structures within the decelluarized SIS. By infusion of RHE-A cells into the BioVaM venous and arterial pedicles, a re-population of the BioVaM vessel bed as well as distribution of RHE-A cells throughout the CC was achieved. Rat endothelial cells within the CC were in contact with RHE-A cells

  6. Noninvasive, near infrared spectroscopic-measured muscle pH and PO2 indicate tissue perfusion for cardiac surgical patients undergoing cardiopulmonary bypass

    NASA Technical Reports Server (NTRS)

    Soller, Babs R.; Idwasi, Patrick O.; Balaguer, Jorge; Levin, Steven; Simsir, Sinan A.; Vander Salm, Thomas J.; Collette, Helen; Heard, Stephen O.

    2003-01-01

    OBJECTIVE: To determine whether near infrared spectroscopic measurement of tissue pH and Po2 has sufficient accuracy to assess variation in tissue perfusion resulting from changes in blood pressure and metabolic demand during cardiopulmonary bypass. DESIGN: Prospective clinical study. SETTING: Academic medical center. SUBJECTS: Eighteen elective cardiac surgical patients. INTERVENTION: Cardiac surgery under cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: A near infrared spectroscopic fiber optic probe was placed over the hypothenar eminence. Reference Po2 and pH sensors were inserted in the abductor digiti minimi (V). Data were collected every 30 secs during surgery and for 6 hrs following cardiopulmonary bypass. Calibration equations developed from one third of the data were used with the remaining data to investigate sensitivity of the near infrared spectroscopic measurement to physiologic changes resulting from cardiopulmonary bypass. Near infrared spectroscopic and reference pH and Po2 measurements were compared for each subject using standard error of prediction. Near infrared spectroscopic pH and Po2 at baseline were compared with values during cardiopulmonary bypass just before rewarming commenced (hypotensive, hypothermic), after rewarming (hypotensive, normothermic) just before discontinuation of cardiopulmonary bypass, and at 6 hrs following cardiopulmonary bypass (normotensive, normothermic) using mixed-model analysis of variance. Near infrared spectroscopic pH and Po2 were well correlated with the invasive measurement of pH (R2 =.84) and Po2 (R 2 =.66) with an average standard error of prediction of 0.022 +/- 0.008 pH units and 6 +/- 3 mm Hg, respectively. The average difference between the invasive and near infrared spectroscopic measurement was near zero for both the pH and Po2 measurements. Near infrared spectroscopic Po2 significantly decreased 50% on initiation of cardiopulmonary bypass and remained depressed throughout the bypass and

  7. Data analysis in cardiac arrhythmias.

    PubMed

    Rodrigo, Miguel; Pedrón-Torecilla, Jorge; Hernández, Ismael; Liberos, Alejandro; Climent, Andreu M; Guillem, María S

    2015-01-01

    Cardiac arrhythmias are an increasingly present in developed countries and represent a major health and economic burden. The occurrence of cardiac arrhythmias is closely linked to the electrical function of the heart. Consequently, the analysis of the electrical signal generated by the heart tissue, either recorded invasively or noninvasively, provides valuable information for the study of cardiac arrhythmias. In this chapter, novel cardiac signal analysis techniques that allow the study and diagnosis of cardiac arrhythmias are described, with emphasis on cardiac mapping which allows for spatiotemporal analysis of cardiac signals.Cardiac mapping can serve as a diagnostic tool by recording cardiac signals either in close contact to the heart tissue or noninvasively from the body surface, and allows the identification of cardiac sites responsible of the development or maintenance of arrhythmias. Cardiac mapping can also be used for research in cardiac arrhythmias in order to understand their mechanisms. For this purpose, both synthetic signals generated by computer simulations and animal experimental models allow for more controlled physiological conditions and complete access to the organ.

  8. A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos.

    PubMed

    Oberholzer, Hester Magdalena; Van Der Schoor, Ciska; Taute, Helena; Bester, Megan Jean

    2015-08-01

    Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose-related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development.

  9. Evaluation of a tissue-engineered bovine pericardial patch in paediatric patients with congenital cardiac anomalies: initial experience with the ADAPT-treated CardioCel® patch

    PubMed Central

    Neethling, William M.L.; Strange, Geoff; Firth, Laura; Smit, Francis E.

    2013-01-01

    OBJECTIVES This study evaluated the safety, efficacy and clinical performance of the tissue-engineered ADAPT® bovine pericardial patch (ABPP) in paediatric patients with a range of congenital cardiac anomalies. METHODS In this single-centre, prospective, non-randomized clinical study, paediatric patients underwent surgery for insertion of the ABPP. Primary efficacy measures included early (<30 day) morbidity; incidence of device-related complications; haemodynamic performance derived from echocardiography assessment at 6- and 12-month follow-up and magnetic resonance imaging findings in 10 randomly selected patients at 12 months. Secondary measures included device-handling characteristics; shape and sizing characteristics and perioperative implant complications. The Aristotle complexity scoring system was used to score the complexity level of all surgical procedures. Patients completing the 12-month study were eligible to enter a long-term evaluation study. RESULTS Between April 2008 and September 2009, the ABPP was used in 30 paediatric patients. In the 30-day postoperative period, no graft-related morbidity was observed. In total, there were 5 deaths (2 in the 30-day postoperative period and 3 within the first 6 postoperative months). All deaths were deemed due to comorbid non-graft-related events. Echocardiography assessment at 6 and 12 months revealed intact anatomical and haemodynamically stable repairs without any visible calcification of the patch. Magnetic resonance imaging assessment in 10 patients at 12 months revealed no signs of calcification. Fisher's exact test demonstrated that patients undergoing more complex, higher risk surgical repairs (Aristotle complexity score >8) were significantly more likely to die (P = 0.0055, 58% survival compared with 100% survival for less complex surgical repairs). In 19 patients, echocardiographic data were available at 18–36 months with no evidence of device calcification, infection, thromboembolic events or

  10. Detection of Soluble ED-A(+) Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling.

    PubMed

    Ziffels, Barbara; Ospel, Johanna; Grün, Katja; Neri, Dario; Pfeil, Alexander; Fritzenwanger, Michael; Figulla, Hans R; Jung, Christian; Berndt, Alexander; Franz, Marcus

    2016-01-01

    Background and Aims. Fibronectin containing the extra domain A (ED-A(+) Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A(+) Fn in serum of heart failure patients. Methods. ED-A(+) Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n = 44) and dilated (DCM, n = 39) cardiomyopathy as well as hypertensive heart disease (HHD, n = 31) compared to healthy controls (n = 12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A(+) Fn (p < 0.001). In particular in ICM patients there were significant associations between ED-A(+) Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p = 0.013), a negative correlation with left ventricular ejection fraction (p = 0.026, r: -0.353), a positive correlation with left atrial diameter (p = 0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p = 0.002, r: 0.485). In multivariate analysis, ED-A(+) Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A(+) Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A(+) Fn. PMID:27635109

  11. Detection of Soluble ED-A+ Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling

    PubMed Central

    Ospel, Johanna; Neri, Dario; Pfeil, Alexander; Fritzenwanger, Michael; Figulla, Hans R.; Jung, Christian; Berndt, Alexander

    2016-01-01

    Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n = 44) and dilated (DCM, n = 39) cardiomyopathy as well as hypertensive heart disease (HHD, n = 31) compared to healthy controls (n = 12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (p < 0.001). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p = 0.013), a negative correlation with left ventricular ejection fraction (p = 0.026, r: −0.353), a positive correlation with left atrial diameter (p = 0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p = 0.002, r: 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn. PMID:27635109

  12. Detection of Soluble ED-A+ Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling

    PubMed Central

    Ospel, Johanna; Neri, Dario; Pfeil, Alexander; Fritzenwanger, Michael; Figulla, Hans R.; Jung, Christian; Berndt, Alexander

    2016-01-01

    Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n = 44) and dilated (DCM, n = 39) cardiomyopathy as well as hypertensive heart disease (HHD, n = 31) compared to healthy controls (n = 12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (p < 0.001). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p = 0.013), a negative correlation with left ventricular ejection fraction (p = 0.026, r: −0.353), a positive correlation with left atrial diameter (p = 0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p = 0.002, r: 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn.

  13. Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

    PubMed Central

    Kertész, Attila; Bombicz, Mariann; Priksz, Daniel; Balla, Jozsef; Balla, Gyorgy; Gesztelyi, Rudolf; Varga, Balazs; Haines, David D.; Tosaki, Arpad; Juhasz, Bela

    2013-01-01

    The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls. PMID:24048247

  14. The implication of tissue Doppler echocardiography and cardiopulmonary exercise in early detection of cardiac dysfunction in systemic lupus erythematosus patients

    PubMed Central

    Elnady, Basant M.; Abdelghafar, Ayman Saeed Mohamed; Khalik, El Shazly Abdul; Algethami, Mohammed Mesfer; Basiony, A.S.; Al-otaibi, Mona Dhaif Allah; Al-otaibi, Maram Eidhah

    2016-01-01

    Objective Systemic lupus erythematosus (SLE) can present limitations to exercise capacity and quality of life (QoL) because of various clinical conditions, such as pulmonary disease or heart disease. Tissue Doppler echocardiography (TDE) offers the promise of an objective measurement to quantify regional and global ventricular function through the assessment of myocardial velocity data. This study aimed to assess the intensity of left ventricular (LV) and right ventricular (RV) systolic and diastolic dysfunction in SLE patients by means of TDE and cardiopulmonary exercise (CPX) testing to determine their impact on QoL. Material and Methods Overall, 56 SLE patients within two tertiary healthcare centers as well as 50 healthy controls were examined with TDE after the exclusion of cardiovascular risk factors. TDE was performed for maximal systolic (S), early diastolic (E′), and late diastolic (A′) velocities of the mitral and tricuspid annulus. Pulsed wave (PW) Doppler of mitral and tricuspid valve inflow was performed in addition to the estimation of the left ventricle ejection fraction and assessment of right ventricle systolic function by tricuspid annular plane systolic excursion (TAPSE). Disease activity was assessed by the Systemic Lupus Activity Measure (SLAM), and the damage index was assessed by the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). CPX tests according to the modified Bruce protocol were performed. Results SLE patients in both subgroups had more or less similar laboratory data and statistically higher values of ESR, CRP, and anticardiolipin (aCL) antibodies compared to the control group. LV function showed statistically insignificant EF compared to the control group, being lower in the patient group. Tissue Doppler image revealed that E′ and A′ of the mitral annulus were lower in the patient group than in the control group. Concerning RV, TAPSE in the patient group was

  15. Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

    PubMed Central

    Gizzi, Alessio; Cherry, Elizabeth M.; Gilmour, Robert F.; Luther, Stefan; Filippi, Simonetta; Fenton, Flavio H.

    2013-01-01

    Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events. PMID:23637684

  16. Apparent Depth.

    ERIC Educational Resources Information Center

    Nassar, Antonio B.

    1994-01-01

    Discusses a well-known optical refraction problem where the depth of an object in a liquid is determined. Proposes that many texts incorrectly solve the problem. Provides theory, equations, and diagrams. (MVL)

  17. Artificial rearing of infant mice leads to n-3 fatty acid deficiency in cardiac, neural and peripheral tissues.

    PubMed

    Hussein, Nahed; Fedorova, Irina; Moriguchi, Toru; Hamazaki, Kei; Kim, Hee-Yong; Hoshiba, Junji; Salem, Norman

    2009-08-01

    The ability to control the fatty acid content of the diet during early development is a crucial requirement for a one-generation model of docosahexaenoic acid (DHA; 22:6n3) deficiency. A hand feeding method using artificial rearing (AR) together with sterile, artificial milk was employed for feeding mice from postnatal day 2-15. The pups were fed an n-3 fatty acid adequate (3% alpha-linolenic acid (LNA; 18:3n3) + 1% 22:6n3) or a deficient diet (0.06% 18:3n3) with linoleic acid (LA; 18:2n6) as the only dietary source of essential fatty acids by AR along with a dam-reared control group (3.1% 18:3n3). The results indicate that restriction of n-3 fatty acid intake during postnatal development leads to markedly lower levels of brain, retinal, liver, plasma and heart 22:6n3 at 20 weeks of age with replacement by docosapentaenoic acid (DPAn6; 22:5n6), arachidonic acid (ARA; 20:4n6) and docosatetraenoic acid (DTA; 22:4n6). A detailed analysis of phospholipid classes of heart tissue indicated that phosphatidylethanolamine, phosphatidylcholine and cardiolipin were the major repositories of 22:6n3, reaching 40, 29 and 15%, respectively. A novel heart cardiolipin species containing four 22:6n3 moieties is described. This is the first report of the application of artificially rearing to mouse pup nutrition; this technique will facilitate dietary studies of knockout animals as well as the study of essential fatty acid (EFA) functions in the cardiovascular, neural and other organ systems.

  18. Effects of thyroid hormones on cardiac structure: a tissue characterization study in patients with thyroid disorders before and after treatment.

    PubMed

    Ciulla, M M; Paliotti, R; Cortelazzi, D; Tortora, G; Barelli, M V; Buonamici, V; Magrini, F; Beck-Peccoz, P

    2001-07-01

    Experimental evidence suggests an involvement of thyroid hormones in myocardial nonmyocyte component growth. We evaluated the possible role of thyroid hormones in myocardial remodeling by ultrasonic tissue characterization (videodensitometry) in 8 hyperthyroid patients, in 10 hypothyroid patients, and in 2 patients with thyroid hormone resistance syndrome (RTH), before, 60, and 120 days after treatment (T0, T60, T120), and in 10 age-matched euthyroids. According to a previously described procedure, the derived collagen volume fraction (dCVF%, an echocardiographic index estimating the collagen content) was predicted from the pixel-level frequency distribution width (broadband, Bb) of the selected echocardiographic images. Thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed by immunometric method. QT interval dispersion (QTd) on basal electrocardiogram was measured as a marker of dyshomogeneous ventricular repolarization. At T0, Bb and dCVF% were normal in hyperthyroid and euthyroid patients, and slightly increased in RTH patients, whereas significantly higher values were found in hypothyroids. At T60, a significant reduction in Bb was observed in hypothyroids, with nearly normal dCVF% values. This trend was confirmed at T120 with complete normalization of echoreflectivity. No echoreflectivity changes were observed in hyperthyroid and RTH patients during treatment. QTd was significantly increased in hypothyroids at T0, while no significant differences were found among groups at T60 and T120. Because the different videodeonsitometric myocardial properties observed in hypothyroid versus hyperthyroid patients correspond to an increase of dCVF%, this study suggests that thyroid hormones exert an inhibitory effect on myocardial collagen synthesis in humans.

  19. Effect of thyroid status on beta-adrenoceptors and calcium channels in rat cardiac and vascular tissue.

    PubMed

    Hawthorn, M H; Gengo, P; Wei, X Y; Rutledge, A; Moran, J F; Gallant, S; Triggle, D J

    1988-05-01

    To determine the influence of thyroid hormone on beta-adrenoceptors and Ca2+ channels, rats were treated with thyroxine (75 micrograms/100 g sc daily for 5 days) or propylthiouracil (0.05% in drinking water for 30 days). beta-Adrenoceptor density in ventricular tissue, measured by [125I]iodocyanopindolol binding, was significantly increased and decreased respectively, following thyroxine or propylthiouracil treatment to 124.7 +/- 7.11 fmol/mg protein and 71.98 +/- 5.37 fmol/mg protein from euthyroid (control) levels of 93.7 +/- 4.58 fmol/mg protein. Ca2+ channel density, measured by [3H]nitrendipine binding, was altered in the opposite direction; it was significantly decreased and increased to 324 +/- 24 fmol/mg protein and 691 +/- 31 fmol/mg protein from 562 +/- 35 fmol/mg protein after thyroxine or propylthiouracil treatment, respectively. No changes in affinity of either ligand were observed. Responses of isolated papillary muscles from propylthiouracil-treated animals accorded with changes seen in the binding studies. The geometric mean EC50 of isoproterenol increased from 9.5 x 10(-9) mol/l to 5.5 x 10(-8) mol/l, and the EC50 for calcium decreased from 3.16 x 10(-3) mol/l to 1.36 x 10(-3) mol/l; moreover, the responsiveness to the Ca2+ channel activator Bay K 8644 was increased. The corresponding responses in thyroxine-treated animals could not be examined because of prominent arrhythmic activity. As with papillary muscles the sensitivity of left atria to isoproterenol was decreased after treatment with propylthiouracil, with geometric mean EC50 values increasing from 3.21 x 10(-9) mol/l to 89.4 x 10(-9) mol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Ultrasound catheters for circumferential cardiac ablation

    NASA Astrophysics Data System (ADS)

    Diederich, Chris J.; Nau, William H.; Taylor, Kevin; Maguire, Mark T.; Picazo, Guillermo; Gangu, Madhuri; Lesh, Michael D.

    1999-05-01

    The purpose of this study was to investigate performance characteristics of a catheter-based ultrasound applicator intended for circumferential ablation of cardiac tissue. The catheter design integrates a cylindrical ultrasound transducer within a distendable water filled balloon in order to produce circumferential lesions at sites in the atria (i.e., pulmonary vein ostia), intended for treatment of certain atrial arrhythmias. Biothermal simulations were used to investigate thermal lesion depths corresponding to variations in applied power, duration, balloon diameter, and acoustic efficiency. Prototype applicators of varying frequency (7 - 12 MHz) and balloon diameter were constructed and characterized using measurements of acoustic efficiency and rotational beam plots. In vitro studies were performed in freshly excised beef hearts to characterize the radial penetration, axial length, and angular uniformity of thermal lesions produced by these applicators. Selected applicators were tested in vivo within pulmonary veins, coronary sinus, and atrial appendage of canine and porcine hearts. These preliminary efforts have indicated that circumferential ablation of cardiac tissue using ultrasound balloon catheters is feasible, and devices between 7 - 12 MHz with balloon diameters of 1.5 - 2.0 cm are capable of producing uniform lesions between 1 - 5 mm depth or greater for treatment durations of 120 seconds or less.

  1. Cardiac Applications of Optogenetics

    PubMed Central

    Ambrosi, Christina M.; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-01-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics. PMID:25035999

  2. Cardiac applications of optogenetics.

    PubMed

    Ambrosi, Christina M; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-08-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics.

  3. Cardiac arrest

    MedlinePlus

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  4. SU-E-T-499: Comparison of Measured Tissue Phantom Ratios (TPR) Against Calculated From Percent Depth Doses (PDD) with and Without Peak Scatter Factor (PSF) in 6MV Open Beam

    SciTech Connect

    Narayanasamy, G; Cruz, W; Gutierrez, Alonso; Mavroidis, Panayiotis; Papanikolaou, N; Stathakis, S; Breton, C

    2014-06-01

    Purpose: To examine the accuracy of measured tissue phantom ratios (TPR) values with TPR calculated from percentage depth dose (PDD) with and without peak scatter fraction (PSF) correction. Methods: For 6MV open beam, TPR and PDD values were measured using PTW Semiflex (31010) ionization field and reference chambers (0.125cc volume) in a PTW MP3-M water tank. PDD curves were measured at SSD of 100cm for 7 square fields from 3cm to 30cm. The TPR values were measured up to 22cm depth for the same fields by continuous water draining method with ionization chamber static at 100cm from source. A comparison study was performed between the (a) measured TPR, (b) TPR calculated from PDD without PSF, (c) TPR calculated from PDD with PSF and (d) clinical TPR from RadCalc (ver 6.2, Sun Nuclear Corp). Results: There is a field size, depth dependence on TPR values. For 10cmx10cm, the differences in surface dose (DDs), dose at 10cm depth (DD10) <0.5%; differences in dmax (Ddmax) <2mm for the 4 methods. The corresponding values for 30cmx30cm are DDs, DD10 <0.2% and Ddmax<3mm. Even though for 3cmx3cm field, DDs and DD10 <1% and Ddmax<1mm, the calculated TPR values with and without PSF correction differed by 2% at >20cm depth. In all field sizes at depths>28cm, (d) clinical TPR values are larger than that from (b) and (c) by >3%. Conclusion: Measured TPR in method (a) differ from calculated TPR in methods (b) and (c) to within 1% for depths < 28cm in all 7 fields in open 6MV beam. The dmax values are within 3mm of each other. The largest deviation of >3% was observed in clinical TPR values in method (d) for all fields at depths < 28cm.

  5. Label-free and depth resolved optical sectioning of iron-complex deposits in sickle cell disease splenic tissue by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Vigil, Genevieve D.; Adami, Alexander J.; Ahmed, Tahsin; Khan, Aamir; Chapman, Sarah; Andemariam, Biree; Thrall, Roger S.; Howard, Scott S.

    2015-06-01

    Multiphoton microscopy (MPM) imaging of intrinsic two-photon excited fluorescence (TPEF) is performed on humanized sickle cell disease (SCD) mouse model splenic tissue. Distinct morphological and spectral features associated with SCD are identified and discussed in terms of diagnostic relevance. Specifically, spectrally unique splenic iron-complex deposits are identified by MPM; this finding is supported by TPEF spectroscopy and object size to standard histopathological methods. Further, iron deposits are found at higher concentrations in diseased tissue than in healthy tissue by all imaging methods employed here including MPM, and therefore, may provide a useful biomarker related to the disease state. These newly characterized biomarkers allow for further investigations of SCD in live animals as a means to gain insight into the mechanisms impacting immune dysregulation and organ malfunction, which are currently not well understood.

  6. Types of muscle tissue (image)

    MedlinePlus

    The 3 types of muscle tissue are cardiac, smooth, and skeletal. Cardiac muscle cells are located in ... heart, appear striated, and are under involuntary control. Smooth muscle fibers are located in walls of hollow ...

  7. Cardiac Sarcoidosis.

    PubMed

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  8. Mechanisms of cardiac arrhythmias

    PubMed Central

    Tse, Gary

    2015-01-01

    Blood circulation is the result of the beating of the heart, which provides the mechanical force to pump oxygenated blood to, and deoxygenated blood away from, the peripheral tissues. This depends critically on the preceding electrical activation. Disruptions in the orderly pattern of this propagating cardiac excitation wave can lead to arrhythmias. Understanding of the mechanisms underlying their generation and maintenance requires knowledge of the ionic contributions to the cardiac action potential, which is discussed in the first part of this review. A brief outline of the different classification systems for arrhythmogenesis is then provided, followed by a detailed discussion for each mechanism in turn, highlighting recent advances in this area. PMID:27092186

  9. Acupuncture therapy related cardiac injury.

    PubMed

    Li, Xue-feng; Wang, Xian

    2013-12-01

    Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.

  10. Cardiac transplantation.

    PubMed

    Shanewise, Jack

    2004-12-01

    Cardiac transplantation is a proven, accepted mode of therapy for selected patients with end-stage heart failure, but the inadequate number of suitable donor hearts available ultimately limits its application. This chapter reviews adult cardiac transplantation, with an emphasis on the anesthetic considerations of the heart transplant operation itself.

  11. Cardiac metastases

    PubMed Central

    Bussani, R; De‐Giorgio, F; Abbate, A; Silvestri, F

    2007-01-01

    Tumours metastatic to the heart (cardiac metastases) are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Although primary cardiac tumours are extremely uncommon (various postmortem studies report rates between 0.001% and 0.28%), secondary tumours are not, and at least in theory, the heart can be metastasised by any malignant neoplasm able to spread to distant sites. In general, cardiac metastases are considered to be rare; however, when sought for, the incidence seems to be not as low as expected, ranging from 2.3% and 18.3%. Although no malignant tumours are known that diffuse preferentially to the heart, some do involve the heart more often than others—for example, melanoma and mediastinal primary tumours. This paper attempts to review the pathophysiology of cardiac metastatic disease, epidemiology and clinical presentation of cardiac metastases, and pathological characterisation of the lesions. PMID:17098886

  12. Redox proteomic identification of HNE-bound mitochondrial proteins in cardiac tissues reveals a systemic effect on energy metabolism after doxorubicin treatment.

    PubMed

    Zhao, Y; Miriyala, S; Miao, L; Mitov, M; Schnell, D; Dhar, S K; Cai, J; Klein, J B; Sultana, R; Butterfield, D A; Vore, M; Batinic-Haberle, I; Bondada, S; St Clair, D K

    2014-07-01

    Doxorubicin (DOX), one of the most effective anticancer drugs, is known to generate progressive cardiac damage, which is due, in part, to DOX-induced reactive oxygen species (ROS). The elevated ROS often induce oxidative protein modifications that result in alteration of protein functions. This study demonstrates that the level of proteins adducted by 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product, is significantly increased in mouse heart mitochondria after DOX treatment. A redox proteomics method involving two-dimensional electrophoresis followed by mass spectrometry and investigation of protein databases identified several HNE-modified mitochondrial proteins, which were verified by HNE-specific immunoprecipitation in cardiac mitochondria from the DOX-treated mice. The majority of the identified proteins are related to mitochondrial energy metabolism. These include proteins in the citric acid cycle and electron transport chain. The enzymatic activities of the HNE-adducted proteins were significantly reduced in DOX-treated mice. Consistent with the decline in the function of the HNE-adducted proteins, the respiratory function of cardiac mitochondria as determined by oxygen consumption rate was also significantly reduced after DOX treatment. Treatment with Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, an SOD mimic, averted the doxorubicin-induced mitochondrial dysfunctions as well as the HNE-protein adductions. Together, the results demonstrate that free radical-mediated alteration of energy metabolism is an important mechanism mediating DOX-induced cardiac injury, suggesting that metabolic intervention may represent a novel approach to preventing cardiac injury after chemotherapy. PMID:24632380

  13. Redox Proteomic identification of HNE-bound mitochondrial proteins in cardiac tissues reveals a systemic effect on energy metabolism after Doxorubicin treatment

    PubMed Central

    Zhao, Y; Miriyala, S; Miao, L; Mitov, M; Schnell, D; Dhar, SK; Cai, J; Klein, JB; Sultana, R; Butterfield, DA; Vore, M; Batinic-Haberle, I; Bondada, S

    2014-01-01

    Doxorubicin (DOX), one of the most effective anticancer drugs, is known to generate progressive cardiac damage, which is due, in part, to DOX-induced reactive oxygen species (ROS). The elevated ROS often induce oxidative protein modifications that result in alteration of protein functions. This study demonstrates that the level of proteins adducted by 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product, is significantly increased in mouse heart mitochondria following DOX treatment. A redox proteomics method involving 2D electrophoresis followed by mass spectrometry and investigation of protein data bases identified several HNE-modified mitochondria proteins, which were verified by HNE-specific immunoprecipitation in cardiac mitochondria from the DOX-treated mice. The majority of the identified proteins are related to mitochondrial energy metabolism. These include proteins in the citric acid cycle (TCA) and electron transport chain (ETC). The enzymatic activities of the HNE-adducted proteins were significantly reduced in DOX-treated mice. Consistent with the decline in the function of the HNE adducted proteins, the respiratory function of cardiac mitochondria as determined by oxygen consumption rate (OCR) was also significantly reduced after DOX treatment. The treatment with Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, MnP, an SOD mimic, averted the doxorubicin-induced mitochondrial dysfunctions as well as the HNE protein adductions. Together, the results demonstrate that free radical-mediated alteration of energy metabolism is an important mechanism mediating DOX-induced cardiac injury suggesting that metabolic intervention may represent a novel approach to preventing cardiac injury after chemotherapy. PMID:24632380

  14. Forensic facial approximation assessment: can application of different average facial tissue depth data facilitate recognition and establish acceptable level of resemblance?

    PubMed

    Herrera, Lara Maria; Strapasson, Raíssa Ananda Paim; da Silva, Jorge Vicente Lopes; Melani, Rodolfo Francisco Haltenhoff

    2016-09-01

    Facial soft tissue thicknesses (FSTT) are important guidelines for modeling faces from skull. Amid so many FSTT data, Forensic artists have to make a subjective choice of a dataset that best meets their needs. This study investigated the performance of four FSTT datasets in the recognition and resemblance of Brazilian living individuals and the performance of assessors in recognizing people, according to sex and knowledge on Human Anatomy and Forensic Dentistry. Sixteen manual facial approximations (FAs) were constructed using three-dimensional (3D) prototypes of skulls (targets). The American method was chosen for the construction of the faces. One hundred and twenty participants evaluated all FAs by means of recognition and resemblance tests. This study showed higher proportions of recognition by FAs conducted with FSTT data from cadavers compared with those conducted with medical imaging data. Targets were also considered more similar to FAs conducted with FSTT data from cadavers. Nose and face shape, respectively, were considered the most similar regions to targets. The sex of assessors (male and female) and the knowledge on Human Anatomy and Forensic Dentistry did not play a determinant role to reach greater recognition rates. It was possible to conclude that FSTT data obtained from imaging may not facilitate recognition and establish acceptable level of resemblance. Grouping FSTT data by regions of the face, as proposed in this paper, may contribute to more accurate FAs.

  15. Cardiac amyloidosis

    MedlinePlus

    ... the way electrical signals move through the heart (conduction system). This can lead to abnormal heartbeats ( arrhythmias ) ... due to medicine) Sick sinus syndrome Symptomatic cardiac conduction system disease (arrhythmias related to abnormal conduction of ...

  16. Cardiac Sarcoidosis

    MedlinePlus

    ... is Cardiac Sarcoidosis? Sarcoidosis is a poorly understood disease that commonly affects the lungs. It can also involve the lymph nodes, liver, spleen, eyes, skin, bones, salivary glands and heart. ...

  17. [Stem cells and cardiac regeneration].

    PubMed

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research.

  18. Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

    PubMed Central

    Chen, Olivia; Qian, Li

    2015-01-01

    Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming. PMID:26176012

  19. Telocytes in exercise-induced cardiac growth.

    PubMed

    Xiao, Junjie; Chen, Ping; Qu, Yi; Yu, Pujiao; Yao, Jianhua; Wang, Hongbao; Fu, Siyi; Bei, Yihua; Chen, Yan; Che, Lin; Xu, Jiahong

    2016-05-01

    Exercise can induce physiological cardiac growth, which is featured by enlarged cardiomyocyte cell size and formation of new cardiomyocytes. Telocytes (TCs) are a recently identified distinct interstitial cell type, existing in many tissues and organs including heart. TCs have been shown to form a tandem with cardiac stem/progenitor cells in cardiac stem cell niches, participating in cardiac regeneration and repair. Although exercise-induced cardiac growth has been confirmed as an important way to promote cardiac regeneration and repair, the response of cardiac TCs to exercise is still unclear. In this study, 4 weeks of swimming training was used to induce robust healthy cardiac growth. Exercise can induce an increase in cardiomyocyte cell size and formation of new cardiomyocytes as determined by Wheat Germ Lectin and EdU staining respectively. TCs were identified by three immunofluorescence stainings including double labelling for CD34/vimentin, CD34/platelet-derived growth factor (PDGF) receptor-α and CD34/PDGF receptor-β. We found that cardiac TCs were significantly increased in exercised heart, suggesting that TCs might help control the activity of cardiac stem/progenitor cells, cardiomyocytes or endothelial cells. Adding cardiac TCs might help promote cardiac regeneration and renewal. PMID:26987685

  20. In Utero Exposure of Female CD-1 Mice to AZT and/or 3TC: I. Persistence of Microscopic Lesions in Cardiac Tissue

    PubMed Central

    Torres, Salina M.; March, Thomas H.; Carter, Meghan M.; McCash, Consuelo L.; Seilkop, Steven K.; Poirier, Miriam C.; Walker, Dale M.

    2010-01-01

    The current study was designed to delineate temporal changes in cardiomyocytes and mitochondria at the light and electron microscopic levels in hearts of mice exposed transplacentally to commonly used nucleoside analogs (NRTIs). Pregnant CD-1 mice were given 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during the last 7 days of gestation, and hearts from female mouse pups were examined at 13 and 26 weeks postpartum for histopathological or ultrastructural changes in cross-sections of both the ventricles and the interventricular septum. Using light microscopy and special staining techniques, transplacental exposure to AZT, 3TC, or AZT/3TC was shown to induce significant histopathological changes in myofibrils; these changes were more widespread at 13 weeks than at 26 weeks postpartum. While most light microscopic lesions resolved, some became more severe between 13 and 26 weeks postpartum. Transplacental NRTI exposure also resulted in progressive drug-specific changes in the number and ultrastructural integrity of cardiac mitochondria. These light and electron microscopic findings show that a subset of changes in cardiac mitochondria and myofibrils persisted and progressed months after transplacental exposure of an animal model to NRTIs, with combined AZT/3TC exposure yielding additive effects compared with either drug alone. PMID:20101476

  1. Computer Generated Cardiac Model For Nuclear Medicine

    NASA Astrophysics Data System (ADS)

    Hills, John F.; Miller, Tom R.

    1981-07-01

    A computer generated mathematical model of a thallium-201 myocardial image is described which is based on realistic geometric and physiological assumptions. The left ventricle is represented by an ellipsoid truncated by aortic and mitral valve planes. Initially, an image of a motionless left ventricle is calculated with the location, size, and relative activity of perfusion defects selected by the designer. The calculation includes corrections for photon attenuation by overlying structures and the relative distribution of activity within the tissues. Motion of the ventricular walls is simulated either by a weighted sum of images at different stages in the cardiac cycle or by a blurring function whose width varies with position. Camera and collimator blurring are estimated by the MTF of the system measured at a representative depth in a phantom. Statistical noise is added using a Poisson random number generator. The usefulness of this model is due to two factors: the a priori characterization of location and extent of perfusion defects and the strong visual similarity of the images to actual clinical studies. These properties should permit systematic evaluation of image processing algorithms using this model. The principles employed in developing this cardiac image model can readily be applied to the simulation of other nuclear medicine studies and to other medical imaging modalities including computed tomography, ultrasound, and digital radiography.

  2. MR imaging of cardiac tumors.

    PubMed

    Sparrow, Patrick J; Kurian, John B; Jones, Tim R; Sivananthan, Mohan U

    2005-01-01

    Magnetic resonance (MR) imaging is an important tool in the evaluation of cardiac neoplasms. T1-weighted, T2-weighted, and gadolinium-enhanced sequences are used for anatomic definition and tissue characterization, whereas cine gradient-echo imaging is used to assess functional effects. Recent improvements in pulse sequences for cardiac MR imaging have led to superior image quality, with reduced motion artifact and improved signal-to-noise ratio and tissue contrast. Although there is some overlap in the MR imaging appearances of cardiac tumors, particularly of primary malignancies, differences in characteristic locations and features should allow confident differentiation between benign and malignant tumors. Indicators of malignancy at MR imaging are invasive behavior, involvement of the right side of the heart or the pericardium, tissue inhomogeneity, diameter greater than 5 cm, and enhancement after administration of gadolinium contrast material (as a result of higher tissue vascularity). Concomitant pericardial or pleural effusions are rare in benign processes but occur in about 50% of cases of malignant tumors. MR imaging offers improved resolution, a larger field of view, and superior soft-tissue contrast compared with those of echocardiography, suggesting that knowledge of the MR imaging features of cardiac neoplasms is important for accurate diagnosis and management. PMID:16160110

  3. Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery

    PubMed Central

    2010-01-01

    Background The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia. Methods/Design The DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment. Discussion The DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three. Trial registration This trial is registered at Clinicaltrials

  4. [Cardiac amyloidosis].

    PubMed

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  5. The Association between Serum Ferritin Level, Tissue Doppler Echocardiography, Cardiac T2* MRI, and Heart Rate Recovery in Patients with Beta Thalassemia Major

    PubMed Central

    Yuksel, Isa Oner; Koklu, Erkan; Kurtoglu, Erdal; Arslan, Sakir; Cagirci, Goksel; Karakus, Volkan; Kus, Gorkem; Cay, Serkan; Kucukseymen, Selcuk

    2016-01-01

    Background It is generally well-understood that iron-mediated cardiomyopathy is the major complication that can arise from beta thalassemia major (TM). Therefore, early diagnosis, risk stratification, and the effective treatment of beta TM patients are clinically important to optimize long-term positive outcomes. Methods This study included 57 beta TM patients with a mean age of 25 ± 7 years. We determined the serum ferritin level, echocardiography, heart rate recovery (HRR), and cardiac magnetic resonance (CMR) T2* in all patients. CMR T2* findings were categorized as normal myocardium (T2* > 20 ms), and myocardial involvement (T2* ≤ 20 ms). HRR values at 1-5 min (HRR1-5) were recorded; Subsequently. HRR was calculated by subtracting the heart rate at each time point from the heart rate at peak exercise. Results There was a significant negative correlation between the serum ferritin level and the cardiac T2* MRI findings (r = -0.34, p = 0.009). A similar result was found in the negative correlation between serum ferritin and all heart rate recovery values. There was a significant positive correlation between HRR1, HRR2, and HRR3 values, and CMR T2* (T2* heart rate recovery (HRR)1: r = 0.51, p < 0.001; T2* HRR2: r = 0.48, p < 0.001; T2* HRR3: r = 0.47, p < 0.001, respectively). Conclusions The serum ferritin level and echocardiography can be used to predict the presence of myocardial iron load in beta TM patients. Therefore, HRR can be used to screen beta TM patients, and the clinical use of HRR can be a predictive marker for autonomic dysfunction in beta TM patients. PMID:27122954

  6. Integrated RFA/OCT catheter for real-time guidance of cardiac RFA therapy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Fu, Xiaoyong; Blumenthal, Colin; Dosluoglu, Deniz; Wang, Yves T.; Jenkins, Michael W.; Souza, Rakesh; Snyder, Christopher; Arruda, Mauricio; Rollins, Andrew M.

    2016-03-01

    Currently, cardiac radiofrequency ablation is guided by indirect signals. We demonstrate an integrated radiofrequency ablation (RFA) and optical coherence tomography (OCT) probe for directly monitoring of the RFA procedure with OCT images in real time. The integrated RFA/OCT probe is modified from a standard commercial RFA catheter, and a newly designed and fabricated miniature forward-viewing cone-scanning OCT probe is integrated into the modified probe. The OCT system is verified with the human finger images, and the results show the integrated RFA/OCT probe can acquire high quality OCT images. The radiofrequency energy delivering function of the integrated probe is verified by comparing the RFA lesion sizes with standard commercial RFA probe. For the standard commercial probe, the average width and depth of the 10 lesions were 3.5 mm and 1.8 mm respectively. For the integrated RFA/OCT probe, the average width and depth of the 10 lesions were 3.6 mm and 1.7 mm respectively. The lesions created by the two probes are indistinguishable in size. This demonstrates that our glass window in the integrated probe has little effect on the RF energy delivery. And the integrated probe is used to monitoring the cardiac RFA procedure in real time. The results show that the RFA lesion formation can be confirmed by the loss of birefringence in the heart tissue. The system can potentially in vivo image of the cardiac wall to aid RFA therapy for cardiac arrhythmias.

  7. Feasibility of In-Vivo Cardiac HIFU Ablation

    NASA Astrophysics Data System (ADS)

    Fujikura, Kana; Otsuka, Ryo; Kalisz, Andrew; Muratore, Robert; Ketterling, Jeffrey A.; Lizzi, Frederic L.; Homma, Shunichi

    2005-03-01

    The potential for cardiac applications of HIFU remains largely unexplored. In order to create reproducible lesions in a beating heart, it is necessary to maintain focusing at a certain position within moving myocardial tissue. One technique is to use multiple short HIFU exposures (0.2 s) and to synchronize them with an EKG signal and respiration. In order to investigate the interaction of HIFU exposures and cardiac tissues, a series of in-vitro experiments was conducted. The left ventricular free wall (LVFW) of calf hearts were cut into 4-cm cubes, degassed in phosphate buffer saline (PBS), and heated to 37C. Several transducers were employed. Most experiments used a 33-mm diameter spherical-cap transducer with focal length of 35 mm, operated at a frequency of 5.075 MHz and a focused intensity of 13 kW/cm2 (in-situ spatial average over the half-power points of the focused beam). The transducer was coupled to the LVFW using degassed PBS. First, the effects of pericardial fat, focal depth, and temperature on lesion size were individually evaluated. We compared the effect of different time pulse duration (0.2 s and 0.3 s) and number of applied pulses. Dimensions of all lesions were measured by visual examination of the fresh, unstained tissue. Histopathological examination of the lesions was also performed.

  8. Cardiac Surgery

    PubMed Central

    Weisse, Allen B.

    2011-01-01

    Well into the first decades of the 20th century, medical opinion held that any surgical attempts to treat heart disease were not only misguided, but unethical. Despite such reservations, innovative surgeons showed that heart wounds could be successfully repaired. Then, extracardiac procedures were performed to correct patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot. Direct surgery on the heart was accomplished with closed commissurotomy for mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary bypass enabled the surgical treatment of other congenital and acquired heart diseases. Advances in aortic surgery paralleled these successes. The development of coronary artery bypass grafting greatly aided the treatment of coronary heart disease. Cardiac transplantation, attempts to use the total artificial heart, and the application of ventricular assist devices have brought us to the present day. Although progress in the field of cardiovascular surgery appears to have slowed when compared with the halcyon times of the past, substantial challenges still face cardiac surgeons. It can only be hoped that sufficient resources and incentive can carry the triumphs of the 20th century into the 21st. This review covers past developments and future opportunities in cardiac surgery. PMID:22163121

  9. Cardiac complications in thalassemia major.

    PubMed

    Auger, Dominique; Pennell, Dudley J

    2016-03-01

    The myocardium is particularly susceptible to complications from iron loading in thalassemia major. In the first years of life, severe anemia leads to high-output cardiac failure and death if not treated. The necessary supportive blood transfusions create loading of iron that cannot be naturally excreted, and this iron accumulates within tissues, including the heart. Free unbound iron catalyzes the formation of toxic hydroxyl radicals, which damage cells and cause cardiac dysfunction. Significant cardiac siderosis may present by the age of 10 and may lead to acute clinical heart failure, which must be treated urgently. Atrial fibrillation is the most frequently encountered iron-related arrhythmia. Iron chelation is effective at removing iron from the myocardium, at the expense of side effects that hamper compliance to therapy. Monitoring of myocardial iron content is mandatory for clinical management of cardiac risk. T2* cardiac magnetic resonance measures myocardial iron and is the strongest biomarker for prediction of heart failure and arrhythmic events. It has been calibrated to human myocardial tissue iron concentration and is highly reproducible across all magnetic resonance scanner vendors. As survival and patient age increases, endothelial dysfunction and diabetes may become new factors in the cardiovascular health of thalassemia patients. Promising new imaging technology and therapies could ameliorate the long-term prognosis.

  10. Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction.

    PubMed

    Peng, Hongmei; Xu, Jiang; Yang, Xiao-Ping; Dai, Xiangguo; Peterson, Edward L; Carretero, Oscar A; Rhaleb, Nour-Eddine

    2014-09-01

    Thymosin-β4 (Tβ4) promotes cell survival, angiogenesis, and tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces the incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg·kg(-1)·day(-1) ip via osmotic minipump) for 7 days or 5 wk. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis, and interstitial collagen fraction histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of ICAM-1 and p53 by immunoblot analysis. Tβ4 reduced cardiac rupture that was associated with a decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, a decrease in gelatinolytic activity and ICAM-1 and p53 expression, and an increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, markedly reduced interstitial collagen fraction, and increased capillary density. In a murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus, the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.

  11. Spread of excitation in 3-D models of the anisotropic cardiac tissue. III. Effects of ventricular geometry and fiber structure on the potential distribution.

    PubMed

    Colli Franzone, P; Guerri, L; Pennacchio, M; Taccardi, B

    1998-07-01

    In a previous paper we studied the spread of excitation in a simplified model of the left ventricle, affected by fiber structure and obliqueness, curvature of the wall and Purkinje network. In the present paper we investigate the extracellular potential distribution u in the same ventricular model. Given the transmembrane potential v, associated with the spreading excitation, the extracellular potential u is obtained as solution of a linear elliptic equation with the source term related to v. The potential distributions were computed for point stimulations at different intramural depths. The results of the simulations enabled us to identify a number of common features which appears in all the potential patterns irrespective of pacing site. In addition, by splitting the sources into an axial and conormal component, we were able to evaluate the contribution of the classical uniform dipole layer to the total potential field and the role of the superimposed axial component.

  12. The effects of α- and β-adrenergic blocking agents on postresuscitation myocardial dysfunction and myocardial tissue injury in a rat model of cardiac arrest.

    PubMed

    Yang, Min; Hu, Xianwen; Lu, Xiaoye; Wu, Xiaobo; Xu, Jiefeng; Yang, Zhengfei; Qian, Jie; Sun, Shijie; Cahoon, Jena; Tang, Wanchun

    2015-05-01

    We investigated the relationship between the severity of postresuscitation (PR) myocardial tissue injury and myocardial dysfunction after the administration of epinephrine as well as the protective effects of α- and β-adrenergic blocking agents. Forty male Sprague-Dawley rats were randomized into 6 groups: (1) placebo; (2) epinephrine; (3) epinephrine pretreated with α1-blocker (prazosin); (4) epinephrine pretreated with α2-blocker (yohimbine); (5) epinephrine pretreated with β-blocker (propranolol); and (6) epinephrine pretreated with β- plus α1-blocker (propranolol and prazosin). Cardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation and continued for an additional 8 minutes. The myocardial function and the serum concentrations of troponin I (Tn I) and N-terminal probrain natriuretic peptide (NT-proBNP) were measured at baseline and after resuscitation. After resuscitation, both Tn I and NT-proBNP were significantly increased in all groups, especially in the epinephrine and epinephrine pretreated with α2-blocker groups. Significantly better PR myocardial function and neurologic deficit score were observed in epinephrine pretreated with the α1- or β-blocker with decreased releases of Tn I and NT-proBNP. However, the most significant improvements were observed in the animals pretreated with β- plus α1-blocker. The present study demonstrated that myocardial stunning may not be the only mechanism of PR myocardial dysfunction. Administration of epinephrine increased the severity of PR myocardial tissue injury and dysfunction. The β- and β- plus α1-blocker pretreatment significantly reduced the severity of PR myocardial tissue injury and myocardial dysfunction with better neurologic function and prolonged duration of survival. PMID:25468485

  13. Feasibility of in vivo cardiac HIFU ablation

    NASA Astrophysics Data System (ADS)

    Fujikura, Kana; Otsuka, Ryo; Homma, Shunichi; Muratore, Robert; Ketterling, Jeffrey A.; Lizzi, Frederic L.

    2001-05-01

    The potential for cardiac applications of HIFU remains unexamined. In order to create reproducible lesions in a beating heart, it is necessary to maintain focusing at a certain position within moving myocardial tissue. One technique is to use multiple short HIFU exposures (0.2 s) and synchronize them with an EKG signal and respiration. The left ventricular free wall (LVFW) of calf hearts were cut into 4-cm cubes, degassed in phosphate buffer saline (PBS), and heated to 37°C. An 80-mm-diam spherical-cap transducer with a focus of 90 mm was operated at a frequency of 4.67 MHz and a nominal focal point intensity of 26.9 kW/cm2. The transducer was coupled to the LVFW using degassed PBS. First, the effect of pericardial fat, focal depth, and temperature on lesion size was individually evaluated. Then the 0.2-s HIFU exposure was applied 10 to 30 times at 4-s intervals. The same HIFU transducer was applied to an open-chest canine LVFW with the same triggering protocol. Dimensions of all lesions were measured by visual examination of the fresh, unstained tissue. A histopathological examination of the lesion was also performed. The in vivo lesions were created in similar size to those in vitro.

  14. Physics of Cardiac Arrhythmogenesis

    NASA Astrophysics Data System (ADS)

    Karma, Alain

    2013-04-01

    A normal heartbeat is orchestrated by the stable propagation of an excitation wave that produces an orderly contraction. In contrast, wave turbulence in the ventricles, clinically known as ventricular fibrillation (VF), stops the heart from pumping and is lethal without prompt defibrillation. I review experimental, computational, and theoretical studies that have shed light on complex dynamical phenomena linked to the initiation, maintenance, and control of wave turbulence. I first discuss advances made to understand the precursor state to a reentrant arrhythmia where the refractory period of cardiac tissue becomes spatiotemporally disordered; this is known as an arrhythmogenic tissue substrate. I describe observed patterns of transmembrane voltage and intracellular calcium signaling that can contribute to this substrate, and symmetry breaking instabilities to explain their formation. I then survey mechanisms of wave turbulence and discuss novel methods that exploit electrical pacing stimuli to control precursor patterns and low-energy pulsed electric fields to control turbulence.

  15. Cardiac conduction system

    MedlinePlus

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals ... to contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  16. Upconversion fluorescent nanoparticles as a potential tool for in-depth imaging

    NASA Astrophysics Data System (ADS)

    Nagarajan, Sounderya; Zhang, Yong

    2011-09-01

    Upconversion nanoparticles (UCNs) are nanoparticles that are excited in the near infrared (NIR) region with emission in the visible or NIR regions. This makes these particles attractive for use in biological imaging as the NIR light can penetrate the tissue better with minimal absorption/scattering. This paper discusses the study of the depth to which cells can be imaged using these nanoparticles. UCNs with NaYF4 nanocrystals doped with Yb3 + , Er3 + (visible emission)/Yb3 + , Tm3 + (NIR emission) were synthesized and modified with silica enabling their dispersion in water and conjugation of biomolecules to their surface. The size of the sample was characterized using transmission electron microscopy and the fluorescence measured using a fluorescence spectrometer at an excitation of 980 nm. Tissue phantoms were prepared by reported methods to mimic skin/muscle tissue and it was observed that the cells could be imaged up to a depth of 3 mm using the NIR emitting UCNs. Further, the depth of detection was evaluated for UCNs targeted to gap junctions formed between cardiac cells.

  17. Role of temperature on nonlinear cardiac dynamics

    NASA Astrophysics Data System (ADS)

    Fenton, Flavio H.; Gizzi, Alessio; Cherubini, Christian; Pomella, Nicola; Filippi, Simonetta

    2013-04-01

    Thermal effects affecting spatiotemporal behavior of cardiac tissue are discussed by relating temperature variations to proarrhythmic dynamics in the heart. By introducing a thermoelectric coupling in a minimal model of cardiac tissue, we are able to reproduce experimentally measured dynamics obtained simultaneously from epicardial and endocardial canine right ventricles at different temperatures. A quantitative description of emergent proarrhythmic properties of restitution, conduction velocity, and alternans regimes as a function of temperature is presented. Complex discordant alternans patterns that enhance tissue dispersion consisting of one wave front and three wave backs are described in both simulations and experiments. Possible implications for model generalization are finally discussed.

  18. Cardiac MRI

    MedlinePlus

    ... a powerful magnetic field, radio waves and a computer to produce detailed pictures of the structures within ... powerful magnetic field, radio frequency pulses and a computer to produce detailed pictures of organs, soft tissues, ...

  19. Animal models of cardiac cachexia.

    PubMed

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. PMID:27317993

  20. Animal models of cardiac cachexia.

    PubMed

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies.

  1. Advancing cardiovascular tissue engineering

    PubMed Central

    Truskey, George A.

    2016-01-01

    Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643

  2. microRNA and Cardiac Regeneration.

    PubMed

    Gnecchi, Massimiliano; Pisano, Federica; Bariani, Riccardo

    2015-01-01

    Heart diseases are a very common health problem in developed as well as developing countries. In particular, ischemic heart disease and heart failure represent a plague for the patients and for the society. Loss of cardiac tissue after myocardial infarction or dysfunctioning tissue in nonischemic cardiomyopathies may result in cardiac failure. Despite great advancements in the treatment of these diseases, there is a substantial unmet need for novel therapies, ideally addressing repair and regeneration of the damaged or lost myocardium. Along this line, cardiac cell based therapies have gained substantial attention. Three main approaches are currently under investigation: stem cell therapy with either embryonic or adult stem cells; generation of patient-specific induced pluripotent stem cells; stimulation of endogenous regeneration trough direct reprogramming of fibroblasts into cardiomyocytes, activation of resident cardiac stem cells or induction of native resident cardiomyocytes to reenter the cell cycle. All these strategies need to be optimized since their efficiency is low.It has recently become clear that cardiac signaling and transcriptional pathways are intimately intertwined with microRNA molecules which act as modulators of cardiac development, function, and disease. Moreover, miRNA also regulates stem cell differentiation. Here we describe how miRNA may circumvent hurdles that hamper the field of cardiac regeneration and stem cell therapy, and how miRNA may result as the most suitable solution for the damaged heart.

  3. A rare case of primary cardiac lymphoma.

    PubMed

    Khan-Kheil, Ayisha Mehtab; Mustafa, Hanif Muhammad; Anand, Dhakshinamurthy Vijay; Banerjee, Prithwish

    2015-01-01

    A 71-year-old man presented with shortness of breath and tachycardia along with systemic symptoms of weight loss and lethargy. A pulmonary embolus was the initial suspected diagnosis but through extensive investigations a rarer cause of his symptoms was identified. This case demonstrates the importance of cardiac imaging in the assessment and non-invasive tissue characterisation of a suspected cardiac tumour; in our case, this was subsequently confirmed by careful histological/immunocytochemical evaluation o