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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. Challenges in cardiac tissue engineering.

    PubMed

    Vunjak-Novakovic, Gordana; Tandon, Nina; Godier, Amandine; Maidhof, Robert; Marsano, Anna; Martens, Timothy P; Radisic, Milica

    2010-04-01

    Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Engineered constructs can also serve as high-fidelity models for studies of cardiac development and disease. In a general case, the biological potential of the cell-the actual "tissue engineer"-is mobilized by providing highly controllable three-dimensional environments that can mediate cell differentiation and functional assembly. For cardiac regeneration, some of the key requirements that need to be met are the selection of a human cell source, establishment of cardiac tissue matrix, electromechanical cell coupling, robust and stable contractile function, and functional vascularization. We review here the potential and challenges of cardiac tissue engineering for developing therapies that could prevent or reverse heart failure.

  4. Challenges in Cardiac Tissue Engineering

    PubMed Central

    Tandon, Nina; Godier, Amandine; Maidhof, Robert; Marsano, Anna; Martens, Timothy P.; Radisic, Milica

    2010-01-01

    Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Engineered constructs can also serve as high-fidelity models for studies of cardiac development and disease. In a general case, the biological potential of the cell—the actual “tissue engineer”—is mobilized by providing highly controllable three-dimensional environments that can mediate cell differentiation and functional assembly. For cardiac regeneration, some of the key requirements that need to be met are the selection of a human cell source, establishment of cardiac tissue matrix, electromechanical cell coupling, robust and stable contractile function, and functional vascularization. We review here the potential and challenges of cardiac tissue engineering for developing therapies that could prevent or reverse heart failure. PMID:19698068

  5. Depth-resolved fluorescence of biological tissue

    NASA Astrophysics Data System (ADS)

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

    2005-06-01

    The depth-resolved autofluorescence ofrabbit oral tissue, normal and dysplastic human ectocervical tissue within l20μm depth were investigated utilizing a confocal fluorescence spectroscopy with the excitations at 355nm and 457nm. From the topmost keratinizing layer of oral and ectocervical tissue, strong keratin fluorescence with the spectral characteristics similar to collagen was observed. The fluorescence signal from epithelial tissue between the keratinizing layer and stroma can be well resolved. Furthermore, NADH and FADfluorescence measured from the underlying non-keratinizing epithelial layer were strongly correlated to the tissue pathology. 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.

  6. Depth Attenuation Degree Based Visualization for Cardiac Ischemic Electrophysiological Feature Exploration.

    PubMed

    Yang, Fei; Zhang, Lei; Lu, Weigang; Liu, Lei; Zhang, Yue; Zuo, Wangmeng; Wang, Kuanquan; Zhang, Henggui

    2016-01-01

    Although heart researches and acquirement of clinical and experimental data are progressively open to public use, cardiac biophysical functions are still not well understood. Due to the complex and fine structures of the heart, cardiac electrophysiological features of interest may be occluded when there is a necessity to demonstrate cardiac electrophysiological behaviors. To investigate cardiac abnormal electrophysiological features under the pathological condition, in this paper, we implement a human cardiac ischemic model and acquire the electrophysiological data of excitation propagation. A visualization framework is then proposed which integrates a novel depth weighted optic attenuation model into the pathological electrophysiological model. The hidden feature of interest in pathological tissue can be revealed from sophisticated overlapping biophysical information. Experiment results verify the effectiveness of the proposed method for intuitively exploring and inspecting cardiac electrophysiological activities, which is fundamental in analyzing and explaining biophysical mechanisms of cardiac functions for doctors and medical staff.

  7. Depth Attenuation Degree Based Visualization for Cardiac Ischemic Electrophysiological Feature Exploration

    PubMed Central

    Liu, Lei; Zuo, Wangmeng; Zhang, Henggui

    2016-01-01

    Although heart researches and acquirement of clinical and experimental data are progressively open to public use, cardiac biophysical functions are still not well understood. Due to the complex and fine structures of the heart, cardiac electrophysiological features of interest may be occluded when there is a necessity to demonstrate cardiac electrophysiological behaviors. To investigate cardiac abnormal electrophysiological features under the pathological condition, in this paper, we implement a human cardiac ischemic model and acquire the electrophysiological data of excitation propagation. A visualization framework is then proposed which integrates a novel depth weighted optic attenuation model into the pathological electrophysiological model. The hidden feature of interest in pathological tissue can be revealed from sophisticated overlapping biophysical information. Experiment results verify the effectiveness of the proposed method for intuitively exploring and inspecting cardiac electrophysiological activities, which is fundamental in analyzing and explaining biophysical mechanisms of cardiac functions for doctors and medical staff. PMID:28004002

  8. 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

  9. Cardiac tissue engineering in magnetically actuated scaffolds

    NASA Astrophysics Data System (ADS)

    Sapir, Yulia; Polyak, Boris; Cohen, Smadar

    2014-01-01

    Cardiac tissue engineering offers new possibilities for the functional and structural restoration of damaged or lost heart tissue by applying cardiac patches created in vitro. Engineering such functional cardiac patches is a complex mission, involving material design on the nano- and microscale as well as the application of biological cues and stimulation patterns to promote cell survival and organization into a functional cardiac tissue. Herein, we present a novel strategy for creating a functional cardiac patch by combining the use of a macroporous alginate scaffold impregnated with magnetically responsive nanoparticles (MNPs) and the application of external magnetic stimulation. Neonatal rat cardiac cells seeded within the magnetically responsive scaffolds and stimulated by an alternating magnetic field of 5 Hz developed into matured myocardial tissue characterized by anisotropically organized striated cardiac fibers, which preserved its features for longer times than non-stimulated constructs. A greater activation of AKT phosphorylation in cardiac cell constructs after applying a short-term (20 min) external magnetic field indicated the efficacy of magnetic stimulation to actuate at a distance and provided a possible mechanism for its action. Our results point to a synergistic effect of magnetic field stimulation together with nanoparticulate features of the scaffold surface as providing the regenerating environment for cardiac cells driving their organization into functionally mature tissue.

  10. Nanomaterials for Cardiac Myocyte Tissue Engineering.

    PubMed

    Amezcua, Rodolfo; Shirolkar, Ajay; Fraze, Carolyn; Stout, David A

    2016-07-19

    Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

  11. Nanomaterials for Cardiac Myocyte Tissue Engineering

    PubMed Central

    Amezcua, Rodolfo; Shirolkar, Ajay; Fraze, Carolyn; Stout, David A.

    2016-01-01

    Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials. PMID:28335261

  12. Cell sheet-based cardiac tissue engineering.

    PubMed

    Matsuura, Katsuhisa; Masuda, Shinako; Shimizu, Tatsuya

    2014-01-01

    Tissue engineering is indispensable for the advancement of regenerative medicine and the development of tissue models. Cell sheet-based method is one the promising strategies for cardiac tissue engineering. To date, cell sheet transplantation using wide variety of cells has been performed for the treatment of various heart diseases. These cell sheet transplantations have shown to ameliorate cardiac dysfunction and improve symptoms of heart failure. Recent progress of the technologies on the layering of cardiac cell sheets accompanied with vascularization and the large scale cultivation system of embryonic stem cell and induced pluripotent stem cell is about to turn the fabrication of thickened human cardiac tissue for transplant and tissue models into reality. Copyright © 2013 Wiley Periodicals, Inc.

  13. Tissue Doppler imaging in cardiac sarcoidosis.

    PubMed

    Smedema, J P

    2008-07-01

    A middle-aged African lady, who presented with ventricular tachycardias, mitral valve regurgitation and congestive heart failure, was diagnosed with cardiac sarcoidosis. Tissue Doppler imaging demonstrated abnormalities suggestive of myocardial scar, which was confirmed by contrast-enhanced cardiac magnetic resonance.

  14. 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. © 2013 Wiley Periodicals, Inc.

  15. Cardiac tissue engineering: state of the art.

    PubMed

    Hirt, Marc N; Hansen, Arne; Eschenhagen, Thomas

    2014-01-17

    The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered cardiac tissues a realistic option and predict that cardiac tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of cardiac tissue engineering for cardiac repair and in vitro testing.

  16. Complicated Electrical Activities in Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Shiau, Yuo-Hsien; Hsueh, Ming-Pin; Hseu, Shu-Shya; Yien, Huey-Wen

    It has become widely accepted that ventricular fibrillation, the most dangerous cardiac arrhythmias, is a major cause of death in the industrialized world. Alternans and conduction block have recently been related to the progression from ventricular tachycardia to ventricular fibrillation. From the point of view in cellular electrophysiology, ventricular tachycardia is the formation of reentrant wave in cardiac tissue. And ventricular fibrillation arises from subsequent breakdown of reentrant wave into multiple drifting and meandering spiral waves. In this paper, we numerically study pulse and vortex dynamics in cardiac tissue. Our numerical results include 1:1 normal sinus rhythm, 2:1 conduction block, complete conduction block, spiral wave, and spiral breakup. All of our numerical findings can be corresponding to clinical measurements in electrocardiogram. Various electrical activities in cardiac tissue will be discussed in detail in the present manuscript.

  17. 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.

  18. 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

  19. Three Dimension Filamentous Human Cardiac Tissue Model

    PubMed Central

    Ma, Zhen; Koo, Sangmo; Finnegan, Micaela A.; Loskill, Peter; Huebsch, Nathaniel; Marks, Natalie C.; Conklin, Bruce R.; Grigoropoulos, Costas P.; Healy, Kevin E.

    2013-01-01

    A human in vitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an in vitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity. PMID:24268663

  20. Dendronized polyaniline nanotubes for cardiac tissue engineering.

    PubMed

    Moura, Renata Mendes; de Queiroz, Alvaro Antonio Alencar

    2011-05-01

    Today, nanobiomaterials represent a very important class of biomaterials because they differ dramatically in their bulk precursors. The properties of these materials are determined by the size and morphology, thus creating a fascinating line in their physicochemical properties. Polyaniline nanotubes (PANINTs) are one of the most promising nanobiomaterials for cardiac tissue engineering applications due to their electroactive properties. The biocompatibility and low hydrophilic properties of PANINTs can be improved by their functionalization with the highly hydrophilic polyglycerol dendrimers (PGLDs). Hydrophilicity plays a fundamental role in tissue regeneration and fundamental forces that govern the process of cell adhesion and proliferation. In this work, the biocompatible properties and cardiomyocyte proliferation onto PANINTs modified by PGLD are described. PGLDs were immobilized onto PANINTs via surface-initiated anionic ring-opening polymerization of glycidol. The microstructure and morphology of PGLD-PANINTs was determined by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively. The cardiac cell growth on the PGLD-PANINTs was investigated. The PGLD-coated PANINTs showed noncytotoxic effects to Chinese hamster ovary cells. It was observed that the application of microcurrent stimulates the differentiation of cardiac cells cultured on PGLD-PANINTs scaffolds. The electroactive and biocompatible results of PGLD-PANINTs observed in this work demonstrate the potential of this nanobiomaterial for the culture of cardiac cells and open the possibility of using this material as a biocompatible electroactive three-dimensional matrix in cardiac tissue engineering.

  1. 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

  2. Mechanostimulation protocols for cardiac tissue engineering.

    PubMed

    Govoni, Marco; Muscari, Claudio; Guarnieri, Carlo; Giordano, Emanuele

    2013-01-01

    Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field.

  3. Mechanostimulation Protocols for Cardiac Tissue Engineering

    PubMed Central

    Govoni, Marco; Muscari, Claudio; Guarnieri, Carlo; Giordano, Emanuele

    2013-01-01

    Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field. PMID:23936858

  4. Modeling bipolar stimulation of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Galappaththige, Suran K.; Gray, Richard A.; Roth, Bradley J.

    2017-09-01

    Unipolar stimulation of cardiac tissue is often used in the design of cardiac pacemakers because of the low current required to depolarize the surrounding tissue at rest. However, the advantages of unipolar over bipolar stimulation are not obvious at shorter coupling intervals when the tissue near the pacing electrode is relatively refractory. Therefore, this paper analyzes bipolar stimulation of cardiac tissue. The strength-interval relationship for bipolar stimulation is calculated using the bidomain model and a recently developed parsimonious ionic current model. The strength-interval curves obtained using different electrode separations and arrangements (electrodes placed parallel to the fibers versus perpendicular to the fibers) indicate that bipolar stimulation results in more complex activation patterns compared to unipolar stimulation. An unusually low threshold stimulus current is observed when the electrodes are close to each other (a separation of 1 mm) because of break excitation. Unlike for unipolar stimulation, anode make excitation is not present during bipolar stimulation, and an abrupt switch from anode break to cathode make excitation can cause dramatic changes in threshold with very small changes in the interval. These results could impact the design of implantable pacemakers and defibrillators.

  5. 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.

  6. Hybrid carbon nanotube-polymer scaffolds for cardiac tissue regeneration

    NASA Astrophysics Data System (ADS)

    Ahadian, Samad; Davenport-Huyer, Locke; Smith, Nathaniel; Radisic, Milica

    2017-02-01

    Due to insufficient supply of heart transplants and limited regenerative ability of heart tissues, cardiac tissue engineering has emerged to restore or regenerate the structure and function of native cardiac tissues. Scaffolds play a major role in fabrication of functional cardiac tissues, providing structural support, biodegradation, and cell affinity. However, currently used scaffolds in cardiac tissue regeneration tend to lack adequate electrical conductivity and favorable mechanical properties. In response to these concerns, carbon nanotubes (CNTs) have been used to enhance electrical and mechanical properties of scaffolds in cardiac tissue engineering. Here, we review different hybrid CNT-biomaterial scaffolds, both natural and synthetic, in cardiac tissue regeneration and their fabrication methods. Furthermore, CNT toxicity is also discussed. We further outline future trends in this research area toward using CNTs as a functional nanomaterial in cardiac tissue engineering.

  7. 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

  8. A Modular Approach to Cardiac Tissue Engineering

    PubMed Central

    Leung, Brendan M.

    2010-01-01

    Functional cardiac tissue was prepared using a modular tissue engineering approach with the goal of creating vascularized tissue. Rat aortic endothelial cells (RAEC) were seeded onto submillimeter-sized modules made of type I bovine collagen supplemented with Matrigel™ (25% v/v) embedded with cardiomyocyte (CM)-enriched neonatal rat heart cells and assembled into a contractile, macroporous, sheet-like construct. Modules (without RAEC) cultured in 10% bovine serum (BS) were more contractile and responsive to external stimulus (lower excitation threshold, higher maximum capture rate, and greater en face fractional area changes) than modules cultured in 10% fetal BS. Incorporating 25% Matrigel in the matrix reduced the excitation threshold and increased the fractional area change relative to collagen only modules (without RAEC). A coculture medium, containing 10% BS, low Mg2+ (0.814 mM), and normal glucose (5.5 mM), was used to maintain RAEC junction morphology (VE-cadherin) and CM contractility, although the responsiveness of CM was attenuated with RAEC on the modules. Macroporous, sheet-like module constructs were assembled by partially immobilizing a layer of modules in alginate gel until day 8, with or without RAEC. RAEC/CM module sheets were electrically responsive; however, like modules with RAEC this responsiveness was attenuated relative to CM-only sheets. Muscle bundles coexpressing cardiac troponin I and connexin-43 were evident near the perimeter of modules and at intermodule junctions. These results suggest the potential of the modular approach as a platform for building vascularized cardiac tissue. PMID:20504074

  9. A modular approach to cardiac tissue engineering.

    PubMed

    Leung, Brendan M; Sefton, Michael V

    2010-10-01

    Functional cardiac tissue was prepared using a modular tissue engineering approach with the goal of creating vascularized tissue. Rat aortic endothelial cells (RAEC) were seeded onto submillimeter-sized modules made of type I bovine collagen supplemented with Matrigel™ (25% v/v) embedded with cardiomyocyte (CM)-enriched neonatal rat heart cells and assembled into a contractile, macroporous, sheet-like construct. Modules (without RAEC) cultured in 10% bovine serum (BS) were more contractile and responsive to external stimulus (lower excitation threshold, higher maximum capture rate, and greater en face fractional area changes) than modules cultured in 10% fetal BS. Incorporating 25% Matrigel in the matrix reduced the excitation threshold and increased the fractional area change relative to collagen only modules (without RAEC). A coculture medium, containing 10% BS, low Mg2+ (0.814mM), and normal glucose (5.5mM), was used to maintain RAEC junction morphology (VE-cadherin) and CM contractility, although the responsiveness of CM was attenuated with RAEC on the modules. Macroporous, sheet-like module constructs were assembled by partially immobilizing a layer of modules in alginate gel until day 8, with or without RAEC. RAEC/CM module sheets were electrically responsive; however, like modules with RAEC this responsiveness was attenuated relative to CM-only sheets. Muscle bundles coexpressing cardiac troponin I and connexin-43 were evident near the perimeter of modules and at intermodule junctions. These results suggest the potential of the modular approach as a platform for building vascularized cardiac tissue.

  10. 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.

  11. Responses of Cardiac Tissue to Simulated Weightlessness

    NASA Technical Reports Server (NTRS)

    Tahimic, Candice; Steczina, Sonette; Terada, Masahiro; Shirazi-Fard, Yasaman; Schreurs, Ann-Sofie; Goukassian, David; Globus, Ruth

    2017-01-01

    Our current study aims to determine the molecular mechanisms that underlie these cardiac changes in response to spaceflight. The central hypothesis of our study is that long duration simulated weightlessness and subsequent recovery causes select and persistent changes in gene expression and oxidative defense-related pathways. In this study, we will first conduct general analyses of three-month old male and female animals, focusing on two key long-duration time points, (i.e. after 90 days of simulated weightlessness (HU) and after 90 days recovery from 90 days of HU. Both rat-specific gene arrays and qPCR will be performed focusing on genes already implicated in oxidative stress responses and cardiac disease. Gene expression analyses will be complemented by biochemical tests of frozen tissue lysates for select markers of oxidative damage.

  12. Tissue Contraction Force Microscopy for Optimization of Engineered Cardiac Tissue

    PubMed Central

    Schaefer, Jeremy A.

    2016-01-01

    We developed a high-throughput screening assay that allows for relative comparison of the twitch force of millimeter-scale gel-based cardiac tissues. This assay is based on principles taken from traction force microscopy and uses fluorescent microspheres embedded in a soft polydimethylsiloxane (PDMS) substrate. A gel-forming cell suspension is simply pipetted onto the PDMS to form hemispherical cardiac tissue samples. Recordings of the fluorescent bead movement during tissue pacing are used to determine the maximum distance that the tissue can displace the elastic PDMS substrate. In this study, fibrin gel hemispheres containing human induced pluripotent stem cell-derived cardiomyocytes were formed on the PDMS and allowed to culture for 9 days. Bead displacement values were measured and compared to direct force measurements to validate the utility of the system. The amplitude of bead displacement correlated with direct force measurements, and the twitch force generated by the tissues was the same in 2 and 4 mg/mL fibrin gels, even though the 2 mg/mL samples visually appear more contractile if the assessment were made on free-floating samples. These results demonstrate the usefulness of this assay as a screening tool that allows for rapid sample preparation, data collection, and analysis in a simple and cost-effective platform. PMID:26538167

  13. 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

  14. 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.

  15. 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

  16. 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

    2016-06-08

    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. Copyright © 2016, American Association for the Advancement of Science.

  17. Snapshot depth sensitive Raman spectroscopy in layered tissues.

    PubMed

    Liu, Wei; Ong, Yi Hong; Yu, Xiao Jun; Ju, Jian; Perlaki, Clint Michael; Liu, Lin Bo; Liu, Quan

    2016-12-12

    Depth sensitive Raman spectroscopy has been shown effective in the detection of depth dependent Raman spectra in layered tissues. However, the current techniques for depth sensitive Raman measurements based on fiber-optic probes suffer from poor depth resolution and significant variation in probe-sample contact. In contrast, those lens based techniques either require the change in objective-sample distance or suffer from slow spectral acquisition. We report a snapshot depth-sensitive Raman technique based on an axicon lens and a ring-to-line fiber assembly to simultaneously acquire Raman signals emitted from five different depths in the non-contact manner without moving any component. A numerical tool was developed to simulate ray tracing and optimize the snapshot depth sensitive setup to achieve the tradeoff between signal collection efficiency and depth resolution for Raman measurements in the skin. Moreover, the snapshot system was demonstrated to be able to acquire depth sensitive Raman spectra from not only transparent and turbid skin phantoms but also from ex vivo pork tissues and in vivo human thumbnails when the excitation laser power was limited to the maximum permissible exposure for human skin. The results suggest the great potential of snapshot depth sensitive Raman spectroscopy in the characterization of the skin and other layered tissues in the clinical setting or other similar applications such as quality monitoring of tablets and capsules in pharmaceutical industry requiring the rapid measurement of depth dependent Raman spectra.

  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. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    DTIC Science & Technology

    2010-10-01

    0701 TITLE: Micro and Nano -mediated 3D Cardiac Tissue Engineering PRINCIPAL INVESTIGATOR: Rashid Bashir, PhD CONTRACTING ORGANIZATION...From - To) 24 Sep 2009 - 23 Sep 2010 4. TITLE AND SUBTITLE Micro and Nano -mediated 3D Cardiac Tissue Engineering 5a. CONTRACT...6. Award Organization: University of Illinois 7. Project Title: Micro and Nano -mediated 3D Cardiac Tissue Engineering 8. Current staff, role and

  20. Heart Regeneration with Embryonic Cardiac Progenitor Cells and Cardiac Tissue Engineering.

    PubMed

    Tian, Shuo; Liu, Qihai; Gnatovskiy, Leonid; Ma, Peter X; Wang, Zhong

    Myocardial infarction (MI) is the leading cause of death worldwide. Recent advances in stem cell research hold great potential for heart tissue regeneration through stem cell-based therapy. While multiple cell types have been transplanted into MI heart in preclinical studies or clinical trials, reduction of scar tissue and restoration of cardiac function have been modest. Several challenges hamper the development and application of stem cell-based therapy for heart regeneration. Application of cardiac progenitor cells (CPCs) and cardiac tissue engineering for cell therapy has shown great promise to repair damaged heart tissue. This review presents an overview of the current applications of embryonic CPCs and the development of cardiac tissue engineering in regeneration of functional cardiac tissue and reduction of side effects for heart regeneration. We aim to highlight the benefits of the cell therapy by application of CPCs and cardiac tissue engineering during heart regeneration.

  1. Cardiac tissue Doppler imaging in sports medicine.

    PubMed

    Krieg, Anne; Scharhag, Jürgen; Kindermann, Wilfried; Urhausen, Axel

    2007-01-01

    The differentiation of training-induced cardiac adaptations from pathological conditions is a key issue in sports cardiology. As morphological features do not allow for a clear delineation of early stages of relevant pathologies, the echocardiographic evaluation of left ventricular function is the technique of first choice in this regard. Tissue Doppler imaging (TDI) is a relatively recent method for the assessment of cardiac function that provides direct, local measurements of myocardial velocities throughout the cardiac cycle. Although it has shown a superior sensitivity in the detection of ventricular dysfunction in clinical and experimental studies, its application in sports medicine is still rare. Besides technical factors, this may be due to a lack in consensus on the characteristics of ventricular function in relevant conditions. For more than two decades there has been an ongoing debate on the existence of a supernormal left ventricular function in athlete's heart. While results from traditional echocardiography are conflicting, TDI studies established an improved diastolic function in endurance-trained athletes with athlete's heart compared with controls.The influence of anabolic steroids on cardiac function also has been investigated by standard echocardiographic techniques with inconsistent results. The only TDI study dealing with this topic demonstrated a significantly impaired diastolic function in bodybuilders with long-term abuse of anabolic steroids compared with strength-trained athletes without abuse of anabolic steroids and controls, respectively.Hypertrophic cardiomyopathy is the most frequent cause of sudden death in young athletes. However, in its early stages, it is difficult to distinguish from athlete's heart. By means of TDI, ventricular dysfunction in hypertrophic cardiomyopathy can be disclosed even before the development of left ventricular hypertrophy. Also, a differentiation of left ventricular hypertrophy due to hypertrophic

  2. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    DTIC Science & Technology

    2009-10-01

    Micro and Nano -mediated 3D Cardiac Tissue Engineering PRINCIPAL INVESTIGATOR:  Rashid Bashir, PhD, PI  Brian Cunningham, PhD, co-PI  Hyunjoon...SUBTITLE Micro and Nano -mediated 3D Cardiac Tissue Engineering 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0701 5c. PROGRAM ELEMENT...Optical  Characterization (Cunningham) Mechano‐Biology  of Cardiac Cells (Saif) Micro / Nano ‐ Medicated  Cardiac Tissue  Engineering Dr. M. Gibb, Head of

  3. Tissue-Engineering for the Study of Cardiac Biomechanics

    PubMed Central

    Ma, Stephen P.; Vunjak-Novakovic, Gordana

    2016-01-01

    The notion that both adaptive and maladaptive cardiac remodeling occurs in response to mechanical loading has informed recent progress in cardiac tissue engineering. Today, human cardiac tissues engineered in vitro offer complementary knowledge to that currently provided by animal models, with profound implications to personalized medicine. We review here recent advances in the understanding of the roles of mechanical signals in normal and pathological cardiac function, and their application in clinical translation of tissue engineering strategies to regenerative medicine and in vitro study of disease. PMID:26720588

  4. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    DTIC Science & Technology

    2011-10-01

    AD_________________ Award Number: W81XWH-08-1-0701 TITLE: Micro and Nano -mediated 3D Cardiac...5a. CONTRACT NUMBER Micro and Nano -mediated 3D Cardiac Tissue Engineering 5b. GRANT NUMBER W81XWH-08-1-0701 5c. PROGRAM ELEMENT NUMBER 6...TATRC-funded Micro and Nano -mediated 3D Cardiac Tissue Engineering is a project of the University of Illinois Center for Nanoscale Science and

  5. Depolarization Diffusion During Weak Suprathreshold Stimulation of Cardiac Tissue

    DTIC Science & Technology

    2001-10-25

    DEPOLARIZATION DIFFUSION DURING WEAK SUPRATHRESHOLD STIMULATION OF CARDIAC TISSUE Vladimir Nikolski, Aleksandre Sambelashvili, and Igor R. Efimov...the depolarized regions. Such an activation pattern appears similar to break activation. The effect of the depolarization diffusion from depolarized...Subtitle Depolarization Diffusion During Weak Suprathreshold Stimulation of Cardiac Tissue Contract Number Grant Number Program Element Number Author(s

  6. 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.

  7. 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.

  8. Engineering Cardiac Muscle Tissue: A Maturating Field of Research.

    PubMed

    Weinberger, Florian; Mannhardt, Ingra; Eschenhagen, Thomas

    2017-04-28

    Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues of different kinds are now generated routinely in many laboratories. Advances in stem cell biology and engineering allow for the generation of constructs that come close to recapitulating the complex structure of heart muscle and might, therefore, be amenable to industrial (eg, drug screening) and clinical (eg, cardiac repair) applications. Whether the more physiological structure of 3-dimensional constructs provides a relevant advantage over standard 2-dimensional cell culture has yet to be shown in head-to-head-comparisons. The present article gives an overview on current strategies of cardiac tissue engineering with a focus on different hydrogel methods and discusses perspectives and challenges for necessary steps toward the real-life application of cardiac tissue engineering for disease modeling, drug development, and cardiac repair. © 2017 American Heart Association, Inc.

  9. 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

  10. Measurement depth enhancement in terahertz imaging of biological tissues.

    PubMed

    Oh, Seung Jae; Kim, Sang-Hoon; Jeong, Kiyoung; Park, Yeonji; Huh, Yong-Min; Son, Joo-Hiuk; Suh, Jin-Suck

    2013-09-09

    We demonstrate the use of a THz penetration-enhancing agent (THz-PEA) to enhance the terahertz (THz) wave penetration depth in tissues. The THz-PEA is a biocompatible material having absorption lower than that of water, and it is easily absorbed into tissues. When using glycerol as a THz-PEA, the peak value of the THz signal which was transmitted through the fresh tissue and reflected by a metal target, was almost doubled compared to that of tissue without glycerol. THz time-of-flight imaging (B-scan) was used to display the sequential glycerol delivery images. Enhancement of the penetration depth was confirmed after an artificial tumor was located below fresh skin. We thus concluded that the THz-PEA technique can potentially be employed to enhance the image contrast of the abnormal lesions below the skin.

  11. Cardiac Tissue Structure, Properties, and Performance: A Materials Science Perspective

    PubMed Central

    Golob, Mark; Moss, Richard L.; Chesler, Naomi C.

    2014-01-01

    From an engineering perspective, many forms of heart disease can be thought of as a reduction in biomaterial performance, in which the biomaterial is the tissue comprising the ventricular wall. In materials science, the structure and properties of a material are recognized to be interconnected with performance. In addition, for most measurements of structure, properties, and performance, some processing is required. Here, we review the current state of knowledge regarding cardiac tissue structure, properties, and performance as well as the processing steps taken to acquire those measurements. Understanding the impact of these factors and their interactions may enhance our understanding of heart function and heart failure. We also review design considerations for cardiac tissue property and performance measurements because, to date, most data on cardiac tissue has been obtained under non-physiological loading conditions. Novel measurement systems that account for these design considerations may improve future experiments and lead to greater insight into cardiac tissue structure, properties, and ultimately performance. PMID:25081385

  12. A critique of impedance measurements in cardiac tissue.

    PubMed

    Plonsey, R; Barr, R C

    1986-01-01

    The specific impedance of cardiac tissue cannot be measured directly. Instead, the investigator obtains voltage and current measurements and places them into a model of the tissue's structure to infer the impedances of elements of the model. If the model fails to describe major aspects of the real tissue, the results may be worthless, although possibly self-consistent. In the literature of impedance measurement in cardiac tissue, only rarely is the model explicitly described; more commonly, the tissue model is adopted implicitly when equations giving the impedance in terms of voltage and current measurements are adopted. This paper examines the series of models that have been used in specific impedance measurements of cardiac tissue and shows how the same or similar measurements can accurately describe tissue impedivity or can lead to significant errors when inadequate models such as isotropic and anisotropic monodomains (although a part of work of historical merit) are used.

  13. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    DTIC Science & Technology

    2012-09-01

    AD_________________ Award Number: W81XWH-08-1-0701 TITLE: Micro and Nano -mediated 3D Cardiac...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Micro and Nano -mediated 3D Cardiac Tissue Engineering 5b. GRANT NUMBER W81XWH-08-1-0701 5c. PROGRAM...ANNUAL REPORT 2011-12 Micro and Nano -mediated

  14. Toxicity of ad lib. overfeeding: effects on cardiac tissue.

    PubMed

    Faine, L A; Diniz, Y S; Almeida, J A; Novelli, E L B; Ribas, B O

    2002-05-01

    The aim of the present study was to determine the effects of ad lib. overfeeding and of dietary restriction (DR) on oxidative stress in cardiac tissue. Lipoperoxide concentrations were decreased and antioxidant enzymes were increased in moderate-DR-fed rats. Severe-DR induced increased lipoperoxide concentrations. Overfeeding increased lipoperoxide levels in cardiac tissue. Total superoxide dismutase (SOD) and Cu-Zn superoxide dismutase (Cu-Zn SOD) activities were decreased in cardiac tissue at 35 days of overfeeding. As no changes in glutathione peroxidase (GSH-Px) were observed in overfed rats, while SOD and Cu-Zn SOD activities were decreased in these animals, it is assumed that superoxide anion is an important intermediate in the toxicity of ad lib. overfeeding. Overfeeding induced alterations in markers of oxidative stress in cardiac tissue.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Excitation wave propagation in a patterned multidomain cardiac tissue

    NASA Astrophysics Data System (ADS)

    Kudryashova, N. N.; Teplenin, A. S.; Orlova, Y. V.; Agladze, K. I.

    2015-06-01

    Electrospun fibrous mats are widely used in the contemporary cardiac tissue engineering as the substrates for growing cardiac cells. The substrate with chaotically oriented nanofibers leads to the growth of cardiac tissue with randomly oriented, but internally morphologically anisotropic clusters or domains. The domain structure affects the stability of the excitation propagation and we studied the stability of the propagating excitation waves versus the average size of the domains and the externally applied excitation rate. In an experimental model based on neonatal rat cardiac tissue monolayers, as well as in the computer simulations, we have found that an increase in domain sizes leads to the decrease in the critical stimulation frequencies, thus evidencing that larger domains are having a higher arrhythmogenic effect.

  2. 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.

  3. 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

  4. Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction.

    PubMed

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

    2015-11-01

    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.

  5. 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

  6. A biophysical model for defibrillation of cardiac tissue.

    PubMed Central

    Keener, J P; Panfilov, A V

    1996-01-01

    We propose a new model for electrical activity of cardiac tissue that incorporates the effects of cellular microstructure. As such, this model provides insight into the mechanism of direct stimulation and defibrillation of cardiac tissue after injection of large currents. To illustrate the usefulness of the model, numerical stimulations are used to show the difference between successful and unsuccessful defibrillation of large pieces of tissue. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 PMID:8874007

  7. Hydrogel based injectable scaffolds for cardiac tissue regeneration.

    PubMed

    Radhakrishnan, Janani; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2014-01-01

    Tissue engineering promises to be an effective strategy that can overcome the lacuna existing in the current pharmacological and interventional therapies and heart transplantation. Heart failure continues to be a major contributor to the morbidity and mortality across the globe. This may be attributed to the limited regeneration capacity after the adult cardiomyocytes are terminally differentiated or injured. Various strategies involving acellular scaffolds, stem cells, and combinations of stem cells, scaffolds and growth factors have been investigated for effective cardiac tissue regeneration. Recently, injectable hydrogels have emerged as a potential candidate among various categories of biomaterials for cardiac tissue regeneration due to improved patient compliance and facile administration via minimal invasive mode that treats complex infarction. This review discusses in detail on the advances made in the field of injectable materials for cardiac tissue engineering highlighting their merits over their preformed counterparts.

  8. 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.

  9. 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.

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

    PubMed

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

    2007-10-05

    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 120ms and increased to approximately 5Hz. 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 cm(2)-size, functional anisotropic cardiac tissue patch.

  11. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. A model of electrical conduction in cardiac tissue including fibroblasts.

    PubMed

    Sachse, Frank B; Moreno, A P; Seemann, G; Abildskov, J A

    2009-05-01

    Fibroblasts are abundant in cardiac tissue. Experimental studies suggested that fibroblasts are electrically coupled to myocytes and this coupling can impact cardiac electrophysiology. In this work, we present a novel approach for mathematical modeling of electrical conduction in cardiac tissue composed of myocytes, fibroblasts, and the extracellular space. The model is an extension of established cardiac bidomain models, which include a description of intra-myocyte and extracellular conductivities, currents and potentials in addition to transmembrane voltages of myocytes. Our extension added a description of fibroblasts, which are electrically coupled with each other and with myocytes. We applied the extended model in exemplary computational simulations of plane waves and conduction in a thin tissue slice assuming an isotropic conductivity of the intra-fibroblast domain. In simulations of plane waves, increased myocyte-fibroblast coupling and fibroblast-myocyte ratio reduced peak voltage and maximal upstroke velocity of myocytes as well as amplitudes and maximal downstroke velocity of extracellular potentials. Simulations with the thin tissue slice showed that inter-fibroblast coupling affected rather transversal than longitudinal conduction velocity. Our results suggest that fibroblast coupling becomes relevant for small intra-myocyte and/or large intra-fibroblast conductivity. In summary, the study demonstrated the feasibility of the extended bidomain model and supports the hypothesis that fibroblasts contribute to cardiac electrophysiology in various manners.

  13. 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

    2015-03-31

    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.

  14. 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

  15. 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.

  16. 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

  17. Cardiac cell culture model as a left ventricle mimic for cardiac tissue generation.

    PubMed

    Nguyen, Mai-Dung; Tinney, Joseph P; Yuan, Fangping; Roussel, Thomas J; El-Baz, Ayman; Giridharan, Guruprasad; Keller, Bradley B; Sethu, Palaniappan

    2013-09-17

    A major challenge in cardiac tissue engineering is the delivery of hemodynamic mechanical cues that play a critical role in the early development and maturation of cardiomyocytes. Generation of functional cardiac tissue capable of replacing or augmenting cardiac function therefore requires physiologically relevant environments that can deliver complex mechanical cues for cardiomyocyte functional maturation. The goal of this work is the development and validation of a cardiac cell culture model (CCCM) microenvironment that accurately mimics pressure-volume changes seen in the left ventricle and to use this system to achieve cardiac cell maturation under conditions where mechanical loads such as pressure and stretch are gradually increased from the unloaded state to conditions seen in vivo. The CCCM platform, consisting of a cell culture chamber integrated within a flow loop was created to accomplish culture of 10 day chick embryonic ventricular cardiomyocytes subject to 4 days of stimulation (10 mmHg, ∼13% stretch at a frequency of 2 Hz). Results clearly show that CCCM conditioned cardiomyocytes accelerate cardiomyocyte structural and functional maturation in comparison to static unloaded controls as evidenced by increased proliferation, alignment of actin cytoskeleton, bundle-like sarcomeric α-actinin expression, higher pacing beat rate at lower threshold voltages, and increased shortening. These results confirm the CCCM microenvironment can accelerate immature cardiac cell structural and functional maturation for potential cardiac regenerative applications.

  18. Mechanisms of unidirectional block in cardiac tissues.

    PubMed Central

    Joyner, R W

    1981-01-01

    We used numerical solutions for cable equations representing nonuniform cardiac strands to investigate possible mechanisms of unidirectional block (UB) of action potential propagation. Because the presence of UB implies spatial asymmetry in some property along the strand, we varied membrane properties (gNa or leakage conductance), cell diameter, or intercellular resistance as functions of distance such that a propagating action potential encountered the parameter changes either gradually or abruptly. For changes in membrane properties there was very little difference in the effects on propagation for the gradual or abrupt encounter; but, for changes in cell diameter or in intercellular resistance, there were large differences leading to the production of UB over a wide range of parameter values. PMID:7260313

  19. 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.

  20. Spatiotemporal Tracking of Cells in Tissue Engineered Cardiac Organoids

    PubMed Central

    Iyer, Rohin K.; Chui, Jane; Radisic, Milica

    2009-01-01

    Cardiac tissue engineering aims to create myocardial patches for repair of defective or damaged native heart muscle. The inclusion of non-myocytes in engineered cardiac tissues has been shown to improve the properties of cardiac tissue compared to tissues engineered from enriched populations of myocytes alone. While attempts to mix non-myocytes (fibroblasts, endothelial cells) with cardiomyocytes have been made, very little is understood about how the tissue properties are affected by varying the respective ratios of the three cell types and how these cells assemble into functional tissues with time. The goal of this study was to investigate the effects of modulating the ratios of the three cell types as well as to spatially and temporally track cardiac tri-cultures of cells. Primary neonatal cardiac fibroblasts and D4T endothelial cells were incubated in 5µM of CellTracker™ Green dye and CellTracker™ Red dye respectively while neonatal cardiomyocytes were labeled with 20µg/mL of DAPI. The non-myocytes were seeded either sequentially (Pre-culture) or simultaneously (Tri-culture) in Matrigel-coated microchannels and allowed to form organoids, as in our previous studies. We also varied the seeding percentage of cardiomyocytes while keeping the total cell number constant in an attempt to improve the functional properties of the organoids. Organoids were imaged on days 1 and 4. Endothelial cells were seen to aggregate into clusters when Simultaneously Tri-cultured with myocytes and fibroblasts, while Pre-cultures contained elongated cells. Functional properties of organoids were improved by increasing the seeding percentage of enriched cardiomyocytes from 40% to 80%. PMID:19235264

  1. Endothelial and cardiac regeneration from adipose tissues.

    PubMed

    Casteilla, Louis; Planat-Bénard, Valérie; Dehez, Stéphanie; De Barros, Sandra; Barreau, Corinne; André, Mireille

    2011-01-01

    For a long time, adipose tissue was only considered for its crucial role in energy balance and associated diseases. The discovery of the presence of immature cells highlights a putative role for these tissues as reservoirs of therapeutic cells. Indeed, since fat pads can be sampled by liposuction under local anesthesia in adult patients, adipose tissue represents a promising source of regenerative cells, particularly in cardiovascular regeneration. Indeed among other potentials, we and others have demonstrated the great angiogenic properties of adipose-derived stromal cells (ASCs) and the existence of peculiar cells, at least in mice, that are able to spontaneously give rise to functional cardiomyocytes. This review deciphers the different steps necessary to isolate, characterize, and manipulate such striking cells.

  2. 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

  3. Patterns of spiral tip motion in cardiac tissues

    NASA Astrophysics Data System (ADS)

    Kim, Dave T.; Kwan, Yvonne; Lee, John J.; Ikeda, Takanori; Uchida, Takumi; Kamjoo, Kamyar; Kim, Young-Hoon; Ong, James J. C.; Athill, Charles A.; Wu, Tsu-Juey; Czer, Lawrence; Karagueuzian, Hrayr S.; Chen, Peng-Sheng

    1998-03-01

    In support of the spiral wave theory of reentry, simulation studies and animal models have been utilized to show various patterns of spiral wave tip motion such as meandering and drifting. However, the demonstration of these or any other patterns in cardiac tissues have been limited. Whether such patterns of spiral tip motion are commonly observed in fibrillating cardiac tissues is unknown, and whether such patterns form the basis of ventricular tachycardia or fibrillation remain debatable. Using a computerized dynamic activation display, 108 episodes of atrial and ventricular tachycardia and fibrillation in isolated and intact canine cardiac tissues, as well as in vitro swine and myopathic human cardiac tissues, were analyzed for patterns of nonstationary, spiral wave tip motion. Among them, 46 episodes were from normal animal myocardium without pharmacological perturbations, 50 samples were from normal animal myocardium, either treated with drugs or had chemical ablation of the subendocardium, and 12 samples were from diseased human hearts. Among the total episodes, 11 of them had obvious nonstationary spiral tip motion with a life span of >2 cycles and with consecutive reentrant paths distinct from each other. Four patterns were observed: (1) meandering with an inward petal flower in 2; (2) meandering with outward petals in 5; (3) irregularly concentric in 3 (core moving about a common center); and (4) drift in 1 (linear core movement). The life span of a single nonstationary spiral wave lasted no more than 7 complete cycles with a mean of 4.6±4.3, and a median of 4.5 cycles in our samples. Conclusion: (1) Patently evident nonstationary spiral waves with long life spans were uncommon in our sample of mostly normal cardiac tissues, thus making a single meandering spiral wave an unlikely major mechanism of fibrillation in normal ventricular myocardium. (2) A tendency toward four patterns of nonstationary spiral tip motion was observed.

  4. [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.

  5. Tissue oxygen saturation and outcome after cardiac surgery.

    PubMed

    Sanders, Julie; Toor, Iqbal Singh; Yurik, Teresa M; Keogh, Bruce E; Mythen, Michael; Montgomery, Hugh E

    2011-03-01

    Cardiopulmonary bypass during cardiac surgery can result in a shortfall in oxygen delivery relative to demand, marked by a decrease in muscle tissue oxygen saturation as blood flow is redistributed to vital organs. Such "tissue shock" might impair postoperative recovery. To determine the association of changes in tissue oxygen saturation with postoperative outcome in cardiac surgery patients. In 74 adults undergoing cardiac surgery, tissue oxygen saturation in the thenar eminence was recorded using near-infrared spectroscopy before and during induction of anesthesia, throughout surgery, and in the intensive care unit until extubation or for a maximum monitoring time of 24 hours. The measurements were related to postoperative outcome. Mean tissue oxygen saturation increased from 81.7% to 88.5% with induction of anesthesia and decreased to 78.9% and 69.9% during surgery and on arrival in the intensive care unit, respectively. Saturation increased to 77.8% by 6 hours after surgery and remained stable. Mean saturation during the first minutes of anesthesia and 20 minutes in the intensive care unit was lower in patients with a postoperative morbidity than in patients without such morbidity on day 15 (81.1% vs 87.6%; P = .04) and on day 3 (72.9% vs 85.5%; P = .009). No associations with other outcome measures were observed. In patients undergoing cardiac surgery, reduced tissue oxygen saturation in the thenar eminence may be associated with poor postoperative outcome. Further studies are needed to confirm these findings and to determine whether measures to improve the balance between oxygen delivery and consumption might improve both tissue oxygen saturation and outcome.

  6. 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.

  7. 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.

  8. Myostatin Regulates Tissue Potency and Cardiac Calcium-Handling Proteins

    PubMed Central

    Jackson, Melissa F.; Li, Naisi

    2014-01-01

    Attenuating myostatin enhances striated muscle growth, reduces adiposity, and improves cardiac contractility. To determine whether myostatin influences tissue potency in a manner that could control such pleiotropic actions, we generated label-retaining mice with wild-type and mstn−/− (Jekyll) backgrounds in which slow-cycling stem, transit-amplifying, and progenitor cells are preferentially labeled by histone 2B/green fluorescent protein. Jekyll mice were born with fewer label-retaining cells (LRCs) in muscle and heart, consistent with increased stem/progenitor cell contributions to embryonic growth of both tissues. Cardiac LRC recruitment from noncardiac sources occurred in both groups, but lasted longer in Jekyll hearts, whereas heightened β-adrenergic sensitivity of mstn−/− hearts was explained by elevated SERCA2a, phospholamban, and β2-adrenergic receptor levels. Jekyll mice were also born with more adipose LRCs despite significantly smaller tissue weights. Reduced adiposity in mstn−/− animals is therefore due to reduced lipid deposition as adipoprogenitor pools appear to be enhanced. By contrast, increased bone densities of mstn−/− mice are likely compensatory to hypermuscularity because LRC counts were similar in Jekyll and wild-type tibia. Myostatin therefore significantly influences the potency of different tissues, not just muscle, as well as cardiac Ca2+-handling proteins. Thus, the pleiotropic phenotype of mstn−/− animals may not be due to enhanced muscle development per se, but also to altered stem/progenitor cell pools that ultimately influence tissue potency. PMID:24517228

  9. Evaluation of telomere length in human cardiac tissues using cardiac quantitative FISH.

    PubMed

    Sharifi-Sanjani, Maryam; Meeker, Alan K; Mourkioti, Foteini

    2017-09-01

    Telomere length has been correlated with various diseases, including cardiovascular disease and cancer. The use of currently available telomere-length measurement techniques is often restricted by the requirement of a large amount of cells (Southern-based techniques) or the lack of information on individual cells or telomeres (PCR-based methods). Although several methods have been used to measure telomere length in tissues as a whole, the assessment of cell-type-specific telomere length provides valuable information on individual cell types. The development of fluorescence in situ hybridization (FISH) technologies enables the quantification of telomeres in individual chromosomes, but the use of these methods is dependent on the availability of isolated cells, which prevents their use with fixed archival samples. Here we describe an optimized quantitative FISH (Q-FISH) protocol for measuring telomere length that bypasses the previous limitations by avoiding contributions from undesired cell types. We have used this protocol on small paraffin-embedded cardiac-tissue samples. This protocol describes step-by-step procedures for tissue preparation, permeabilization, cardiac-tissue pretreatment and hybridization with a Cy3-labeled telomeric repeat complementing (CCCTAA)3 peptide nucleic acid (PNA) probe coupled with cardiac-specific antibody staining. We also describe how to quantify telomere length by means of the fluorescence intensity and area of each telomere within individual nuclei. This protocol provides comparative cell-type-specific telomere-length measurements in relatively small human cardiac samples and offers an attractive technique to test hypotheses implicating telomere length in various cardiac pathologies. The current protocol (from tissue collection to image procurement) takes ∼28 h along with three overnight incubations. We anticipate that the protocol could be easily adapted for use on different tissue types.

  10. Multiscale Determinants of Delayed Afterdepolarization Amplitude in Cardiac Tissue.

    PubMed

    Ko, Christopher Y; Liu, Michael B; Song, Zhen; Qu, Zhilin; Weiss, James N

    2017-05-09

    Spontaneous calcium (Ca) waves in cardiac myocytes underlie delayed afterdepolarizations (DADs) that trigger cardiac arrhythmias. How these subcellular/cellular events overcome source-sink factors in cardiac tissue to generate DADs of sufficient amplitude to trigger action potentials is not fully understood. Here, we evaluate quantitatively how factors at the subcellular scale (number of Ca wave initiation sites), cellular scale (sarcoplasmic reticulum (SR) Ca load), and tissue scale (synchrony of Ca release in populations of myocytes) determine DAD features in cardiac tissue using a combined experimental and computational modeling approach. Isolated patch-clamped rabbit ventricular myocytes loaded with Fluo-4 to image intracellular Ca were rapidly paced during exposure to elevated extracellular Ca (2.7 mmol/L) and isoproterenol (0.25 μmol/L) to induce diastolic Ca waves and subthreshold DADs. As the number of paced beats increased from 1 to 5, SR Ca content (assessed with caffeine pulses) increased, the number of Ca wave initiation sites increased, integrated Ca transients and DADs became larger and shorter in duration, and the latency period to the onset of Ca waves shortened with reduced variance. In silico analysis using a computer model of ventricular tissue incorporating these experimental measurements revealed that whereas all of these factors promoted larger DADs with higher probability of generating triggered activity, the latency period variance and SR Ca load had the greatest influences. Therefore, incorporating quantitative experimental data into tissue level simulations reveals that increased intracellular Ca promotes DAD-mediated triggered activity in tissue predominantly by increasing both the synchrony (decreasing latency variance) of Ca waves in nearby myocytes and SR Ca load, whereas the number of Ca wave initiation sites per myocyte is less important. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. 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.

  12. 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

  13. Fabrication and characterization of bio-engineered cardiac pseudo tissues

    PubMed Central

    Xu, Tao; Baicu, Catalin; Aho, Michael; Zile, Michael; Boland, Thomas

    2014-01-01

    We report to fabricate functional three-dimensional (3D) tissue constructs by using an inkjet based bio-prototyping method. With the use of the modified inkjet printers, contractile cardiac hybrids that exhibit the forms of the 3D rectangular sheet and even the “half heart” (with two connected ventricles) have been fabricated by arranging alternate layers of biocompatible alginate hydrogels and mammalian cardiac cells according to pre-designed 3D patterns. In this study, primary feline adult and H1 cardiomyocytes were used as model cardiac cells. Alginate hydrogels with controlled micro-shell structures were built by spraying cross-linkers in micro drops onto un-gelled alginic acid. The cells remained viable in constructs as thick as 1 cm due to the programmed porosity. Microscopic and macroscopic contractile functions of these cardiomyocytes constructs were observed in vitro. These results suggest that the inkjet bio-prototyping method could be used for hierarchical design of functional cardiac pseudo tissues, balanced with porosity for mass transport and structural support. PMID:20811105

  14. Electrophysiological heterogeneity and stability of reentry in simulated cardiac tissue.

    PubMed

    Xie, F; Qu, Z; Garfinkel, A; Weiss, J N

    2001-02-01

    Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca(2+) current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.

  15. Fabrication and characterization of bio-engineered cardiac pseudo tissues.

    PubMed

    Xu, Tao; Baicu, Catalin; Aho, Michael; Zile, Michael; Boland, Thomas

    2009-09-01

    We report on fabricating functional three-dimensional (3D) tissue constructs using an inkjet based bio-prototyping method. With the use of modified inkjet printers, contractile cardiac hybrids that exhibit the forms of the 3D rectangular sheet and even the 'half heart' (with two connected ventricles) have been fabricated by arranging alternate layers of biocompatible alginate hydrogels and mammalian cardiac cells according to pre-designed 3D patterns. In this study, primary feline adult and H1 cardiomyocytes were used as model cardiac cells. Alginate hydrogels with controlled micro-shell structures were built by spraying cross-linkers in micro-drops onto un-gelled alginic acid. The cells remained viable in constructs as thick as 1 cm due to the programmed porosity. Microscopic and macroscopic contractile functions of these cardiomyocyte constructs were observed in vitro. These results suggest that the inkjet bio-prototyping method could be used for hierarchical design of functional cardiac pseudo tissues, balanced with porosity for mass transport and structural support.

  16. Nuclear morphology and deformation in engineered cardiac myocytes and tissues.

    PubMed

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

    2010-07-01

    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.

  17. 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.

  18. Optical control of excitation waves in cardiac tissue

    PubMed Central

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

    2016-01-01

    In nature, macroscopic excitation waves1,2 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 states2,3. 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 reaction4. 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. PMID:27057206

  19. Overcoming the Roadblocks to Cardiac Cell Therapy Using Tissue Engineering.

    PubMed

    Yanamandala, Mounica; Zhu, Wuqiang; Garry, Daniel J; Kamp, Timothy J; Hare, Joshua M; Jun, Ho-Wook; Yoon, Young-Sup; Bursac, Nenad; Prabhu, Sumanth D; Dorn, Gerald W; Bolli, Roberto; Kitsis, Richard N; Zhang, Jianyi

    2017-08-08

    Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart's contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Model of electrical activity in cardiac tissue under electromagnetic induction.

    PubMed

    Wu, Fuqiang; Wang, Chunni; Xu, Ying; Ma, Jun

    2016-12-01

    Complex electrical activities in cardiac tissue can set up time-varying electromagnetic field. Magnetic flux is introduced into the Fitzhugh-Nagumo model to describe the effect of electromagnetic induction, and then memristor is used to realize the feedback of magnetic flux on the membrane potential in cardiac tissue. It is found that a spiral wave can be triggered and developed by setting specific initials in the media, that is to say, the media still support the survival of standing spiral waves under electromagnetic induction. Furthermore, electromagnetic radiation is considered on this model as external stimuli, it is found that spiral waves encounter breakup and turbulent electrical activities are observed, and it can give guidance to understand the occurrence of sudden heart disorder subjected to heavily electromagnetic radiation.

  1. Model of electrical activity in cardiac tissue under electromagnetic induction.

    PubMed

    Wu, Fuqiang; Wang, Chunni; Xu, Ying; Ma, Jun

    2016-12-23

    Complex electrical activities in cardiac tissue can set up time-varying electromagnetic field. Magnetic flux is introduced into the Fitzhugh-Nagumo model to describe the effect of electromagnetic induction, and then memristor is used to realize the feedback of magnetic flux on the membrane potential in cardiac tissue. It is found that a spiral wave can be triggered and developed by setting specific initials in the media, that is to say, the media still support the survival of standing spiral waves under electromagnetic induction. Furthermore, electromagnetic radiation is considered on this model as external stimuli, it is found that spiral waves encounter breakup and turbulent electrical activities are observed, and it can give guidance to understand the occurrence of sudden heart disorder subjected to heavily electromagnetic radiation.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering.

    PubMed

    Navaei, Ali; Truong, Danh; Heffernan, John; Cutts, Josh; Brafman, David; Sirianni, Rachael W; Vernon, Brent; Nikkhah, Mehdi

    2016-03-01

    Injectable biomaterials offer a non-invasive approach to deliver cells into the myocardial infarct region to maintain a high level of cell retention and viability and initiate the regeneration process. However, previously developed injectable matrices often suffer from low bioactivity or poor mechanical properties. To address this need, we introduced a biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with excellent bioactivity as well as mechanical robustness for cardiac tissue engineering. A unique feature of our work was that we performed extensive in vitro biological analyses to assess the functionalities of cardiomyocytes (CMs) alone and in co-culture with cardiac fibroblasts (CFs) (2:1 ratio) within the hydrogel matrix. The synthesized hydrogel exhibited viscoelastic behavior (storage modulus: 1260 Pa) and necessary water content (75%) to properly accommodate the cardiac cells. The encapsulated cells demonstrated a high level of cell survival (90% for co-culture condition, day 7) and spreading throughout the hydrogel matrix in both culture conditions. A dense network of stained F-actin fibers (∼ 6 × 10(4) μm(2) area coverage, co-culture condition) illustrated the formation of an intact and three dimensional (3D) cell-embedded matrix. Furthermore, immunostaining and gene expression analyses revealed mature phenotypic characteristics of cardiac cells. Notably, the co-culture group exhibited superior structural organization and cell-cell coupling, as well as beating behavior (average ∼ 45 beats per min, co-culture condition, day 7). The outcome of this study is envisioned to open a new avenue for extensive in vitro characterization of injectable matrices embedded with 3D mono- and co-culture of cardiac cells prior to in vivo experiments. In this work, we synthesized a new class of biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with suitable

  7. 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

  8. 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

  9. Effects of regulatory factors on engineered cardiac tissue in vitro.

    PubMed

    Cheng, Mingyu; Park, Hyoungshin; Engelmayr, George C; Moretti, Matteo; Freed, Lisa E

    2007-11-01

    We tested the hypothesis that supplemental regulatory factors can improve the contractile properties and viability of cardiac tissue constructs cultured in vitro. Neonatal rat heart cells were cultured on porous collagen sponges for up to 8 days in basal medium or medium supplemented with insulin-like growth factor-I (IGF), insulin-transferrin-selenium (ITS), platelet-derived growth factor-BB (PDGF), or angiopoietin-1 (ANG). IGF and ITS enhanced contractile properties of the 8-day constructs significantly more than with unsupplemented controls according to contractile amplitude and excitation threshold, and IGF also significantly increased the amount of cardiac troponin-I and enhanced cell viability according to different assays (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and terminal deoxynucleotidyl transferase biotin-2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL)). PDGF significantly increased the contractile amplitude of 4-day constructs and enhanced cell viability according to MTT, LDH, and TUNEL; ANG enhanced cell viability according to the LDH assay. Our results demonstrate that supplemental regulatory molecules can differentially enhance properties of cardiac tissue constructs and imply that these constructs can provide a platform for systematic in vitro studies of the effects of complex stimuli that occur in vivo to improve our basic understanding of cardiogenesis and identify underlying mechanisms that can potentially be exploited to enhance myocardial regeneration.

  10. Cardiac adipose tissue and atrial fibrillation: the perils of adiposity.

    PubMed

    Hatem, Stéphane N; Redheuil, Alban; Gandjbakhch, Estelle

    2016-04-01

    The amount of adipose tissue that accumulates around the atria is associated with the risk, persistence, and severity of atrial fibrillation (AF). A strong body of clinical and experimental evidence indicates that this relationship is not an epiphenomenon but is the result of complex crosstalk between the adipose tissue and the neighbouring atrial myocardium. For instance, epicardial adipose tissue is a major source of adipokines, inflammatory cytokines, or reactive oxidative species, which can contribute to the fibrotic remodelling of the atrial myocardium. Fibro-fatty infiltrations of the subepicardium could also contribute to the functional disorganization of the atrial myocardium. The observation that obesity is associated with distinct structural and functional remodelling of the atria has opened new perspectives of treating AF substrate with aggressive risk factor management. Advances in cardiac imaging should lead to an improved ability to visualize myocardial fat depositions and to localize AF substrates.

  11. 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.

  12. 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 +.

  13. Probing multifractality in depth-resolved refractive index fluctuations in biological tissues using backscattering spectral interferometry

    NASA Astrophysics Data System (ADS)

    Das, Nandan Kumar; Dey, Rajib; Chakraborty, Semanti; Panigrahi, P. K.; Ghosh, Nirmalya

    2016-12-01

    Fourier domain low coherence interferometry is a promising method for quantification of the depth distribution of the refractive index in a layered scattering medium such as biological tissue. Here, we have explored backscattering spectral interferometric measurement in combination with multifractal detrended fluctuation analysis to probe and quantify multifractality in depth distribution of the refractive index in tissue. The depth resolution of the experimental system was validated on model systems comprising of polystyrene microspheres and mica sheet, and was initially tested on turbid collagen layer, the main building blocks of the connective tissue. Following successful evaluation, the method was applied on ex vivo tissues of human cervix. The derived multifractal parameters of depth-resolved index fluctuations of tissue, namely, the generalized Hurst exponent and the width of the singularity spectrum showed interesting differences between tissues having different grades of precancers. The depth-resolved index fluctuations exhibited stronger multifractality with increasing pathological grades, demonstrating its promise as a potential biomarker for precancer detection.

  14. Modeling dynamics in diseased cardiac tissue: Impact of model choice

    NASA Astrophysics Data System (ADS)

    Gokhale, Tanmay A.; Medvescek, Eli; Henriquez, Craig S.

    2017-09-01

    Cardiac arrhythmias have been traditionally simulated using continuous models that assume tissue homogeneity and use a relatively large spatial discretization. However, it is believed that the tissue fibrosis and collagen deposition, which occur on a micron-level, are critical factors in arrhythmogenesis in diseased tissues. Consequently, it remains unclear how well continuous models, which use averaged electrical properties, are able to accurately capture complex conduction behaviors such as re-entry in fibrotic tissues. The objective of this study was to compare re-entrant behavior in discrete microstructural models of fibrosis and in two types of equivalent continuous models, a homogenous continuous model and a hybrid continuous model with distinct heterogeneities. In the discrete model, increasing levels of tissue fibrosis lead to a substantial increase in the re-entrant cycle length which is inadequately reflected in the homogenous continuous models. These cycle length increases appear to be primarily due to increases in the tip path length and to altered restitution behavior, and suggest that it is critical to consider the discrete effects of fibrosis on conduction when studying arrhythmogenesis in fibrotic myocardium. Hybrid models are able to accurately capture some aspects of re-entry and, if carefully tuned, may provide a framework for simulating conduction in diseased tissues with both accuracy and efficiency.

  15. In vivo facial tissue depth for Canadian aboriginal children: a case study from Nova Scotia, Canada.

    PubMed

    Peckmann, Tanya R; Manhein, Mary H; Listi, Ginesse A; Fournier, Michel

    2013-11-01

    This study examines facial tissue depth in Canadian Aboriginal children. Using ultrasound, measurements were taken at 19 points on the faces of 392 individuals aged 3-18 years old. The relationships between tissue thickness, age, and sex were investigated. A positive linear trend may exist between tissue thickness and age for Aboriginal females and males at multiple points. No points show significant differences in facial tissue depth between males and females aged 3-8 years old; seven points show significant differences in facial tissue depth between males and females aged 9-13 years old; and five points show significant differences in facial tissue depth between males and females aged 14-18 years old. Comparisons were made with White Americans and African Nova Scotians. These data can assist in 3-D facial reconstructions and aid in establishing an individual's identity. Previously, no data existed for facial tissue thickness in Canadian Aboriginal populations. © 2013 American Academy of Forensic Sciences.

  16. Engineered cardiac micromodules for the in vitro fabrication of 3D endogenous macro-tissues.

    PubMed

    Totaro, A; Urciuolo, F; Imparato, G; Netti, P A

    2016-05-23

    The in vitro fabrication of an endogenous cardiac muscle would have a high impact for both in vitro studies concerning cardiac tissue physiology and pathology, as well as in vivo application to potentially repair infarcted myocardium. To reach this aim, we engineered a new class of cardiac tissue precursor (CTP), specifically conceived in order to promote the synthesis and the assembly of a cardiac extracellular matrix (ECM). The CTPs were obtained by culturing a mixed cardiac cell population, composed of myocyte and non-myocyte cells, into porous gelatin microspheres in a dynamic bioreactor. By engineering the culture conditions, the CTP developed both beating properties and an endogenous immature cardiac ECM. By following a bottom-up approach, a macrotissue was fabricated by molding and packing the engineered tissue precursor in a maturation chamber. During the macrotissue formation, the tissue precursors acted as cardiac tissue depots by promoting the formation of an endogenous and interconnected cardiac network embedding the cells and the microbeads. The myocytes cell fraction pulled on ECM network and induced its compaction against the internal posts represented by the initial porous microbeads. This reciprocal interplay induced ECM consolidation without the use of external biophysical stimuli by leading to the formation of a beating and endogenous macrotissue. We have thus engineered a new class of cardiac micromodules and show its potential for the fabrication of endogenous cardiac tissue models useful for in vitro studies that involve the cardiac tissue remodeling.

  17. Robots and lasers: the future of cardiac tissue ablation?

    PubMed

    Smith, J Michael

    2006-12-01

    The future of medicine is tied-up in robotics and lasers. We've heard the hype for years, but only in the last 10 years has it actually started to come to fruition that robotic systems are beginning to play a role in surgery. Multiple groups have reported over the past 10 years on increasingly complex cardiac surgical procedures being performed with the aid of robotic systems. With an increasing percentage of atrial fibrillation and with insight that atrial fibrillation results in poor long-term survival, attempts have been made to create a surgical cure. Much work has been done in the past several years to develop a less-invasive surgical option than the standard cut-and-sew Maze to achieve pulmonary vein ablation. Laser is a unique energy source for tissue ablation because it is a form of light. While traditional energy sources focus on applying heat-based elements to the tissue's surface allowing temperature to propagate across the thickness of the tissue laser is an innovative, tissue-specific energy for creating tissue ablation. Copyright 2006 John Wiley & Sons, Ltd.

  18. Optical imaging predicts mechanical properties during decellularization of cardiac tissue.

    PubMed

    Merna, Nick; Robertson, Claire; La, Anh; George, Steven C

    2013-10-01

    Decellularization of xenogeneic hearts offers an acellular, naturally occurring, 3D scaffold that may aid in the development of an engineered human heart tissue. However, decellularization impacts the structural and mechanical properties of the extracellular matrix (ECM), which can strongly influence a cell response during recellularization. We hypothesized that multiphoton microscopy (MPM), combined with image correlation spectroscopy (ICS), could be used to characterize the structural and mechanical properties of the decellularized cardiac matrix in a noninvasive and nondestructive fashion. Whole porcine hearts were decellularized for 7 days by four different solutions of Trypsin and/or Triton. The compressive modulus of the cardiac ECM decreased to < 20% of that of the native tissue in three of the four conditions (range 2-8 kPa); the modulus increased by -150% (range 125-150 kPa) in tissues treated with Triton only. The collagen and elastin content decreased steadily over time for all four decellularization conditions. The ICS amplitude of second harmonic generation (SHG, ASHG) collagen images increased in three of the four decellularization conditions characterized by a decrease in fiber density; the ICS amplitude was approximately constant in tissues treated with Triton only. The ICS ratio (R(SHG), skew) of collagen images increased significantly in the two conditions characterized by a loss of collagen crimping or undulations. The ICS ratio of two-photon fluorescence (TPF, R(TPF)) elastin images decreased in three of the four conditions, but increased significantly in Triton-only treated tissue characterized by retention of densely packed elastin fibers. There were strong linear relationships between both the log of A(SHG) (R(2) = 0.86) and R(TPF) (R(2) = 0.92) with the compressive modulus. Using these variables, a linear model predicts the compressive modulus: E=73.9 × Log(A(SHG))+70.1 × R(TPF) - 131 (R(2) = 0.94). This suggests that the collagen

  19. Modeling Unipolar and Bipolar Stimulation of Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Galappaththige, Suran Kokila

    Out of all non-communicable diseases, heart diseases have become the leading cause of death and disease burden worldwide. Heart diseases describe a variety of circumstances that affect your heart. One common condition is the heart rhythm problem often called an arrhythmia. The rhythmic beating of the human heart can be altered due to various reasons. This inconsistency in beating can lead to a lethal form of arrhythmia that we call ventricular fibrillation. We treat fibrillation by applying an electrical shock to the heart using a unipolar electrode or bipolar electrodes. To build better pace makers and defibrillators, we must understand how the heart responds to an electrical shock. One way to study cardiac arrhythmias is using a mathematical model. The computational biology of the heart is one of the most important recent applications of mathematical modeling in biology. By using mathematical models, we can understand the mechanisms responsible of the heart's electrical behavior. We investigate if the time-independent, inwardly rectifying potassium current through the cell membrane inhibits the hyperpolarization after a stimulus electrical pulse is applied to the resting heart tissue. The inhibition of hyperpolarization is due to long duration stimulus pulses, but not short duration pulses. We also investigate the minimum conditions required for the dip in strength-interval curves using a simple but not so simple parsimonious ionic current model coupled with the bidomain model. Unipolar anodal stimulations still results in the dip in the strength-interval curves and this explains the minimum conditions for this phenomenon to occur. Bipolar stimulation of cardiac tissue using the parsimonious ionic current model revels that the strength-interval curves are sensitive to the separation between electrodes and the electrode orientation relative to the fiber direction. One of the ionic currents in the parsimonious ionic current model mimics the time

  20. An active strain electromechanical model for cardiac tissue.

    PubMed

    Nobile, F; Quarteroni, A; Ruiz-Baier, R

    2012-01-01

    We propose a finite element approximation of a system of partial differential equations describing the coupling between the propagation of electrical potential and large deformations of the cardiac tissue. The underlying mathematical model is based on the active strain assumption, in which it is assumed that there is a multiplicative decomposition of the deformation tensor into a passive and active part holds, the latter carrying the information of the electrical potential propagation and anisotropy of the cardiac tissue into the equations of either incompressible or compressible nonlinear elasticity, governing the mechanical response of the biological material. In addition, by changing from a Eulerian to a Lagrangian configuration, the bidomain or monodomain equations modeling the evolution of the electrical propagation exhibit a nonlinear diffusion term. Piecewise quadratic finite elements are employed to approximate the displacements field, whereas for pressure, electrical potentials and ionic variables are approximated by piecewise linear elements. Various numerical tests performed with a parallel finite element code illustrate that the proposed model can capture some important features of the electromechanical coupling and show that our numerical scheme is efficient and accurate.

  1. Tissue-engineered heart valve: future of cardiac surgery.

    PubMed

    Rippel, Radoslaw A; Ghanbari, Hossein; Seifalian, Alexander M

    2012-07-01

    Heart valve disease is currently a growing problem, and demand for heart valve replacement is predicted to increase significantly in the future. Existing "gold standard" mechanical and biological prosthesis offers survival at a cost of significantly increased risks of complications. Mechanical valves may cause hemorrhage and thromboembolism, whereas biologic valves are prone to fibrosis, calcification, degeneration, and immunogenic complications. A literature search was performed to identify all relevant studies relating to tissue-engineered heart valve in life sciences using the PubMed and ISI Web of Knowledge databases. Tissue engineering is a new, emerging alternative, which is reviewed in this paper. To produce a fully functional heart valve using tissue engineering, an appropriate scaffold needs to be seeded using carefully selected cells and proliferated under conditions that resemble the environment of a natural human heart valve. Bioscaffold, synthetic materials, and preseeded composites are three common approaches of scaffold formation. All available evidence suggests that synthetic scaffolds are the most suitable material for valve scaffold formation. Different cell sources of stem cells were used with variable results. Mesenchymal stem cells, fibroblasts, myofibroblasts, and umbilical blood stem cells are used in vitro tissue engineering of heart valve. Alternatively scaffold may be implanted and then autoseeded in vivo by circulating endothelial progenitor cells or primitive circulating cells from patient's blood. For that purpose, synthetic heart valves were developed. Tissue engineering is currently the only technology in the field with the potential for the creation of tissues analogous to a native human heart valve, with longer sustainability, and fever side effects. Although there is still a long way to go, tissue-engineered heart valves have the capability to revolutionize cardiac surgery of the future.

  2. 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.

  3. 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

  4. Microstructured Cocultures of Cardiac Myocytes and Fibroblasts: A Two-Dimensional In Vitro Model of Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Camelliti, Patrizia; McCulloch, Andrew D.; Kohl, Peter

    2005-06-01

    Cardiac myocytes and fibroblasts are essential elements of myocardial tissue structure and function. In vivo, myocytes constitute the majority of cardiac tissue volume, whereas fibroblasts dominate in numbers. In vitro, cardiac cell cultures are usually designed to exclude fibroblasts, which, because of their maintained proliferative potential, tend to overgrow the myocytes. Recent advances in microstructuring of cultures and cell growth on elastic membranes have greatly enhanced in vitro preservation of tissue properties and offer a novel platform technology for producing more in vivo-like models of myocardium. We used microfluidic techniques to grow two-dimensional structured cardiac tissue models, containing both myocytes and fibroblasts, and characterized cell morphology, distribution, and coupling using immunohistochemical techniques. In vitro findings were compared with in vivo ventricular cyto-architecture. Cardiac myocytes and fibroblasts, cultured on intersecting 30-[mu]m-wide collagen tracks, acquire an in vivo-like phenotype. Their spatial arrangement closely resembles that observed in native tissue: Strands of highly aligned myocytes are surrounded by parallel threads of fibroblasts. In this in vitro system, fibroblasts form contacts with other fibroblasts and myocytes, which can support homogeneous and heterogeneous gap junctional coupling, as observed in vivo. We conclude that structured cocultures of cardiomyocytes and fibroblasts mimic in vivo ventricular tissue organization and provide a novel tool for in vitro research into cardiac electromechanical function.

  5. [Changes of mitogen-activated protein kinase activity in cardiac tissues, Ang II and cardiac hypertrophy in spontaneously hypertensive rats].

    PubMed

    He, K L; Zheng, Q F; Mu, S C; Li, T C; Pang, Y Z; Tang, C S

    1998-10-01

    Mitogen-activated protein kinases (MAPKs) are thought to be critical components in signal transduction pathways in regulation of cell growth and differentiation. The purpose of the present investigation is to study possible involvement of MAPKs in the progress of cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and effects of age on Angiotensin II (Ang II), MAPK activity and cardiac hypertrophy. The animals were divided into three groups: 4 months old WKY rats (n = 8), 4 month old SHRs (n = 8) and 15 month old SHRs (n = 6). Ratio of heart to body weight was measured. Ang II was determined by RIA. MAPK activity in cardiac tissue was assayed by the "in-gel" myelin basic protein phosphorylation. The results show that in comparison with 4 month old WKY rats, Ang II in plasma and cardiac tissues were elevated (216.4%, P < 0.01; 101.2%, P < 0.01) in 4 months old SHRs, while the MAPK activity was increased 107.0% (P < 0.01) with a parallel cardiac hypertrophy (P < 0.01). In comparison with 4 month old SHRs, Ang II and MAPK activity in cardiac tissue of the 15 months old SHRs were decreased (31.3%, P < 0.01; 29.7%, P < 0.05) but the cardiac hypertrophy increased by 38.5% (P < 0.01). MAPK may be involved in the progress of cardiac hypetrophy in SHR and the increased MAPK activity may be partly induced by Ang II.

  6. 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.

  7. 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

  8. Electrically conductive chitosan/carbon scaffolds for cardiac tissue engineering.

    PubMed

    Martins, Ana M; Eng, George; Caridade, Sofia G; Mano, João F; Reis, Rui L; Vunjak-Novakovic, Gordana

    2014-02-10

    In this work, carbon nanofibers were used as doping material to develop a highly conductive chitosan-based composite. Scaffolds based on chitosan only and chitosan/carbon composites were prepared by precipitation. Carbon nanofibers were homogeneously dispersed throughout the chitosan matrix, and the composite scaffold was highly porous with fully interconnected pores. Chitosan/carbon scaffolds had an elastic modulus of 28.1 ± 3.3 KPa, similar to that measured for rat myocardium, and excellent electrical properties, with a conductivity of 0.25 ± 0.09 S/m. The scaffolds were seeded with neonatal rat heart cells and cultured for up to 14 days, without electrical stimulation. After 14 days of culture, the scaffold pores throughout the construct volume were filled with cells. The metabolic activity of cells in chitosan/carbon constructs was significantly higher as compared to cells in chitosan scaffolds. The incorporation of carbon nanofibers also led to increased expression of cardiac-specific genes involved in muscle contraction and electrical coupling. This study demonstrates that the incorporation of carbon nanofibers into porous chitosan scaffolds improved the properties of cardiac tissue constructs, presumably through enhanced transmission of electrical signals between the cells.

  9. Electrically Conductive Chitosan/Carbon Scaffolds for Cardiac Tissue Engineering

    PubMed Central

    2015-01-01

    In this work, carbon nanofibers were used as doping material to develop a highly conductive chitosan-based composite. Scaffolds based on chitosan only and chitosan/carbon composites were prepared by precipitation. Carbon nanofibers were homogeneously dispersed throughout the chitosan matrix, and the composite scaffold was highly porous with fully interconnected pores. Chitosan/carbon scaffolds had an elastic modulus of 28.1 ± 3.3 KPa, similar to that measured for rat myocardium, and excellent electrical properties, with a conductivity of 0.25 ± 0.09 S/m. The scaffolds were seeded with neonatal rat heart cells and cultured for up to 14 days, without electrical stimulation. After 14 days of culture, the scaffold pores throughout the construct volume were filled with cells. The metabolic activity of cells in chitosan/carbon constructs was significantly higher as compared to cells in chitosan scaffolds. The incorporation of carbon nanofibers also led to increased expression of cardiac-specific genes involved in muscle contraction and electrical coupling. This study demonstrates that the incorporation of carbon nanofibers into porous chitosan scaffolds improved the properties of cardiac tissue constructs, presumably through enhanced transmission of electrical signals between the cells. PMID:24417502

  10. 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.

  11. A Protocol for Collecting Human Cardiac Tissue for Research

    PubMed Central

    Blair, Cheavar A.; Haynes, Premi; Campbell, Stuart G.; Chung, Charles; Mitov, Mihail I.; Dennis, Donna; Bonnell, Mark R.; Hoopes, Charles W.; Guglin, Maya; Campbell, Kenneth S.

    2016-01-01

    This manuscript describes a protocol at the University of Kentucky that allows a translational research team to collect human myocardium that can be used for biological research. We have gained a great deal of practical experience since we started this protocol in 2008, and we hope that other groups might be able to learn from our endeavors. To date, we have procured ~4000 samples from ~230 patients. The tissue that we collect comes from organ donors and from patients who are receiving a heart transplant or a ventricular assist device because they have heart failure. We begin our manuscript by describing the importance of human samples in cardiac research. Subsequently, we describe the process for obtaining consent from patients, the cost of running the protocol, and some of the issues and practical difficulties that we have encountered. We conclude with some suggestions for other researchers who may be considering starting a similar protocol. PMID:28042604

  12. 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.

  13. 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.

  14. Changes in IGFs in cardiac tissue following myocardial infarction.

    PubMed

    Matthews, K G; Devlin, G P; Conaglen, J V; Stuart, S P; Mervyn Aitken, W; Bass, J J

    1999-12-01

    We have studied changes in the IGF axis in an ovine model of myocardial infarction (MI), in order to determine the relationship between time-based changes in post-infarct myocardium and IGF levels. IGF localization was studied by immunocytochemistry, production by in situ hybridization, and specific binding by radioligand studies. In surviving tissue, IGF-I peptide localized to cardiomyocytes, with strongest immunostaining at 1 and 2 days post-infarct in the immediate border area adjoining the infarct, where IGF-I mRNA also increased, reaching a maximum at 2 days. Binding of radiolabelled IGF-I in surviving tissue was initially lower than that seen in cardiomyocytes in control myocardium, subsequently increasing to become significantly greater by 6 days post-infarct. In necrotic tissue, IGF-I peptide was still detectable in cardiomyocytes at 0.5 days post-infarct, but had cleared from this area by 1 day, becoming detectable again at 6 days post-infarct in macrophages and fibroblasts infiltrating the repair zone. IGF-I mRNA was not detected in necrotic tissue until 6 days, when probe hybridized to macrophages and fibroblasts. Within the necrotic zone, high levels of radiolabelled IGF-I binding to a combination of receptors and binding proteins were observed in cardiomyocytes in islands of viable tissue located close to the border. Weak immunostaining for IGF-II was observed in cardiomyocytes of the surviving tissue. IGF-II mRNA was not detected in either surviving or necrotic areas. Binding of radiolabelled IGF-II was predominantly to macrophages in both surviving and infarct areas, although as with IGF-I, high levels of binding of radiolabelled IGF-II to a combination of receptors and binding proteins were observed in islands of viable tissue close to the border within the necrotic area. We conclude that, following MI, surviving cardiomyocytes at the infarct border show marked changes in IGF-I localization, production, and specific binding, indicating that the IGF

  15. Tissue diagnostics by depth profiling of optical characteristics using broadband fiber optic interferometry

    NASA Astrophysics Data System (ADS)

    Splinter, Robert; Farahi, Faramarz; Raja, M. Yasin A.; Svenson, Robert H.

    1996-02-01

    A broadband interferometer is used to acquire scattered light as a function of depth in biological media. The `tissue-light-signature' that is obtained by this depth scan can be correlated with the computer simulated light distributions for well defined tissue parameters, and wavelengths of specific interest. In theory, the collimated irradiation of heart tissue, by low coherence light will generate a statistically significant different light signature for respective myocardial tissues, and pathological tissue conditions. Interferometric axial scanning of in vitro myocardial tissues confirmed the statistically significant difference between normal, coagulated myocardium, and aneurysm at the 790 nm wavelength. The scanning depth however is presented limited by the intensity of the illumination and the choice of detection scheme. Identification of the local optical characteristics as a function of depth directly underneath the target zone will provide discrimination between healthy and pathological conditions in addition to real time assessment of laser dosimetry. Theoretically the scanning depth is limited to a maximum of 4 mm. The beam profile of the irradiation source significantly affects the ability to distinguish between certain tissues. Broadband interferometric axial tissue scanning, will provide a tool for an accurate light energy delivery guided by the desired outcome, while being able to verify the appropriate target location, in real time.

  16. Acceleration of cardiac tissue simulation with graphic processing units.

    PubMed

    Sato, Daisuke; Xie, Yuanfang; Weiss, James N; Qu, Zhilin; Garfinkel, Alan; Sanderson, Allen R

    2009-09-01

    In this technical note we show the promise of using graphic processing units (GPUs) to accelerate simulations of electrical wave propagation in cardiac tissue, one of the more demanding computational problems in cardiology. We have found that the computational speed of two-dimensional (2D) tissue simulations with a single commercially available GPU is about 30 times faster than with a single 2.0 GHz Advanced Micro Devices (AMD) Opteron processor. We have also simulated wave conduction in the three-dimensional (3D) anatomic heart with GPUs where we found the computational speed with a single GPU is 1.6 times slower than with a 32-central processing unit (CPU) Opteron cluster. However, a cluster with two or four GPUs is faster than the CPU-based cluster. These results demonstrate that a commodity personal computer is able to perform a whole heart simulation of electrical wave conduction within times that enable the investigators to interact more easily with their simulations.

  17. Thymosin β4 coated nanofiber scaffolds for the repair of damaged cardiac tissue

    PubMed Central

    2014-01-01

    After a cardiac event, proper treatment and care of the damaged tissue is crucial in restoring optimal cardiac function and preventing future cardiac events. Recently, thymosin β4 has been found to play a vital role in cardiac cell health and development by regulating angiogenesis, inflammatory responses, and wound healing. We proposed that defined poly(ϵ-caprolactone) (PCL) nanoscaffolds coated with thymosin β4 could efficiently differentiate murine-derived cardiomyocytes into functioning cardiac tissue. PCL nanoscaffolds were developed through electrospinning technology, and subsequently coated with a thymosin β4 solution. Cardiomyocytes were seeded on coated and uncoated nanoscaffolds and observed for six days via fluorescent and electron microscopy. Our results demonstrated a robust growth and differentiation of cardiomyocytes on coated nanoscaffolds compared with uncoated, showing potential for nanoscaffold-mediated cardiac cell replacement in vivo after an MI or other cardiac event. PMID:24661328

  18. Computer Simulation of Electrical Propagation in Cardiac Tissue

    DTIC Science & Technology

    2001-10-25

    model, that are cardiac action potential models with Hodgkin - Huxley like representation.[2][3] Each simulation models is two dimensional electric...ircuit network model where many electric circuit models of cardiac membrane action potential were connected with electric resistance...controlled the sodium current , IN a , and the potassium current, IK 1 , of the cardiac action potential models and investigated the obtained

  19. On the Feasibility of Depth Profiling of Animal Tissue by Ultrashort Pulse Laser Ablation

    PubMed Central

    Milasinovic, Slobodan; Liu, Yaoming; Bhardwaj, Chhavi; Melvin, Blaze M.T.; Gordon, Robert J.; Hanley, Luke

    2012-01-01

    Experiments were performed to examine the feasibility of MS depth profiling of animal tissue by ~75 fs, 800 nm laser pulses to expose underlying layers of tissue for subsequent MS analysis. Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) was used to analyze phospholipids and proteins from both intact bovine eye lens tissue and tissue ablated by ultrashort laser pulses. Laser desorption postionization (LDPI-MS) with 10.5 eV single photon ionization was also used to analyze cholesterol and other small molecules in the tissue before and after laser ablation. Scanning electron microscopy was applied to examine the ablation patterns in the tissue and estimate the depth of the ablation craters. Ultrashort pulse laser ablation was found able to remove a layer of several tens of micrometers from the surface of eye lens tissue while leaving the underlying tissue relatively undamaged for subsequent MS analysis. MS analysis of cholesterol, phospholipids, peptides, and various unidentified species did not reveal any chemical damage caused by ultrashort pulse laser ablation for analytes smaller than ~6 kDa. However, a drop in intensity of larger protein ions was detected by MALDI-MS following laser ablation. An additional advantage was that ablated tissue displayed up to an order of magnitude higher signal intensities than intact tissue when subsequently analyzed by MS. These results support the use of ultrashort pulse laser ablation in combination with MS analysis to permit depth profiling of animal tissue. PMID:22482364

  20. Depth-sensitive optical spectroscopy for layered tissue measurements (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Liu, Wei; Yu, Xiaojun; Liu, Quan; Liu, Linbo; Ong, Yi Hong

    2017-02-01

    Disease diagnosis based on the visual inspection of the pathological presentations or symptoms on the epithelial tissue such as the skin are subjective and highly depend on the experience of the doctors. Vital diagnostic information for the accurate identification of diseases is usually located underneath the surface and its depth distribution is known to be related to disease progression. Although optical spectroscopic measurements are fast and non-invasive, the accurate retrieval of the depth-specific diagnostic information is complicated by the heterogeneous nature of epithelial tissues. The optical signal measured from a tissue is often the result of averaging from a large tissue volume that mixes information from the region of interest and the surrounding tissue region, especially from the overlaying layers. Our group has developed a series of techniques for depth sensitive optical measurements from such layered tissues. We will first review the earlier development of composite fiber-optic probe, in which the source-detector separation and the angles of source and detector fibers are varied to achieve depth sensitive measurements. Then the more recent development of non-contact axicon lens based probes for depth sensitive fluorescence measurements and the corresponding numerical methods for optimization will be introduced. Finally, the most recently developed snapshot axicon lens based probe that can measure Raman spectra from five different depths at the same time will be discussed. Results from tissue phantoms, ex vivo pork samples and in vivo fingernail measurements will be presented, which indicates the great potential of depth sensitive optical spectroscopy for clinical tissue diagnosis.

  1. 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.

  2. Measurement of optical penetration depth and refractive index of human tissue

    NASA Astrophysics Data System (ADS)

    Xie, Shusen; Li, Hui; Li, Buhong

    2003-01-01

    Experimental techniques for measurement of optical penetration depth and refractive index of human tissue are presented, respectively. Optical penetration depth can be obtained from the measurement of the relative fluence-depth distribution inside the target tissue. The depth of normal and carcinomatous human lung tissues irradiated with the wavelengths of 406.7, 632.8 and 674.4 nm in vitro are respectively determined. In addition, a novel simple method based on total internal reflection for measuring the refractive index of biotissue in vivo is developed, and the refractive indices of skin from people of different age, sex and skin color are measured. Their refractive indices are almost same and the average is 1.533.

  3. Water content distribution imaging of skin tissue using near-infrared camera and measurement depth analysis

    NASA Astrophysics Data System (ADS)

    Arimoto, Hidenobu; Egawa, Mariko

    2013-02-01

    Wavelength-dependent light penetration depth in the measurement of water distribution of the skin tissue is analyzed. Near-infrared (NIR) imaging enables 2-D water content map on the skin tissue because water absorbs light strongly in the NIR region particularly around the wavelengths of 1450 and 1920 nm. However, the depth of the light penetration depends largely on wavelength as the absorption coefficient of water changes considerably in the NIR range. We investigate the measurement depth of the water content mapping with a NIR camera and bandpass filters at the wavelengths of 1300, 1450 and 1920 nm. Analysis is performed with Monte Carlo light scattering simulation adopting the optical parameters which is derived from the depth profile of the water contents measured by the confocal Raman spectroscopy. It is found that the NIR image in 1920 nm gives the highest sensitivity to the water content in the surface layer of the skin tissue.

  4. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

    NASA Astrophysics Data System (ADS)

    Rogozhnikov, Dmitry; O'Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

    2016-12-01

    There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

  6. Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

    PubMed Central

    Rogozhnikov, Dmitry; O’Brien, Paul J.; Elahipanah, Sina; Yousaf , Muhammad N.

    2016-01-01

    There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity. PMID:28008983

  7. Quantitative determination of maximal imaging depth in all-NIR multiphoton microscopy images of thick tissues

    NASA Astrophysics Data System (ADS)

    Sarder, Pinaki; Akers, Walter J.; Sudlow, Gail P.; Yazdanfar, Siavash; Achilefu, Samuel

    2014-02-01

    We report two methods for quantitatively determining maximal imaging depth from thick tissue images captured using all-near-infrared (NIR) multiphoton microscopy (MPM). All-NIR MPM is performed using 1550 nm laser excitation with NIR detection. This method enables imaging more than five-fold deep in thick tissues in comparison with other NIR excitation microscopy methods. In this study, we show a correlation between the multiphoton signal along the depth of tissue samples and the shape of the corresponding empirical probability density function (pdf) of the photon counts. Histograms from this analysis become increasingly symmetric with the imaging depth. This distribution transitions toward the background distribution at higher imaging depths. Inspired by these observations, we propose two independent methods based on which one can automatically determine maximal imaging depth in the all-NIR MPM images of thick tissues. At this point, the signal strength is expected to be weak and similar to the background. The first method suggests the maximal imaging depth corresponds to the deepest image plane where the ratio between the mean and median of the empirical photon-count pdf is outside the vicinity of 1. The second method suggests the maximal imaging depth corresponds to the deepest image plane where the squared distance between the empirical photon-count mean obtained from the object and the mean obtained from the background is greater than a threshold. We demonstrate the application of these methods in all-NIR MPM images of mouse kidney tissues to study maximal depth penetration in such tissues.

  8. Maximum imaging depth of two-photon autofluorescence microscopy in epithelial tissues.

    PubMed

    Durr, Nicholas J; Weisspfennig, Christian T; Holfeld, Benjamin A; Ben-Yakar, Adela

    2011-02-01

    Endogenous fluorescence provides morphological, spectral, and lifetime contrast that can indicate disease states in tissues. Previous studies have demonstrated that two-photon autofluorescence microscopy (2PAM) can be used for noninvasive, three-dimensional imaging of epithelial tissues down to approximately 150 μm beneath the skin surface. We report ex-vivo 2PAM images of epithelial tissue from a human tongue biopsy down to 370 μm below the surface. At greater than 320 μm deep, the fluorescence generated outside the focal volume degrades the image contrast to below one. We demonstrate that these imaging depths can be reached with 160 mW of laser power (2-nJ per pulse) from a conventional 80-MHz repetition rate ultrafast laser oscillator. To better understand the maximum imaging depths that we can achieve in epithelial tissues, we studied image contrast as a function of depth in tissue phantoms with a range of relevant optical properties. The phantom data agree well with the estimated contrast decays from time-resolved Monte Carlo simulations and show maximum imaging depths similar to that found in human biopsy results. This work demonstrates that the low staining inhomogeneity (∼ 20) and large scattering coefficient (∼ 10 mm(-1)) associated with conventional 2PAM limit the maximum imaging depth to 3 to 5 mean free scattering lengths deep in epithelial tissue.

  9. Investigation of reflectance sampling depth in biological tissues for various common illumination/collection configurations.

    PubMed

    Zonios, George

    2014-09-01

    Knowledge of light penetration characteristics is very important in almost all studies in biomedical optics. In this work, the reflectance sampling depth in biological tissues was investigated using Monte Carlo simulations for various common illumination/collection configurations. The analysis shows that the average sampling depth can be described by two simple empirical analytical expressions over the entire typical ranges of absorption and scattering properties relevant to in vivo biological tissue, regardless of the specific illumination/collection configuration details. These results are promising and helpful for the quick, efficient, and accurate design of reflectance studies for various biological tissue applications.

  10. Transmembrane potentials during high voltage shocks in ischemic cardiac tissue.

    PubMed

    Holley, L K; Knisley, S B

    1997-01-01

    Transmembrane, voltage sensitive fluorescent dye (TMF) recording techniques have shown that high voltage shocks (HVS), typically used in defibrillation, produce either hyper- or depolarization of the transmembrane potential (TMP) when delivered in the refractory period of an action potential (AP) in normal cardiac tissue (NT). Further, HVS produce an extension of the AP, which has been hypothesized as a potential mechanism for electrical defibrillation. We examined whether HVS modify TMP of ischemic tissue (IT) in a similar manner. In seven Langendorff rabbit hearts, recordings of APs were obtained in both NT and IT with TMF using di-4-ANEPPS, and diacetylmonoxime (23 microM) to avoid motion artifacts. Local ischemia was produced by occlusion of the LAD, HVS of either biphasic (5 + 5 ms) or (3 + 2 ms) or monophasic shapes (5 ms) were delivered at varying times (20%-90%) of the paced AP. Intracardiac ECG and TMF recordings of the TMP were each amplified, recorded, and digitized at a frequency of 1 kHz. The paced AP in IT was triangular in shape with no obvious phase 3 plateau, typically seen in NT. There was normally a reduced AP amplitude (expressed as fractional fluorescence) in IT (2.6% +/- 1.79%) compared to 3.8% +/- 0.66% in NT, and shortened AP duration (137 +/- 42 vs 171 +/- 11 ms). One hundred-Volt HVS delivered during the refractory period of paced AP in IT in five rabbits, elicited a depolarization response of the TMP with an amplitude up to three times greater than the paced AP. This is in contrast to NT where the 100-V HVS produced hyperpolarization in four hearts, and only a slight depolarization response in one heart. These results suggest that HVS, typically delivered by a defibrillation shock, modify TMPs in a significantly different manner for ischemic cells, which may influence success in defibrillation.

  11. Interaction between spiral and paced waves in cardiac tissue.

    PubMed

    Agladze, Konstantin; Kay, Matthew W; Krinsky, Valentin; Sarvazyan, Narine

    2007-07-01

    For prevention of lethal arrhythmias, patients at risk receive implantable cardioverter-defibrillators, which use high-frequency antitachycardia pacing (ATP) to convert tachycardias to a normal rhythm. One of the suggested ATP mechanisms involves paced-induced drift of rotating waves followed by their collision with the boundary of excitable tissue. This study provides direct experimental evidence of this mechanism. In monolayers of neonatal rat cardiomyocytes in which rotating waves of activity were initiated by premature stimuli, we used the Ca(2+)-sensitive indicator fluo 4 to observe propagating wave patterns. The interaction of the spiral tip with a paced wave was then monitored at a high spatial resolution. In the course of the experiments, we observed spiral wave pinning to local heterogeneities within the myocyte layer. High-frequency pacing led, in a majority of cases, to successful termination of spiral activity. Our data show that 1) stable spiral waves in cardiac monolayers tend to be pinned to local heterogeneities or areas of altered conduction, 2) overdrive pacing can shift a rotating wave from its original site, and 3) the wave break, formed as a result of interaction between the spiral tip and a paced wave front, moves by a paced-induced drift mechanism to an area where it may become unstable or collide with a boundary. The data were complemented by numerical simulations, which was used to further analyze experimentally observed behavior.

  12. Interaction between spiral and paced waves in cardiac tissue

    PubMed Central

    Agladze, Konstantin; Kay, Matthew W.; Krinsky, Valentin; Sarvazyan, Narine

    2010-01-01

    For prevention of lethal arrhythmias, patients at risk receive implantable cardioverter-defibrillators, which use high-frequency antitachycardia pacing (ATP) to convert tachycardias to a normal rhythm. One of the suggested ATP mechanisms involves paced-induced drift of rotating waves followed by their collision with the boundary of excitable tissue. This study provides direct experimental evidence of this mechanism. In monolayers of neonatal rat cardiomyocytes in which rotating waves of activity were initiated by premature stimuli, we used the Ca2+-sensitive indicator fluo 4 to observe propagating wave patterns. The interaction of the spiral tip with a paced wave was then monitored at a high spatial resolution. In the course of the experiments, we observed spiral wave pinning to local heterogeneities within the myocyte layer. High-frequency pacing led, in a majority of cases, to successful termination of spiral activity. Our data show that 1) stable spiral waves in cardiac monolayers tend to be pinned to local heterogeneities or areas of altered conduction, 2) overdrive pacing can shift a rotating wave from its original site, and 3) the wave break, formed as a result of interaction between the spiral tip and a paced wave front, moves by a paced-induced drift mechanism to an area where it may become unstable or collide with a boundary. The data were complemented by numerical simulations, which was used to further analyze experimentally observed behavior. PMID:17384124

  13. Accordion-like honeycombs for tissue engineering of cardiac anisotropy

    NASA Astrophysics Data System (ADS)

    Engelmayr, George C.; Cheng, Mingyu; Bettinger, Christopher J.; Borenstein, Jeffrey T.; Langer, Robert; Freed, Lisa E.

    2008-12-01

    Tissue-engineered grafts may be useful in myocardial repair; however, previous scaffolds have been structurally incompatible with recapitulating cardiac anisotropy. Here, we use microfabrication techniques to create an accordion-like honeycomb microstructure in poly(glycerol sebacate), which yields porous, elastomeric three-dimensional (3D) scaffolds with controllable stiffness and anisotropy. Accordion-like honeycomb scaffolds with cultured neonatal rat heart cells demonstrated utility through: (1) closely matched mechanical properties compared to native adult rat right ventricular myocardium, with stiffnesses controlled by polymer curing time; (2) heart cell contractility inducible by electric field stimulation with directionally dependent electrical excitation thresholds (p<0.05) and (3) greater heart cell alignment (p<0.0001) than isotropic control scaffolds. Prototype bilaminar scaffolds with 3D interconnected pore networks yielded electrically excitable grafts with multi-layered neonatal rat heart cells. Accordion-like honeycombs can thus overcome principal structural-mechanical limitations of previous scaffolds, promoting the formation of grafts with aligned heart cells and mechanical properties more closely resembling native myocardium.

  14. Low Energy Defibrillation in Human Cardiac Tissue: A Simulation Study

    PubMed Central

    Morgan, Stuart W.; Plank, Gernot; Biktasheva, Irina V.; Biktashev, Vadim N.

    2009-01-01

    We aim to assess the effectiveness of feedback-controlled resonant drift pacing as a method for low energy defibrillation. Antitachycardia pacing is the only low energy defibrillation approach to have gained clinical significance, but it is still suboptimal. Low energy defibrillation would avoid adverse side effects associated with high voltage shocks and allow the application of implantable cardioverter defibrillator (ICD) therapy, in cases where such therapy is not tolerated today. We present results of computer simulations of a bidomain model of cardiac tissue with human atrial ionic kinetics. Reentry was initiated and low energy shocks were applied with the same period as the reentry, using feedback to maintain resonance. We demonstrate that such stimulation can move the core of reentrant patterns, in the direction that depends on the location of the electrodes and the time delay in the feedback. Termination of reentry is achieved with shock strength one-order-of-magnitude weaker than in conventional single-shock defibrillation. We conclude that resonant drift pacing can terminate reentry at a fraction of the shock strength currently used for defibrillation and can potentially work where antitachycardia pacing fails, due to the feedback mechanisms. Success depends on a number of details that these numerical simulations have uncovered. PMID:19217854

  15. Cardiac tissue development for delivery of embryonic stem cell-derived endothelial and cardiac cells in natural matrices.

    PubMed

    Turner, William S; Wang, Xiaoling; Johnson, Scott; Medberry, Christopher; Mendez, Jose; Badylak, Stephen F; McCord, Marian G; McCloskey, Kara E

    2012-11-01

    The packaging and delivery of cells for cardiac regeneration has been explored using a variety biomaterials and delivery methods, but these studies often ignore one or more important design factors critical for rebuilding cardiac tissue. These include the biomaterial architecture, strength and stiffness, cell alignment, and/or incorporation of multiple cell types. In this article, we explore the combinatorial use of decellularized tissues, moldable hydrogels, patterned cell-seeding, and cell-sheet engineering and find that a combination of these methods is optimal in the recreation of transplantable cardiac-like tissue in vivo. We show that decellularized urinary bladder matrix (UBM), that is compliant and suturable, supports the survival of cell cultures but does not allow maintenance of cell-to-cell contacts of transferred cell-sheets (presumably, due to its rough surface). Moreover, the UBM material must be filled with hyaluronan (HA) hydrogels for smoothing rough surfaces and allowing the delivery of greater cell numbers. We additionally incorporated our previously developed "wrinkled" microchip for inducing alignment of cardiac cells with a laser-etched mask for co-seeding patterned "channels" of cells. This article also introduces a novel method of plasma coating for cell-sheet engineering that compares well with electron bean irradiation methods and may be combined with our "wrinkled" surfaces to facilitate the alignment of cardiac cells into sheets. Our data shows that an optimal design for generating cardiac tissue would include (1) decellularized matrix seeded with endothelial cells in a HA layered with (2) prealigned cardiac cell-sheets fabricated using our "wrinkled" microchips and thermo-responsive polymer [poly(N-isopropylacrylamide)] cell sheet transfer system.

  16. 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.

  17. Tubular Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells Generate Pulse Pressure In Vivo

    PubMed Central

    Seta, Hiroyoshi; Matsuura, Katsuhisa; Sekine, Hidekazu; Yamazaki, Kenji; Shimizu, Tatsuya

    2017-01-01

    Human induced pluripotent stem (iPS) cell-derived cardiac cells provide the possibility to fabricate cardiac tissues for transplantation. However, it remains unclear human bioengineered cardiac tissues function as a functional pump in vivo. Human iPS cells induced to cardiomyocytes in suspension were cultured on temperature-responsive dishes to fabricate cardiac cell sheets. Two pairs of triple-layered sheets were transplanted to wrap around the inferior vena cava (IVC) of nude rats. At 4 weeks after transplantation, inner pressure changes in the IVC were synchronized with electrical activations of the graft. Under 80 pulses per minute electrical stimulation, the inner pressure changes at 8 weeks increased to 9.1 ± 3.2 mmHg, which were accompanied by increases in the baseline inner pressure of the IVC. Immunohistochemical analysis revealed that 0.5-mm-thick cardiac troponin T-positive cardiac tissues, which contained abundant human mitochondria, were clearly engrafted lamellar around the IVC and surrounded by von Willebrand factor-positive capillary vessels. The mRNA expression of several contractile proteins in cardiac tissues at 8 weeks in vivo was significantly upregulated compared with those at 4 weeks. We succeeded in generating pulse pressure by tubular human cardiac tissues in vivo. This technology might lead to the development of a bioengineered heart assist pump. PMID:28358136

  18. Photon path depth in tissue phantoms: a comparison of visible and near-infrared (NIR) wavelengths

    NASA Astrophysics Data System (ADS)

    Asplund, Karin M.; Schenkman, Kenneth A.; Ciesielski, Wayne A.; Arakaki, Lorilee S. L.

    2014-03-01

    Optical spectroscopy is being used increasingly in medical applications to noninvasively investigate tissues below the skin. In order to assure adequate sampling of tissues underlying the skin, photon penetration depth must be known. Photon penetration in tissues has been studied with near-infrared (NIR) light, but experimental study of visible light propagation in tissue has been limited. In this study, a micro-motion system coupled with a reflectance spectroscopy system was used to determine the penetration depth of visible-range and NIR photons (535-800 nm) in phantoms composed of Intralipid and hemoglobin. An absorbing target was placed at intervals of 0.1mm along a 15mm line perpendicular to and bisecting the line between the ends of the source and detector optical fiber bundles. Comparisons between detected light intensities at different target positions were used to determine the most probable photon path depths at 576 nm and at 760 nm. Scattering coefficients, hemoglobin concentrations, and source-detector separations were varied to evaluate their effects on the penetration depth of photons. Results from phantoms containing Intralipid only showed that the most-probable penetration depth at 576 nm was comparable to that at 760 nm. Larger sourcedetector separations resulted in deeper photon penetration depths for both spectral regions. Changes in scattering over a 4-fold range did not affect the photon path depth appreciably. In the presence of hemoglobin with a source-detector separation of 13 mm, the most probable depth of photon penetration in the visible range was greater than 2.5 mm, and was within 1 mm of the most probable depth of photon penetration in the NIR. This study demonstrates the feasibility of using the visible and NIR regions in transcutaneous reflectance spectroscopy.

  19. 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.

  20. Quantitative assessment of brain microvascular and tissue oxygenation during cardiac arrest and resuscitation in pigs.

    PubMed

    Yu, J; Ramadeen, A; Tsui, A K Y; Hu, X; Zou, L; Wilson, D F; Esipova, T V; Vinogradov, S A; Leong-Poi, H; Zamiri, N; Mazer, C D; Dorian, P; Hare, G M T

    2013-07-01

    Cardiac arrest is associated with a very high rate of mortality, in part due to inadequate tissue perfusion during attempts at resuscitation. Parameters such as mean arterial pressure and end-tidal carbon dioxide may not accurately reflect adequacy of tissue perfusion during cardiac resuscitation. We hypothesised that quantitative measurements of tissue oxygen tension would more accurately reflect adequacy of tissue perfusion during experimental cardiac arrest. Using oxygen-dependent quenching of phosphorescence, we made measurements of oxygen in the microcirculation and in the interstitial space of the brain and muscle in a porcine model of ventricular fibrillation and cardiopulmonary resuscitation. Measurements were performed at baseline, during untreated ventricular fibrillation, during resuscitation and after return of spontaneous circulation. After achieving stable baseline brain tissue oxygen tension, as measured using an Oxyphor G4-based phosphorescent microsensor, ventricular fibrillation resulted in an immediate reduction in all measured parameters. During cardiopulmonary resuscitation, brain oxygen tension remained unchanged. After the return of spontaneous circulation, all measured parameters including brain oxygen tension recovered to baseline levels. Muscle tissue oxygen tension followed a similar trend as the brain, but with slower response times. We conclude that measurements of brain tissue oxygen tension, which more accurately reflect adequacy of tissue perfusion during cardiac arrest and resuscitation, may contribute to the development of new strategies to optimise perfusion during cardiac resuscitation and improve patient outcomes after cardiac arrest.

  1. Tissue Doppler characterization of cardiac phenotype in mouse.

    PubMed

    Fayssoil, Abdallah

    2009-10-01

    Mice allow biologists to study various genes playing a role in cardiac function and pathophysiological situations. Echocardiography is a non-invasive tool for assessing cardiac phenotype. Because of load dependence of conventional parameters (left ventricular shortening fraction, left ventricular ejection fraction and mitral pulsed Doppler), we have to perform Doppler tissular velocity imaging and strain imaging for the characterization of cardiomyopathies mice models.

  2. Porous nanofibrous poly(L-lactic acid) scaffolds supporting cardiovascular progenitor cells for cardiac tissue engineering.

    PubMed

    Liu, Qihai; Tian, Shuo; Zhao, Chao; Chen, Xin; Lei, Ienglam; Wang, Zhong; Ma, Peter X

    2015-10-01

    Myocardial infarction (MI) is the irreversible necrosis of heart with approximately 1.5 million cases every year in the United States. Tissue engineering offers a promising strategy for cardiac repair after MI. However, the optimal cell source for heart tissue regeneration and the ideal scaffolds to support cell survival, differentiation, and integration, remain to be developed. To address these issues, we developed the technology to induce cardiovascular progenitor cells (CPCs) derived from mouse embryonic stem cells (ESCs) towards desired cardiomyocytes as well as smooth muscle cells and endothelial cells. We fabricated extracellular matrix (ECM)-mimicking nanofibrous poly(l-lactic acid) (PLLA) scaffolds with porous structure of high interconnection for cardiac tissue formation. The CPCs were seeded into the scaffolds to engineer cardiac constructs in vitro. Fluorescence staining and RT-PCR assay showed that the scaffolds facilitated cell attachment, extension, and differentiation. Subcutaneous implantation of the cell/scaffold constructs in a nude mouse model showed that the scaffolds favorably supported survival of the grafted cells and their commitment to the three desired lineages in vivo. Thus, our study suggested that the porous nanofibrous PLLA scaffolds support cardiac tissue formation from CPCs. The integration of CPCs with the nanofibrous PLLA scaffolds represents a promising tissue engineering strategy for cardiac repair. Myocardial infarction is the irreversible necrosis of heart with approximately 1.5 million cases every year in the United States. Tissue engineering offers a promising strategy for cardiac repair after MI. However, the optimal cell source for heart tissue regeneration and the ideal scaffolds to support cell survival, differentiation, and integration, remain to be developed. To address these issues, we developed porous nanofibrous PLLA scaffolds that mimic natural extracellular matrix to support cardiac tissue formation from CPCs. The

  3. Transitory ventricular tachycardia associated with influenza A infection of cardiac conduction tissue.

    PubMed

    Frustaci, Andrea; Petrosillo, Nicola; Ippolito, Giuseppe; Chimenti, Cristina

    2016-06-01

    To describe the influence of cardiac conduction tissue infection by Influenza A virus. A 54-year-old man with non-sustained ventricular tachycardia underwent noninvasive and invasive cardiac studies including left ventricular endomyocardial biopsy (LVEMB). Non-invasive studies showed normal cardiac parameters with no signal abnormalities. LVEMB revealed an influenza virus focal myocarditis with inflammatory infiltration of conduction tissue. Non-invasive studies showed normal cardiac parameters with preserved bi-ventricular function. CMR failed to show signal abnormalities including edema and areas of late-gadolinium enhancement. Endomyocardial biopsy (EMB) revealed an influenza virus focal lymphocytic myocarditis. Biopsy samples included sections of conduction tissue with inflammatory infiltration and cell necrosis. Therapy with oseltamivir was followed by disappearance of electrical instability at ECG and Holter monitoring. Acute myocarditis in its arrhythmic phenotype is probably characterized by a significant inflammation of conduction tissue. Antiviral agents have an actually underestimated and potentially more contributive therapeutic role.

  4. 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

  5. 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

  6. 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

  7. Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues

    PubMed Central

    Liau, Brian; Jackman, Christopher P.; Li, Yanzhen; Bursac, Nenad

    2017-01-01

    We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium. The functional improvements in mESC-CM + fetal CF patches were associated with differences in structural remodeling and increased expression of proteins involved in cardiac function. To determine role of paracrine signaling, we cultured pure mESC-CMs within miniature tissue “micro-patches” supplemented with media conditioned by adult or fetal CFs. Fetal CF-conditioned media distinctly enhanced CM spreading and contractile activity, which was shown by pathway inhibitor experiments and Western blot analysis to be mediated via MEK-ERK signaling. In mESC-CM monolayers, CF-conditioned media did not alter CM spreading or MEK-ERK activation. Collectively, our studies show that 3D co-culture of mESC-CMs with embryonic CFs is superior to co-culture with adult CFs for in vitro generation of functional myocardium. Ensuring consistent developmental stages of cardiomyocytes and supporting non-myocytes may be a critical factor for promoting functional maturation of engineered cardiac tissues. PMID:28181589

  8. 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

  9. What is the optimal chest compression depth during out-of-hospital cardiac arrest resuscitation of adult patients?

    PubMed

    Stiell, Ian G; Brown, Siobhan P; Nichol, Graham; Cheskes, Sheldon; Vaillancourt, Christian; Callaway, Clifton W; Morrison, Laurie J; Christenson, James; Aufderheide, Tom P; Davis, Daniel P; Free, Cliff; Hostler, Dave; Stouffer, John A; Idris, Ahamed H

    2014-11-25

    The 2010 American Heart Association guidelines suggested an increase in cardiopulmonary resuscitation compression depth with a target >50 mm and no upper limit. This target is based on limited evidence, and we sought to determine the optimal compression depth range. We studied emergency medical services-treated out-of-hospital cardiac arrest patients from the Resuscitation Outcomes Consortium Prehospital Resuscitation Impedance Valve and Early Versus Delayed Analysis clinical trial and the Epistry-Cardiac Arrest database. We calculated adjusted odds ratios for survival to hospital discharge, 1-day survival, and any return of circulation. We included 9136 adult patients from 9 US and Canadian cities with a mean age of 67.5 years, mean compression depth of 41.9 mm, and a return of circulation of 31.3%, 1-day survival of 22.8%, and survival to hospital discharge of 7.3%. For survival to discharge, the adjusted odds ratios were 1.04 (95% CI, 1.00-1.08) for each 5-mm increment in compression depth, 1.45 (95% CI, 1.20-1.76) for cases within 2005 depth range (>38 mm), and 1.05 (95% CI, 1.03-1.08) for percentage of minutes in depth range (10% change). Covariate-adjusted spline curves revealed that the maximum survival is at a depth of 45.6 mm (15-mm interval with highest survival between 40.3 and 55.3 mm) with no differences between men and women. This large study of out-of-hospital cardiac arrest patients demonstrated that increased cardiopulmonary resuscitation compression depth is strongly associated with better survival. Our adjusted analyses, however, found that maximum survival was in the depth interval of 40.3 to 55.3 mm (peak, 45.6 mm), suggesting that the 2010 American Heart Association cardiopulmonary resuscitation guideline target may be too high. http://www.clinicaltrials.gov. Unique identifier: NCT00394706. © 2014 American Heart Association, Inc.

  10. 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.

  11. 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

  12. 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.

  13. Effects of mechanical stimulation induced by compression and medium perfusion on cardiac tissue engineering.

    PubMed

    Shachar, Michal; Benishti, Nessi; Cohen, Smadar

    2012-01-01

    Cardiac tissue engineering presents a challenge due to the complexity of the muscle tissue and the need for multiple signals to induce tissue regeneration in vitro. We investigated the effects of compression (1 Hz, 15% strain) combined with fluid shear stress (10(-2) -10(-1) dynes/cm(2) ) provided by medium perfusion on the outcome of cardiac tissue engineering. Neonatal rat cardiac cells were seeded in Arginine-Glycine-Aspartate (RGD)-attached alginate scaffolds, and the constructs were cultivated in a compression bioreactor. A daily, short-term (30 min) compression (i.e., "intermittent compression") for 4 days induced the formation of cardiac tissue with typical striation, while in the continuously compressed constructs (i.e., "continuous compression"), the cells remained spherical. By Western blot, on day 4 the expression of the gap junction protein connexin 43 was significantly greater in the "intermittent compression" constructs and the cardiomyocyte markers (α-actinin and N-cadherin) showed a trend of better preservation compared to the noncompressed constructs. This regime of compression had no effect on the proliferation of nonmyocyte cells, which maintained low expression level of proliferating cell nuclear antigen. Elevated secretion levels of basic fibroblast growth factor and transforming growth factor-β in the daily, intermittently compressed constructs likely attributed to tissue formation. Our study thus establishes the formation of an improved cardiac tissue in vitro, when induced by combined mechanical signals of compression and fluid shear stress provided by perfusion.

  14. 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.

  15. Optimized preservation of extracellular matrix in cardiac tissues: implications for long-term graft durability.

    PubMed

    Schenke-Layland, Katja; Xie, Jiansong; Heydarkhan-Hagvall, Sepideh; Hamm-Alvarez, Sarah F; Stock, Ulrich A; Brockbank, Kelvin G M; MacLellan, W Robb

    2007-05-01

    Cryopreservation of human tissues, particularly heart valves, is widespread in clinical practice although the effects of this process on underlying tissue structures and its potential impact on valve durability have been poorly studied. Multiphoton imaging and second-harmonic generation (SHG) microscopy permit high-resolution, noninvasive analysis of living tissues at a subcellular level. In the present study we used these novel imaging modalities to compare the effects of vitreous and frozen cryopreservation on the extracellular matrix (ECM) of cardiac tissues. Conventional histology, electron microscopy, and multiphoton imaging to obtain autofluorescence and SHG images were performed on cardiac tissues to characterize the ECM in fresh, vitrified, and frozen cryopreserved tissues. Autofluorescence and particularly SHG images revealed that conventional frozen cryopreservation of cardiac valves, when compared with fresh or vitrified tissues, leads to the loss of normal ECM structures in valve leaflets. Similar results were found in all other cardiac tissues suggesting that structural deterioration of the ECM is a common consequence of frozen cryopreservation. Our results demonstrate that conventional cryopreservation, when compared with fresh or vitrified tissues, causes more destruction of normal ECM structure, which might contribute to eventual graft dysfunction. Whether vitrification preservation will translate into greater durability or less valve failure will need to be determined.

  16. Cardiac tissue Doppler and tissue velocity imaging in anesthetized New Zealand white rabbits.

    PubMed

    Pelosi, Augusta; St John, Linda; Gaymer, Jean; Ferguson, Danielle; Goyal, Sandeep K; Abela, George S; Rubinstein, Jack

    2011-05-01

    New Zealand white rabbits are commonly used in cardiovascular research. Complete echocardiographic examination of the heart includes the evaluation of tissue Doppler (TDI) parameters, yet normal data are unavailable for rabbits. In addition, tissue velocity imaging (TV) is a potentially useful measure of myocardial function that has not yet been applied to rabbits. Anesthetized New Zealand white rabbits (n = 31) underwent echocardiography to establish the feasibility of performing TDI and TV and establishing corresponding reference values. Standard 2D, M-mode, and Doppler measurements were obtained in all rabbits and showed values comparable to previously published data. Interpretable TDI images were obtained in all 31 rabbits and TV in 24 of 31 rabbits. The values obtained were similar to those seen in healthy cats and are comparable to the values found in adult humans. TDI and TV can easily be added to standard echocardiographic evaluation in rabbits. The values from the current study, obtained in normal rabbits, can be used as reference values to improve characterization of cardiac disease in this species.

  17. Cardiac Tissue Doppler and Tissue Velocity Imaging in Anesthetized New Zealand White Rabbits

    PubMed Central

    Pelosi, Augusta; John, Linda St; Gaymer, Jean; Ferguson, Danielle; Goyal, Sandeep K; Abela, George S; Rubinstein, Jack

    2011-01-01

    New Zealand white rabbits are commonly used in cardiovascular research. Complete echocardiographic examination of the heart includes the evaluation of tissue Doppler (TDI) parameters, yet normal data are unavailable for rabbits. In addition, tissue velocity imaging (TV) is a potentially useful measure of myocardial function that has not yet been applied to rabbits. Anesthetized New Zealand white rabbits (n = 31) underwent echocardiography to establish the feasibility of performing TDI and TV and establishing corresponding reference values. Standard 2D, M-mode, and Doppler measurements were obtained in all rabbits and showed values comparable to previously published data. Interpretable TDI images were obtained in all 31 rabbits and TV in 24 of 31 rabbits. The values obtained were similar to those seen in healthy cats and are comparable to the values found in adult humans. TDI and TV can easily be added to standard echocardiographic evaluation in rabbits. The values from the current study, obtained in normal rabbits, can be used as reference values to improve characterization of cardiac disease in this species. PMID:21640025

  18. Laser photothermoacoustic heterodyned lock-in depth profilometry in turbid tissue phantoms.

    PubMed

    Fan, Ying; Mandelis, Andreas; Spirou, Gloria; Vitkin, I Alex; Whelan, William M

    2005-11-01

    Frequency-domain correlation and spectral analysis photothermoacoustic (FD-PTA) imaging is a promising new technique, which is being developed to detect tumor masses in turbid biological tissue. Unlike conventional biomedical photoacoustics which uses time-of-flight acoustic information induced by a pulsed laser to indicate the tumor size and location, in this research, a new FD-PTA instrument featuring frequency sweep (chirp) and heterodyne modulation and lock-in detection of a continuous-wave laser source at wavelength is constructed and tested for its depth profilometric capabilities with regard to turbid media imaging. Owing to the linear relationship between the depth of acoustic signal generation and the delay time of signal arrival to the transducer, information specific to a particular depth can be associated with a particular frequency in the chirp signal. Scanning laser-fluence modulation frequencies with a linear frequency sweep method preserves the depth-to-delay time linearity and recovers FD-PTA signals from a range of depths. Combining with the depth information carried by the back-propagated acoustic chirp signal at each scanning position, one could rapidly generate subsurface three-dimensional images of the scanning area at optimal signal-to-noise ratios and low laser fluences, a combination of tasks that is difficult or impossible by use of pulsed photoacoustic detection. In this paper, results of PTA scans performed on tissue mimicking control phantoms with various optical, acoustical, and geometrical properties are presented. A mathematical model is developed to study the laser-induced photothermoacoustic waves in turbid media. The model includes both the scattering and absorption properties of the turbid medium. A good agreement is obtained between the experimental and numerical results. It is concluded that frequency domain photothermoacoustics using a linear frequency sweep method and heterodyne lock-in detection has the potential to be a

  19. [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.

  20. 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

  1. Connective Tissue Growth Factor Regulates Cardiac Function and Tissue Remodeling in a Mouse Model of Dilated Cardiomyopathy

    PubMed Central

    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.

    2015-01-01

    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 function 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 were 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. PMID:26549358

  2. Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function.

    PubMed

    Liau, Brian; Christoforou, Nicolas; Leong, Kam W; Bursac, Nenad

    2011-12-01

    Recent advances in pluripotent stem cell research have provided investigators with potent sources of cardiogenic cells. However, tissue engineering methodologies to assemble cardiac progenitors into aligned, 3-dimensional (3D) myocardial tissues capable of physiologically relevant electrical conduction and force generation are lacking. In this study, we introduced 3D cell alignment cues in a fibrin-based hydrogel matrix to engineer highly functional cardiac tissues from genetically purified mouse embryonic stem cell-derived cardiomyocytes (CMs) and cardiovascular progenitors (CVPs). Procedures for CM and CVP derivation, purification, and functional differentiation in monolayer cultures were first optimized to yield robust intercellular coupling and maximize velocity of action potential propagation. A versatile soft-lithography technique was then applied to reproducibly fabricate engineered cardiac tissues with controllable size and 3D architecture. While purified CMs assembled into a functional 3D syncytium only when supplemented with supporting non-myocytes, purified CVPs differentiated into cardiomyocytes, smooth muscle, and endothelial cells, and autonomously supported the formation of functional cardiac tissues. After a total culture time similar to period of mouse embryonic development (21 days), the engineered cardiac tissues exhibited unprecedented levels of 3D organization and functional differentiation characteristic of native neonatal myocardium, including: 1) dense, uniformly aligned, highly differentiated and electromechanically coupled cardiomyocytes, 2) rapid action potential conduction with velocities between 22 and 25 cm/s, and 3) significant contractile forces of up to 2 mN. These results represent an important advancement in stem cell-based cardiac tissue engineering and provide the foundation for exploiting the exciting progress in pluripotent stem cell research in the future tissue engineering therapies for heart disease. Copyright © 2011

  3. Experimental evidence for deeper interrogation inside cardiac tissue using transillumination and a fluorescence absorber

    NASA Astrophysics Data System (ADS)

    Ramshesh, Venkat K.; Knisley, Stephen B.

    2006-02-01

    Limited optical interrogation depth prevents studies of arrhythmias in 3D tissue. Our experiments with single photon excitation and computer simulations with single and two-photon excitation show that the addition of a fluorescence absorber can modify the region of tissue interrogated with transillumination. Experiments were performed with a pair of 0.1 cm thick rabbit cardiac slices. The slices were excited with 488 nm single photon laser excitation while light from opposite side was collected for transillumination. One slice was stained with di-4-ANEPPS while the other was not. In different measurements, both slices were also stained with the red light absorbing dye, blue 1. In our models fluorescent photons were launched from specific regions of the tissue to mimic staining of different layers with di-4-ANEPPS. In additional simulations the fluorescence absorption coefficient was increased 3-fold. In our experiments with the di-4-ANEPPS slice facing away from the laser, measured light intensity was 68% of the value found with di-4-ANEPPS slice facing the laser while it was 21% in the model. This reduction in intensity from the deeper layer became less pronounced after addition of the red absorber. Then with di-4-ANEPPS slice facing away from the laser the measured light intensity was 81% of the value found with di-4-ANEPPS slice facing the laser in experiments while it was 34% in the model. This indicates deepening of the interrogated region by addition of red absorbing dye. In computer simulations using two-photon excitation at 1064 nm, increasing the fluorescence absorption further deepend the interrogated region compared with one photon excitation at 488 nm.

  4. Stem cells for cardiac regeneration by cell therapy and myocardial tissue engineering.

    PubMed

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

    2009-01-01

    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.

  5. 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

  6. 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.

  7. 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

  8. Early postnatal rat ventricle resection leads to long‐term preserved cardiac function despite tissue hypoperfusion

    PubMed Central

    Zogbi, Camila; Saturi de Carvalho, Ana E. T.; Nakamuta, Juliana S.; Caceres, Viviane de M.; Prando, Silvana; Giorgi, Maria C. P.; Rochitte, Carlos E.; Meneghetti, Jose C.; Krieger, Jose E.

    2014-01-01

    Abstract One‐day‐old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long‐term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End‐Diastolic Pressure–Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long‐term preservation of cardiac function despite tissue hypoperfusion. PMID:25168870

  9. 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.

  10. Modeling and incorporating cardiac-induced lung tissue motion in a breathing motion model

    PubMed Central

    White, Benjamin M.; Santhanam, Anand; Thomas, David; Min, Yugang; Lamb, James M.; Neylon, Jack; Jani, Shyam; Gaudio, Sergio; Srinivasan, Subashini; Ennis, Daniel; Low, Daniel A.

    2014-01-01

    Purpose: The purpose of this work is to develop a cardiac-induced lung motion model to be integrated into an existing breathing motion model. Methods: The authors’ proposed cardiac-induced lung motion model represents the lung tissue's specific response to the subject's cardiac cycle. The model is mathematically defined as a product of a converging polynomial function h of the cardiac phase (c) and the maximum displacement \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\smash{\\mathord{\\buildrel{\\lower3pt\\hbox{\\scriptscriptstyle\\rightharpoonup}}\\over \\gamma } ( {\\mathord{\\buildrel{\\lower3pt\\hbox{\\scriptscriptstyle\\rightharpoonup}}\\over X} _0 } )}\\end{document}γ⇀(X⇀0) of each voxel (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\smash{\\mathord{\\buildrel{\\lower3pt\\hbox{\\scriptscriptstyle\\rightharpoonup}}\\over X} _0 }\\end{document}X⇀0) among all the cardiac phases. The function h(c) was estimated from cardiac-gated MR imaging of ten healthy volunteers using an Akaike Information Criteria optimization algorithm. For each volunteer, a total of 24 short-axis and 18 radial planar views were acquired on a 1.5 T MR scanner during a series of 12–15 s breath-hold maneuvers. Each view contained 30 temporal frames of equal time-duration beginning with the end-diastolic cardiac phase. The frames in each of the planar views were resampled to create a set of three-dimensional (3D) anatomical volumes representing thoracic anatomy at different cardiac phases. A 3D multiresolution optical flow deformable image registration algorithm was used to quantify the difference

  11. Human Thymus Mesenchymal Stromal Cells Augment Force Production in Self-Organized Cardiac Tissue

    PubMed Central

    Sondergaard, Claus S.; Hodonsky, Chani J.; Khait, Luda; Shaw, John; Sarkar, Bedabrata; Birla, Ravi; Bove, Edward; Nolta, Jan; Si, Ming-Sing

    2011-01-01

    Background Mesenchymal stromal cells have been recently isolated from thymus gland tissue discarded after surgical procedures. The role of this novel cell type in heart regeneration has yet to be defined. The purpose of this study was to evaluate the therapeutic potential of human thymus-derived mesenchymal stromal cells using self-organized cardiac tissue as an in vitro platform for quantitative assessment. Methods Mesenchymal stromal cells were isolated from discarded thymus tissue from neonates undergoing heart surgery and were incubated in differentiation media to demonstrate multipotency. Neonatal rat cardiomyocytes self-organized into cardiac tissue fibers in a custom culture dish either alone or in combination with varying numbers of mesenchymal stromal cells. A transducer measured force generated by spontaneously contracting self-organized cardiac tissue fibers. Work and power outputs were calculated from force tracings. Immunofluorescence was performed to determine the fate of the thymus-derived mesenchymal stromal cells. Results Mesenchymal stromal cells were successfully isolated from discarded thymus tissue. After incubation in differentiation media, mesenchymal stromal cells attained the expected phenotypes. Although mesenchymal stromal cells did not differentiate into mature cardiomyocytes, addition of these cells increased the rate of fiber formation, force production, and work and power outputs. Self-organized cardiac tissue containing mesenchymal stromal cells acquired a defined microscopic architecture. Conclusions Discarded thymus tissue contains mesenchymal stromal cells, which can augment force production and work and power outputs of self-organized cardiac tissue fibers by several-fold. These findings indicate the potential utility of mesenchymal stromal cells in treating heart failure. PMID:20732499

  12. Tissue-Specific Cell Cycle Indicator Reveals Unexpected Findings for Cardiac Myocyte Proliferation

    PubMed Central

    Hirai, Maretoshi; Chen, Ju; Evans, Sylvia M.

    2017-01-01

    Rationale Discerning cardiac myocyte cell cycle behavior is challenging owing to commingled cell types with higher proliferative activity. Objective To investigate cardiac myocyte cell cycle activity in development and the early postnatal period. Methods and Results To facilitate studies of cell type–specific proliferation, we have generated tissue-specific cell cycle indicator BAC transgenic mouse lines. Experiments using embryonic fibroblasts from CyclinA2-LacZ-floxed-EGFP, or CyclinA2-EGFP mice, demonstrated that CyclinA2-βgal and CyclinA2-EGFP were expressed from mid-G1 to mid-M phase. Using Troponin T-Cre;CyclinA2-LacZ-EGFP mice, we examined cardiac myocyte cell cycle activity during embryogenesis and in the early postnatal period. Our data demonstrated that right ventricular cardiac myocytes exhibited reduced cell cycle activity relative to left ventricular cardiac myocytes in the immediate perinatal period. Additionally, in contrast to a recent report, we could find no evidence to support a burst of cardiac myocyte cell cycle activity at postnatal day 15. Conclusions Our data highlight advantages of a cardiac myocyte–specific cell cycle reporter for studies of cardiac myocyte cell cycle regulation. PMID:26472817

  13. Technical note: An algorithm to calculate the tissue phantom ratio from depth dose in radiosurgery.

    PubMed

    Ramos Garcia, Luis Isaac; Almansa, Julio F

    2011-05-01

    To propose a method to calculate the tissue phantom ratio (TPR) using the depth dose and to compare the proposed method with two other methods. An analytical dose model from Bjärngard was used to describe the depth dose and the TPR. The parameters of the model were derived from depth dose measurements, which were then used to calculate the TPR. The calculated TPR values were compared with actual measurements as well as with TPR values predicted from two methods that also use depth dose, namely, the method proposed by BrainLAB and the conventional method that sets the quotients of the scatter phantom ratios (Sp) to 1. TPR values calculated from the proposed algorithm deviated by -0.2 +/- 0.1% (mean deviation) from the experimental measurements, over a range of field sizes and depths. The results of the proposed method were in better agreement with the experimental measurements than were results using the other two methods. Furthermore, the differences between the proposed method and the other methods are statistically significant.

  14. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Colliding jets provide depth control for water jetting in bone tissue.

    PubMed

    den Dunnen, S; Dankelman, J; Kerkhoffs, G M; Tuijthof, G

    2017-08-01

    In orthopaedic surgery, water jet drilling provides several advantages over classic drilling with rigid drilling bits, such as the always sharp cut, absence of thermal damage and increased manoeuvrability. Previous research showed that the heterogeneity of bone tissue can cause variation in drilling depth whilst water jet drilling. To improve control over the drilling depth, a new method is tested consisting of two water jets that collide directly below the bone surface. The expected working principle is that after collision the jets will disintegrate, with the result of eliminating the destructive power of the coherent jets and leaving the bone tissue underneath the focal point intact. To assess the working principle of colliding water jets (CWJ), the influence of inhomogeneity of the bone tissue on the variation of the drilling depth and the impact of jet time (twj) on the drilling depth were compared to a single water jet (SWJ) with a similar power. 98 holes were drilled in 14 submerged porcine tali with two conditions CWJ (impact angle of 30° and 90°) and SWJ. The water pressure was 70MPa for all conditions. The water jet diameter was 0.3 mm for CWJ and 0.4 mm for SWJ. twj was set at 1, 3, 5 and 8s. Drilling depth and hole diameter were measured using microCT scans. A non-parametric Levene's test was performed to assess a significant difference in variance between conditions SWJ and CWJ. A regression analysis was used to determine differences in influence of twj on the drilling depth. Hole diameter differences were assessed using a one way Anova. A significance level of p<0.05 was set. Condition CWJ significantly decreases the drilling depth variance caused by the heterogeneity of the bone when compared to SWJ. The mean depth for CWJ was 0.9 mm (SD 0.3 mm) versus 4.8 mm (SD 2.0) for SWJ. twj affects the drilling depth less for condition CWJ (p<0.01, R(2)=0.30) than for SWJ (p<0.01, R(2)=0.46). The impact angle (30° or 90°) of the CWJ does not influence the

  16. Reentrant excitation in an analog-digital hybrid circuit model of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Mahmud, Farhanahani; Shiozawa, Naruhiro; Makikawa, Masaaki; Nomura, Taishin

    2011-06-01

    We propose an analog-digital hybrid circuit model of one-dimensional cardiac tissue with hardware implementation that allows us to perform real-time simulations of spatially conducting cardiac action potentials. Each active nodal compartment of the tissue model is designed using analog circuits and a dsPIC microcontroller, by which the time-dependent and time-independent nonlinear current-voltage relationships of six types of ion channel currents employed in the Luo-Rudy phase I (LR-I) model for a single mammalian cardiac ventricular cell can be reproduced quantitatively. Here, we perform real-time simulations of reentrant excitation conduction in a ring-shaped tissue model that includes eighty nodal compartments. In particular, we show that the hybrid tissue model can exhibit real-time dynamics for initiation of reentries induced by uni-directional block, as well as those for phase resetting that leads to annihilation of the reentry in response to impulsive current stimulations at appropriate nodes and timings. The dynamics of the hybrid model are comparable to those of a spatially distributed tissue model with LR-I compartments. Thus, it is conceivable that the hybrid model might be a useful tool for large scale simulations of cardiac tissue dynamics, as an alternative to numerical simulations, leading toward further understanding of the reentrant mechanisms.

  17. Biophysical stimulation for in vitro engineering of functional cardiac tissues.

    PubMed

    Korolj, Anastasia; Wang, Erika Yan; Civitarese, Robert A; Radisic, Milica

    2017-07-01

    Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  18. In-depth proteomic profiling of left ventricular tissues in human end-stage dilated cardiomyopathy

    PubMed Central

    Liu, Shanshan; Xia, Yan; Liu, Xiaohui; Wang, Yi; Chen, Zhangwei; Xie, Juanjuan; Qian, Juying; Shen, Huali; Yang, Pengyuan

    2017-01-01

    Dilated cardiomyopathy (DCM) is caused by reduced left ventricular (LV) myocardial function, which is one of the most common causes of heart failure (HF). We performed iTRAQ-coupled 2D-LC-MS/MS to profile the cardiac proteome of LV tissues from healthy controls and patients with end-stage DCM. We identified 4263 proteins, of which 125 were differentially expressed in DCM tissues compared to LV controls. The majority of these were membrane proteins related to cellular junctions and neuronal metabolism. In addition, these proteins were involved in membrane organization, mitochondrial organization, translation, protein transport, and cell death process. Four key proteins involved in the cell death process were also detected by western blotting, indicated that cell death was activated in DCM tissues. Furthermore, S100A1 and eEF2 were enriched in the “cellular assembly and organization” and “cell cycle” networks, respectively. We verified decreases in these two proteins in end-stage DCM LV samples through multiple reaction monitoring (MRM). These observations demonstrate that our understanding of the mechanisms underlying DCM can be deepened through comparison of the proteomes of normal LV tissues with that from end-stage DCM in humans. PMID:28427148

  19. Incorporating inductances in tissue-scale models of cardiac electrophysiology

    NASA Astrophysics Data System (ADS)

    Rossi, Simone; Griffith, Boyce E.

    2017-09-01

    In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and we examine the effect of intracellular and extracellular inductances on the virtual electrode phenomenon.

  20. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

    PubMed Central

    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  1. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct.

    PubMed

    Valarmathi, Mani T; Fuseler, John W; Davis, Jeffrey M; Price, Robert L

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.

  2. Mathematical models based on transfer functions to estimate tissue temperature during RF cardiac ablation in real time.

    PubMed

    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.

  3. Moldable elastomeric polyester-carbon nanotube scaffolds for cardiac tissue engineering.

    PubMed

    Ahadian, Samad; Davenport Huyer, Locke; Estili, Mehdi; Yee, Bess; Smith, Nathaniel; Xu, Zhensong; Sun, Yu; Radisic, Milica

    2017-04-01

    Polymer biomaterials are used to construct scaffolds in tissue engineering applications to assist in mechanical support, organization, and maturation of tissues. Given the flexibility, electrical conductance, and contractility of native cardiac tissues, it is desirable that polymeric scaffolds for cardiac tissue regeneration exhibit elasticity and high electrical conductivity. Herein, we developed a facile approach to introduce carbon nanotubes (CNTs) into poly(octamethylene maleate (anhydride) 1,2,4-butanetricarboxylate) (124 polymer), and developed an elastomeric scaffold for cardiac tissue engineering that provides electrical conductivity and structural integrity to 124 polymer. 124 polymer-CNT materials were developed by first dispersing CNTs in poly(ethylene glycol) dimethyl ether porogen and mixing with 124 prepolymer for molding into shapes and crosslinking under ultraviolet light. 124 polymers with 0.5% and 0.1% CNT content (wt) exhibited improved conductivity against pristine 124 polymer. With increasing the CNT content, surface moduli of hybrid polymers were increased, while their bulk moduli were decreased. Furthermore, increased swelling of hybrid 124 polymer-CNT materials was observed, suggesting their improved structural support in an aqueous environment. Finally, functional characterization of engineered cardiac tissues using the 124 polymer-CNT scaffolds demonstrated improved excitation threshold in materials with 0.5% CNT content (3.6±0.8V/cm) compared to materials with 0% (5.1±0.8V/cm) and 0.1% (5.0±0.7V/cm), suggesting greater tissue maturity. 124 polymer-CNT materials build on the advantages of 124 polymer elastomer to give a versatile biomaterial for cardiac tissue engineering applications. Achieving a high elasticity and a high conductivity in a single cardiac tissue engineering material remains a challenge. We report the use of CNTs in making electrically conductive and mechanically strong polymeric scaffolds in cardiac tissue regeneration

  4. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation.

    PubMed

    Fujiu, Katsuhito; Shibata, Munehiko; Nakayama, Yukiteru; Ogata, Fusa; Matsumoto, Sahohime; Noshita, Koji; Iwami, Shingo; Nakae, Susumu; Komuro, Issei; Nagai, Ryozo; Manabe, Ichiro

    2017-05-01

    Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells. Cell-cell interactions among activated CD cells, tissue macrophages and endothelial cells within the kidney led to secretion of the cytokine CSF2, which in turn stimulated cardiac-resident Ly6C(lo) macrophages, which are essential for the myocardial adaptive response to pressure overload. The renal response to cardiac pressure overload was disrupted by renal sympathetic denervation, adrenergic β2-receptor blockade or CD-cell-specific deficiency of the transcription factor KLF5. Moreover, we identified amphiregulin as an essential cardioprotective mediator produced by cardiac Ly6C(lo) macrophages. Our results demonstrate a dynamic interplay between the heart, brain and kidneys that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages and the sympathetic nervous system.

  5. Negative filament tension in the Luo-Rudy model of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Alonso, S.; Panfilov, A. V.

    2007-03-01

    Scroll waves are vortices that occur in three-dimensional excitable media. Scroll waves have been observed in a variety of systems including cardiac tissue, where they are associated with cardiac arrhythmias. The disorganization of scroll waves into chaotic behavior is thought to be the mechanism of ventricular fibrillation, which lethality is widely known. One of the possible mechanisms of scroll wave instability is negative filament tension, which was studied theoretically using low-dimensional models of excitable medium. In this article we perform a numerical study of negative filament tension using the Luo-Rudy phase 1 model, which is widely used in cardiac electrophysiology. We show that this instability exists in this model, study its manifestation and discuss its relation to cardiac arrhythmogenesis.

  6. 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.

  7. PGS:Gelatin Nanofibrous Scaffolds with Tunable Mechanical and Structural Properties for Engineering Cardiac Tissues

    PubMed Central

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

    2013-01-01

    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 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 mimics 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. PMID:23747008

  8. Chromatic confocal microscopy for multi-depth imaging of epithelial tissue

    PubMed Central

    Olsovsky, Cory; Shelton, Ryan; Carrasco-Zevallos, Oscar; Applegate, Brian E.; Maitland, Kristen C.

    2013-01-01

    We present a novel chromatic confocal microscope capable of volumetric reflectance imaging of microstructure in non-transparent tissue. Our design takes advantage of the chromatic aberration of aspheric lenses that are otherwise well corrected. Strong chromatic aberration, generated by multiple aspheres, longitudinally disperses supercontinuum light onto the sample. The backscattered light detected with a spectrometer is therefore wavelength encoded and each spectrum corresponds to a line image. This approach obviates the need for traditional axial mechanical scanning techniques that are difficult to implement for endoscopy and susceptible to motion artifact. A wavelength range of 590-775 nm yielded a >150 µm imaging depth with ~3 µm axial resolution. The system was further demonstrated by capturing volumetric images of buccal mucosa. We believe these represent the first microstructural images in non-transparent biological tissue using chromatic confocal microscopy that exhibit long imaging depth while maintaining acceptable resolution for resolving cell morphology. Miniaturization of this optical system could bring enhanced speed and accuracy to endomicroscopic in vivo volumetric imaging of epithelial tissue. PMID:23667789

  9. Chromatic confocal microscopy for multi-depth imaging of epithelial tissue.

    PubMed

    Olsovsky, Cory; Shelton, Ryan; Carrasco-Zevallos, Oscar; Applegate, Brian E; Maitland, Kristen C

    2013-05-01

    We present a novel chromatic confocal microscope capable of volumetric reflectance imaging of microstructure in non-transparent tissue. Our design takes advantage of the chromatic aberration of aspheric lenses that are otherwise well corrected. Strong chromatic aberration, generated by multiple aspheres, longitudinally disperses supercontinuum light onto the sample. The backscattered light detected with a spectrometer is therefore wavelength encoded and each spectrum corresponds to a line image. This approach obviates the need for traditional axial mechanical scanning techniques that are difficult to implement for endoscopy and susceptible to motion artifact. A wavelength range of 590-775 nm yielded a >150 µm imaging depth with ~3 µm axial resolution. The system was further demonstrated by capturing volumetric images of buccal mucosa. We believe these represent the first microstructural images in non-transparent biological tissue using chromatic confocal microscopy that exhibit long imaging depth while maintaining acceptable resolution for resolving cell morphology. Miniaturization of this optical system could bring enhanced speed and accuracy to endomicroscopic in vivo volumetric imaging of epithelial tissue.

  10. 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.

  11. Acute ischemic stroke after cardiac catheterization: the protamine low-dose recombinant tissue plasminogen activator pathway.

    PubMed

    Guevara, Carlos; Quijada, Alonso; Rosas, Carolina; Bulatova, Katya; Lara, Hugo; Nieto, Elena; Morales, Marcelo

    2016-05-20

    Intravenous thrombolysis is the preferred treatment for acute ischemic stroke; however, it remains unestablished in the area of cardiac catheterization. We report three patients with acute ischemic stroke after cardiac catheterization. After reversing the anticoagulant effect of unfractionated heparin with protamine, all of the patients were successfully off-label thrombolyzed with reduced doses of intravenous recombinant tissue plasminogen activator (0.6 mg/kg). This dose was preferred to reduce the risk of symptomatic cerebral or systemic bleeding. The sequential pathway of protamine recombinant tissue plasminogen activator at reduced doses may be safer for reducing intracranial or systemic bleeding events, whereas remaining efficacious for the treatment of acute ischemic stroke after cardiac catheterization.

  12. 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.

  13. 'Browning' the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk.

    PubMed

    Aldiss, Peter; Davies, Graeme; Woods, Rachel; Budge, Helen; Sacks, Harold S; Symonds, Michael E

    2017-02-01

    Excess visceral adiposity, in particular that located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. In the pathophysiological state, dysfunctional adipose tissue secretes an array of factors modulating vascular function and driving atherogenesis. Conversely, brown and beige adipose tissues utilise glucose and lipids to generate heat and are associated with improved cardiometabolic health. The cardiac and thoracic perivascular adipose tissues are now understood to be composed of brown adipose tissue in the healthy state and undergo a brown-to-white transition i.e. during obesity which may be a driving factor of cardiovascular disease. In this review we discuss the risks of excess cardiac and vascular adiposity and potential mechanisms by which restoring the brown phenotype i.e. "re-browning" could potentially be achieved in clinically relevant populations.

  14. A quantitative assessment of the depth sensitivity of an optical topography system using a solid dynamic tissue-phantom

    NASA Astrophysics Data System (ADS)

    Correia, Teresa; Banga, Anil; Everdell, N. L.; Gibson, Adam P.; Hebden, Jeremy C.

    2009-10-01

    A solid dynamic phantom with tissue-like optical properties is presented, which contains seven discrete targets impregnated with thermochromic pigment located at different depths from the surface. Changes in absorption are obtained in response to localized heating of the targets, simulating haemodynamic changes occurring in the brain and other tissues. The depth sensitivity of a continuous wave optical topography system was assessed successfully using the phantom. Images of the targets have been reconstructed using a spatially variant regularization, and the determined spatial localization in the depth direction is shown to be accurate within an uncertainty of about 3 mm down to a depth of about 30 mm.

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

    PubMed

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

    2013-01-01

    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.

  16. Effects Of Continuous Argon Laser Irradiation On Canine And Autopsied Human Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Ben-Shachar, Giora; Sivakoff, Mark; Bernard, Steven L.; Dahms, Beverly B.; Riemenschneider, Thomas A.

    1984-10-01

    In eight human formalin preserved cardiac specimens, various cardiac and vascular obstructions were relieved by argon laser irradiation. Interatrial communication was also produced by a transar'rial approach in a live dog. In-vivo fresh canine cardiac tissues required power density of at feast 80, 90, and 110 watts/cm2 for vaporization of myocardial, vascular and valvular tissues respectively. The fiber tip to tissue distance (effective irradiation distance) for effective vaporization was less than I mm for vascular and valvular tissues and less than 4 mm for myocardium. Light microscopy showed four zones of histological damage common to all tissues - central crater surrounded by layers of charring, vacuolization and coagulation necorsis. Myocardium showed additionally a layer of normal appearing muscle cells (skip area) surrounded by a peripheral coagulation halo. Laser irradiation effects on valvular tissue showed the most lateral extension of coagulation necrosis. It is concluded that palliation and treatment of certain congenital heart defects by laser irradiation is anatomi-cally feasible and may be safe for in vivo application when low power output and short exposure time are used from a very short irradiation distance.

  17. Cerebellar transcranial magnetic stimulation: the role of coil geometry and tissue depth.

    PubMed

    Hardwick, Robert M; Lesage, Elise; Miall, R Chris

    2014-01-01

    While transcranial magnetic stimulation (TMS) coil geometry has important effects on the evoked magnetic field, no study has systematically examined how different coil designs affect the effectiveness of cerebellar stimulation. The depth of the cerebellar targets will limit efficiency. Angled coils designed to stimulate deeper tissue are more effective in eliciting cerebellar stimulation. Experiment 1 examined basic input-output properties of the figure-of-eight, batwing and double-cone coils, assessed with stimulation of motor cortex. Experiment 2 assessed the ability of each coil to activate cerebellum, using cerebellar-brain inhibition (CBI). Experiment 3 mapped distances from the scalp to cerebellar and motor cortical targets in a sample of 100 subjects' structural magnetic resonance images. Experiment 1 showed batwing and double-cone coils have significantly lower resting motor thresholds, and recruitment curves with steeper slopes than the figure-of-eight coil. Experiment 2 showed the double-cone coil was the most efficient for eliciting CBI. The batwing coil induced CBI only at higher stimulus intensities. The figure-of-eight coil did not elicit reliable CBI. Experiment 3 confirmed that cerebellar tissue is significantly deeper than primary motor cortex tissue, and we provide a map of scalp-to-target distances. The double-cone and batwing coils designed to stimulate deeper tissue can effectively stimulate cerebellar targets. The double-cone coil was found to be most effective. The depth map provides a guide to the accessible regions of the cerebellar volume. These results can guide coil selection and stimulation parameters when designing cerebellar TMS studies. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  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. Delayed afterdepolarizations generate both triggers and a vulnerable substrate promoting reentry in cardiac tissue

    PubMed Central

    Liu, Michael B; de Lange, Enno; Garfinkel, Alan; Weiss, James N; Qu, Zhilin

    2015-01-01

    Background Delayed afterdepolarizations (DADs) have been well-characterized as arrhythmia triggers but their role in generating a tissue substrate vulnerable to reentry is not well understood. Objective To test the hypothesis that random DADs can self-organize to generate both an arrhythmia trigger and a vulnerable substrate simultaneously in cardiac tissue as a result of gap junction coupling. Methods Computer simulations in one-dimensional cable and two-dimensional tissue models were carried out. The cellular DAD amplitude was varied by changing the strength of sarcoplasmic reticulum Ca release. Random DAD latency and amplitude in different cells were simulated using Gaussian distributions. Results Depending on the strength of spontaneous sarcoplasmic reticulum Ca release and other conditions, random DADs in cardiac tissue resulted in the following behaviors: 1) triggered activity (TA); 2) a vulnerable tissue substrate causing unidirectional conduction block and reentry by inactivating Na channels; 3) both triggers and a vulnerable substrate simultaneously by generating TA in regions next to regions with subthreshold DADs susceptible to unidirectional conduction block and reentry. The probability of the latter two behaviors was enhanced by reduced Na channel availability, reduced gap junction coupling, increased tissue heterogeneity, and less synchronous DAD latency. Conclusions DADs can self-organize in tissue to generate arrhythmia triggers, a vulnerable tissue substrate, and both simultaneously. Reduced Na channel availability and gap junction coupling potentiate this mechanism of arrhythmias, which are relevant to a variety of heart disease conditions. PMID:26072025

  1. Two-wavelength approach for control of coagulation depth during laser tissue soldering

    NASA Astrophysics Data System (ADS)

    Wehner, Martin; Aden, Mirko; Toedter, Nina; Rosenkranz, Beate

    2015-03-01

    In laser tissue soldering (LTS) protein solutions are used for closing of incisions or fixation of wound dressings. During coagulation and thermal denaturation of the protein solutions their morphology changes significantly such that light is strongly scattered. When scattering becomes major component extinction increases and the optical penetration depth shrinks which could lead to unsufficient coagulation and bonding. For adaption of extinction during coagulation we are investigating a two-wavelength approach. A strongly absorbed laser wavelength (1540 nm) and weakly absorbed wavelength (980 nm) can be applied simultaneously. Simulation of beam propagation is performed in natural and coagulated state of the solder. The model describes a three-layer system consisting of membrane, solder and phantom. The optical properties are determined by spectrometric measurements both in natural and coagulated state. The absorption coefficient μa, scattering coefficient μs and anisotropy factor γ are determined by numerical analysis from the spectrometric data. Beam propagation is simulated for 980 nm and 1540 nm radiation with ZEMAX® software based on the Monte Carlo method. For both wavelengths the beginning of the process with a clear solder layer, and the final state characterized by a coagulated solder layer are examined. The optical penetration depth depends mainly on the optical properties of the solder, which change in the course of coagulation process. The coagulation depth can be varied between 1.5 mm to 3.5 mm by changing the proportion of both laser sources. This leads to concepts for minimizing heat input while maintaining a constant coagulation depth.

  2. Intradermally focused infrared laser pulses: thermal effects at defined tissue depths.

    PubMed

    Khan, Misbah Huzaira; Sink, R Kehl; Manstein, Dieter; Eimerl, David; Anderson, R Rox

    2005-04-01

    To produce controlled, spatially confined thermal effects in dermis. A 1 W, 1,500 nm fiber-coupled diode laser was focused with a high numerical aperture (NA) objective to achieve a tight optical focus within the upper dermis of skin held in contact with a glass window. The delivery optics was moved using a computer-controlled translator to generate an array of individual exposure spots. Fresh human facial skin samples were exposed to a range of pulse energies at specific focal depths, and to a range of focal depths at constant pulse energy. Cellular damage was evaluated in frozen sections using nitro-blue tetrazolium chloride (NBTC), a lactate dehydrogenase (LDH) activity stain. Loss of birefringence due to thermal denaturation of collagen was evaluated using cross-polarized light microscopy. The extent of focal thermal injury was compared with a model for photon migration (Monte Carlo Simulation), heat diffusion, and protein denaturation (Arrhenius model). Arrays of confined, microscopic intradermal foci of thermal injury were created. At high NA, epidermal damage was avoided without active cooling. Foci of thermal injury were typically 50-150 microm in diameter, elliptical, and at controllable depths from 0 to 550 microm. Both LDH inactivation and extracellular matrix denaturation were achieved. Spatially confined foci of thermal effects can be achieved by focusing a low-power infrared laser into skin. Size, depth, and density of microscopic, thermal damage foci may be arbitrarily controlled while sparing surrounding tissue. This may offer a new approach for nonablative laser therapy of dermal disorders. Copyright 2005 Wiley-Liss, Inc.

  3. 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

  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

    2015-06-11

    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. Noninvasive Assessment of Tissue Heating During Cardiac Radiofrequency Ablation Using MRI Thermography

    PubMed Central

    Kolandaivelu, Aravindan; Zviman, Menekhem M.; Castro, Valeria; Lardo, Albert C.; Berger, Ronald D.; Halperin, Henry R.

    2010-01-01

    Background Failure to achieve properly localized, permanent tissue destruction is a common cause of arrhythmia recurrence after cardiac ablation. Current methods of assessing lesion size and location during cardiac radiofrequency ablation are unreliable or not suited for repeated assessment during the procedure. MRI thermography could be used to delineate permanent ablation lesions because tissue heating above 50°C is the cause of permanent tissue destruction during radiofrequency ablation. However, image artifacts caused by cardiac motion, the ablation electrode, and radiofrequency ablation currently pose a challenge to MRI thermography in the heart. In the current study, we sought to demonstrate the feasibility of MRI thermography during cardiac ablation. Methods and Results An MRI-compatible electrophysiology catheter and filtered radiofrequency ablation system was used to perform ablation in the left ventricle of 6 mongrel dogs in a 1.5-T MRI system. Fast gradient-echo imaging was performed before and during radiofrequency ablation, and thermography images were derived from the preheating and postheating images. Lesion extent by thermography was within 20% of the gross pathology lesion. Conclusions MR thermography appears to be a promising technique for monitoring lesion formation and may allow for more accurate placement and titration of ablation, possibly reducing arrhythmia recurrences. PMID:20657028

  6. Cardiac tissue engineering: renewing the arsenal for the battle against heart disease.

    PubMed

    Georgiadis, Vassilis; Knight, Richard A; Jayasinghe, Suwan N; Stephanou, Anastasis

    2014-02-01

    The development of therapies that lead to the regeneration or functional repair of compromised cardiac tissue is the most important challenge facing translational cardiovascular research today. During the last 25 years huge efforts have been made towards restoring the physiologic functions of the heart by means of delivering cell implants into the insulted heart, initially through 'naked cell' injections and more recently through the principle of cardiac tissue engineering and the use of elaborate delivery systems and priming mechanisms that include scaffolds, bioreactors or ex vivo manipulations of cells and support structures. In this review we summarise various approaches towards cardiac repair and highlight advances in the field of tissue engineering, ranging from a review of cell types used, to advances that attempt to address mechanistic and functional elements that are critical for successful restoration of the heart, including the maintenance of the extracellular matrix through scaffoldless cardiac sheets, strategies that promote neovascularisation and the precise micro-delivery of cell populations to form three-dimensional structures through bioengineering methods such as microfabrication.

  7. 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.

  8. 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.

  9. Entrainment by an extracellular AC stimulus in a computational model of cardiac tissue.

    PubMed

    Meunier, J M; Trayanova, N A; Gray, R A

    2001-10-01

    Cardiac tissue can be entrained when subjected to sinusoidal stimuli, often responding with action potentials sustained for the duration of the stimulus. To investigate mechanisms responsible for both entrainment and extended action potential duration, computer simulations of a two-dimensional grid of cardiac cells subjected to sinusoidal extracellular stimulation were performed. The tissue is represented as a bidomain with unequal anisotropy ratios. Cardiac membrane dynamics are governed by a modified Beeler-Reuter model. The stimulus, delivered by a bipolar electrode, has a duration of 750 to 1,000 msec, an amplitude range of 800 to 3,200 microA/cm, and a frequency range of 10 to 60 Hz. The applied stimuli create virtual electrode polarization (VEP) throughout the sheet. The simulations demonstrate that periodic extracellular stimulation results in entrainment of the tissue. This phase-locking of the membrane potential to the stimulus is dependent on the location in the sheet and the magnitude of the stimulus. Near the electrodes, the oscillations are 1:1 or 1:2 phase-locked; at the middle of the sheet, the oscillations are 1:2 or 1:4 phase-locked and occur on the extended plateau of an action potential. The 1:2 behavior near the electrodes is due to periodic change in the voltage gradient between VEP of opposite polarity; at the middle of the sheet, it is due to spread of electrotonic current following the collision of a propagating wave with refractory tissue. The simulations suggest that formation of VEP in cardiac tissue subjected to periodic extracellular stimulation is of paramount importance to tissue entrainment and formation of an extended oscillatory action potential plateau.

  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. Depth profiling of cells and tissues by using C 60+ and SF 5+ as sputter ions

    NASA Astrophysics Data System (ADS)

    Malmberg, Per; Kriegeskotte, Christian; Arlinghaus, Heinrich F.; Hagenhoff, Birgit; Holmgren, Jan; Nilsson, Mikael; Nygren, Håkan

    2008-12-01

    In the present study, SF 5+ and C 60+ were used as primary ions for sputtering and Bi 3+ was used as primary ions for analysis. The depth profiling procedure was utilized to make 3D images of the chemistry of single cultured cells and tissue samples of intact intestinal epithelium. The results show sputtering of organic material from cells and tissue with both SF 5+ and C 60+ sources. Cholesterol fragments were found in the superficial layers when sputtering with C 60+. Spectra were collected revealing the change in yield along the z-axis of the sample. 3D images of the localization of Na, K, phosphocholine and cholesterol were constructed with both ion sources for single cell cultures and the mouse intestine. Cryostate sections of mouse intestine were analysed in 2D and the results were compared with the 3D image of the intestine. The localization of cholesterol and phosphocholine was found to be similar in cryostate sections analysed in two dimensions and the sputtered, freeze-dried intestine analysed in 3D. The comparison of 2D and 3D images suggest that the phosphocholine signal faded with C 60+ sputtering. In conclusion, both C 60+ and SF 5+ can be used as primary ion sources for sputtering of organic material from cells and tissues. Consecutive analysis with a Bi 3+ source can be used to obtain image stacks that could be used for reconstruction of 3D images.

  12. Conversion of measured percentage depth dose to tissue maximum ratio values in stereotactic radiotherapy.

    PubMed

    van Battum, L J; Essers, M; Storchi, P R M

    2002-09-21

    For many treatment planning systems tissue maximum ratios (TMR) are required as input. These tissue maximum ratios can be measured with a 3D computer-controlled water phantom; however, a TMR measurement option is not always available on such a system. Alternatively TMR values can be measured 'manually' by lowering the detector and raising the water phantom with the same distance, but this makes TMR measurements time consuming. Therefore we have derived TMR values from percentage depth dose (PDD) curves. Existing conversion methods express TMR values in terms of PDD, phantom scatter factor (Sp), and inverse square law. For stereotactic treatments circular fields ranging from 5-50 mm (19 cones) are used with the treatment planning system XKnife (Radionics). The calculation of TMR curves for this range is not possible with existing methods. This is because PDD curves of field sizes smaller than 5 mm (smallest cone size) are needed, but these cones are not provided. Besides, for field sizes smaller than 40 mm, the phantom scatter factor is difficult to determine and will introduce significant errors. To overcome these uncertainties, an alternative method has been developed to obtain TMR values from PDD data, where absolute doses are expressed in terms of PDD, total scatter factor and inverse square law. For each depth, the dose as a function of field size is fitted to a double exponential function. Then the TMR is calculated by taking the ratio of this function at the depth of interest and the reference depth, for the correct field size. For all 19 cones the total scatter factor and PDDs have been measured with a shielded diode in water for a 6 MV photon beam. Calculated TMR curves are compared with TMR values measured with a diode. The agreement is within 2%. Therefore this relatively simple conversion method meets the required accuracy for daily dose calculation in stereotactic radiotherapy. In principle this method could also be applied for other small field sizes

  13. Ephaptic coupling rescues conduction failure in weakly coupled cardiac tissue with voltage-gated gap junctions.

    PubMed

    Weinberg, S H

    2017-09-01

    Electrical conduction in cardiac tissue is usually considered to be primarily facilitated by gap junctions, providing a pathway between the intracellular spaces of neighboring cells. However, recent studies have highlighted the role of coupling via extracellular electric fields, also known as ephaptic coupling, particularly in the setting of reduced gap junction expression. Further, in the setting of reduced gap junctional coupling, voltage-dependent gating of gap junctions, an oft-neglected biophysical property in computational studies, produces a positive feedback that promotes conduction failure. We hypothesized that ephaptic coupling can break the positive feedback loop and rescue conduction failure in weakly coupled cardiac tissue. In a computational tissue model incorporating voltage-gated gap junctions and ephaptic coupling, we demonstrate that ephaptic coupling can rescue conduction failure in weakly coupled tissue. Further, ephaptic coupling increased conduction velocity in weakly coupled tissue, and importantly, reduced the minimum gap junctional coupling necessary for conduction, most prominently at fast pacing rates. Finally, we find that, although neglecting gap junction voltage-gating results in negligible differences in well coupled tissue, more significant differences occur in weakly coupled tissue, greatly underestimating the minimal gap junctional coupling that can maintain conduction. Our study suggests that ephaptic coupling plays a conduction-preserving role, particularly at rapid heart rates.

  14. Ephaptic coupling rescues conduction failure in weakly coupled cardiac tissue with voltage-gated gap junctions

    NASA Astrophysics Data System (ADS)

    Weinberg, S. H.

    2017-09-01

    Electrical conduction in cardiac tissue is usually considered to be primarily facilitated by gap junctions, providing a pathway between the intracellular spaces of neighboring cells. However, recent studies have highlighted the role of coupling via extracellular electric fields, also known as ephaptic coupling, particularly in the setting of reduced gap junction expression. Further, in the setting of reduced gap junctional coupling, voltage-dependent gating of gap junctions, an oft-neglected biophysical property in computational studies, produces a positive feedback that promotes conduction failure. We hypothesized that ephaptic coupling can break the positive feedback loop and rescue conduction failure in weakly coupled cardiac tissue. In a computational tissue model incorporating voltage-gated gap junctions and ephaptic coupling, we demonstrate that ephaptic coupling can rescue conduction failure in weakly coupled tissue. Further, ephaptic coupling increased conduction velocity in weakly coupled tissue, and importantly, reduced the minimum gap junctional coupling necessary for conduction, most prominently at fast pacing rates. Finally, we find that, although neglecting gap junction voltage-gating results in negligible differences in well coupled tissue, more significant differences occur in weakly coupled tissue, greatly underestimating the minimal gap junctional coupling that can maintain conduction. Our study suggests that ephaptic coupling plays a conduction-preserving role, particularly at rapid heart rates.

  15. 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

  16. Tissue-specific transcription of the cardiac myosin light-chain 2 gene is regulated by an upstream repressor element.

    PubMed

    Shen, R A; Goswami, S K; Mascareno, E; Kumar, A; Siddiqui, M A

    1991-03-01

    Physiological expression of the cardiac muscle myosin light-chain 2 (MLC-2) gene in chickens is restricted to cardiac muscle tissue only, at least during the late embryonic to adult stages of development. The mechanism by which cardiac MLC-2 gene expression is repressed in differentiated noncardiac muscle tissues is unknown. Using sequential 5'-deletion mutants of the cardiac MLC-2 promoter introduced into primary skeletal muscle cells in culture, we have demonstrated that a 89-bp region, designated the cardiac-specific sequence (CSS), is essential for repression of cardiac MLC-2 expression in skeletal muscle. Removal of the CSS sequence alone allows transcription in skeletal muscle cells without affecting the transcriptional activity of the promoter in cardiac muscle cells. DNase I footprinting and gel shift assays indicate that protein binding to sequences in the CSS domain occurs readily in nuclear extracts obtained from skeletal muscle but not in extracts isolated under identical conditions from cardiac muscle. Thus, it appears that a negative regulatory mechanism accounts for the lack of expression of the cardiac MLC-2 gene in skeletal muscle and that the CSS element and its binding proteins are important functional components of the regulatory apparatus which ensures the developmental program for cardiac tissue-specific gene expression.

  17. Tissue-specific transcription of the cardiac myosin light-chain 2 gene is regulated by an upstream repressor element.

    PubMed Central

    Shen, R A; Goswami, S K; Mascareno, E; Kumar, A; Siddiqui, M A

    1991-01-01

    Physiological expression of the cardiac muscle myosin light-chain 2 (MLC-2) gene in chickens is restricted to cardiac muscle tissue only, at least during the late embryonic to adult stages of development. The mechanism by which cardiac MLC-2 gene expression is repressed in differentiated noncardiac muscle tissues is unknown. Using sequential 5'-deletion mutants of the cardiac MLC-2 promoter introduced into primary skeletal muscle cells in culture, we have demonstrated that a 89-bp region, designated the cardiac-specific sequence (CSS), is essential for repression of cardiac MLC-2 expression in skeletal muscle. Removal of the CSS sequence alone allows transcription in skeletal muscle cells without affecting the transcriptional activity of the promoter in cardiac muscle cells. DNase I footprinting and gel shift assays indicate that protein binding to sequences in the CSS domain occurs readily in nuclear extracts obtained from skeletal muscle but not in extracts isolated under identical conditions from cardiac muscle. Thus, it appears that a negative regulatory mechanism accounts for the lack of expression of the cardiac MLC-2 gene in skeletal muscle and that the CSS element and its binding proteins are important functional components of the regulatory apparatus which ensures the developmental program for cardiac tissue-specific gene expression. Images PMID:1996116

  18. 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

    2013-09-03

    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.

  19. 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

    2016-05-06

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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

  1. 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.

  2. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium

    PubMed Central

    Turnbull, Irene C.; Karakikes, Ioannis; Serrao, Gregory W.; Backeris, Peter; Lee, Jia-Jye; Xie, Chaoqin; Senyei, Grant; Gordon, Ronald E.; Li, Ronald A.; Akar, Fadi G.; Hajjar, Roger J.; Hulot, Jean-Sébastien; Costa, Kevin D.

    2014-01-01

    Cardiac experimental biology and translational research would benefit from an in vitro surrogate for human heart muscle. This study investigated structural and functional properties and interventional responses of human engineered cardiac tissues (hECTs) compared to human myocardium. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs, >90% troponin-positive) were mixed with collagen and cultured on force-sensing elastomer devices. hECTs resembled trabecular muscle and beat spontaneously (1.18±0.48 Hz). Microstructural features and mRNA expression of cardiac-specific genes (α-MHC, SERCA2a, and ACTC1) were comparable to human myocardium. Optical mapping revealed cardiac refractoriness with loss of 1:1 capture above 3 Hz, and cycle length dependence of the action potential duration, recapitulating key features of cardiac electrophysiology. hECTs reconstituted the Frank-Starling mechanism, generating an average maximum twitch stress of 660 μN/mm2 at Lmax, approaching values in newborn human myocardium. Dose-response curves followed exponential pharmacodynamics models for calcium chloride (EC50 1.8 mM) and verapamil (IC50 0.61 μM); isoproterenol elicited a positive chronotropic but negligible inotropic response, suggesting sarcoplasmic reticulum immaturity. hECTs were amenable to gene transfer, demonstrated by successful transduction with Ad.GFP. Such 3-D hECTs recapitulate an early developmental stage of human myocardium and promise to offer an alternative preclinical model for cardiology research.—Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J.-J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., Hajjar, R. J., Hulot, J.-S., Costa, K. D. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. PMID:24174427

  3. 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.

  4. Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue

    PubMed Central

    Lee, Eun Jung; Luo, Jianwen; Duan, Yi; Yeager, Keith; Konofagou, Elisa; Vunjak-Novakovic, Gordana

    2012-01-01

    Maintenance of normal myocardial function depends intimately on synchronous tissue contraction driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue, but due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation, and unconstrained (i.e., not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate in concert these three key factors. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modeling studies. We then culture cardiac cells obtained from neonatal rats in porous, channeled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After eight days of culture, constructs grown with the simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23±0.10% vs. 0.14±0.05, 0.13±0.08, or 0.09±0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization than either control group. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs. PMID:22170772

  5. Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue.

    PubMed

    Maidhof, Robert; Tandon, Nina; Lee, Eun Jung; Luo, Jianwen; Duan, Yi; Yeager, Keith; Konofagou, Elisa; Vunjak-Novakovic, Gordana

    2012-11-01

    Maintenance of normal myocardial function depends intimately on synchronous tissue contraction, driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue but, due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation and unconstrained (i.e. not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate these three key factors in concert. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modelling studies. We then cultured cardiac cells obtained from neonatal rats in porous, channelled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After 8 days of culture, constructs grown with simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23 ± 0.10% vs 0.14 ± 0.05%, 0.13 ± 0.08% or 0.09 ± 0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization compared to control groups. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue.

    PubMed

    Majumder, Rupamanjari; Pandit, Rahul; Panfilov, A V

    2014-10-01

    Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model [fast inward Na(+) current (INa), L-type slow inward Ca(2+) current (ICaL), slow delayed-rectifier current (IKs), rapid delayed-rectifier current (IKr), inward rectifier K(+) current (IK1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is ∼2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

  7. Defining the mid-diastolic imaging period for cardiac CT - lessons from tissue Doppler echocardiography.

    PubMed

    Otton, James M; Phan, Justin; Feneley, Michael; Yu, Chung-yao; Sammel, Neville; McCrohon, Jane

    2013-02-01

    Aggressive dose reduction strategies for cardiac CT require the prospective selection of limited cardiac phases. At lower heart rates, the period of mid-diastole is typically selected for image acquisition. We aimed to identify the effect of heart rate on the optimal CT acquisition phase within the period of mid-diastole. We utilized high temporal resolution tissue Doppler to precisely measure coronary motion within diastole. Tissue-Doppler waveforms of the myocardium corresponding to the location of the circumflex artery (100 patients) and mid-right coronary arteries (50 patients) and the duration and timing of coronary motion were measured. Using regression analysis an equation was derived for the timing of the period of minimal coronary motion within the RR interval. In a validation set of 50 clinical cardiac CT examinations, we assessed coronary motion artifact and the effect of using a mid-diastolic imaging target that was adjusted according to heart rate vs a fixed 75% phase target. Tissue Doppler analysis shows the period of minimal cardiac motion suitable for CT imaging decreases almost linearly as the RR interval decreases, becoming extinguished at an average heart rate of 91 bpm for the circumflex (LCX) and 78 bpm for the right coronary artery (RCA). The optimal imaging phase has a strong linear relationship with RR duration (R2 = 0.92 LCX, 0.89 RCA). The optimal phase predicted by regression analysis of the tissue-Doppler waveforms increases from 74% at a heart rate of 55 bpm to 77% at 75 bpm. In the clinical CT validation set, the optimal CT acquisition phase similarly occurred later with increasing heart rate. When the selected cardiac phase was adjusted according to heart rate the result was closer to the optimal phase than using a fixed 75% phase. While this effect was statistically significant (p < 0.01 RCA/LCx), the mean effect of heart-rate adjustment was minor relative to typical beat-to-beat variability and available precision of

  8. Defining the mid-diastolic imaging period for cardiac CT – lessons from tissue Doppler echocardiography

    PubMed Central

    2013-01-01

    Background Aggressive dose reduction strategies for cardiac CT require the prospective selection of limited cardiac phases. At lower heart rates, the period of mid-diastole is typically selected for image acquisition. We aimed to identify the effect of heart rate on the optimal CT acquisition phase within the period of mid-diastole. Methods We utilized high temporal resolution tissue Doppler to precisely measure coronary motion within diastole. Tissue-Doppler waveforms of the myocardium corresponding to the location of the circumflex artery (100 patients) and mid-right coronary arteries (50 patients) and the duration and timing of coronary motion were measured. Using regression analysis an equation was derived for the timing of the period of minimal coronary motion within the RR interval. In a validation set of 50 clinical cardiac CT examinations, we assessed coronary motion artifact and the effect of using a mid-diastolic imaging target that was adjusted according to heart rate vs a fixed 75% phase target. Results Tissue Doppler analysis shows the period of minimal cardiac motion suitable for CT imaging decreases almost linearly as the RR interval decreases, becoming extinguished at an average heart rate of 91 bpm for the circumflex (LCX) and 78 bpm for the right coronary artery (RCA). The optimal imaging phase has a strong linear relationship with RR duration (R2 = 0.92 LCX, 0.89 RCA). The optimal phase predicted by regression analysis of the tissue-Doppler waveforms increases from 74% at a heart rate of 55 bpm to 77% at 75 bpm. In the clinical CT validation set, the optimal CT acquisition phase similarly occurred later with increasing heart rate. When the selected cardiac phase was adjusted according to heart rate the result was closer to the optimal phase than using a fixed 75% phase. While this effect was statistically significant (p < 0.01 RCA/LCx), the mean effect of heart-rate adjustment was minor relative to typical beat-to-beat variability and

  9. 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.

  10. Development and application of human virtual excitable tissues and organs: from premature birth to sudden cardiac death.

    PubMed

    Holden, Arun V

    2010-12-01

    The electrical activity of cardiac and uterine tissues has been reconstructed by detailed computer models in the form of virtual tissues. Virtual tissues are biophysically and anatomically detailed, and represent quantitatively predictive models of the physiological and pathophysiological behaviours of tissue within an isolated organ. The cell excitation properties are quantitatively reproduced by equations that describe the kinetics of a few dozen proteins. These equations are derived from experimental measurements of membrane potentials, ionic currents, fluxes, and concentrations. Some of the measurements were taken from human cells and human ion channel proteins expressed in non-human cells, but they were mostly taken from cells of other animal species. Data on tissue geometry and architecture are obtained from the diffusion tensor magnetic resonance imaging of ex vivo or post mortem tissue, and are used to compute the spread of current in the tissue. Cardiac virtual tissues are well established and reproduce normal and pathological patterns of cardiac excitation within the atria or ventricles of the human heart. They have been applied to increase the understanding of normal cardiac electrophysiology, to evaluate the candidate mechanisms for re-entrant arrhythmias that lead to sudden cardiac death, and to predict the tissue level effects of mutant or pharmacologically-modified ion channels. The human full-term virtual uterus is still in development. This virtual tissue reproduces the in vitro behaviour of uterine tissue biopsies, and provides possible mechanisms for premature labour.

  11. 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. © 2014 Wiley Periodicals, Inc.

  12. Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

    PubMed

    Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

    2017-09-01

    The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

  13. Tissue Tracking Technology for Assessing Cardiac Mechanics: Principles, Normal Values, and Clinical Applications.

    PubMed

    Claus, Piet; Omar, Alaa Mabrouk Salem; Pedrizzetti, Gianni; Sengupta, Partho P; Nagel, Eike

    2015-12-01

    Tissue tracking technologies such as speckle tracking echocardiography and feature tracking cardiac magnetic resonance have enhanced the noninvasive assessment of myocardial deformation in clinical research and clinical practice. The widespread enthusiasm for using tissue tracking techniques in research and clinical practice stems from the ready applicability of these technologies to routine echocardiographic or cardiac magnetic resonance images. The technology is common to both modalities, and derived parameters to describe myocardial mechanics are the similar, albeit with different accuracies. We provide an overview of the normal values and reproducibility of the clinically applicable parameters, together with their clinical validation. The use of these technologies in different clinical scenarios, and the additive value to current imaging diagnostics are discussed. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Experimental and theoretical description of higher order periods in cardiac tissue action potential duration

    NASA Astrophysics Data System (ADS)

    Herndon, Conner; Fenton, Flavio; Uzelac, Ilija

    Much theoretical, experimental, and clinical research has been devoted to investigating the initiation of cardiac arrhythmias by alternans, the first period doubling bifurcation in the duration of cardiac action potentials. Although period doubling above alternans has been shown to exist in many mammalian hearts, little is understood about their emergence or behavior. There currently exists no physiologically correct theory or model that adequately describes and predicts their emergence in stimulated tissue. In this talk we present experimental data of period 2, 4, and 8 dynamics and a mathematical model that describes these bifurcations. This model extends current cell models through the addition of memory and includes spatiotemporal nonlinearities arising from cellular coupling by tissue heterogeneity.

  15. Towards optical spectroscopic anatomical mapping (OSAM) for lesion validation in cardiac tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

    Electroanatomical mapping (EAM) is an invaluable tool for guiding cardiac radiofrequency ablation (RFA) therapy. The principle roles of EAM is the identification of candidate ablation sites by detecting regions of abnormal electrogram activity and lesion validation subsequent to RF energy delivery. However, incomplete lesions may present interim electrical inactivity similar to effective treatment in the acute setting, despite efforts to reveal them with pacing or drugs, such as adenosine. Studies report that the misidentification and recovery of such lesions is a leading cause of arrhythmia recurrence and repeat procedures. In previous work, we demonstrated spectroscopic characterization of cardiac tissues using a fiber optic-integrated RF ablation catheter. In this work, we introduce OSAM (optical spectroscopic anatomical mapping), the application of this spectroscopic technique to obtain 2-dimensional biodistribution maps. We demonstrate its diagnostic potential as an auxiliary method for lesion validation in treated swine preparations. Endocardial lesion sets were created on fresh swine cardiac samples using a commercial RFA system. An optically-integrated catheter console fabricated in-house was used for measurement of tissue optical spectra between 600-1000nm. Three dimensional, Spatio-spectral datasets were generated by raster scanning of the optical catheter across the treated sample surface in the presence of whole blood. Tissue optical parameters were recovered at each spatial position using an inverse Monte Carlo method. OSAM biodistribution maps showed stark correspondence with gross examination of tetrazolium chloride stained tissue specimens. Specifically, we demonstrate the ability of OSAM to readily distinguish between shallow and deeper lesions, a limitation faced by current EAM techniques. These results showcase the OSAMs potential for lesion validation strategies for the treatment of cardiac arrhythmias.

  16. Development of a bioengineered tissue model and its application in the investigation of the depth selectivity of polarization gating.

    PubMed

    Liu, Yang; Kim, Young L; Backman, Vadim

    2005-04-20

    Understanding the propagation of polarized light in tissue is crucial for a number of biomedical optics applications. Here we report the development of a bioengineered connective tissue model fabricated by the combination of scaffolding and cross-linking techniques to study light transport in biological tissue. It demonstrates great similarity to real connective tissue in its optical properties as well as microarchitecture. Moreover, the optical properties of the model can be reproducibly controlled. As an example, we report the utilization of this model to study the effect of epithelium and the underlying connective tissue on the depth selectivity of polarization gating.

  17. 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.

  18. 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.

  19. 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

  20. Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering

    PubMed Central

    Singelyn, Jennifer M.; DeQuach, Jessica A.; Seif-Naraghi, Sonya B.; Littlefield, Robert B.; Schup-Magoffin, Pamela J.; Christman, Karen L.

    2009-01-01

    Myocardial tissue lacks the ability to significantly regenerate itself following a myocardial infarction, thus tissue engineering strategies are required for repair. Several injectable materials have been examined for cardiac tissue engineering; however, none have been designed specifically to mimic the myocardium. The goal of this study was to investigate the in vitro properties and in vivo potential of an injectable myocardial matrix designed to mimic the natural myocardial extracellular environment. Porcine myocardial tissue was decellularized and processed to form a myocardial matrix with the ability to gel in vitro at 37°C and in vivo upon injection into rat myocardium. The resulting myocardial matrix maintained a complex composition, including glycosaminoglycan content, and was able to self-assemble to form a nanofibrous structure. Endothelial cells and smooth muscle cells were shown to migrate towards the myocardial matrix both in vitro and in vivo, with a significant increase in arteriole formation at 11 days post-injection. The matrix was also successfully pushed through a clinically used catheter, demonstrating its potential for minimally invasive therapy. Thus, we have demonstrated the initial feasibility and potential of a naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. PMID:19608268

  1. Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels

    PubMed Central

    Tang, Wanjian; Blair, Cheavar A.; Walton, Shane D.; Málnási-Csizmadia, András; Campbell, Kenneth S.; Yengo, Christopher M.

    2017-01-01

    Inherited cardiomyopathies are a common form of heart disease that are caused by mutations in sarcomeric proteins with beta cardiac myosin (MYH7) being one of the most frequently affected genes. Since the discovery of the first cardiomyopathy associated mutation in beta-cardiac myosin, a major goal has been to correlate the in vitro myosin motor properties with the contractile performance of cardiac muscle. There has been substantial progress in developing assays to measure the force and velocity properties of purified cardiac muscle myosin but it is still challenging to correlate results from molecular and tissue-level experiments. Mutations that cause hypertrophic cardiomyopathy are more common than mutations that lead to dilated cardiomyopathy and are also often associated with increased isometric force and hyper-contractility. Therefore, the development of drugs designed to decrease isometric force by reducing the duty ratio (the proportion of time myosin spends bound to actin during its ATPase cycle) has been proposed for the treatment of hypertrophic cardiomyopathy. Para-Nitroblebbistatin is a small molecule drug proposed to decrease the duty ratio of class II myosins. We examined the impact of this drug on human beta cardiac myosin using purified myosin motor assays and studies of permeabilized muscle fiber mechanics. We find that with purified human beta-cardiac myosin para-Nitroblebbistatin slows actin-activated ATPase and in vitro motility without altering the ADP release rate constant. In permeabilized human myocardium, para-Nitroblebbistatin reduces isometric force, power, and calcium sensitivity while not changing shortening velocity or the rate of force development (ktr). Therefore, designing a drug that reduces the myosin duty ratio by inhibiting strong attachment to actin while not changing detachment can cause a reduction in force without changing shortening velocity or relaxation. PMID:28119616

  2. Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

    PubMed

    Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

    2013-11-01

    To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

  3. The Effects of Radiofrequency or Cryothermal Ablation on Biomechanical Properties of Isolated Human or Swine Cardiac Tissues.

    PubMed

    Quallich, Stephen G; Kriege, Kevin E; Iaizzo, Paul A

    2016-01-01

    Changes in cardiac tissue properties following the application of various ablation modalities may lead to the development of an array of associated complications. The application of either radio frequency (RF) or cryothermal ablations will alter the biomechanical properties of various cardiac tissues in a differential manner; in some cases, this may be attributable to increased incidences of cardiac tamponade, pulmonary vein stenosis, and/or atrial-esophageal fistula. Thus, a greater understanding of the underlying changes in tissue properties induced by ablative therapies will ultimately promote safer and more efficacious procedures. The effects of applied RF or cryothermal energies on the biomechanical properties of the pulmonary vein, left atrial, or right atrial samples ([Formula: see text]) were examined from fresh excised porcine ([Formula: see text]) and donated human tissue ([Formula: see text]). RF ablations were found to reduce the tensile strength of the porcine cardiac specimens ([Formula: see text]), and a similar trend was noted for human samples. Cryoablations did not have a significant impact on the tissue properties compared with the untreated tissue specimens. Locational and species differences were also observed in this experimental paradigm ([Formula: see text]. Incorporating these findings into cardiac device design and computational modeling should aid to reduce the risks of complications associated with tissue property changes resulting from cardiac ablative procedures.

  4. Semi-automatic segmentation of nonviable cardiac tissue using cine and delayed enhancement magnetic resonance images

    NASA Astrophysics Data System (ADS)

    O'Donnell, Thomas P.; Xu, Ning; Setser, Randolph M.; White, Richard D.

    2003-05-01

    Post myocardial infarction, the identification and assessment of non-viable (necrotic) tissues is necessary for effective development of intervention strategies and treatment plans. Delayed Enhancement Magnetic Resonance (DEMR) imaging is a technique whereby non-viable cardiac tissue appears with increased signal intensity. Radiologists typically acquire these images in conjunction with other functional modalities (e.g., MR Cine), and use domain knowledge and experience to isolate the non-viable tissues. In this paper, we present a technique for automatically segmenting these tissues given the delineation of myocardial borders in the DEMR and in the End-systolic and End-diastolic MR Cine images. Briefly, we obtain a set of segmentations furnished by an expert and employ an artificial intelligence technique, Support Vector Machines (SVMs), to "learn" the segmentations based on features culled from the images. Using those features we then allow the SVM to predict the segmentations the expert would provide on previously unseen images.

  5. Human cardiac tissue in a microperfusion chamber simulating extracorporeal circulation - ischemia and apoptosis studies

    PubMed Central

    2010-01-01

    Background After coronary artery bypass grafting ischemia/reperfusion injury inducing cardiomyocyte apoptosis may occur. This surgery-related inflammatory reaction appears to be of extreme complexity with regard to its molecular, cellular and tissue mechanisms and many studies have been performed on animal models. However, finding retrieved from animal studies were only partially confirmed in humans. To investigate this phenomenon and to evaluate possible therapies in vitro, adequate human cardiomyocyte models are required. We established a tissue model of human cardiomyocytes preserving the complex tissue environment. To our knowledge human cardiac tissue has not been investigated in an experimental setup mimicking extracorporeal circulation just in accordance to clinical routine, yet. Methods Cardiac biopsies were retrieved from the right auricle of patients undergoing elective coronary artery bypass grafting before cardiopulmonary bypass. The extracorporeal circulation was simulated by submitting the biopsies to varied conditions simulating cardioplegia (cp) and reperfusion (rep) in a microperfusion chamber. Cp/rep time sets were 20/7, 40/13 and 60/20 min. For analyses of the calcium homoeostasis the fluorescent calcium ion indicator FURA-2 and for apoptosis detection PARP-1 cleavage immunostaining were employed. Further the anti-apoptotic effect of carvedilol [10 μM] was investigated by adding into the perfusate. Results Viable cardiomyocytes presented an intact calcium homoeostasis under physiologic conditions. Following cardioplegia and reperfusion a time-dependent elevation of cytosolic calcium as a sign of disarrangement of the calcium homoeostasis occurred. PARP-1 cleavage also showed a time-dependence whereas reperfusion had the highest impact on apoptosis. Cardioplegia and carvedilol could reduce apoptosis significantly, lowering it between 60-70% (p < 0.05). Conclusions Our human cardiac preparation served as a reliable cellular model tool to study

  6. 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

  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. 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.

  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. Melt Electrospinning Writing of Poly-Hydroxymethylglycolide-co-ε-Caprolactone-Based Scaffolds for Cardiac Tissue Engineering.

    PubMed

    Castilho, Miguel; Feyen, Dries; Flandes-Iparraguirre, María; Hochleitner, Gernot; Groll, Jürgen; Doevendans, Pieter A F; Vermonden, Tina; Ito, Keita; Sluijter, Joost P G; Malda, Jos

    2017-09-01

    Current limitations in cardiac tissue engineering revolve around the inability to fully recapitulate the structural organization and mechanical environment of native cardiac tissue. This study aims at developing organized ultrafine fiber scaffolds with improved biocompatibility and architecture in comparison to the traditional fiber scaffolds obtained by solution electrospinning. This is achieved by combining the additive manufacturing of a hydroxyl-functionalized polyester, (poly(hydroxymethylglycolide-co-ε-caprolactone) (pHMGCL), with melt electrospinning writing (MEW). The use of pHMGCL with MEW vastly improves the cellular response to the mechanical anisotropy. Cardiac progenitor cells (CPCs) are able to align more efficiently along the preferential direction of the melt electrospun pHMGCL fiber scaffolds in comparison to electrospun poly(ε-caprolactone)-based scaffolds. Overall, this study describes for the first time that highly ordered microfiber (4.0-7.0 µm) scaffolds based on pHMGCL can be reproducibly generated with MEW and that these scaffolds can support and guide the growth of CPCs and thereby potentially enhance their therapeutic potential. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Mind the Gap: A Semicontinuum Model for Discrete Electrical Propagation in Cardiac Tissue.

    PubMed

    Costa, Caroline Mendonca; Silva, Pedro Andre Arroyo; dos Santos, Rodrigo Weber

    2016-04-01

    Electrical propagation in cardiac tissue is a discrete or discontinuous phenomenon that reflects the complexity of the anatomical structures and their organization in the heart, such as myocytes, gap junctions, microvessels, and extracellular matrix, just to name a few. Discrete models or microscopic and discontinuous models are, so far, the best options to accurately study how structural properties of cardiac tissue influence electrical propagation. These models are, however, inappropriate in the context of large scale simulations, which have been traditionally performed by the use of continuum and macroscopic models, such as the monodomain and the bidomain models. However, continuum models may fail to reproduce many important physiological and physiopathological aspects of cardiac electrophysiology, for instance, those related to slow conduction. In this study, we develop a new mathematical model that combines characteristics of both continuum and discrete models. The new model was evaluated in scenarios of low gap-junctional coupling, where slow conduction is observed, and was able to reproduce conduction block, increase of the maximum upstroke velocity and of the repolarization dispersion. None of these features can be captured by continuum models. In addition, the model overcomes a great disadvantage of discrete models, as it allows variation of the spatial resolution within a certain range.

  12. Investigating a Period-Doubling Bifurcation in Cardiac Tissue Using Alternate Pacing

    NASA Astrophysics Data System (ADS)

    Berger, C. M.

    2005-03-01

    The action potential duration (APD) of cardiac cells undergoes a period-doubling bifurcation when the pacing rate (PR) is increased, resulting in a period-2 behavior called alternans. Studying the susceptibility of cardiac tissue to alternans is crucial because alternans can lead to ventricular fibrillation and sudden cardiac death. One way to study this behavior is to alternate the PR from beat-to-beat, which results in beat-to-beat alternation in APD. Recent mathematical models predict that these small beat-to-beat changes in PR will result in divergent beat-to-beat variations in APD near the period-doubling bifurcation. Thus, the appearance of divergent behavior during alternate pacing can uncover the tissue's propensity to alternans. In an experiment to test this hypothesis, we observed beat-to-beat APD variations that are only a fraction of the beat-to-beat change in the PR, despite proximity to the bifurcation point. This study demonstrates the discrepancy between experiment and theory, which may be due to changes in ionic concentrations and wave propagation.

  13. Optimal iodine staining of cardiac tissue for X-ray computed tomography.

    PubMed

    Butters, Timothy D; Castro, Simon J; Lowe, Tristan; Zhang, Yanmin; Lei, Ming; Withers, Philip J; Zhang, Henggui

    2014-01-01

    X-ray computed tomography (XCT) has been shown to be an effective imaging technique for a variety of materials. Due to the relatively low differential attenuation of X-rays in biological tissue, a high density contrast agent is often required to obtain optimal contrast. The contrast agent, iodine potassium iodide ([Formula: see text]), has been used in several biological studies to augment the use of XCT scanning. Recently I2KI was used in XCT scans of animal hearts to study cardiac structure and to generate 3D anatomical computer models. However, to date there has been no thorough study into the optimal use of I2KI as a contrast agent in cardiac muscle with respect to the staining times required, which has been shown to impact significantly upon the quality of results. In this study we address this issue by systematically scanning samples at various stages of the staining process. To achieve this, mouse hearts were stained for up to 58 hours and scanned at regular intervals of 6-7 hours throughout this process. Optimal staining was found to depend upon the thickness of the tissue; a simple empirical exponential relationship was derived to allow calculation of the required staining time for cardiac samples of an arbitrary size.

  14. 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.

  15. Assessment of cardiac functions using tissue Doppler imaging in children with familial Mediterranean fever.

    PubMed

    Ozdemir, Osman; Agras, Pinar Isik; Aydin, Yusuf; Abaci, Ayhan; Hizli, Samil; Akkus, Halil Ibrahim; Fidan, Cihan

    2012-04-01

    Familial Mediterranean fever may carry a potential for cardiovascular disorders because of sustained inflammation during its course; however, there has been a limited number of studies investigating the cardiac functions in children. The aim of this study was to assess both ventricular diastolic functions using conventional echocardiography and tissue Doppler imaging in children with familial Mediterranean fever. The study population included 25 patients with familial Mediterranean fever - mean age was 11.8 plus or minus 5.30 years - and 23 healthy patients as controls - mean age was 9.88 plus or minus 3.69 years. Both ventricular functions were measured using echocardiography comprising standard M-mode and conventional Doppler and tissue Doppler imaging during an attack-free period. The conventional echocardiographic parameters with myocardial performance index were in normal ranges and similar in patients with familial Mediterranean fever and controls, with a p-value more than 0.05. However, right ventricular diastolic dysfunction was observed in patients with familial Mediterranean fever documented by tissue Doppler imaging, with a p-value less than 0.05 for E't and A't wave ratio. Using tissue Doppler imaging, we have demonstrated that although left ventricular functions were comparable in the patients and healthy children, right ventricular diastolic function indices were impaired in patients with familial Mediterranean fever during childhood. Impaired right ventricular diastolic function may be an early manifestation of cardiac involvement in children with familial Mediterranean fever.

  16. 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

  17. Development of In Vitro Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues.

    PubMed

    Takeda, Maki; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Ito, Emiko; Harada, Akima; Matsuura, Ryohei; Iseoka, Hiroko; Sougawa, Nagako; Mochizuki-Oda, Noriko; Matsusaki, Michiya; Akashi, Mitsuru; Sawa, Yoshiki

    2017-10-01

    An in vitro drug-induced cardiotoxicity assay is a critical step in drug discovery for clinical use. The use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is promising for this purpose. However, single hiPSC-CMs are limited in their ability to mimic native cardiac tissue structurally and functionally, and the generation of artificial cardiac tissue using hiPSC-CMs is an ongoing challenging. We therefore developed a new method of constructing three-dimensional (3D) artificial tissues in a short time by coating extracellular matrix components on cell surfaces. We hypothesized that 3D cardiac tissues derived from hiPSC-CMs (3D-hiPSC-CT) could be used for an in vitro drug-induced cardiotoxicity assay. 3D-hiPSC-CT were generated by fibronectin and gelatin nanofilm coated single hiPSC-CMs. Histologically, the 3D-hiPSC-CT exhibited a sarcomere structure in the myocytes and extracellular matrix proteins, such as fibronectin, collagen type I/III, and laminin. The administration of cytotoxic doxorubicin at 5.0 μM induced the release of lactate dehydrogenase (LDH), while that at 2.0 μM reduced the cell viability. E-4031, hERG-type potassium channel blocker, and isoproterenol induced significant changes both in the Ca transient parameters and contractile parameters in a dose-dependent manner. The 3D-hiPSC-CT exhibited doxorubicin-sensitive cytotoxicity and hERG channel blocker/isoproterenol-sensitive electrical activity in vitro, indicating its usefulness for drug-induced cardiotoxicity assays or drug screening systems for drug discovery.

  18. Effect of fibre rotation on the initiation of re-entry in cardiac tissue.

    PubMed

    Vigmond, E J; Leon, L J

    2001-07-01

    Transmural rotation of cardiac fibres can have a big influence on the initiation of re-entry in the heart. However, owing to computational demands, this has not been fully explored in a three-dimensional model of cardiac tissue that has a microscopic description of membrane currents, such as the Luo-Rudy model. Using a previously described model that is computationally fast, re-entry in three-dimensional blocks of cardiac tissue is induced by a cross-shock protocol, and the activity is examined. In the study, the effect of the transmural fibre rotation is ascertained by examining differences between a tissue block with no rotation and ones with 1, 2 and 3 degrees of rotation per fibre layer. The direction of the re-entry is significant in establishing whether or not re-entry can be induced, with clockwise re-entry being easier to initiate. Owing to the rotating anisotropy that results in preferential propagation along the fibre axis, the timing of the second stimulus in the cross-shock protocol has to be changed for different rates of fibre rotation. The fibre rotation either increases or decreases the window of opportunity for re-entry, depending on whether the activation front is perpendicular or parallel to the fibre direction. By varying the transmural extent of the S2, it is found that a deeper stimulus has to be applied to the blocks with fibre rotation to create re-entry. Increasing the transmural resistance also tends to reduce the extent of the S2 required to induce re-entry. Results suggest that increasing fibre rotation reduces the susceptibility of the tissue to re-entry, but that more complex spatiotemporal patterns are possible, e.g. stable figure-of-eight re-entries and transient rotors. Three mechanisms of re-entry annihilation are identified: front catchup, filling of the excitable gap and core wander.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

    PubMed

    Gaer, J A; Wharton, J; Gordon, L; Swift, R I; Munsch, C; Inglis, G C; Polak, J M; Taylor, K M

    1992-01-01

    Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

  4. 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

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

    PubMed

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

    2015-08-25

    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.

  6. Development of a multi-frequency diffuse photon density wave device for the characterization of tissue damage at multiple depths

    NASA Astrophysics Data System (ADS)

    Diaz, David; Weingarten, Michael S.; Neidrauer, Michael T.; Samuels, Joshua A.; Huneke, Richard B.; Kuzmin, Vladimir L.; Lewin, Peter A.; Zubkov, Leonid A.

    2014-02-01

    The ability to determine the depth and degree of cutaneous and subcutaneous tissue damage is critical for medical applications such as burns and pressure ulcers. The Diffuse Photon Density Wave (DPDW) methodology at near infrared wavelengths can be used to non-invasively measure the optical absorption and reduced scattering coefficients of tissue at depths of several millimeters. A multi-frequency DPDW system with one light source and one detector was constructed so that light is focused onto the tissue surface using an optical fiber and lens mounted to a digitally-controlled actuator which changes the distance between light source and detector. A variable RF generator enables the modulation frequency to be selected between 50 to 400MHz. The ability to digitally control both source-detector separation distance and modulation frequency allows for virtually unlimited number of data points, enabling precise selection of the volume and depth of tissue that will be characterized. Suspensions of Intralipid and india ink with known absorption and reduced scattering coefficients were used as optical phantoms to assess device accuracy. Solid silicon phantoms were formulated for stability testing. Standard deviations for amplitude and phase shift readings were found to be 0.9% and 0.2 degrees respectively, over a one hour period. The ability of the system to quantify tissue damage in vivo at multiple depths was tested in a porcine burn model.

  7. Penetration depth of photons in biological tissues from hyperspectral imaging in shortwave infrared in transmission and reflection geometries

    NASA Astrophysics Data System (ADS)

    Zhang, Hairong; Salo, Daniel; Kim, David M.; Komarov, Sergey; Tai, Yuan-Chuan; Berezin, Mikhail Y.

    2016-12-01

    Measurement of photon penetration in biological tissues is a central theme in optical imaging. A great number of endogenous tissue factors such as absorption, scattering, and anisotropy affect the path of photons in tissue, making it difficult to predict the penetration depth at different wavelengths. Traditional studies evaluating photon penetration at different wavelengths are focused on tissue spectroscopy that does not take into account the heterogeneity within the sample. This is especially critical in shortwave infrared where the individual vibration-based absorption properties of the tissue molecules are affected by nearby tissue components. We have explored the depth penetration in biological tissues from 900 to 1650 nm using Monte-Carlo simulation and a hyperspectral imaging system with Michelson spatial contrast as a metric of light penetration. Chromatic aberration-free hyperspectral images in transmission and reflection geometries were collected with a spectral resolution of 5.27 nm and a total acquisition time of 3 min. Relatively short recording time minimized artifacts from sample drying. Results from both transmission and reflection geometries consistently revealed that the highest spatial contrast in the wavelength range for deep tissue lies within 1300 to 1375 nm however, in heavily pigmented tissue such as the liver, the range 1550 to 1600 nm is also prominent.

  8. Experimental evaluation of angularly-variable fiber geometry for targeting depth-resolved reflectance from layered epithelial tissue phantoms

    NASA Astrophysics Data System (ADS)

    Wang, Adrien; Nammalvar, Vengadesan; Drezek, Rebekah

    2007-02-01

    The aim of the present study focuses on experimentally demonstrating the efficacy of using angularly-variable fiber geometry to achieve the desired tissue-layer selection and probing depths with the further objective of enhancing the sensitivity and specificity of spectral diagnosis in stratified architectures that resemble human cervical epithelia. The morphological and biochemical features of epithelial tissue vary in accordance with tissue depths; consequently, the accuracy of spectroscopic diagnosis of epithelial dysplasia may be enhanced by probing the optical properties of this tissue. When correlated to cellular dysplasia, layer-specific changes in tissue optical properties may be deciphered by reflectance spectroscopy coupled with angularly-variable fiber geometry. This study addresses the utility of using such angularly-variable fiber geometry for resolving spatially-specific spectral signatures of tissue pathology. This is accomplished by interpreting and analyzing the reflectance spectra of increasingly dysplastic epithelial tissue in two-layer epithelial phantoms. Spectral sensitivity to tissue abnormalities in the epithelial layer is significantly improved as the obliquity of the collection fibers increases from 0 to 40 degrees. Conversely, conventionally orthogonal fibers are found to be more sensitive to changes in stromal tissue properties.

  9. 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.

  10. MicroRNA transcriptome profiling in cardiac tissue of hypertrophic cardiomyopathy patients with MYBPC3 mutations.

    PubMed

    Kuster, Diederik W D; Mulders, Joyce; Ten Cate, Folkert J; Michels, Michelle; Dos Remedios, Cristobal G; da Costa Martins, Paula A; van der Velden, Jolanda; Oudejans, Cees B M

    2013-12-01

    Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in genes encoding sarcomeric proteins. One of the most frequent affected genes is MYBPC3, which encodes the thick filament protein cardiac myosin binding protein C. Despite the prevalence of HCM, disease pathology and clinical outcome of sarcomeric mutations are largely unknown. We hypothesized that microRNAs (miRNAs) could play a role in the disease process. To determine which miRNAs were changed in expression, miRNA arrays were performed on heart tissue from HCM patients with a MYBPC3 mutation (n=6) and compared with hearts of non-failing donors (n=6). 532 out of 664 analyzed miRNAs were expressed in at least one heart sample. 13 miRNAs were differentially expressed in HCM compared with donors (at p<0.01, fold change ≥ 2). The genomic context of these differentially expressed miRNAs revealed that miR-204 (fold change 2.4 in HCM vs. donor) was located in an intron of the TRPM3 gene, encoding an aspecific cation channel involved in calcium entry. RT-PCR analysis revealed a trend towards TRPM3 upregulation in HCM compared with donor myocardium (fold change 2.3, p=0.078). In silico identification of mRNA targets of differentially expressed miRNAs showed a large proportion of genes involved in cardiac hypertrophy and cardiac beta-adrenergic receptor signaling and we showed reduced phosphorylation of cardiac troponin I in the HCM myocardium when compared with donor. HCM patients with MYBPC3 mutations have a specific miRNA expression profile. Downstream mRNA targets reveal possible involvement in cardiac signaling pathways.

  11. 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.

  12. Cardiac strength-interval curves calculated using a bidomain tissue with a parsimonious ionic current

    PubMed Central

    Roth, Bradley J.

    2017-01-01

    The strength-interval curve plays a major role in understanding how cardiac tissue responds to an electrical stimulus. This complex behavior has been studied previously using the bidomain formulation incorporating the Beeler-Reuter and Luo-Rudy dynamic ionic current models. The complexity of these models renders the interpretation and extrapolation of simulation results problematic. Here we utilize a recently developed parsimonious ionic current model with only two currents—a sodium current that activates rapidly upon depolarization INa and a time-independent inwardly rectifying repolarization current IK—which reproduces many experimentally measured action potential waveforms. Bidomain tissue simulations with this ionic current model reproduce the distinctive dip in the anodal (but not cathodal) strength-interval curve. Studying model variants elucidates the necessary and sufficient physiological conditions to predict the polarity dependent dip: a voltage and time dependent INa, a nonlinear rectifying repolarization current, and bidomain tissue with unequal anisotropy ratios. PMID:28222136

  13. "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.

  14. Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles

    PubMed Central

    Qin, Xulei; Riegler, Johannes; Tiburcy, Malte; Zhao, Xin; Chour, Tony; Ndoye, Babacar; Nguyen, Michael; Adams, Jackson; Ameen, Mohamed; Denney, Thomas S.; Yang, Phillip C.; Nguyen, Patricia; Zimmermann, Wolfram H.; Wu, Joseph C.

    2017-01-01

    Background The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance following such treatments are plagued by relatively low detection ability. As the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility. Methods and Results Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds. EHMs were transplanted (n=12) to cover infarct and border zones of recipient rat hearts one month after ischemia reperfusion injury. A control group (n=10) received only sham placement of sutures without EHMs. To assess the efficacy of EHMs, MRI and ultrasound-based strain imaging were performed prior to and four weeks after transplantation. In addition to strain imaging, global cardiac performance was estimated from cardiac MRI. Although no significant differences were found with global changes in left ventricular ejection fraction (EF) (Control −9.6±1.3% vs. EHM −6.2±1.9%, P=0.17), regional myocardial strain from tagged MRI was able to detect preserved systolic function in EHM-treated animals compared to control (Control 4.4±1.0% vs. EHM 1.0±0.6%, P=0.04). However, ultrasound-based strain failed to detect any significant change (Control 2.1±3.0% vs. EHM 6.3±2.9%, P=0.46). Conclusions This study highlights the feasibility of using cardiac strain from tagged MRI to assess functional changes in rat models due to localized regenerative therapies, which may not be detected by conventional measures of global systolic performance. PMID:27903535

  15. 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

  16. 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.

  17. Avermectin induced global DNA hypomethylation and over-expression of heat shock proteins in cardiac tissues of pigeon.

    PubMed

    Liu, Ci; Cao, Ye; Zhou, Shuo; Khoso, Pervez Ahmed; Li, Shu

    2017-01-01

    Despite increasing evidences pointing to residues of avermectin (AVM) pose toxic effects on non-target organisms in environment, but the data in pigeon is insufficient. The alteration of global DNA methylation and response of heat shock proteins (Hsps) are important for assessing the AVM toxicity in cardiac tissues of pigeon (Columba livia). To investigate the effects of AVM exposure in cardiac tissues of pigeon, we detected the expression levels of DNA methyltransferases (Dnmts), methylated DNA-binding domain protein 2 (MBD2), and Hsp 60, 70 and 90. Pigeons were exposed to feed containing AVM (0, 20, 40 and 60mg/kg diet) for 30, 60, 90days respectively, and cardiac tissues were collected and analyzed. We found the transcriptional levels of Dnmt1, Dnmt3a and Dnmt3b mRNA were down-regulated, but the transcriptional levels of MBD2 mRNA were up-regulated by AVM exposure in cardiac tissues of pigeon. Necrocytosis, hemorrhage, infiltration of inflammatory cells and abundant vacuoles appeared in cardiac tissues after AVM exposure. Accompanying this phenotype, the mRNA transcriptional and/or protein levels of Hsp30, Hsp60, Hsp70 and Hsp90 increased. In conclusion, these results underscored AVM exposure caused DNA methylation machinery malfunctions, and induced over-expression of Hsps to improve the protective function against cardiac injury.

  18. MOSFET dosimeter depth-dose measurements in heterogeneous tissue-equivalent phantoms at diagnostic x-ray energies

    SciTech Connect

    Jones, A.K.; Pazik, F.D.; Hintenlang, D.E.; Bolch, W.E.

    2005-10-15

    The objective of the present study was to explore the use of the TN-1002RD metal-oxide-semiconductor field effect transistor (MOSFET) dosimeter for measuring tissue depth dose at diagnostic photon energies in both homogeneous and heterogeneous tissue-equivalent materials. Three cylindrical phantoms were constructed and utilized as a prelude to more complex measurements within tomographic physical phantoms of pediatric patients. Each cylindrical phantom was constructed as a stack of seven 5-cm-diameter and 1-cm-thick discs of materials radiographically representative of either soft tissue (S), bone (B), or lung tissue (L) at diagnostic photon energies. In addition to a homogeneous phantom of soft tissue (SSSSSSS), two heterogeneous phantoms were constructed: SSBBSSS and SBLLBSS. MOSFET dosimeters were then positioned at the interface of each disc, and the phantoms were then irradiated at 66 kVp and 200 mAs. Measured values of absorbed dose at depth were then compared to predicated values of point tissue dose as determined via Monte Carlo radiation transport modeling. At depths exceeding 2 cm, experimental results matched the computed values of dose with high accuracy regardless of the dosimeter orientation (epoxy bubble facing toward or away from the x-ray beam). Discrepancies were noted, however, between measured and calculated point doses near the surface of the phantom (surface to 2 cm depth) when the dosimeters were oriented with the epoxy bubble facing the x-ray beam. These discrepancies were largely eliminated when the dosimeters were placed with the flat side facing the x-ray beam. It is therefore recommended that the MOSFET dosimeters be oriented with their flat sides facing the beam when they are used at shallow depths or on the surface of either phantoms or patients.

  19. Influence of cardiac tissue anisotropy on re-entrant activation in computational models of ventricular fibrillation

    NASA Astrophysics Data System (ADS)

    Clayton, Richard H.

    2009-06-01

    The aim of this study was to establish the role played by anisotropic diffusion in (i) the number of filaments and epicardial phase singularities that sustain ventricular fibrillation in the heart, (ii) the lifetimes of filaments and phase singularities, and (iii) the creation and annihilation dynamics of filaments and phase singularities. A simplified monodomain model of cardiac tissue was used, with membrane excitation described by a simplified 3-variable model. The model was configured so that a single re-entrant wave was unstable, and fragmented into multiple re-entrant waves. Re-entry was then initiated in tissue slabs with varying anisotropy ratio. The main findings of this computational study are: (i) anisotropy ratio influenced the number of filaments sustaining simulated ventricular fibrillation, with more filaments present in simulations with smaller values of transverse diffusion coefficient, (ii) each re-entrant filament was associated with around 0.9 phase singularities on the surface of the slab geometry, (iii) phase singularities were longer lived than filaments, and (iv) the creation and annihilation of filaments and phase singularities were linear functions of the number of filaments and phase singularities, and these relationships were independent of the anisotropy ratio. This study underscores the important role played by tissue anisotropy in cardiac ventricular fibrillation.

  20. Experimental high-intensity focused ultrasound lesion formation in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Muratore, Robert; Kalisz, Andrew; Lee, Paul; Lizzi, Frederic; Fujikura, Kana; Otsuka, Ryo; Homma, Shunichi

    2004-05-01

    High-intensity focused ultrasound (HIFU) (4.5-7.5 MHz) was used to form lesions in cardiac tissue, with an ultimate objective of treating conditions such as hypertrophic cardiomyopathy and ventricular tachycardia. Ultrasound attenuation coefficients were experimentally determined in vitro for calf myocardial tissue, both muscle and pericardial fat. These coefficients were employed in computational models of linear beam propagation, tissue heating profiles and thermal lesion formation for a variety of focused transducers. Modeling was performed for continuous and pulsed exposures. These models suggested initial power levels and exposure durations for in vitro experiments on calf ventricles and septa and ex vivo experiments on canine whole hearts. Repeatability of lesion size and placement was studied as power and exposure parameters varied around the initial values. With these experimental results, power and exposure parameters were selected to create lesions in vivo in canine ventricles and septa in open-chest, anesthetized dogs. Pulsed exposures were synchronized to cardiac and respiration cycles to ensure accurate placement of the lesions. These initial in vivo experiments showed that HIFU treatments in the beating heart are feasible; they also identified refinements that are now being implemented for better control of lesion size and placement. [Work supported by NCI and NHLBI Grant 5R01 CA84588.

  1. 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.

  2. Cardiac arrhythmogenesis in urban air pollution: Optical mapping in a tissue-engineered model

    NASA Astrophysics Data System (ADS)

    Bien, Harold H.

    Recent epidemiological evidence has implicated particulate matter air pollution in cardiovascular disease. We hypothesized that inflammatory mediators released from lung macrophages after exposure to particulate matter predisposes the heart to disturbances in rhythm. Using a rational design approach, a fluorescent optical mapping system was devised to image spatiotemporal patterns of excitation in a tissue engineered model of cardiac tissue. Algorithms for automated data analysis and characterization of rhythm stability were developed, implemented, and verified. Baseline evaluation of spatiotemporal instability patterns in normal cardiac tissue was performed for comparison to an in-vitro model of particulate matter air pollution exposure. Exposure to particulate-matter activated alveolar macrophage conditioned media resulted in paradoxical functional changes more consistent with improved growth. These findings might be indicative of a "stress" response to particulate-matter induced pulmonary inflammation, or may be specific to the animal model (neonatal rat) employed. In the pursuit of elucidating the proposed pathway, we have also furthered our understanding of fundamental behaviors of arrhythmias in general and established a model where further testing might ultimately reveal the mechanism for urban air pollution associated cardiovascular morbidity.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Validation of targets and drug candidates in an engineered three-dimensional cardiac tissue model.

    PubMed

    Navé, Barbara T; Becker, Michael; Roenicke, Volker; Henkel, Thomas

    2002-04-01

    High-throughput target discovery confronts the biopharmaceutical industry with a plethora of target candidates. The validation of these candidates in disease-specific animal models often lacks the required throughput. Here, we discuss perspectives and limitations of a novel engineered three-dimensional cardiac tissue, which enables the influence of gene and drug intervention to be monitored on a cellular and molecular level under physiological conditions in sufficient throughput. The model is an extremely helpful filter to prioritize multiple development candidates before moving a project into large animal models with higher predictivity.

  8. A numerical method for the solution of the bidomain equations in cardiac tissue.

    PubMed

    Keener, J. P.; Bogar, K.

    1998-03-01

    A numerical scheme for efficient integration of the bidomain model of action potential propagation in cardiac tissue is presented. The scheme is a mixed implicit-explicit scheme with no stability time step restrictions and requires that only linear systems of equations be solved at each time step. The method is faster than a fully explicit scheme and there is no increase in algorithmic complexity to use this method instead of a fully explicit method. The speedup factor depends on the timestep size, which can be set solely on the basis of the demands for accuracy. (c) 1998 American Institute of Physics.

  9. Facial soft tissue depths in craniofacial identification (part I): An analytical review of the published adult data.

    PubMed

    Stephan, Carl N; Simpson, Ellie K

    2008-11-01

    With the ever increasing production of average soft tissue depth studies, data are becoming increasingly complex, less standardized, and more unwieldy. So far, no overarching review has been attempted to determine: the validity of continued data collection; the usefulness of the existing data subcategorizations; or if a synthesis is possible to produce a manageable soft tissue depth library. While a principal components analysis would provide the best foundation for such an assessment, this type of investigation is not currently possible because of a lack of easily accessible raw data (first, many studies are narrow; second, raw data are infrequently published and/or stored and are not always shared by some authors). This paper provides an alternate means of investigation using an hierarchical approach to review and compare the effects of single variables on published mean values for adults whilst acknowledging measurement errors and within-group variation. The results revealed: (i) no clear secular trends at frequently investigated landmarks; (ii) wide variation in soft tissue depth measures between different measurement techniques irrespective of whether living persons or cadavers were considered; (iii) no clear clustering of non-Caucasoid data far from the Caucasoid means; and (iv) minor differences between males and females. Consequently, the data were pooled across studies using weighted means and standard deviations to cancel out random and opposing study-specific errors, and to produce a single soft tissue depth table with increased sample sizes (e.g., 6786 individuals at pogonion).

  10. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats.

    PubMed

    Jumabay, Medet; Matsumoto, Taro; Yokoyama, Shin-ichiro; Kano, Koichiro; Kusumi, Yoshiaki; Masuko, Takayuki; Mitsumata, Masako; Saito, Satoshi; Hirayama, Atsushi; Mugishima, Hideo; Fukuda, Noboru

    2009-11-01

    Adipose tissue-derived stem cells have been demonstrated to differentiate into cardiomyocytes and vascular endothelial cells. Here we investigate whether mature adipocyte-derived dedifferentiated fat (DFAT) cells can differentiate to cardiomyocytes in vitro and in vivo by establishing DFAT cell lines via ceiling culture of mature adipocytes. DFAT cells were obtained by dedifferentiation of mature adipocytes from GFP-transgenic rats. We evaluated the differentiating ability of DFAT cells into cardiomyocytes by detection of the cardiac phenotype markers in immunocytochemical and RT-PCR analyses in vitro. We also examined effects of the transplantation of DFAT cells into the infarcted heart of rats on cardiomyocytes regeneration and angiogenesis. DFAT cells expressed cardiac phenotype markers when cocultured with cardiomyocytes and also when grown in MethoCult medium in the absence of cardiomyocytes, indicating that DFAT cells have the potential to differentiate to cardiomyocyte lineage. In a rat acute myocardial infarction model, transplanted DFAT cells were efficiently accumulated in infarcted myocardium and expressed cardiac sarcomeric actin at 8 weeks after the cell transplantation. The transplantation of DFAT cells significantly (p<0.05) increased capillary density in the infarcted area when compared with hearts from saline-injected control rats. We demonstrated that DFAT cells have the ability to differentiate to cardiomyocyte-like cells in vitro and in vivo. In addition, transplantation of DFAT cells led to neovascuralization in rats with myocardial infarction. We propose that DFAT cells represent a promising candidate cell source for cardiomyocyte regeneration in severe ischemic heart disease.

  11. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction.

    PubMed

    Protti, Andrea; Mongue-Din, Heloise; Mylonas, Katie J; Sirker, Alexander; Sag, Can Martin; Swim, Megan M; Maier, Lars; Sawyer, Greta; Dong, Xuebin; Botnar, Rene; Salisbury, Jon; Gray, Gillian A; Shah, Ajay M

    2016-01-01

    Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response. Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI. The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Superaligned Carbon Nanotubes Guide Oriented Cell Growth and Promote Electrophysiological Homogeneity for Synthetic Cardiac Tissues.

    PubMed

    Ren, Jing; Xu, Quanfu; Chen, Xiaomeng; Li, Wei; Guo, Kai; Zhao, Yang; Wang, Qian; Zhang, Zhitao; Peng, Huisheng; Li, Yi-Gang

    2017-10-11

    Cardiac engineering of patches and tissues is a promising option to restore infarcted hearts, by seeding cardiac cells onto scaffolds and nurturing their growth in vitro. However, current patches fail to fully imitate the hierarchically aligned structure in the natural myocardium, the fast electrotonic propagation, and the subsequent synchronized contractions. Here, superaligned carbon-nanotube sheets (SA-CNTs) are explored to culture cardiomyocytes, mimicking the aligned structure and electrical-impulse transmission behavior of the natural myocardium. The SA-CNTs not only induce an elongated and aligned cell morphology of cultured cardiomyocytes, but also provide efficient extracellular signal-transmission pathways required for regular and synchronous cell contractions. Furthermore, the SA-CNTs can reduce the beat-to-beat and cell-to-cell dispersion in repolarization of cultured cells, which is essential for a normal beating rhythm, and potentially reduce the occurrence of arrhythmias. Finally, SA-CNT-based flexible one-piece electrodes demonstrate a multipoint pacing function. These combined high properties make SA-CNTs promising in applications in cardiac resynchronization therapy in patients with heart failure and following myocardial infarctions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Ex vivo paracrine properties of cardiac tissue: Effects of chronic heart failure.

    PubMed

    Boucek, Robert J; Steele, Jasmine; Jacobs, Jeffery P; Steele, Peter; Asante-Korang, Alfred; Quintessenza, James; Steele, Ann

    2015-06-01

    Cardiac regenerative responses are responsive to paracrine factors. We hypothesize that chronic heart failure (HF) in pediatric patients affects cardiac paracrine signaling relevant to resident c-kit(+)cluster of differentiation (CD)34- cardiac stem cells (CSCs). Discarded atrial septum (huAS) and atrial appendages (huAA) from pediatric patients with HF (huAA-HF; n = 10) or without HF (n = 3) were explanted and suspension explant cultured in media. Conditioned media were screened for 120 human factors using unedited monoclonal antibody-based arrays. Significantly expressed (relative chemiluminescence >30 of 100) factors are reported (secretome). Emigrated cells were immunoselected for c-kit and enumerated as CSCs. After culture Day 7, CSCs emigrate from huAA but not huAS. The huAA secretome during CSC emigration included hepatocyte growth factor (HGF), epithelial cell-derived neutrophil attractant-78 (ENA-78)/chemokine (C-X-C motif) ligand (CXCL) 5, growth-regulated oncogene-α (GRO-α)/CXCL1, and macrophage migration inhibitory factor (MIF), candidate pro-migratory factors not present in the huAS secretome. Survival/proliferation of emigrated CSCs required coculture with cardiac tissue or tissue-conditioned media. Removal of huAA (Day 14) resulted in the loss of all emigrated CSCs (Day 28) and in decreased expression of 13 factors, including HGF, ENA-78/CXCL5, urokinase-type plasminogen activator receptor (uPAR)/CD87, and neutrophil-activating protein-2 (NAP-2)/CXCL7 candidate pro-survival factors. Secretomes of atrial appendages from HF patients have lower expression of 14 factors, including HGF, ENA-78/CXCL5, GRO-α/CXCL1, MIF, NAP-2/CXCL7, uPAR/CD87, and macrophage inflammatory protein-1α compared with AA from patients without HF. Suspension explant culturing models paracrine and innate CSC interactions in the heart. In pediatric patients, heart failure has an enduring effect on the ex vivo cardiac-derived secretome, with lower expression of candidate pro

  14. 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

  15. Prediction of hospital outcome in septic shock: a prospective comparison of tissue Doppler and cardiac biomarkers

    PubMed Central

    2010-01-01

    Introduction Diastolic dysfunction as demonstrated by tissue Doppler imaging (TDI), particularly E/e' (peak early diastolic transmitral/peak early diastolic mitral annular velocity) is common in critical illness. In septic shock, the prognostic value of TDI is undefined. This study sought to evaluate and compare the prognostic significance of TDI and cardiac biomarkers (B-type natriuretic peptide (BNP); N-terminal proBNP (NTproBNP); troponin T (TnT)) in septic shock. The contribution of fluid management and diastolic dysfunction to elevation of BNP was also evaluated. Methods Twenty-one consecutive adult patients from a multidisciplinary intensive care unit underwent transthoracic echocardiography and blood collection within 72 hours of developing septic shock. Results Mean ± SD APACHE III score was 80.1 ± 23.8. Hospital mortality was 29%. E/e' was significantly higher in hospital non-survivors (15.32 ± 2.74, survivors 9.05 ± 2.75; P = 0.0002). Area under ROC curves were E/e' 0.94, TnT 0.86, BNP 0.78 and NTproBNP 0.67. An E/e' threshold of 14.5 offered 100% sensitivity and 83% specificity. Adjustment for APACHE III, cardiac disease, fluid balance and grade of diastolic function, demonstrated E/e' as an independent predictor of hospital mortality (P = 0.019). Multiple linear regression incorporating APACHE III, gender, cardiac disease, fluid balance, noradrenaline dose, C reactive protein, ejection fraction and diastolic dysfunction yielded APACHE III (P = 0.033), fluid balance (P = 0.001) and diastolic dysfunction (P = 0.009) as independent predictors of BNP concentration. Conclusions E/e' is an independent predictor of hospital survival in septic shock. It offers better discrimination between survivors and non-survivors than cardiac biomarkers. Fluid balance and diastolic dysfunction were independent predictors of BNP concentration in septic shock. PMID:20331902

  16. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges.

    PubMed

    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.

  17. Probing neural tissue with airy light-sheet microscopy: investigation of imaging performance at depth within turbid media

    NASA Astrophysics Data System (ADS)

    Nylk, Jonathan; McCluskey, Kaley; Aggarwal, Sanya; Tello, Javier A.; Dholakia, Kishan

    2017-02-01

    Light-sheet microscopy (LSM) has received great interest for fluorescent imaging applications in biomedicine as it facilitates three-dimensional visualisation of large sample volumes with high spatiotemporal resolution whilst minimising irradiation of, and photo-damage to the specimen. Despite these advantages, LSM can only visualize superficial layers of turbid tissues, such as mammalian neural tissue. Propagation-invariant light modes have played a key role in the development of high-resolution LSM techniques as they overcome the natural divergence of a Gaussian beam, enabling uniform and thin light-sheets over large distances. Most notably, Bessel and Airy beam-based light-sheet imaging modalities have been demonstrated. In the single-photon excitation regime and in lightly scattering specimens, Airy-LSM has given competitive performance with advanced Bessel-LSM techniques. Airy and Bessel beams share the property of self-healing, the ability of the beam to regenerate its transverse beam profile after propagation around an obstacle. Bessel-LSM techniques have been shown to increase the penetration-depth of the illumination into turbid specimens but this effect has been understudied in biologically relevant tissues, particularly for Airy beams. It is expected that Airy-LSM will give a similar enhancement over Gaussian-LSM. In this paper, we report on the comparison of Airy-LSM and Gaussian-LSM imaging modalities within cleared and non-cleared mouse brain tissue. In particular, we examine image quality versus tissue depth by quantitative spatial Fourier analysis of neural structures in virally transduced fluorescent tissue sections, showing a three-fold enhancement at 50 μm depth into non-cleared tissue with Airy-LSM. Complimentary analysis is performed by resolution measurements in bead-injected tissue sections.

  18. Increase in the calcium content of cardiac tissue after postfixation with osmium tetroxide.

    PubMed

    Blaineau, S; Amsellem, J; Nicaise, G

    1988-11-01

    The concentration of osmium has been measured by destructive chemical analysis in glutaraldehyde fixed heart tissue postfixed with osmium tetroxide and embedded in epoxy resin. After such treatment, the mean atomic number of the specimen (Z) is close to 10, which permits a quantitative analysis of calcium (Ca) by the continuum method, using Z2/A as a correcting factor (A: atomic weight). Wavelength-dispersive X-ray microanalysis has been used to determine the Ca concentration of frog cardiac tissue fixed in glutaraldehyde and embedded in resin. These measurements have been repeated on tissue postfixed in osmium tetroxide; contrary to expectations, the apparent Ca concentration is much higher in osmium treated than in nontreated tissue. However, this result is observed with OsO4 solutions prepared in glass, not with solutions prepared in plastic. It is shown by energy dispersive X-ray analysis of droplets that OsO4 solutions prepared in glass contain large amounts of calcium, potassium and silicon. Care must be taken in preparing OsO4 fixatives when the fixed tissues are to be subjected to X-ray microanalysis of such elements as Ca or Si.

  19. 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.

  20. Studies of Impedance in Cardiac Tissue Using Sucrose Gap and Computer Techniques

    PubMed Central

    McCann, Frances V.; Stibitz, George R.; Huguenin, Jan

    1973-01-01

    Impedances of cardiac cells of an insect were determined as a function of time to test the effects of sucrose and oil as insulating media in a gap arrangement. Impedance values are shown to increase markedly with time when sucrose is used as the insulating agent. Although impedance values are steady when oil is used, it is suggested that a layer of trapped electrolyte provides a shunt pathway and seriously impairs the validity of the measurements. A quick wash with sucrose followed by oil does not alleviate the situation but leaves a layer of sucrose trapped at the tissue-medium interface into which ions diffuse. The hypotheses (a) that the diffusion of intracellular K+ into the sucrose would result in an increase in tissue impedance and (b) that a layer of trapped electrolyte under the oil film provides a shunt pathway are examined by computer analyses of a simple model. ImagesFigure 1AFigure 1B PMID:4754198

  1. Material modeling of cardiac valve tissue: Experiments, constitutive analysis and numerical investigation.

    PubMed

    Heyden, Stefanie; Nagler, Andreas; Bertoglio, Cristóbal; Biehler, Jonas; Gee, Michael W; Wall, Wolfgang A; Ortiz, Michael

    2015-12-16

    A key element of the cardiac cycle of the human heart is the opening and closing of the four valves. However, the material properties of the leaflet tissues, which fundamentally contribute to determine the mechanical response of the valves, are still an open field of research. The main contribution of the present study is to provide a complete experimental data set for porcine heart valve samples spanning all valve and leaflet types under tensile loading. The tests show a fair degree of reproducibility and are clearly indicative of a number of fundamental tissue properties, including a progressively stiffening response with increasing elongation. We then propose a simple anisotropic constitutive model, which is fitted to the experimental data set, showing a reasonable interspecimen variability. Furthermore, we present a dynamic finite element analysis of the aortic valve to show the direct usability of the obtained material parameters in computational simulations.

  2. An investigation of thrust, depth and the impedance cardiogram as measures of cardiopulmonary resuscitation efficacy in a porcine model of cardiac arrest.

    PubMed

    Howe, Andrew; O'Hare, Peter; Crawford, Paul; Delafont, Bruno; McAlister, Olibhear; Di Maio, Rebecca; Clutton, Eddie; Adgey, Jennifer; McEneaney, David

    2015-11-01

    Optimising the depth and rate of applied chest compressions following out of hospital cardiac arrest is crucial in maintaining end organ perfusion and improving survival. The impedance cardiogram (ICG) measured via defibrillator pads produces a characteristic waveform during chest compressions with the potential to provide feedback on cardiopulmonary resuscitation (CPR) and enhance performance. The objective of this pre-clinical study was to investigate the relationship between mechanical and physiological markers of CPR efficacy in a porcine model and examine the strength of correlation between the ICG amplitude, compression depth and end-tidal CO2 (ETCO2). Two experiments were performed using 24 swine (12 per experiment). For experiment 1, ventricular fibrillation (VF) was induced and mechanical CPR commenced at varying thrusts (0-60 kg) for 2 min intervals. Chest compression depth was recorded using a Philips QCPR device with additional recording of invasive physiological parameters: systolic blood pressure, ETCO2, cardiac output and carotid flow. For experiment 2, VF was induced and mechanical CPR commenced at varying depths (0-5 cm) for 2 min intervals. The ICG was recorded via defibrillator pads attached to the animal's sternum and connected to a Heartsine 500 P defibrillator. ICG amplitude, chest compression depth, systolic blood pressure and ETCO2 were recorded during each cycle. In both experiments the within-animal correlation between the measured parameters was assessed using a mixed effect model. In experiment 1 moderate within-animal correlations were observed between physiological parameters and compression depth (r=0.69-0.77) and thrust (r=0.66-0.82). A moderate correlation was observed between compression depth and thrust (r=0.75). In experiment 2 a strong within-animal correlation and moderate overall correlations were observed between ICG amplitude and compression depth (r=0.89, r=0.79) and ETCO2 (r=0.85, r=0.64). In this porcine model of induced

  3. Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

    PubMed

    Nishio, Y; Kashiwagi, A; Taki, H; Shinozaki, K; Maeno, Y; Kojima, H; Maegawa, H; Haneda, M; Hidaka, H; Yasuda, H; Horiike, K; Kikkawa, R

    1998-08-01

    Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P < 0.01 and P < 0.05, respectively). Insulin treatment also consistently prevented changes in the mRNA content of heme oxygenase-1. The oral administration of an antioxidant, probucol, to these diabetic rats partially prevented the elevation of the activity of both NF-kappaB and AP-1, and normalized the mRNA content of heme oxygenase-1 without producing any change in the plasma glucose concentration. These results suggest that elevated oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

  4. Considerations for the use of cellular electrophysiology models within cardiac tissue simulations.

    PubMed

    Cooper, Jonathan; Corrias, Alberto; Gavaghan, David; Noble, Denis

    2011-10-01

    The use of mathematical models to study cardiac electrophysiology has a long history, and numerous cellular scale models are now available, covering a range of species and cell types. Their use to study emergent properties in tissue is also widespread, typically using the monodomain or bidomain equations coupled to one or more cell models. Despite the relative maturity of this field, little has been written looking in detail at the interface between the cellular and tissue-level models. Mathematically this is relatively straightforward and well-defined. There are however many details and potential inconsistencies that need to be addressed, in order to ensure correct operation of a cellular model within a tissue simulation. This paper will describe these issues and how to address them. Simply having models available in a common format such as CellML is still of limited utility, with significant manual effort being required to integrate these models within a tissue simulation. We will thus also discuss the facilities available for automating this in a consistent fashion within Chaste, our robust and high-performance cardiac electrophysiology simulator. It will be seen that a common theme arising is the need to go beyond a representation of the model mathematics in a standard language, to include additional semantic information required in determining the model's interface, and hence to enhance interoperability. Such information can be added as metadata, but agreement is needed on the terms to use, including development of appropriate ontologies, if reliable automated use of CellML models is to become common.

  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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  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. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering.

    PubMed

    Baei, Payam; Jalili-Firoozinezhad, Sasan; Rajabi-Zeleti, Sareh; Tafazzoli-Shadpour, Mohammad; Baharvand, Hossein; Aghdami, Nasser

    2016-06-01

    Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues.

  8. 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.

  9. Tbx18-dependent differentiation of brown adipose tissue-derived stem cells toward cardiac pacemaker cells.

    PubMed

    Chen, Lei; Deng, Zi-Jun; Zhou, Jian-Sheng; Ji, Rui-Juan; Zhang, Xi; Zhang, Chuan-Sen; Li, Yu-Quan; Yang, Xiang-Qun

    2017-04-05

    A cell-sourced biological pacemaker is a promising therapeutic approach for sick sinus syndrome (SSS) or severe atrial ventricular block (AVB). Adipose tissue-derived stem cells (ATSCs), which are optimal candidate cells for possible use in regenerative therapy for acute or chronic myocardial injury, have the potential to differentiate into spontaneous beating cardiomyocytes. However, the pacemaker characteristics of the beating cells need to be confirmed, and little is known about the underlying differential mechanism. In this study, we found that brown adipose tissue-derived stem cells (BATSCs) in mice could differentiate into spontaneous beating cells in 15% FBS Dulbecco's modified Eagle's medium (DMEM) without additional treatment. Subsequently, we provide additional evidence, including data regarding ultrastructure, protein expression, electrophysiology, and pharmacology, to support the differentiation of BATSCs into a cardiac pacemaker phenotype during the course of early cultivation. Furthermore, we found that silencing Tbx18, a key transcription factor in the development of pacemaker cells, terminated the differentiation of BATSCs into a pacemaker phenotype, suggesting that Tbx18 is required to direct BATSCs toward a cardiac pacemaker fate. The expression of Tbx3 and shox2, the other two important transcription factors in the development of pacemaker cells, was decreased by silencing Tbx18, which suggests that Tbx18 mediates the differentiation of BATSCs into a pacemaker phenotype via these two downstream transcription factors.

  10. Pushing the Envelope in Tissue Engineering: Ex Vivo Production of Thick Vascularized Cardiac Extracellular Matrix Constructs

    PubMed Central

    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.

    2015-01-01

    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. PMID:25602926

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

    PubMed

    Jousset, Florian; Rohr, Stephan

    2015-04-01

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

  12. Alternans Resonance and Propagation Block during Supernormal Conduction in Cardiac Tissue with Decreased [K+]o

    PubMed Central

    de Lange, Enno; Kucera, Jan P.

    2010-01-01

    Cardiac restitution is an important factor in arrhythmogenesis. Steep positive action potential duration and conduction velocity (CV) restitution slopes promote alternans and reentrant arrhythmias. We examined the consequences of supernormal conduction (characterized by a negative CV restitution slope) on patterns of conduction and alternans in strands of Luo-Rudy model cells and in cultured cardiac cell strands. Interbeat intervals (IBIs) were analyzed as a function of distance during S1S2 protocols and during pacing at alternating cycle lengths. Supernormal conduction was induced by decreasing [K+]o. In control [K+]o simulations, S1S2 intervals converged toward basic cycle length with a length constant determined by both CV and the CV restitution slope. During alternant pacing, the amplitude of IBI alternans converged with a shorter length constant, determined also by the action potential duration restitution slope. In contrast, during supernormal conduction, S1S2 intervals and the amplitude of alternans diverged. This amplification (resonance) led to phase-locked or more complex alternans patterns, and then to distal conduction block. The convergence/divergence of IBIs was verified in the cultured strands, in which naturally occurring tissue heterogeneities resulted in prominent discontinuities of the spatial IBI profiles. We conclude that supernormal conduction potentiates alternans and spatial analysis of IBIs represents a powerful method to locate tissue heterogeneities. PMID:20371312

  13. Rate-dependent activation failure in isolated cardiac cells and tissue due to Na+ channel block

    PubMed Central

    Spindler, Anthony J.; Paterson, David; Noble, Denis

    2015-01-01

    While it is well established that class-I antiarrhythmics block cardiac sodium channels, the mechanism of action of therapeutic levels of these drugs is not well understood. Using a combination of mathematical modeling and in vitro experiments, we studied the failure of activation of action potentials in single ventricular cells and in tissue caused by Na+ channel block. Our computations of block and unblock of sodium channels by a theoretical class-Ib antiarrhythmic agent predict differences in the concentrations required to cause activation failure in single cells as opposed to multicellular preparations. We tested and confirmed these in silico predictions with in vitro experiments on isolated guinea-pig ventricular cells and papillary muscles stimulated at various rates (2–6.67 Hz) and exposed to various concentrations (5 × 10−6 to 500 × 10−6 mol/l) of lidocaine. The most salient result was that whereas large doses (5 × 10−4 mol/l or higher) of lidocaine were required to inhibit action potentials temporarily in single cells, much lower doses (5 × 10−6 mol/l), i.e., therapeutic levels, were sufficient to have the same effect in papillary muscles: a hundredfold difference. Our experimental results and mathematical analysis indicate that the syncytial nature of cardiac tissue explains the effects of clinically relevant doses of Na+ channel blockers. PMID:26342072

  14. 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.

  15. Comparison of the depth of tissue necrosis between double-freeze and single-freeze nitrous oxide-based cryotherapy

    PubMed Central

    Adepiti, Akinfolarin Clement; Ajenifuja, Olusegun Kayode; Fadahunsi, Oluwaseyi Olatunji; Osasan, Stephen Adebayo; Pelemo, Olumuyiwa Eyitayo; Loto, Morebishe Olabisi

    2016-01-01

    Background: Cryotherapy is one the methods of treating cervical premalignant lesions. It is particularly suitable for low-resource countries because of it is relative cheaper, has low cost of maintenance, ease of use and that does not require electricity which is in short supply in many rural areas of developing countries where the incidence and mortality from cervical cancer is very high. In this study we compared single and double freezing on the cervices of women admitted for hysterectomy for benign conditions using Nitrous-based cryotherapy. Materials and Methods: Patients admitted for elective hysterectomy for benign gynaecological conditions were randomized into two arms. The first group had single freeze cryotherapy while the second arm received double freeze cryotherapy. The cervices were examined 24 hours later to determine the depth of tissue necrosis. Results: In this comparative study, the depth of tissue necrosis was deeper with double freeze compared with single freeze. Also in both arms, the depth of necrosis was deeper on anterior lips than on posterior lips of the cervix. Conclusion: Double freeze technique achieve more depth of tissue necrosis than single-freeze on both anterior and posterior lips of the cervix. PMID:27185971

  16. 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.

  17. Evaluation of menstrual blood stem cells seeded in biocompatible Bombyx mori silk fibroin scaffold for cardiac tissue engineering.

    PubMed

    Rahimi, Maryam; Mohseni-Kouchesfehani, Homa; Zarnani, Amir-Hassan; Mobini, Sahba; Nikoo, Shohreh; Kazemnejad, Somaieh

    2014-08-01

    Recently, silk fibroin scaffolds have been introduced as novel and promising biomaterials in the field of cardiac tissue engineering. This study was designed to compare infiltration, proliferation, and cardiac differentiation potential of menstrual blood-derived stem cells (MenSCs) versus bone marrow-derived mesenchymal stem cells (BMSCs) in Bombyx mori-derived silk scaffold. Our primary data revealed that the fabricated scaffold has mechanical and physical qualities suitable for cardiac tissue engineering. The MenSCs tracking in scaffolds using immunofluorescent staining and scanning electron microscopy confirmed MenSCs attachment, penetration, and distribution within the porous scaffold matrix. Based on proliferation assay using propidium iodide DNA quantification, the significantly higher level of growth rates of both MenSCs and BMSCs was documented in scaffolds than that in two-dimensional culture (p < 0.01). The expression level of TNNT2, a bona fide cardiac differentiation marker, in BMSCs differentiated on silk scaffolds was markedly higher than those cultured in two-dimensional culture indicating the improvement of cardiac differentiation in the silk scaffolds. Furthermore, differentiated MenSCs exhibited higher expression of TNNT2 compared with induced BMSCs. It seems that silk scaffold-seeded MenSCs could be viewed as a novel, safe, natural, and accessible construct for cardiac tissue engineering. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. Effects of Thread Depth in the Neck Area on Peri-Implant Hard and Soft Tissues: An Animal Study.

    PubMed

    Sun, Shan-Pao; Lee, Dong-Won; Yun, Jeong-Ho; Park, Kwang-Ho; Park, Kwang-Bum; Moon, Ik-Sang

    2016-11-01

    Implants with deep thread depth have been developed for the purpose of increasing total implant surface area. However, effects of implant thread depth remain controversial. The aim of this study is to examine effects of thread depth on peri-implant tissues in terms of bone-implant contact (BIC), bone-implant volume (BIV), and hard and soft tissue dimensions using comprehensive analyses, including microcomputed tomography (micro-CT). Five beagle dogs received experimental intramandibular implants 3 months after removal of their premolars and first molars (P2, P3, P4, and M1). Two different types of implants were installed in each animal: deep threaded (DT) and shallow threaded (ST). Resonance frequency testing was performed on the day of implantation as well as 4 and 8 weeks after implantation. Intraoral radiography, micro-CT, and histomorphometry were used to evaluate peri-implant tissues 4 and 8 weeks after implantation. There were no significant differences in resonance frequency test results between the two groups. Although radiographic analysis showed no group differences, micro-CT (P = 0.01) and histomorphometry (P = 0.003) revealed the DT group had significantly lower BIC values than the ST group at 4 weeks. However, by 8 weeks, BIC values of the two groups did not differ significantly. No significant differences in BIV or soft tissue height were observed between the two groups at either time point. DT implants showed no benefits over ST implants when inserted in dog mandibles.

  19. Local tissue water assessed by tissue dielectric constant: anatomical site and depth dependence in women prior to breast cancer treatment-related surgery.

    PubMed

    Mayrovitz, Harvey N; Davey, Suzanne; Shapiro, Elizabeth

    2008-09-01

    Assessing local tissue water using tissue dielectric constant (TDC) values is useful to evaluate oedema/lymphoedema features and their change. Knowledge of anatomical site and tissue depth dependence of TDC values could extend this method's utility. Our goal was to compare TDC values obtained at anatomically paired sites and to investigate their depth dependence. In 22 women (12 awaiting surgery for breast cancer and 10 cancer-free control subjects), four sites (mid-forearm, mid-biceps, axilla and lateral thorax) on both body sides were measured with a 2.5-mm sampling depth probe. Also, at forearm, four different probes with sampling depths of 0.5, 1.5, 2.5 and 5 mm were used. TDC values range between 1 for zero water to 78.5 for 100% water. Site comparisons showed TDC values (mean+/-SD) to be largest at axilla (36.4+/-8.9), least at biceps (21.6+/-3.5) and not different between forearm and thorax (24.3+/-4.0 versus 24.8+/-5.0). Group comparisons showed slightly greater values in patients at forearm and biceps (P<0.05) but no group difference at other sites. Dominant-non-dominant side comparisons showed no significant difference in paired-TDC values in either group at any site. Forearm TDC values decreased with increasing depth from 36.4+/-4.8 at 0.5 mm to a minimum of 21.4+/-3.9 at 5.0 mm, with a sharp decline between 1.5 and 2.5 mm. The composite findings suggest that TDC measurements have the necessary features for usefully assessing oedema/lymphoedema and its change on limbs and at body sites not routinely amenable to assessment by other techniques. The depth dependence feature provides additional flexibility to investigate oedematous or lymphoedematous conditions.

  20. 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

  1. Three-Dimensional Human Cardiac Tissue Engineered by Centrifugation of Stacked Cell Sheets and Cross-Sectional Observation of Its Synchronous Beatings by Optical Coherence Tomography

    PubMed Central

    Hasegawa, Akiyuki; Matsuura, Katsuhisa; Kobayashi, Mari; Iwana, Shin-ichi; Kabetani, Yasuhiro

    2017-01-01

    Three-dimensional (3D) tissues are engineered by stacking cell sheets, and these tissues have been applied in clinical regenerative therapies. The optimal fabrication technique of 3D human tissues and the real-time observation system for these tissues are important in tissue engineering, regenerative medicine, cardiac physiology, and the safety testing of candidate chemicals. In this study, for aiming the clinical application, 3D human cardiac tissues were rapidly fabricated by human induced pluripotent stem (iPS) cell-derived cardiac cell sheets with centrifugation, and the structures and beatings in the cardiac tissues were observed cross-sectionally and noninvasively by two optical coherence tomography (OCT) systems. The fabrication time was reduced to approximately one-quarter by centrifugation. The cross-sectional observation showed that multilayered cardiac cell sheets adhered tightly just after centrifugation. Additionally, the cross-sectional transmissions of beatings within multilayered human cardiac tissues were clearly detected by OCT. The observation showed the synchronous beatings of the thicker 3D human cardiac tissues, which were fabricated rapidly by cell sheet technology and centrifugation. The rapid tissue-fabrication technique and OCT technology will show a powerful potential in cardiac tissue engineering, regenerative medicine, and drug discovery research. PMID:28326324

  2. 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.

  3. Exploring PTX3 expression in Sus scrofa cardiac tissue using RNA sequencing.

    PubMed

    Cabiati, Manuela; Caselli, Chiara; Savelli, Sara; Prescimone, Tommaso; Lionetti, Vincenzo; Giannessi, Daniela; Del Ry, Silvia

    2012-02-10

    The prototypic long pentraxin PTX3 is a novel vascular inflammatory marker sharing similarities with the classic short pentraxin (C-reactive protein). PTX3 is rapidly produced and released by several cell types in response to local inflammation of the cardiovascular system. Plasma PTX3 levels are very low in normal conditions and increase in heart failure (HF) patients with advancing NYHA functional class, but its exact role during HF pathogenetic mechanisms is not yet established. No data about PTX3 cardiac expression in normal and pathological conditions are currently available, either in human or in large-size animals. Of the latter, the pig has a central role in "in vivo" clinical settings but its genome has not been completely sequenced and the PTX3 gene sequence is still lacking. The aim of this study was to sequence the PTX3 in Sus scrofa, whose sequence is not yet present in GenBank. Utilizing our knowledge of this sequence, PTX3 mRNA expression was evaluated in cardiac tissue of normal (n=6) and HF pigs (n=5), obtained from the four chambers. To sequence PTX3 gene in S. scrofa, the high homology between Homo sapiens and S. scrofa was exploited. Pig PTX3 mRNA was sequenced using polymerase chain reaction primers designed from human consensus sequences. The DNA, obtained from different RT-PCR reactions, was sequenced using the Sanger method. S. scrofa PTX3 mRNA, 1-336 bp, was submitted to GenBank (ID: GQ412351). The sequence obtained from pig cardiac tissue shared an 84% sequence identity with human homolog. The presence of PTX3 mRNA expression was detected in all the cardiac chambers sharing an increase after 3 weeks of pacing compared to controls (p=0.036 HF right atrium vs. N; p=0.022, HF left ventricle vs. N). Knowledge of the PTX3 sequence could be a useful starting point for future studies devoted to better understanding the specific role of this molecule in the pathogenesis of cardiovascular diseases.

  4. [Left ventricular functions in patients with cardiac syndrome X: a tissue Doppler study].

    PubMed

    Yazici, Hüseyin Uğur; Sen, Nihat; Tavil, Yusuf; Hizal, Fatma; Turfan, Murat; Poyraz, Fatih; Boyaci, Bülent; Cengel, Atiye

    2009-12-01

    The aim of the study was to compare diagnostic accuracy of tissue Doppler imaging (TDI) and conventional Doppler echocardiography in diagnosis of left ventricular diastolic dysfunction in patients with cardiac syndrome X. Our study was designed as cross-sectional study. In our study, we compared 35 patients with cardiac syndrome X (19 female, mean age 47.2+/- 7.3 years) with 33 healthy persons as control group (18 female, mean age 49.5+/- 7.1 years) with no coronary artery disease and having no ischemic complaints or findings at exercise test. Left ventricular systolic function was found by considering mean values of modified Simpson method for left ventricular ejection fraction and TDI assessment of systolic wave peak velocity. The diastolic function of left ventricle was assessed with conventional echocardiography and TDI. Unpaired t test for independent samples or Mann-Whitney U test were used for comparison of continuous variables, Chi square test - for comparison of categorical variables. To define the capability of predicting diastolic dysfunction for conventional Doppler echocardiography and tissue Doppler imaging ROC curve analysis was applied. Left ventricular ejection fraction and systolic wave peak velocity were similar for both groups. Conventional Doppler echocardiographic measurements for left ventricular diastolic functions delineated the more frequent presence of diastolic dysfunction in cardiac syndrome X group As compared with controls (48% vs 18%; p<0.01). When both methods used for assessing diastolic dysfunction, it was found more apparent (66% vs 24%; p<0.01). When ROC curve was drawn for conventional Doppler echocardiography the AUC was 0.623, the sensitivity and the specificity were 49% and 76%, respectively. When the same was done for TDI the values were AUC=0.669, the sensitivity - 66% and the specificity - 68%. Our study revealed the deterioration of left ventricular diastolic function in patients with cardiac syndrome X. We found TDI

  5. Spiral-Wave Turbulence and Its Control in the Presence of Inhomogeneities in Four Mathematical Models of Cardiac Tissue

    PubMed Central

    Shajahan, T. K.; Nayak, Alok Ranjan; Pandit, Rahul

    2009-01-01

    Regular electrical activation waves in cardiac tissue lead to the rhythmic contraction and expansion of the heart that ensures blood supply to the whole body. Irregularities in the propagation of these activation waves can result in cardiac arrhythmias, like ventricular tachycardia (VT) and ventricular fibrillation (VF), which are major causes of death in the industrialised world. Indeed there is growing consensus that spiral or scroll waves of electrical activation in cardiac tissue are associated with VT, whereas, when these waves break to yield spiral- or scroll-wave turbulence, VT develops into life-threatening VF: in the absence of medical intervention, this makes the heart incapable of pumping blood and a patient dies in roughly two-and-a-half minutes after the initiation of VF. Thus studies of spiral- and scroll-wave dynamics in cardiac tissue pose important challenges for in vivo and in vitro experimental studies and for in silico numerical studies of mathematical models for cardiac tissue. A major goal here is to develop low-amplitude defibrillation schemes for the elimination of VT and VF, especially in the presence of inhomogeneities that occur commonly in cardiac tissue. We present a detailed and systematic study of spiral- and scroll-wave turbulence and spatiotemporal chaos in four mathematical models for cardiac tissue, namely, the Panfilov, Luo-Rudy phase 1 (LRI), reduced Priebe-Beuckelmann (RPB) models, and the model of ten Tusscher, Noble, Noble, and Panfilov (TNNP). In particular, we use extensive numerical simulations to elucidate the interaction of spiral and scroll waves in these models with conduction and ionic inhomogeneities; we also examine the suppression of spiral- and scroll-wave turbulence by low-amplitude control pulses. Our central qualitative result is that, in all these models, the dynamics of such spiral waves depends very sensitively on such inhomogeneities. We also study two types of control schemes that have been suggested for

  6. Evaluation of an established pericardium patch for delivery of mesenchymal stem cells to cardiac tissue.

    PubMed

    Vashi, Aditya V; White, Jacinta F; McLean, Keith M; Neethling, William M L; Rhodes, David I; Ramshaw, John A M; Werkmeister, Jerome A

    2015-06-01

    The present study has evaluated a commercial pericardial material for its capacity to assist as a natural extracellular matrix (ECM) patch for the delivery and retention of mesenchymal stem cells for cardiac repair. The repair of cardiac tissue with cells delivered by an appropriate bioscaffold is expected to offer a superior, long-lasting treatment strategy. The present material, CardioCel®, is based on acellular pericardium that has been stabilized by treatments, including a low concentration of glutaraldehyde, that eliminate calcification after implantation. In the present study, we have assessed this material using human bone marrow mesenchymal stem cells at various cell densities under standard, static cell culture conditions. The initial seeding densities were monitored to evaluate the extent of cell attachment and cell viability, with subsequent cell proliferation assessed up to 4 weeks using an MTS assay. Cell morphology, infiltration, and spreading were tracked using scanning electron microscopy and phalloidin staining. The efficacy of long-term cell survival was further assessed by examining the extent and type of new tissue formation on seeded scaffolds at 70 days; both type I and type III collagens were present in fibrillar structures on these scaffolds indicating that the seeded stem cells had the capacity to differentiate into collagen-producing cells necessary to repair damaged ECM. These data show that the CardioCel® scaffold is an appropriate substrate for the stem cells and has the potential to both retain seeded stem cells and to act as a template for cell propagation and new tissue formation. © 2014 Wiley Periodicals, Inc.

  7. Electrospun PLGA Fibers Incorporated with Functionalized Biomolecules for Cardiac Tissue Engineering

    PubMed Central

    Yu, Jiashing; Lee, An-Rei; Lin, Wei-Han; Lin, Che-Wei; Wu, Yuan-Kun

    2014-01-01

    Structural similarity of electrospun fibers (ESFs) to the native extracellular matrix provides great potential for the application of biofunctional ESFs in tissue engineering. This study aimed to synthesize biofunctionalized poly (L-lactide-co-glycolide) (PLGA) ESFs for investigating the potential for cardiac tissue engineering application. We developed a simple but novel strategy to incorporate adhesive peptides in PLGA ESFs. Two adhesive peptides derived from laminin, YIGSR, and RGD, were covalently conjugated to poly-L-lysine, and then mingled with PLGA solution for electrospinning. Peptides were uniformly distributed on the surface and in the interior of ESFs. PLGA ESFs incorporated with YIGSR or RGD or adsorbed with laminin significantly enhanced the adhesion of cardiomyocytes isolated from neonatal rats. Furthermore, the cells were found to adhere better on ESFs compared with flat substrates after 7 days of culture. Immunofluorescent staining of F-actin, vinculin, a-actinin, and N-cadherin indicated that cardiomyocytes adhered and formed striated α-actinin better on the laminin-coated ESFs and the YIGSR-incorporated ESFs compared with the RGD-incorporated ESFs. The expression of α-myosin heavy chain and β-tubulin on the YIGSR-incorporated ESFs was significantly higher compared with the expression level on PLGA and RGD-incorporated samples. Furthermore, the contraction of cardiomyocytes was faster and lasted longer on the laminin-coated ESFs and YIGSR-incorporated ESFs. The results suggest that aligned YIGSR-incorporated PLGA ESFs is a better candidate for the formation of cardiac patches. This study demonstrated the potential of using peptide-incorporated ESFs as designable-scaffold platform for tissue engineering. PMID:24471778

  8. 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. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. In-depth quantitative cardiac proteomics combining electron transfer dissociation and the metalloendopeptidase Lys-N with the SILAC mouse.

    PubMed

    Scholten, Arjen; Mohammed, Shabaz; Low, Teck Y; Zanivan, Sara; van Veen, Toon A B; Delanghe, Bernard; Heck, Albert J R

    2011-10-01

    In quantitative proteomics stable isotope labeling has progressed from cultured cells toward the total incorporation of labeled atoms or amino acids into whole multicellular organisms. For instance, the recently introduced (13)C(6)-lysine labeled SILAC mouse allows accurate comparison of protein expression directly in tissue. In this model, only lysine, but not arginine, residues are isotope labeled, as the latter may cause complications to the quantification by in vivo conversion of arginine to proline. The sole labeling of lysines discourages the use of trypsin, as not all peptides will be quantifiable. Therefore, in the initial work Lys-C was used for digestion. Here, we demonstrate that the lysine-directed protease metalloendopeptidase Lys-N is an excellent alternative. As lysine directed peptides generally yield longer and higher charged peptides, alongside the more traditional collision induced dissociation we also implemented electron transfer dissociation in a quantitative stable isotope labeling with amino acid in cell culture workflow for the first time. The utility of these two complementary approaches is highlighted by investigating the differences in protein expression between the left and right ventricle of a mouse heart. Using Lys-N and electron transfer dissociation yielded coverage to a depth of 3749 proteins, which is similar as earlier investigations into the murine heart proteome. In addition, this strategy yields quantitative information on ∼ 2000 proteins with a median coverage of four peptides per protein in a single strong cation exchange-liquid chromatography-MS experiment, revealing that the left and right ventricle proteomes are very similar qualitatively as well as quantitatively.

  10. Soft tissue modelling of cardiac fibres for use in coupled mechano-electric simulations.

    PubMed

    Whiteley, Jonathan P; Bishop, Martin J; Gavaghan, David J

    2007-10-01

    The numerical solution of the coupled system of partial differential and ordinary differential equations that model the whole heart in three dimensions is a considerable computational challenge. As a consequence, it is not computationally practical--either in terms of memory or time--to repeat simulations on a finer computational mesh to ensure that convergence of the solution has been attained. In an attempt to avoid this problem while retaining mathematical rigour, we derive a one dimensional model of a cardiac fibre that takes account of elasticity properties in three structurally defined axes within the myocardial tissue. This model of a cardiac fibre is then coupled with an electrophysiological cell model and a model of cellular electromechanics to allow us to simulate the coupling of the electrical and mechanical activity of the heart. We demonstrate that currently used numerical methods for coupling electrical and mechanical activity do not work in this case, and identify appropriate numerical techniques that may be used when solving the governing equations. This allows us to perform a series of simulations that: (i) investigate the effect of some of the assumptions inherent in other models; and (ii) reproduce qualitatively some experimental observations.

  11. 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

  12. 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

    2015-07-06

    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.

  13. 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.

  14. Three-dimensional pseudospectral modelling of cardiac propagation in an inhomogeneous anisotropic tissue.

    PubMed

    Ng, K T; Yan, R

    2003-11-01

    Various investigators have used the monodomain model to study cardiac propagation behaviour. In many cases, the governing non-linear parabolic equation is solved using the finite-difference method. An adequate discretisation of cardiac tissue with realistic dimensions, however, often leads to a large model size that is computationally demanding. Recently, it has been demonstrated, for a two-dimensional homogeneous monodomain, that the Chebyshev pseudospectral method can offer higher computational efficiency than the finite-difference technique. Here, an extension of the pseudospectral approach to a three-dimensional inhomogeneous case with fibre rotation is presented. The unknown transmembrane potential is expanded in terms of Chebyshev polynomial trial functions, and the monodomain equation is enforced at the Gauss-Lobatto node points. The forward Euler technique is used to advance the solution in time. Numerical results are presented that demonstrate that the Chebyshev pseudospectral method offered an even larger improvement in computational performance over the finite-difference method in the three-dimensional case. Specifically, the pseudospectral method allowed the number of nodes to be reduced by approximately 85 times, while the same solution accuracy was maintained. Depending on the model size, simulations were performed with approximately 18-41 times less memory and approximately 99-169 times less CPU time.

  15. Fate of modular cardiac tissue constructs in a syngeneic rat model

    PubMed Central

    Leung, Brendan M; Miyagi, Yasuo; Li, Ren-Ke; Sefton, Michael V

    2014-01-01

    Modular cardiac tissues developed both vascular and cardiac structures in vivo, provided the host response was attenuated by omitting xenoproteins from the modules. Collagen gel modules (with Matrigel™) containing cardiomyocytes (CM) alone or CM with surface seeded endothelial cells (EC; CM/EC modules) were injected into the peri-infarct zone of the heart in syngeneic Lewis rats. After 3 weeks, donor EC developed into blood vessel-like structures that also contained erythrocytes. However, no donor CM were found within the implant sites, presumably because host cells including macrophages and T-cells infiltrated extensively into the injection sites. To lessen the host response, Matrigel™ was omitted from matrix and modules were rinsed with serum-free medium prior to implantation. Host cell infiltration was attenuated, resulting in a higher degree of vascularization with CM/EC modules, than with CM modules without EC. Most importantly, donor CM matured into striated muscle-like structures in Matrigel™-free implants. PMID:23505249

  16. 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.

    PubMed

    Jang, Jinah; Park, Hun-Jun; Kim, Seok-Won; Kim, Heejin; Park, Ju Young; Na, Soo Jin; Kim, Hyeon Ji; Park, Moon Nyeo; Choi, Seung Hyun; Park, Sun Hwa; Kim, Sung Won; Kwon, Sang-Mo; Kim, Pum-Joon; Cho, Dong-Woo

    2017-01-01

    Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures. The printed structure composed of spatial patterning of dual stem cells improves cell-to-cell interactions and differentiation capability and promotes functionality for tissue regeneration. The developed stem cell patch promoted strong vascularization and tissue matrix formation in vivo. The patterned patch exhibited enhanced cardiac functions, reduced cardiac hypertrophy and fibrosis, increased migration from patch to the infarct area, neo-muscle and capillary formation along with improvements in cardiac functions. Therefore, pre-vascularized stem cell patch provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.

  17. A Novel Pulsatile Bioreactor for Mechanical Stimulation of Tissue Engineered Cardiac Constructs

    PubMed Central

    Hollweck, Trixi; Akra, Bassil; Häussler, Simon; Überfuhr, Peter; Schmitz, Christoph; Pfeifer, Stefan; Eblenkamp, Markus; Wintermantel, Erich; Eissner, Günther

    2011-01-01

    After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC) colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro. PMID:24956300

  18. Determining the light scattering and absorption parameters from forward-directed flux measurements in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Costantino, Anthony J.; Hyatt, Christopher J.; Kollisch-Singule, Michaela C.; Beaumont, Jacques; Roth, Bradley J.; Pertsov, Arkady M.

    2017-07-01

    We describe a method to accurately measure the light scattering model parameters from forward-directed flux (FDF) measurements carried out with a fiber-optic probe (optrode). Improved determination of light scattering parameters will, in turn, permit better modeling and interpretation of optical mapping in the heart using voltage-sensitive dyes. Using our optrode-based system, we carried out high spatial resolution measurements of FDF in intact and homogenized cardiac tissue, as well as in intralipid-based tissue phantoms. The samples were illuminated with a broad collimated beam at 660 and 532 nm. Measurements were performed with a plunge fiber-optic probe (NA=0.22) at a spatial resolution of up to 10 μm. In the vicinity of the illuminated surface, the FDF consistently manifested a fast decaying exponent with a space constant comparable with the decay rate of ballistic photons. Using a Monte Carlo model, we obtained a simple empirical formula linking the rate of the fast exponent to the scattering coefficient, the anisotropy parameter g, and the numerical aperture of the probe. The estimates of scattering coefficient based on this formula were validated in tissue phantoms. Potential applications of optical fiber-based FDF measurements for the evaluation of optical parameters in turbid media are discussed.

  19. Determining the light scattering and absorption parameters from forward-directed flux measurements in cardiac tissue.

    PubMed

    Costantino, Anthony J; Hyatt, Christopher J; Kollisch-Singule, Michaela C; Beaumont, Jacques; Roth, Bradley J; Pertsov, Arkady M

    2017-07-01

    We describe a method to accurately measure the light scattering model parameters from forward-directed flux (FDF) measurements carried out with a fiber-optic probe (optrode). Improved determination of light scattering parameters will, in turn, permit better modeling and interpretation of optical mapping in the heart using voltage-sensitive dyes. Using our optrode-based system, we carried out high spatial resolution measurements of FDF in intact and homogenized cardiac tissue, as well as in intralipid-based tissue phantoms. The samples were illuminated with a broad collimated beam at 660 and 532 nm. Measurements were performed with a plunge fiber-optic probe (NA=0.22) at a spatial resolution of up to 10  μm. In the vicinity of the illuminated surface, the FDF consistently manifested a fast decaying exponent with a space constant comparable with the decay rate of ballistic photons. Using a Monte Carlo model, we obtained a simple empirical formula linking the rate of the fast exponent to the scattering coefficient, the anisotropy parameter g, and the numerical aperture of the probe. The estimates of scattering coefficient based on this formula were validated in tissue phantoms. Potential applications of optical fiber-based FDF measurements for the evaluation of optical parameters in turbid media are discussed.

  20. Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study.

    PubMed

    Huffaker, Ray B; Weiss, James N; Kogan, Boris

    2007-06-01

    Early afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs may also occur at rapid heart rates if repolarization reserve is sufficiently reduced. In this setting, spontaneous diastolic sarcoplasmic reticulum (SR) Ca release can facilitate cellular EAD formation by augmenting inward currents during the action potential plateau, allowing reactivation of the window L-type Ca current to reverse repolarization. Here, we investigated the effects of spontaneous SR Ca release-induced EADs on reentrant wave propagation in simulated one-, two-, and three-dimensional homogeneous cardiac tissue using a version of the Luo-Rudy dynamic ventricular action potential model modified to increase the likelihood of these EADs. We found: 1) during reentry, nonuniformity in spontaneous SR Ca release related to subtle differences in excitation history throughout the tissue created adjacent regions with and without EADs. This allowed EADs to initiate new wavefronts propagating into repolarized tissue; 2) EAD-generated wavefronts could propagate in either the original or opposite direction, as a single new wave or two new waves, depending on the refractoriness of tissue bordering the EAD region; 3) by suddenly prolonging local refractoriness, EADs caused rapid rotor displacement, shifting the electrical axis; and 4) rapid rotor displacement promoted self-termination by collision with tissue borders, but persistent EADs could regenerate single or multiple focal excitations that reinitiated reentry. These findings may explain many features of Torsades des pointes, such as perpetuation by focal excitations, rapidly changing electrical axis, frequent self-termination, and occasional degeneration to fibrillation.

  1. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. 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

    2016-01-07

    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.

  4. 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

  5. Trichostatin A enhances differentiation of human induced pluripotent stem cells to cardiogenic cells for cardiac tissue engineering.

    PubMed

    Lim, Shiang Y; Sivakumaran, Priyadharshini; Crombie, Duncan E; Dusting, Gregory J; Pébay, Alice; Dilley, Rodney J

    2013-09-01

    Human induced pluripotent stem (iPS) cells are a promising source of autologous cardiomyocytes to repair and regenerate myocardium for treatment of heart disease. In this study, we have identified a novel strategy to enhance cardiac differentiation of human iPS cells by treating embryoid bodies (EBs) with a histone deacetylase inhibitor, trichostatin A (TSA), together with activin A and bone morphogenetic protein 4 (BMP4). Over a narrow window of concentrations, TSA (1 ng/ml) directed the differentiation of human iPS cells into a cardiomyocyte lineage. TSA also exerted an additive effect with activin A (100 ng/ml) and BMP4 (20 ng/ml). The resulting cardiomyocytes expressed several cardiac-specific transcription factors and contractile proteins at both gene and protein levels. Functionally, the contractile EBs displayed calcium cycling and were responsive to the chronotropic agents isoprenaline (0.1 μM) and carbachol (1 μM). Implanting microdissected beating areas of iPS cells into tissue engineering chambers in immunocompromised rats produced engineered constructs that supported their survival, and they maintained spontaneous contraction. Human cardiomyocytes were identified as compact patches of muscle tissue incorporated within a host fibrocellular stroma and were vascularized by host neovessels. In conclusion, human iPS cell-derived cardiomyocytes can be used to engineer functional cardiac muscle tissue for studying the pathophysiology of cardiac disease, for drug discovery test beds, and potentially for generation of cardiac grafts to surgically replace damaged myocardium.

  6. 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.

  7. Micro-perfusion for cardiac tissue engineering: development of a bench-top system for the culture of primary cardiac cells.

    PubMed

    Khait, Luda; Hecker, Louise; Radnoti, Desmond; Birla, Ravi K

    2008-05-01

    Tissue-engineered constructs have high metabolic requirements during in vitro culture necessitating the development of micro-perfusion systems to maintain high functional performance. In this study, we describe the design, fabrication, and testing of a novel micro-perfusion system to support the culture of primary cardiac cells. Our system consists of a micro-incubator with independent stages for 35-mm tissue culture plates with inflow/outflow manifolds for fluid delivery and aspiration. A peristaltic pump is utilized for fluid delivery and vacuum for fluid aspiration. Oxygen saturation, pH, and temperature are regulated for the media while temperature is regulated within the micro-incubator, fluid reservoir, and oxygenation chamber. Validation of the perfusion system was carried out using primary cardiac myocytes, isolated from 2- to 3-day-old neonatal rat hearts, plated on collagen-coated tissue culture plates. Two million cells/plate were used and the perfusion system was run for 1 h (without the need for a cell culture incubator) while controls were maintained in a standard cell culture incubator. We evaluated the cell viability, cell adhesion, total protein, total RNA, and changes in the expression of SERCA2 and phospholamban using RT-PCR, with N = 6 for each group. We found that there was no significant change in any variable during the 1-h run in the perfusion system. These studies served to demonstrate the compatibility of the perfusion system to support short-term culture of primary cardiac cells.

  8. Esophageal tissue engineering: an in-depth review on scaffold design.

    PubMed

    Tan, J Y; Chua, C K; Leong, K F; Chian, K S; Leong, W S; Tan, L P

    2012-01-01

    Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non-biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design.

  9. Effects of ice packs on tissue temperatures at various depths before and after quadriceps hematoma: studies using sheep.

    PubMed

    Walton, M; Roestenburg, M; Hallwright, S; Sutherland, J C

    1986-01-01

    A standard form of ice pack was applied to the shaved lateral surface of the thighs of anesthetized sheep and temperatures of the underlying tissues were measured by thermocouples inserted to various depths down to 4 cm as well as on the skin surface. An ice pack was applied for a single 20 minute period followed, in some sheep, by a second application 20 minutes later. This procedure was repeated a week later, immediately after physical trauma had been applied to the same area of the thigh. Temperature changes were depth dependent; after a single treatment, temperatures rose rapidly at first but after 2 hours did not regain pretreatment values; during a second application, the temperatures of the deep tissues continued to fall whereas the superficial tissue fell again to similar values as on the first application; temperatures did not fall as much after trauma and this was attributed to an increase in blood flow through the tissues. J Orthop Sports Phys Ther 1986;8(6):294-300.

  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. 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.

  12. Accuracy and reliability of facial soft tissue depth measurements using cone beam computer tomography.

    PubMed

    Fourie, Zacharias; Damstra, Janalt; Gerrits, Peter O; Ren, Yijin

    2010-06-15

    It is important to have accurate and reliable measurements of soft tissue thickness for specific landmarks of the face and scalp when producing a facial reconstruction. In the past several methods have been created to measure facial soft tissue thickness (FSTT) in cadavers and in the living. The conventional spiral CT is mostly used to determine the FSTT but is associated with high radiation doses. The cone beam CT (CBCT) is a relatively new computer tomography system that focuses on head and neck regions and has much lower radiation doses. The aim of this study is to determine the accuracy and reliability of CBCT scans to measure the soft tissue thicknesses of the face. Seven cadaver heads were used. Eleven soft tissue landmarks were identified on each head and a punch hole was made on each landmark using a dermal biopsy punch. The seven cadaver heads were scanned in the CBCT with 0.3 and 0.4mm resolution. The FSTT at the 11 different sites (soft tissue landmarks) were measured using SimPlant-ortho volumetric software. These measurements were compared to the physical measurements. Statistical analysis for the reliability was done by means of the interclass coefficient (ICC) and the accuracy by means of the absolute error (AE) and absolute percentage error (APE). The intra-observer (0.976-0.999) and inter-observer (0.982-0.997) correlations of the CBCT and physical measurements were very high. There was no clinical significant difference between the measurements made on the CBCT images and the physical measurements. Increasing the voxel size from 0.4 to 0.3mm resulted in a slight increase of accuracy. Cone beam CT images of the face using routine scanning protocols are reliable for measuring soft tissue thickness in the facial region and give a good representation of the facial soft tissues. For more accurate data collection the 0.3mm voxel size should be considered.

  13. Scroll wave dynamics in a three-dimensional cardiac tissue model: roles of restitution, thickness, and fiber rotation.

    PubMed Central

    Qu, Z; Kil, J; Xie, F; Garfinkel, A; Weiss, J N

    2000-01-01

    Scroll wave (vortex) breakup is hypothesized to underlie ventricular fibrillation, the leading cause of sudden cardiac death. We simulated scroll wave behaviors in a three-dimensional cardiac tissue model, using phase I of the Luo-Rudy (LR1) action potential model. The effects of action potential duration (APD) restitution, tissue thickness, filament twist, and fiber rotation were studied. We found that APD restitution is the major determinant of scroll wave behavior and that instabilities arising from APD restitution are the main determinants of scroll wave breakup in this cardiac model. We did not see a "thickness-induced instability" in the LR1 model, but a minimum thickness is required for scroll breakup in the presence of fiber rotation. The major effect of fiber rotation is to maintain twist in a scroll wave, promoting filament bending and thus scroll breakup. In addition, fiber rotation induces curvature in the scroll wave, which weakens conduction and further facilitates wave break. PMID:10827961

  14. 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

  15. Alteration of serum and cardiac tissue adropin, copeptin, irisin and TRPM2 expressions in DOX treated male rats.

    PubMed

    Aydin, S; Eren, M N; Kuloglu, T; Aydin, S; Yilmaz, M; Gul, E; Kalayci, M; Yel, Y; Cakmak, T; Bico, S

    2015-04-01

    Doxorubicin (DOX) cardiotoxicity is a significant side effect in cancer survivors. DOX and its metabolites alter cardiac gene expression and affect metabolic energy-related peptides. Adropin, copeptin, irisin and TRPM2 are produced locally in the heart and play a role in energy homeostasis. We investigated the fates of adropin, copeptin, irisin and TRPM2 in serum and cardiac tissues of DOX treated rats. Animals were divided into three groups of six: 1) untreated controls, 2) DOX treated and 3) saline treated. The rats were fed a standard diet ad libitum for 14 days then were sacrificed and heart and serum samples were taken. Adropin, copeptin, irisin levels in tissue homogenates and serum were measured using ELISA. Immunoreactivity of heart tissue adropin, copeptin, irisin and TRPM2 also were investigated. The peptides increased in both serum and cardiac tissue homogenates in animals treated with DOX compared to the other groups. DOX increased adropin in endocardial and myocardial cells, but it decreased expression of copeptin. DOX did not affect endocardial irisin and TRPM2 expressions, but myocardial irisin and TRPM2 expressions were increased. Serum adropin, irisin and copeptin were increased in DOX treated rats. Cardiac adropin, copeptin, irisin and TRPM2 are affected by DOX and may play a role in DOX cardiotoxicity.

  16. Ambient molecular imaging and depth profiling of live tissue by infrared laser ablation electrospray ionization mass spectrometry.

    PubMed

    Nemes, Peter; Barton, Alexis A; Li, Yue; Vertes, Akos

    2008-06-15

    Mass spectrometry in conjunction with atmospheric pressure ionization methods enables the in vivo investigation of biochemical changes with high specificity and sensitivity. Laser ablation electrospray ionization (LAESI) is a recently introduced ambient ionization method suited for the analysis of biological samples with sufficient water content. With LAESI mass spectrometric analysis of chimeric Aphelandra squarrosa leaf tissue, we identify the metabolites characteristic for the green and yellow sectors of variegation. Significant parts of the related biosynthetic pathways (e.g., kaempferol biosynthesis) are ascertained from the detected metabolites and metabolomic databases. Scanning electron microscopy of the ablated areas indicates the feasibility of both two-dimensional imaging and depth profiling with a approximately 350 microm lateral and approximately 50 microm depth resolution. Molecular distributions of some endogenous metabolites show chemical contrast between the sectors of variegation and quantitative changes as the ablation reaches the epidermal and mesophyll layers. Our results demonstrate that LAESI mass spectrometry opens a new way for ambient molecular imaging and depth profiling of metabolites in biological tissues and live organisms.

  17. Root hard-tissue demineralization rate measured by sup 125 I absorptiometry: Comparison with lesion-depth measurements

    SciTech Connect

    Almqvist, H.; Wefel, J.S.; Lagerloef, F. )

    1990-08-01

    The aim of the present study was to compare demineralization of root hard tissue, monitored by {sup 125}I absorptiometry, with lesion-depth measurements under polarized light microscopy. The intact roots of ten human molars, which had not been exposed to the oral environment, were divided into 39 cementum/dentin blocks and exposed to a buffer solution of pH 4.5 containing 2.2 mmol/L calcium and inorganic phosphate. After demineralization for 3.5, 7, 14, and 21 days, transmission measurements by {sup 125}I absorptiometry were performed, and one block from each tooth was taken out of the solution for lesion-depth measurement. The results showed a high degree of correlation (r = 0.952) between lesion depth and change in transmission, with a more rapid increase initially in both variables. A linear relationship with the square root of time was found. Conversion of transmission data to lesion-depth data was possible when this caries model system was used on cementum dentin blocks.

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

    PubMed Central

    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. PMID:26045804

  19. 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.

  20. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Modelling far field pacing for terminating spiral waves pinned to ischaemic heterogeneities in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Boccia, E.; Luther, S.; Parlitz, U.

    2017-05-01

    In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be unpinned (and eventually terminated) using electric far field pulses and recruiting the heterogeneity as a virtual electrode. While for isotropic media the process of unpinning is much better understood, the case of an anisotropic substrate with different conductivities in different directions still needs intensive investigation. To study the impact of anisotropy on the unpinning process, we present numerical simulations based on the bidomain formulation of the phase I of the Luo and Rudy action potential model modified due to the occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave pinned to an ischaemic heterogeneity, we compare the success of sequences of far field pulses in the isotropic and the anisotropic case for spirals still in transient or in steady rotation states. Our results clearly indicate that the range of pacing parameters resulting in successful termination of pinned spiral waves is larger in anisotropic tissue than in an isotropic medium. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

  2. 3D Printed Polycaprolactone Carbon Nanotube Composite Scaffolds for Cardiac Tissue Engineering.

    PubMed

    Ho, Chee Meng Benjamin; Mishra, Abhinay; Lin, Pearlyn Teo Pei; Ng, Sum Huan; Yeong, Wai Yee; Kim, Young-Jin; Yoon, Yong-Jin

    2017-04-01

    Fabrication of tissue engineering scaffolds with the use of novel 3D printing has gained lot of attention, however systematic investigation of biomaterials for 3D printing have not been widely explored. In this report, well-defined structures of polycaprolactone (PCL) and PCL- carbon nanotube (PCL-CNT) composite scaffolds have been designed and fabricated using a 3D printer. Conditions for 3D printing has been optimized while the effects of varying CNT percentages with PCL matrix on the thermal, mechanical and biological properties of the printed scaffolds are studied. Raman spectroscopy is used to characterise the functionalized CNTs and its interactions with PCL matrix. Mechanical properties of the composites are characterised using nanoindentation. Maximum peak load, elastic modulus and hardness increases with increasing CNT content. Differential scanning calorimetry (DSC) studies reveal the thermal and crystalline behaviour of PCL and its CNT composites. Biodegradation studies are performed in Pseudomonas Lipase enzymatic media, showing its specificity and effect on degradation rate. Cell imaging and viability studies of H9c2 cells from rat origin on the scaffolds are performed using fluorescence imaging and MTT assay, respectively. PCL and its CNT composites are able to show cell proliferation and have the potential to be used in cardiac tissue engineering.

  3. Multiphoton microscopy using intrinsic signals for pharmacological studies in unstained cardiac and vascular tissue

    NASA Astrophysics Data System (ADS)

    Beaurepaire, Emmanuel; Boulesteix, Thierry; Pena, Ana-Maria; Pages, Nicole; Senni, Karim; Godeau, Gaston; Sauviat, Martin-Pierre; Schanne-Klein, Marie-Claire

    2005-03-01

    We report two novel applications of multiphoton microscopy for pharmacological studies of unstained cardiovascular tissue. First, we show that second harmonic generation (SHG) microscopy of unstained cardiac myocytes can be used to determine the sarcomere length with sub-resolution accuracy, owing to the remarkable contrast of the SHG signal originating from myosin filaments. A measurement precision of 20 nm is achieved, taking the sample variability into account. We used this technique to measure sarcomere contracture in the presence of saxitoxin, and results were in agreement with mechanical measurements of atrial tissue contracture. Second, we characterized multiphoton microscopy of intact unlabeled arteries. We performed simultaneous detection of two-photon-excited fluorescence (2PEF) from elastin laminae and SHG from collagen fibers upon 860 nm excitation. Combined 2PEF/SHG images provide a highly specific, micron scale description of the architecture of these two major components of the vessel wall. We used this methodology to study the effects of lindane (a pesticide) on the artery wall structure and evidenced structural alteration of the vessel morphology.

  4. Modelling far field pacing for terminating spiral waves pinned to ischaemic heterogeneities in cardiac tissue.

    PubMed

    Boccia, E; Luther, S; Parlitz, U

    2017-06-28

    In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be unpinned (and eventually terminated) using electric far field pulses and recruiting the heterogeneity as a virtual electrode. While for isotropic media the process of unpinning is much better understood, the case of an anisotropic substrate with different conductivities in different directions still needs intensive investigation. To study the impact of anisotropy on the unpinning process, we present numerical simulations based on the bidomain formulation of the phase I of the Luo and Rudy action potential model modified due to the occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave pinned to an ischaemic heterogeneity, we compare the success of sequences of far field pulses in the isotropic and the anisotropic case for spirals still in transient or in steady rotation states. Our results clearly indicate that the range of pacing parameters resulting in successful termination of pinned spiral waves is larger in anisotropic tissue than in an isotropic medium.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'. © 2017 The Authors.

  5. 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.

  6. 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

  7. 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

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

    PubMed

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

    2013-12-06

    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.

  9. Genetic Analysis of Connective Tissue Growth Factor as an Effector of Transforming Growth Factor β Signaling and Cardiac Remodeling

    PubMed Central

    Accornero, Federica; van Berlo, Jop H.; Correll, Robert N.; Elrod, John W.; Sargent, Michelle A.; York, Allen; Rabinowitz, Joseph E.; Leask, Andrew

    2015-01-01

    The matricellular secreted protein connective tissue growth factor (CTGF) is upregulated in response to cardiac injury or with transforming growth factor β (TGF-β) stimulation, where it has been suggested to function as a fibrotic effector. Here we generated transgenic mice with inducible heart-specific CTGF overexpression, mice with heart-specific expression of an activated TGF-β mutant protein, mice with heart-specific deletion of Ctgf, and mice in which Ctgf was also deleted from fibroblasts in the heart. Remarkably, neither gain nor loss of CTGF in the heart affected cardiac pathology and propensity toward early lethality due to TGF-β overactivation in the heart. Also, neither heart-specific Ctgf deletion nor CTGF overexpression altered cardiac remodeling and function with aging or after multiple acute stress stimuli. Cardiac fibrosis was also unchanged by modulation of CTGF levels in the heart with aging, pressure overload, agonist infusion, or TGF-β overexpression. However, CTGF mildly altered the overall cardiac response to TGF-β when pressure overload stimulation was applied. CTGF has been proposed to function as a critical TGF-β effector in underlying tissue remodeling and fibrosis throughout the body, although our results suggest that CTGF is of minimal importance and is an unlikely therapeutic vantage point for the heart. PMID:25870108

  10. Interactive Hierarchical-Flow Segmentation of Scar Tissue From Late-Enhancement Cardiac MR Images.

    PubMed

    Rajchl, Martin; Yuan, Jing; White, James A; Ukwatta, Eranga; Stirrat, John; Nambakhsh, Cyrus M S; Li, Feng P; Peters, Terry M

    2014-01-01

    We propose a novel multi-region image segmentation approach to extract myocardial scar tissue from 3-D whole-heart cardiac late-enhancement magnetic resonance images in an interactive manner. For this purpose, we developed a graphical user interface to initialize a fast max-flow-based segmentation algorithm and segment scar accurately with progressive interaction. We propose a partially-ordered Potts (POP) model to multi-region segmentation to properly encode the known spatial consistency of cardiac regions. Its generalization introduces a custom label/region order constraint to Potts model to multi-region segmentation. The combinatorial optimization problem associated with the proposed POP model is solved by means of convex relaxation, for which a novel multi-level continuous max-flow formulation, i.e., the hierarchical continuous max-flow (HMF) model, is proposed and studied. We demonstrate that the proposed HMF model is dual or equivalent to the convex relaxed POP model and introduces a new and efficient hierarchical continuous max-flow based algorithm by modern convex optimization theory. In practice, the introduced hierarchical continuous max-flow based algorithm can be implemented on the parallel GPU to achieve significant acceleration in numerics. Experiments are performed in 50 whole heart 3-D LE datasets, 35 with left-ventricular and 15 with right-ventricular scar. The experimental results are compared to full-width-at-half-maximum and Signal-threshold to reference-mean methods using manual expert myocardial segmentations and operator variabilities and the effect of user interaction are assessed. The results indicate a substantial reduction in image processing time with robust accuracy for detection of myocardial scar. This is achieved without the need for additional region constraints and using a single optimization procedure, substantially reducing the potential for error.

  11. [Serum/tissue interleukin-6 concentrations and constitutional abnormalities in 4 patients with cardiac myxoma].

    PubMed

    Saji, T; Matsuo, N; Shiono, N; Yokomuro, H; Watanabe, Y; Takanashi, Y; Komatsu, H

    1993-09-01

    Immunological features and the production of interleukin-6 (IL-6) in 4 patients with cardiac myxoma were studied. The patients' age ranged from 11 years old to 57 years old; all 4 patients were female. Case 1, an 11-year-old female patient with myxoma located in the right ventricle, was considered to be a familial case. Her mother had myxomas in the right and left atrium, and had undergone removal of both tumors 3 years before. Peripheral blood examination revealed various inflammatory parameters in all of these patients. White blood cell (WBC) count was over 8,000/cmm in 3 of the 4 patients, positive CRP was found in 2 patients, IgG was higher than 1,500 mg/dl in 3 patients, positive anti-nuclear antibody was seen in 1 patient, and positive rheumatoid factor was identified in 1 patient. The OKT 4/8 ratio of lymphocyte subpopulation was 4.65 in one patient. The lymphocyte mitogenic response to PHA was increased in 2 patients. Serum IL-6 increased in 3 of 4 patients, and returned to normal within 3 to 4 weeks after operation. The IL-6 concentration in the homogenized sample remarkably increased in all 4 patients. Tumors larger than 4 cm contained higher tissue IL-6 concentrations than those smaller than 2 cm. The cultured myxoma cells produced abundant IL-6 in the culture medium supernatant. We conclude that inflammatory signs and immunological abnormalities are common in patients with large cardiac myxoma, and, in addition, serum IL-6 levels may increase in such patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Handheld spatial frequency domain spectrographic imager for depth-sensitive, quantitative spectroscopy of skin tissue

    NASA Astrophysics Data System (ADS)

    Saager, Rolf B.; Dang, An N.; Huang, Samantha S.; Kelly, Kristen M.; Durkin, Anthony J.

    2017-02-01

    Here we present a handheld, implementation of Spatial Frequency Domain Spectroscopy (SFDS) that employs line imaging. The new instrument can measure 1088 spatial locations that span a 3 cm line as opposed to our benchtop system that only collects a single 1 mm diameter spot. This imager, however, retains the spectral resolution ( 1 nm) and range (450 to 1000 nm) of our benchtop system. The device also has tremendously improved mobility and portability, allowing for greater ease of use in clinical setting. A smaller size also enables access to different tissue locations, which increases the flexibility of the device. The design of this portable system not only enables SFDS to be used in clinical settings, but also enables visualization of properties of layered tissues such as skin.

  13. 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

  14. 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

  15. 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.

  16. Dependence of light fluence on treated depth with photosensitization reaction shortly after photosensitizer injection in rabbit myocardial tissue in vivo

    NASA Astrophysics Data System (ADS)

    Suenari, T.; Matsuo, H.; Ito, A.; Miyoshi, S.; Arai, T.

    2010-02-01

    We investigated experimentally dependence of light fluence on treated depth with photosensitization reaction shortly after photosensitizer injection in rabbit myocardial tissue in vivo. In this particular photosensitization reaction scheme, the photosensitizer accumulation characteristics for target region are not available. Meanwhile, the photosensitizer dose and hospitalization period under restricted light circumstance might be reduced. Since both photosensitizer and oxygen supply are governed by blood flow, this photosensitization reaction is influenced significantly by blood flow variation in particular blood vessel occlusion. We employed the myocardial tissue to keep tissue blood flow during the photosensitization reaction because vessel blood flow speed in myocardial tissue is fast to resist vascular occlusion. Surgically exposed rabbits myocardial tissues were irradiated with the light fluence ranging 25-100 J/cm2 by a 663 nm diode laser 30 min after the injection of 2 mg/kg water soluble chlorin photosensitizer, Talaporfin sodium. Two weeks after the irradiation, the rabbits were sacrificed and the histological specimens of the irradiated area were made to measure scar layer thickness. The scar layer tissue thickness of 0.2-3.0 mm was observed microscopically by the light fluence ranging 25-100 J/cm2. The scarring threshold in the deposit light fluence was estimated to 15-25 J/cm3 based on the above mentioned relation assuming constant and uniform myocardial effective attenuation coefficient of 0.72 mm-1. The estimated scarring threshold in the deposit light fluence was lower than the threshold of conventional PDT. Large variation of the estimated threshold value might be attributed to unconsidered PDT parameter such as flow rate inhomogeneity in the myocardial tissue. These results suggested that the photosensitization reaction investigated in this study would be available to apply arrhythmia therapy such as atrial fibrillation.

  17. Creation of a bioreactor for the application of variable amplitude mechanical stimulation of fibrin gel-based engineered cardiac tissue.

    PubMed

    Morgan, Kathy Y; Black, Lauren D

    2014-01-01

    This chapter details the creation of three-dimensional fibrin hydrogels as an engineered myocardial tissue and introduces a mechanical stretch bioreactor system that allows for the cycle-to-cycle variable amplitude mechanical stretch of the constructs as a method of conditioning the constructs to be more similar to native tissue. Though mechanical stimulation has been established as a standard method of improving construct development, most studies have been performed under constant frequency and constant amplitude, even though variability is a critical aspect of healthy cardiac physiology. The introduction of variability in other organ systems has demonstrated beneficial effects to cell function in vitro. We hypothesize that the introduction of variability in engineered cardiac tissue could have a similar effect.

  18. A method for depth-dose distribution measurements in tissue irradiated by a proton beam

    SciTech Connect

    Gambarini, G.; Birattari, C.; Bartolo, D. de

    1994-12-31

    The use of protons and heavy ions for the treatment of malignant and non-malignant disease has aroused a growing interest in the last decade. The notable advantage of heavy charged particles over photons in external beam radiotherapy lies in the possibility of irradiating a small localized region within the body, keeping a low value for the entrance dose. Owing to this high disuniformity of energy deposition, an essential requirement for treatment planning is a precise evaluation of the spatial distribution of absorbed dose. The proposed method for depth-dose distribution measurements utilizes a chemical dosimeter (ferrous sulphate solution plus sulfuric acid and eventually xylenol orange) incorporated in a gelatine, whose role is the maintenance of spatial information. Ionizing radiation causes a variation in some parameters of the system such as the proton relaxation rates in the solution (measurable by NMR analysis) or the optical absorption of the gel in the visible spectrum (measurable by spectrophotometry).

  19. Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice

    PubMed Central

    Kawamura, Ai; Miyagawa, Shigeru; Fukushima, Satsuki; Kawamura, Takuji; Kashiyama, Noriyuki; Ito, Emiko; Watabe, Tadashi; Masuda, Shigeo; Toda, Koichi; Hatazawa, Jun; Morii, Eiichi; Sawa, Yoshiki

    2016-01-01

    Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic, and time courses, as assessed by imaging tools including 18F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells, and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models. PMID:26763872

  20. The assessment of cardiac functions by tissue Doppler-derived myocardial performance index in patients with Behcet's disease.

    PubMed

    Tavil, Yusuf; Ozturk, Mehmet Akif; Sen, Nihat; Kaya, Mehmet Gungor; Hizal, Fatma; Poyraz, Fatih; Turfan, Murat; Onder, Meltem; Gurer, Mehmet Ali; Cengel, Atiye

    2008-03-01

    Vascular involvement is one of the major characteristics of Behcet's disease (BD). However, there are controversial findings regarding cardiac involvement in BD. Although early reports demonstrated that there is diastolic dysfunction in BD, conflicting results were found in the following trials. Hence, a new method for more objectively estimating the cardiac functions is needed. For this aim, we used high-usefulness tissue Doppler echocardiography for detailed analysis of cardiac changes in BD patients because this method was superior to other conventional echocardiographic techniques. The study population included 42 patients with BD (19 men, 23 women; mean age, 35 +/- 10 years, mean disease duration, 2.7 +/- 1.6 years) and 30 healthy subjects (14 men, 16 women; mean age, 38 +/- 7 years). Cardiac functions were determined using echocardiography, comprising standard two-dimensional and conventional Doppler and tissue Doppler imaging (TDI). Peak systolic myocardial velocity at mitral annulus, early diastolic mitral annular velocity (Em), late diastolic mitral annular velocity (Am), Em/Am, and myocardial performance index (MPI) were calculated by TDI. The conventional echocardiographic parameters and tissue Doppler measurements were similar between the groups. Tissue Doppler derived mitral relaxation time was longer (75 +/- 13 vs 63 +/- 16 msn, p = 0.021) in patients with BD. There was statistically significant difference between the two groups regarding left ventricular MPI (0.458 +/- 0.072 vs 0.416 +/- 0.068%, p = 0.016), which were calculated from tissue Doppler systolic time intervals. There was also significant correlation between the disease duration and MPI (r = 0.38, p = 0.017). We have demonstrated that tissue Doppler-derived myocardial left ventricular relaxation time and MPI were impaired in BD patients, although systolic and diastolic function parameters were comparable in the patients and controls.

  1. 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

  2. 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

  3. TRIPAS: A triapplicator system with relocatable 'hot spot' at tissue depth

    SciTech Connect

    Bicher, H.I.; Afuwape, S.A.; Wolfstein, R.S.; Bruley, D.F.; Reesman, K. )

    1990-01-01

    Solving the problem of heat focusing and standardization of the clinical application of hyperthermia requires a mathematical prediction model. The model should include the medium constitutive parameter, and be able to predict positioning of the microwave applicators to optimize treatment planning and provide for reproducible treatment set-up. We present a configuration of 3 applicators subtended by an equilateral triangle in order to target and relocate a 'hot spot' for improved treatment of deep tumors. A simple geometric analysis is illustrated. The microwave beam absorption profile, from the three power sources, was obtained from phantom studies depicting the radiative heat pattern for the triapplicator system (TRIPAS). A complex mathematical model was developed to demonstrate interaction of the beams in the medium. It was observed empirically that under coherent propagation in the near field electromagnetic (EM) waves tend to add at the center, while varying the propagation axial focal length caused a relocation of the summing focal points. Mathematical prediction correlated very well with the phantom studies. SAR values above 100 W/kg were achieved at 12.5 cm phantom depth, creating a relocatable 'hot spot' at the concentric foci of the 3 air cooled horn microwave applicators operating at 300 MHz.

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

    PubMed

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

    2009-01-01

    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.

  5. 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.

  6. 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.

  7. Tissue synchronisation imaging accurately measures left ventricular dyssynchrony and predicts response to cardiac resynchronisation therapy

    PubMed Central

    Van de Veire, Nico R; Bleeker, Gabe B; De Sutter, Johan; Ypenburg, Claudia; Holman, Eduard R; van der Wal, Ernst E; Schalij, Martin J; Bax, Jeroen J

    2007-01-01

    Background Tissue synchronisation imaging (TSI) is a new technique to assess left ventricular (LV) dyssynchrony. Objectives The value of using TSI to automatically assess LV dyssynchrony compared with manual assessment of LV dyssynchrony from colour‐coded tissue Doppler imaging (TDI), and to evaluate the value of TSI to predict response to cardiac resynchronisation therapy (CRT). Methods 60 symptomatic patients with heart failure with depressed LV ejection fraction (LVEF) and QRS >120 ms were evaluated clinically and echocardiographically at baseline and after 6 months of CRT. LV dyssynchrony was measured manually using velocity tracings from the colour‐coded TDI and automatically using TSI. LV volumes and LVEF were assessed from two‐dimensional echocardiography. Clinical responders had to exhibit an improvement in New York Heart Association functional class by ⩾1 score and an improvement by ⩾25% in 6 min walking distance after 6 months. Reverse LV remodelling was defined as a reduction of ⩾15% LV end‐systolic volume. Results An excellent correlation was observed between LV dyssynchrony measured manually and automatically derived by TSI (r = 0.95, p<0.001). 34 patients showed clinical response after 6 months of CRT and 32 patients showed reverse remodelling. Baseline characteristics were comparable between responders and non‐responders, except for more extensive LV dyssynchrony in the responders: 78 (26) vs 29 (29) ms (p<0.001) as assessed manually, and 79 (29) vs 28 (27) ms (p<0.001) as assessed with TSI. Using a cut‐off value of 65 ms to define extensive LV dyssynchrony, TSI had a sensitivity of 81% with a specificity of 89% to predict reverse LV remodelling. Conclusion TSI allows automatic and reliable assessment of LV dyssynchrony and predicts reverse LV remodelling after CRT. PMID:17309912

  8. Evidence for an immunological relationship between Streptococcus mutans and human cardiac tissue.

    PubMed Central

    Hughes, M; Machardy, S M; Sheppard, A J; Woods, N C

    1980-01-01

    Two-dimensional immunoelectrophoresis, indirect immunofluorescence, and radioimmunoassay were used to demonstrate that antisera from rabbits immunized with some strains of Streptococcus mutans contain antibodies that cross-react with human cardiac tissue. These rabbits were sensitized to a shocking dose of human heart antigen, and anaphylactic deaths were sometimes produced. Myocarditis was also a result of the immunization procedure. Data obtained with all five techniques were comparable. Cross-reactivity could be associated with three antigens designated ID, IF, and HL. Antigens ID and IF were major immunogens of S. mutans Ingbritt, but HL antibodies were produced only after hyperimmunization. Corss-reactivity was of an immunological nature and not the result of nonspecific factors such as bacterial Fc reactive components or antibody elicited to growth medium constituents. These findings support the hypothesis that immunization with S. mutans can induce autoimmune reactions and indicate that antigens must be selected with caution before formulating any dental caries vaccine. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6991419

  9. Anisotropic x-ray scattering and orientation fields in cardiac tissue cells

    NASA Astrophysics Data System (ADS)

    Bernhardt, M.; Nicolas, J.-D.; Eckermann, M.; Eltzner, B.; Rehfeldt, F.; Salditt, T.

    2017-01-01

    X-ray diffraction from biomolecular assemblies is a powerful technique which can provide structural information about complex architectures such as the locomotor systems underlying muscle contraction. However, in its conventional form, macromolecular diffraction averages over large ensembles. Progress in x-ray optics has now enabled to probe structures on sub-cellular scales, with the beam confined to a distinct organelle. Here, we use scanning small angle x-ray scattering (scanning SAXS) to probe the diffraction from cytoskeleton networks in cardiac tissue cells. In particular, we focus on actin-myosin composites, which we identify as the dominating contribution to the anisotropic diffraction patterns, by correlation with optical fluorescence microscopy. To this end, we use a principal component analysis approach to quantify direction, degree of orientation, nematic order, and the second moment of the scattering distribution in each scan point. We compare the fiber orientation from micrographs of fluorescently labeled actin fibers to the structure orientation of the x-ray dataset and thus correlate signals of two different measurements: the native electron density distribution of the local probing area versus specifically labeled constituents of the sample. Further, we develop a robust and automated fitting approach based on a power law expansion, in order to describe the local structure factor in each scan point over a broad range of the momentum transfer {q}{{r}}. Finally, we demonstrate how the methodology shown for freeze dried cells in the first part of the paper can be translated to alive cell recordings.

  10. 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.

  11. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 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%.

  13. 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%.

  14. Engineered early embryonic cardiac tissue increases cardiomyocyte proliferation by cyclic mechanical stretch via p38-MAP kinase phosphorylation.

    PubMed

    Clause, Kelly C; Tinney, Joseph P; Liu, Li J; Keller, Bradley B; Tobita, Kimimasa

    2009-06-01

    Cardiomyocyte (CM) transplantation is one therapeutic option for cardiac repair. Studies suggest that fetal CMs display the best cell type for cardiac repair, which can finitely proliferate, integrate with injured host myocardium, and restore cardiac function. We have recently developed an engineered early embryonic cardiac tissue (EEECT) using embryonic cardiac cells and have shown that EEECT contractile properties and cellular proliferative response to cyclic mechanical stretch stimulation mimic developing fetal myocardium. However, it remains unknown whether cyclic mechanical stretch-mediated high cellular proliferation activity within EEECT reflects CM or non-CM population. Studies have shown that p38-mitogen-activated protein kinase (p38MAPK) plays an important role in both cyclic mechanical stretch stimulation and cellular proliferation. Therefore, in the present study, we tested the hypothesis that cyclic mechanical stretch (0.5 Hz, 5% strain for 48 h) specifically increases EEECT CM proliferation mediated by p38MAPK activity. Cyclic mechanical stretch increased CM, but not non-CM, proliferation and increased p38MAPK phosphorylation. Treatment of EEECT with the p38MAPK inhibitor, SB202190, reduced CM proliferation. The negative CM proliferation effects of SB202190 were not reversed by concurrent stretch stimulation. Results suggest that immature CM proliferation within EEECT can be positively regulated by mechanical stretch and negatively regulated by p38MAPK inhibition.

  15. Enhancement of image quality and imaging depth with Airy light-sheet microscopy in cleared and non-cleared neural tissue.

    PubMed

    Nylk, Jonathan; McCluskey, Kaley; Aggarwal, Sanya; Tello, Javier A; Dholakia, Kishan

    2016-10-01

    We have investigated the effect of Airy illumination on the image quality and depth penetration of digitally scanned light-sheet microscopy in turbid neural tissue. We used Fourier analysis of images acquired using Gaussian and Airy light-sheets to assess their respective image quality versus penetration into the tissue. We observed a three-fold average improvement in image quality at 50 μm depth with the Airy light-sheet. We also used optical clearing to tune the scattering properties of the tissue and found that the improvement when using an Airy light-sheet is greater in the presence of stronger sample-induced aberrations. Finally, we used homogeneous resolution probes in these tissues to quantify absolute depth penetration in cleared samples with each beam type. The Airy light-sheet method extended depth penetration by 30% compared to a Gaussian light-sheet.

  16. Enhancement of image quality and imaging depth with Airy light-sheet microscopy in cleared and non-cleared neural tissue

    PubMed Central

    Nylk, Jonathan; McCluskey, Kaley; Aggarwal, Sanya; Tello, Javier A.; Dholakia, Kishan

    2016-01-01

    We have investigated the effect of Airy illumination on the image quality and depth penetration of digitally scanned light-sheet microscopy in turbid neural tissue. We used Fourier analysis of images acquired using Gaussian and Airy light-sheets to assess their respective image quality versus penetration into the tissue. We observed a three-fold average improvement in image quality at 50 μm depth with the Airy light-sheet. We also used optical clearing to tune the scattering properties of the tissue and found that the improvement when using an Airy light-sheet is greater in the presence of stronger sample-induced aberrations. Finally, we used homogeneous resolution probes in these tissues to quantify absolute depth penetration in cleared samples with each beam type. The Airy light-sheet method extended depth penetration by 30% compared to a Gaussian light-sheet. PMID:27867712

  17. Measurement of signal intensity depth profiles in rat brains with cardiac arrest maintaining primary temperature by wide-field optical coherence tomography.

    PubMed

    Sato, Manabu; Nomura, Daisuke; Tsunenari, Takashi; Nishidate, Izumi

    2010-09-10

    We have already reported that after an injection for euthanasia, the signal intensity of optical coherence tomography (OCT) images are 2.7 times increased before cardiac arrest (CA) using OCT and rat brains without temperature control to show the potential of OCT to monitor tissue viability in brains [Appl. Opt.48, 4354 (2009)APOPAI0003-693510.1364/AO.48.004354]. In this paper, we similarly measured maintaining the primary temperature of rat brains. It was confirmed that when maintaining the primary temperature, the time courses of the ratios of signal intensity (RSIs) were almost the same as those without temperature control. RSIs after CA varied from 1.6 to 4.5 and depended on positions measured in tissues. These results mean that the OCT technique has clinical potential for applications to monitor or diagnose a focal degraded area, such as cerebral infarctions due to focal ischemia in brains.

  18. Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue.

    PubMed

    Garcia, Jordan A; Benboujja, Fouzi; Beaudette, Kathy; Rogers, Derek; Maurer, Rie; Boudoux, Caroline; Hartnick, Christopher J

    2016-11-01

    Vocal fold scarring, a condition defined by increased collagen content, is challenging to treat without a method of noninvasively assessing vocal fold structure in vivo. The goal of this study was to observe the effects of vocal fold collagen content on optical coherence tomography imaging to develop a quantifiable marker of disease. Excised specimen study. Massachusetts Eye and Ear Infirmary. Porcine vocal folds were injected with collagenase to remove collagen from the lamina propria. Optical coherence tomography imaging was performed preinjection and at 0, 45, 90, and 180 minutes postinjection. Mean pixel intensity (or image brightness) was extracted from images of collagenase- and control-treated hemilarynges. Texture analysis of the lamina propria at each injection site was performed to extract image contrast. Two-factor repeated measure analysis of variance and t tests were used to determine statistical significance. Picrosirius red staining was performed to confirm collagenase activity. Mean pixel intensity was higher at injection sites of collagenase-treated vocal folds than control vocal folds (P < .0001). Fold change in image contrast was significantly increased in collagenase-treated vocal folds than control vocal folds (P = .002). Picrosirius red staining in control specimens revealed collagen fibrils most prominent in the subepithelium and above the thyroarytenoid muscle. Specimens treated with collagenase exhibited a loss of these structures. Collagen removal from vocal fold tissue increases image brightness of underlying structures. This inverse relationship may be useful in treating vocal fold scarring in patients. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  19. Increased connective tissue growth factor associated with cardiac fibrosis in the mdx mouse model of dystrophic cardiomyopathy.

    PubMed

    Au, Carol G; Butler, Tanya L; Sherwood, Megan C; Egan, Jonathan R; North, Kathryn N; Winlaw, David S

    2011-02-01

    Cardiomyopathy contributes to morbidity and mortality in Duchenne muscular dystrophy (DMD), a progressive muscle-wasting disorder. A major feature of the hearts of DMD patients and the mdx mouse model of the disease is cardiac fibrosis. Connective tissue growth factor (CTGF) is involved in the fibrotic process in many organs. This study utilized the mdx mouse model to assess the role of CTGF and other extracellular matrix components during the development of fibrosis in the dystrophic heart. Left ventricular function of mdx and control mice at 6, 29 and 43 weeks was measured by echocardiography. Young (6 weeks old) mdx hearts had normal function and histology. At 29 weeks of age, mdx mice developed cardiac fibrosis and increased collagen expression. The onset of fibrosis was associated with increased CTGF transcript and protein expression. Increased intensity of CTGF immunostaining was localized to fibrotic areas in mdx hearts. The upregulation of CTGF was also concurrent with increased expression of tissue inhibitor of matrix metalloproteinases (TIMP-1). These changes persisted in 43 week old mdx hearts and were combined with impaired cardiac function and increased gene expression of transforming growth factor (TGF)-β1 and matrix metalloproteinases (MMP-2, MMP-9). In summary, an association was observed between cardiac fibrosis and increased CTGF expression in the mdx mouse heart. CTGF may be a key mediator of early and persistent fibrosis in dystrophic cardiomyopathy.

  20. How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

    PubMed Central

    Perán, Macarena; García, María Angel; Lopez-Ruiz, Elena; Jiménez, Gema; Marchal, Juan Antonio

    2013-01-01

    Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac. PMID:28809213

  1. 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. © 2016. Published by The Company of Biologists Ltd.

  2. 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.

  3. 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.

  4. I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology.

    PubMed

    Sidorov, Veniamin Y; Samson, Philip C; Sidorova, Tatiana N; Davidson, Jeffrey M; Lim, Chee C; Wikswo, John P

    2017-01-15

    Engineered 3D cardiac tissue constructs (ECTCs) can replicate complex cardiac physiology under normal and pathological conditions. Currently, most measurements of ECTC contractility are either made isometrically, with fixed length and without control of the applied force, or auxotonically against a variable force, with the length changing during the contraction. The "I-Wire" platform addresses the unmet need to control the force applied to ECTCs while interrogating their passive and active mechanical and electrical characteristics. A six-well plate with inserted PDMS casting molds containing neonatal rat cardiomyocytes cultured with fibrin for 13-15days is mounted on the motorized mechanical stage of an inverted microscope equipped with a fast sCMOS camera. A calibrated flexible probe provides strain load of the ECTC via lateral displacement, and the microscope detects the deflections of both the probe and the ECTC. The ECTCs exhibited longitudinally aligned cardiomyocytes with well-developed sarcomeric structure, recapitulated the Frank-Starling force-tension relationship, and demonstrated expected transmembrane action potentials, electrical and mechanical restitutions, and responses to both β-adrenergic stimulation and blebbistatin. The I-Wire platform enables creation and mechanical and electrical characterization of ECTCs, and hence can be valuable in the study of cardiac diseases, drug screening, drug development, and the qualification of cells for tissue-engineered regenerative medicine. There is a growing interest in creating engineered heart tissue constructs for basic cardiac research, applied research in cardiac pharmacology, and repair of damaged hearts. We address an unmet need to characterize fully the performance of these tissues with our simple "I-Wire" assay that allows application of controlled forces to three-dimensional cardiac fiber constructs and measurement of both the electrical and mechanical properties of the construct. The advantage of I

  5. Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation

    PubMed Central

    Biermann, Daniel; Eder, Alexandra; Arndt, Florian; Seoudy, Hatim; Reichenspurner, Hermann; Mir, Thomas; Riso, Arlindo; Kozlik-Feldmann, Rainer; Peldschus, Kersten; Kaul, Michael G.; Schuler, Tillman; Krasemann, Susanne; Hansen, Arne; Eschenhagen, Thomas; Sachweh, Jörg S.

    2016-01-01

    The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit. PMID:27875570

  6. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    PubMed

    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

    2010-08-10

    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). 99mTc-labeled ASCs (1x10(6) 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 gamma-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. 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 administering co-injection of ASCs with biopolymers.

  7. 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

  8. 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 Central

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

    2013-01-01

    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. PMID:23265414

  9. 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.

  10. Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study.

    PubMed

    Coelho-Filho, Otavio Rizzi; Shah, Ravi; Lavagnoli, Carlos Fernando Ramos; Barros, Jose Carlos; Neilan, Tomas G; Murthy, Venkatesh L; de Oliveira, Pedro Paulo Martins; Souza, Jose Roberto Matos; de Oliveira Severino, Elaine Soraya Barbosa; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira Filho, Lindemberg; Garcia, Jose; Semigran, Marc J; Coelho, Otavio Rizzi; Jerosch-Herold, Michael; Petrucci, Orlando

    2016-07-20

    After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.

  11. 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.

  12. Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3β pathway

    PubMed Central

    Yao, Yu-Yu; Yin, Hang; Shen, Bo; Smith, Robert S.; Liu, Yuying; Gao, Lin; Chao, Lee; Chao, Julie

    2008-01-01

    Aims We investigated the role of the Akt-glycogen synthase kinase (GSK)-3β signalling pathway in mediating the protective effects of tissue kallikrein on myocardial injury by promoting angiogenesis and blood flow in rats after myocardial infarction (MI). Methods and results Human tissue kallikrein gene in an adenoviral vector, with or without co-administration of dominant-negative Akt (Ad.DN-Akt) or constitutively active GSK-3β (Ad.GSK-3βS9A), was injected into rat myocardium after MI. The expression of recombinant human kallikrein in rat heart significantly improved cardiac function and reduced infarct size 10 days after gene delivery. Kallikrein administration significantly increased myocardial blood flow as well as capillary and arteriole densities in the infarcted myocardium. Kallikrein increased cardiac Akt and GSK-3β phosphorylation in conjunction with decreased GSK-3β activity and the upregulation of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2). All of kallikrein’s effects on the myocardium were abrogated by Ad.DN-Akt and Ad.GSK-3βS9A. Moreover, in cultured human aortic endothelial cells, tissue kallikrein stimulated capillary tube formation and promoted cell migration; however, these effects were blocked by Ad.DN-Akt, Ad.GSK-3βS9A, icatibant (a kinin B2 receptor antagonist), Tki (a VEGF receptor tyrosine kinase inhibitor), and a neutralizing VEGF antibody. In addition, tissue kallikrein decreased GSK-3β activity via the phosphatidylinositol 3-kinase-Akt pathway and enhanced VEGF and VEGFR-2 expression in endothelial cells. Conclusion These data provide the first direct evidence that tissue kallikrein protects against acute-phase MI by promoting neovascularization, restoring regional blood flow and improving cardiac function through the kinin B2 receptor-Akt-GSK-3β and VEGF signalling pathways. PMID:18689794

  13. 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

  14. DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors.

    PubMed

    Stenzig, Justus; Hirt, Marc N; Löser, Alexandra; Bartholdt, Lena M; Hensel, Jan-Tobias; Werner, Tessa R; Riemenschneider, Mona; Indenbirken, Daniela; Guenther, Thomas; Müller, Christian; Hübner, Norbert; Stoll, Monika; Eschenhagen, Thomas

    2016-01-01

    DNA methylation affects transcriptional regulation and constitutes a drug target in cancer biology. In cardiac hypertrophy, DNA methylation may control the fetal gene program. We therefore investigated DNA methylation signatures and their dynamics in an in vitro model of cardiac hypertrophy based on engineered heart tissue (EHT). We exposed EHTs from neonatal rat cardiomyocytes to a 12-fold increased afterload (AE) or to phenylephrine (PE 20 µM) and compared DNA methylation signatures to control EHT by pull-down assay and DNA methylation microarray. A 7-day intervention sufficed to induce contractile dysfunction and significantly decrease promoter methylation of hypertrophy-associated upregulated genes such as Nppa (encoding ANP) and Acta1 (α-skeletal actin) in both intervention groups. To evaluate whether pathological consequences of AE are affected by inhibiting de novo DNA methylation we applied AE in the absence and presence of DNA methyltransferase (DNMT) inhibitors: 5-aza-2'-deoxycytidine (aza, 100 µM, nucleosidic inhibitor), RG108 (60 µM, non-nucleosidic) or methylene disalicylic acid (MDSA, 25 µM, non-nucleosidic). Aza had no effect on EHT function, but RG108 and MDSA partially prevented the detrimental consequences of AE on force, contraction and relaxation velocity. RG108 reduced AE-induced Atp2a2 (SERCA2a) promoter methylation. The results provide evidence for dynamic DNA methylation in cardiac hypertrophy and warrant further investigation of the potential of DNA methylation in the treatment of cardiac hypertrophy.

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

    PubMed Central

    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.

    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. PMID:26224885

  16. Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue

    PubMed Central

    Nakane, Takeichiro; Masumoto, Hidetoshi; Tinney, Joseph P.; Yuan, Fangping; Kowalski, William J.; Ye, Fei; LeBlanc, Amanda J.; Sakata, Ryuzo; Yamashita, Jun K.; Keller, Bradley B.

    2017-01-01

    The current study describes a scalable, porous large-format engineered cardiac tissue (LF-ECT) composed of human induced pluripotent stem cells (hiPSCs) derived multiple lineage cardiac cells with varied 3D geometries and cell densities developed towards the goal of scale-up for large animal pre-clinical studies. We explored multiple 15 × 15 mm ECT geometries using molds with rectangular internal staggered posts (mesh, ME), without posts (plain sheet, PS), or long parallel posts (multiple linear bundles, ML) and a gel matrix containing hiPSC-derived cardiomyocytes, endothelial, and vascular mural cells matured in vitro for 14 days. ME-ECTs displayed the lowest dead cell ratio (p < 0.001) and matured into 0.5 mm diameter myofiber bundles with greater 3D cell alignment and higher active stress than PS-ECTs. Increased initial ECT cell number beyond 6 M per construct resulted in reduced cell survival and lower active stress. The 6M-ME-ECTs implanted onto 1 week post-infarct immune tolerant rat hearts engrafted, displayed evidence for host vascular coupling, and recovered myocardial structure and function with reduced scar area. We generated a larger (30 × 30 mm) ME-ECT to confirm scalability. Thus, large-format ECTs generated from hiPSC-derived cardiac cells may be feasible for large animal preclinical cardiac regeneration paradigms. PMID:28368043

  17. Cardiac Arrests Associated with Low Plasma and Tissue Levels of Local Anaesthetics.

    PubMed

    Alexandre, Joachim; Humbert, Xavier; Sassier, Marion; Cesbron, Alexandre; Le Naourès, Cécile; Pottier, Véronique; Puddu, Paolo-Emilio; Milliez, Paul; Coquerel, Antoine; Fedrizzi, Sophie

    2015-10-16

    Although local anaesthetics cardiac toxicity is usually the result of high local anaesthetics dose, based on a pharmacovigilance case report and an analyze of the French Pharmacovigilance Database between January 1(st), 2007 and December 31(st), 2013, we hypothesized that in some patients, the combination of medical or drug risk factors may be responsible for cardiac anaesthetics toxicity at lower plasma concentrations. © 2015 Société Française de Pharmacologie et de Thérapeutique.

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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

  19. The proliferative potential of human cardiac stem cells was unaffected after a long-term cryopreservation of tissue blocks

    PubMed Central

    Iguchi, Nobuo; Cho, Yasunori; Inoue, Masaki; Murakami, Tsutomu; Tabata, Minoru; Takanashi, Shuichiro; Tomoike, Hitonobu

    2017-01-01

    Background Human c-kit-positive cardiac stem cells (CSCs) have been used to treat patients suffering from ischemic cardiomyopathy. This study aimed to investigate whether a long-term storage of cardiac tissues would influence the growth potential of the subsequently isolated CSCs. Methods A total of 34 fresh samples were obtained from various cardiac regions [right atrium (RA), left atrium (LA), and/or left ventricle (LV)] of 21 patients. From 12 of these patients, 18 samples kept frozen for ~2 years were employed to prepare and characterize the CSCs. After confirming the specificity of the cell sorting by c-kit immunolabeling, the growth rate (number of doublings per day), BrdU positivity, and colony forming unit (CFU) were measured in each CSC population; the values were compared among distinct cardiac regions as well as between fresh and frozen tissues from which CSCs were derived. Results Among independent measurements indicating growth potential, the growth rate and BrdU positivity remarkably correlated in freshly prepared CSCs. The cells obtained from every examined region displayed a high proliferative capacity with the growth rate of 0.48±0.19 and the BrdU positivity of 15.0%±7.6%. The right atrial CSCs tended to show a greater growth than those in the other two areas. Similarly, the CSCs were isolated from tissue blocks, cryopreserved for ~2 years, and compared with CSCs derived from the fresh specimens of the same patients. Importantly, we were able to obtain and culture CSCs from every frozen material, and their proliferative potential, represented by the growth rate of 0.47±0.22 and the BrdU positivity of 13.7%±7.9%, was not inferior to that of the freshly prepared cells. Conclusions The long-term cryopreservation of cardiac tissues did not affect the growth potential of the derivative CSCs. Our findings should expand the therapeutic applications of these cells over a longer time span. PMID:28251120

  20. Early improvement in cardiac function detected by tissue Doppler and strain imaging after melphalan-dexamethasone therapy in a 51-year old subject with severe cardiac amyloidosis.

    PubMed

    Ballo, Piercarlo; Motto, Andrea; Corsini, Francesca; Orlandini, Francesco; Mondillo, Sergio

    2008-11-12

    We report the case of a 51-year old man with symptoms of heart failure due to severe cardiac amyloidosis, in whom treatment with melphalan and dexamethasone yielded significant improvement in clinical status and both systolic and diastolic left ventricular (LV) function over a 12-week follow-up. The improvement in LV performance was detected by Tissue Doppler (TD) and strain analysis, despite no changes in standard indices such as ejection fraction and Doppler pattern of mitral inflow. Color TD-derived myocardial velocity and deformation indices also revealed a reduction in intra-ventricular early diastolic asynchrony after therapy. In addition, an improvement in intra-ventricular systolic synchrony was detected by strain rate and strain, but not by color TD velocity imaging. These findings suggest that treatment with melphalan and dexamethasone may improve symptoms of heart failure and LV performance in subjects with cardiac amyloidosis, and that TD and particularly strain imaging could represent useful techniques to monitor the effect of therapy on LV function in the follow-up of these patients.

  1. Metabolic aspects of cardiac and skeletal muscle tissues in the condition of hypoxia, ischaemia and reperfusion induced by extracorporeal circulation.

    PubMed

    Corbucci, G G; Menichetti, A; Cogliati, A; Ruvolo, C

    1995-01-01

    Extracorporeal circulation (ECC) during aortopulmonary bypass surgery allows the investigation of the metabolic and biochemical effects of hypoxia (skeletal muscle), ischaemia (cardiac muscle) and reperfusion (skeletal and cardiac muscle) in homogeneous groups of patients. In this study we examined the mitochondrial enzymic response to oxidative stress in 40 subjects, and analysis was carried out on heart and skeletal-muscle biopsies taken before, during and after aortic clamping and 115 min of ECC. The results obtained constitute a clinical and biochemical picture characterized by some peculiar adaptive changes of enzymic activities which thus antagonize the oxidative damage due to acute hypoxia, ischaemia and reperfusion. Consequently it seems that this cellular protective mechanism plays a crucial role in the reversibility of oxidative damage in hypoxic and ischaemic tissues.

  2. 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.

  3. Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

    PubMed

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

    2014-12-02

    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. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (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. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  4. Hypoxia-induced epigenetic modifications are associated with cardiac tissue fibrosis and the development of a myofibroblast-like phenotype.

    PubMed

    Watson, Chris J; Collier, Patrick; Tea, Isaac; Neary, Roisin; Watson, Jenny A; Robinson, Claire; Phelan, Dermot; Ledwidge, Mark T; McDonald, Kenneth M; McCann, Amanda; Sharaf, Osama; Baugh, John A

    2014-04-15

    Ischemia caused by coronary artery disease and myocardial infarction leads to aberrant ventricular remodeling and cardiac fibrosis. This occurs partly through accumulation of gene expression changes in resident fibroblasts, resulting in an overactive fibrotic phenotype. Long-term adaptation to a hypoxic insult is likely to require significant modification of chromatin structure in order to maintain the fibrotic phenotype. Epigenetic changes may play an important role in modulating hypoxia-induced fibrosis within the heart. Therefore, the aim of the study was to investigate the potential pro-fibrotic impact of hypoxia on cardiac fibroblasts and determine whether alterations in DNA methylation could play a role in this process. This study found that within human cardiac tissue, the degree of hypoxia was associated with increased expression of collagen 1 and alpha-smooth muscle actin (ASMA). In addition, human cardiac fibroblast cells exposed to prolonged 1% hypoxia resulted in a pro-fibrotic state. These hypoxia-induced pro-fibrotic changes were associated with global DNA hypermethylation and increased expression of the DNA methyltransferase (DNMT) enzymes DNMT1 and DNMT3B. Expression of these methylating enzymes was shown to be regulated by hypoxia-inducible factor (HIF)-1α. Using siRNA to block DNMT3B expression significantly reduced collagen 1 and ASMA expression. In addition, application of the DNMT inhibitor 5-aza-2'-deoxycytidine suppressed the pro-fibrotic effects of TGFβ. Epigenetic modifications and changes in the epigenetic machinery identified in cardiac fibroblasts during prolonged hypoxia may contribute to the pro-fibrotic nature of the ischemic milieu. Targeting up-regulated expression of DNMTs in ischemic heart disease may prove to be a valuable therapeutic approach.

  5. 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 vascularizatio