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Sample records for myocardial tissue construct

  1. Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds?

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    Domenech, Maribella; Polo-Corrales, Lilliana; Ramirez-Vick, Jaime E; Freytes, Donald O

    2016-12-01

    Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.

  2. Biomaterials in myocardial tissue engineering

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    Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica

    2016-01-01

    Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

  3. Myocardial regeneration potential of adipose tissue-derived stem cells

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    Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

    2010-10-22

    Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

  4. Myocardial regeneration potential of adipose tissue-derived stem cells

    International Nuclear Information System (INIS)

    Bai, Xiaowen; Alt, Eckhard

    2010-01-01

    Research highlights: → Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. → For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. → This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying

  5. Design Approaches to Myocardial and Vascular Tissue Engineering.

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    Akintewe, Olukemi O; Roberts, Erin G; Rim, Nae-Gyune; Ferguson, Michael A H; Wong, Joyce Y

    2017-06-21

    Engineered tissues represent an increasingly promising therapeutic approach for correcting structural defects and promoting tissue regeneration in cardiovascular diseases. One of the challenges associated with this approach has been the necessity for the replacement tissue to promote sufficient vascularization to maintain functionality after implantation. This review highlights a number of promising prevascularization design approaches for introducing vasculature into engineered tissues. Although we focus on encouraging blood vessel formation within myocardial implants, we also discuss techniques developed for other tissues that could eventually become relevant to engineered cardiac tissues. Because the ultimate solution to engineered tissue vascularization will require collaboration between wide-ranging disciplines such as developmental biology, tissue engineering, and computational modeling, we explore contributions from each field.

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

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    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.

  7. Hypercholesterolemia and Myocardial function evaluated via Tissue Doppler Imaging

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    Kotaru Pavan

    2009-11-01

    Full Text Available Abstract Objective To establish a link between hypercholesterolemia and myocardial dysfunction. Background Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI. Methods Twenty-seven rabbits were studied: 7 were fed normal chow (group 1 and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3. Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia. Results Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 ± 305 mg/dl vs. 114 ± 95 mg/dl and 87 ± 37 mg/dl; p 2 = 0.17 p = 0.04, r2 = 0.37 p = 0.001 and r2 = 0.24 p = 0.01. Conclusion Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective.

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

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    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.

  9. Myocardial ultrasonic tissue characterization in patients with thyroid dysfunction

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    Schmidt André

    2010-04-01

    Full Text Available Abstract Background Structural myocardial abnormalities have been extensively documented in hypothyroidism. Experimental studies in animal models have also shown involvement of thyroid hormones in gene expression of myocardial collagen. This study was planned to investigate the ability of ultrasonic tissue characterization, as evaluated by integrated backscatter (IBS, to early identify myocardial involvement in thyroid dysfunction. Patients and Methods We studied 15 patients with hyperthyroidism (HYPER, 8 patients with hypothyroidism (HYPO, 14 patients with subclinical hypothyroidism (SCH and 19 normal (N subjects, who had normal LV systolic function. After treatment, 10 HYPER, 6 HYPO, and 8 SCH patients were reevaluated. IBS images were obtained and analyzed in parasternal short axis (papillary muscle level view, at left ventricular (LV posterior wall. The following IBS variables were analyzed: 1 the corrected coefficient (CC of IBS, obtained by dividing IBS intensity by IBS intensity measured in a rubber phantom, using the same equipment adjustments, at the same depth; 2 cardiac cyclic variation (CV of IBS - peak-to-peak difference between maximal and minimal values of IBS during cardiac cycle; 3 cardiac cyclic variation index (CVI of IBS - percentual relationship between the cyclic variation (CV and the mean value of IBS intensity. Results CC of IBS was significantly larger (p Conclusions CC of IBS was able to differentiate cardiac involvement in patients with overt HYPO and HYPER who had normal LV systolic function. These early myocardial structural abnormalities were partially reversed by drug therapy in HYPER group. On the other hand, although mean IBS intensity tended to be slightly larger in patients with SCH as compared to N, this difference was not statistical significant.

  10. Effect of nicorandil on the myocardial tissue perfusion and myocardial cell injury in patients with diabetes after PCI

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    Xue-Li Ren1

    2017-04-01

    Full Text Available Objective: To study the effect of nicorandil on the myocardial tissue perfusion and myocardial cell damage in patients with diabetes after percutaneous coronary intervention (PCI. Methods: 68 patients with coronary heart disease and type 2 diabetes mellitus who received PCI in our hospital between May 2011 and September 2015 were collected and then divided into observation group and control group (n=34 according to the single-blind randomized control method. Control group of patients received PCI alone, and the observation group of patients received nicorandil therapy after PCI. After treatment, real-time myocardial ultrasound contrast was used to evaluate the myocardial perfusion of two groups of patients; blood biochemical analyzer was used to detect the contents of peripheral blood myocardial enzyme spectrum indexes; the ELISA method was used to detect the contents of serum oxidative stress indicators; RIA method was used to detect the contents of serum apoptosis molecules. Results: After treatment, the myocardial tissue perfusion parameters plateau peak intensity (A, slope rate of curve (β and myocardial blood flow (A×β levels of observation group were significantly higher than those of control group (P<0.05; peripheral blood myocardial enzyme spectrum indexes creatine kinase (CK, lactate dehydrogenase (LDH, troponin I (cTnI and glutamic oxalacetic transaminase (GOT contents of observation group were significantly lower than those of control group (P<0.05; serum vitamin E (VitE and vitamin C (VitC contents of observation group were significantly higher than those of control group while malondialdehyde (MDA, advanced oxidation protein products (AOPPs, soluble apoptosis-associated factor (sFas and soluble apoptosis-associated factor ligand (sFasL contents were lower than those of control group (P<0.05. Conclusion: Adjuvant nicorandil therapy can improve the myocardial perfusion and reduce the myocardial cell injury in patients with coronary

  11. Polarization image segmentation of radiofrequency ablated porcine myocardial tissue.

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    Iftikhar Ahmad

    Full Text Available Optical polarimetry has previously imaged the spatial extent of a typical radiofrequency ablated (RFA lesion in myocardial tissue, exhibiting significantly lower total depolarization at the necrotic core compared to healthy tissue, and intermediate values at the RFA rim region. Here, total depolarization in ablated myocardium was used to segment the total depolarization image into three (core, rim and healthy zones. A local fuzzy thresholding algorithm was used for this multi-region segmentation, and then compared with a ground truth segmentation obtained from manual demarcation of RFA core and rim regions on the histopathology image. Quantitative comparison of the algorithm segmentation results was performed with evaluation metrics such as dice similarity coefficient (DSC = 0.78 ± 0.02 and 0.80 ± 0.02, sensitivity (Sn = 0.83 ± 0.10 and 0.91 ± 0.08, specificity (Sp = 0.76 ± 0.17 and 0.72 ± 0.17 and accuracy (Acc = 0.81 ± 0.09 and 0.71 ± 0.10 for RFA core and rim regions, respectively. This automatic segmentation of parametric depolarization images suggests a novel application of optical polarimetry, namely its use in objective RFA image quantification.

  12. Vascularization of soft tissue engineering constructs

    DEFF Research Database (Denmark)

    Pimentel Carletto, Rodrigo

    with mechanical properties in the range of soft tissues has not been fully achieved. My project focused on the fabrication and the active perfusion of hydrogel constructs with multi-dimensional vasculature and controlled mechanical properties targeting soft tissues. Specifically, the initial part of the research...... nanotechnology-based paradigm for engineering vascularised liver tissue for transplantation”) and the Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics (Danish National Research Foundation (DNRF122)....

  13. Cryopreservation of tissue engineered constructs for bone.

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    Kofron, Michelle D; Opsitnick, Natalie C; Attawia, Mohamed A; Laurencin, Cato T

    2003-11-01

    The large-scale clinical use of tissue engineered constructs will require provisions for its mass availability and accessibility. Therefore, it is imperative to understand the effects of low temperature (-196 degrees C) on the tissue engineered biological system. Initial studies used samples of the osteoblast-like cell line (SaOS-2) adhered to a two-dimensional poly(lactide-co-glycolide) thin film (2D-PLAGA) or a three-dimensional poly(lactide-co-glycolide) sintered microsphere matrix (3D-PLAGA) designed for bone tissue engineering. Experimental samples were tested for their ability to maintain cell viability, following low temperature banking for one week, in solutions of the penetrating cryoprotective agents, dimethylsulfoxide (DMSO), ethylene glycol, and glycerol. Results indicated the DMSO solution yielded the greatest percent cell survival for SaOS-2 cells adhered to both the 2D- and 3D-PLAGA scaffolds; therefore, DMSO was used to cryopreserve mineralizing primary rabbit osteoblasts cells adhered to 2D-PLAGA matrices for 35 days. Results indicated retention of the extracellular matrix architecture as no statistically significant difference in the pre- and post-thaw mineralized structures was measured. Percent cell viability of the mineralized constructs following low temperature storage was approximately 50%. These are the first studies to address the issue of preservation techniques for tissue engineered constructs. The ability to successfully cryopreserve mineralized tissue engineered matrices for bone may offer an unlimited and readily available source of bone-like materials for orthopaedic applications.

  14. Vascularization of soft tissue engineering constructs

    DEFF Research Database (Denmark)

    Pimentel Carletto, Rodrigo

    nanotechnology-based paradigm for engineering vascularised liver tissue for transplantation”) and the Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics (Danish National Research Foundation (DNRF122).......Vascularization is recognized to be the biggest challenge for the fabrication of tissues and finally, organs in vitro. So far, several fabrication techniques have been proposed to create a perfusable vasculature within hydrogels, however, the vascularization and perfusion of hydrogels...... with mechanical properties in the range of soft tissues has not been fully achieved. My project focused on the fabrication and the active perfusion of hydrogel constructs with multi-dimensional vasculature and controlled mechanical properties targeting soft tissues. Specifically, the initial part of the research...

  15. Fabrication of myogenic engineered tissue constructs.

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    Pacak, Christina A; Cowan, Douglas B

    2009-05-01

    Despite the fact that electronic pacemakers are life-saving medical devices, their long-term performance in pediatric patients can be problematic owing to the restrictions imposed by a child's small size and their inevitable growth. Consequently, there is a genuine need for innovative therapies designed specifically for pediatric patients with cardiac rhythm disorders. We propose that a conductive biological alternative consisting of a collagen-based matrix containing autologously-derived cells could better adapt to growth, reduce the need for recurrent surgeries, and greatly improve the quality of life for these patients. In the present study, we describe a procedure for incorporating primary skeletal myoblast cell cultures within a hydrogel matrix to fashion a surgically-implantable tissue construct that will serve as an electrical conduit between the upper and lower chambers of the heart. Ultimately, we anticipate using this type of engineered tissue to restore atrioventricular electrical conduction in children with complete heart block. In view of that, we isolate myoblasts from the skeletal muscles of neonatal Lewis rats and plate them onto laminin-coated tissue culture dishes using a modified version of established protocols. After one to two days, cultured cells are collected and mixed with antibiotics, type 1 collagen, Matrigel, and NaHCO(3). The result is a viscous, uniform solution that can be cast into a mold of nearly any shape and size. For our tissue constructs, we employ type 1 collagen isolated from fetal lamb skin using standard procedures. Once the tissue has solidified at 37 degrees C, culture media is carefully added to the plate until the construct is submerged. The engineered tissue is then allowed to further condense through dehydration for 2 more days, at which point it is ready for in vitro assessment or surgical-implantation.

  16. Assessment of residual tissue viability by exercise testing in recent myocardial infarction: comparison of the electrocardiogram and myocardial perfusion scintigraphy.

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    Margonato, A; Ballarotto, C; Bonetti, F; Cappelletti, A; Sciammarella, M; Cianflone, D; Chierchia, S L

    1992-04-01

    The assessment of residual myocardial viability in infarcted areas is relevant for subsequent management and prognosis but requires expensive technology. To evaluate the possibility that simple, easily obtainable clinical markers may detect the presence of within-infarct viable tissue, the significance of exercise-induced ST elevation occurring in leads exploring the area of a recent Q wave myocardial infarction was assessed. Twenty-five patients with recent (less than 6 months) myocardial infarction were studied. All had angiographically documented coronary artery disease, diagnostic Q waves (n = 24) or negative T waves (n = 25) on the rest 12-lead electrocardiogram and exhibited during exercise greater than or equal to 1.5 mm ST segment elevation (n = 17) or isolated T wave pseudonormalization (n = 8) in the infarct-related leads. ST-T wave changes were reproduced in all patients during thallium-201 exercise myocardial scintigraphy. A fixed perfusion defect was observed in 24 of the 25 patients. A reversible defect was seen in 16 (94%) of 17 patients who exhibited transient ST elevation during exercise but in only 4 (50%) of the 8 patients who had only T wave pseudonormalization. In conclusion, in patients with recent myocardial infarction, analysis of simple ST segment variables obtained during exercise testing may allow a first-line discrimination of those who may potentially benefit from a revascularization procedure.

  17. Hierarchical Design of Tissue Regenerative Constructs.

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    Rose, Jonas C; De Laporte, Laura

    2018-03-01

    The worldwide shortage of organs fosters significant advancements in regenerative therapies. Tissue engineering and regeneration aim to supply or repair organs or tissues by combining material scaffolds, biochemical signals, and cells. The greatest challenge entails the creation of a suitable implantable or injectable 3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell-induced tissue formation. This review gives an overview of the essential components of tissue regenerating scaffolds, ranging from the molecular to the macroscopic scale in a hierarchical manner. Further, this review elaborates about recent pivotal technologies, such as photopatterning, electrospinning, 3D bioprinting, or the assembly of micrometer-scale building blocks, which enable the incorporation of local heterogeneities, similar to most native extracellular matrices. These methods are applied to mimic a vast number of different tissues, including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the tremendous progress that has been made in the last decade, it remains a hurdle to build biomaterial constructs in vitro or in vivo with a native-like structure and architecture, including spatiotemporal control of biofunctional domains and mechanical properties. New chemistries and assembly methods in water will be crucial to develop therapies that are clinically translatable and can evolve into organized and functional tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Plasma Ceramides as Prognostic Biomarkers and Their Arterial and Myocardial Tissue Correlates in Acute Myocardial Infarction

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    Leonardo P. de Carvalho, MD, PhD

    2018-04-01

    Full Text Available Summary: We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI. Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature’s 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature. Key Words: acute coronary syndrome, ceramides, dihydroceramides, major adverse cardiovascular and cerebrovascular events, prognosis, risk prediction

  19. Parametric techniques for characterizing myocardial tissue by magnetic resonance imaging (part 1): T1 mapping.

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    Perea Palazón, R J; Ortiz Pérez, J T; Prat González, S; de Caralt Robira, T M; Cibeira López, M T; Solé Arqués, M

    2016-01-01

    The development of myocardial fibrosis is a common process in the appearance of ventricular dysfunction in many heart diseases. Magnetic resonance imaging makes it possible to accurately evaluate the structure and function of the heart, and its role in the macroscopic characterization of myocardial fibrosis by late enhancement techniques has been widely validated clinically. Recent studies have demonstrated that T1-mapping techniques can quantify diffuse myocardial fibrosis and the expansion of the myocardial extracellular space in absolute terms. However, further studies are necessary to validate the usefulness of this technique in the early detection of tissue remodeling at a time when implementing early treatment would improve a patient's prognosis. This article reviews the state of the art for T1 mapping of the myocardium, its clinical applications, and its limitations. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  20. Parametric methods for characterizing myocardial tissue by magnetic resonance imaging (part 2): T2 mapping.

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    Perea Palazón, R J; Solé Arqués, M; Prat González, S; de Caralt Robira, T M; Cibeira López, M T; Ortiz Pérez, J T

    2015-01-01

    Cardiac magnetic resonance imaging is considered the reference technique for characterizing myocardial tissue; for example, T2-weighted sequences make it possible to evaluate areas of edema or myocardial inflammation. However, traditional sequences have many limitations and provide only qualitative information. Moreover, traditional sequences depend on the reference to remote myocardium or skeletal muscle, which limits their ability to detect and quantify diffuse myocardial damage. Recently developed magnetic resonance myocardial mapping techniques enable quantitative assessment of parameters indicative of edema. These techniques have proven better than traditional sequences both in acute cardiomyopathy and in acute ischemic heart disease. This article synthesizes current developments in T2 mapping as well as their clinical applications and limitations. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  1. Reduction of myocardial ischemia-reperfusion injury by mechanical tissue resuscitation using sub-atmospheric pressure.

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    Argenta, Louis C; Morykwas, Michael J; Mays, Jennifer J; Thompson, Edreca A; Hammon, John W; Jordan, James E

    2010-03-01

    Reperfusion-induced injury after myocardial infarction is associated with a well-defined sequence of early and late cardiomyocyte death. Most present attempts to ameliorate this sequence focus on a single facet of the complex process in an attempt to salvage cardiomyocytes. We examined, as proof of concept, the effects of mechanical tissue resuscitation (MTR) with controlled negative pressure on myocardial injury following acute myocardial infarction. Anesthetized swine were subjected to 75 minutes of left coronary artery occlusion and three hours of reperfusion. Animals were assigned to one of three groups: (A) untreated control; treatment of involved myocardium for 180 minutes of MTR with (B) -50 mmHg, or (C) -125 mmHg. All three groups were subjected to equivalent ischemic stress. Treatment of the ischemic area with MTR for 180 minutes significantly (p control: 9.3 +/- 1.8% (-50 mmHg) and 11.9 +/- 1.2% (-125 mmHg) versus 26.4 +/- 2.1% (control). Total area of cell death was reduced by 65% with -50 mmHg treatment and 55% in the -125 mmHg group. Treatment of ischemic myocardium with MTR, for a controlled period of time during reperfusion, successfully reduced the extent of myocardial death after acute myocardial infarction. These data provide evidence that MTR using subatmospheric pressure may be a simple, efficacious, nonpharmacological, mechanical strategy for decreasing cardiomyocyte death following myocardial infarction, which can be delivered in the operating room.

  2. Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers.

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    Aljakna, Aleksandra; Fracasso, Tony; Sabatasso, Sara

    2018-03-01

    Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.

  3. 3D whole-heart myocardial tissue analysis

    NARCIS (Netherlands)

    van den Broek, HT; de Jong, Leon; Doevendans, Pieter A.; Chamuleau, Steven A.J.; van Slochteren, Frebus J.; Van Es, René

    2017-01-01

    Cardiac regenerative therapies aim to protect and repair the injured heart in patients with ischemic heart disease. By injecting stem cells or other biologicals that enhance angio- or vasculogenesis into the infarct border zone (IBZ), tissue perfusion is improved, and the myocardium can be protected

  4. Quantitative analysis of myocardial tissue with digital autofluorescence microscopy

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    Thomas Jensen

    2016-01-01

    Full Text Available Background: The opportunity offered by whole slide scanners of automated histological analysis implies an ever increasing importance of digital pathology. To go beyond the importance of conventional pathology, however, digital pathology may need a basic histological starting point similar to that of hematoxylin and eosin staining in conventional pathology. This study presents an automated fluorescence-based microscopy approach providing highly detailed morphological data from unstained microsections. This data may provide a basic histological starting point from which further digital analysis including staining may benefit. Methods: This study explores the inherent tissue fluorescence, also known as autofluorescence, as a mean to quantitate cardiac tissue components in histological microsections. Data acquisition using a commercially available whole slide scanner and an image-based quantitation algorithm are presented. Results: It is shown that the autofluorescence intensity of unstained microsections at two different wavelengths is a suitable starting point for automated digital analysis of myocytes, fibrous tissue, lipofuscin, and the extracellular compartment. The output of the method is absolute quantitation along with accurate outlines of above-mentioned components. The digital quantitations are verified by comparison to point grid quantitations performed on the microsections after Van Gieson staining. Conclusion: The presented method is amply described as a prestain multicomponent quantitation and outlining tool for histological sections of cardiac tissue. The main perspective is the opportunity for combination with digital analysis of stained microsections, for which the method may provide an accurate digital framework.

  5. Advanced myocardial tissue characterisation by a multi-component CMR protocol in patients with rheumatoid arthritis

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    Greulich, Simon; Kaesemann, Philipp; Patrascu, Alexandru; Sechtem, Udo; Mahrholdt, Heiko [Robert-Bosch-Medical Center Stuttgart, Division of Cardiology, Stuttgart (Germany); Mayr, Agnes [University Hospital Innsbruck, Division of Radiology, Innsbruck (Austria); Kitterer, Daniel; Latus, Joerg; Braun, Niko; Alscher, M.D. [Robert-Bosch-Medical Center Stuttgart, Division of Nephrology, Department of Internal Medicine, Stuttgart (Germany); Henes, Joerg [University Hospital Tuebingen, Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases and Department of Internal Medicine II (Oncology, Haematology, Immunology, Rheumatology, Pulmology), Tuebingen (Germany); Vecchio, Francesco [Robert-Bosch-Medical Center Stuttgart, Division of Cardiology, Stuttgart (Germany); Universita degli Studi di Roma ' ' Tor Vergata' ' , Division of Cardiology, Rome (Italy); Greiser, Andreas; Groeninger, Stefan [Siemens Healthcare GmbH, Erlangen (Germany); Romeo, Francesco [Universita degli Studi di Roma ' ' Tor Vergata' ' , Division of Cardiology, Rome (Italy)

    2017-11-15

    Rheumatoid arthritis (RA) patients are at increased risk of suffering from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) mapping techniques might be appropriate tools to complement late gadolinium enhancement (LGE) for the assessment of myocardial involvement. This study aimed to perform advanced myocardial tissue characterisation in RA patients by a multicomponent CMR protocol. 22 RA patients were prospectively enrolled and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers served as controls. Mean LV-EF was 66%; prevalence of LGE was 18%. RA patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49 ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2 mapping showed the highest prevalence of values beyond the 95% percentile of controls. RA patients demonstrated higher T1, ECV and T2 values compared to controls, with most significant differences for T2. Since these results seem to be independent of the presence of LGE, advanced myocardial tissue characterisation including CMR mapping techniques in addition to LGE-CMR might be useful in the evaluation of myocardial involvement in RA patients. (orig.)

  6. Quantitative analysis of myocardial tissue with digital autofluorescence microscopy

    DEFF Research Database (Denmark)

    Jensen, Thomas; Holten-Rossing, Henrik; Svendsen, Ida M H

    2016-01-01

    to that of hematoxylin and eosin staining in conventional pathology. This study presents an automated fluorescence-based microscopy approach providing highly detailed morphological data from unstained microsections. This data may provide a basic histological starting point from which further digital analysis including...... staining may benefit. METHODS: This study explores the inherent tissue fluorescence, also known as autofluorescence, as a mean to quantitate cardiac tissue components in histological microsections. Data acquisition using a commercially available whole slide scanner and an image-based quantitation algorithm......BACKGROUND: The opportunity offered by whole slide scanners of automated histological analysis implies an ever increasing importance of digital pathology. To go beyond the importance of conventional pathology, however, digital pathology may need a basic histological starting point similar...

  7. Development of multilayer constructs for tissue engineering

    NARCIS (Netherlands)

    Bettahalli, N. M. S.; Groen, N.; Steg, H.; Unadkat, H.; de Boer, J.; van Blitterswijk, C. A.; Wessling, M.; Stamatialis, D.

    The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

  8. Development of multilayer constructs for tissue engineering

    NARCIS (Netherlands)

    Bettahalli Narasimha, M.S.; Groen, N.; Steg, H.; Unadkat, H.V.; de Boer, Jan; van Blitterswijk, Clemens; Wessling, Matthias; Stamatialis, Dimitrios

    2014-01-01

    The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

  9. Construction of retroviral recombinant containing human tissue ...

    African Journals Online (AJOL)

    USER

    2010-03-29

    Mar 29, 2010 ... Recombinant retroviral vector containing human tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) gene was ..... heavy metal ions, the protein could be express in an .... involves adhesion, degradation and movement. To.

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

    Directory of Open Access Journals (Sweden)

    Günther Eissner

    2011-07-01

    Full Text Available 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.

  11. Potential cost effectiveness of intravenous tissue plasminogen activator versus streptokinase for acute myocardial infarction.

    Science.gov (United States)

    Goel, V; Naylor, C D

    1992-01-01

    An economic evaluation of the potential incremental benefits of intravenous tissue plasminogen activator (tPA) versus streptokinase (SK) for treatment of acute myocardial infarction. Cost effectiveness analysis from a third-party payer perspective (Ontario Ministry of Health). ECONOMIC INPUTS: Fully allocated costs for cardiovascular procedures and hospitalization for myocardial infarction were obtained anonymously for four Ontario teaching hospitals and converted to 1988 Canadian dollars. Professional charges were taken from the provincial health insurance fee schedule and drug costs obtained from the manufacturers. CLINICAL INPUTS: The baseline analysis was for nonelderly patients with uncomplicated myocardial infarctions; sensitivity analyses allowed extrapolation to higher risk subgroups. Short and longer term mortality and short term invasive procedure rates were estimated using data from clinical trials. If tPA achieves a 1% short term mortality advantage over SK with no advantages for other survivors, cost per life-year gained can be comparable to other cardiovascular interventions at $58,600. In the absence of immediate survival advantages, but assuming greater left ventricular preservation, the constant annual hazard rate advantage must be about 0.5% per year for competitive cost effectiveness ratios. A full range of projections is presented to help guide the policy decisions that will arise in the wake of the Global Utilization of SK and tPA for Occluded Coronary Arteries (GUSTO) trial. The analysis also illustrates the general importance of considering longer term effects of in-hospital therapies for acute myocardial infarction.

  12. Myocardial response to a triathlon in male athletes evaluated by Doppler tissue imaging and biochemical parameters

    DEFF Research Database (Denmark)

    Leetmaa, T H; Dam, A; Glintborg, D

    2008-01-01

    (cTnT) and pro-brain natriuretic peptide (pro-BNP)] and echocardiography. Conventional echocardiography techniques and new Doppler tissue imaging (DTI) modalities were applied before and immediately after the competition. Blood samples were drawn 1 week before, immediately after and 12-24 h post...... and systolic velocities decreased, thus suggesting reversible cardiac fatigue. When using cardiac markers and echocardiographic findings, a triathlon was found to have no significant negative effects on left ventricular function or myocardial tissue in male athletes....

  13. The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies

    DEFF Research Database (Denmark)

    Nielsen, Trine Skov; Hansen, Jakob; Nielsen, Lars Peter

    2014-01-01

    of adenovirus, enterovirus, and parvovirus B19 (PVB) in myocardial autopsy samples from myocarditis related deaths and in non-inflamed control hearts in an effort to clarify their significance as the causes of myocarditis in a forensic material. METHODS: We collected all autopsy cases diagnosed with myocarditis...... from 1992 to 2010. Eighty-four suicidal deaths with morphologically normal hearts served as controls. Polymerase chain reaction was used for the detection of the viral genomes (adenovirus, enterovirus, and PVB) in myocardial tissue specimens. The distinction between acute and persistent PVB infection...... was made by the serological determination of PVB-specific immunoglobulins M and G. RESULTS: PVB was detected in 33 of 112 (29 %) myocarditis cases and 37 of 84 (44 %) control cases. All of the samples were negative for the presence of adenovirus and enterovirus. Serological evidence of an acute PVB...

  14. Tissue engineered constructs: perspectives on clinical translation.

    Science.gov (United States)

    Lu, Lichun; Arbit, Harvey M; Herrick, James L; Segovis, Suzanne Glass; Maran, Avudaiappan; Yaszemski, Michael J

    2015-03-01

    In this article, a "bedside to bench and back" approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the U.S. Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or new drug application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented.

  15. Ready to Use Tissue Construct for Military Bone & Cartilage Trauma

    Science.gov (United States)

    2015-12-01

    scaffold by laying down small droplets of the liquid 90% poly-caprolactone (PCL) and 10% hydroxyapatite (HA) by weight using a 25 G needle. The resulting...Award Number: W81XWH-10-1-0933 TITLE: Ready to Use Tissue Construct for Military Bone & Cartilage Trauma PRINCIPAL INVESTIGATOR: Francis Y...TITLE AND SUBTITLE Ready to Use Tissue Construct for Military Bone & Cartilage Trauma 5a. CONTRACT NUMBER W81XWH-10-1-0933 5b. GRANT NUMBER

  16. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink

    Science.gov (United States)

    Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D.; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

    2016-01-01

    Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

  17. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

    Science.gov (United States)

    Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

    2016-04-21

    Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types.

  18. Does intravenous administration of recombinant tissue plasminogen activator for ischemic stroke can cause inferior myocardial infarction?

    Directory of Open Access Journals (Sweden)

    Mostafa Almasi

    2016-06-01

    Full Text Available Recombinant tissue plasminogen activator (rTPA is one of the main portions of acute ischemic stroke management, but unfortunately has some complications. Myocardial infarction (MI is a hazardous complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to diagnosis of inferior MI, and the symptoms were resolved.

  19. Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

    Directory of Open Access Journals (Sweden)

    Sarah L. Tao

    2010-03-01

    Full Text Available One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

  20. 3D Bioprinting of Artificial Tissues: Construction of Biomimetic Microstructures.

    Science.gov (United States)

    Luo, Yongxiang; Lin, Xin; Huang, Peng

    2018-04-24

    It is promising that artificial tissues/organs for clinical application can be produced via 3D bioprinting of living cells and biomaterials. The construction of microstructures biomimicking native tissues is crucially important to create artificial tissues with biological functions. For instance, the fabrication of vessel-like networks to supply cells with initial nutrient and oxygen, and the arrangement of multiple types of cells for creating lamellar/complex tissues through 3D bioprinting are widely reported. The current advances in 3D bioprinting of artificial tissues from the view of construction of biomimetic microstructures, especially the fabrication of lamellar, vascular, and complex structures are summarized. In the end, the conclusion and perspective of 3D bioprinting for clinical applications are elaborated. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

    Science.gov (United States)

    Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

    2015-01-01

    Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

  2. Anomalous optical behavior of biological media: modifying the optical window of myocardial tissues

    Science.gov (United States)

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

    1996-05-01

    In medical experimental and clinical treatment modalities of light, laser photocoagulation of ventricular tachycardia amongst others, the success of the application relies on whether or not the procedure operates in the optical window of the light-tissue interaction. The optical window of biological tissues can be determined by spectral scans of the optical properties. Optical anomalies may result from the irradiance, the wavelength, or from the tissue composition itself. The transmission of cw Nd:YAG laser light on myocardial tissue showed a nonlinearity in the transmission curve at approximately 3 kW/mm2 irradiance. The total attenuation coefficient dropped sharp from 1.03 plus or minus 0.04 mm-1 to 0.73 plus or minus 0.05 mm-1 at this point in the curve. On the other hand, aneurysm tissue has a highly organized fiber structure, which serves as light-guides, since the transmission of light along the length of the collagen fibers is approximately 50% higher than the transmission perpendicular to the fiber orientation. In addition, changes in optical properties due to tissue phase changes also influence the penetration depth. These phenomena can be utilized to manipulate the optical penetration to an advantage.

  3. Bioprinting of hybrid tissue constructs with tailorable mechanical properties

    International Nuclear Information System (INIS)

    Schuurman, W; Khristov, V; Pot, M W; Dhert, W J A; Malda, J; Van Weeren, P R

    2011-01-01

    Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels. (communication)

  4. Bioprinting of hybrid tissue constructs with tailorable mechanical properties

    Energy Technology Data Exchange (ETDEWEB)

    Schuurman, W; Khristov, V; Pot, M W; Dhert, W J A; Malda, J [Department of Orthopaedics, University Medical Center Utrecht (Netherlands); Van Weeren, P R, E-mail: j.malda@umcutrecht.nl [Faculty of Veterinary Sciences, Department of Equine Sciences, Utrecht University (Netherlands)

    2011-06-15

    Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels. (communication)

  5. Changes of blood and myocardial tissue contents of IGF-I after development of acute myocardial infarction in rat models

    International Nuclear Information System (INIS)

    Cao Heng; Wei Youquan

    2006-01-01

    Objective: To study the changes of IGF-I contents in blood and myocardium after experimental acute myocardial infarction in rat models. Methods: Rat models of acute myocardial infarction were prepared with intraperitoneal injection of isoproterenol. Eight models were sacrificed 48h later and another 8 models were sacrificed 14 days after preparation. Serum and myocardium homogenate contents of IGF-I were measured with RIA in these models as well as 8 control rats. Results: The serum and myocardial contents of IGF-I increased in the models sacrificed at 48h, but were not significantly higher than those in the controls (P>0.05). At 14 th day, the levels were significantly higher than those in controls and at 48h (both P<0.05). The serum and myocardial contents of IGF-I were mutually correlated in the controls and 14 day models (r=0.9987, r=0.9992; P<0.01). Conclusion After myocardial infarction, the serum and myocardial IGF-I contents increased along with the course of disease in the rat models. (authors)

  6. Artificial urinary conduit construction using tissue engineering methods.

    Science.gov (United States)

    Kloskowski, Tomasz; Pokrywczyńska, Marta; Drewa, Tomasz

    2015-01-01

    Incontinent urinary diversion using an ileal conduit is the most popular method used by urologists after bladder cystectomy resulting from muscle invasive bladder cancer. The use of gastrointestinal tissue is related to a series of complications with the necessity of surgical procedure extension which increases the time of surgery. Regenerative medicine together with tissue engineering techniques gives hope for artificial urinary conduit construction de novo without affecting the ileum. In this review we analyzed history of urinary diversion together with current attempts in urinary conduit construction using tissue engineering methods. Based on literature and our own experience we presented future perspectives related to the artificial urinary conduit construction. A small number of papers in the field of tissue engineered urinary conduit construction indicates that this topic requires more attention. Three main factors can be distinguished to resolve this topic: proper scaffold construction along with proper regeneration of both the urothelium and smooth muscle layers. Artificial urinary conduit has a great chance to become the first commercially available product in urology constructed by regenerative medicine methods.

  7. Colloidal gas aphron foams: A novel approach to a hydrogel based tissue engineered myocardial patch

    Science.gov (United States)

    Johnson, Elizabeth Edna

    Cardiovascular disease currently affects an estimated 58 million Americans and is the leading cause of death in the US. Over 2.3 million Americans are currently living with heart failure a leading cause of which is acute myocardial infarction, during which a part of the heart muscle is damaged beyond repair. There is a great need to develop treatments for damaged heart tissue. One potential therapy involves replacement of nonfunctioning scar tissue with a patch of healthy, functioning tissue. A tissue engineered cardiac patch would be ideal for such an application. Tissue engineering techniques require the use of porous scaffolds, which serve as a 3-D template for initial cell attachment and grow-th leading to tissue formation. The scaffold must also have mechanical properties closely matching those of the tissues at the site of implantation. Our research presents a new approach to meet these design requirements. A unique interaction between poly(vinyl alcohol) and amino acids has been discovered by our lab, resulting in the production of novel gels. These unique synthetic hydrogels along with one natural hydrogel, alginate (derived from brown seaweed), have been coupled with a new approach to tissue scaffold fabrication using solid colloidal gas aphrons (CGAs). CGAs are colloidal foams containing uniform bubbles with diameters on the order of micrometers. Upon solidification the GCAs form a porous, 3-D network suitable for a tissue scaffold. The project encompasses four specific aims: (I) characterize hydrogel formation mechanism, (II) use colloidal gas aphrons to produce hydrogel scaffolds, (III) chemically and physically characterize scaffold materials and (IV) optimize and evaluate scaffold biocompatibility.

  8. Exercise training does not improve myocardial diastolic tissue velocities in Type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nenonen Arja

    2007-09-01

    Full Text Available Abstract Background Myocardial diastolic tissue velocities are reduced already in newly onset Type 2 diabetes mellitus (T2D. Poor disease control may lead to left ventricular (LV systolic dysfunction and heart failure. The aim of this study was to assess the effects of exercise training on myocardial diastolic function in T2D patients without ischemic heart disease. Methods 48 men (52.3 ± 5.6 yrs with T2D were randomized to supervised training four times a week and standard therapy (E, or standard treatment alone (C for 12 months. Glycated hemoglobin (HbA1c, oxygen consumption (VO2max, and muscle strength (Sit-up were measured. Tissue Doppler Imaging (TDI was used to determine the average maximal mitral annular early (Ea and late (Aa diastolic as well as systolic (Sa velocities, systolic strain (ε and strain rate (έ from the septum, and an estimation of left ventricular end diastolic pressure (E/Ea. Results Exercise capacity (VO2max, E 32.0 to 34.7 vs. C 32.6 to 31.5 ml/kg/min, p = .001, muscle strength (E 12.7 to 18.3 times vs. C 14.6 to 14.7 times, p 1c (E 8.2 to 7.5% vs. C 8.0 to 8.4%, p = .006 improved significantly in the exercise group compared to the controls (ANOVA. Systolic blood pressure decreased in the E group (E 144 to 138 mmHg vs. C 146 to 144 mmHg, p = .04. Contrary to risk factor changes diastolic long axis relaxation did not improve significantly, early diastolic velocity Ea from 8.1 to 7.9 cm/s for the E group vs. C 7.4 to 7.8 cm/s (p = .85, ANOVA. Likewise, after 12 months the mitral annular systolic velocity, systolic strain and strain rate, as well as E/Ea were unchanged. Conclusion Exercise training improves endurance and muscle fitness in T2D, resulting in better glycemic control and reduced blood pressure. However, myocardial diastolic tissue velocities did not change significantly. Our data suggest that a much longer exercise intervention may be needed in order to reverse diastolic impairment in diabetics, if at all

  9. Tellurium labeled analogues of the fatty acid hexadecenoic acid for imaging of myocardial tissue

    International Nuclear Information System (INIS)

    Mills, S.L.

    1980-01-01

    Non-invasive nuclear diagnostic procedures for the evaluation of acute myocardial infarction and ischemia are currently limited by problems associated with the availablity of radiopharmaceuticals, development of imaging equipment, and inherent characteristics of radionuclides. Myocardial tissue requires high levels of substrates which provide energy for the continuous functioning of this vital organ. Of the major sources of energy, the most utilized source is fatty acids. Tellurium-123m, with excellent gamma imaging characteristics was chosen as the radionuclide. A 16 carbon fatty acid, hexadecenoic acid, was chosen as the carrier molecule. The tellurium-123m fatty acid radiopharmaceuticals were formulated either in a solution of 20 percent ethanol, two percent polysorbate 80, and brought to volume with normal saline or in 12.5 percent human serum ablumin and brought to volume with normal saline. Biodistribution was performed in three animal species: Sprague-Dawley rats (three rats per time frame), Australian white rabbits (three rabbits per time frame), and mongrel dogs (one dog per time frame). Dosimetry calculations were performed to assess the radiation dose

  10. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  11. The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics.

    Science.gov (United States)

    Liu, Yue-tao; Jia, Hong-mei; Chang, Xing; Ding, Gang; Zhang, Hong-wu; Zou, Zhong-Mei

    2013-11-01

    Myocardial infarction (MI) is a leading cause of morbidity and mortality but the precise mechanism of its pathogenesis remains obscure. To achieve the most comprehensive screening of the entire metabolome related to isoproterenol (ISO) induced-MI, we present a tissue targeted metabonomic study using an integrated approach of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) and proton nuclear magnetic resonance (1H NMR). Twenty-two metabolites were detected as potential biomarkers related to the formation of MI, and the levels of pantothenic acid (), lysoPC(18:0) (), PC(18:4(6Z,9Z,12Z,15Z)/18:0) (), taurine (), lysoPC(20:3(8Z,11Z,14Z)) (), threonine (), alanine (), creatine (), phosphocreatine (), glucose 1-phosphate (), glycine (), xanthosine (), creatinine () and glucose () were decreased significantly, while the concentrations of histamine (), L-palmitoylcarnitine (), GSSG (), inosine (), arachidonic acid (), linoelaidic acid (), 3-methylhistamine () and glycylproline () were increased significantly in the MI rats compared with the control group. The identified potential biomarkers were involved in twelve metabolic pathways and achieved the most entire metabolome contributing to the injury of the myocardial tissue. Five pathways, including taurine and hypotaurine metabolism, glycolysis, arachidonic acid metabolism, glycine, serine and threonine metabolism and histidine metabolism, were significantly influenced by ISO-treatment according to MetPA analysis and suggested that the most prominent changes included inflammation, interference of calcium dynamics, as well as alterations of energy metabolism in the pathophysiologic process of MI. These findings provided a unique perspective on localized metabolic information of ISO induced-MI, which gave us new insights into the pathogenesis of MI, discovery of targets for clinical diagnosis and treatment.

  12. Bioprinting scale-up tissue and organ constructs for transplantation.

    Science.gov (United States)

    Ozbolat, Ibrahim T

    2015-07-01

    Bioprinting is an emerging field that is having a revolutionary impact on the medical sciences. It offers great precision for the spatial placement of cells, proteins, genes, drugs, and biologically active particles to better guide tissue generation and formation. This emerging biotechnology appears to be promising for advancing tissue engineering toward functional tissue and organ fabrication for transplantation, drug testing, research investigations, and cancer or disease modeling, and has recently attracted growing interest worldwide among researchers and the general public. In this Opinion, I highlight possibilities for the bioprinting scale-up of functional tissue and organ constructs for transplantation and provide the reader with alternative approaches, their limitations, and promising directions for new research prospects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63-Integrin β1 Interaction.

    Science.gov (United States)

    Takawale, Abhijit; Zhang, Pu; Patel, Vaibhav B; Wang, Xiuhua; Oudit, Gavin; Kassiri, Zamaneh

    2017-06-01

    Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway. We examined the function of TIMP1 in myocardial fibrosis using Timp1 -deficient mice and 2 in vivo models of myocardial fibrosis (angiotensin II infusion and cardiac pressure overload), in vitro analysis of adult cardiac fibroblasts, and fibrotic myocardium from patients with dilated cardiomyopathy (DCM). Timp1 deficiency significantly reduced myocardial fibrosis in both in vivo models of cardiomyopathy. We identified a novel mechanism for TIMP1 action whereby, independent from its matrix metalloproteinase-inhibitory function, it mediates an association between CD63 (cell surface receptor for TIMP1) and integrin β1 on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and β-catenin, leading to de novo collagen synthesis. This mechanism was consistently observed in vivo, in cultured cardiac fibroblasts, and in human fibrotic myocardium. In addition, after long-term pressure overload, Timp1 deficiency persistently reduced myocardial fibrosis and ameliorated diastolic dysfunction. This study defines a novel matrix metalloproteinase-independent function of TIMP1 in promoting myocardial fibrosis. As such targeting TIMP1 could prove to be a valuable approach in developing antifibrosis therapies. © 2017 American Heart Association, Inc.

  14. Additive manufacturing techniques for the production of tissue engineering constructs.

    Science.gov (United States)

    Mota, Carlos; Puppi, Dario; Chiellini, Federica; Chiellini, Emo

    2015-03-01

    'Additive manufacturing' (AM) refers to a class of manufacturing processes based on the building of a solid object from three-dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue-engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue-engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt-extrusion-based techniques, solution/slurry extrusion-based techniques, and tissue and organ printing) employed for the development of tissue-engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions. Copyright © 2012 John Wiley & Sons, Ltd.

  15. The interplay between tissue growth and scaffold degradation in engineered tissue constructs

    KAUST Repository

    O’Dea, R. D.

    2012-09-18

    In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of

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

    Science.gov (United States)

    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.

  17. Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs.

    Science.gov (United States)

    Navaei, Ali; Saini, Harpinder; Christenson, Wayne; Sullivan, Ryan Tanner; Ros, Robert; Nikkhah, Mehdi

    2016-09-01

    The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly

  18. Opening of the inward rectifier potassium channel alleviates maladaptive tissue repair following myocardial infarction.

    Science.gov (United States)

    Liu, Chengfang; Liu, Enli; Luo, Tiane; Zhang, Weifang; He, Rongli

    2016-08-01

    Activation of the inward rectifier potassium current (IK1) channel has been reported to be associated with suppression of ventricular arrhythmias. In this study, we tested the hypothesis that opening of the IK1 channel with zacopride (ZAC) was involved in the modulation of tissue repair after myocardial infarction. Sprague-Dawley rats were subject to coronary artery ligation and ZAC was administered intraperitoneally (15 µg/kg/day) for 28 days. Compared with the ischemia group, treatment with ZAC significantly reduced the ratio of heart/body weight and the cross-sectional area of cardiomyocytes, suggesting less cardiac hypertrophy. ZAC reduced the accumulation of collagen types I and III, accompanied with decrease of collagen area, which were associated with a reduction of collagen deposition in the fibrotic myocardium. Echocardiography showed improved cardiac function, evidenced by the reduced left ventricular end-diastolic dimension and left ventricular end-systolic dimension, and the increased ejection fraction and fractional shortening in ZAC-treated animals (all P < 0.05 vs. ischemia group). In coincidence with these changes, ZAC up-regulated the protein level of the IK1 channel and down-regulated the phosphorylation of mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 (p70S6) kinase. Administration of chloroquine alone, an IK1 channel antagonist, had no effect on all the parameters measured, but significantly blocked the beneficial effects of ZAC on cardiac repair. In conclusion, opening of the IK1 channel with ZAC inhibits maladaptive tissue repair and improves cardiac function, potentially mediated by the inhibition of ischemia-activated mTOR-p70S6 signaling pathway via the IK1 channel. So the development of pharmacological agents specifically targeting the activation of the IK1 channel may protect the heart against myocardial ischemia-induced cardiac dysfunction. © The Author 2016. Published by Oxford University Press on behalf of

  19. Importance of tissue perfusion in ST segment elevation myocardial infarction patients undergoing reperfusion strategies: role of adenosine.

    Science.gov (United States)

    Forman, Mervyn B; Jackson, Edwin K

    2007-11-01

    High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the "no-reflow" phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well-characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the "no reflow" phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri-reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6-month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the "no-reflow" phenomenon, support its use in high risk STEMI undergoing reperfusion.

  20. Morphological changes in paraurethral area after introduction of tissue engineering construct on the basis of adipose tissue stromal cells.

    Science.gov (United States)

    Makarov, A V; Arutyunyan, I V; Bol'shakova, G B; Volkov, A V; Gol'dshtein, D V

    2009-10-01

    We studied morphological changes in the paraurethral area of Wistar rats after introduction of tissue engineering constructs on the basis of multipotent mesenchymal stem cells and gelatin sponge. The tissue engineering construct containing autologous culture of the stromal fraction of the adipose tissue was most effective. After introduction of this construct we observed more rapid degradation of the construct matrix and more intensive formation of collagen fibers.

  1. Overview on Techniques to Construct Tissue Arrays with Special Emphasis on Tissue Microarrays

    Science.gov (United States)

    Vogel, Ulrich

    2014-01-01

    With the advent of new histopathological staining techniques (histochemistry, immunohistochemistry, in situ hybridization) and the discovery of thousands of new genes, mRNA, and proteins by molecular biology, the need grew for a technique to compare many different cells or tissues on one slide in a cost effective manner and with the possibility to easily track the identity of each specimen: the tissue array (TA). Basically, a TA consists of at least two different specimens per slide. TAs differ in the kind of specimens, the number of specimens installed, the dimension of the specimens, the arrangement of the specimens, the embedding medium, the technique to prepare the specimens to be installed, and the technique to construct the TA itself. A TA can be constructed by arranging the tissue specimens in a mold and subsequently pouring the mold with the embedding medium of choice. In contrast, preformed so-called recipient blocks consisting of the embedding medium of choice have punched, drilled, or poured holes of different diameters and distances in which the cells or tissue biopsies will be deployed manually, semi-automatically, or automatically. The costs of constructing a TA differ from a few to thousands of Euros depending on the technique/equipment used. Remarkably high quality TAs can be also achieved by low cost techniques. PMID:27600339

  2. Relevance of tissue Doppler in the quantification of stress echocardiography for the detection of myocardial ischemia in clinical practice

    Directory of Open Access Journals (Sweden)

    Sicari Rosa

    2005-01-01

    Full Text Available Abstract In the present article we review the main published data on the application of Tissue Doppler Imaging (TDI to stress echocardiography for the detection of myocardial ischemia. TDI has been applied to stress echocardiography in order to overcome the limitations of visual analysis for myocardial ischemia. The introduction of a new technology for clinical routine use should pass through the different phases of scientific assessment from feasibility studies to large multicenter studies, from efficacy to effectiveness studies. Nonetheless the pro-technology bias plays a major role in medicine and expensive and sophisticated techniques are accepted before their real usefulness and incremental value to the available ones is assessed. Apparently, TDI is not exempted by this approach : its applications are not substantiated by strong and sound results. Nonetheless, conventional stress echocardiography for myocardial ischemia detection is heavily criticized on the basis of its subjectivity. Stress echocardiography has a long lasting history and the evidence collected over 20 years positioned it as an established tool for the detection and prognostication of coronary artery disease. The quantitative assessment of myocardial ischemia remains a scientific challenge and a clinical goal but time has not come for these newer ultrasonographic techniques which should be restricted to research laboratories.

  3. [Construction of injectable tissue engineered nucleus pulposus in vitro].

    Science.gov (United States)

    Tian, Huake; Wang, Jian; Chen, Chao; Liu, Jie; Zhou, Yue

    2009-02-01

    To investigate the feasibility of using thermo-sensitive chitosan hydrogen as a scaffold to construct tissue engineered injectable nucleus pulposus (NP). Three-month-old neonatal New Zealand rabbits (male or female) weighing 150-200 g were selected to isolate and culture NP cells. The thermo-sensitive chitosan hydrogel scaffold was made of chitosan, disodium beta-glycerophosphate and hydroxyethyl cellulose. Its physical properties and gross condition were observed. The tissue engineered NP was constructed by compounding the scaffold and rabbit NP cells. Then, the viability of NP cells in the chitosan hydrogel was observed 2 days after compound culture and the growth condition of NP cells on the scaffold was observed by SEM 7 days after compound culture. NP cells went through histology and immunohistochemistry detection and their secretion of aggrecan and expression of Col II mRNA were analyzed by RT-PCR 21 days after compound culture. The thermo-sensitive chitosan hydrogel was liquid at room temperature and solidified into gel at 37 degrees C (15 minutes) due to crosslinking reaction. Acridine orange-propidium iodide staining showed that the viability rate of NP cells in chitosan hydrogel was above 90%. Scanning electron microscope observation demonstrated that the NP cells were distributed in the reticulate scaffold, with ECM on their surfaces. The results of HE, toluidine blue, safranin O and histology and immunohistochemistry staining confirmed that the NP cells in chitosan hydrogel were capable of producing ECM. RT-PCR results showed that the secretion of Col II and aggrecan mRNA in NP cells cultured three-dimensionally by chitosan hydrogen scaffold were 0.631 +/- 0.064 and 0.832 +/- 0.052, respectively, showing more strengths of producing matrix than that of monolayer culture (0.528 +/- 0.039, 0.773 +/- 0.046) with a significant difference (P compound culture, and may be a potential NP cells carrier for tissue engineered NP.

  4. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    Directory of Open Access Journals (Sweden)

    Matthew A Schechter

    Full Text Available The molecular differences between ischemic (IF and non-ischemic (NIF heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins and 823 phosphopeptides (corresponding to 400 proteins from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05 when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  5. Subclinical myocardial dysfunction by tissue Doppler echocardiography in primary antiphospholipid syndrome: Preliminary results

    Directory of Open Access Journals (Sweden)

    Tarcila Fontes de Lima Gomes Lucena

    2018-01-01

    Conclusion: The present study demonstrated subclinical myocardial dysfunction using TDI in asymptomatic PAPS patients. TDI is non-invasive and cost effective. Prospective studies including a large number of participants in order to confirm these preliminary data are needed.

  6. [Differential gene expression profile in ischemic myocardium of Wistar rats with acute myocardial infarction: the study on gene construction, identification and function].

    Science.gov (United States)

    Guo, Chun Yu; Yin, Hui Jun; Jiang, Yue Rong; Xue, Mei; Zhang, Lu; Shi, Da Zhuo

    2008-06-18

    To construct the differential genes expressed profile in the ischemic myocardium tissue reduced from acute myocardial infarction(AMI), and determine the biological functions of target genes. AMI model was generated by ligation of the left anterior descending coronary artery in Wistar rats. Total RNA was extracted from the normal and the ischemic heart tissues under the ligation point 7 days after the operation. Differential gene expression profiles of the two samples were constructed using Long Serial Analysis of Gene Expression(LongSAGE). Real time fluorescence quantitative PCR was used to verify gene expression profile and to identify the expression of 2 functional genes. The activities of enzymes from functional genes were determined by histochemistry. A total of 15,966 tags were screened from the normal and the ischemic LongSAGE maps. The similarities of the sequences were compared using the BLAST algebra in NCBI and 7,665 novel tags were found. In the ischemic tissue 142 genes were significantly changed compared with those in the normal tissue (Ppathways of oxidation and phosphorylation, ATP synthesis and glycolysis. The partial genes identified by LongSAGE were confirmed using real time fluorescence quantitative PCR. Two genes related to energy metabolism, COX5a and ATP5e, were screened and quantified. Expression of two functional genes down-regulated at their mRNA levels and the activities of correlative functional enzymes decreased compared with those in the normal tissue. AMI causes a series of changes in gene expression, in which the abnormal expression of genes related to energy metabolism could be one of the molecular mechanisms of AMI. The intervention of the expressions of COX5a and ATP5e may be a new target for AMI therapy.

  7. Microarray Expression Profile of Circular RNAs in Heart Tissue of Mice with Myocardial Infarction-Induced Heart Failure

    Directory of Open Access Journals (Sweden)

    Hong-Jin Wu

    2016-06-01

    Full Text Available Background/Aims: Myocardial infarction (MI is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. This study is aimed to assess the global changes in and characteristics of the transcriptome of circular RNAs (circRNAs in heart tissue during MI induced heart failure (HF. Methods: Using a post-myocardial infarction (MI model of HF in mice, we applied microarray assay to examine the transcriptome of circRNAs deregulated in the heart during HF. We confirmed the changes in circRNAs by quantitative PCR. Results: We revealed and confirmed a number of circRNAs that were deregulated during HF, which suggests a potential role of circRNAs in HF. Conclusions: The distinct expression patterns of circulatory circRNAs during HF indicate that circRNAs may actively respond to stress and thus serve as biomarkers of HF diagnosis and treatment.

  8. Tissue Clearance of {sup 131}I and Total Peripheral Resistance in Myocardial Infarction and Hypertension, and During Angiotensin Infusion

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, F. K.; Bors, K. J.; Long, T. E.; Lestina, J. [University of Southern California School of Medicine, Los Angeles, CA (United States)

    1971-02-15

    Tissue clearance of {sup 131}I from the thigh, cardiac output and peripheral resistance was determined in 25 patients: 13 normotensive with recent myocardial infarction but not in congestive heart failure, 7 with hypertension and 5 normotensive control subjects. The effect of the synthesized pressor agent Angiotensin II on the same three measurements was also studied. The present investigation continues a previous one of ours, where a tracer dose of {sup 131}I was injected into the thigh of patients with recent myocardial infarction without signs of heart failure, and its clearance was found to be longer than that of normal subjects. This was thought to be due to increased peripheral resistance or to reduced perfusion of the capillary bed secondary to lowered cardiac output, With the 25 subjects, injection into the thigh of tracer amounts of radioactive iodine was done by Hypospray, a method with distinct advantages over needle injection. After measuring tissue clearance of the tracer, cardiac output was determined by a method which records the transit of the injected radioactive bolus through the heart. The Angiotensin was administered by intravenous infusion to four of the normotensive and one of the hypertensive patients. Calculations of cardiac output, total peripheral resistance, mean blood pressure and blood volume were made by means of standard formulae. Results of the study confirmed expectations. Those patients with myocardial infarction who had delayed tissue clearance of {sup 131}I also had reduced cardiac output. The patients with hypertension had normal tissue clearance of {sup 131}I and normal cardiac output in the presence of increased peripheral resistance. Equivalent hypertension and increased peripheral resistance induced in normotensive subjects by Angiotensin resulted in lowered cardiac output and delayed tissue clearance of {sup 131}I. An increased sensitivity to Angiotensin was noted in hypertensive patients. The tissue clearance of {sup 131}I

  9. Stem cell regenerative potential combined with nanotechnology and tissue engineering for myocardial regeneration.

    Science.gov (United States)

    Calin, Manuela; Stan, Daniela; Simion, Viorel

    2013-07-01

    The stem cell-based therapy for post-infarction myocardial regeneration has been introduced more than a decade ago, but the functional improvement obtained is limited due to the poor retention and short survival rate of transplanted cells into the damaged myocardium. More recently, the emerging nanotechnology concepts for advanced diagnostics and therapy provide promising opportunities of using stem cells for myocardial regeneration. In this paper will be provided an overview of the use of nanotechnology approaches in stem cell research for: 1) cell labeling to track the distribution of stem cells after transplantation, 2) nanoparticle-mediated gene delivery to stem cells to promote their homing, engraftment, survival and differentiation in the ischemic myocardium and 3) obtaining of bio-inspired materials to provide suitable myocardial scaffolds for delivery of stem cells or stem cell-derived factors.

  10. Wavelet analysis of polarization azimuths maps for laser images of myocardial tissue for the purpose of diagnosing acute coronary insufficiency

    Science.gov (United States)

    Wanchuliak, O. Ya.; Peresunko, A. P.; Bakko, Bouzan Adel; Kushnerick, L. Ya.

    2011-09-01

    This paper presents the foundations of a large scale - localized wavelet - polarization analysis - inhomogeneous laser images of histological sections of myocardial tissue. Opportunities were identified defining relations between the structures of wavelet coefficients and causes of death. The optical model of polycrystalline networks of myocardium protein fibrils is presented. The technique of determining the coordinate distribution of polarization azimuth of the points of laser images of myocardium histological sections is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order) parameters are presented which characterize distributions of wavelet - coefficients polarization maps of myocardium layers and death reasons.

  11. Functional evaluation of artificial skeletal muscle tissue constructs fabricated by a magnetic force-based tissue engineering technique.

    Science.gov (United States)

    Yamamoto, Yasunori; Ito, Akira; Fujita, Hideaki; Nagamori, Eiji; Kawabe, Yoshinori; Kamihira, Masamichi

    2011-01-01

    Skeletal muscle tissue engineering is currently applied in a variety of research fields, including regenerative medicine, drug screening, and bioactuator development, all of which require the fabrication of biomimic and functional skeletal muscle tissues. In the present study, magnetite cationic liposomes were used to magnetically label C2C12 myoblast cells for the construction of three-dimensional artificial skeletal muscle tissues by an applied magnetic force. Skeletal muscle functions, such as biochemical and contractile properties, were evaluated for the artificial tissue constructs. Histological studies revealed that elongated and multinucleated myotubes were observed within the tissue. Expression of muscle-specific markers, such as myogenin, myosin heavy chain and tropomyosin, were detected in the tissue constructs by western blot analysis. Further, creatine kinase activity increased during differentiation. In response to electric pulses, the artificial tissue constructs contracted to generate a physical force (the maximum twitch force, 33.2 μN [1.06 mN/mm2]). Rheobase and chronaxie of the tissue were determined as 4.45 V and 0.72 ms, respectively. These results indicate that the artificial skeletal muscle tissue constructs fabricated in this study were physiologically functional and the data obtained for the evaluation of their functional properties may provide useful information for future skeletal muscle tissue engineering studies.

  12. Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

    NARCIS (Netherlands)

    Silva, J.M.; Georgi, Nicole; Costa, R.; Sher, P.; Reis, R L; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes; Mano, J.F.

    2013-01-01

    Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and

  13. Transient myocardial tissue and function changes during a marathon in less fit marathon runners.

    Science.gov (United States)

    Gaudreault, Valerie; Tizon-Marcos, Helena; Poirier, Paul; Pibarot, Philippe; Gilbert, Philippe; Amyot, Marc; Rodés-Cabau, Josep; Després, Jean-Pierre; Bertrand, Olivier; Larose, Eric

    2013-10-01

    Although regular physical activity improves health, strenuous exercise might transiently increase cardiac risk. Training and fitness might provide protection. We prospectively studied 20 recreational marathon runners without known cardiovascular disease or symptoms: at peak training before, immediately after, and 3 months after a 42.2-km marathon. Changes in global/segmental myocardial function, edema, resting perfusion, and fibrosis were measured. At peak training, runners exercised 8.1 ± 2.3 hours and 62 ± 18 km per week with mean maximal oxygen consumption (VO2max) of 53.2 ± 8.3 mL/kg/min. In response to the marathon, global left ventricular and right ventricular ejection fraction decreased in half of the runners; these runners had poorer peak training distance, training time, and fitness level. Change in global left ventricular ejection fraction was associated with VO2max. Overall, 36% of segments developed edema, 53% decreased function, and 59% decreased perfusion. Significant agreement was observed between segment decreasing function, decreasing perfusion, and developing edema. Myocardial changes were reversible at 3 months. Completing a marathon leads to localized myocardial edema, diminished perfusion, and decreased function occurring more extensively in less trained and fit runners. Although reversible, these changes might contribute to the transient increase in cardiac risk reported during sustained vigorous exercise. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  14. Characterizing the inflammatory tissue response to acute myocardial infarction by clinical multimodality noninvasive imaging.

    Science.gov (United States)

    Wollenweber, Tim; Roentgen, Philipp; Schäfer, Andreas; Schatka, Imke; Zwadlo, Caroline; Brunkhorst, Thomas; Berding, Georg; Bauersachs, Johann; Bengel, Frank M

    2014-09-01

    Myocardial infarction (MI) triggers a systemic inflammatory response which determines subsequent healing. Experimentally, cardiac positron emission tomography and magnetic resonance imaging have been used successfully to obtain mechanistic insights. We explored the translational potential in patients early after MI. Positron emission tomography/computed tomography and cardiac magnetic resonance were performed in 15 patients sources of inflammatory cells. Positron emission tomography and cardiac magnetic resonance multimodality characterization of the acutely infarcted, inflamed myocardium may provide multiparametric end points for clinical studies aiming at support of infarct healing. © 2014 American Heart Association, Inc.

  15. Left ventricular regional myocardial motion and twist function in repaired tetralogy of Fallot evaluated by magnetic resonance tissue phase mapping

    International Nuclear Information System (INIS)

    Chang, Meng-Chu; Peng, Hsu-Hsia; Wu, Ming-Ting; Weng, Ken-Pen; Su, Mao-Yuan; Menza, Marius; Huang, Hung-Chieh

    2018-01-01

    We aimed to characterise regional myocardial motion and twist function in the left ventricles (LV) in patients with repaired tetralogy of Fallot (rTOF) and preserved LV global function. We recruited 47 rTOF patients and 38 age-matched normal volunteers. Tissue phase mapping (TPM) was performed for evaluating the LV myocardial velocity in longitudinal, radial, and circumferential (Vz, Vr, and VOe) directions in basal, middle, and apical slices. The VOe peak-to-peak (PTP) during systolic phases, the rotation angle of each slice, and VOe inconsistency were computed for evaluating LV twist function and VOe dyssynchrony. As compared to the controls, the rTOF patients presented decreased RV ejection fraction (RVEF) (p = 0.002) and preserved global LV ejection fraction (LVEF). They also demonstrated decreased systolic and diastolic Vz in several LV segments and higher diastolic Vr in the septum (all p < 0.05). A lower VOe PTP, higher VOe inconsistency, and reduced peak net rotation angle (all p < 0.05) were observed. The aforementioned indices demonstrated an altered LV twist function in rTOF patients in an early disease stage. MR TPM could provide information about early abnormalities of LV regional motion and twist function in rTOF patients with preserved LV global function. (orig.)

  16. Left ventricular regional myocardial motion and twist function in repaired tetralogy of Fallot evaluated by magnetic resonance tissue phase mapping

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Meng-Chu; Peng, Hsu-Hsia [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Wu, Ming-Ting [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung (China); National Yang-Ming University, Faculty of Medicine, Taipei (China); Weng, Ken-Pen [National Yang-Ming University, Faculty of Medicine, Taipei (China); Kaohsiung Veterans General Hospital, Department of Pediatrics, Kaohsiung (China); Shu-Zen Junior College of Medicine and Management, Department of Physical Therapy, Kaohsiung (China); Su, Mao-Yuan [National Taiwan University Hospital, Department of Medical Imaging, Taipei (China); Menza, Marius [Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Department of Radiology, Medical Physics, Freiburg (Germany); Huang, Hung-Chieh [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung (China)

    2018-01-15

    We aimed to characterise regional myocardial motion and twist function in the left ventricles (LV) in patients with repaired tetralogy of Fallot (rTOF) and preserved LV global function. We recruited 47 rTOF patients and 38 age-matched normal volunteers. Tissue phase mapping (TPM) was performed for evaluating the LV myocardial velocity in longitudinal, radial, and circumferential (Vz, Vr, and VOe) directions in basal, middle, and apical slices. The VOe peak-to-peak (PTP) during systolic phases, the rotation angle of each slice, and VOe inconsistency were computed for evaluating LV twist function and VOe dyssynchrony. As compared to the controls, the rTOF patients presented decreased RV ejection fraction (RVEF) (p = 0.002) and preserved global LV ejection fraction (LVEF). They also demonstrated decreased systolic and diastolic Vz in several LV segments and higher diastolic Vr in the septum (all p < 0.05). A lower VOe PTP, higher VOe inconsistency, and reduced peak net rotation angle (all p < 0.05) were observed. The aforementioned indices demonstrated an altered LV twist function in rTOF patients in an early disease stage. MR TPM could provide information about early abnormalities of LV regional motion and twist function in rTOF patients with preserved LV global function. (orig.)

  17. Development and characterization of a synthetic PVC/DEHP myocardial tissue analogue material for CT imaging applications.

    Science.gov (United States)

    Ramadan, Sherif; Paul, Narinder; Naguib, Hani E

    2018-04-01

    A simple myocardial analogue material has great potential to help researchers in the creation of medical CT Imaging phantoms. This work aims to outline a Bis(2-ethylhexyl) phthalate (DEHP) plasticizer/PVC material to achieve this. DEHP-PVC was manufactured in three ratios, 75, 80, and 85% DEHP by heating at 110 °C for 10 min to promote DEHP-PVC binding followed by heating at 150 °C to melt the blend. The material was then tested utilizing FTIR, tensile testing, dynamic mechanical analysis and imaged with computed tomography. The FTIR testing finds the presence of C-CL and carbonyl bonds that demonstrate the binding required in this plasticized material. The tensile testing finds a modulus of 180-20 kPa that increases with the proportion of plasticizer. The dynamic mechanical analysis finds a linear increase in viscoelastic properties with a storage/loss modulus of 6/.5-120/18 kPa. Finally, the CT number of the material increases with higher PVC content from 55 to 144HU. The 80% DEHP-PVC ratio meets the mechanical and CT properties necessary to function as a myocardial tissue analogue.

  18. Emerging Biofabrication Strategies for Engineering Complex Tissue Constructs

    DEFF Research Database (Denmark)

    Pedde, R. Daniel; Mirani, Bahram; Navaei, Ali

    2017-01-01

    , outlines the use of common biomaterials and advanced hybrid scaffolds, and describes several design considerations including the structural, physical, biological, and economical parameters that are crucial for the fabrication of functional, complex, engineered tissues. Finally, the applications...... of these biofabrication strategies in neural, skin, connective, and muscle tissue engineering are explored.......The demand for organ transplantation and repair, coupled with a shortage of available donors, poses an urgent clinical need for the development of innovative treatment strategies for long-term repair and regeneration of injured or diseased tissues and organs. Bioengineering organs, by growing...

  19. Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs.

    Science.gov (United States)

    Colosi, Cristina; Costantini, Marco; Barbetta, Andrea; Dentini, Mariella

    2017-01-01

    3D bioprinting is an emerging field that can be described as a robotic additive biofabrication technology that has the potential to build tissues or organs. In general, bioprinting uses a computer-controlled printing device to accurately deposit cells and biomaterials into precise architectures with the goal of creating on demand organized multicellular tissue structures and eventually intra-organ vascular networks. The latter, in turn, will promote the host integration of the engineered tissue/organ in situ once implanted. Existing biofabrication techniques still lay behind this goal. Here, we describe a novel microfluidic printing head-integrated within a custom 3D bioprinter-that allows for the deposition of multimaterial and/or multicellular within a single scaffold by extruding simultaneously different bioinks or by rapidly switching between one bioink and another. The designed bioprinting method effectively moves toward the direction of creating viable tissues and organs for implantation in clinic and research in lab environments.

  20. Variation in tissue outcome of ovine and human engineered heart valve constructs : relevance for tissue engineering

    NARCIS (Netherlands)

    Geemen, van D.; Driessen - Mol, A.; Grootzwagers, L.G.M.; Soekhradj - Soechit, R.S.; Riem Vis, P.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    AIM: Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and

  1. Detection of von Willebrand factor and tissue factor in platelets-fibrin rich coronary thrombi in acute myocardial infarction.

    Science.gov (United States)

    Yamashita, Atsushi; Sumi, Takahiro; Goto, Shinya; Hoshiba, Yasunari; Nishihira, Kensaku; Kawamoto, Riichirou; Hatakeyama, Kinta; Date, Haruhiko; Imamura, Takuroh; Ogawa, Hisao; Asada, Yujiro

    2006-01-01

    The rapid closure of coronary arteries due to occlusive thrombi is the major cause of acute myocardial infarction. However, the mechanisms of coronary thrombus formation have not been elucidated. We immunohistochemically assessed the localizations and their changes over time of glycoprotein IIb/IIIa, fibrin, von Willebrand factor (vWF), and tissue factor (TF), after the onset of chest pain (platelets, fibrin, vWF, and TF from the early phase of onset, and glycoprotein IIb/IIIa and fibrin were closely associated with vWF and TF, respectively. vWF and/or TF may contribute to occlusive thrombus formation and be novel therapeutic candidates for treating patients with coronary thrombosis.

  2. Assessment of regional systolic and diastolic myocardial function using tissue Doppler and strain imaging in dogs with dilated cardiomyopathy.

    Science.gov (United States)

    Chetboul, Valérie; Gouni, Vassiliki; Sampedrano, Carolina Carlos; Tissier, Renaud; Serres, François; Pouchelon, Jean-Louis

    2007-01-01

    Tissue Doppler Imaging (TDI) or strain (St) imaging could provide sensitive indices for early detection and treatment follow-up of canine dilated cardiomyopathy (DCM). Analysis of TDI and St features in dogs with overt DCM is a prerequisite before using these new criteria in prospective screenings of predisposed families or in clinical trials. Radial and longitudinal right and left myocardial motion, assessed by TDI and St variables, is altered in dogs with DCM. Case records for 26 dogs; 14 with DCM and 12 healthy controls of comparable age and weight were reviewed. A retrospective analysis was conducted of conventional echocardiography, 2-dimensional color TDI, and St imaging data. The DCM group was characterized by decreases in radial and longitudinal systolic velocity gradients of the left ventricular free wall (LVFW), radial and longitudinal absolute values of peak systolic St of the LVFW, and longitudinal systolic right ventricular (RV) velocities (all P canine DCM.

  3. Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans.

    Science.gov (United States)

    Rutkovskiy, Arkady; Sagave, Julia; Czibik, Gabor; Baysa, Anton; Zihlavnikova Enayati, Katarina; Hillestad, Vigdis; Dahl, Christen Peder; Fiane, Arnt; Gullestad, Lars; Gravning, Jørgen; Ahmed, Shakil; Attramadal, Håvard; Valen, Guro; Vaage, Jarle

    2017-09-01

    We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.

  4. Two-photon Microscopy and Polarimetry for Assessment of Myocardial Tissue Organization

    Science.gov (United States)

    Archambault-Wallenburg, Marika

    Optical methods can provide useful tissue characterization tools. For this project, two-photon microscopy and polarized light examinations (polarimetry) were used to assess the organizational state of myocardium in healthy, infarcted, and stem-cell regenerated states. Two-photon microscopy visualizes collagen through second-harmonic generation and myocytes through two-photon excitation autofluorescence, providing information on the composition and structure/organization of the tissue. Polarimetry measurements yield a value of linear retardance that can serve as an indicator of tissue anisotropy, and with a dual-projection method, information about the anisotropy axis orientation can also be extracted. Two-photon microscopy results reveal that stem-cell treated tissue retains more myocytes and structure than infarcted myocardium, while polarimetry findings suggest that the injury caused by temporary ligation of a coronary artery is less severe and more diffuse that than caused by a permanent ligation. Both these methods show potential for tissue characterization.

  5. An antibody based approach for multi-coloring osteogenic and chondrogenic proteins in tissue engineered constructs.

    Science.gov (United States)

    Leferink, Anne M; Reis, Diogo Santos; van Blitterswijk, Clemens A; Moroni, Lorenzo

    2018-04-11

    When tissue engineering strategies rely on the combination of three-dimensional (3D) polymeric or ceramic scaffolds with cells to culture implantable tissue constructs in vitro, it is desirable to monitor tissue growth and cell fate to be able to more rationally predict the quality and success of the construct upon implantation. Such a 3D construct is often referred to as a 'black-box' since the properties of the scaffolds material limit the applicability of most imaging modalities to assess important construct parameters. These parameters include the number of cells, the amount and type of tissue formed and the distribution of cells and tissue throughout the construct. Immunolabeling enables the spatial and temporal identification of multiple tissue types within one scaffold without the need to sacrifice the construct. In this report, we concisely review the applicability of antibodies (Abs) and their conjugation chemistries in tissue engineered constructs. With some preliminary experiments, we show an efficient conjugation strategy to couple extracellular matrix Abs to fluorophores. The conjugated probes proved to be effective in determining the presence of collagen type I and type II on electrospun and additive manufactured 3D scaffolds seeded with adult human bone marrow derived mesenchymal stromal cells. The conjugation chemistry applied in our proof of concept study is expected to be applicable in the coupling of any other fluorophore or particle to the Abs. This could ultimately lead to a library of probes to permit high-contrast imaging by several imaging modalities.

  6. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  7. Effect of recombinant tissue-type plasminogen activator on acute myocardial infarction; Limitation of infarct size and preservation of left ventricular function evaluated by radionuclide methods

    Energy Technology Data Exchange (ETDEWEB)

    Fukuyama, Takaya; Inou, Tetsuji; Ashihara, Toshiaki; Ogata, Ikuo; Nabeyama, Shouzou; Yamada, Akira; Murakami, Satoshi; Kodama, Mayuko; Matsui, Kanji (Matsuyama Red Cross Hospital, Ehime (Japan))

    1989-12-01

    Radionuclide studies were performed in 18 patients with acute myocardial infarction receiving i.v. injection of recombinant tissue-type plasminogen activator (rt-PA) within 12 hr after an attack. Thallium-201 single photon emission computed tomography revealed that infarct size decreased by 42% in the rt-PA treated group, as compared with 25% in the control group. Left ventricular ejection fraction, as found on first-pass radionuclide angiography with Tc-99m PYP, was significantly higher in the rt-PA treated group than the control group (49% vs 38%). Radionuclide imagings were helpful in confirming myocardial salvage after rt-PA intravenous therapy. It was also considered necessary to perform rt-PA therapy as early as possible after an acute myocardial attack. (N.K.).

  8. Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity.

    Science.gov (United States)

    Sojka, Stephen; Amin, Nirav M; Gibbs, Devin; Christine, Kathleen S; Charpentier, Marta S; Conlon, Frank L

    2014-08-01

    The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development. © 2014. Published by The Company of Biologists Ltd.

  9. Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction

    Science.gov (United States)

    Marks, Edward D.

    The burden of cardiovascular disease around the world is growing, despite improvements in hospital care and time to treatment. As more people survive an initial myocardial infarction (MI), the decompensated heart tissue is strained, leading to heart failure (HF) and an increased risk for a second MI. While extensive progress has been made in treating the symptoms after MI, including HF and angina, little success has come from repairing the damaged heart tissue to alleviate the progression to these end- stage symptoms. One promising area of regenerative research has been the use of adult stem cells, particularly from the bone marrow (BMSCs). These cells can differentiate towards the cardiac cell lineage in vitro while producing trophic factors that can repair damaged tissue. When placed in the heart after MI though, BMSCs have mixed results, producing profound changes in some patients but zero or even negative effects in others. In this report, we used BMSCs as a stem cell base for a regenerative medicine system for the repair of damaged cardiac tissue. These cells are seeded on a polycaprolactone nanoscaffolding support system, which provides a growth substrate for in vitro work, as well as a housing system for protected in vivo delivery. When the nanoscaffold is pre-coated with a novel combination of a cardiac protein, thymosin beta4 (Tbeta4), and a small molecule effector of the WNT protein pathway, IWP-2, BMSCs differentiated towards the cardiac lineage in as little as 24hours. When injected into rat hearts that have been given an ischemic MI, the nanoscaffolding system slowly dissolves, leaving the cells in place of the damaged cardiac tissue. After two weeks of monitoring, BMSCs are present within the damaged hearts, as evidenced by immunofluorescence and nanoparticle tracking. Injections of the nanoscaffolding/cell system led to robust healing of the rat hearts that had been given small- and medium- damage heart attacks, outperforming PBS sham and cell

  10. Monitoring sinew contraction during formation of tissue-engineered fibrin-based ligament constructs.

    Science.gov (United States)

    Paxton, Jennifer Z; Wudebwe, Uchena N G; Wang, Anqi; Woods, Daniel; Grover, Liam M

    2012-08-01

    The ability to study the gross morphological changes occurring during tissue formation is vital to producing tissue-engineered structures of clinically relevant dimensions in vitro. Here, we have used nondestructive methods of digital imaging and optical coherence tomography to monitor the early-stage formation and subsequent maturation of fibrin-based tissue-engineered ligament constructs. In addition, the effect of supplementation with essential promoters of collagen synthesis, ascorbic acid (AA) and proline (P), has been assessed. Contraction of the cell-seeded fibrin gel occurs unevenly within the first 5 days of culture around two fixed anchor points before forming a longitudinal ligament-like construct. AA+P supplementation accelerates gel contraction in the maturation phase of development, producing ligament-like constructs with a higher collagen content and distinct morphology to that of unsupplemented constructs. These studies highlight the importance of being able to control the methods of tissue formation and maturation in vitro to enable the production of tissue-engineered constructs with suitable replacement tissue characteristics for repair of clinical soft-tissue injuries.

  11. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.

    NARCIS (Netherlands)

    Levato, Riccardo; Visser, Jetze; Planell, Josep a; Engel, Elisabeth; Malda, Jos|info:eu-repo/dai/nl/412461099; Mateos-Timoneda, Miguel a

    2014-01-01

    Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the

  12. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity.

    Science.gov (United States)

    Kang, Hyun-Wook; Lee, Sang Jin; Ko, In Kap; Kengla, Carlos; Yoo, James J; Atala, Anthony

    2016-03-01

    A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.

  13. The interplay between tissue growth and scaffold degradation in engineered tissue constructs

    KAUST Repository

    O’ Dea, R. D.; Osborne, J. M.; El Haj, A. J.; Byrne, H. M.; Waters, S. L.

    2012-01-01

    of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a

  14. Distribution patterns of Gd-DTPA-enhanced magnetic resonance imaging after intravenous tissue plasminogen activator therapy for acute myocardial infarction

    International Nuclear Information System (INIS)

    Fukuzawa, Shigeru; Watanabe, Hiroyuki; Shimada, Kazuhiro; Katagiri, Nakoto; Ozawa, Shun

    1994-01-01

    In patients who received thrombolytic therapy for acute myocardial infarction (AMI), we observed 3 distinct patterns in gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging. To clarify the significance of these distribution patterns of Gd-DTPA, 20 consecutive patients underwent Gd-DTPA-enhanced MR imaging 7-10 days after AMI. All of the patients received intravenous recombinant tissue plasminogen activator (IVTPA) within 6 h of onset. Echocardiograms were obtained prior to and serially over 10 days, and interpreted for regional wall motion. Coronary angiograms were obtained the day before discharge. None of the 6 patients with a closed infarct-related artery, and 9 of the 14 patients with an open artery, demonstrated subendocardial enhancement (p<0.05). All of these latter 9 patients demonstrated a significant improvement in wall motion between days 1 and 10 after AMI. In contrast, only 1 of the 7 patients with transmural enhancement and none of the 4 patients with non-homogeneous enhancement demonstrated improvement of wall motion on day 10 (p<0.05). We concluded that subendocardial enhancement was a fair prognostic sign for restoration of regional cardiac function in patients who received IVTPA during AMI. (author)

  15. Direct measurement of the lethal isotherm for radiofrequency ablation of myocardial tissue.

    Science.gov (United States)

    Wood, Mark; Goldberg, Scott; Lau, Melissa; Goel, Aneesh; Alexander, Daniel; Han, Frederick; Feinstein, Shawn

    2011-06-01

    The lethal isotherm for radiofrequency catheter ablation of cardiac myocardium is widely accepted to be 50°C, but this has not been directly measured. The purpose of this study was to directly measure the tissue temperature at the edge of radiofrequency lesions in real time using infrared thermal imaging. Fifteen radiofrequency lesions of 6 to 240 seconds in duration were applied to the left ventricular surface of isolated perfused pig hearts. At the end of radiofrequency delivery, a thermal image of the tissue surface was acquired with an infrared camera. The lesion was then stained and an optical image of the lesion was obtained. The thermal and optical images were electronically merged to allow determination of the tissue temperature at the edge of the lesion at the end of radiofrequency delivery. By adjusting the temperature overlay display to conform with the edge of the radiofrequency lesion, the lethal isotherm was measured to be 60.6°C (interquartile ranges, 59.7° to 62.4°C; range, 58.1° to 64.2°C). The areas encompassed by the lesion border in the optical image and the lethal isotherm in the thermal image were statistically similar and highly correlated (Spearman ρ=0.99, Pradiofrequency delivery or to lesion size (both P>0.64). The areas circumscribed by 50°C isotherms were significantly larger than the areas of the lesions on optical imaging (P=0.002). By direct measurement, the lethal isotherm for cardiac myocardium is near 61°C for radiofrequency energy deliveries radiofrequency ablation is important to clinical practice as well as mathematical modeling of radiofrequency lesions.

  16. Early myocardial impairment in type 1 diabetes patients without known heart disease assessed with tissue Doppler echocardiography

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Søgaard, Peter; Andersen, Henrik Ullits

    2016-01-01

    PURPOSE: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls. METHODS:...

  17. Myocardial Bridge

    Science.gov (United States)

    ... Center > Myocardial Bridge Menu Topics Topics FAQs Myocardial Bridge En español Your heart is made of muscle, ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

  18. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications

    International Nuclear Information System (INIS)

    Xu Tao; Binder, Kyle W; Albanna, Mohammad Z; Dice, Dennis; Zhao Weixin; Yoo, James J; Atala, Anthony

    2013-01-01

    Bioprinting is an emerging technique used to fabricate viable, 3D tissue constructs through the precise deposition of cells and hydrogels in a layer-by-layer fashion. Despite the ability to mimic the native properties of tissue, printed 3D constructs that are composed of naturally-derived biomaterials still lack structural integrity and adequate mechanical properties for use in vivo, thus limiting their development for use in load-bearing tissue engineering applications, such as cartilage. Fabrication of viable constructs using a novel multi-head deposition system provides the ability to combine synthetic polymers, which have higher mechanical strength than natural materials, with the favorable environment for cell growth provided by traditional naturally-derived hydrogels. However, the complexity and high cost associated with constructing the required robotic system hamper the widespread application of this approach. Moreover, the scaffolds fabricated by these robotic systems often lack flexibility, which further restrict their applications. To address these limitations, advanced fabrication techniques are necessary to generate complex constructs with controlled architectures and adequate mechanical properties. In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications. Electrospinning of polycaprolactone fibers was alternated with inkjet printing of rabbit elastic chondrocytes suspended in a fibrin–collagen hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness. The chondrocytes survived within the printed hybrid construct with more than 80% viability one week after printing. In addition, the cells proliferated and maintained their basic biological properties within the printed layered constructs. Furthermore, the fabricated constructs formed cartilage-like tissues both in vitro and in vivo as evidenced by the

  19. Myocardial left ventricular dysfunction in patients with systemic lupus erythematosus: new insights from tissue Doppler and strain imaging.

    Science.gov (United States)

    Buss, Sebastian J; Wolf, David; Korosoglou, Grigorios; Max, Regina; Weiss, Celine S; Fischer, Christian; Schellberg, Dieter; Zugck, Christian; Kuecherer, Helmut F; Lorenz, Hanns-Martin; Katus, Hugo A; Hardt, Stefan E; Hansen, Alexander

    2010-01-01

    Systemic lupus erythematosus (SLE) is associated with high cardiovascular morbidity and mortality. Cardiovascular involvement is frequently underestimated by routine imaging techniques. Our aim was to determine if new echocardiographic imaging modalities like tissue Doppler (TDI), strain rate (SRR), and strain (SRI) imaging detect abnormalities in left ventricular (LV) function in asymptomatic patients with SLE. Sixty-seven young patients with SLE (mean age 42 +/- 10 yrs) without typical symptoms or signs of heart failure or angina, and a matched healthy control group (n = 40), underwent standard transthoracic echocardiography, TDI, SRR, and SRI imaging of the LV as well as assessment of disease characteristics. Despite findings within the normal range on routine standard 2-dimensional echocardiography, SLE was associated with significantly impaired systolic and diastolic myocardial velocities of the LV measured by TDI [mean global TDI: systolic (s): 2.9 +/- 0.9 vs 3.9 +/- 0.7 cm/s, p < 0.05; early (e): 4.3 +/- 1.5 vs 6.3 +/- 1.3 cm/s, p < 0.05; late (a): 2.9 +/- 0.8 vs 3.4 +/- 0.8 cm/s, p < 0.05; values +/- SD); SRR (s: -0.8 +/- 0.1 vs -1.1 +/- 0.1 s(-1); e: 1.1 +/- 0.2 vs 1.6 +/- 0.3 s(-1); a: 0.7 +/- 0.1 vs 1.0 +/- 0.2 s(-1); all p < 0.05); and SR (-15.11 +/- 2.2% vs -19.7 +/- 1.9%; p < 0.05) compared to the control group. Further, elevated disease activity, measured with the ECLAM and the SLEDAI score, resulted in significantly lower values for LV longitudinal function measured by SRR and SR, but not by TDI. SLE is associated with a significant impairment of systolic and diastolic LV longitudinal function in patients without cardiac symptoms. New imaging modalities provide earlier insight into cardiovascular involvement in SLE and seem to be superior to standard echocardiography to detect subclinical myocardial disease.

  20. Estimation of left ventricular end diastolic pressure by tissue doppler imaging in patients with acute myocardial infarction

    International Nuclear Information System (INIS)

    Ali, M.; Abid, A.R.; Rehman, T.A.; Masood, A.; Sohail, S.

    2010-01-01

    Objective: To evaluate sensitivity and specificity of E / Ea > 10 for prediction of LVEDP > 15 mmHg in patients with coronary artery disease undergoing left heart catheterization. Materials and Methods: Sixty patients of acute transmural myocardial infarction at Jinnah Hospital Lahore were enrolled in study from December 2008 to December 2009. Patients with sinus rhythm were included in the study. Patients with valvular heart disease, complete right/left bundle branch block, Pacemaker dependence, Atrial fibrillation and Post mitral valve replacement were excluded. All patients were examined by performing trans thoracic Doppler echocardiography. The trans-mitral LV filling signal was traced manually and the following variables were obtained: peak early (E) and late (A) trans-mitral velocities, and E/A ratio. Tissue - Doppler derived indices were recorded at the lateral mitral annulus. These indices included systolic velocities (S'), early diastolic (Ea) velocities and late diastolic (Aa) velocities. Finally, the dimensionless index of E/Ea was calculated. All were averaged from at least three beats. Cardiac catheterization was performed via trans-femoral / trasradial route using six French (6F) sheaths. Left ventricular diastolic pressure was directly measured by fluid filled pigtail catheter attached to a pressure transducer. Results: Mean age of the study population was 56.8 +- 12.7 years. There were 47 (78.3%) males and 13 (21.7%) females. Diabetes mellitus was present in 12(20%), hypertension in 32 (53.3%), smoking in 35 (58.3%), dyslipidemia in 24 (40%). Anterior wall myocardial infarction occurred in 44 (73.3%) and inferior wall MI in 16 (26.7%). Grade I diastolic dysfunction was present in 22 (36.7%), Grade II in 31 (51.7%) and Grade III in 7 (11.7%) patients. E/E 15 in 9 (15%). Overall 21 patients were true positive, 6 were false positive, 25 were true negative and 8 were false negative. By applying 2 X 2 table sensitivity was 77.7%, specificity was 80

  1. Estimation of left ventricular end diastolic pressure by tissue doppler imaging in patients with acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Ali, M; Abid, A R; Rehman, T A; Masood, A; Sohail, S [Allama Iqbal Medical College/Jinnah Hospital, Lahore(Pakistan)

    2010-10-15

    Objective: To evaluate sensitivity and specificity of E / Ea > 10 for prediction of LVEDP > 15 mmHg in patients with coronary artery disease undergoing left heart catheterization. Materials and Methods: Sixty patients of acute transmural myocardial infarction at Jinnah Hospital Lahore were enrolled in study from December 2008 to December 2009. Patients with sinus rhythm were included in the study. Patients with valvular heart disease, complete right/left bundle branch block, Pacemaker dependence, Atrial fibrillation and Post mitral valve replacement were excluded. All patients were examined by performing trans thoracic Doppler echocardiography. The trans-mitral LV filling signal was traced manually and the following variables were obtained: peak early (E) and late (A) trans-mitral velocities, and E/A ratio. Tissue - Doppler derived indices were recorded at the lateral mitral annulus. These indices included systolic velocities (S'), early diastolic (Ea) velocities and late diastolic (Aa) velocities. Finally, the dimensionless index of E/Ea was calculated. All were averaged from at least three beats. Cardiac catheterization was performed via trans-femoral / trasradial route using six French (6F) sheaths. Left ventricular diastolic pressure was directly measured by fluid filled pigtail catheter attached to a pressure transducer. Results: Mean age of the study population was 56.8 +- 12.7 years. There were 47 (78.3%) males and 13 (21.7%) females. Diabetes mellitus was present in 12(20%), hypertension in 32 (53.3%), smoking in 35 (58.3%), dyslipidemia in 24 (40%). Anterior wall myocardial infarction occurred in 44 (73.3%) and inferior wall MI in 16 (26.7%). Grade I diastolic dysfunction was present in 22 (36.7%), Grade II in 31 (51.7%) and Grade III in 7 (11.7%) patients. E/E < 10 was observed in 31 (51.7%), 11 - 15 in 20 (33.3%) and > 15 in 9 (15%). Overall 21 patients were true positive, 6 were false positive, 25 were true negative and 8 were false negative. By

  2. A Lindenmayer system-based approach for the design of nutrient delivery networks in tissue constructs

    Energy Technology Data Exchange (ETDEWEB)

    Yasar, Ozlem; Starly, Binil [School of Industrial Engineering, University of Oklahoma, Norman, OK 73019 (United States); Lan, S-F [University of Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK 73019 (United States)

    2009-12-15

    Large thick tissue constructs have reported limited success primarily due to the inability of cells to survive deep within the scaffold. Without access to adequate nutrients, cells placed deep within the tissue construct will die out, leading to non-uniform tissue regeneration. Currently, there is a necessity to design nutrient conduit networks within the tissue construct to enable cells to survive in the matrix. However, the design of complex networks within a tissue construct is challenging. In this paper, we present the Lindenmayer system, an elegant fractal-based language algorithm framework, to generate conduit networks in two- and three-dimensional architecture with several degrees of complexity. The conduit network maintains a parent-child relationship between each branch of the network. Several L-system parameters have been studied-branching angle, branch length, ratio of parent to child branch diameter, etc-to simulate several architectures under a given L-system notation. We have also presented a layered manufacturing-based UV-photopolymerization process using the Texas Instruments DLP(TM) system to fabricate the branched structures. This preliminary work showcases the applicability of L-system-based construct designs to drive scaffold fabrication systems.

  3. A Lindenmayer system-based approach for the design of nutrient delivery networks in tissue constructs

    International Nuclear Information System (INIS)

    Yasar, Ozlem; Starly, Binil; Lan, S-F

    2009-01-01

    Large thick tissue constructs have reported limited success primarily due to the inability of cells to survive deep within the scaffold. Without access to adequate nutrients, cells placed deep within the tissue construct will die out, leading to non-uniform tissue regeneration. Currently, there is a necessity to design nutrient conduit networks within the tissue construct to enable cells to survive in the matrix. However, the design of complex networks within a tissue construct is challenging. In this paper, we present the Lindenmayer system, an elegant fractal-based language algorithm framework, to generate conduit networks in two- and three-dimensional architecture with several degrees of complexity. The conduit network maintains a parent-child relationship between each branch of the network. Several L-system parameters have been studied-branching angle, branch length, ratio of parent to child branch diameter, etc-to simulate several architectures under a given L-system notation. We have also presented a layered manufacturing-based UV-photopolymerization process using the Texas Instruments DLP(TM) system to fabricate the branched structures. This preliminary work showcases the applicability of L-system-based construct designs to drive scaffold fabrication systems.

  4. [Research progress of co-culture system for constructing vascularized tissue engineered bone].

    Science.gov (United States)

    Fu, Weili; Xiang, Zhou

    2014-02-01

    To review the research progress of the co-culture system for constructing vascularized tissue engineered bone. The recent literature concerning the co-culture system for constructing vascularized tissue engineered bone was reviewed, including the selection of osteogenic and endothelial lineages, the design and surface modification of scaffolds, the models and dimensions of the co-culture system, the mechanism, the culture conditions, and their application progress. The construction of vascularized tissue engineered bone is the prerequisite for their survival and further clinical application in vivo. Mesenchymal stem cells (owning the excellent osteogenic potential) and endothelial progenitor cells (capable of directional differentiation into endothelial cell) are considered as attractive cell types for the co-culture system to construct vascularized tissue engineered bone. The culture conditions need to be further optimized. Furthermore, how to achieve the clinical goals of minimal invasion and autologous transplantation also need to be further studied. The strategy of the co-culture system for constructing vascularized tissue engineered bone would have a very broad prospects for clinical application in future.

  5. A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

    Science.gov (United States)

    Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

    2016-03-21

    Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue

    Science.gov (United States)

    Seke, Mariana; Petrovic, Danijela; Djordjevic, Aleksandar; Jovic, Danica; Labudovic Borovic, Milica; Kanacki, Zdenko; Jankovic, Milan

    2016-12-01

    Fullerenol (C60(OH)24) is present in aqueous solutions in the form of polyanion nanoparticles with particles’ size distribution within the range from 15 to 42 nm. In this research it is assumed that these features could enable fullerenol nanoparticles (FNPs) to bind positively charged molecules like doxorubicin (DOX) and serve as drug carriers. Considering this, fullerenol/doxorubicin nanocomposite (FNP/DOX) is formed and characterized by ultra-performance liquid chromatography tandem mass spectrometry, dynamic light scattering, atomic force microscopy and transmission electron microscopy. Measurements have shown that DOX did not significantly affect particle size (23 nm). It is also assumed that FNP/DOX could reduce the acute cardiotoxic effects of DOX in vivo (Wistar rats treated i.p.). In this study, quantitative real time polymerase chain reaction results have shown that treatment with DOX alone caused significant increase in mRNA levels of catalase (p effect is significantly reduced by the treatment with FNP/DOX (p < 0.05). Furthermore, mRNA levels of antiapoptotic enzyme (Bcl-2) are significantly increased (p < 0.05) in all treated groups, particularly where FNP/DOX was applied, suggesting cell resistance to apoptosis. Moreover, ultrastructural analysis has shown the absence of myelin figures within the mitochondria in the heart tissue with FNP/DOX treatment, indicating reduction of oxidative stress. Hence, our results have implied that FNP/DOX is generally less harmful to the heart compared to DOX.

  7. p53 and telomerase control rat myocardial tissue response to hypoxia and ageing

    Directory of Open Access Journals (Sweden)

    A. Cataldi

    2009-12-01

    Full Text Available Cellular senescence implies loss of proliferative and tissue regenerative capability. Also hypoxia, producing Reactive Oxygen Species (ROS, can damage cellular components through the oxidation of DNA, proteins and lipids, thus influencing the shortening of telomeres. Since ribonucleoprotein Telomerase (TERT, catalyzing the replication of the ends of eukaryotic chromosomes, promotes cardiac muscle cell proliferation, hypertrophy and survival, here we investigated its role in the events regulating apoptosis occurrence and life span in hearts deriving from young and old rats exposed to hypoxia. TUNEL (terminal-deoxinucleotidyl -transferase- mediated dUTP nick end-labeling analysis reveals an increased apoptotic cell number in both samples after hypoxia exposure, mainly in the young with respect to the old. TERT expression lowers either in the hypoxic young, either in the old in both experimental conditions, with respect to the normoxic young. These events are paralleled by p53 and HIF-1 ? expression dramatic increase and by p53/ HIF-1 ? co-immunoprecipitation in the hypoxic young, evidencing the young subject as the most stressed by such challenge. These effects could be explained by induction of damage to genomic DNA by ROS that accelerates cell senescence through p53 activation. Moreover, by preventing TERT enzyme down-regulation, cell cycle exit and apoptosis occurrence could be delayed and new possibilities for intervention against cell ageing and hypoxia could be opened.

  8. Magnetic resonance microscopy for monitoring osteogenesis in tissue-engineered construct in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huihui [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Othman, Shadi F [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Hong Liu [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Peptan, Ioana A [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Magin, Richard L [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States)

    2006-02-07

    Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue-engineered constructs. Measurements of the developing tissue's MR relaxation times (T{sub 1} and T{sub 2}), apparent diffusion coefficient (ADC) and elastic shear modulus were conducted over a 4-week growth period using an 11.74 T Bruker spectrometer with an imaging probe adapted for MR elastography (MRE). Both the relaxation times and the ADC show a statistically significant decrease after only one week of tissue development while the tissue stiffness increases progressively during the first two weeks of in vitro growth. The measured MR parameters are correlated with histologically monitored osteogenic tissue development. This study shows that MRM can provide quantitative data with which to characterize the growth and development of tissue-engineered bone.

  9. A new construction technique for tissue-engineered heart valves using the self-assembly method.

    Science.gov (United States)

    Tremblay, Catherine; Ruel, Jean; Bourget, Jean-Michel; Laterreur, Véronique; Vallières, Karine; Tondreau, Maxime Y; Lacroix, Dan; Germain, Lucie; Auger, François A

    2014-11-01

    Tissue engineering appears as a promising option to create new heart valve substitutes able to overcome the serious drawbacks encountered with mechanical substitutes or tissue valves. The objective of this article is to present the construction method of a new entirely biological stentless aortic valve using the self-assembly method and also a first assessment of its behavior in a bioreactor when exposed to a pulsatile flow. A thick tissue was created by stacking several fibroblast sheets produced with the self-assembly technique. Different sets of custom-made templates were designed to confer to the thick tissue a three-dimensional (3D) shape similar to that of a native aortic valve. The construction of the valve was divided in two sequential steps. The first step was the installation of the thick tissue in a flat preshaping template followed by a 4-week maturation period. The second step was the actual cylindrical 3D forming of the valve. The microscopic tissue structure was assessed using histological cross sections stained with Masson's Trichrome and Picrosirius Red. The thick tissue remained uniformly populated with cells throughout the construction steps and the dense extracellular matrix presented corrugated fibers of collagen. This first prototype of tissue-engineered heart valve was installed in a bioreactor to assess its capacity to sustain a light pulsatile flow at a frequency of 0.5 Hz. Under the light pulsed flow, it was observed that the leaflets opened and closed according to the flow variations. This study demonstrates that the self-assembly method is a viable option for the construction of complex 3D shapes, such as heart valves, with an entirely biological material.

  10. Constructing a Computer Model of the Human Eye Based on Tissue Slice Images

    OpenAIRE

    Dai, Peishan; Wang, Boliang; Bao, Chunbo; Ju, Ying

    2010-01-01

    Computer simulation of the biomechanical and biological heat transfer in ophthalmology greatly relies on having a reliable computer model of the human eye. This paper proposes a novel method on the construction of a geometric model of the human eye based on tissue slice images. Slice images were obtained from an in vitro Chinese human eye through an embryo specimen processing methods. A level set algorithm was used to extract contour points of eye tissues while a principle component analysi...

  11. Left ventricular diastolic dyssynchrony assessed with phase analysis of gated myocardial perfusion SPECT: a comparison with tissue Doppler imaging

    International Nuclear Information System (INIS)

    Boogers, Mark J.; Veltman, Caroline E.; Chen, Ji; Garcia, Ernest V.; Bommel, Rutger J. van; Mooyaart, Eline A.Q.; Wall, Ernst E. van der; Schalij, Martin J.; Bax, Jeroen J.; Delgado, Victoria; Younis, Imad Al; Hiel, Bernies van der; Dibbets-Schneider, Petra

    2011-01-01

    The aim of the current study was to evaluate the feasibility of phase analysis on gated myocardial perfusion SPECT (GMPS) for the assessment of left ventricular (LV) diastolic dyssynchrony in a head-to-head comparison with tissue Doppler imaging (TDI). The population consisted of patients with end-stage heart failure of New York Heart Association functional class III or IV with a reduced LV ejection fraction of ≤35%. LV diastolic dyssynchrony was calculated using TDI as the maximal time delay between early peak diastolic velocities of two opposing left ventricle walls (diastolic mechanical delay). Significant LV diastolic dyssynchrony was defined as a diastolic mechanical delay of >55 ms on TDI. Furthermore, phase analysis on GMPS was performed to evaluate LV diastolic dyssynchrony; diastolic phase standard deviation (SD) and histogram bandwidth (HBW) were used as markers of LV diastolic dyssynchrony. A total of 150 patients (114 men, mean age 66.0 ± 10.4 years) with end-stage heart failure were enrolled. Both diastolic phase SD (r = 0.81, p 55 ms) showed significantly larger diastolic phase SD (68.1 ± 13.4 vs. 40.7 ± 14.0 , p < 0.01) and diastolic HBW (230.6 ± 54.3 vs. 129.0 ± 55.6 , p < 0.01) as compared to patients without LV diastolic dyssynchrony on TDI (≤55 ms). Finally, phase analysis on GMPS showed a good intra- and interobserver reproducibility for the determination of diastolic phase SD (ICC 0.97 and 0.88) and diastolic HBW (ICC 0.98 and 0.93). Phase analysis on GMPS showed good correlations with TDI for the assessment of LV diastolic dyssynchrony. (orig.)

  12. Synthesis and tissue distribution of fluorine-18 labeled trifluorohexadecanoic acids. Considerations in the development of metabolically blocked myocardial imaging agents

    International Nuclear Information System (INIS)

    Pochapsky, S.S.; Katzenellenbogen, J.A.; VanBrocklin, H.F.; Welch, M.J.

    1990-01-01

    A versatile method for the synthesis of trifluoro fatty acids, potential metabolically blocked myocardial imaging agents, has been developed. Two trifluorohexadecanoic (palmitic) acids have been prepared [6,6,16-trifluorohexadecanoic acid (I) and 7,7,16-trifluorohexadecanoic acid (II)], each of which bears two of the fluorine atoms as a gem-difluoromethylene unit on the fatty acid chain (at C-6 or C-7) and the third at the ω (C-16) position. The metabolic stability of carbon-fluorine bonds suggests the gem-difluoro group may block the β-oxidation pathway, while the terminal fluorine could be the site for labeling with fluorine-18. The convergent synthetic approach utilizes a 2-lithio-1,3-dithiane derived from 10-undecenal or 9-decenal, which is alkylated with the OBO (oxabicyclooctyl) ester of 5-bromopentanoic acid or 6-bromohexanoic acid, respectively. Hydroboration-oxidation and alcohol protection are followed by halofluorination to convert the 1,3-dithiane system to a gem-difluoro group. The third fluorine is introduced by fluoride ion displacement of a trifluoromethanesulfonate. This synthesis is adapted to the labeling of these trifluoro fatty acids with the short-lived radionuclide fluorine-18 (t 1/2 = 110 min), with the third fluorine introduced as fluoride ion in the penultimate step. The radiochemical syntheses proceed in 3-34% radiochemical yield (decay corrected), with an overall synthesis and purification time of 90 min. Tissue distribution studies in rats were performed with I and II, as well as with 16-[ 18 F]fluoropalmitic acid (III), [ 11 C]palmitic acid, and [ 11 C]octanoic acid. The heart uptake of the fluoropalmitic acids decreases with substitution, the 2-min activity level for 16-fluoropalmitic acid being 65% and that for both 6,6,16-and 7,7,17-trifluoropalmitic acids being 30% that of palmitic acid

  13. Differential Mechanisms of Myocardial Conduction Slowing by Adipose Tissue-Derived Stromal Cells Derived From Different Species

    NARCIS (Netherlands)

    ten Sande, Judith N.; Smit, Nicoline W.; Parvizi, Mojtaba; van Amersfoorth, Shirley C. M.; Plantinga, Josee A.; van Dessel, Pascal F. H. M.; de Bakker, Jacques M. T.; Harmsen, Marco C.; Coronel, Ruben

    : Stem cell therapy is a promising therapeutic option to treat patients after myocardial infarction. However, the intramyocardial administration of large amounts of stem cells might generate a proarrhythmic substrate. Proarrhythmic effects can be explained by electrotonic and/or paracrine

  14. The design and construction of an electrohydrodynamic cartesian robot for the preparation of tissue engineering constructs.

    Directory of Open Access Journals (Sweden)

    Shaikh Hafeez Hashimdeen

    Full Text Available In this work we bring together replicating rapid prototyping technology with electrohydrodynamic phenomena to develop a device with the ability to build structures in three-dimensions while simultaneously affording the user a degree of designing versatility and ease that is not seen in conventional computer numerically controlled machines. An attempt at reproducing an actual human ear using polycaprolactone was pursued to validate the hardware. Five different polycaprolactone solution concentrations between 7-15 wt% were used and printing was performed at applied voltages that ranged from 1 to 6 kV and at flow rates from 5 µl/min to 60 µl/min. The corresponding geometrical and aesthetic features of the printed constructs were studied to determine the effectiveness of the device. The 15 wt% concentration at 60 µl/min under an applied electric field of 6 kV was identified as the best operating parameters to work with.

  15. Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends.

    Science.gov (United States)

    Oliveira, Sara M; Reis, Rui L; Mano, João F

    2015-11-01

    The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation are achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemical control than top-down strategies, and are the main focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force.

    Science.gov (United States)

    Shimizu, Kazunori; Ito, Akira; Yoshida, Tatsuro; Yamada, Yoichi; Ueda, Minoru; Honda, Hiroyuki

    2007-08-01

    An in vitro reconstruction of three-dimensional (3D) tissues without the use of scaffolds may be an alternative strategy for tissue engineering. We have developed a novel tissue engineering strategy, termed magnetic force-based tissue engineering (Mag-TE), in which magnetite cationic liposomes (MCLs) with a positive charge at the liposomal surface, and magnetic force were used to construct 3D tissue without scaffolds. In this study, human mesenchymal stem cells (MSCs) magnetically labeled with MCLs were seeded onto an ultra-low attachment culture surface, and a magnet (4000 G) was placed on the reverse side. The MSCs formed multilayered sheet-like structures after a 24-h culture period. MSCs in the sheets constructed by Mag-TE maintained an in vitro ability to differentiate into osteoblasts, adipocytes, or chondrocytes after a 21-day culture period using each induction medium. Using an electromagnet, MSC sheets constructed by Mag-TE were harvested and transplanted into the bone defect in the crania of nude rats. Histological observation revealed that new bone surrounded by osteoblast-like cells was formed in the defect area 14 days after transplantation with MSC sheets, whereas no bone formation was observed in control rats without the transplant. These results indicated that Mag-TE could be used for the transplantation of MSC sheets using magnetite nanoparticles and magnetic force, providing novel methodology for bone tissue engineering.

  17. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology.

    Science.gov (United States)

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony

    2013-01-01

    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: Measurement and modeling

    NARCIS (Netherlands)

    Malda, J.; Rouwkema, Jeroen; Martens, D.E.; le Comte, EP; Kooy, F.K.; Tramper, J.; van Blitterswijk, Clemens; Riesle, J.U.

    2004-01-01

    The supply of oxygen within three-dimensional tissue-engineered (TE) cartilage polymer constructs is mainly by diffusion. Oxygen consumption by cells results in gradients in the oxygen concentration. The aims of this study were, firstly, to identify the gradients within TE cartilage polymer

  19. Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: measurement and modeling

    NARCIS (Netherlands)

    Malda, J.; Rouwkema, J.; Martens, D.E.; Paul le Comte, E.; Kooy, F.K.; Tramper, J.; Blitterswijk, van C.A.; Riesle, J.

    2004-01-01

    The supply of oxygen within three-dimensional tissue-engineered (TE) cartilage polymer constructs is mainly by diffusion. Oxygen consumption by cells results in gradients in the oxygen concentration. The aims of this study were, firstly, to identify the gradients within TE: cartilage polymer

  20. The effect of PEGT/PBT scaffold architecture on oxygen gradients in tissue engineered cartilaginous constructs

    NARCIS (Netherlands)

    Malda, J.; Woodfield, T.B.F.; van der Vloodt, F.; Kooy, F.K.; Martens, D.E.; Tramper, J.C.; van Blitterswijk, Clemens; Riesle, J.U.

    2004-01-01

    Repair of articular cartilage defects using tissue engineered constructs composed of a scaffold and cultured autologous cells holds promise for future treatments. However, nutrient limitation (e.g. oxygen) has been suggested as a cause of the onset of chondrogenesis solely within the peripheral

  1. Magnetic nanoparticle-loaded alginate beads for local micro-actuation of in vitro tissue constructs.

    Science.gov (United States)

    Alshehri, Awatef M; Wilson, Otto C; Dahal, Bishnu; Philip, John; Luo, Xiaolong; Raub, Christopher B

    2017-11-01

    Magnetic nanoparticles (MNPs) self-align and transduce magnetic force, two properties which lead to promising applications in cell and tissue engineering. However, the toxicity of MNPs to cells which uptake them is a major impediment to applications in engineered tissue constructs. To address this problem, MNPs were embedded in millimeter-scale alginate beads, coated with glutaraldehyde cross-linked chitosan, and loaded in acellular and MDA-MB-231 cancer cell-seeded collagen hydrogels, providing local micro-actuation under an external magnetic field. Brightfield microscopy was used to assess nanoparticle diffusion from the bead. Phase contrast microscopy and digital image correlation were used to track collagen matrix displacement and estimate intratissue strain under magnetic actuation. Coating the magnetic alginate beads with glutaraldehyde-chitosan prevents bulk diffusion of nanoparticles into the surrounding microenvironment. Further, the beads exert force on the surrounding collagen gel and cells, resulting in intratissue strains of 0-10% tunable with bead dimensions, collagen density, and distance from the bead. Cells seeded adjacent to the embedded beads are subjected to strain gradients without loss of cell viability over two days culture. This study describes a simple way to fabricate crosslinked magnetic alginate beads to load in a collagen tissue construct without direct exposure of the construct to nanoparticles. The findings are significant to in vitro studies of mechanobiology in enabling precise control over dynamic mechanical loading of tissue constructs. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.

    Science.gov (United States)

    Hsiao, Amy Y; Okitsu, Teru; Onoe, Hiroaki; Kiyosawa, Mahiro; Teramae, Hiroki; Iwanaga, Shintaroh; Kazama, Tomohiko; Matsumoto, Taro; Takeuchi, Shoji

    2015-01-01

    The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D) cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT) cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.

  3. Ready-to-Use Tissue Construct for Military Bone and Cartilage Trauma

    Science.gov (United States)

    2012-10-01

    physiologic hyaline cartilage - osseous transition in massive osteochondral defects in large animals. We will conduct functional outcome analysis, X...10-1-0933 TITLE: Ready-to-Use Tissue Construct for Military Bone and Cartilage Trauma PRINCIPAL INVESTIGATOR: Francis Y. Lee... Cartilage Trauma” addresses the current limitations in treating complex, high-energy musculoskeletal wounds incurred in active combat. High-energy

  4. A Hyaluronan-Based Scaffold for the in Vitro Construction of Dental Pulp-Like Tissue

    Directory of Open Access Journals (Sweden)

    Letizia Ferroni

    2015-03-01

    Full Text Available Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D hyaluronan scaffold and human dental pulp stem cells (DPSCs to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  5. A hyaluronan-based scaffold for the in vitro construction of dental pulp-like tissue.

    Science.gov (United States)

    Ferroni, Letizia; Gardin, Chiara; Sivolella, Stefano; Brunello, Giulia; Berengo, Mario; Piattelli, Adriano; Bressan, Eriberto; Zavan, Barbara

    2015-03-02

    Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D) hyaluronan scaffold and human dental pulp stem cells (DPSCs) to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF) staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  6. Postmortem mRNA expression patterns in left ventricular myocardial tissues and their implications for forensic diagnosis of sudden cardiac death.

    Science.gov (United States)

    Son, Gi Hoon; Park, Seong Hwan; Kim, Yunmi; Kim, Ji Yeon; Kim, Jin Wook; Chung, Sooyoung; Kim, Yu-Hoon; Kim, Hyun; Hwang, Juck-Joon; Seo, Joong-Seok

    2014-03-01

    Sudden cardiac death (SCD), which is primarily caused by lethal heart disorders resulting in structural and arrhythmogenic abnormalities, is one of the prevalent modes of death in most developed countries. Myocardial ischemia, mainly due to coronary artery disease, is the most common type of heart disease leading to SCD. However, postmortem diagnosis of SCD is frequently complicated by obscure histological evidence. Here, we show that certain mRNA species, namely those encoding hemoglobin A1/2 and B (Hba1/2 and Hbb, respectively) as well as pyruvate dehydrogenase kinase 4 (Pdk4), exhibit distinct postmortem expression patterns in the left ventricular free wall of SCD subjects when compared with their expression patterns in the corresponding tissues from control subjects with non-cardiac causes of death. Hba1/2 and Hbb mRNA expression levels were higher in ischemic SCD cases with acute myocardial infarction or ischemic heart disease without recent infarction, and even in cardiac death subjects without apparent pathological signs of heart injuries, than control subjects. By contrast, Pdk4 mRNA was expressed at lower levels in SCD subjects. In conclusion, we found that altered myocardial Hba1/2, Hbb, and Pdk4 mRNA expression patterns can be employed as molecular signatures of fatal cardiac dysfunction to forensically implicate SCD as the primary cause of death.

  7. Usefulness of the myocardial performance index determined by tissue Doppler imaging m-mode for predicting mortality in the general population

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Møgelvang, Rasmus; Haahr-Pedersen, Sune Ammentorp

    2011-01-01

    The objective of this study was to evaluate the prognostic value of the myocardial performance index (MPI), assessed by color-coded tissue Doppler imaging (TDI) M-mode through the anterior mitral leaflet. Color TDI M-mode through the mitral leaflet is an easy, very fast, and precise method...... ventricular in- and outflow using standard procedures (MPI(conv)) and by color-coded TDI M-mode through the mitral leaflet in the apical 4-chamber view (MPI(TDI)). MPI(TDI) was increased in subjects with coronary heart disease (CHD) compared to controls, even after multivariable adjustment (p

  8. [Construction of a capsular tissue-engineered ureteral stent seeded with autologous urothelial cells].

    Science.gov (United States)

    Tan, Haisong; Fu, Weijun; Li, Jianqiang; Wang, Zhongxin; Li, Gang; Ma, Xin; Dong, Jun; Gao, Jiangping; Wang, Xiaoxiong; Zhang, Xu

    2013-01-01

    To investigate the feasibility of constructing a capsular poly L-lactic acid (PLLA) ureteral stent seeded with autologous urothelial cells using tissue engineering methods. The capsular ureteral stent was constructed by subcutaneously embedding PLLA ureteral stent in the back of beagles for 3 weeks to induce the formation of connective tissue on the surfaces. After decellularization of the stent, the expanded autologous urothelial cells were seeded on the stent. The surface structure and cell adhesion of the stent were observed using HE staining, scanning electron microscope (SEM) and immunocytochemical staining. MTT assay was used to evaluate urothelial cell proliferation on the capsular PLLA ureteral stent and on circumferential small intestinal submucosa graft. HE staining and VIII factor immunohistochemistry revealed numerous capillaries in the connective tissue encapsulating the stent without obvious local inflammatory response. The results of SEM and immunocytochemical staining showed that the capsule contained rich collagenic fibers forming three-dimensional structures, and the seeded autologous urothelial cells could adhere and well aligned on the surface. MTT assay showed normal growth of the cells on the stent as compared with the cells grown on circumferential small intestinal submucosa graft. The capsular PLLA ureteral stent allows adhesion and proliferation of autologous urothelial cells and shows a potential in applications of constructing tissue-engineered ureter.

  9. Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

    Science.gov (United States)

    Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

    2018-02-01

     Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. Serotonin concentrations in platelets, plasma, mitral valve leaflet, and left ventricular myocardial tissue in dogs with myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Cremer, Signe Emilie; Singletary, G.E.; Olsen, Lisbeth Høier

    2014-01-01

    HYPOTHESIS/OBJECTIVES: Altered serotonin (5-hydroxytryptamine, 5HT) signaling is postulated in development and progression of canine myxomatous mitral valve disease (MMVD). Little is known regarding platelet, plasma, valvular, or myocardial 5HT concentration ([5HT]) in affected dogs. We quantifie...

  11. A novel bioprinting method and system for forming hybrid tissue engineering constructs.

    Science.gov (United States)

    Shanjani, Y; Pan, C C; Elomaa, L; Yang, Y

    2015-12-18

    Three dimensional (3D) bioprinting is a promising approach to form tissue engineering constructs (TECs) via positioning biomaterials, growth factors, and cells with controlled spatial distribution due to its layer-by-layer manufacturing nature. Hybrid TECs composed of relatively rigid porous scaffolds for structural and mechanical integrity and soft hydrogels for cell- and growth factor-loading have a tremendous potential to tissue regeneration under mechanical loading. However, despite excessive progress in the field, the current 3D bioprinting techniques and systems fall short in integration of such soft and rigid multifunctional components. Here we present a novel 3D hybrid bioprinting technology (Hybprinter) and its capability enabling integration of soft and rigid components for TECs. Hybprinter employs digital light processing-based stereolithography (DLP-SLA) and molten material extrusion techniques for soft and rigid materials, respectively. In this study, poly-ethylene glycol diacrylate (PEGDA) and poly-(ε-caprolactone) (PCL) were used as a model material for soft hydrogel and rigid scaffold, respectively. It was shown that geometrical accuracy, swelling ratio and mechanical properties of the hydrogel component can be tailored by DLP-SLA module. We have demonstrated the printability of variety of complex hybrid construct designs using Hybprinter technology and characterized the mechanical properties and functionality of such constructs. The compressive mechanical stiffness of a hybrid construct (90% hydrogel) was significantly higher than hydrogel itself (∼6 MPa versus 100 kPa). In addition, viability of cells incorporated within the bioprinted hybrid constructs was determined approximately 90%. Furthermore, a functionality of a hybrid construct composed of porous scaffold with an embedded hydrogel conduit was characterized for vascularized tissue engineering applications. High material diffusion and high cell viability in about 2.5 mm distance

  12. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers

    International Nuclear Information System (INIS)

    Levato, Riccardo; Planell, Josep A; Engel, Elisabeth; Visser, Jetze; Malda, Jos; Mateos-Timoneda, Miguel A

    2014-01-01

    Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology. This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied. This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment. These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs. (paper)

  13. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.

    Science.gov (United States)

    Levato, Riccardo; Visser, Jetze; Planell, Josep A; Engel, Elisabeth; Malda, Jos; Mateos-Timoneda, Miguel A

    2014-09-01

    Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology. This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied. This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment. These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs.

  14. Characterization of tissue-equivalent materials for use in construction of physical phantoms

    International Nuclear Information System (INIS)

    Souza, Edvan V. de; Oliveira, Alex C.H. de; Vieira, Jose W.; Lima, Fernando R.A.

    2013-01-01

    Phantoms are physical or computational models used to simulate the transport of ionizing radiation, their interactions with human body tissues and evaluate the deposition of energy. Depending on the application, you can build phantoms of various types and features. The physical phantoms are made of materials with behavior similar to human tissues exposed to ionizing radiation, the so-called tissue-equivalent materials. The characterization of various tissue-equivalent materials is important for the choice of materials to be used is appropriate, seeking a better cost-benefit ratio. The main objective of this work is to produce tables containing the main characteristics of tissue-equivalent materials. These tables were produced in Microsoft Office Excel. Among the main features of tissue-equivalent materials that were added to the tables, are density, chemical composition, physical state, chemical stability and solubility. The main importance of this work is to contribute to the construction of high-quality physical phantoms and avoid the waste of materials

  15. Crosstalk between Substrates and Rho-Associated Kinase Inhibitors in Cryopreservation of Tissue-Engineered Constructs

    Directory of Open Access Journals (Sweden)

    Arindam Bit

    2017-01-01

    Full Text Available It is documented that human mesenchymal stem cells (hMSCs can be differentiated into various types of cells to present a tool for tissue engineering and regenerative medicine. Thus, the preservation of stem cells is a crucial factor for their effective long-term storage that further facilitates their continuous supply and transportation for application in regenerative medicine. Cryopreservation is the most important, practicable, and the only established mechanism for long-term preservation of cells, tissues, and organs, and engineered tissues; thus, it is the key step for the improvement of tissue engineering. A significant portion of MSCs loses cellular viability while freeze-thawing, which represents an important technical limitation to achieving sufficient viable cell numbers for maximum efficacy. Several natural and synthetic materials are extensively used as substrates for tissue engineering constructs and cryopreservation because they promote cell attachment and proliferation. Rho-associated kinase (ROCK inhibitors can improve the physiological function and postthaw viability of cryopreserved MSCs. This review proposes a crosstalk between substrate topology and interaction of cells with ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the presence of an external electrical field improves the generation of ROCK inhibitors to safeguard cellular viability for the enhanced cryopreservation of engineered tissues.

  16. Constructing Tissue Microarrays: Protocols and Methods Considering Potential Advantages and Disadvantages for Downstream Use.

    Science.gov (United States)

    Bingle, Lynne; Fonseca, Felipe P; Farthing, Paula M

    2017-01-01

    Tissue microarrays were first constructed in the 1980s but were used by only a limited number of researchers for a considerable period of time. In the last 10 years there has been a dramatic increase in the number of publications describing the successful use of tissue microarrays in studies aimed at discovering and validating biomarkers. This, along with the increased availability of both manual and automated microarray builders on the market, has encouraged even greater use of this novel and powerful tool. This chapter describes the basic techniques required to build a tissue microarray using a manual method in order that the theory behind the practical steps can be fully explained. Guidance is given to ensure potential disadvantages of the technique are fully considered.

  17. Release of Tissue-specific Proteins into Coronary Perfusate as a Model for Biomarker Discovery in Myocardial Ischemia/Reperfusion Injury

    DEFF Research Database (Denmark)

    Cordwell, Stuart; Edwards, Alistair; Liddy, Kiersten

    2012-01-01

    -rich plasma, in which the wide dynamic range of the native protein complement hinders classical proteomic investigations. We employed an ex vivo rabbit model of myocardial ischemia/reperfusion (I/R) injury using Langendorff buffer perfusion. Nonrecirculating perfusate was collected over a temporal profile...... reperfusion post-15I. Proteins released during irreversible I/R (60I/60R) were profiled using gel-based (2-DE and one-dimensional gel electrophoresis coupled to liquid chromatography and tandem mass spectrometry; geLC–MS) and gel-free (LC–MS/MS) methods. A total of 192 tissue-specific proteins were identified...... release using ex vivo buffer perfused tissue to limit the presence of obfuscating plasma proteins may identify candidates for further study in humans....

  18. Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue-Engineered Cartilage Constructs Across Testing Platforms.

    Science.gov (United States)

    Meloni, Gregory R; Fisher, Matthew B; Stoeckl, Brendan D; Dodge, George R; Mauck, Robert L

    2017-07-01

    Cartilage tissue engineering is emerging as a promising treatment for osteoarthritis, and the field has progressed toward utilizing large animal models for proof of concept and preclinical studies. Mechanical testing of the regenerative tissue is an essential outcome for functional evaluation. However, testing modalities and constitutive frameworks used to evaluate in vitro grown samples differ substantially from those used to evaluate in vivo derived samples. To address this, we developed finite element (FE) models (using FEBio) of unconfined compression and indentation testing, modalities commonly used for such samples. We determined the model sensitivity to tissue radius and subchondral bone modulus, as well as its ability to estimate material parameters using the built-in parameter optimization tool in FEBio. We then sequentially tested agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation platform, followed by unconfined compression. Similarly, we evaluated the ability of the model to generate material parameters for living constructs by evaluating engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 × 10 7 cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested sequentially in indentation and unconfined compression. The model successfully completed parameter optimization routines for each testing modality for both acellular and cell-based constructs. Traditional outcome measures and the FE-derived outcomes showed significant changes in material properties during the maturation of engineered cartilage tissue, capturing dynamic changes in functional tissue mechanics. These outcomes were significantly correlated with one another, establishing this FE modeling approach as a singular method for the evaluation of functional engineered and native tissue regeneration, both in vitro and in vivo.

  19. A mathematical model for fluid shear-sensitive 3D tissue construct development.

    Science.gov (United States)

    Liu, Dan; Chua, Chee-Kai; Leong, Kah-Fai

    2013-01-01

    This research studies dynamic culture for 3D tissue construct development with computational fluid dynamics. It proposes a mathematical model to evaluate the impact of flow rates and flow shear stress on cell growth in 3D constructs under perfusion. The modeling results show that dynamic flow, even at flow rate as low as 0.002 cm/s, can support much better mass exchange, higher cell number, and more even cell and nutrient distribution compared to static culture. Higher flow rate can further improve nutrient supply and mass exchange in the construct, promoting better nutritious environment and cell proliferation compared to lower flow rate. In addition, consideration of flow shear stress predicts much higher cell number in the construct compared to that without shear consideration. While the nutrient can dominate shear stress in influencing cell proliferation, the shear effect increases with flow rate. The proposed model helps tissue engineers better understand the cell-flow relationship at the molecular level during dynamic culture.

  20. Rapid expression of transgenes driven by seed-specific constructs in leaf tissue: DHA production

    Directory of Open Access Journals (Sweden)

    Zhou Xue-Rong

    2010-03-01

    Full Text Available Abstract Background Metabolic engineering of seed biosynthetic pathways to diversify and improve crop product quality is a highly active research area. The validation of genes driven by seed-specific promoters is time-consuming since the transformed plants must be grown to maturity before the gene function can be analysed. Results In this study we demonstrate that genes driven by seed-specific promoters contained within complex constructs can be transiently-expressed in the Nicotiana benthamiana leaf-assay system by co-infiltrating the Arabidopsis thaliana LEAFY COTYLEDON2 (LEC2 gene. A real-world case study is described in which we first assembled an efficient transgenic DHA synthesis pathway using a traditional N. benthamiana Cauliflower Mosaic Virus (CaMV 35S-driven leaf assay before using the LEC2-extended assay to rapidly validate a complex seed-specific construct containing the same genes before stable transformation in Arabidopsis. Conclusions The LEC2-extended N. benthamiana assay allows the transient activation of seed-specific promoters in leaf tissue. In this study we have used the assay as a rapid preliminary screen of a complex seed-specific transgenic construct prior to stable transformation, a feature that will become increasingly useful as genetic engineering moves from the manipulation of single genes to the engineering of complex pathways. We propose that the assay will prove useful for other applications wherein rapid expression of transgenes driven by seed-specific constructs in leaf tissue are sought.

  1. Chitosan-based scaffolds for the support of smooth muscle constructs in intestinal tissue engineering

    Science.gov (United States)

    Zakhem, Elie; Raghavan, Shreya; Gilmont, Robert R; Bitar, Khalil N

    2012-01-01

    Intestinal tissue engineering is an emerging field due to a growing demand for intestinal lengthening and replacement procedures secondary to massive resections of the bowel. Here, we demonstrate the potential use of a chitosan/collagen scaffold as a 3D matrix to support the bioengineered circular muscle constructs maintain their physiological functionality. We investigated the biocompatibility of chitosan by growing rabbit colonic circular smooth muscle cells (RCSMCs) on chitosan-coated plates. The cells maintained their spindle-like morphology and preserved their smooth muscle phenotypic markers. We manufactured tubular scaffolds with central openings composed of chitosan and collagen in a 1:1 ratio. Concentrically-aligned 3D circular muscle constructs were bioengineered using fibrin-based hydrogel seeded with RCSMCs. The constructs were placed around the scaffold for 2 weeks, after which they were taken off and tested for their physiological functionality. The muscle constructs contracted in response to Acetylcholine (Ach) and potassium chloride (KCl) and they relaxed in response to vasoactive intestinal peptide (VIP). These results demonstrate that chitosan is a biomaterial possibly suitable for intestinal tissue engineering applications. PMID:22483012

  2. Three-dimensional assembly of tissue-engineered cartilage constructs results in cartilaginous tissue formation without retainment of zonal characteristics.

    Science.gov (United States)

    Schuurman, W; Harimulyo, E B; Gawlitta, D; Woodfield, T B F; Dhert, W J A; van Weeren, P R; Malda, J

    2016-04-01

    Articular cartilage has limited regenerative capabilities. Chondrocytes from different layers of cartilage have specific properties, and regenerative approaches using zonal chondrocytes may yield better replication of the architecture of native cartilage than when using a single cell population. To obtain high seeding efficiency while still mimicking zonal architecture, cell pellets of expanded deep zone and superficial zone equine chondrocytes were seeded and cultured in two layers on poly(ethylene glycol)-terephthalate-poly(butylene terephthalate) (PEGT-PBT) scaffolds. Scaffolds seeded with cell pellets consisting of a 1:1 mixture of both cell sources served as controls. Parallel to this, pellets of superficial or deep zone chondrocytes, and combinations of the two cell populations, were cultured without the scaffold. Pellet cultures of zonal chondrocytes in scaffolds resulted in a high seeding efficiency and abundant cartilaginous tissue formation, containing collagen type II and glycosaminoglycans (GAGs) in all groups, irrespective of the donor (n = 3), zonal population or stratified scaffold-seeding approach used. However, whereas total GAG production was similar, the constructs retained significantly more GAG compared to pellet cultures, in which a high percentage of the produced GAGs were secreted into the culture medium. Immunohistochemistry for zonal markers did not show any differences between the conditions. We conclude that spatially defined pellet culture in 3D scaffolds is associated with high seeding efficiency and supports cartilaginous tissue formation, but did not result in the maintenance or restoration of the original zonal phenotype. The use of pellet-assembled constructs leads to a better retainment of newly produced GAGs than the use of pellet cultures alone. Copyright © 2013 John Wiley & Sons, Ltd.

  3. The endothelial glycocalyx protects against myocardial edema

    NARCIS (Netherlands)

    van den Berg, Bernard M.; Vink, Hans; Spaan, Jos A. E.

    2003-01-01

    Myocardial tissue edema attributable to increased microvascular fluid loss contributes to cardiac dysfunction after myocardial ischemia, cardiopulmonary bypass, hypertension, and sepsis. Recent studies suggest that carbohydrate structures on the luminal surface of microvascular endothelium are

  4. Prognostic Value of Cardiac Time Intervals by Tissue Doppler Imaging M-Mode in Patients With Acute ST-Segment-Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Mogelvang, Rasmus; Søgaard, Peter

    2013-01-01

    Background- Color tissue Doppler imaging M-mode through the mitral leaflet is an easy and precise method to estimate all cardiac time intervals from 1 cardiac cycle and thereby obtain the myocardial performance index (MPI). However, the prognostic value of the cardiac time intervals and the MPI...... assessed by color tissue Doppler imaging M-mode through the mitral leaflet in patients with ST-segment-elevation myocardial infarction (MI) is unknown. Methods and Results- In total, 391 patients were admitted with an ST-segment-elevation MI, treated with primary percutaneous coronary intervention...

  5. Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model.

    Science.gov (United States)

    Lee-Barthel, Ann; Baar, Keith; West, Daniel W D

    2017-06-11

    In vitro experiments are essential to understand biological mechanisms; however, the gap between monolayer tissue culture and human physiology is large, and translation of findings is often poor. Thus, there is ample opportunity for alternative experimental approaches. Here we present an approach in which human cells are isolated from human anterior cruciate ligament tissue remnants, expanded in culture, and used to form engineered ligaments. Exercise alters the biochemical milieu in the blood such that the function of many tissues, organs and bodily processes are improved. In this experiment, ligament construct culture media was supplemented with experimental human serum that has been 'conditioned' by exercise. Thus the intervention is more biologically relevant since an experimental tissue is exposed to the full endogenous biochemical milieu, including binding proteins and adjunct compounds that may be altered in tandem with the activity of an unknown agent of interest. After treatment, engineered ligaments can be analyzed for mechanical function, collagen content, morphology, and cellular biochemistry. Overall, there are four major advantages versus traditional monolayer culture and animal models, of the physiological model of ligament tissue that is presented here. First, ligament constructs are three-dimensional, allowing for mechanical properties (i.e., function) such as ultimate tensile stress, maximal tensile load, and modulus, to be quantified. Second, the enthesis, the interface between boney and sinew elements, can be examined in detail and within functional context. Third, preparing media with post-exercise serum allows for the effects of the exercise-induced biochemical milieu, which is responsible for the wide range of health benefits of exercise, to be investigated in an unbiased manner. Finally, this experimental model advances scientific research in a humane and ethical manner by replacing the use of animals, a core mandate of the National

  6. Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells.

    Science.gov (United States)

    Simmons, Aaron D; Sikavitsas, Vassilios I

    2018-01-01

    Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.

  7. Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs.

    Science.gov (United States)

    Chung, C A; Lin, Tze-Hung; Chen, Shih-Di; Huang, Hsing-I

    2010-01-21

    Mathematic models help interpret experimental results and accelerate tissue engineering developments. We develop in this paper a hybrid cellular automata model that combines the differential nutrient transport equation to investigate the nutrient limited cell construct development for cartilage tissue engineering. Individual cell behaviors of migration, contact inhibition and cell collision, coupled with the cell proliferation regulated by oxygen concentration were carefully studied. Simplified two-dimensional simulations were performed. Using this model, we investigated the influence of cell migration speed on the overall cell growth within in vitro cell scaffolds. It was found that intense cell motility can enhance initial cell growth rates. However, since cell growth is also significantly modulated by the nutrient contents, intense cell motility with conventional uniform cell seeding method may lead to declined cell growth in the final time because concentrated cell population has been growing around the scaffold periphery to block the nutrient transport from outside culture media. Therefore, homogeneous cell seeding may not be a good way of gaining large and uniform cell densities for the final results. We then compared cell growth in scaffolds with various seeding modes, and proposed a seeding mode with cells initially residing in the middle area of the scaffold that may efficiently reduce the nutrient blockage and result in a better cell amount and uniform cell distribution for tissue engineering construct developments.

  8. Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

    Science.gov (United States)

    Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

    2013-02-01

    Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

  9. Study of the Myocardial Contraction and Relaxation Velocities through Doppler Tissue Imaging Echocardiography: A New Alternative in the Assessment of the Segmental Ventricular Function

    Directory of Open Access Journals (Sweden)

    Silva Carlos Eduardo Suaide

    2002-01-01

    Full Text Available OBJECTIVE: Doppler tissue imaging (DTI enables the study of the velocity of contraction and relaxation of myocardial segments. We established standards for the peak velocity of the different myocardial segments of the left ventricle in systole and diastole, and correlated them with the electrocardiogram. METHODS: We studied 35 healthy individuals (27 were male with ages ranging from 12 to 59 years (32.9 ± 10.6. Systolic and diastolic peak velocities were assessed by Doppler tissue imaging in 12 segments of the left ventricle, establishing their mean values and the temporal correlation with the cardiac cycle. RESULTS: The means (and standard deviation of the peak velocities in the basal, medial, and apical regions (of the septal, anterior, lateral, and posterior left ventricle walls were respectively, in cm/s, 7.35(1.64, 5.26(1.88, and 3.33(1.58 in systole and 10.56(2.34, 7.92(2.37, and 3.98(1.64 in diastole. The mean time in which systolic peak velocity was recorded was 131.59ms (±19.12ms, and diastolic was 459.18ms (±18.13ms based on the peak of the R wave of the electrocardiogram. CONCLUSION: In healthy individuals, maximum left ventricle segment velocities decreased from the bases to the ventricular apex, with certain proportionality between contraction and relaxation (P<0.05. The use of Doppler tissue imaging may be very helpful in detecting early alterations in ventricular contraction and relaxation.

  10. Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping

    International Nuclear Information System (INIS)

    Baessler, Bettina; Treutlein, Melanie; Maintz, David; Bunck, Alexander C.; Schaarschmidt, Frank; Stehning, Christian; Schnackenburg, Bernhard; Michels, Guido

    2017-01-01

    To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. (orig.)

  11. Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping

    Energy Technology Data Exchange (ETDEWEB)

    Baessler, Bettina; Treutlein, Melanie; Maintz, David; Bunck, Alexander C. [University Hospital of Cologne, Department of Radiology, Cologne (Germany); Schaarschmidt, Frank [Leibniz Universitaet Hannover, Institute of Biostatistics, Faculty of Natural Sciences, Hannover (Germany); Stehning, Christian [Philips Research, Hamburg (Germany); Schnackenburg, Bernhard [Philips, Healthcare Germany, Hamburg (Germany); Michels, Guido [University Hospital of Cologne, Department III of Internal Medicine, Heart Centre, Cologne (Germany)

    2017-12-15

    To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. (orig.)

  12. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  13. Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes.

    LENUS (Irish Health Repository)

    Davis, Niall F

    2012-01-31

    OBJECTIVE: To design and construct a urinary bladder bioreactor for urologic tissue-engineering purposes and to compare the viability and proliferative activity of cell-seeded extracellular matrix scaffolds cultured in the bioreactor with conventional static growth conditions. MATERIALS AND METHODS: A urinary bladder bioreactor was designed and constructed to replicate physiologic bladder dynamics. The bioreactor mimicked the filling pressures of the human bladder by way of a cyclical low-delivery pressure regulator. In addition, cell growth was evaluated by culturing human urothelial cells (UCs) on porcine extracellular matrix scaffolds in the bioreactor and in static growth conditions for 5 consecutive days. The attachment, viability, and proliferative potential were assessed and compared with quantitative viability indicators and by fluorescent markers for intracellular esterase activity and plasma membrane integrity. Scaffold integrity was characterized with scanning electron microscopy and 4\\

  14. On The Construction of Models for Electrical Conduction in Biological Tissues

    International Nuclear Information System (INIS)

    Gomez-Aguilar, F.; Bernal-Alvarado, J.; Cordova-Fraga, T.; Rosales-Garcia, J.; Guia-Calderon, M.

    2010-01-01

    Applying RC circuit theory, a theoretical representation for the electrical conduction in a biological multilayer system was developed. In particular an equivalent circuit for the epidermis, dermis and the subcutaneous tissue was constructed. This model includes an equivalent circuit, inside the dermis, in order to model a small formation like tumor. This work shows the feasibility to apply superficial electrodes to detect subcutaneous abnormalities. The behavior of the model is shown in the form of a frequency response chart. The Bode and Nyquist plots are also obtained. This theoretical frame is proposed to be a general treatment to describe the bioelectrical transport in a three layer bioelectrical system.

  15. Heritable Genetic Changes in Cells Recovered From Irradiated 3D Tissue Constructs

    Energy Technology Data Exchange (ETDEWEB)

    Michael Cornforth

    2012-03-26

    Combining contemporary cytogenetic methods with DNA CGH microarray technology and chromosome flow-sorting increases substantially the ability to resolve exchange breakpoints associated with interstitial deletions and translocations, allowing the consequences of radiation damage to be directly measured at low doses, while also providing valuable insights into molecular mechanisms of misrepair processes that, in turn, identify appropriate biophysical models of risk at low doses. Specific aims apply to cells recovered from 3D tissue constructs of human skin and, for the purpose of comparison, the same cells irradiated in traditional 2D cultures. The project includes research complementary to NASA/HRP space radiation project.

  16. Nanostructured 3D constructs based on chitosan and chondroitin sulphate multilayers for cartilage tissue engineering.

    Directory of Open Access Journals (Sweden)

    Joana M Silva

    Full Text Available Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT and chondroitin sulphate (CS on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH. The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs.

  17. Nanostructured 3D constructs based on chitosan and chondroitin sulphate multilayers for cartilage tissue engineering.

    Science.gov (United States)

    Silva, Joana M; Georgi, Nicole; Costa, Rui; Sher, Praveen; Reis, Rui L; Van Blitterswijk, Clemens A; Karperien, Marcel; Mano, João F

    2013-01-01

    Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs.

  18. Tissue-engineered cartilaginous constructs for the treatment of caprine cartilage defects, including distribution of laminin and type IV collagen.

    Science.gov (United States)

    Jeng, Lily; Hsu, Hu-Ping; Spector, Myron

    2013-10-01

    The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

  19. CD34/CD133 enriched bone marrow progenitor cells promote neovascularization of tissue engineered constructs in vivo

    Directory of Open Access Journals (Sweden)

    Marietta Herrmann

    2014-11-01

    We demonstrate that this population of cells, isolated in a clinically relevant manner and cultured with autologous growth factors readily promoted neovascularization in tissue engineered constructs in vivo enabling a potential translation into the clinic.

  20. Hydrogels for lung tissue engineering: Biomechanical properties of thin collagen-elastin constructs.

    Science.gov (United States)

    Dunphy, Siobhán E; Bratt, Jessica A J; Akram, Khondoker M; Forsyth, Nicholas R; El Haj, Alicia J

    2014-10-01

    In this study, collagen-elastin constructs were prepared with the aim of producing a material capable of mimicking the mechanical properties of a single alveolar wall. Collagen has been used in a wide range of tissue engineering applications; however, due to its low mechanical properties its use is limited to non load-bearing applications without further manipulation using methods such as cross-linking or mechanical compression. Here, it was hypothesised that the addition of soluble elastin to a collagen hydrogel could improve its mechanical properties. Hydrogels made from collagen only and collagen plus varying amounts elastin were prepared. Young׳s modulus of each membrane was measured using the combination of a non-destructive indentation and a theoretical model previously described. An increase in Young׳s modulus was observed with increasing concentration of elastin. The use of non-destructive indentation allowed for online monitoring of the elastic moduli of cell-seeded constructs over 8 days. The addition of lung fibroblasts into the membrane increased the stiffness of the hydrogels further and cell-seeded collagen hydrogels were found to have a stiffness equal to the theoretical value for a single alveolar wall (≈5kPa). Through provision of some of the native extracellular matrix components of the lung parenchyma these scaffolds may be able to provide an initial building block toward the regeneration of new functional lung tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Fabrication of Trabecular Bone-Templated Tissue-Engineered Constructs by 3D Inkjet Printing.

    Science.gov (United States)

    Vanderburgh, Joseph P; Fernando, Shanik J; Merkel, Alyssa R; Sterling, Julie A; Guelcher, Scott A

    2017-11-01

    3D printing enables the creation of scaffolds with precisely controlled morphometric properties for multiple tissue types, including musculoskeletal tissues such as cartilage and bone. Computed tomography (CT) imaging has been combined with 3D printing to fabricate anatomically scaled patient-specific scaffolds for bone regeneration. However, anatomically scaled scaffolds typically lack sufficient resolution to recapitulate the 3D constructs are fabricated via a new micro-CT/3D inkjet printing process. It is shown that this process reproducibly fabricates bone-templated constructs that recapitulate the anatomic site-specific morphometric properties of trabecular bone. A significant correlation is observed between the structure model index (a morphometric parameter related to surface curvature) and the degree of mineralization of human mesenchymal stem cells, with more concave surfaces promoting more extensive osteoblast differentiation and mineralization compared to predominately convex surfaces. These findings highlight the significant effects of trabecular architecture on osteoblast function. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Bioprinting three-dimensional cell-laden tissue constructs with controllable degradation.

    Science.gov (United States)

    Wu, Zhengjie; Su, Xin; Xu, Yuanyuan; Kong, Bin; Sun, Wei; Mi, Shengli

    2016-04-19

    Alginate hydrogel is a popular biologically inert material that is widely used in 3D bioprinting, especially in extrusion-based printing. However, the printed cells in this hydrogel could not degrade the surrounding alginate gel matrix, causing them to remain in a poorly proliferating and non-differentiating state. Here, we report a novel study of the 3D printing of human corneal epithelial cells (HCECs)/collagen/gelatin/alginate hydrogel incubated with a medium containing sodium citrate to obtain degradation-controllable cell-laden tissue constructs. The 3D-printed hydrogel network with interconnected channels and a macroporous structure was stable and achieved high cell viability (over 90%). By altering the mole ratio of sodium citrate/sodium alginate, the degradation time of the bioprinting constructs can be controlled. Cell proliferation and specific marker protein expression results also revealed that with the help of sodium citrate degradation, the printed HCECs showed a higher proliferation rate and greater cytokeratin 3(CK3) expression, indicating that this newly developed method may help to improve the alginate bioink system for the application of 3D bioprinting in tissue engineering.

  3. Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.

    Science.gov (United States)

    Cha, Jae Min; Mantalaris, Athanasios; Jung, Sunyoung; Ji, Yurim; Bang, Oh Young; Bae, Hojae

    2017-09-01

    Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Concentration of labelled polyphosphates in soft tissue lesions. Application to the study of cerebral and myocardial infarction

    International Nuclear Information System (INIS)

    Guillemart, Alain.

    1975-01-01

    The biological behavior and tissue localization of phosphorus compounds used in Nuclear Medicine are reviewed. The mechanism of skeletal localization is emphasized. Labeled pyrophosphate compounds have proved extremely useful for skeletal imaging, however the mechanism of increased accumulation of these agents has been observed also in soft tissues. They localize in the acutely infarcted myocardium and in brain lesions. Clinical results obtained with sup(99m)Tc stannous pyrophosphate in brain and myocardium imaging are reported [fr

  5. Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping.

    Science.gov (United States)

    Baeßler, Bettina; Schaarschmidt, Frank; Treutlein, Melanie; Stehning, Christian; Schnackenburg, Bernhard; Michels, Guido; Maintz, David; Bunck, Alexander C

    2017-12-01

    To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. • A novel quantitative approach to myocardial oedema imaging in myocarditis was re-evaluated. • The T2-mapping-derived parameters maxT2 and madSD were compared to traditional Lake-Louise criteria. • Using maxT2 and madSD with dedicated cut-offs performs similarly to Lake-Louise criteria. • Adding maxT2 and madSD to LGE results in further increased diagnostic performance. • This novel approach has the potential to overcome the limitations of T2-mapping.

  6. PROSPECTS OF APPLICATION OF TISSUE-ENGINEERED PANCREATIC CONSTRUCTS IN THE TREATMENT OF TYPE 1 DIABETES

    Directory of Open Access Journals (Sweden)

    G. N. Skaletskaya

    2016-01-01

    Full Text Available Allotransplantation of pancreatic islets remains the most effective method of treatment of diabetes mellitus type 1 being capable under combination of favorable conditions (suffi cient number of isolated islets, effective combination of immunosuppressive drugs to reach the recipients’ insulin independence for several years. However, the overwhelming shortage of donor pancreas and limited post-transplantation islet survival do not allow increasing the number of such transplants and their effectiveness. This review presents a critical analysis of the work done by Russian and foreign authors onto creation of tissue-engineered pancreatic constructs that may lead to the resolution of the three main pancreatic islet transplantation issues: 1 lack of donor material; 2 necessity of immunosuppressive therapy; 3 limited survival and functional activity of the islet.

  7. Confocal fluorometer for diffusion tracking in 3D engineered tissue constructs

    Science.gov (United States)

    Daly, D.; Zilioli, A.; Tan, N.; Buttenschoen, K.; Chikkanna, B.; Reynolds, J.; Marsden, B.; Hughes, C.

    2016-03-01

    We present results of the development of a non-contacting instrument, called fScan, based on scanning confocal fluorometry for assessing the diffusion of materials through a tissue matrix. There are many areas in healthcare diagnostics and screening where it is now widely accepted that the need for new quantitative monitoring technologies is a major pinch point in patient diagnostics and in vitro testing. With the increasing need to interpret 3D responses this commonly involves the need to track the diffusion of compounds, pharma-active species and cells through a 3D matrix of tissue. Methods are available but to support the advances that are currently only promised, this monitoring needs to be real-time, non-invasive, and economical. At the moment commercial meters tend to be invasive and usually require a sample of the medium to be removed and processed prior to testing. This methodology clearly has a number of significant disadvantages. fScan combines a fiber based optical arrangement with a compact, free space optical front end that has been integrated so that the sample's diffusion can be measured without interference. This architecture is particularly important due to the "wet" nature of the samples. fScan is designed to measure constructs located within standard well plates and a 2-D motion stage locates the required sample with respect to the measurement system. Results are presented that show how the meter has been used to evaluate movements of samples through collagen constructs in situ without disturbing their kinetic characteristics. These kinetics were little understood prior to these measurements.

  8. Construction of tissue-engineered small-diameter vascular grafts in fibrin scaffolds in 30 days.

    Science.gov (United States)

    Gui, Liqiong; Boyle, Michael J; Kamin, Yishai M; Huang, Angela H; Starcher, Barry C; Miller, Cheryl A; Vishnevetsky, Michael J; Niklason, Laura E

    2014-05-01

    Tissue-engineered small-diameter vascular grafts have been developed as a promising alternative to native veins or arteries for replacement therapy. However, there is still a crucial need to improve the current approaches to render the tissue-engineered blood vessels more favorable for clinical applications. A completely biological blood vessel (3-mm inner diameter) was constructed by culturing a 50:50 mixture of bovine smooth muscle cells (SMCs) with neonatal human dermal fibroblasts in fibrin gels. After 30 days of culture under pulsatile stretching, the engineered blood vessels demonstrated an average burst pressure of 913.3±150.1 mmHg (n=6), a suture retention (53.3±15.4 g) that is suitable for implantation, and a compliance (3.1%±2.5% per 100 mmHg) that is comparable to native vessels. These engineered grafts contained circumferentially aligned collagen fibers, microfibrils and elastic fibers, and differentiated SMCs, mimicking a native artery. These promising mechanical and biochemical properties were achieved in a very short culture time of 30 days, suggesting the potential of co-culturing SMCs with fibroblasts in fibrin gels to generate functional small-diameter vascular grafts for vascular reconstruction surgery.

  9. Development of Three-Dimensional Multicellular Tissue-Like Constructs for Mutational Analysis Using Macroporous Microcarriers

    Science.gov (United States)

    Jordan, Jacqueline A.; Fraga, Denise N.; Gonda, Steve R.

    2002-01-01

    A three-dimensional (3-D), tissue-like model was developed for the genotoxic assessment of space environment. In previous experiments, we found that culturing mammalian cells in a NASA-designed bioreactor, using Cytodex-3 beads as a scaffold, generated 3-D multicellular spheroids. In an effort to generate scaffold-free spheroids, we developed a new 3-D tissue-like model by coculturing fibroblast and epithelial cell in a NASA bioreactor using macroporous Cultispher-S(TradeMark) microcarriers. Big Blue(Registered Trademark) Rat 2(Lambda) fibroblasts, genetically engineered to contain multiple copies (>60 copies/cell) of the Lac I target gene, were cocultured with radio-sensitive human epithelial cells, H184F5. Over an 8-day period, samples were periodically examined by microscopy and histology to confirm cell attachment, growth, and viability. Immunohistochemistry and western analysis were used to evaluate the expression of specific cytoskeletal and adhesion proteins. Key cell culture parameters (glucose, pH, and lactate concentrations) were monitored daily. Controls were two-dimensional mono layers of fibroblast or epithelial cells cultured in T-flasks. Analysis of 3-D spheroids from the bioreactor suggests fibroblast cells attached to and completely covered the bead surface and inner channels by day 3 in the bioreactor. Treatment of the 3-day spheroids with dispase II dissolved the Cultisphers(TradeMark) and produced multicellular, bead-less constructs. Immunohistochemistry confirmed the presence of vi.mentin, cytokeratin and E-cadherin in treated spheroids. Examination of the dispase II treated spheroids with transmission electron microscopy (TEM) also showed the presence of desmosomes. These results suggest that the controlled enzymatic degradation of an artificial matrix in the low shear environment of the NASA-designed bioreactor can produce 3-D tissue-like spheroids. 2

  10. The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts.

    Science.gov (United States)

    Nielsen, Trine Skov; Hansen, Jakob; Nielsen, Lars Peter; Baandrup, Ulrik Thorngren; Banner, Jytte

    2014-09-01

    Multiple viruses have been detected in cardiac tissue, but their role in causing myocarditis remains controversial. Viral diagnostics are increasingly used in forensic medicine, but the interpretation of the results can sometimes be challenging. In this study, we examined the prevalence of adenovirus, enterovirus, and parvovirus B19 (PVB) in myocardial autopsy samples from myocarditis related deaths and in non-inflamed control hearts in an effort to clarify their significance as the causes of myocarditis in a forensic material. We collected all autopsy cases diagnosed with myocarditis from 1992 to 2010. Eighty-four suicidal deaths with morphologically normal hearts served as controls. Polymerase chain reaction was used for the detection of the viral genomes (adenovirus, enterovirus, and PVB) in myocardial tissue specimens. The distinction between acute and persistent PVB infection was made by the serological determination of PVB-specific immunoglobulins M and G. PVB was detected in 33 of 112 (29 %) myocarditis cases and 37 of 84 (44 %) control cases. All of the samples were negative for the presence of adenovirus and enterovirus. Serological evidence of an acute PVB infection, determined by the presence of immunoglobulin M, was only present in one case. In the remaining cases, PVB was considered to be a bystander with no or limited association to myocardial inflammation. In this study, adenovirus, enterovirus, and PVB were found to be rare causes of myocarditis. The detection of PVB in myocardial autopsy samples most likely represents a persistent infection with no or limited association with myocardial inflammation. The forensic investigation of myocardial inflammation demands a thorough examination, including special attention to non-viral causes and requires a multidisciplinary approach.

  11. Multifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs.

    Directory of Open Access Journals (Sweden)

    Maarten Sonnaert

    Full Text Available To progress the fields of tissue engineering (TE and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial 'design of experiments' approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology.

  12. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    International Nuclear Information System (INIS)

    Shim, Jin-Hyung; Lee, Jung-Seob; Cho, Dong-Woo; Kim, Jong Young

    2012-01-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed. (paper)

  13. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    Science.gov (United States)

    Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo

    2012-08-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed.

  14. Tissue Doppler echocardiography reveals distinct patterns of impaired myocardial velocities in different degrees of coronary artery disease

    DEFF Research Database (Denmark)

    Hoffmann, Soren; Mogelvang, Rasmus; Olsen, Niels Thue

    2010-01-01

    Aim To determine how the left ventricular wall motion assessed by echocardiographic Tissue Doppler Imaging (TDI) is affected by increasing severity of coronary artery disease (CAD) among patients with stable angina pectoris and preserved ejection fraction. METHODS AND RESULTS: This study comprise...

  15. [Construction and evaluation of the tissue engineered nerve of bFGF-PLGA sustained release microspheres].

    Science.gov (United States)

    Wang, Guanglin; Lin, Wei; Gao, Weiqiang; Xiao, Yuhua; Dong, Changchao

    2008-12-01

    To study the outcomes of nerve defect repair with the tissue engineered nerve, which is composed of the complex of SCs, 30% ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable poly (D, L-lactic acid) (PDLLA) catheters. SCs were cultured and purified from the sciatic nerves of 1-day-old neonatal SD rats. The 1st passage cells were compounded with bFGF-PLGA sustained release microspheres and ECM gel, and then were injected into permeable PDLLA catheters with PLGA microfilaments inside. In this way, the tissue engineered nerve was constructed. Sixty SD rats were included. The model of 15-mm sciatic nerve defects was made, and then the rats were randomly divided into 5 groups, with 12 rats in each. In group A, autograft was adopted. In group B, the blank PDLLA catheters with PBS inside were used. In group C, PDLLA catheters, with PLGA microfilaments and 30% ECM gel inside, were used. In group D, PDLLA catheters, with PLGA microfilaments, SCs and 30% ECM gel inside, were used. In group E, the tissue engineered nerve was applied. After the operation, observation was made for general conditions of the rats. The sciatic function index (SFI) analysis was performed at 12, 16, 20 and 24 weeks after the operation, respectively. Electrophysiological detection and histological observation were performed at 12 and 24 weeks after the operation, respectively. All rats survived to the end of the experiment. At 12 and 16 weeks after the operation, group E was significantly different from group B in SFI (P fibers in group E were significantly differents from those in groups A, B and C (P fibers in group E were smaller than those in group A (P fibers in group E was significantly different from those in groups A, B, C (P fibers in group E were bigger than those in groups B and C (P < 0.05). The tissue engineered nerve with the complex of SCs, ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable PDLLA catheters promote

  16. Myocardial Bridging

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2016-02-01

    Full Text Available Abstract Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results.

  17. A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy

    Directory of Open Access Journals (Sweden)

    Manka Robert

    2012-07-01

    Full Text Available Abstract Background In acute myocardial infarction (AMI, both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. Methods Patients with a first AMI underwent percutaneous coronary interventions (PCI of the infarct-related artery within 24 h of onset of chest pain. Within 5–7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony. On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk. In analogy, on late-gadolinium enhancement (LGE images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass. Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference. Results After successful PCI (n = 22, 2 female, mean age: 57 ± 12y, peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = −0.63, p 2 = −0.19, p = 0.05. PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE decreased at 4 months from 0.91

  18. CRYOPRESERVATION STRATEGY FOR TISSUE ENGINEERING CONSTRUCTS CONSISTING OF HUMAN MESENHYMAL STEM CELLS AND HYDROGEL BIOMATERIALS.

    Science.gov (United States)

    Wu, Y; Wen, F; Gouk, S S; Lee, E H; Kuleshova, L

    2015-01-01

    The development of vitrification strategy for cell-biomaterial constructs, particularly biologically inspired nanoscale materials and hydrogels mimicking the in vivo environment is an active area. A cryopreservation strategy mimicking the in vivo environment for cell-hydrogel constructs may enhance cell proliferation and biological function. To demonstrate the efficacy of vitrification as a platform technology involving tissue engineering and human mesenchymal stem cells (hMSCs). Microcarriers made from alginate coated with chitosan and collagen are used. Conventional freezing and vitrification were compared. The vitrification strategy includes 10 min step-wise exposure to a vitrification solution (40% v/v EG, 0.6M sucrose) and immersion into liquid nitrogen. Confocal imaging of live/dead staining of hMSCs cultured on the surface of microcarriers demonstrated that vitrified cells had excellent appearance and prolonged spindle shape morphology. The proliferation ability of post-vitrified cells arbitrated to protein Ki-67 gene expression was not significantly different in comparison to untreated control, while that of post-freezing cells was almost lost. The ability of hMSCs cultured on the surface of microcarriers to proliferate has been not affected by vitrification and it was significantly better after vitrification than after conventional freezing during continuous culture. Collagen II related mRNA expression by 4 weeks post-vitrification and post-freezing showed that ability to differentiate into cartilage was sustained during vitrification and reduced during conventional freezing. No significant difference was found between control and vitrification groups only. Vitrification strategy coupled with advances in hMSC-expansion platform that completely preserves the ability of stem cells to proliferate and subsequently differentiate allows not only to reach a critical cell number, but also demonstrate prospects for effective utilization and transportation of cells

  19. Tissue microarray design and construction for scientific, industrial and diagnostic use

    Directory of Open Access Journals (Sweden)

    Daniela Pilla

    2012-01-01

    Full Text Available Context: In 2013 the high throughput technology known as Tissue Micro Array (TMA will be fifteen years old. Its elements (design, construction and analysis are intuitive and the core histopathology technique is unsophisticated, which may be a reason why has eluded a rigorous scientific scrutiny. The source of errors, particularly in specimen identification and how to control for it is unreported. Formal validation of the accuracy of segmenting (also known as de-arraying hundreds of samples, pairing with the sample data is lacking. Aims: We wanted to address these issues in order to bring the technique to recognized standards of quality in TMA use for research, diagnostics and industrial purposes. Results: We systematically addressed the sources of error and used barcode-driven data input throughout the whole process including matching the design with a TMA virtual image and segmenting that image back to individual cases, together with the associated data. In addition we demonstrate on mathematical grounds that a TMA design, when superimposed onto the corresponding whole slide image, validates on each and every sample the correspondence between the image and patient′s data. Conclusions: High throughput use of the TMA technology is a safe and efficient method for research, diagnosis and industrial use if all sources of errors are identified and addressed.

  20. Co-purification of arrestin like proteins with alpha-enolase from bovine myocardial tissues and the possible role in heart diseases as an autoantigen

    Energy Technology Data Exchange (ETDEWEB)

    Mirshahi, M., E-mail: massoud.mirshahi@inserm.fr; Le Marchand, S.

    2015-05-08

    Aim: Previously, we reported that visual arrestin co-purified with glycolytic enzymes. The aim of this study was to analyze the co-purification of arrestin like proteins (ALP) in bovine cardiac tissues with enolases. Methods: The soluble extract of bovine myocardial tissues from different regions such as left and right atriums and ventricles of the bovine heart (n = 3) was analyzed by ACA-34 gel filtration, immuno-affinity column, SDS-PAGE, ELISA, western blot and a sandwich immune assay for quantification of ALP and sequence analysis. Results: We observed that; 1) The cardiac muscle contained a 50 kDa ALP at a concentration of 751 pg/mg of soluble protein extract, 2) ALP purified, by immunoaffinity, contained alpha-enolase of 48 kDa confirmed by protein sequence analysis; 3) Cardiomyocyte cells exposed to anti arrestin and anti enolase monoclonal antibodies showed decreased proliferation in vitro, 4) High level of autoantibodies were detected by ELISA (3.57% for arrestin and 9.12% for α-enolase) in serum of patients with infarcted heart disease. Conclusion: We suggest a possible interaction between ALP and alpha-enolases yielding a complex that may be involved in the induction of cardiac autoimmune diseases. - Highlights: • We examine a possible interaction between arrestin like protein and alpha-enolases in cardiomyocyte. • We demonstrated the effect of antibodies against arrestin and enolase on cardiomyocyte cell proliferation. • We suggest that this proteins complex may be involved in the induction of cardiac autoimmune diseases.

  1. An impedance method for spatial sensing of 3D cell constructs – towards applications in tissue engineering

    DEFF Research Database (Denmark)

    Canali, Chiara; Mazzoni, Chiara; Larsen, Layla Bashir

    2015-01-01

    ) cells were encapsulated in gelatin to form artificial 3D cell constructs and detected when placed in different positions inside large gelatin scaffolds. Taken together, these results open new perspectives for impedance-based sensing technologies for non-invasive monitoring in tissue engineering...

  2. Bi-layered constructs of poly(glycerol-sebacate)-β-tricalcium phosphate for bone-soft tissue interface applications

    Energy Technology Data Exchange (ETDEWEB)

    Tevlek, Atakan [Bioengineering Division, Institute of Science and Engineering, Hacettepe University, Ankara (Turkey); Hosseinian, Pezhman; Ogutcu, Cansel [Nanotechnology and Nanomedicine Division, Institute of Science and Engineering, Hacettepe University, Ankara (Turkey); Turk, Mustafa [Biology Department, Kirikkale University, Kirikkale (Turkey); Aydin, Halil Murat, E-mail: hmaydin@hacettepe.edu.tr [Environmental Engineering Department, Bioengineering Division, Centre for Bioengineering, Hacettepe University, Ankara (Turkey)

    2017-03-01

    This study aims to establish a facile protocol for the preparation of a bi-layered poly(glycerol-sebacate) (PGS)/β-tricalcium phosphate (β-TCP) construct and to investigate its potential for bone-soft tissue engineering applications. The layered structure was prepared by distributing the ceramic particles within a prepolymer synthesized in a microwave reactor followed by a cross-linking of the final construct in vacuum (< 10 mbar). The vacuum stage led to the separation of cross-linked elastomer (top) and ceramic (bottom) phases. Results showed that addition of β-TCP particles to the elastomer matrix after the polymerization led to an increase in compression strength (up to 14 ± 2.3 MPa). Tensile strength (σ), Young's modulus (E), and elongation at break (%) values were calculated as 0.29 ± 0.03 MPa and 0.21 ± 0.03; 0.38 ± 0.02 and 1.95 ± 0.4; and 240 ± 50% and 24 ± 2% for PGS and PGS/β-TCP bi-layered constructs, respectively. Morphology was characterized by using Scanning Electron Microscopy (SEM) and micro-computed tomography (μ-CT). Tomography data revealed an open porosity of 35% for the construct, mostly contributed from the ceramic phase since the elastomer side has no pore. Homogeneous β-TCP distribution within the elastomeric structure was observed. Cell culture studies confirmed biocompatibility with poor elastomer-side and good bone-side cell attachment. In a further study to investigate the osteogenic properties, the construct were loaded with BMP-2 and/or TGF-β1. The PGS/β-TCP bi-layered constructs with improved mechanical and biological properties have the potential to be used in bone-soft tissue interface applications where soft tissue penetration is a problem. - Highlights: • Biodegradable bi-layered constructs with elastomer and ceramic sides were prepared. • The constructs could be a promising material in guided bone regeneration. • Elastomer side of the construct acts as a barrier to prevent soft tissue ingrowth.

  3. Impact of iso-osmolar versus low-osmolar contrast agents on contrast-induced nephropathy and tissue reperfusion in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial).

    Science.gov (United States)

    Bolognese, Leonardo; Falsini, Giovanni; Schwenke, Carsten; Grotti, Simone; Limbruno, Ugo; Liistro, Francesco; Carrera, Arcangelo; Angioli, Paolo; Picchi, Andrea; Ducci, Kenneth; Pierli, Carlo

    2012-01-01

    Conflicting data have been reported on the effects of low-osmolar and iso-osmolar contrast media on contrast-induced acute kidney injury (CI-AKI). In particular, no clinical trial has yet focused on the effect of contemporary contrast media on CI-AKI, epicardial flow, and microcirculatory function in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI) trial is a prospective, randomized, single-blind, parallel-group, noninferiority study aiming to evaluate the effects of the low-osmolar contrast medium iopromide compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion in patients with ST-segment elevation acute myocardial infarction. Four hundred seventy-five consecutive, unselected patients who underwent primary percutaneous coronary intervention were randomized to iopromide (n = 239) or iodixanol (n = 236). All patients received high-dose N-acetylcysteine and hydration. The primary end point was the proportion of patients with serum creatinine (sCr) increases ≥25% from baseline to 72 hours. Secondary end points were Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr ≥50%, increase in sCr ≥0.5 or ≥1 mg/dl, and 1-month major adverse cardiac events. The primary end point occurred in 10% of the iopromide group and in 13% of the iodixanol group (95% confidence interval -9% to 3%, p for noninferiority = 0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of patients in the 2 groups. No differences between the 2 groups were found in any of the secondary analyses of sCr increase. No significant difference in 1-month major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a population of unselected patients with ST-segment elevation acute myocardial infarction

  4. Construction of a self-supporting tissue-equivalent dividing wall and operational characteristics of a coaxial double-cylindrical tissue-equivalent proportional counter

    International Nuclear Information System (INIS)

    Saion, E.B.; Watt, D.E.

    1994-01-01

    An additional feature incorporated in a coaxial double-cylindrical tissue-equivalent proportional counter, is the presence of a common tissue-equivalent dividing wall between the inner and outer counters of thickness equivalent to the corresponding maximum range of protons at the energy of interest. By appropriate use of an anti-coincidence arrangement with the outer counter, the inner counter could be used to discriminate microdosimetric spectra of neutrons at the desired low energy range from those of the faster neutrons. The construction of an A-150 self-supporting tissue-equivalent dividing wall and an anti-coincidence unit are described. Some operational characteristic tests have been performed to determine the operation of the new microdosimeter. (author)

  5. Bayesian state space models for dynamic genetic network construction across multiple tissues.

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

    Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

  6. Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with Ranolazine

    Science.gov (United States)

    Nelson, Michael D.; Sharif, Behzad; Shaw, Jaime L.; Cook-Wiens, Galen; Wei, Janet; Shufelt, Chrisandra; Mehta, Puja K.; Thomson, Louise EJ; Berman, Daniel S.; Thompson, Richard B.; Handberg, Eileen M.; Pepine, Carl J.; Li, Debiao; Bairey Merz, C. Noel

    2016-01-01

    Background Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine—a late-sodium current inhibitor—improves diastolic function in animal models, and subjects with obstructive CAD. We hypothesized that ranolazine would beneficially alter diastolic function in CMD. Methods To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images: a) acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD, and b) from 43 healthy reference controls. Results Diastolic strain rate was impaired in CMD vs. controls (circumferential diastolic strain rate: 99.9 ± 2.5%/s vs. 120.1 ± 4.0%/s, p=0.0003; radial diastolic strain rate: −199.5 ± 5.5%/s vs. −243.1 ± 9.6%/s, p=0.0008, case vs. control). Moreover, peak systolic circumferential (CS) and radial (RS) strain were also impaired in cases vs. controls (CS: −18.8 ± 0.3% vs. −20.7 ± 0.3%; RS: 35.8 ± 0.7% vs. 41.4 ± 0.9%; respectively; both p < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis however, we observed no significant changes in left ventricular diastolic function in CMD cases after two weeks of ranolazine vs. placebo. Conclusions The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have sub-clinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD. PMID:28004395

  7. Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity.

    Directory of Open Access Journals (Sweden)

    Gemma Chiva-Blanch

    Full Text Available Circulating microparticles (cMPs are phospholipid-rich vesicles released from cells when activated or injured, and contribute to the formation of intracoronary thrombi. Tissue factor (TF, CD142 is the main trigger of fibrin formation and TF-carrying cMPs are considered one of the most procoagulant cMPs. Similar types of atherosclerotic lesions may lead to different types of AMI, although the mechanisms behind are unresolved. Therefore, we aimed to investigate the phenotype of cMPs found in plasma of ACS patients and its relation to AMI severity and thrombotic burden.In a cross-sectional study, two hundred patients aged 75±4 years were included in the study 2-8 weeks after suffering an AMI. Annexin V positive (AV+-cMPs derived from blood and vascular cells were measured by flow cytometry. Plasma procoagulant activity (TF-PCA was measured through a chromogenic assay.STEMI patients (n = 75 showed higher levels of platelet-derived cMPs [CD61+/AV+, CD31+/AV+, CD42b+/AV+ and CD31+/CD42b+/AV+, P = 0.048, 0.038, 0.009 and 0.006, respectively], compared to NSTEMI patients (n = 125. Patients who suffered a heart failure during AMI (n = 17 had increased levels of platelet (CD61+-and monocyte (CD14+-derived cMPs carrying TF (CD142+ (P<0.0001 and 0.004, respectively. Additionally, NYHA class III (n = 23 patients showed higher levels of CD142+/AV+, CD14+/AV+ and CD14+/CD142+/AV+ cMPs than those in class I/II (P = 0.001, 0.015 and 0.014, respectively. The levels of these cMPs positively correlated with TF-PCA (r≥0.166, P≤0.027, all.Platelets and monocytes remain activated in AMI patients treated as per guidelines and release cMPs that discriminate AMI severity. Therefore, TF-MPs, and platelet- and monocyte-MPs may reflect thrombotic burden in AMI patients.

  8. Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

    Science.gov (United States)

    Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

    2014-10-01

    Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

  9. Matrix production and organization by endothelial colony forming cells in mechanically strained engineered tissue constructs.

    Directory of Open Access Journals (Sweden)

    Nicky de Jonge

    Full Text Available AIMS: Tissue engineering is an innovative method to restore cardiovascular tissue function by implanting either an in vitro cultured tissue or a degradable, mechanically functional scaffold that gradually transforms into a living neo-tissue by recruiting tissue forming cells at the site of implantation. Circulating endothelial colony forming cells (ECFCs are capable of differentiating into endothelial cells as well as a mesenchymal ECM-producing phenotype, undergoing Endothelial-to-Mesenchymal-transition (EndoMT. We investigated the potential of ECFCs to produce and organize ECM under the influence of static and cyclic mechanical strain, as well as stimulation with transforming growth factor β1 (TGFβ1. METHODS AND RESULTS: A fibrin-based 3D tissue model was used to simulate neo-tissue formation. Extracellular matrix organization was monitored using confocal laser-scanning microscopy. ECFCs produced collagen and also elastin, but did not form an organized matrix, except when cultured with TGFβ1 under static strain. Here, collagen was aligned more parallel to the strain direction, similar to Human Vena Saphena Cell-seeded controls. Priming ECFC with TGFβ1 before exposing them to strain led to more homogenous matrix production. CONCLUSIONS: Biochemical and mechanical cues can induce extracellular matrix formation by ECFCs in tissue models that mimic early tissue formation. Our findings suggest that priming with bioactives may be required to optimize neo-tissue development with ECFCs and has important consequences for the timing of stimuli applied to scaffold designs for both in vitro and in situ cardiovascular tissue engineering. The results obtained with ECFCs differ from those obtained with other cell sources, such as vena saphena-derived myofibroblasts, underlining the need for experimental models like ours to test novel cell sources for cardiovascular tissue engineering.

  10. Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells

    Directory of Open Access Journals (Sweden)

    W Ando

    2012-09-01

    Full Text Available The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

  11. Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells.

    Science.gov (United States)

    Ando, Wataru; Fujie, Hiromichi; Moriguchi, Yu; Nansai, Ryosuke; Shimomura, Kazunori; Hart, David A; Yoshikawa, Hideki; Nakamura, Norimasa

    2012-09-28

    The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

  12. Myocardial infarction

    International Nuclear Information System (INIS)

    Ando, Jyoji; Yasuda, Hisakazu; Miyamoto, Atsushi; Kobayashi, Tsuyoshi

    1980-01-01

    sup(99m)Tc-pyrophosphate (PYP) scintigraphy and 201 Tl myocardial scintigraphy were utilized for the diagnoses of the presence, the region, and the extent of myocardial infarction. Exercise 201 Tl myocardial scintigrams and exercise radionuclide ventriculography were utilized for diagnosis of coronary artery lesions in angina pectoris. Radionuclide ventriculography was used to investigate effects of coronary artery lesions on cardiac function and hemodynamics. In order to select adequate treatments for myocardial infarction and estimate the prognosis, it was necessary to detect the presence, the region, and the extent of acute myocardial infarction and to investigate effects of partial infarction on hemodynamics by using radionuclide imaging. Exercise myocardial scintigraphy could be carried out noninvasively and repeatedly for diagnosis of coronal artery disease. Therefore, this method could be applied widely. It was possible to use this method as a screening test of coronary artery diseases for the diagnoses of asymptomatic patients who showed ST changes in ECG, the patients with cardiac neurosis and the patency after a reconstructive surgery of coronary artery. (Tsunoda, M.)

  13. Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

    Science.gov (United States)

    Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

    2017-10-15

    Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this

  14. Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs.

    Science.gov (United States)

    Riehl, Brandon D; Park, Jae-Hong; Kwon, Il Keun; Lim, Jung Yul

    2012-08-01

    Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.

  15. Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs.

    Science.gov (United States)

    Dikina, Anna D; Strobel, Hannah A; Lai, Bradley P; Rolle, Marsha W; Alsberg, Eben

    2015-06-01

    There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage tissue engineering

    Science.gov (United States)

    Zhu, Wei; Cui, Haitao; Boualam, Benchaa; Masood, Fahed; Flynn, Erin; Rao, Raj D.; Zhang, Zhi-Yong; Zhang, Lijie Grace

    2018-05-01

    Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-β1) embedded nanospheres fabricated via a core-shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-β1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-β1-containing nanospheres is a promising strategy for cartilage regeneration.

  17. Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve.

    Science.gov (United States)

    Huang, Lanfeng; Li, Rui; Liu, Wanguo; Dai, Jin; Du, Zhenwu; Wang, Xiaonan; Ma, Jianchao; Zhao, Jinsong

    2014-07-15

    Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material.

  18. Myocardial scintigraphy

    International Nuclear Information System (INIS)

    Bunko, Hisashi; Hisada, Kinichi

    1982-01-01

    Among the various methods of image diagnosis of the cardiovascular disorder, nuclear cardiology provides noninvasive means for evaluation of myocardial perfusion as well as morphological and functional informations. In this article, clinical application and image diagnosis of myocardial scintigraphy including Tl-201 myocardial perfusion scintigraphy, single photon emission computed tomography with Tl-201, acute myocardial infarction scintigraphy with Tc-99m-pyrophosphate and Ga-67 imaging of the heart, were discussed. Multiplanar imaging of the heart with Tl-201 after stress and at redistribution was the accepted method for detection and evaluation of the ischemic heart disease. Although it achieved high sensitivity and specificity for ischemic heart disease, detection of the small ischemia and quantation of the regional Tl-201 accumulation were difficult with conventional multiplanar imaging. Application of emission computed tomography improved detectability and quantitativity of the ischemia. However, 7-pinhole tomography did not increase the diagnostic accuracy significantly. It had limited clinical applicability due to poor quantitativity in spite of improved image contrast and its tomographic nature. Advantage and limitation of these tomographic imaging and multiplanar imaging were discussed. Problems and prognostic significance of pyrophosphate imaging of the acute myocardial infarction were also discussed. Visualization of the heart with Ga-67 was helpful for identification of the tumor or inflammation of the heart as well as evaluation of the effect of the therapy. (author)

  19. The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo. Engineered cartilage reorganises fibre network

    Directory of Open Access Journals (Sweden)

    H Paetzold

    2012-04-01

    Full Text Available For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself.

  20. Mechanical evaluation of a tissue-engineered zone of calcification in a bone–hydrogel osteochondral construct

    Science.gov (United States)

    Hollenstein, Jérôme; Terrier, Alexandre; Cory, Esther; Chen, Albert C.; Sah, Robert L.; Pioletti, Dominique P.

    2016-01-01

    The objective of this study was to test the hypothesis that mechanical properties of artificial osteochondral constructs can be improved by a tissue-engineered zone of calcification (teZCC) at the bone–hydrogel interface. Experimental push-off tests were performed on osteochondral constructs with or without a teZCC. In parallel, a numerical model of the osteochondral defect treatment was developed and validated against experimental results. Experimental results showed that the shear strength at the bone–hydrogel interface increased by 100% with the teZCC. Numerical predictions of the osteochondral defect treatment showed that the shear stress at the bone–hydrogel interface was reduced with the teZCC. We conclude that a teZCC in osteochondral constructs can provide two improvements. First, it increases the strength of the bone–hydrogel interface and second, it reduces the stress at this interface. PMID:23706035

  1. Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix.

    Science.gov (United States)

    Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

    2015-11-01

    Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen

  2. Bioactive glass 13-93 as a subchondral substrate for tissue-engineered osteochondral constructs: a pilot study.

    Science.gov (United States)

    Jayabalan, Prakash; Tan, Andrea R; Rahaman, Mohammed N; Bal, B Sonny; Hung, Clark T; Cook, James L

    2011-10-01

    Replacement of diseased areas of the joint with tissue-engineered osteochondral grafts has shown potential in the treatment of osteoarthritis. Bioactive glasses are candidates for the osseous analog of these grafts. (1) Does Bioactive Glass 13-93 (BG 13-93) as a subchondral substrate improve collagen and glycosaminoglycan production in a tissue-engineered cartilage layer? (2) Does BG 13-93 as a culture medium supplement increase the collagen and glycosaminoglycan production and improve the mechanical properties in a tissue-engineered cartilage layer? In Study 1, bioactive glass samples (n = 4) were attached to a chondrocyte-seeded agarose layer to form an osteochondral construct, cultured for 6 weeks, and compared to controls. In Study 2, bioactive glass samples (n = 5) were cocultured with cell-seeded agarose for 6 weeks. The cell-seeded agarose layer was exposed to BG 13-93 either continuously or for the first or last 2 weeks in culture or had no exposure. Osteochondral constructs with a BG 13-93 base had improved glycosaminoglycan deposition but less collagen II content. Agarose scaffolds that had a temporal exposure to BG 13-93 within the culture medium had improved mechanical and biochemical properties compared to continuous or no exposure. When used as a subchondral substrate, BG 13-93 did not improve biochemical properties compared to controls. However, as a culture medium supplement, BG 13-93 improved the biochemical and mechanical properties of a tissue-engineered cartilage layer. BG 13-93 may not be suitable in osteochondral constructs but could have potential as a medium supplement for neocartilage formation.

  3. In situ monitoring of localized shear stress and fluid flow within developing tissue constructs by Doppler optical coherence tomography

    Science.gov (United States)

    Jia, Yali; Bagnaninchi, Pierre O.; Wang, Ruikang K.

    2008-02-01

    Mechanical stimuli can be introduced to three dimensional (3D) cell cultures by use of perfusion bioreactor. Especially in musculoskeletal tissues, shear stress caused by fluid flow generally increase extra-cellular matrix (ECM) production and cell proliferation. The relationship between the shear stress and the tissue development in situ is complicated because of the non-uniform pore distribution within the cell-seeded scaffold. In this study, we firstly demonstrated that Doppler optical coherence tomography (DOCT) is capable of monitoring localized fluid flow and shear stress in the complex porous scaffold by examining their variation trends at perfusion rate of 5, 8, 10 and 12 ml/hr. Then, we developed the 3D porous cellular constructs, cell-seeded chitosan scaffolds monitored during several days by DOCT. The fiber based fourier domain DOCT employed a 1300 nm superluminescent diode with a bandwidth of 52 nm and a xyz resolution of 20×20×15 μm in free space. This setup allowed us not only to assess the cell growth and ECM deposition by observing their different scattering behaviors but also to further investigate how the cell attachment and ECM production has the effect on the flow shear stress and the relationship between flow rate and shear stress in the developing tissue construct. The possibility to monitor continuously the constructs under perfusion will easily indicate the effect of flow rate or shear stress on the cell viability and cell proliferation, and then discriminate the perfusion parameters affecting the pre-tissue formation rate growth.

  4. Skin equivalent tissue-engineered construct: co-cultured fibroblasts/ keratinocytes on 3D matrices of sericin hope cocoons.

    Directory of Open Access Journals (Sweden)

    Sunita Nayak

    Full Text Available The development of effective and alternative tissue-engineered skin replacements to autografts, allografts and xenografts has became a clinical requirement due to the problems related to source of donor tissue and the perceived risk of disease transmission. In the present study 3D tissue engineered construct of sericin is developed using co-culture of keratinocytes on the upper surface of the fabricated matrices and with fibroblasts on lower surface. Sericin is obtained from "Sericin Hope" silkworm of Bombyx mori mutant and is extracted from cocoons by autoclave. Porous sericin matrices are prepared by freeze dried method using genipin as crosslinker. The matrices are characterized biochemically and biophysically. The cell proliferation and viability of co-cultured fibroblasts and keratinocytes on matrices for at least 28 days are observed by live/dead assay, Alamar blue assay, and by dual fluorescent staining. The growth of the fibroblasts and keratinocytes in co-culture is correlated with the expression level of TGF-β, b-FGF and IL-8 in the cultured supernatants by enzyme-linked immunosorbent assay. The histological analysis further demonstrates a multi-layered stratified epidermal layer of uninhibited keratinocytes in co-cultured constructs. Presence of involucrin, collagen IV and the fibroblast surface protein in immuno-histochemical stained sections of co-cultured matrices indicates the significance of paracrine signaling between keratinocytes and fibroblasts in the expression of extracellular matrix protein for dermal repair. No significant amount of pro inflammatory cytokines (TNF-α, IL-1β and nitric oxide production are evidenced when macrophages grown on the sericin matrices. The results all together depict the potentiality of sericin 3D matrices as skin equivalent tissue engineered construct in wound repair.

  5. Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

    Science.gov (United States)

    Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

    2014-11-01

    Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

  6. Supplementation of exogenous adenosine 5'-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering.

    Science.gov (United States)

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2013-10-01

    Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5'-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.

  7. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning

    DEFF Research Database (Denmark)

    Schmidt, Michael Rahbek; Smerup, M; Konstantinov, I E

    2006-01-01

    . Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K(ATP) channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range...

  8. Assessment of mitral annular velocities by Doppler tissue imaging in predicting left ventricular thrombus formation after first anterior acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Ahmed Fathy

    2011-09-01

    Conclusion: From our study, we can conclude that TDE can be used for estimation of systolic and diastolic functions of LV and hence identification of patients at high risk for LV thrombus formation after first time acute anterior myocardial infarction and we recommend more studies to support our results about the importance of the role of oral anticoagulant after AMI.

  9. A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs.

    Science.gov (United States)

    Athirasala, Avathamsa; Lins, Fernanda; Tahayeri, Anthony; Hinds, Monica; Smith, Anthony J; Sedgley, Christine; Ferracane, Jack; Bertassoni, Luiz E

    2017-06-12

    The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-vascularized, cell-laden hydrogel pulp-like tissue constructs in full-length root canals for dental pulp regeneration. We utilized gelatin methacryloyl (GelMA) hydrogels with tunable physical and mechanical properties to determine the microenvironmental conditions (microstructure, degradation, swelling and elastic modulus) that enhanced viability, spreading and proliferation of encapsulated odontoblast-like cells (OD21), and the formation of endothelial monolayers by endothelial colony forming cells (ECFCs). GelMA hydrogels with higher polymer concentration (15% w/v) and stiffness enhanced OD21 cell viability, spreading and proliferation, as well as endothelial cell spreading and monolayer formation. We then fabricated pre-vascularized, full-length, dental pulp-like tissue constructs by dispensing OD21 cell-laden GelMA hydrogel prepolymer in root canals of extracted teeth and fabricating 500 µm channels throughout the root canals. ECFCs seeded into the microchannels successfully formed monolayers and underwent angiogenic sprouting within 7 days in culture. In summary, the proposed approach is a simple and effective strategy for engineering of pre-vascularized dental pulp constructs offering potentially beneficial translational outcomes.

  10. Acute myocardial infarction

    International Nuclear Information System (INIS)

    RISCHPLER, Christoph

    2016-01-01

    Inflammatory processes after myocardial infarction have gained major interest in recent cardiovascular research. It is believed that not only the degree of cell recruitment to the heart plays a pivotal role in the quality of wound healing after myocardial infarction, but also the balance between different types or even subtypes of cells. It is also this balance which is thought to control key processes in tissue repair, such as apoptosis and neoangiogenesis. In this paper, we aim to review imaging strategies (with a special focus on nuclear molecular imaging strategies) that target cells and processes involved in postischemic inflammation and that have a high potential to be translated into clinic or that are already being used and evaluated in humans.

  11. Thallium-201 myocardial imaging

    International Nuclear Information System (INIS)

    Wackers, F.J.Th.

    1980-01-01

    Three views are routinely obtained for 201 Tl scintigraphy: 0 0 anterior, 45 0 left-anterior-oblique, both views with the patient supine and a left-lateral view, with the patient lying on his right side. Following intravenous injection of 201 Tl, the scintiscans of a normal subject only demonstrate the left ventricle. In patients with normal myocardial perfusion, the left ventricle appears horseshoe or ovoid in shape. The central area of decreased activity represents the left ventricular cavity and is normal. The accumulation of 201 Tl in the normal left ventricle is usually homogeneous. However, some areas with apparent diminished uptake may occur in the normal subject. These variations of the normal image are discussed. The right ventricle, because of its smaller myocardial mass and relatively less 201 Tl accumulation per gram of tissue, is usually on a resting study not, or only faintly, visualized. However, following exercise, the right ventricle is clearly visualized. (Auth.)

  12. [Experimental study of tissue engineered cartilage construction using oriented scaffold combined with bone marrow mesenchymal stem cells in vivo].

    Science.gov (United States)

    Duan, Wei; Da, Hu; Wang, Wentao; Lü, Shangjun; Xiong, Zhuo; Liu, Jian

    2013-05-01

    To investigate the feasibility of fabricating an oriented scaffold combined with chondrogenic-induced bone marrow mesenchymal stem cells (BMSCs) for enhancement of the biomechanical property of tissue engineered cartilage in vivo. Temperature gradient-guided thermal-induced phase separation was used to fabricate an oriented cartilage extracellular matrix-derived scaffold composed of microtubules arranged in parallel in vertical section. No-oriented scaffold was fabricated by simple freeze-drying. Mechanical property of oriented and non-oriented scaffold was determined by measurement of compressive modulus. Oriented and non-oriented scaffolds were seeded with chondrogenic-induced BMSCs, which were obtained from the New Zealand white rabbits. Proliferation, morphological characteristics, and the distribution of the cells on the scaffolds were analyzed by MTT assay and scanning electron microscope. Then cell-scaffold composites were implanted subcutaneously in the dorsa of nude mice. At 2 and 4 weeks after implantation, the samples were harvested for evaluating biochemical, histological, and biomechanical properties. The compressive modulus of oriented scaffold was significantly higher than that of non-oriented scaffold (t=201.099, P=0.000). The cell proliferation on the oriented scaffold was significantly higher than that on the non-oriented scaffold from 3 to 9 days (P fibers with chondrocyte-like cells on the oriented-structure constructs. Total DNA, glycosaminoglycan (GAG), and collagen contents increased with time, and no significant difference was found between 2 groups (P > 0.05). The compressive modulus of the oriented tissue engineered cartilage was significantly higher than that of the non-oriented tissue engineered cartilage at 2 and 4 weeks after implantation (P < 0.05). Total DNA, GAG, collagen contents, and compressive modulus in the 2 tissue engineered cartilages were significantly lower than those in normal cartilage (P < 0.05). Oriented extracellular

  13. Bladder tissue engineering using biocompatible nanofibrous electrospun constructs: feasibility and safety investigation.

    Science.gov (United States)

    Shakhssalim, Nasser; Dehghan, Mohammad Mehdi; Moghadasali, Reza; Soltani, Mohammad Hossein; Shabani, Iman; Soleimani, Masoud

    2012-01-01

    To investigate the feasibility and safety of using biocompatible, nanofibrous electrospun polycaprolactone (PCL) and combination of polylactic acid (PLLA) and PCL mats in a canine model. Plasma-treated electrospun unseeded mats were implanted in three dogs. The first dog was sacrificed after 3 months and the second and third ones after 4 months, and then, the graft was examined macroscopically with subsequent morphological and histochemical evaluation. Both films showed high levels of cell infiltration and tissue formation, but body response to PLLA/PCL mat in comparison to PCL mat was very low. All three implantation models showed the same light microscopic morphology, immunohistochemistry, and scanning electron microscopy results; nevertheless, only the PCL/PLLA model showed favorable clinical results. Based on these data, nanofibrous PLLA/PCL scaffolding could be a suitable material for the bladder tissue engineering; however, it deserves further investigations.

  14. The development of radioiodinated fatty acids for myocardial imaging

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.

    1993-01-01

    Since free fatty acids are the principal energy source for the normally oxygenated myocardium, the use of iodine-123-labeled fatty acid analogues is an attractive approach for myocardial imaging. Interest in the use of these substances results from divergent fatty acid metabolic pathways in ischemic (triglyceride storage) versus normoxic tissue (β-oxidative clearance), following flow-dependent delivery. Iodine-123-labeled fatty acids may offer a unique opportunity to identity myocardial viability using single photon emission tomography. The development of structurally-modified fatty acids became of interest because of the relatively long acquisition periods required for SPECT. The significant time required by early generation single- or dual-head SPECT systems for data acquisition requires minimal redistribution during the acquisition period to ensure accurate evaluation of the regional fatty acid distribution pattern after re-construction. Research has focussed on the evaluation of structural modifications which can be introduced into the fatty acid chain which would inhibit the subsequent β-oxidative catabolism which normally results in rapid myocardial clearance. Introduction of a methyl group in position-3 of the fatty acid carbon chain has been shown to significantly delay myocardial clearance and iodine-123-labeled 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) is a new tracer based on this strategy

  15. 3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A.

    2016-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

  16. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  17. Construction of tissue compensating filters for extended areas in Hodgkin-irradiation on the basis of moire topography

    International Nuclear Information System (INIS)

    Binder, W.; Cabaj, A.; Kaercher, K.H.; Windischbauer, G.; Tieraerztliche Hochschule, Vienna

    1977-01-01

    In order to obtain a homogeneous distribution of the dose over extended fields in radiotherapy of Hodgkin's disease, for an exact dose within the irradiated region it is necessary to consider the topography of the patient. The skin protective build-up effect due to the use of bolus materials would be lost with telecobalt irradiation, and therefore tissue compensating filters with a large surface are to be preferred. A simple method of making such filters by means of the moire topography is described. The way to obtain a compensation filter for extended areas is demonstrated by an example showing how to construct it from layered lead plates. (orig./HP) [de

  18. Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs Using Low-Viscosity Bioink.

    Science.gov (United States)

    Colosi, Cristina; Shin, Su Ryon; Manoharan, Vijayan; Massa, Solange; Costantini, Marco; Barbetta, Andrea; Dokmeci, Mehmet Remzi; Dentini, Mariella; Khademhosseini, Ali

    2016-01-27

    A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented. The technique incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures. The extrusion system is then coupled to a microfluidic device to control the bioink arrangement deposition, demonstrating the versatility of the bioprinting technique. This low-viscosity cell-responsive bioink promotes cell migration and alignment within each fiber organizing the encapsulated cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Myocardial scintigraphy: methods and indications

    International Nuclear Information System (INIS)

    Knapp, W.H.

    1993-01-01

    Myocardial scintigraphy comprises perfusion imaging using TI-201 or - more recently - Tc-99m-labeled compounds with high affinity to myocytes. Imaging with these agents has become an important procedure in the detection of coronary artery disease, particularly in patients with non-diagnostic stress-ECG, in the functional evaluation of coronary stenoses after angiographical documentation in order to meet the adequate therapy decision, in therapy monitoring and follow-up, in the post infarction assessment of myocardial viability and differentiation between severe ischemia and scar and, occasionally, in acute ischemia. The use of positron emitters does not offer significant advantages for mere perfusion imaging, but is indispensable for the scintigraphic investigation of certain aspects of myocardial metabolism, particularly for the differentiation of viable ischemic wall segments from irreversibly damaged tissue. Imaging of myocardial necrosis has been improved by the introduction of labeled antimyosin antibody fragments and offers a considerable clinical potential in the diagnosis of myocarditis and cardiac transplant rejection. Neurohumoral aspects are increasingly involved in our understanding of myocardial failure. Scintigraphy of innervation/neurotransmission contributes to the investigation of pathophysiological alterations in myocardial insufficiency and in heart transplants. (orig.) [de

  20. Evaluation of the growth environment of a hydrostatic force bioreactor for preconditioning of tissue-engineered constructs.

    Science.gov (United States)

    Reinwald, Yvonne; Leonard, Katherine H L; Henstock, James R; Whiteley, Jonathan P; Osborne, James M; Waters, Sarah L; Levesque, Philippe; El Haj, Alicia J

    2015-01-01

    Bioreactors have been widely acknowledged as valuable tools to provide a growth environment for engineering tissues and to investigate the effect of physical forces on cells and cell-scaffold constructs. However, evaluation of the bioreactor environment during culture is critical to defining outcomes. In this study, the performance of a hydrostatic force bioreactor was examined by experimental measurements of changes in dissolved oxygen (O2), carbon dioxide (CO2), and pH after mechanical stimulation and the determination of physical forces (pressure and stress) in the bioreactor through mathematical modeling and numerical simulation. To determine the effect of hydrostatic pressure on bone formation, chick femur skeletal cell-seeded hydrogels were subjected to cyclic hydrostatic pressure at 0-270 kPa and 1 Hz for 1 h daily (5 days per week) over a period of 14 days. At the start of mechanical stimulation, dissolved O2 and CO2 in the medium increased and the pH of the medium decreased, but remained within human physiological ranges. Changes in physiological parameters (O2, CO2, and pH) were reversible when medium samples were placed in a standard cell culture incubator. In addition, computational modeling showed that the distribution and magnitude of physical forces depends on the shape and position of the cell-hydrogel constructs in the tissue culture format. Finally, hydrostatic pressure was seen to enhance mineralization of chick femur skeletal cell-seeded hydrogels.

  1. Preclinical study of mouse pluripotent parthenogenetic embryonic stem cell derivatives for the construction of tissue-engineered skin equivalent.

    Science.gov (United States)

    Rao, Yang; Cui, Jihong; Yin, Lu; Liu, Wei; Liu, Wenguang; Sun, Mei; Yan, Xingrong; Wang, Ling; Chen, Fulin

    2016-10-22

    Embryonic stem cell (ESC) derivatives hold great promise for the construction of tissue-engineered skin equivalents (TESE). However, harvesting of ESCs destroys viable embryos and may lead to political and ethical concerns over their application. In the current study, we directed mouse parthenogenetic embryonic stem cells (pESCs) to differentiate into fibroblasts, constructed TESE, and evaluated its function in vivo. The stemness marker expression and the pluripotent differentiation ability of pESCs were tested. After embryoid body (EB) formation and adherence culture, mesenchymal stem cells (MSCs) were enriched and directed to differentiate into fibroblastic lineage. Characteristics of derived fibroblasts were assessed by quantitative real-time PCR and ELISA. Functional ability of the constructed TESE was tested by a mouse skin defects repair model. Mouse pESCs expressed stemness marker and could form teratoma containing three germ layers. MSCs could be enriched from outgrowths of EBs and directed to differentiate into fibroblastic lineage. These cells express a high level of growth factors including FGF, EGF, VEGF, TGF, PDGF, and IGF1, similar to those of ESC-derived fibroblasts and mouse fibroblasts. Seeded into collagen gels, the fibroblasts derived from pESCs could form TESE. Mouse skin defects could be successfully repaired 15 days after transplantation of TESE constructed by fibroblasts derived from pESCs. pESCs could be induced to differentiate into fibroblastic lineage, which could be applied to the construction of TESE and skin defect repair. Particularly, pESC derivatives avoid the limitations of political and ethical concerns, and provide a promising source for regenerative medicine.

  2. Electrically conductive poly-ɛ-caprolactone/polyethylene glycol/multi-wall carbon nanotube nanocomposite scaffolds coated with fibrin glue for myocardial tissue engineering

    Science.gov (United States)

    Mehdikhani, Mehdi; Ghaziof, Sharareh

    2018-01-01

    In this research, poly-ɛ-caprolactone (PCL), polyethylene glycol (PEG), multi-wall carbon nanotubes (MWCNTs), and nanocomposite scaffolds containing 0.5 and 1% (w/w) MWCNTs coated with fibrin glue (FG) were prepared via solvent casting and freeze-drying technique for cardiac tissue engineering. Scanning electron microscopy, transmission electron microscopy, Fourier transform-infrared spectroscopy, and X-ray diffraction were used to characterize the samples. Furthermore, mechanical properties, electrical conductivity, degradation, contact angle, and cytotoxicity of the samples were evaluated. Results showed the uniform distribution of the MWCNTs with some aggregates in the prepared nanocomposite scaffolds. The scaffolds containing 1% (w/w) MWCNTs with and without FG coating illustrated optimum modulus of elasticity, high electrical conductivity, and wettability compared with PCL/PEG and PCL/PEG/0.5%(w/w) MWCNTs' scaffolds. FG coating enhanced electrical conductivity and cell response, and increased wettability of the constructs. The prepared scaffolds were degraded significantly after 60 days of immersion in PBS. Meanwhile, the nanocomposite containing 1% (w/w) MWCNTs with FG coating (S3) showed proper spreading and viability of the myoblasts seeded on it after 1, 4, and 7 days of culture. The scaffold containing 1% (w/w) MWCNTs with FG coating demonstrated optimal properties including acceptable mechanical properties, proper wettability, high electrical conductivity, satisfactory degradation, and excellent myoblasts response to it.

  3. [Preliminary study of constructing tissue-engineered cartilage with the endoskeletal scaffold of HDPE by bone marrow stromal cells].

    Science.gov (United States)

    Zhu, Lie; Jiang, Hua; Zhou, Guang-Dong; Wu, Yu-Jia; Luo, Xu-Song

    2008-09-01

    To explore the feasibility of using a nonreactive, permanent endoskeletal scaffold to create the prothesis in special shape which is covered with tissue-engineered cartilage. Porcine BMSCs and articular chondrocytes were isolated and expanded respectively in vitro. Porcine BMSC of passage 1 in the concentration of 10 x 10(7)/ml were seeded onto a cylinder-shaped PGA (1 mm in thickness)/Medpor (3mm in diameter and 5mm in highness) scaffold as the experimental group. After the cell-scaffold constructs were cultured for 5 days, the primary medium, high-glucose DMEM medium with 10% fetal bovine serum (FBS), was replaced by chondrogenically inductive medium for 4 weeks. BMSCs and chondrocytes of the same concentration were seeded respectively onto the scaffold as the negative control group and the positive control group. After cultured in vitro for 4 weeks, the cell-scaffolds construct were implanted into subcutaneous pockets on the back of nude mice. Four and eight weeks later, the formed cartilage prosthesis were harvested and then evaluated by gross view, histology, immunohistochemistry and glycosamino-glycan (GAG) content. Cells in all groups had fine adhesion to the scaffold and could secrete extracellular matrix. All specimens in experimental group and positive control group formed mature cartilage with collagen II expression.The mature catrtilage wraped HDPE compactly and grown into the gap of HDPE. Mature lacuna structures and metachromatic matrices were also observed in these specimens. GAG contents in experimental group were (5.13 +/- 0.32) mg/g (4 weeks), (5.37 +/- 0.12) mg/g (8 weeks). In contrast, specimens in BMSC group showed mainly fibrous tissue. It indicates that it is feasible to create special shaped tissue-engineering cartilage with the permanent internal support using BMSCs as seed cell.

  4. Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct.

    Science.gov (United States)

    Volkov, A V; Alekseeva, I S; Kulakov, A A; Gol'dshtein, D V; Shustrov, S A; Shuraev, A I; Arutyunyan, I V; Bukharova, T B; Rzhaninova, A A; Bol'shakova, G B; Grigor'yan, A S

    2010-10-01

    We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.

  5. Constructing Failure: Leonard Hayflick, Biomedicine, and the Problems with Tissue Culture.

    Science.gov (United States)

    Park, Hyung Wook

    2016-07-01

    By examining the use of tissue culture in post-war American biomedicine, this paper investigates how scientists experience and manage failure. I study how Leonard Hayflick forged his new definition of failure and ways of managing it by refuting Alexis Carrel's definition of failure alongside his theory of the immortality of cultured cells. Unlike Carrel, Hayflick claimed that every vertebrate somatic cell should eventually die, unless it transformed into a tumour cell. This claim defined cell death, which had been a problem leading to a laboratory failure, as a normal phenomenon. On the other hand, permanent life, which had been considered a normal cellular characteristic, became a major factor causing scientific failure, since it implied malignant transformation that scientists hoped to control. Hayflick then asserted that his cell strains and method would partly enable scientists to manage this factor-especially that occurred through viral infection-alongside other causes of failure in routine tasks, including bacterial contamination. I argue that the growing biomedical enterprise fostered this work of Hayflick's, which had repercussions in both his career and the uses of cells in diverse investigations. His redefinition of failure in the age of biomedicine resulted in the broad dissemination of his cells, medium, and method as well as his long struggle with the National Institutes of Health (NIH), which caused his temporarily failed career.

  6. From iPSC towards cardiac tissue-a road under construction.

    Science.gov (United States)

    Peischard, Stefan; Piccini, Ilaria; Strutz-Seebohm, Nathalie; Greber, Boris; Seebohm, Guiscard

    2017-10-01

    The possibility to generate induced pluripotent stem cells (iPSC) opens the way to generate virtually all cell types of our human body. In combination with modern gene editing techniques like CRISPR/CAS, a new set of powerful tools becomes available for life science. Scientific fields like genotype and cell type-specific pharmacology, disease modeling, stem cell biology, and developmental biology have been dramatically fostered and their faces have been changed. However, as golden as the age of iPSC-derived cells and their manipulation has started, the shine begins to tarnish. Researchers face more and more practical problems intrinsic to the system. These problems are related to the specific culturing conditions which are not yet sufficient to mimic the natural environment of native stem cells differentiating towards adult cells. However, researchers work hard to uncover these factors. Here, we review a common standard approach to generate iPSCs and transduce these to iPSC cardiomyocytes. Further, we review recent achievements and discuss their current limitations and future perspectives. We are on track, but the road is still under construction.

  7. Construction and Development of a Cardiac Tissue-Specific and Hypoxia-Inducible Expression Vector

    Directory of Open Access Journals (Sweden)

    Shahrooz Ghaderi

    2018-03-01

    Full Text Available Purpose: Cardiovascular gene therapy is a sophisticated approach, thanks to the safety of vectors, stable transgene expression, delivery method, and different layers of the heart. To date, numerous expression vectors have been introduced in biotechnology and biopharmacy industries in relation to genetic manipulation. Despite the rapid growth of these modalities, they must be intelligently designed, addressing the cardiac-specific transgene expression and less side effects. Herein, we conducted a pilot project aiming to design a cardiac-specific hypoxia-inducible expression cassette. Methods: We explored a new approach to design an expression cassette containing cardiac specific enhancer, hypoxia response elements (HRE, cardiac specific promoter, internal ribosome entry site (IRES, and beta globin poly A sequence to elicit specific and inducible expression of the gene of interest. Enhanced green fluorescent protein (eGFP was sub-cloned by BglII and NotI into the cassette. The specificity and inducible expression of the cassette was determined in both mouse myoblast C2C12 and mammary glandular tumor 4T1 as ‘twin’ cells. eGFP expression was evaluated by immunofluorescence microscope and flow cytometry at 520 nm emission peak. Results: Our data revealed that the designed expression cassette provided tissue specific and hypoxia inducible (O2<1% transgene expression. Conclusion: It is suggested that cardiac-specific enhancer combined with cardiac-specific promoter are efficient for myoblast specific gene expression. As well, this is for the first time that HRE are derived from three well known hypoxia-regulated promoters. Therefore, there is no longer need to overlap PCR process for one repeated sequence just in one promoter.

  8. Doppler Tissue Imaging Is an Independent Predictor of Outcome in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Jensen, Jan Skov; Pedersen, Sune

    2014-01-01

    in patients treated with primary percutaneous coronary intervention. METHOD: In total, 391 patients who were admitted with STEMIs and treated with primary percutaneous coronary intervention were prospectively included. All participants were examined by echocardiography 2 days (interquartile range, 1-3 days......) after STEMI. Longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured using color DTI at six mitral annular sites and averaged to provide global estimates. RESULTS: The median follow-up period was 25 months (interquartile range, 19-32 months...

  9. Automatic quantitative micro-computed tomography evaluation of angiogenesis in an axially vascularized tissue-engineered bone construct.

    Science.gov (United States)

    Arkudas, Andreas; Beier, Justus Patrick; Pryymachuk, Galyna; Hoereth, Tobias; Bleiziffer, Oliver; Polykandriotis, Elias; Hess, Andreas; Gulle, Heinz; Horch, Raymund E; Kneser, Ulrich

    2010-12-01

    We invented an automatic observer-independent quantitative method to analyze vascularization using micro-computed tomography (CT) along with three-dimensional (3D) reconstruction in a tissue engineering model. An arteriovenous loop was created in the medial thigh of 30 rats and was placed in a particulated porous hydroxyapatite and beta-tricalcium phosphate matrix, filled with fibrin (10 mg/mL fibrinogen and 2 IU/mL thrombin) without (group A) or with (group B) application of fibrin-gel-immobilized angiogenetic growth factors vascular endothelial growth factor (VEGF¹⁶⁵) and basic fibroblast growth factor (bFGF). The explantation intervals were 2, 4, and 8 weeks. Specimens were investigated by means of micro-CT followed by an automatic 3D analysis, which was correlated to histomorphometrical findings. In both groups, the arteriovenous loop led to generation of dense vascularized connective tissue with differentiated and functional vessels inside the matrix. Quantitative analysis of vascularization using micro-CT showed to be superior to histological analysis. The micro-CT analysis also allows the assessment of different other, more complex vascularization parameters within 3D constructs, demonstrating an early improvement of vascularization by application of fibrin-gel-immobilized VEGF¹⁶⁵ and bFGF. In this study quantitative analysis of vascularization using micro-CT along with 3D reconstruction and automatic analysis exhibit to be a powerful method superior to histological evaluation of cross sections.

  10. [Construction of forward and reverse subtracted cDNA libraries between muscle tissue of Meishan and Landrace pigs].

    Science.gov (United States)

    Xu, De-Quan; Zhang, Yi-Bing; Xiong, Yuan-Zhu; Gui, Jian-Fang; Jiang, Si-Wen; Su, Yu-Hong

    2003-07-01

    Using suppression subtractive hybridization (SSH) technique, forward and reverse subtracted cDNA libraries were constructed between Longissimus muscles from Meishan and Landrace pigs. A housekeeping gene, G3PDH, was used to estimate the efficiency of subtractive cDNA. In two cDNA libraries, G3PDH was subtracted very efficiently at appropriate 2(10) and 2(5) folds, respectively, indicating that some differentially expressed genes were also enriched at the same folds and the two subtractive cDNA libraries were very successful. A total of 709 and 673 positive clones were isolated from forward and reverse subtracted cDNA libraries, respectively. Analysis of PCR showed that most of all plasmids in the clones contained 150-750 bp inserts. The construction of subtractive cDNA libraries between muscle tissue from different pig breeds laid solid foundations for isolating and identifying the genes determining muscle growth and meat quality, which will be important to understand the mechanism of muscle growth, determination of meat quality and practice of molecular breeding.

  11. Construction of a preclinical multimodality phantom using tissue-mimicking materials for quality assurance in tumor size measurement.

    Science.gov (United States)

    Lee, Yongsook C; Fullerton, Gary D; Goins, Beth A

    2013-07-29

    World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) working groups advocated standardized criteria for radiologic assessment of solid tumors in response to anti-tumor drug therapy in the 1980s and 1990s, respectively. WHO criteria measure solid tumors in two-dimensions, whereas RECIST measurements use only one-dimension which is considered to be more reproducible (1, 2, 3,4,5). These criteria have been widely used as the only imaging biomarker approved by the United States Food and Drug Administration (FDA) (6). In order to measure tumor response to anti-tumor drugs on images with accuracy, therefore, a robust quality assurance (QA) procedures and corresponding QA phantom are needed. To address this need, the authors constructed a preclinical multimodality (for ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) phantom using tissue-mimicking (TM) materials based on the limited number of target lesions required by RECIST by revising a Gammex US commercial phantom (7). The Appendix in Lee et al. demonstrates the procedures of phantom fabrication (7). In this article, all protocols are introduced in a step-by-step fashion beginning with procedures for preparing the silicone molds for casting tumor-simulating test objects in the phantom, followed by preparation of TM materials for multimodality imaging, and finally construction of the preclinical multimodality QA phantom. The primary purpose of this paper is to provide the protocols to allow anyone interested in independently constructing a phantom for their own projects. QA procedures for tumor size measurement, and RECIST, WHO and volume measurement results of test objects made at multiple institutions using this QA phantom are shown in detail in Lee et al. (8).

  12. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okura, Hanayuki [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Saga, Ayami; Soeda, Mayumi [Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Miyagawa, Shigeru; Sawa, Yoshiki [Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Daimon, Takashi [Division of Biostatistics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Ichinose, Akihiro [Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); Matsuyama, Akifumi, E-mail: akifumi-matsuyama@umin.ac.jp [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); RIKEN Program for Drug Discovery and Medical Technology Platforms, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of

  13. Chronic myocardial infarction detection and characterization during coronary artery calcium scoring acquisitions.

    LENUS (Irish Health Repository)

    Rodríguez-Granillo, Gastón A

    2012-01-05

    Hypoenhanced regions on multidetector CT (MDCT) coronary angiography correlate with myocardial hyperperfusion. In addition to a limited capillary density, chronic myocardial infarction (MI) commonly contains a considerable amount of adipose tissue.

  14. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

    Science.gov (United States)

    Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

    2015-05-01

    During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue

  15. Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

    Science.gov (United States)

    Dyment, Nathaniel A.; Lu, Yinhui; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Butler, David L.

    2015-01-01

    The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair. PMID:25266738

  16. Mimicking the micro-environment. Construction and evaluation of complex collagen-based scaffolds for tissue engineering

    NARCIS (Netherlands)

    Nillesen, S.T.M.

    2012-01-01

    The ultimate goal in tissue engineering is to create biomaterials that mimic normal tissue or are able to encourage cells cells to generate new functional tissue. For these biomaterials, it is important to use highly purified components in order to moderate the tissue response and to control the

  17. Morphological aspects of myocardial bridges.

    Science.gov (United States)

    Lujinović, Almira; Kulenović, Amela; Kapur, Eldan; Gojak, Refet

    2013-11-01

    Although some myocardial bridges can be asymptomatic, their presence often causes coronary disease either through direct compression of the "tunnel" segment or through stimulation and accelerated development of atherosclerosis in the segment proximally to the myocardial bridge. The studied material contained 30 human hearts received from the Department of Anatomy. The hearts were preserved 3 to 5 days in 10% formalin solution. Thereafter, the fatty tissue was removed and arterial blood vessels prepared by careful dissection with special reference to the presence of the myocardial bridges. Length and thickness of the bridges were measured by the precise electronic caliper. The angle between the myocardial bridge fibre axis and other axis of the crossed blood vessel was measured by a goniometer. The presence of the bridges was confirmed in 53.33% of the researched material, most frequently (43.33%) above the anterior interventricular branch. The mean length of the bridges was 14.64 ± 9.03 mm and the mean thickness was 1.23 ± 1.32 mm. Myocardial bridge fibres pass over the descending blood vessel at the angle of 10-90 degrees. The results obtained on a limited sample suggest that the muscular index of myocardial bridge is the highest for bridges located on RIA, but that the difference is not significant in relation to bridges located on other branches. The results obtained suggest that bridges located on other branches, not only those on RIA, could have a great contractive power and, consequently, a great compressive force, which would be exerted on the wall of a crossed blood vessel.

  18. Myocardial perfusion in silent myocardial ischemia

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

    1989-01-01

    To investigate myocardial perfusion in silent myocardial ischemia, we performed exercise stress myocardial tomography with thallium-201 (Tl) in 85 patients with coronary artery disease (CAD). Exercise stress myocardial tomography was obtained both immediately after exercise and three hours later. Patients were classified into two groups according to the presence (Symptomatic Group, n=36) or absence (Silent Group, n=49) of chest pain during exercise stress. Clinical features (age, gender and history of myocardial infarction) and arteriographically determined severity of CAD were the same in both groups. The extent of myocardial ischemia (% Ischemia) estimated by exercise stress myocardial tomography was the same in each group (30±10 % in Silent Group, 28±12 % in Symptomatic Group, NS). The severity of exercise-induced myocardial ischemia was expressed as a minimal value of myocardial Tl washout rate (minimal WOR) of each patient. Although exercise heart rate was identical in both groups, minimal WOR in Silent Group was significantly higher than that of Symptomatic Group (4±10% vs -16±14%, p<0.001). The study in patients who exhibited both silent and symptomatic ischemia showed the same results. These findings suggest that the severity of ischemia is a fundamental factor in determining the presence or absence of pain during exercise induced ischemia. (author)

  19. Dosimetry in myocardial perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Toledo, Janine M.; Trindade, Bruno; Ribeiro, Tarcisio P.C. [Universidade Federal de Minas Gerais (DEN/UFMG), Belo Horizonte (Brazil). Dept. de Engenharia Nuclear. Programa de Pos-Graduacao em Ciencias e Tecnicas Nucleares

    2011-07-01

    This paper conducts a dosimetric investigation on the myocardial perfusion image protocol, together with a literature reviewing, motivated by the significant statistic increasing on mortality, morbidity and disability associated with cardiovascular disease, surpassing infectious diseases. Nuclear Cardiology plays a role n the diagnostic functional evaluation of the heart and in the prognostic of patients with suspected or known cardiac ischemia. In the context of unstable myocardial ischemic syndrome, myocardial perfusion scintigraphy is a non-invasive procedure performed by administering a radiopharmaceutical targeted to the heart. As tool for this study are that the images obtained by thoracic angiotomography and abdominal aorta as a anatomic and functional information for model reproduction in SISCODES - System of Codes for Absorbed Dose Calculations based on Stochastic Methods. Data were manipulated in order to create a voxel computational model of the heart to be running in MCNP - Monte Carlo Neutron Particle Code. . It was assumed a homogeneous distribution of Tl-201 in cardiac muscle. Simulations of the transport of particles through the voxel and the interaction with the heart tissue were performed. As a result, the isodose curves in the heart model are displayed as well as the dose versus volume histogram of the heart muscle. We conclude that the present computational tools can generate doses distributed in myocardial perfusion. (author)

  20. Dosimetry in myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Toledo, Janine M.; Trindade, Bruno; Ribeiro, Tarcisio P.C.

    2011-01-01

    This paper conducts a dosimetric investigation on the myocardial perfusion image protocol, together with a literature reviewing, motivated by the significant statistic increasing on mortality, morbidity and disability associated with cardiovascular disease, surpassing infectious diseases. Nuclear Cardiology plays a role n the diagnostic functional evaluation of the heart and in the prognostic of patients with suspected or known cardiac ischemia. In the context of unstable myocardial ischemic syndrome, myocardial perfusion scintigraphy is a non-invasive procedure performed by administering a radiopharmaceutical targeted to the heart. As tool for this study are that the images obtained by thoracic angiotomography and abdominal aorta as a anatomic and functional information for model reproduction in SISCODES - System of Codes for Absorbed Dose Calculations based on Stochastic Methods. Data were manipulated in order to create a voxel computational model of the heart to be running in MCNP - Monte Carlo Neutron Particle Code. . It was assumed a homogeneous distribution of Tl-201 in cardiac muscle. Simulations of the transport of particles through the voxel and the interaction with the heart tissue were performed. As a result, the isodose curves in the heart model are displayed as well as the dose versus volume histogram of the heart muscle. We conclude that the present computational tools can generate doses distributed in myocardial perfusion. (author)

  1. delta-Opioid-induced pharmacologic myocardial hibernation during cardiopulmonary resuscitation.

    Science.gov (United States)

    Fang, Xiangshao; Tang, Wanchun; Sun, Shijie; Weil, Max Harry

    2006-12-01

    Cardiac arrest and cardiopulmonary resuscitation is an event of global myocardial ischemia and reperfusion, which is associated with severe postresuscitation myocardial dysfunction and fatal outcome. Evidence has demonstrated that mammalian hibernation is triggered by cyclic variation of a delta-opiate-like compound in endogenous serum, during which the myocardial metabolism is dramatically reduced and the myocardium tolerates the stress of ischemia and reperfusion without overt ischemic and reperfusion injury. Previous investigations also proved that the delta-opioid agonist elicited the cardioprotection in a model of regional ischemic intact heart or myocyte. Accordingly, we were prompted to search for an alternative intervention of pharmacologically induced myocardial hibernation that would result in rapid reductions of myocardial metabolism and therefore minimize the myocardial ischemic and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation. Prospective, controlled laboratory study. University-affiliated research laboratory. In the series of studies performed in the established rat and pig model of cardiac arrest and cardiopulmonary resuscitation, the delta-opioid receptor agonist, pentazocine, was administered during ventricular fibrillation. : The myocardial metabolism reflected by the concentration of lactate, or myocardial tissue PCO2 and PO2, is dramatically reduced during cardiac arrest and cardiopulmonary resuscitation. These are associated with less severe postresuscitation myocardial dysfunction and longer duration of postresuscitation survival. delta-Opioid-induced pharmacologic myocardial hibernation is an option to minimize the myocardial ischemia and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation.

  2. pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia

    Directory of Open Access Journals (Sweden)

    S. Zara

    2012-01-01

    Full Text Available In premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms and consequences which take place after hyperoxia exposure are different and related to animals age. The aim of our work has been to analyze the role played by HIF-1α in the occurrence of the morphological modifications upon hyperoxia exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment increase which seems to allow enhanced blood vessels growth. An increased hypoxia inducible factor-1α (HIF-1α translocation and vascular endothelial growth factor (VEGF expression has been found upon 95% oxygen exposure to induce morphological modifications. Upstream pPKC-α expression increase in newborn rats exposed to 95% oxygen can suggest PKC involvement in HIF-1α activation. Since nitric oxide synthase (NOS are involved in heart vascular regulation, endothelial NOS (e-NOS and inducible NOS (i-NOS expression has been investigated: a lower eNOS and an higher iNOS expression has been found in newborn rats exposed to 95% oxygen related to the evidence that hyperoxia provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action, respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax expression analyses, seems more evident in sample exposed to severe hyperoxia. All in all such results suggest that in newborn rats hyperoxia can trigger oxygen free radical mediated membrane injury through a pPKCα mediated HIF-1α signalling system, even though specificity of such response could be obtained by in vivo administration to the rats of specific inhibitors of PKCα. This intracellular signalling can switch molecular events leading to blood vessels development in parallel to pro-apoptotic events

  3. Reasons for the lack of benefit of immediate angioplasty during recombinant tissue plasminogen activator therapy for acute myocardial infarction: a regional wall motion analysis. European Cooperative Study Group

    NARCIS (Netherlands)

    Arnold, A. E.; Serruys, P. W.; Rutsch, W.; Simoons, M. L.; de Bono, D. P.; Tijssen, J. G.; Lubsen, J.; Verstraete, M.

    1991-01-01

    Regional ventricular wall motion analysis utilizing three different methods was performed on predischarge left ventriculograms from 291 of 367 patients enrolled in a randomized trial of single chain recombinant tissue-type plasminogen activator (rt-PA), aspirin and heparin with and without immediate

  4. Strain-induced collagen organization at the micro-level in fibrin-based engineered tissue constructs

    NARCIS (Netherlands)

    Jonge, de N.; Kanters, F.M.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    2013-01-01

    Full understanding of strain-induced collagen organization in complex tissue geometries to create tissues with predefined collagen architecture has not been achieved. This is mainly due to our limited knowledge of collagen remodeling in developing tissues. Here we investigate strain-induced collagen

  5. Classification of myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Hosbond, Susanne Elisabeth

    2013-01-01

    The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture-related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand...

  6. The influence of construct scale on the composition and functional properties of cartilaginous tissues engineered using bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Buckley, Conor T; Meyer, Eric G; Kelly, Daniel J

    2012-02-01

    Engineering cartilaginous tissue of a scale necessary to treat defects observed clinically is a well-documented challenge in the field of cartilage tissue engineering. The objective of this study was to determine how the composition and mechanical properties of cartilaginous tissues that are engineered by using bone marrow-derived mesenchymal stem cells (MSCs) depend on the scale of the construct. Porcine bone marrow-derived MSCs were encapsulated in agarose hydrogels, and constructs of different cylindrical geometries (Ø4×1.5 mm; Ø5×3 mm; Ø6×4.5 mm; Ø8×4.5 mm) were fabricated and maintained in a chemically defined serum-free medium supplemented with transforming growth factor-β3 for 42 days. Total sulfated glycosaminoglycan (sGAG) accumulation by day 42 increased from 0.14% w/w to 0.88% w/w as the construct geometry increased from Ø4×1.5 to Ø8×4.5 mm, with collagen accumulation increasing from 0.31% w/w to 1.62% w/w. This led to an increase in the dynamic modulus from 90.81 to 327.51 kPa as the engineered tissue increased in scale from Ø4×1.5 to Ø8×4.5 mm. By decreasing the external oxygen tension from 20% to 5%, it was possible to achieve these higher levels of mechanical functionality in the smaller engineered tissues. Constructs were then sectioned into smaller subregions to quantify the spatial accumulation of extracellular matrix components, and a model of oxygen diffusion and consumption was used to predict spatial gradients in oxygen concentration throughout the construct. sGAG accumulation was always highest in regions where oxygen concentration was predicted to be lowest. In addition, as the size of the engineered construct increased, different regions of the construct preferentially supported either sGAG or collagen accumulation, thus suggesting that gradients in regulatory factors other than oxygen were playing a role in determining levels of collagen synthesis. The identification of such factors and the means to control their

  7. Nitrogen-13-labeled ammonia for myocardial imaging

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, W.F.; Fill, H.R.; Harper, P.V.

    1977-01-01

    Cyclotron-produced nitrogen-13 (half-life 10 min), as labeled ammonia (/sup 13/NH/sub 4//sup +/), has been evaluated as a myocardial perfusion imaging agent. The regional myocardial uptake of /sup 13/NH/sub 4//sup +/ has been shown to be proportional to regional tissue perfusion in animal studies. Intravenously administered /sup 13/NH/sub 4//sup +/ is rapidly cleared from the circulation, being extracted by the liver (15 percent), lungs, myocardium (2 percent--4 percent), brain, kidney, and bladder. Myocardial ammonia is metabolized mainly to glutamine via the glutamine synthetase pathway. Pulmonary uptake is substantial, but usually transient, except in smokers where clearance may be delayed. The positron annihilation irradiation (511 keV) of /sup 13/N may be imaged with a scintillation camera, using either a specially designed tungsten collimator or a pinhole collimator. After early technical problems with collimation and the production method of /sup 13/NH/sub 4//sup +/ were overcome, reproducible high quality myocardial images were consistently obtained. The normal myocardial image was established to be of a homogeneous ''doughnut'' configuration. Imaging studies performed in patients with varying manifestations of ischemic and valvular heart disease showed a high incidence of localized perfusion defects, especially in patients with acute myocardial infarction. Sequential studies at short intervals in patients with acute infarction showed correlation between alterations in regional perfusion and the clinical course of the patient. It is concluded that myocardial imaging with /sup 13/NH/sub 4//sup +/ and a scintillation camera provides a valid and noninvasive means of assessing regional myocardial perfusion. This method is especially suitable for sequential studies of acute cardiac patients at short intervals. Coincidence imaging of the 511 keV annihilation irradiation provides a tomographic and potentially quantitative assessment of the

  8. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    Science.gov (United States)

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

  9. The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs.

    LENUS (Irish Health Repository)

    Lyons, Frank G

    2010-12-01

    One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.

  10. Myocardial imaging. Coxsackie myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  11. Myocardial imaging. Coxsackie myocarditis

    International Nuclear Information System (INIS)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-01-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1

  12. Myocardial imaging with cesium-130

    International Nuclear Information System (INIS)

    Harper, P.V.; Resnekov, L.; Stark, V.; Odeh, N.

    1984-01-01

    Recently comparative studies using nitrogen-13 ammonia and cesium-130 have shown strikingly different myocardial localization patterns in the same subjects with ischemic heart disease. Initial localization of ammonia, an avidly extracted agent, reflects the perfusion pattern in viable myocardial tissue. The myocardial localization of cesium ion, taking place more slowly over 15 to 20 minutes, is apparently much less flow dependent, causing uptake defects shown with ammonia to be largely filled in. Cesium thus appears to provide information on the extent of the viable myocardial mass, apart from perfusion. Cesium-130 (t1/2 30 m) decays by positron emission and electron capture. The whole body radiation absorbed dose, assuming uniform distribution, is 24 mrad/mCi. While abundant production of Cs-130 results from proton bombardment of natural xenon [Xe-130(rho,n)Cs-130] at 15 MeV, small amounts of Cs-129, -131, and -132 are also produced, and enriched Xe-130 is not available. Alternatively almost completely uncontaminated Cs-130 is available by alpha bombardment of natural I-127. Anhydrous sodium iodide is dissolved in acetone and a thin layer (≅20 mg per centimeter squared) is evaporated onto the gold plated tip of the internal target backing which is oscillated vertically to spread out the area upon which the beam is incident. The target surface is inclined 2.5 degrees to the beam giving a power density of about 400 watts per centimeter squared at 100μA which is adequately handled by water cooling. A 30-minute bombardment yields 4 to 5 mCi of Cs-130 which is dissolved directly from the target. This approach appears to offer a new and helpful method for evaluating ischemic heart disease by permitting evaluation of viable myocardial mass

  13. Acceleration of tissue phase mapping by k-t BLAST: a detailed analysis of the influence of k-t-BLAST for the quantification of myocardial motion at 3T

    Directory of Open Access Journals (Sweden)

    Nienhaus G Ulrich

    2011-01-01

    Full Text Available Abstract Background The assessment of myocardial motion with tissue phase mapping (TPM provides high spatiotemporal resolution and quantitative motion information in three directions. Today, whole volume coverage of the heart by TPM encoding at high spatial and temporal resolution is limited by long data acquisition times. Therefore, a significant increase in imaging speed without deterioration of the quantitative motion information is required. For this purpose, the k-t BLAST acceleration technique was combined with TPM black-blood functional imaging of the heart. Different k-t factors were evaluated with respect to their impact on the quantitative assessment of cardiac motion. Results It is demonstrated that a k-t BLAST factor of two can be used with a marginal, but statistically significant deterioration of the quantitative motion data. Further increasing the k-t acceleration causes substantial alteration of the peak velocities and the motion pattern, but the temporal behavior of the contraction is well maintained up to an acceleration factor of six. Conclusions The application of k-t BLAST for the acceleration of TPM appears feasible. A reduction of the acquisition time of almost 45% could be achieved without substantial loss of quantitative motion information.

  14. A regenerative biology view on artificial tissue construction and 3D bioprinting: what may we learn from natural regenerative phenomena?

    DEFF Research Database (Denmark)

    Lauridsen, Henrik

    2017-01-01

    The implications of the low tissue regenerative potential in humans are severe and widespread. Several of our major diseases are direct results of this deficiency that leaves us vulnerable to events of tissue damage. This is opposed to some animal groups, such as the urodele amphibians (salamanders...

  15. Decreased mechanical properties of heart valve tissue constructs cultured in platelet lysate as compared to fetal bovine serum

    NARCIS (Netherlands)

    Geemen, van D.; Riem Vis, P.W.; Soekhradj - Soechit, R.S.; Sluijter, J.P.G.; Liefde - van Beest, de M.; Kluin, J.; Bouten, C.V.C.

    2011-01-01

    In autologous heart valve tissue engineering, there is an ongoing search for alternatives of fetal bovine serum (FBS). Human platelet-lysate (PL) might be a promising substitute. In the present article, we aimed to examine the tissue formation, functionality, and mechanical properties of engineered

  16. Comparison of blood biochemics between acute myocardial infarction models with blood stasis and simple acute myocardial infarction models in rats

    International Nuclear Information System (INIS)

    Qu Shaochun; Yu Xiaofeng; Wang Jia; Zhou Jinying; Xie Haolin; Sui Dayun

    2010-01-01

    Objective: To construct the acute myocardial infarction models in rats with blood stasis and study the difference on blood biochemics between the acute myocardial infarction models with blood stasis and the simple acute myocardial infarction models. Methods: Wistar rats were randomly divided into control group, acute blood stasis model group, acute myocardial infarction sham operation group, acute myocardial infarction model group and of acute myocardial infarction model with blood stasis group. The acute myocardial infarction models under the status of the acute blood stasis in rats were set up. The serum malondialdehyde (MDA), nitric oxide (NO), free fatty acid (FFA), tumor necrosis factor-α (TNF-α) levels were detected, the activities of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of prostacycline (PGI2), thromboxane A 2 (TXA 2 ) and endothelin (ET) in plasma were determined. Results: There were not obvious differences in MDA, SOD, GSH-Px and FFA between the acute myocardial infarction models with blood stasis in rats and the simple acute myocardial infarction models (P 2 and NO, and the increase extents of TXA 2 , ET and TNF-α in the acute myocardial infarction models in rats with blood stasis were higher than those in the simple acute myocardial infarction models (P 2 and NO, are significant when the acute myocardial infarction models in rats with blood stasis and the simple acute myocardial infarction models are compared. The results show that it is defective to evaluate pharmacodynamics of traditional Chinese drug with only simple acute myocardial infarction models. (authors)

  17. [Tribological assessment of articular cartilage. A system for the analysis of the friction coefficient of cartilage, regenerates and tissue engineering constructs; initial results].

    Science.gov (United States)

    Schwarz, M L R; Schneider-Wald, B; Krase, A; Richter, W; Reisig, G; Kreinest, M; Heute, S; Pott, P P; Brade, J; Schütte, A

    2012-10-01

    Values for the friction coefficient of articular cartilage are given in ranges of percentage and lower and are calculated as a quotient of the friction force and the perpendicular loading force acting on it. Thus, a sophisticated system has to be provided for analysing the friction coefficient under different conditions in particular when cartilage should be coupled as friction partner. It is possible to deep-freeze articular cartilage before measuring the friction coefficient as the procedure has no influence on the results. The presented tribological system was able to distinguish between altered and native cartilage. Furthermore, tissue engineered constructs for cartilage repair were differentiated from native cartilage probes by their friction coefficient. In conclusion a tribological equipment is presented to analyze the friction coefficient of articular cartilage, in vivo generated cartilage regenerates and in vitro tissue engineered constructs regarding their biomechanical properties for quality assessment.

  18. Characterization of tissue-equivalent materials for use in construction of physical phantoms; Caracterizacao de materiais tecido-equivalentes para uso em construcao de fantomas fisicos

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Edvan V. de, E-mail: edvanmsn@hotmail.com [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFFPE), Recife, PE (Brazil); Oliveira, Alex C.H. de, E-mail: oliveira_ach@yahoo.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Vieira, Jose W., E-mail: jose.wilson59@uol.com.br [Escola Politecnica de Pernambuco (UPE), Recife, PE (Brazil); Lima, Fernando R.A., E-mail: falima@cenen.gov.br [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2013-07-01

    Phantoms are physical or computational models used to simulate the transport of ionizing radiation, their interactions with human body tissues and evaluate the deposition of energy. Depending on the application, you can build phantoms of various types and features. The physical phantoms are made of materials with behavior similar to human tissues exposed to ionizing radiation, the so-called tissue-equivalent materials. The characterization of various tissue-equivalent materials is important for the choice of materials to be used is appropriate, seeking a better cost-benefit ratio. The main objective of this work is to produce tables containing the main characteristics of tissue-equivalent materials. These tables were produced in Microsoft Office Excel. Among the main features of tissue-equivalent materials that were added to the tables, are density, chemical composition, physical state, chemical stability and solubility. The main importance of this work is to contribute to the construction of high-quality physical phantoms and avoid the waste of materials.

  19. The effect of mechanical stimulation on the maturation of TDSCs-poly(L-lactide-co-e-caprolactone)/collagen scaffold constructs for tendon tissue engineering.

    Science.gov (United States)

    Xu, Yuan; Dong, Shiwu; Zhou, Qiang; Mo, Xiumei; Song, Lei; Hou, Tianyong; Wu, Jinglei; Li, Songtao; Li, Yudong; Li, Pei; Gan, Yibo; Xu, Jianzhong

    2014-03-01

    Mechanical stimulation plays an important role in the development and remodeling of tendons. Tendon-derived stem cells (TDSCs) are an attractive cell source for tendon injury and tendon tissue engineering. However, these cells have not yet been fully explored for tendon tissue engineering application, and there is also lack of understanding to the effect of mechanical stimulation on the maturation of TDSCs-scaffold construct for tendon tissue engineering. In this study, we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation for tendon tissue engineering both in vitro and in vivo, and evaluated the utility of the transplanted TDSCs-scaffold construct to promote rabbit patellar tendon defect regeneration. TDSCs displayed good proliferation and positive expressed tendon-related extracellular matrix (ECM) genes and proteins under mechanical stimulation in vitro. After implanting into the nude mice, the fluorescence imaging indicated that TDSCs had long-term survival, and the macroscopic evaluation, histology and immunohistochemistry examinations showed high-quality neo-tendon formation under mechanical stimulation in vivo. Furthermore, the histology, immunohistochemistry, collagen content assay and biomechanical testing data indicated that dynamically cultured TDSCs-scaffold construct could significantly contributed to tendon regeneration in a rabbit patellar tendon window defect model. TDSCs have significant potential to be used as seeded cells in the development of tissue-engineered tendons, which can be successfully fabricated through seeding of TDSCs in a P(LLA-CL)/Col scaffold followed by mechanical stimulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging.

    Science.gov (United States)

    Yu, Jiao; Takanari, Keisuke; Hong, Yi; Lee, Kee-Won; Amoroso, Nicholas J; Wang, Yadong; Wagner, William R; Kim, Kang

    2013-04-01

    The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Potential of Bioactive Glasses for Cardiac and Pulmonary Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Saeid Kargozar

    2017-12-01

    Full Text Available Repair and regeneration of disorders affecting cardiac and pulmonary tissues through tissue-engineering-based approaches is currently of particular interest. On this matter, different families of bioactive glasses (BGs have recently been given much consideration with respect to treating refractory diseases of these tissues, such as myocardial infarction. The inherent properties of BGs, including their ability to bond to hard and soft tissues, to stimulate angiogenesis, and to elicit antimicrobial effects, along with their excellent biocompatibility, support these newly proposed strategies. Moreover, BGs can also act as a bioactive reinforcing phase to finely tune the mechanical properties of polymer-based constructs used to repair the damaged cardiac and pulmonary tissues. In the present study, we evaluated the potential of different forms of BGs, alone or in combination with other materials (e.g., polymers, in regards to repair and regenerate injured tissues of cardiac and pulmonary systems.

  2. Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

    Science.gov (United States)

    Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

    2011-11-01

    Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Design, construction and performance evaluation of the target tissue thickness measurement system in intraoperative radiotherapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, Mohammad Reza, E-mail: myazdani@aut.ac.ir [Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Setayeshi, Saeed, E-mail: setayesh@aut.ac.ir [Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Arabalibeik, Hossein, E-mail: arabalibeik@tums.ac.ir [Research Center for Biomedical Technology and Robotics (RCBTR), Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Akbari, Mohammad Esmaeil [Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2017-05-21

    Intraoperative electron radiation therapy (IOERT), which uses electron beams for irradiating the target directly during the surgery, has the advantage of delivering a homogeneous dose to a controlled layer of tissue. Since the dose falls off quickly below the target thickness, the underlying normal tissues are spared. In selecting the appropriate electron energy, the accuracy of the target tissue thickness measurement is critical. In contrast to other procedures applied in IOERT, the routine measurement method is considered to be completely traditional and approximate. In this work, a novel mechanism is proposed for measuring the target tissue thickness with an acceptable level of accuracy. An electronic system has been designed and manufactured with the capability of measuring the tissue thickness based on the recorded electron density under the target. The results indicated the possibility of thickness measurement with a maximum error of 2 mm for 91.35% of data. Aside from system limitation in estimating the thickness of 5 mm phantom, for 88.94% of data, maximum error is 1 mm.

  4. Comparison of the effects of streptokinase and tissue plasminogen activator on regional wall motion after first myocardial infarction: analysis by the centerline method with correction for area at risk.

    Science.gov (United States)

    Cross, D B; Ashton, N G; Norris, R M; White, H D

    1991-04-01

    In a trial of streptokinase versus recombinant tissue-type plasminogen activator (rt-PA) for a first myocardial infarction, 270 patients were randomized. Regional left ventricular function was assessed in 214 patients at 3 weeks. The infarct-related artery was the left anterior descending artery in 78 patients, the right coronary artery in 122 and a dominant left circumflex artery in 14. Analysis was by the centerline method with a novel correction for the area of myocardium at risk, whereby the search region was determined by the anatomic distribution of the infarct-related artery. Infarct-artery patency at 3 weeks was 73% in the streptokinase group and 71% in the rt-PA group. Global left ventricular function did not differ between the two groups. Mean chord motion (+/- SD) in the most hypokinetic half of the defined search region was similar in the streptokinase and rt-PA groups (-2.4 +/- 1.5 versus -2.3 +/- 1.3, p = 0.63). There were no differences in hyperkinesia of the noninfarct zone. Compared with conventional centerline analysis, regional wall motion in the defined area at risk was significantly more abnormal. The two methods correlated strongly, however (r = 0.99, p less than 0.0001), and both methods produced similar overall results. Patients with a patent infarct-related artery and those with an occluded artery at the time of catheterization had similar levels of global function (ejection fraction 58 +/- 12% versus 57 +/- 12%, p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Construction of engineering adipose-like tissue in vivo utilizing human insulin gene-modified umbilical cord mesenchymal stromal cells with silk fibroin 3D scaffolds.

    Science.gov (United States)

    Li, Shi-Long; Liu, Yi; Hui, Ling

    2015-12-01

    We evaluated the use of a combination of human insulin gene-modified umbilical cord mesenchymal stromal cells (hUMSCs) with silk fibroin 3D scaffolds for adipose tissue engineering. In this study hUMSCs were isolated and cultured. HUMSCs infected with Ade-insulin-EGFP were seeded in fibroin 3D scaffolds with uniform 50-60 µm pore size. Silk fibroin scaffolds with untransfected hUMSCs were used as control. They were cultured for 4 days in adipogenic medium and transplanted under the dorsal skins of female Wistar rats after the hUMSCs had been labelled with chloromethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (CM-Dil). Macroscopical impression, fluorescence observation, histology and SEM were used for assessment after transplantation at 8 and 12 weeks. Macroscopically, newly formed adipose tissue was observed in the experimental group and control group after 8 and 12 weeks. Fluorescence observation supported that the formed adipose tissue originated from seeded hUMSCs rather than from possible infiltrating perivascular tissue. Oil red O staining of newly formed tissue showed that there was substantially more tissue regeneration in the experimental group than in the control group. SEM showed that experimental group cells had more fat-like cells, whose volume was larger than that of the control group, and degradation of the silk fibroin scaffold was greater under SEM observation. This study provides significant evidence that hUMSCs transfected by adenovirus vector have good compatibility with silk fibroin scaffold, and adenoviral transfection of the human insulin gene can be used for the construction of tissue-engineered adipose. Copyright © 2013 John Wiley & Sons, Ltd.

  6. Identification of local myocardial repolarization time by bipolar electrode potential.

    Science.gov (United States)

    Namba, Tsunetoyo; Todo, Takahiro; Yao, Takenori; Ashihara, Takashi; Haraguchi, Ryo; Nakazawa, Kazuo; Ikeda, Takanori; Ohe, Tohru

    2007-01-01

    The aim of this study was to investigate whether bipolar electrode potentials (BEPs) reflect local myocardial repolarization dynamics, using computer simulation. Simulated action potential and BEP mapping of myocardial tissue during fibrillation was performed. The BEP was modified to make all the fluctuations have the same polarity. Then, the modified BEP (mBEP) was transformed to "dynamic relative amplitude" (DRA) designed to make all the fluctuations have the similar amplitude. The repolarization end point corresponded to the end of the repolarization-related small fluctuation that clearly appeared in the DRA of mBEP. Using the DRA of mBEP, we could reproduce the repolarization dynamics in the myocardial tissue during fibrillation. The BEP may facilitate identifying the repolarization time. Furthermore, BEP mapping has the possibility that it would be available for evaluating repolarization behavior in myocardial tissue even during fibrillation. The accuracy of activation-recovery interval was also reconfirmed.

  7. Fact versus artifact: Avoiding erroneous estimates of sulfated glycosaminoglycan content using the dimethylmethylene blue colorimetric assay for tissue-engineered constructs

    Directory of Open Access Journals (Sweden)

    CH Zheng

    2015-04-01

    Full Text Available The 1,9-dimethylmethylene blue (DMMB assay is widely used to quantify sulfated glycosaminoglycan (sGAG contents of engineered tissues, culture media, tissue samples and bodily fluids, but the assay is subject to interference from polyanions such as hyaluronic acid (HA, DNA and RNA. We examined whether specific combinations of dye pH and absorbance wavelength could minimize non-sGAG artifacts without compromising DMMB assay sensitivity. HA and DNA solutions generated substantial signal at pH 3 but not at pH 1.5. Reducing dye pH did not significantly alter sGAG measurements for normal cartilage and meniscus tissues, but eliminated anomalously high apparent sGAG contents for enzymatically isolated chondrocytes, adipose-derived stem cell (ADSC-agarose constructs and ADSC pellets. In a cartilage tissue-engineering case study, pH 3 dye indicated high apparent sGAG readings throughout culture in both basal and chondrogenic media, with a marked decline between day 14 and 21 for chondrogenic constructs. The pH 1.5 dye, however, indicated minimal sGAG accumulation in basal medium and stable sGAG content throughout culture in chondrogenic medium. As it is often difficult to know a priori whether all groups in a study will have sGAG contents high enough to overwhelm artifacts, we recommend modifying the standard DMMB assay to reduce the risk of spurious findings in tissue engineering and clinical research. Specifically, we recommend shifting to a pH 1.5 DMMB dye and basing quantification on the absorbance difference between 525 nm (µ peak and 595 nm (β peak to compensate for the moderate loss of sensitivity associated with reducing the dye pH.

  8. Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

    Science.gov (United States)

    Dearth, Christopher L; Slivka, Peter F; Stewart, Scott A; Keane, Timothy J; Tay, Justin K; Londono, Ricardo; Goh, Qingnian; Pizza, Francis X; Badylak, Stephen F

    2016-02-01

    Extracellular matrix (ECM) has been used as a biologic scaffold material to both reinforce the surgical repair of soft tissue and serve as an inductive template to promote a constructive tissue remodeling response. Success of such an approach is dependent on macrophage-mediated degradation and remodeling of the biologic scaffold. Macrophage phenotype during these processes is a predictive factor of the eventual remodeling outcome. ECM scaffolds have been shown to promote an anti-inflammatory or M2-like macrophage phenotype in vitro that includes secretion of downstream products of cycolooxygenases 1 and 2 (COX1/2). The present study investigated the effect of a common COX1/2 inhibitor (Aspirin) on macrophage phenotype and tissue remodeling in a rodent model of ECM scaffold treated skeletal muscle injury. Inhibition of COX1/2 reduced the constructive remodeling response by hindering myogenesis and collagen deposition in the defect area. The inhibited response was correlated with a reduction in M2-like macrophages in the defect area. The effects of Aspirin on macrophage phenotype were corroborated using an established in vitro macrophage model which showed a reduction in both ECM induced prostaglandin secretion and expression of a marker of M2-like macrophages (CD206). These results raise questions regarding the common peri-surgical administration of COX1/2 inhibitors when biologic scaffold materials are used to facilitate muscle repair/regeneration. COX1/2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely administered post-surgically for analgesic purposes. While COX1/2 inhibitors are important in pain management, they have also been shown to delay or diminish the healing process, which calls to question their clinical use for treating musculotendinous injuries. The present study aimed to investigate the influence of a common NSAID, Aspirin, on the constructive remodeling response mediated by an ECM scaffold (UBM) in a rat skeletal

  9. Development and validation of a novel bioreactor system for load- and perfusion-controlled tissue engineering of chondrocyte-constructs

    NARCIS (Netherlands)

    Schulz, R.M.; Wüstneck, N.; Donkelaar, van C.C.; Shelton, J.C; Bader, A.

    2008-01-01

    Osteoarthritis is a severe socio-economical disease,for which a suitable treatment modality does not exist.Tissue engineering of cartilage transplants is the most promisingmethod to treat focal cartilage defects. However,current culturing procedures do not yet meet the requirementsfor clinical

  10. The relationship between myocardial blood flow and myocardial viability after reperfusion. Myocardial viability assessed by 15O-water-PET

    International Nuclear Information System (INIS)

    Tsukagoshi, Joichi

    1994-01-01

    The purpose of this study was to examine the relationship between myocardial blood flow and myocardial viability in the ischemic canine myocardium after reperfusion. Transient ischemia was induced by 60-, 90-, and 180-minute occlusion of the left anterior descending coronary artery. Myocardial blood flow (MBF) was measured in the areas in which regional contractility was severely impaired (ehocardiographically akinetic or dyskinetic) in the early reperfusion period by 15 O-water positron emission tomography (PET) 12 hours and 4 weeks after reperfusion. An MBF ratio of ischemic to nonischemic regions 12 hours after reperfusion was inversely correlated with the amount of histologically determined tissue necrosis (r=-0.74). The regional contractility recovered 4 weeks later in the areas where an MBF ratio was 0.48 or greater, but did not recover in the areas with a lower MBF ratio. Thus, myocardial viability can be appropriately predicted in the early phase of myocardial perfusion by PET with 15 O-water even in the absence of metabolic imaging. (author)

  11. Construction and characterization of an electrospun tubular scaffold for small-diameter tissue-engineered vascular grafts: a scaffold membrane approach.

    Science.gov (United States)

    Hu, Jin-Jia; Chao, Wei-Chih; Lee, Pei-Yuan; Huang, Chih-Hao

    2012-09-01

    Based on a postulate that the microstructure of a scaffold can influence that of the resulting tissue and hence its mechanical behavior, we fabricated a small-diameter tubular scaffold (∼3 mm inner diameter) that has a microstructure similar to the arterial media using a scaffold membrane approach. Scaffold membranes that contain randomly oriented, moderately aligned, or highly aligned fibers were fabricated by collecting electrospun poly([epsilon]-caprolactone) fibers on a grounded rotating drum at three different drum rotation speeds (250, 1000, and 1500 rpm). Membranes of each type were wrapped around a small-diameter mandrel to form the tubular scaffolds. Particularly, the tubular scaffolds with three different off-axis fiber angles (30, 45, and 60 degree) were formed using membranes that contain aligned fibers. These scaffolds were subjected to biaxial mechanical testing to examine the effects of fiber directions as well as the distribution of fiber orientations on their mechanical properties. The circumferential elastic modulus of the tubular scaffold was closely related to the fiber directions; the larger the off-axis fiber angle the greater the circumferential elastic modulus. The distribution of fiber orientations, on the other hand, manifested itself in the mechanical behavior via the Poisson effect. Similar to cell sheet-based vascular tissue engineering, tubular cell-seeded constructs were prepared by wrapping cell-seeded scaffold membranes, alleviating the difficulty associated with cell seeding in electrospun scaffolds. Histology of the construct illustrated that cells were aligned to the fiber directions in the construct, demonstrating the potential to control the microstructure of tissue-engineered vascular grafts using the electrospun scaffold membrane. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Sudhira Begum

    2007-12-01

    Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

  13. Nanoscale Resolution 3D Printing with Pin-Modified Electrified Inkjets for Tailorable Nano/Macrohybrid Constructs for Tissue Engineering.

    Science.gov (United States)

    Kim, Jeong In; Kim, Cheol Sang

    2018-04-18

    Cells respond to their microenvironment, which is of a size comparable to that of the cells. The macroscale features of three-dimensional (3D) printing struts typically result in whole cell contact guidance (CCG). In contrast, at the nanoscale, where features are of a size similar to that of receptors of cells, the response of cells is more complex. The cell-nanotopography interaction involves nanoscale adhesion localized structures, which include cell adhesion-related particles that change in response to the clustering of integrin. For this reason, it is necessary to develop a technique for manufacturing tailorable nano/macrohybrid constructs capable of freely controlling the cellular activity. In this study, a hierarchical 3D nano- to microscale hybrid structure was fabricated by combinational processing of 3D printing and electrified inkjet spinning via pin motions. This method overcomes the disadvantages of conventional 3D printing, providing a novel combinatory technique for the fabrication of 3D hybrid constructs with excellent cell proliferation. Through a pin-modified electrified inkjet spinning, we have successfully fabricated customizable nano-/microscale hybrid constructs in a fibrous or mesh form, which can control the cell fate. We have conducted this study of cell-topography interactions from the fabrication approach to accelerate the development of next-generation 3D scaffolds.

  14. Assessment of myocardial viability by MR imaging

    International Nuclear Information System (INIS)

    Sandstede, Joern J.W.

    2003-01-01

    Diagnosis of myocardial viability after infarction focuses on the prediction of functional improvement of dysfunctional myocardium after revascularization therapy. Magnetic resonance imaging provides different approaches for the detection of myocardial viability. Measurement of end-diastolic wall thickness is easy to perform and has a high sensitivity, but a low specificity, and can only be used 4 months after myocardial infarction due to infarct healing processes. Low-dose dobutamine stress has a good sensitivity with a high specificity for the prediction of wall motion improvement, but this is only true for patients with a singular dysfunctional area and only slightly depressed cardiac function. Late enhancement allows for direct visualization of necrotic or scarred tissue. By measuring the transmural extent of late enhancement, the probability of mechanical improvement can precisely be given. Imaging of microvascular obstruction by first-pass perfusion or late enhancement gives additional information on viability and patient prognosis. Metabolic imaging techniques, such as 31 P-MR spectroscopy and 23 Na-MR imaging, provide further insights into the mechanisms of myocardial infarction and viability. In conclusion, cardiac MRI offers several clinically usable approaches for the assessment of myocardial viability and will probably become the method of choice in the near future. (orig.)

  15. 3D Printing of Personalized Organs and Tissues

    Science.gov (United States)

    Ye, Kaiming

    2015-03-01

    Authors: Kaiming Ye and Sha Jin, Department of Biomedical Engineering, Watson School of Engineering and Applied Science, Binghamton University, State University of New York, Binghamton, NY 13902-6000 Abstract: Creation of highly organized multicellular constructs, including tissues and organs or organoids, will revolutionize tissue engineering and regenerative medicine. The development of these technologies will enable the production of individualized organs or tissues for patient-tailored organ transplantation or cell-based therapy. For instance, a patient with damaged myocardial tissues due to an ischemic event can receive a myocardial transplant generated using the patient's own induced pluripotent stem cells (iPSCs). Likewise, a type-1 diabetic patient can be treated with lab-generated islets to restore his or her physiological insulin secretion capability. These lab-produced, high order tissues or organs can also serve as disease models for pathophysiological study and drug screening. The remarkable advances in stem cell biology, tissue engineering, microfabrication, and materials science in the last decade suggest the feasibility of generating these tissues and organoids in the laboratory. Nevertheless, major challenges still exist. One of the critical challenges that we still face today is the difficulty in constructing or fabricating multicellular assemblies that recapitulate in vivo microenvironments essential for controlling cell proliferation, migration, differentiation, maturation and assembly into a biologically functional tissue or organoid structure. These challenges can be addressed through developing 3D organ and tissue printing which enables organizing and assembling cells into desired tissue and organ structures. We have shown that human pluripotent stem cells differentiated in 3D environments are mature and possess high degree of biological function necessary for them to function in vivo.

  16. About the specialized myocardial conducting tissue.

    Science.gov (United States)

    de Micheli Serra, Alfredo; Iturralde Torres, Pedro; Aranda Fraustro, Alberto

    2013-01-01

    The chronological succession of discoveries on the location and structure of the atrio-ventricular conducting system are described. The starting point of this system is located in the sinus atrial node, identified by the English scientists A. Keith and M. W. Flack in 1907. The atrioventricular conducting system was pointed out by the Swiss physician Wilhelm His Jr. in 1893. The atrioventricular node (AV) was first identified by the Japanese pathologist Sumao Tawara and his German professor Ludwig Aschoff in 1906. Likewise the structure and routes of the three internodal bundles are described. These bundles include: Bachmann's bundle (1916) connecting the right with the left atrium and the AV node; the middle Wenckebach's bundle (1910) and the posterior or Thörel's bundle (1910), extending from the region of the sinus atrial node towards the posterior margin of the AV node. Lastly, the ventricular left and right conduction systems are detailed. These include the main trunk and their peripheral subdivisions with respective networks. Regarding the controversial existence of the left middle subdivision, it can exist in animal and human hearts. Nevertheless, an intermediate left septal network of specialized fibers seems to act as a functional equivalent of this subdivision. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  17. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  18. Construction of an efficient two-photon fluorescent probe for imaging nitroreductase in live cells and tissues

    Science.gov (United States)

    Zhou, Liyi; Gong, Liang; Hu, Shunqin

    2018-06-01

    Compared with traditional confocal microscopy, two-photon fluorescence microscopy (TPFM), which excites a two-photon (TP) fluorophore by near-infrared light, provides improved three-dimensional image resolution with increased tissue-image depth (>500 μm) and an extended observation time. Therefore, the development of novel functional TP fluorophores has attracted great attention in recent years. Herein, a novel TP fluorophore CM-NH2, which have the donor-π-acceptor (D-π-A)-structure, was designed and synthesized. We further used this dye developed a new type of TP fluorescent probe CM-NO2 for detecting nitroreductase (NTR). Upon incubated with NTR for 15 min, CM-NO2 displayed a 90-fold fluorescence enhancement at 505 nm and the maximal TP action cross-section value after reaction was detected and calculated to be 200 GM at 760 nm. The probe exhibited excellent properties such as high sensitivity, high selectivity, low cytotoxicity, and high photostability. Moreover, the probe was utilized to image the tumor hypoxia in live HeLa cells. Finally, using the CM-NO2 to image NTR in tissues was demonstrated.

  19. Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

    Science.gov (United States)

    Korosoglou, G; Hansen, A; Bekeredjian, R; Filusch, A; Hardt, S; Wolf, D; Schellberg, D; Katus, H A; Kuecherer, H

    2006-03-01

    To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

  20. Construction of multifunctional proteins for tissue engineering: epidermal growth factor with collagen binding and cell adhesive activities.

    Science.gov (United States)

    Hannachi Imen, Elloumi; Nakamura, Makiko; Mie, Masayasu; Kobatake, Eiry

    2009-01-01

    The development of different techniques based on natural and polymeric scaffolds are useful for the design of different biomimetic materials. These approaches, however, require supplementary steps for the chemical or physical modification of the biomaterial. To avoid such steps, in the present study, we constructed a new multifunctional protein that can be easily immobilized onto hydrophobic surfaces, and at the same time helps enhance specific cell adhesion and proliferation onto collagen substrates. A collagen binding domain was fused to a previously constructed protein, which had an epidermal growth factor fused to a hydrophobic peptide that allows for cell adhesion. The new fusion protein, designated fnCBD-ERE-EGF is produced in Escherichia coli, and its abilities to bind to collagen and promote cell proliferation were investigated. fnCBD-ERE-EGF was shown to keep both collagen binding and cell growth-promoting activities comparable to those of the corresponding unfused proteins. The results obtained in this study also suggest the use of a fnCBD-ERE-EGF as an alternative for the design of multifunctional ECM-bound growth factor based materials.

  1. Effect of Kaempferol Pretreatment on Myocardial Injury in Rats.

    Science.gov (United States)

    Vishwakarma, Anamika; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Kandasamy, Arunvikram; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Kumar, Ajay; Kumar, Asok; Kumar, Dinesh

    2018-01-20

    The present study was undertaken to evaluate the effect of kaempferol in isoprenaline (ISP)-induced myocardial injury in rats. ISP was administered subcutaneously for two subsequent days to induce myocardial injury. Assessment of myocardial injury was done by estimation of hemodynamic functions, myocardial infarcted area, cardiac injury markers, lipid profile, oxidative stress, pro-inflammatory cytokines and histopathology of heart and liver. Rats pretreated with kaempferol showed reduction in the myocardial infarcted area and heart rate. However, no improvement was observed in change in body weight, mean arterial, systolic and diastolic blood pressure. Kaempferol showed significant decrease in serum LDH, CK-MB, troponin-I and lipid profile. However, highest dose of kaempferol did not reduce the serum triglyceride level. Further, antioxidant enzymes, SOD and catalase, were also higher. However, reduced glutathione, serum SGOT and creatinine did not show any improvement. Kaempferol showed reduction in MDA level. Kaempferol at highest dose showed reduction in pro-MMP-2 expression and MMP-9 level. mRNA expression level of TNF-α was not different in kaempferol-pretreated myocardial injured rats with ISP-alone group. Pretreatment with kaempferol at highest dose showed mild mononuclear infiltration and degenerative changes in heart tissue section of myocardial injured rats. Rats pretreated with kaempferol at higher concentration showed normal cordlike arrangement of hepatocytes with moderate swelling of hepatocytes (vacuolar degeneration) around the central vein. Study suggests that kaempferol attenuated lipid profile, infarcted area and oxidative stress in ISP-induced myocardial injury in rats.

  2. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism

    DEFF Research Database (Denmark)

    Høst, N B; Hansen, S S; Jensen, L T

    1994-01-01

    The objective of the study was to monitor collagen metabolism after thrombolytic therapy. Sequential measurements of serum aminoterminal type-III procollagen propeptide (S-PIIINP) and carboxyterminal type-I procollagen propeptide (S-PICP) were made in 62 patients suspected of acute myocardial.......05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered...... for at least 6 months. Furthermore, fibrin-specific and nonspecific thrombolytic agents appear to affect collagen metabolism differently....

  3. Automatic extraction of left ventricle in SPECT myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Liu Li; Zhao Shujun; Yao Zhiming; Wang Daoyu

    1999-01-01

    An automatic method of extracting left ventricle from SPECT myocardial perfusion data was introduced. This method was based on the least square analysis of the positions of all short-axis slices pixels from the half sphere-cylinder myocardial model, and used a iterative reconstruction technique to automatically cut off the non-left ventricular tissue from the perfusion images. Thereby, this technique provided the bases for further quantitative analysis

  4. Myocardial overexpression of TIMP3 after myocardial infarction exerts beneficial effects by promoting angiogenesis and suppressing early proteolysis.

    Science.gov (United States)

    Takawale, Abhijit; Zhang, Pu; Azad, Abul; Wang, Wang; Wang, Xiuhua; Murray, Allan G; Kassiri, Zamaneh

    2017-08-01

    Myocardial infarction (MI) results in loss of cardiomyocytes, adverse extracellular matrix (ECM) and structural remodeling, and left ventricular (LV) dilation and dysfunction. Tissue inhibitors of metalloproteinase (TIMPs) inhibit matrix metalloproteinases (MMPs), the main regulators of ECM turnover. TIMPs also have MMP-independent functions. TIMP3 levels are reduced in the heart within 24 h of MI in mice. We investigated if overexpression of TIMP3 post-MI limits adverse remodeling and LV dilation and dysfunction. MI was induced by left anterior descending coronary artery ligation in 10- to 12-wk-old male C57BL/6J mice, and adenoviral constructs expressing human (h)TIMP3 (Ad-hTIMP3) or no TIMP (Ad-Null) were injected in the peri-infarct zone (5.4 × 10 7 plaque-forming units/heart, 5 injections/heart). Cardiac function assessed by echocardiography showed improved LV physiology and reduced LV dilation after TIMP3 overexpression compared with the Ad-Null-MI group. Post-MI adverse remodeling was attenuated in the Ad-hTIMP3-MI group, as assessed by greater cardiomyocyte density, less infarct expansion, and ECM disruption. TIMP3 overexpression blunted the early rise in proteolytic activities post-MI. A higher density of coronary arteries and a greater number of proliferating endothelial cells were detected in the infarct and peri-infarct regions in the Ad-hTIMP3-MI group compared with the Ad-Null-MI group. In vitro three-dimensional angiogenesis assay confirmed that recombinant TIMP3 promotes angiogenesis in human endothelial cells, although biphasically and in a dose-dependent manner. Intriguingly, overexpression of Ad-hTIMP3 at 10-fold higher concentration had no beneficial effects, consistent with antiangiogenic effects of TIMP3 at higher doses. In conclusion, optimal overexpression of TIMP3 can be a promising therapeutic approach to limit adverse post-MI remodeling by dually inhibiting early proteolysis and promoting angiogenesis. NEW & NOTEWORTHY Here, we report

  5. Effects of stroke on medical resource use and costs in acute myocardial infarction. GUSTO I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Study

    NARCIS (Netherlands)

    C.Y. Tung; H.D. White (Harvey); N. Clapp-Channing; D.B. Mark (Daniel); M.L. Simoons (Maarten); R.M. Califf (Robert); J.M. Gore (Joel); C.B. Granger (Christopher); M.A. Sloan (Michael); E.J. Topol (Eric); J.D. Knight (David); W.D. Weaver; K.W. Mahaffey (Kenneth)

    1999-01-01

    textabstractBACKGROUND: Stroke occurs concurrently with myocardial infarction (MI) in approximately 30 000 US patients each year. This number is expected to rise with the increasing use of thrombolytic therapy for MI. However, no data exist for the economic effect of stroke in the

  6. Generating 3D tissue constructs with mesenchymal stem cells and a cancellous bone graft for orthopaedic applications

    International Nuclear Information System (INIS)

    Arca, Turkan; Genever, Paul; Proffitt, Joanne

    2011-01-01

    Bone matrix (BM) is an acellular crosslinked porcine-derived cancellous bone graft, and therefore may provide advantages over other synthetic and naturally derived materials for use in orthopaedic surgery. Here, we analysed the potential of BM to support the growth and differentiation of primary human multipotent stromal cells/mesenchymal stem cells (MSCs) in order to predict in vivo bone regeneration events. Imaging with laser scanning confocal microscopy and scanning electron microscopy showed that 1 day after static seeding, a dense population of viable MSCs could be achieved on scaffolds suggesting they could be used for in vivo delivery of cells to the implant site. Long-term growth analysis by confocal imaging and histology demonstrated that BM was permissive to the growth and the 3D population of primary MSCs and an enhanced green fluorescent protein expressing osteosarcoma cell line, eGFP.MG63s, over several days in culture. Measurement of alkaline phosphatase (ALP) activities and mRNA expression levels of osteogenic markers (Runx-2, ALP, collagen type I, osteonectin, osteocalcin and osteopontin) indicated that BM supported osteogenesis of MSCs when supplemented with osteogenic stimulants. Upregulation of some of these osteogenic markers on BM, but not on tissue culture plastic, under non-osteogenic conditions suggested that BM also had osteoinductive capacities.

  7. Generating 3D tissue constructs with mesenchymal stem cells and a cancellous bone graft for orthopaedic applications

    Energy Technology Data Exchange (ETDEWEB)

    Arca, Turkan; Genever, Paul [Department of Biology, University of York, York, YO10 5DD (United Kingdom); Proffitt, Joanne, E-mail: paul.genever@york.ac.uk [TSL Centre of Biologics, Covidien, Allerton Bywater, Castleford, WF10 2DB (United Kingdom)

    2011-04-15

    Bone matrix (BM) is an acellular crosslinked porcine-derived cancellous bone graft, and therefore may provide advantages over other synthetic and naturally derived materials for use in orthopaedic surgery. Here, we analysed the potential of BM to support the growth and differentiation of primary human multipotent stromal cells/mesenchymal stem cells (MSCs) in order to predict in vivo bone regeneration events. Imaging with laser scanning confocal microscopy and scanning electron microscopy showed that 1 day after static seeding, a dense population of viable MSCs could be achieved on scaffolds suggesting they could be used for in vivo delivery of cells to the implant site. Long-term growth analysis by confocal imaging and histology demonstrated that BM was permissive to the growth and the 3D population of primary MSCs and an enhanced green fluorescent protein expressing osteosarcoma cell line, eGFP.MG63s, over several days in culture. Measurement of alkaline phosphatase (ALP) activities and mRNA expression levels of osteogenic markers (Runx-2, ALP, collagen type I, osteonectin, osteocalcin and osteopontin) indicated that BM supported osteogenesis of MSCs when supplemented with osteogenic stimulants. Upregulation of some of these osteogenic markers on BM, but not on tissue culture plastic, under non-osteogenic conditions suggested that BM also had osteoinductive capacities.

  8. The prognostic value of bleeding academic research consortium (BARC)-defined bleeding complications in ST-segment elevation myocardial infarction: a comparison with the TIMI (Thrombolysis In Myocardial Infarction), GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries), and ISTH (International Society on Thrombosis and Haemostasis) bleeding classifications

    NARCIS (Netherlands)

    Kikkert, Wouter J.; van Geloven, Nan; van der Laan, Mariet H.; Vis, Marije M.; Baan, Jan; Koch, Karel T.; Peters, Ron J.; de Winter, Robbert J.; Piek, Jan J.; Tijssen, Jan G. P.; Henriques, José P. S.

    2014-01-01

    The aim of the present analysis was to compare 1-year mortality prediction of Bleeding Academic Research Consortium (BARC)-defined bleeding complications with existing bleeding definitions in patients with ST-segment elevation myocardial infarction (STEMI) and to investigate the prognostic value of

  9. Management of myocardial damage in muscular dystrophy

    International Nuclear Information System (INIS)

    Tamura, Takuhisa

    2011-01-01

    Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future. (author)

  10. Myocardial scintigraphy with thallium-201

    Energy Technology Data Exchange (ETDEWEB)

    Lichte, H [Zentralkrankenhaus Gauting (Germany, F.R.). Nuklearmedizinische Abt.

    1977-04-01

    Myocardial scintigraphy with /sup 201/thallium is a non-invasive method for detection of myocardial infarction and coronary heart disease. Redistribution-analysis as a sequential-scintigraphy of an exercise-scan permits to distinguish between myocardial scars and coronary vessel disease.

  11. Assessment for prognosis during and after myocardial infarction. A plea for a stratified approach

    NARCIS (Netherlands)

    P.G. Hugenholtz (Paul); P.M. Fioretti (Paolo); M.L. Simoons (Maarten); P.W.J.C. Serruys (Patrick); J.R.T.C. Roelandt (Jos)

    1986-01-01

    textabstractRight after the first signs and symptoms of acute myocardial infarctions the prognosis is determined by the interventions which are carried out at that time. Preservation of as much myocardial tissue is the key element. Early deobstruction and reperfusion of the myocardium at jeopardy

  12. Myocardial myoglobin release after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, P S; Saltissi, S; Coltart, D J; Croft, D N [Saint Thomas' Hospital, London (UK)

    1980-03-01

    The magnitude and time course of myoglobin release from the myocardium following infarction was assessed by radioimmunoassay. The assay showed acceptable precision over a working range from 50 to 750 ng cm/sup -3/, provided careful control of the assay temperature was maintained. The use of this radioimmunoassay as an early diagnostic test for infarction and as a potential measure of the extent of necrosis is considered and comparison made with the release of CK-MB, the myocardial specific isoenzyme of creatine kinase. Of the twenty patients studied with myocardial infarction, all had elevated levels of serum myoglobin including those admitted within 3 hours of the onset of pain. In contrast, CK-MB was not detected in the serum within 5 hours of the onset of pain. Peak serum levels of myoglobin (mean 852 +- 365 ng cm/sup -3/) and CK-MB (mean 71 +- 25 mIU cm/sup -3/) were detected at 8-16 hours and 20-24 hours respectively after the onset of pain. A comparison of peak serum levels of myoglobin and CK-MB showed a good correlation (r = 0.84).

  13. Reversible myocardial ischaemia or irreversible myocardial fibrosis

    International Nuclear Information System (INIS)

    Mathey, D.; Hanrath, P.; Kupper, W.; Bleifeld, W.; Montz, R.; Knop, J.; Stritzke, P.; Kroeger, E.; Bleese, N.

    1978-01-01

    The results of biphasis 201 thallium ( 201 Tl) scanning were compared with those of coronary arteriography, left ventricular angiography and stress ECG in 56 patients with coronary artery disease and six with no evidence of heart disease. There were 104 201 Tl defects, 50 of them reversible. The defects were always located in the area supplied by a critically stenotic coronary artery. Correlation of regional wall motion with 201 Tl activity demonstrated that in all forms of abnormal wall motion there was either ischaemia or fibrosis. The resting LV angiogram thus does not make it possible to distinguish between myocardial ischaemia and fibrosis. Taking the LV angiogram as a standard, the rate of false-positive 201 Tl scintigrams was 5%, that of false-negative ones 23%. The biphasic 201 Tl scintigram was more sensitive than the stress ECG in detecting myocardial ischaemia. It furthermore made it possible to localize the ischaemic (or fibrotic) region within the LV and to estimate its size. (orig.) [de

  14. 3D-fibroblast tissues constructed by a cell-coat technology enhance tight-junction formation of human colon epithelial cells.

    Science.gov (United States)

    Matsusaki, Michiya; Hikimoto, Daichi; Nishiguchi, Akihiro; Kadowaki, Koji; Ohura, Kayoko; Imai, Teruko; Akashi, Mitsuru

    2015-02-13

    Caco-2, human colon carcinoma cell line, has been widely used as a model system for intestinal epithelial permeability because Caco-2 cells express tight-junctions, microvilli, and a number of enzymes and transporters characteristic of enterocytes. However, the functional differentiation and polarization of Caco-2 cells to express sufficient tight-junctions (a barrier) usually takes over 21 days in culture. This may be due to the cell culture environment, for example inflammation induced by plastic petri dishes. Three-dimensional (3D) sufficient cell microenvironments similar to in vivo natural conditions (proteins and cells), will promote rapid differentiation and higher functional expression of tight junctions. Herein we report for the first time an enhancement in tight-junction formation by 3D-cultures of Caco-2 cells on monolayered (1L) and eight layered (8L) normal human dermal fibroblasts (NHDF). Trans epithelial electric resistance (TEER) of Caco-2 cells was enhanced in the 3D-cultures, especially 8L-NHDF tissues, depending on culture times and only 10 days was enough to reach the same TEER value of Caco-2 monolayers after a 21 day incubation. Relative mRNA expression of tight-junction proteins of Caco-2 cells on 3D-cultures showed higher values than those in monolayer structures. Transporter gene expression patterns of Caco-2 cells on 3D-constructs were almost the same as those of Caco-2 monolayers, suggesting that there was no effect of 3D-cultures on transporter protein expression. The expression correlation between carboxylesterase 1 and 2 in 3D-cultures represented similar trends with human small intestines. The results of this study clearly represent a valuable application of 3D-Caco-2 tissues for pharmaceutical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Abnormal myocardial capillary density in apical hypertrophic cardiomyopathy can be assessed by myocardial contrast echocardiography

    International Nuclear Information System (INIS)

    Moon, Jeonggeun; Cho, In-Jeong; Shim, Chi-Young; Ha, Jong-Won; Jang, Yangsoo; Chung, Namsik; Rim, Se-Joong

    2010-01-01

    Myocardial ischemia and dysfunction can occur in hypertrophic cardiomyopathy (HCM) because of the high muscle-to-blood ratio, even without significant coronary artery disease. Microbubbles reside only in the intravascular space and myocardial video-intensity during systole results mostly from microbubbles within capillaries. The hypothesis explored in the present study was that an abnormal capillary density in apical HCM (ApHCM) can be demonstrated using myocardial contrast echocardiography (MCE). The 56 patients were investigated (31 males, age 58±9 years; 33 ApHCM, 9 hypertensive left ventricular hypertrophy [LVH], 14 controls). MCE was performed with low-mechanical-index power modulation imaging. Tissue Doppler imaging to assess myocardial contractile function was obtained at the mitral annulus (S'), and 99m Tc-MIBI single photon emission computed tomography (SPECT) was also performed. All ApHCM patients exhibited perfusion defects at the hypertrophied segments in the systolic phase during MCE, whereas SPECT showed normal or rather increased perfusion at those sites. The cyclic variation of video-intensity was exaggerated in ApHCM when compared with the LVH or control group (% of [systolic video-intensity]/[diastolic video-intensity]: 33.0±12.3%, 88.3±19.2% and 79.4±13.9%, respectively [P<0.05]). Concurrently, MCE cyclic variation and perfusion defect size were related to decreased S' (P<0.05 for all). A perfusion defect at the hypertrophied segment, representing abnormal myocardial capillary density, was observed in ApHCM patients during MCE. The extent of MCE cyclic variation and the perfusion defect size both correlate with decreased myocardial contractile property in ApHCM. (author)

  16. Myocardial perfusion SPECT imaging in patients with myocardial bridging

    International Nuclear Information System (INIS)

    Fang Wei; Qiu Hong; Yang Weixian; Wang Feng; He Zuoxiang

    2008-01-01

    Objective: Stress myocardial perfusion SPECT imaging was used to assess myocardial ischemia in patients with myocardial bridging. Methods: Ninety-six patients with myocardial bridging of the left anterior descending artery documented by coronary angiography were included in this study. All under- went exercise or pharmacological stress myocardial perfusion SPECT assessing myocardial ischemia. None had prior myocardial infarction. One year follow-up by telephone interview was performed in all patients. Results The mean stenotic severity of systolic phase on angiography was (65 ± 19)%. In the SPECT study, 20 of 96 (20.8%) patients showed abnormal perfusion. This percentage was significantly higher than that of stress electrocardiogram (ECG). The higher positive rate of SPECT perfusion images was showed in the group of patients with severe systolic narrowing (≥75%) than that with mild-to-moderate systolic narrowing (50% vs 6.3%, P<0.001). The prevalence of abnormal image was significantly higher in ELDERLY PEOPLE; patients with STT change on rest ECG than in those with normal rest ECG (54.2% vs 9.7%, P<0.001). During follow-up, one patient with abnormal SPECT perfusion image sustained angina and accepted percutaneous coronary intervention, and no cardiac event occurred in patients with normal images. Conclusions: Stress myocardial perfusion SPECT imaging can be used effectively for assessing myocardial ischemia and has potential prognostic value for patients with myocardial bridging. (authors)

  17. Correlation of the myocardial perfusion corrected by attenuation with the coronariography. Preliminary results

    International Nuclear Information System (INIS)

    Garcia C, S.E.; Garcia O, R.

    2005-01-01

    The attenuation that suffers the radiation in the soft tissues of the hinders the appropriate interpretation of the myocardial perfusion studies, for what have been implemented attenuation correction systems to reduce the attenuation for soft tissues and to provide myocardial perfusion images more accurate in the diagnosis of coronary illness. The objective was to evaluate the utility of an attenuation correction system (with source of Gadolinium 153) to minimize the devices that look like true defects of myocardial perfusion, caused by soft tissues (mammary tissue, thoracic wall, abdomen, left hemi diaphragm), and to compare those interpretations of the studies with the interpretations of the corresponding coronariographies. The method consists of 95 electronic files which were revised with the concept of heart catheterization, being identified 20 patients from the masculine sex to those that underwent coronariography among May 1999 and December 2002, and that they had study of myocardial perfusion in a maximum period of 3 months foresaw to the invasive procedure. (Author)

  18. Cardioprotection against experimental myocardial ischemic injury using cornin

    Directory of Open Access Journals (Sweden)

    Y. Xu

    2016-01-01

    Full Text Available Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

  19. Myocardial injury and protection related to cardiopulmonary bypass

    NARCIS (Netherlands)

    de Hert, Stefan; Moerman, Anneliese

    2015-01-01

    During cardiac surgery with cardiopulmonary bypass, the heart is isolated from the circulation. This inevitably induces myocardial ischemia. In addition to this ischemic insult, an additional hit will occur upon reperfusion, which may worsen the extent of tissue damage and organ dysfunction. Over

  20. Vitamin D Levels and myocardial function in preterm infants

    LENUS (Irish Health Repository)

    Armstrong, K

    2013-08-20

    Bakground Low Vitamin D levels have been linked to cardiac failure in the adults and children. Tissue Doppler Imaging (TDI) is evolving as a superior measure of subtle changes in myocardial contractility in preterm infants. We aimed to correlate Vitamin D levels at birth with TDI measures of systolic and diastolic function. \\r\

  1. Biomimetic material strategies for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Prabhakaran, Molamma P.; Venugopal, J.; Kai, Dan; Ramakrishna, Seeram

    2011-01-01

    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  2. Biomimetic material strategies for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Venugopal, J. [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (Singapore); Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

    2011-04-08

    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  3. Myocardial ischemia in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio

    2000-01-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  4. Acute myocardial infarcts

    International Nuclear Information System (INIS)

    Just, H.

    1988-01-01

    Acute myocardial infarction is a major complication of stenosing coronary artery disease and constitutes the most frequent single cause of death. It is caused by thrombotic occlusion of one of the major epicardial coronary arterial branches in most cases. Sudden death due to ventricular fibrillation is responsible for the majority of early fatalities. In 60% of all fatal infarcts, death occurs within 1 h of the onset of pain. The final extension of myocardial necrosis is reached within 2-4 h. An integrated programme has therefore been developed for the supervision and treatment of patients suffering acute coronary attack; it has been shown that it can markedly lower infarct mortality. It includes mobile prehospital care, intensive care treatment in the hospital, and rehabilitative procedures for application during reconvalescence. Early antiarrhythmic treatment and myocardial reperfusion via fibrinolysis are the main therapeutic procedures in the earliest stage. In hospital an operating room and an operating team must be available round the clock for the performance of coronary angiography followed by percutaneous transluminal coronary angioplasty or bypass surgery, which can be safely carried out in the acute stage provided the indications are strictly observed. Mortality and morbidity can be significantly lowered and both life expectancy and quality of life can be remarkably improved. (orig.) [de

  5. Scintigraphic characteristics of experimental myocardial infarct extension

    International Nuclear Information System (INIS)

    Kronenberg, M.W.; Wooten, N.E.; Friesinger, G.C.; Page, D.L.; Higgins, S.B.; Collins, J.C.; O'Connor, J.L.; Price, R.R.; Brill, A.B.

    1979-01-01

    Technetium-99m-stannous pyrophosphate scintiphotos were evaluated for diagnosing and quantitating myocardial infarct (MI) extension in sedated dogs. Infarction and extension were produced by serial left anterior descending coronary artery ligations at 0 and 48 hours. We compared serial scintiphoto data with regional myocardial blood flow (MBF) (microsphere technique) and infarct histopathology. In eight control dogs, the scintigraphic MI area was stable at 24, 48, and 72 hours. In each of 11 dogs undergoing extension, the MI area increased after the 48-hour occlusion, averaging a 48.9% increase (p < 0.001). Grossly, most extensions were mixtures of confluent necrosis and moderate (patchy) necrosis. MBF to confluent infarct tissue decreased significantly, allowing the documentation of extension by totaling the grams of newly flow-deprived tissue, but patchy infarct tissue had little flow deprivation, making it difficult to quantitate this type of extension accurately by flow criteria alone. Rarely, extension could be diagnosed using conventional histologic criteria. We concluded that the scintiphoto MI area was related quantitatively to infarct weight in both control and extension. However, it was not possible to determine that an increase in the MI scintiphoto area was an accurate predictor of the degree of extension using independent flow or pathologic criteria

  6. Construction of an Aptamer-SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery.

    Science.gov (United States)

    Chen, Wen; Zeng, Wen; Sun, Jiansen; Yang, Mingcan; Li, Li; Zhou, Jingting; Wu, Yangxiao; Sun, Jun; Liu, Ge; Tang, Rui; Tan, Ju; Zhu, Chuhong

    2015-06-23

    The application of tissue-engineered blood vessels (TEBVs) is the main developmental direction of vascular replacement therapy. Due to few and/or dysfunctional endothelial progenitor cells (EPCs), it is difficult to successfully construct EPC capture TEBVs in diabetes. RNA has a potential application in cell protection and diabetes treatment, but poor specificity and low efficiency of RNA transfection in vivo limit the application of RNA. On the basis of an acellular vascular matrix, we propose an aptamer-siRNA chimera-modified TEBV that can maintain a satisfactory patency in diabetes. This TEBV consists of two parts, CD133-adenosine kinase (ADK) chimeras and a TEBV scaffold. Our results showed that CD133-ADK chimeras could selectively capture the CD133-positive cells in vivo, and then captured cells can internalize the bound chimeras to achieve RNA self-transfection. Subsequently, CD133-ADK chimeras were cut into ADK siRNA by a dicer, resulting in depletion of ADK. An ADK-deficient cell may act as a bioreactor that sustainably releases adenosine. To reduce nonspecific RNA transfection, we increased the proportion of HAuCl4 during the material preparation, through which the transfection capacity of polyethylenimine (PEI)/polyethylene glycol (PEG)-capped gold nanoparticles (PEI/PEG-AuNPs) was significantly decreased and the ability of TEBV to resist tensile and liquid shear stress was greatly enhanced. PEG and 2'-O-methyl modification was used to enhance the in vivo stability of RNA chimeras. At day 30 postgrafting, the patency rate of CD133-ADK chimera-modified TEBVs reached 90% in diabetic rats and good endothelialization was observed.

  7. Fresh and Frozen Tissue-Engineered Three-Dimensional Bone–Ligament–Bone Constructs for Sheep Anterior Cruciate Ligament Repair Following a 2-Year Implantation

    Directory of Open Access Journals (Sweden)

    Vasudevan Mahalingam

    2016-10-01

    Full Text Available njuries to the anterior cruciate ligament (ACL often require surgical reconstruction utilizing tendon grafts to restore knee function and stability. Some current graft options for ACL repair are associated with poor long-term outcomes. Our laboratory has fabricated tissue-engineered bone–ligament–bone (BLB constructs that demonstrate native ligament regeneration and advancement toward native ACL mechanical properties in a sheep ACL reconstruction model. Prior work has shown that freezing BLBs as a method of preservation resulted in similar outcomes compared with fresh BLBs after 6-month implantation. The purpose of this study was to evaluate the long-term efficacy of fresh and frozen BLBs. We hypothesized that both fresh and frozen BLBs would show continued regeneration of structural and functional properties toward those of native ACL after a 2-year implantation. Following removal of the native ACL, fresh (n = 2 and frozen (n = 2 BLBs were implanted arthroscopically. After 2 years of recovery, sheep were euthanized and both the experimental and contralateral hindlimbs were removed and radiographs were performed. Explanted knees were initially evaluated for joint laxity and were then further dissected for uniaxial tensile testing of the isolated ACL or BLB. Following mechanical testing, explanted contralateral ACL (C-ACL and BLBs were harvested for histology. Two years post-ACL reconstruction, fresh and frozen BLBs exhibited similar morphological and biomechanical properties as well as more advanced regeneration compared with our 6-month recovery study. These data indicate that an additional 1.5-year regeneration period allows the BLB to continue ligament regeneration in vivo. In addition, freezing the BLBs is a viable option for the preservation of the graft after fabrication.

  8. The relationship between myocardial blood flow and myocardial viability after reperfusion. Myocardial viability assessed by [sup 15]O-water-PET

    Energy Technology Data Exchange (ETDEWEB)

    Tsukagoshi, Joichi (Gunma Univ., Maebashi (Japan). School of Medicine)

    1994-09-01

    The purpose of this study was to examine the relationship between myocardial blood flow and myocardial viability in the ischemic canine myocardium after reperfusion. Transient ischemia was induced by 60-, 90-, and 180-minute occlusion of the left anterior descending coronary artery. Myocardial blood flow (MBF) was measured in the areas in which regional contractility was severely impaired (ehocardiographically akinetic or dyskinetic) in the early reperfusion period by [sup 15]O-water positron emission tomography (PET) 12 hours and 4 weeks after reperfusion. An MBF ratio of ischemic to nonischemic regions 12 hours after reperfusion was inversely correlated with the amount of histologically determined tissue necrosis (r=-0.74). The regional contractility recovered 4 weeks later in the areas where an MBF ratio was 0.48 or greater, but did not recover in the areas with a lower MBF ratio. Thus, myocardial viability can be appropriately predicted in the early phase of myocardial perfusion by PET with [sup 15]O-water even in the absence of metabolic imaging. (author).

  9. The potential of 3-dimensional construct engineered from poly(lactic-co-glycolic acid)/fibrin hybrid scaffold seeded with bone marrow mesenchymal stem cells for in vitro cartilage tissue engineering.

    Science.gov (United States)

    Abdul Rahman, Rozlin; Mohamad Sukri, Norhamiza; Md Nazir, Noorhidayah; Ahmad Radzi, Muhammad Aa'zamuddin; Zulkifly, Ahmad Hafiz; Che Ahmad, Aminudin; Hashi, Abdurezak Abdulahi; Abdul Rahman, Suzanah; Sha'ban, Munirah

    2015-08-01

    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (ptissue engineered cartilage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Quantitative characterization of myocardial infarction by cardiovascular magnetic resonance predicts future cardiovascular events in patients with ischemic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Pauly John M

    2008-04-01

    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR can provide quantitative data of the myocardial tissue utilizing high spatial and temporal resolution along with exquisite tissue contrast. Previous studies have correlated myocardial scar tissue with the occurrence of ventricular arrhythmia. This study was conducted to evaluate whether characterization of myocardial infarction by CMR can predict cardiovascular events in patients with ischemic cardiomyopathy (ICM. Results We consecutively studied 86 patients with ICM (LVEF Conclusion Quantification of the scar volume and scar percentage by CMR is superior to LVEDV, LVESV, and LVEF in prognosticating the future likelihood of the development of cardiovascular events in patients with ICM.

  11. SURGERY OF SYMPTOMATIC MYOCARDIAL BRIDGING

    Directory of Open Access Journals (Sweden)

    N. Maghamipour N. Safaei

    2007-06-01

    Full Text Available Myocardial bridging with systolic compression of the left anterior descending coronary artery (LAD may be associated with myocardial ischemia. In symptomatic myocardial bridging unresponsive to medical treatment, surgical unroofing of the left LAD can be performed. Little information is available about the long-term prognosis of patients with this coronary anomaly after the surgical unroofing, so we decided to evaluate the result of this operation. A total of 26 patients underwent surgical unroofing of myocardial bridging. Patients had a myocardial bridge of at least 3 cm in length in the middle of LAD and with more than 70% compression during systole. Unroofing was performed with cardiopulmonary bypass in 16 and with off pump technique in 10 patients. In 6 patients repeat angiographies for control of myotomy were done. In one of them a nonsignificant 20% narrowing was seen. Postoperative scintigraphic and angiographic studies demonstrated restoration of coronary flow and myocardial perfusion without residual myocardial bridges under beta-stimulation in 24 patients. Two patients had residual narrowing. With off pump technique, 1 patient had perforation of the right ventricle and 1 patient underwent reoperation because of incomplete unroofing during the first operation. None of the patients with cardiopulmonary bypass technique had residual chest pain or other complications. Surgical unroofing of myocardial bridging with the aid of cardiopulmonary bypass is a safe and easy procedure with low operative risk and with excellent functional results.

  12. Synthesis of polyester urethane urea and fabrication of elastomeric nanofibrous scaffolds for myocardial regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Jamadi, Elham Sadat; Ghasemi-Mobarakeh, Laleh [Department of Textile engineering, Isfahan university of technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Morshed, Mohammad, E-mail: morshed@cc.iut.ac.ir [Department of Textile engineering, Isfahan university of technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Sadeghi, Morteza [Department of Chemical Engineering, Isfahan university of technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Prabhakaran, Molamma P., E-mail: nanotechmpp@gmail.com [Department of Mechanical Engineering, Faculty of Engineering, 2 Engineering Drive 3, National University of Singapore, Singapore 117576 (Singapore); Ramakrishna, Seeram [Department of Mechanical Engineering, Faculty of Engineering, 2 Engineering Drive 3, National University of Singapore, Singapore 117576 (Singapore)

    2016-06-01

    Fabrication of bioactive scaffolds is one of the most promising strategies to reconstruct the infarcted myocardium. In this study, we synthesized polyester urethane urea (PEUU), further blended it with gelatin and fabricated PEUU/G nanofibrous scaffolds. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and X-ray diffraction were used for the characterization of the synthesized PEUU and properties of nanofibrous scaffolds were evaluated using scanning electron microscopy (SEM), ATR-FTIR, contact angle measurement, biodegradation test, tensile strength analysis and dynamic mechanical analysis (DMA). In vitro biocompatibility studies were performed using cardiomyocytes. DMA analysis showed that the scaffolds could be reshaped with cyclic deformations and might remain stable in the frequencies of the physiological activity of the heart. On the whole, our study suggests that aligned PEUU/G 70:30 nanofibrous scaffolds meet the required specifications for cardiac tissue engineering and could be used as a promising construct for myocardial regeneration. - Highlights: • PEUU was synthesized to fabricate elastomeric scaffolds for myocardial regeneration. • FTIR, DSC and XRD analysis showed that polymer synthesis was well. • PEUU/gelatin nanofibrous scaffolds could be reshaped with cyclic deformations of the heart. • Gelatin in structure of PEUU nanofibers improved proliferation of cardiomyocytes. • Aligned PEUU/gelatin 70:30 nanofibrous scaffold support the alignment of cardiomyocytes.

  13. Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo

    DEFF Research Database (Denmark)

    Hansen, P R; Svendsen, Jesper Hastrup; Høyer, S

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis of tissue injury, and high circulating levels of TNF-alpha are found in a variety of pathological conditions. In open-chest anesthetized dogs, the effects of intracoronary recombinant human TNF-alpha (rTNF-alpha; 100...... in cardiac output and was associated with the appearance of areas with myocardial necrosis in the regional left ventricular wall. The myocardial plasma flow rate and maximum plasma flow rate in response to a 30-s coronary occlusion were not influenced by rTNF-alpha, although a decrease in the myocardial...... ng/kg for 60 min) on myocardial microvascular transport of a small hydrophilic indicator was examined by the single-injection, residue-detection method. Intracoronary infusion of rTNF-alpha increased myocardial microvascular transport after 120 min. This increase was preceded by a sustained decline...

  14. Regional Longitudinal Myocardial Deformation Provides Incremental Prognostic Information in Patients with ST-Segment Elevation Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Tor Biering-Sørensen

    Full Text Available Global longitudinal systolic strain (GLS has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI. The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information.In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI, treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI and two-dimensional strain echocardiography (2DSE.During a median-follow-up of 5.3 (IQR 2.5-6.1 years the primary endpoint (death, heart failure or a new MI was reached by 145 (38.9% patients. After adjustment for significant confounders (including conventional echocardiographic parameters and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032. In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters.Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse outcome.

  15. Effects of heat stimulation and l-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs.

    Science.gov (United States)

    Ikeda, Kazushi; Ito, Akira; Sato, Masanori; Kanno, Shota; Kawabe, Yoshinori; Kamihira, Masamichi

    2017-05-01

    Although skeletal muscle tissue engineering has been extensively studied, the physical forces produced by tissue-engineered skeletal muscles remain to be improved for potential clinical utility. In this study, we examined the effects of mild heat stimulation and supplementation of a l-ascorbic acid derivative, l-ascorbic acid 2-phosphate (AscP), on myoblast differentiation and physical force generation of tissue-engineered skeletal muscles. Compared with control cultures at 37°C, mouse C2C12 myoblast cells cultured at 39°C enhanced myotube diameter (skeletal muscle hypertrophy), whereas mild heat stimulation did not promote myotube formation (differentiation rate). Conversely, AscP supplementation resulted in an increased differentiation rate but did not induce skeletal muscle hypertrophy. Following combined treatment with mild heat stimulation and AscP supplementation, both skeletal muscle hypertrophy and differentiation rate were enhanced. Moreover, the active tension produced by the tissue-engineered skeletal muscles was improved following combined treatment. These findings indicate that tissue culture using mild heat stimulation and AscP supplementation is a promising approach to enhance the function of tissue-engineered skeletal muscles. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Preparation of Preproinsulin Gene Construct Containing the Metallothionein2A (pBINDMTChIns and Its Expression in NIH3T3 Cell Line and Muscle Tissue of Alloxan Diabetic Rabbits

    Directory of Open Access Journals (Sweden)

    Piri

    2014-08-01

    Full Text Available Background Diabetes mellitus type 1, formerly called insulin-dependent diabetes, is one of the autoimmune diseases where insulin-producing cells are destroyed by autoimmune response via T cells. The new approaches in treatment of diabetes are using the stem cells, cell transplantation of islet β cell, gene transfer by virus based plasmids, and non-viral gene constructs. Objectives The purpose of this study was to construct glucose inducible insulin gene plasmid and use it in the muscle tissue of the rabbit. Materials and Methods To achieve this goal, the preproinsulin, metallothionein2A promoter and the response element to carbohydrate genes were cloned into pBIND plasmid by standard cloning methods, to construct pBINDMTChIns. The gene cloning products were confirmed by the polymerase chain reaction (PCR and restriction enzyme digestion template. The recombinant plasmid, containing the preproinsulin gene, was transferred into NIH3T3 cells and insulin gene expression was evaluated by reverse transcriptase PCR and western blotting techniques. Plasmid naked DNA containing the preproinsulin gene was injected into the rabbits’ thigh muscles, and its expression was confirmed by western blotting method. Results This study shows the prepared gene construct is inducible by glucose. Gene expression of preproinsulin was observed in muscle tissue of rabbits. Conclusions These finding indicated that research in diabetes mellitus gene therapy could be performed on larger animals.

  17. Effects of activation of endocannabinoid system on myocardial metabolism

    Directory of Open Access Journals (Sweden)

    Agnieszka Polak

    2016-05-01

    Full Text Available Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described.

  18. Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, S.; Karanikas, G.; Rodrigues, M.; Sinzinger, H. [Dept. of Nuclear Medicine, University of Vienna (Austria)

    2000-03-01

    About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with{sup 123}I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%{+-}3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 {mu}M. This indicates an unsaturable uptake process in the tested concentrations. Pre-incubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism. (orig.)

  19. [Myocardial ultrastructural changes in rats following different levels of acute +Gz exposure].

    Science.gov (United States)

    Zheng, Jun; Liu, Cheng-gang; Ren, Li; Xiao, Xiao-guang; Xu, Shu-xuan; Wang, Ping; Ji, Gui-ying

    2004-06-01

    To observe the effects of different levels of acute +Gz exposure on myocardial ultrastructure of rats and provide experimental basis for further development of anti-G measures. Twenty male Wistar rats were randomly divided into 4 groups (n=5): normal control group, +20 Gz group, +10 Gz group and +5 Gz group. Profile of the centrifuge +Gz exposure was trapezoidal, in which +20 Gz lasted for 30 s, +10 Gz for 1.5 min. +5 Gz exposure was repeated for 3 times with 30 min interval and each for 1.5 min. Myocardial tissue of left ventricle was sampled for transmission electron microscopy 5 h after exposure. +20 Gz and +10 Gz exposure caused obvious edema of myocardial and endothelial cells, myofibril disorder and injuries of mitochondria and nucleus. Breaks of myocardial fiber, formation of contraction bands and rupture of mitochondria were also observed in +20 Gz group. In +5 Gz group, there was still slight edema of myocardial and endothelial cells, while organic changes of myocardial ultrastructure were not observed. High +Gz exposure can cause myocardial ultrastructural injury in rats. Slight reversible injured response can also be observed in myocardial cell after repeated moderate level of +Gz exposure. This indicates that attention should be paid to the study of the effect of high +Gz on heart in pilots.

  20. Depression following myocardial infarction

    DEFF Research Database (Denmark)

    Larsen, Karen Kjær

    2013-01-01

    whether the mental burden of MI is so heavy that it increases the risk of suicide. Although post-MI depression is common and burdensome, the condition remains under-recognised and under-treated. The development of new strategies to improve the quality of care for people with post-MI depression requires...... between post-MI depression and new cardiovascular events or death, taking potential mediators into account (Paper III); 4. To examine the association between MI and suicide (Paper IV). Two different study designs were employed: a population-based cohort study using data obtained from registers......Myocardial infarction (MI) is a severe life event that is accompanied by an increased risk of depression. Mounting evidence suggests that post-MI depression is associated with adverse outcomes, but the underlying mechanisms of this association remain unclear, and no previous studies have examined...

  1. Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair.

    Science.gov (United States)

    Zimmermann, Wolfram-Hubertus

    2013-01-01

    The heart is a continuously pumping organ with an average lifespan of eight decades. It develops from the onset of embryonic cardiogenesis under biomechanical load, performs optimally within a defined range of hemodynamic load, and fails if acutely or chronically overloaded. Unloading of the heart leads to defective cardiogenesis in utero, but can also lead to a desired therapeutic outcome (for example, in patients with heart failure under left ventricular assist device therapy). In light of the well-documented relevance of mechanical loading for cardiac physiology and pathology, it is plausible that tissue engineers have integrated mechanical stimulation regimens into protocols for heart muscle construction. To achieve optimal results, physiological principles of beat-to-beat myocardial loading and unloading should be simulated. In addition, heart muscle engineering, in particular if based on pluripotent stem cell-derived cardiomyocytes, may benefit from staggered tonic loading protocols to simulate viscoelastic properties of the prenatal and postnatal myocardial stroma. This review will provide an overview of heart muscle mechanics, summarize observations on the role of mechanical loading for heart development and postnatal performance, and discuss how physiological loading regimens can be exploited to advance myocardial tissue engineering towards a therapeutic application.

  2. Construction of a tissue microarray with two millimeters cores of endometrioid endometrial cancer: factors affecting the quality of the recipient block.

    Science.gov (United States)

    Gottwald, L; Sęk, P; Piekarski, J; Pasz-Walczak, G; Kubiak, R; Szwalski, J; Spych, M; Suzin, J; Tyliński, W; Topczewska-Tylinska, K; Jeziorski, A

    2012-11-01

    The tissue microarray (TMA) method currently is not used to render a primary diagnosis of cancer, but its scientific value has been proved in studies of various cancer types. TMA technology still is not used often for uterine tumors, however. We investigated the repeatability of histological diagnosis of endometrioid endometrial cancer (EEC) using conventional histology and TMA using 2 mm cores. We examined EEC tissues from 171 patients. Formalin fixed, paraffin embedded tissue donor blocks from EEC specimens were selected and examined histologically. Duplicate 2 mm tissue cores were inserted into a TMA recipient block. EEC tissues were examined as hematoxylin-eosin stained sections from the TMAs. EEC tissue was identified in the TMAs in 158 cases (92.4%) and not found in 13 cases (7.6%). On the TMA slides, both EEC positive cores were identified in 129 cases (75.4%), but only one core in 29 cases (17.0%). Among 342 biopsies of the donor blocks (each case in duplicate), EEC was found in 287 cases (83.9%) using the TMA: 124/146 (84.9%) with superficial infiltration, 153/178 (86.0%) with deep myometrial infiltration, and 10/18 (55.6%) without myometrial infiltration. We concluded that two 2 mm tissue cores from a biopsy of a donor block inserted into a TMA recipient block were sufficient to diagnose EEC in more than 90% of cases. EEC was identified in the TMAs with similar frequency with respect to superficial and deep myometrial infiltration. Cases without myometrial infiltration were identified less often.

  3. Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

    OpenAIRE

    Luo, Min; Guan, Xiaoqun; Luczak, Elizabeth D.; Lang, Di; Kutschke, William; Gao, Zhan; Yang, Jinying; Glynn, Patric; Sossalla, Samuel; Swaminathan, Paari D.; Weiss, Robert M.; Yang, Baoli; Rokita, Adam G.; Maier, Lars S.; Efimov, Igor R.

    2013-01-01

    Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabeti...

  4. Scan analysis in myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J [Landesunfallkrankenhaus, Feldkirch (Austria). Inst. fuer Strahlenmedizin

    1976-08-01

    Myocardial scans with sup(99m)Tc-labelled phosphates are reported to be useful in the diagnosis of acute myocardial infarction. A retrospective survey of 205 patients referred for sup(99m)Tc-phophate bone scanning and with no evidence of recent heart disease revealed an occurrence of 10% of false positive images, that is to say, uptake of phosphate in non-infarcted mayocardium. These striking findings stress the need for critical assessment of the usefulness of this diagnostic technique.

  5. Polymorphisms in the 5' regulatory region of the tissue factor gene and the risk of myocardial infarction and venous thromboembolism: the ECTIM and PATHROS studies. Etude Cas-Témoins de l'Infarctus du Myocarde. Paris Thrombosis case-control Study.

    Science.gov (United States)

    Arnaud, E; Barbalat, V; Nicaud, V; Cambien, F; Evans, A; Morrison, C; Arveiler, D; Luc, G; Ruidavets, J B; Emmerich, J; Fiessinger, J N; Aiach, M

    2000-03-01

    Tissue factor (TF) is a transmembrane protein considered to be responsible for the initiation of coagulation. TF gene expression may be induced in monocytes and endothelial cells and is present in atherosclerotic plaque to initiate thrombus formation. To investigate whether individual differences in TF gene expression could predispose subjects to thrombosis, we sequenced the 5' domain of the gene up to nucleotide 2732 and found 6 different polymorphisms: 4 of them were completely concordant and defined 2 haplotypes with similar frequencies, designated as 1208 D and 1208 I. Genotyping of patients with myocardial infarction in a case-control study involving 2354 subjects showed no association between the polymorphisms and nonfatal coronary thrombosis. In another study involving 255 patients with venous thromboembolism and 1204 controls, allele D was less common in the cases (P=0.022). The odds ratio associated with the presence of at least 1 D allele was 0.72 (P=0. 031). Comparison of subgroups of control subjects who were homozygous for the D or I allele demonstrated a lower plasma TF concentration in DD homozygotes. These results indicate that the TF gene promoter exists in 2 major forms differing at 4 sites. The 1208 D haplotype is not associated with coronary thrombosis but is associated with reduced plasma TF levels and a lower risk of venous thrombosis.

  6. Effects of Chronic and Acute Zinc Supplementation on Myocardial Ischemia-Reperfusion Injury in Rats.

    Science.gov (United States)

    Ozyıldırım, Serhan; Baltaci, Abdulkerim Kasim; Sahna, Engin; Mogulkoc, Rasim

    2017-07-01

    The present study aims to explore the effects of chronic and acute zinc sulfate supplementation on myocardial ischemia-reperfusion injury in rats. The study registered 50 adult male rats which were divided into five groups in equal numbers as follows: group 1, normal control; group 2, sham; group 3, myocardial ischemia reperfusion (My/IR): the group which was fed on a normal diet and in which myocardial I/R was induced; group 4, myocardial ischemia reperfusion + chronic zinc: (5 mg/kg i.p. zinc sulfate for 15 days); and group 5, myocardial ischemia reperfusion + acute zinc: the group which was administered 15 mg/kg i.p. zinc sulfate an hour before the operation and in which myocardial I/R was induced. The collected blood and cardiac tissue samples were analyzed using spectrophotometric method to determine levels of MDA, as an indicator of tissue injury, and GSH, as an indicator of antioxidant activity. The highest plasma and heart tissue MDA levels were measured in group 3 (p zinc administration and markedly by chronic zinc supplementation.

  7. Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

    Directory of Open Access Journals (Sweden)

    Sun HY

    2017-04-01

    Full Text Available Hongyu Sun,* Jing Zhou,* Zhu Huang,* Linlin Qu,* Ning Lin,* Chengxiao Liang, Ruiwu Dai, Lijun Tang, Fuzhou Tian General Surgery Center, Chengdu Military General Hospital, Chengdu, China *These authors contributed equally to this work Abstract: Carbon nanotubes (CNTs provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt% exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. Keywords: carbon nanotubes, collagen hydrogel, cardiac constructs, cell alignment, tissue functionality

  8. Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Timmer, Stefan A.J.; Germans, Tjeerd; Goette, Marco J.W.; Ruessel, Iris K.; Dijkmans, Pieter A.; Knaapen, Paul; Rossum, Albert C. van; Lubberink, Mark; Lammertsma, Adriaan A.; Berg, Jurrien M. ten; Cate, Folkert J. ten

    2010-01-01

    Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO 2 ), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). Twenty patients with HCM (12 men, mean age: 55.2 ± 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 ± 10 years) were studied with [ 11 C]acetate PET to assess MVO 2 . CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. Between study groups, MVO 2 (controls: 0.12 ± 0.04 ml.min -1 .g -1 , HCM: 0.13 ± 0.05 ml.min -1 .g -1 , p = 0.64) and EW (controls: 9,139 ± 2,484 mmHg.ml, HCM: 9,368 ± 2,907 mmHg.ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 ± 21 g, HCM: 200 ± 76 g, p 2 -terminal pro-brain natriuretic peptide (NT-proBNP) and serum free fatty acid levels (all p 2 , impaired EW generation per gram of myocardial tissue and subsequent deteriorated myocardial efficiency. Mechanical external efficiency could independently be predicted by SV and LVM. (orig.)

  9. Myocardial Architecture, Mechanics, and Fibrosis in Congenital Heart Disease

    Directory of Open Access Journals (Sweden)

    Sarah Ghonim

    2017-05-01

    Full Text Available Congenital heart disease (CHD is the most common category of birth defect, affecting 1% of the population and requiring cardiovascular surgery in the first months of life in many patients. Due to advances in congenital cardiovascular surgery and patient management, most children with CHD now survive into adulthood. However, residual and postoperative defects are common resulting in abnormal hemodynamics, which may interact further with scar formation related to surgical procedures. Cardiovascular magnetic resonance (CMR has become an important diagnostic imaging modality in the long-term management of CHD patients. It is the gold standard technique to assess ventricular volumes and systolic function. Besides this, advanced CMR techniques allow the acquisition of more detailed information about myocardial architecture, ventricular mechanics, and fibrosis. The left ventricle (LV and right ventricle have unique myocardial architecture that underpins their mechanics; however, this becomes disorganized under conditions of volume and pressure overload. CMR diffusion tensor imaging is able to interrogate non-invasively the principal alignments of microstructures in the left ventricular wall. Myocardial tissue tagging (displacement encoding using stimulated echoes and feature tracking are CMR techniques that can be used to examine the deformation and strain of the myocardium in CHD, whereas 3D feature tracking can assess the twisting motion of the LV chamber. Late gadolinium enhancement imaging and more recently T1 mapping can help in detecting fibrotic myocardial changes and evolve our understanding of the pathophysiology of CHD patients. This review not only gives an overview about available or emerging CMR techniques for assessing myocardial mechanics and fibrosis but it also describes their clinical value and how they can be used to detect abnormalities in myocardial architecture and mechanics in CHD patients.

  10. Regional myocardial metabolism in patients with acute myocardial infarction assessed by positron emission tomography

    International Nuclear Information System (INIS)

    Schwaiger, M.; Brunken, R.; Grover-McKay, M.; Krivokapich, J.; Child, J.; Tillisch, J.H.; Phelps, M.E.; Schelbert, H.R.

    1986-01-01

    Positron emission tomography has been shown to distinguish between reversible and irreversible ischemic tissue injury. Using this technique, 13 patients with acute myocardial infarction were studied within 72 hours of onset of symptoms to evaluate regional blood flow and glucose metabolism with nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose, respectively. Serial noninvasive assessment of wall motion was performed to determine the prognostic value of metabolic indexes for functional tissue recovery. Segmental blood flow and glucose utilization were evaluated using a circumferential profile technique and compared with previously established semiquantitative criteria. Relative N-13 ammonia uptake was depressed in 32 left ventricular segments. Sixteen segments demonstrated a concordant decrease in flow and glucose metabolism. Regional function did not change over time in these segments. In contrast, 16 other segments with reduced blood flow revealed maintained F-18 deoxyglucose uptake consistent with remaining viable tissue. The average wall motion score improved significantly in these segments (p less than 0.01), yet the degree of recovery varied considerably among patients. Coronary anatomy was defined in 9 of 13 patients: patent infarct vessels supplied 8 of 10 segments with F-18 deoxyglucose uptake, while 10 of 13 segments in the territory of an occluded vessel showed concordant decreases in flow and metabolism (p less than 0.01). Thus, positron emission tomography reveals a high incidence of residual tissue viability in ventricular segments with reduced flow and impaired function during the subacute phase of myocardial infarction. Absence of residual tissue metabolism is associated with irreversible injury, while preservation of metabolic activity identifies segments with a variable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Dogan, I.; Sonmez, B. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Nuclear Medicine; Sezen, O.; Zengin, A.Y.; Bahat, Z. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Radiation Oncology; Yenilmez, E.; Yulug, E. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Histology and Embryology; Abidin, I. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Biophysics

    2010-07-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ({sup 99m}Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  12. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    International Nuclear Information System (INIS)

    Dogan, I.; Sonmez, B.; Sezen, O.; Zengin, A.Y.; Bahat, Z.; Yenilmez, E.; Yulug, E.; Abidin, I.

    2010-01-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ( 99m Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  13. Acute Myocardial Infarction Patients

    Directory of Open Access Journals (Sweden)

    Bruce Ovbiagele

    2011-01-01

    Full Text Available Background. Diabetes mellitus (DM confers high vascular risk and is a growing national epidemic. We assessed clinical characteristics and prevalence of diagnosed DM among patients hospitalized with acute myocardial infarction (AMI in the US over the last decade. Methods. Data were obtained from all states within the US that contributed to the Nationwide Inpatient Sample. All patients admitted to hospitals between 1997 and 2006 with a primary discharge diagnosis of AMI were included. Time trends in the proportion of these patients with DM diagnosis were computed. Results. The portion of patients with comorbid diabetes among AMI hospitalizations increased substantially from 18% in 1997 to 30% in 2006 (<.0001. Absolute numbers of AMI hospitalizations in the US decreased 8% (from 729, 412 to 672, 243, while absolute numbers of AMI hospitalizations with coexisting DM rose 51% ((131, 189 to 198, 044, both (<.0001. Women with AMI were significantly more likely to have DM than similarly aged men, but these differences diminished with increasing age. Conclusion. Although overall hospitalizations for AMI in the US diminished over the last decade, prevalence of diabetes rose substantially. This may have important consequences for the future societal vascular disease burden.

  14. Early spontaneous intermittent myocardial reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less myocardial damage

    NARCIS (Netherlands)

    Haider, A.W.; Andreotti, F.; Hackett, D.R.; Tousoulis, D.; Kluft, C.; Maseri, A.; Davies, G.J.

    1995-01-01

    Objectives. This study investigated the influence of early spontaneous intermittent reperfusion on the extent of myocardial damage and its relation to endogenous hemostatic activity, Background. In the early phase of acute myocardial infarction coronary occlusion is often intermittent, even before

  15. High-resolution cellular MRI: gadolinium and iron oxide nanoparticles for in-depth dual-cell imaging of engineered tissue constructs.

    Science.gov (United States)

    Di Corato, Riccardo; Gazeau, Florence; Le Visage, Catherine; Fayol, Delphine; Levitz, Pierre; Lux, François; Letourneur, Didier; Luciani, Nathalie; Tillement, Olivier; Wilhelm, Claire

    2013-09-24

    Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components.

  16. Mechanisms of thallium-201 myocardial accumulation

    International Nuclear Information System (INIS)

    Wackers, F.J.Th.; Samson, G.

    1980-01-01

    The practical advantages of 201 Tl over other suitable myocardial imaging agents such as potassium-43 ( 43 K), rubidium-81 ( 81 Rb), and cesium-129 ( 129 Cs), are its relatively low energy photons which makes it possible to employ high-resolution low-energy collimators and its physical half-life of 73 hr which provides sufficiently long shelf-life for practical clinical imaging. Toxicological considerations do not play a role using 201 Tl as thallous chloride. The concentration of thallous chloride in a dose of 2 mCi of 201 Tl is less than 4μg. The LD 50 of thallous chloride is a factor 10 4 more. The minimal lethal dose in man is reported to be 12 mg/kg. The kinetics of 201 Tl, its tissue distributions and radiation doses are assessed, and the effect of cardiac drugs on thallium-201 uptake are discussed. (Auth.)

  17. Thallium-201 myocardial imaging in acute-myocardial infarction

    International Nuclear Information System (INIS)

    Wackers, F.J.Th.; Lie, K.I.; Sokole, E.B.; Wellens, H.J.J.; Samson, G.; Schoot, J.B. van der

    1980-01-01

    Thallium-201 scintigraphy has proven to be an early and highly sensitive technique to detect myocardial perfusion abnormalities in patients with acute myocardial infarction. During the early phase of acute myocardial infarction, patients may be hemodynamically and electrically unstable. Therefore, scintigraphy is performed preferably at the bed side in the Coronary Care Unit using a mobile gamma camera. Additionally, in order to shorten imaging time in these often critically ill patients, the authors recommend injecting no less than 2 mCi of 201 Tl. Using this dosage, the imaging time per view will be approximately five minutes. Routinely, three views are taken: the first view is a supine 45 0 left-anterior-oblique view, followed by a supine anterior view and finally a left-lateral view, the latter with the patient turned on the right side. (Auth.)

  18. Myocardial perfusion imaging for detection of silent myocardial ischemia

    International Nuclear Information System (INIS)

    Beller, G.A.

    1988-01-01

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references

  19. Diffuse Myocardial Uptake of 99mTc-HDP in Multiple Myeloma

    International Nuclear Information System (INIS)

    Demirel, Koray; Sadic, Murat; Korkmaz, Meliha; Comak, Aylin; Atilgan, Hasan Ikbal; Koca, Goekhan

    2013-01-01

    Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate ( 99m Tc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14 years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, 99m Tc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM

  20. Diffuse Myocardial Uptake of {sup 99m}Tc-HDP in Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Demirel, Koray; Sadic, Murat; Korkmaz, Meliha; Comak, Aylin; Atilgan, Hasan Ikbal; Koca, Goekhan [Ministry of Health Ankara Training and Research Hospital, Ankara (Turkmenistan)

    2013-09-15

    Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate ({sup 99m}Tc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14 years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, {sup 99m}Tc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM.

  1. Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs

    International Nuclear Information System (INIS)

    Horton, J.W.

    1987-01-01

    An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h or hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace [ 14 C]inulin, values (ml H 2 O/g dry wt) for control nonshocked myocardial slices were 4.03 /plus minus/ 0.11 (SE) for total water, 2.16 /plus minus/ 0.07 for inulin impermeable space, and 1.76 /plus minus/ 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation. After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo

  2. Myocardial scintigraphy with thallium-201

    International Nuclear Information System (INIS)

    Schwaiger, M.; Silber, S.; Klein, U.; Rudolph, W.

    1980-01-01

    Thallium-201 myocardial scintigraphy is an important non-invasive method for assessment of coronary artery disease. Other applications of the method such as delineation of the right ventricular free wall in right ventricular overload, or the detection of hypertrophic cardiomyopathies or myocardial infiltrations are of subordinate importance. In heart disease such as congestive cardiomyopathy and mitral valve prolapse thallium-201 uptake defects have been described, the clinical implications of these findings, however, cannot be adequately interpreted at this time. Myocardial uptake of thallium-201 is an active process, dependent on and proportional to perfusion. Differentiation between myocardial ischemia and myocardial scar is based on the presence or absence of thallium-201 'redistribution'. That is, in the presence of acute reversible ischemia there is increased thallium-201 uptake in the post-ischemic phase in previously hypoperfused myocardium and, subsequently, equilibrium of the initially registered activity differences. 'Redistribution' has also been described in the resting scintigram of patients with severe coronary artery disease and chronic hypoperfusion. (orig.) [de

  3. Mortality rate in type 2 myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Diederichsen, Axel Cosmus Pyndt

    2014-01-01

    myocardial infarction, hypercholesterolemia, high p-creatinine, and diabetes mellitus. The multivariable-adjusted hazard ratio for type 2 myocardial infarction was 2.0 (95% confidence interval, 1.3-3.0). With shock as the only exception, mortality was independent of the triggering conditions leading to type....../119) in those with type 2 myocardial infarction and 26% (92/360) in those with type 1 myocardial infarction (P high age, prior myocardial infarction, type 2...... 2 myocardial infarction. CONCLUSIONS: Mortality in patients with type 2 myocardial infarction is high, reaching approximately 50% after 2 years. Further descriptive and survival studies are needed to improve the scientific evidence on which treatment of type 2 myocardial infarction is based....

  4. Sgarbossa criteria and acute myocardial infarction.

    Science.gov (United States)

    Alang, Neha; Bathina, Jaya; Kranis, Mark; Angelis, Dimitrios

    2010-01-01

    Diagnosis of acute ST-elevation myocardial infarction in the presence of left bundle branch block is difficult. present a case of acute myocardial infarction with LBBB diagnosed and treated using the Sgarbossa criteria.

  5. Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2014-01-01

    Full Text Available This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE. The myocardial ischemia/reperfusion (I/R injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP and the maximum up/downrate of left ventricular pressure (±dp/dtmax were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH and creatine kinase (CK activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD and malondialdehyde (MDA in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

  6. The usefulness of the nuclear cardiology in the cellular implant in patients with severe myocardial damage

    International Nuclear Information System (INIS)

    Omelas A, M.; Arguero S, R.; Garrido G, M.H.; Rodriguez C, A.; Careaga, G.; Castano G, R.; Nambo, M.J.; Pascual P, J.; Ortega R, A.; Gaxiola A, A.; Magana S, J.A.; Estrada A, H.; Equipo de Tecnicos en Medicina Nuclear

    2005-01-01

    The recent therapeutic advances as the cellular implant as well as those different protocols of image acquisition in the field of the Nuclear Cardiology its have allowed that the patient with severe myocardial damage and without some possibility of revascularization is benefited with these advances. Doubtless the Tl-201 par excellence has an important paper for standardize the more appropriate therapeutic behavior for the heart attack patient; reason by this investigation protocol was developed. The objective of the study was to identify the heart attack regions without viable tissue with SPECT in patient with important myocardial damage without some possibility of traditional revascularization; for the 'Stem cell' cellular implantation therapy. The methodology it was carried out by a study of myocardial perfusion in 10 patients with important myocardial damage previous cellular implants, with PICANUC/ SPECT methodology and using a software (Emory Tool Box) for the image processing validated by the University of Emory Atlanta GA; and using as tracer the Tl - 201 to identify the heart attack regions without presence of viable tissue with an analysis model of 17 segments standardized for the left ventricle; qualifying this way the myocardial perfusion in: 0 (normal), 1 (light), 2 (moderate), 3 (severe), 4 (absent) and x (bad technique). The conclusions were that the SPECT study with PICANUC methodology with Tl-201 is safe and effective for the precise localization for the cellular implantation via direct intra myocardial. (Author)

  7. Regional myocardial perfusion assessed by N-13 labeled ammonia and positron emission computerized axial tomography

    International Nuclear Information System (INIS)

    Schelbert, H.R.; Phelps, M.E.; Hoffman, E.J.; Huang, S.C.; Selin, C.E.; Kuhl, D.E.

    1978-01-01

    The usefulness of 13 NH 3 as an indicator of regional myocardial perfusion suitable for positron emission computerized axial tomography (PCT) has been suggested. However, the relationship between myocardial blood flow and uptake of 13 NH 3 has not been examined quantitatively. It was therefore the purpose of the current investigation to quantitate the relationship of myocardial 13 NH 3 tissue concentration to myocardial blood flow and to examine its suitability for PCT imaging. Twelve open chest dogs were studied. In 8 of the dogs 25 imaging procedures with 13 NH 3 and PCT were performed. In the remaining four dogs the relationship between flow and myocardial 13 NH 3 tissue concentration was assessed by in vitro techniques. The PCT technique provided high quality cross-sectional images of the distribution of 13 NH 3 in left ventricular myocardium. No significant redistribution of 13 NH 3 in myocardium occurred with time. Alterations in regional myocardial blood flow resulted in changes of the regional distribution of 13 NH 3 that were readily appreciated on the PCT images

  8. Myocardial infarction after near drowning.

    Science.gov (United States)

    Chen, Li-Bang; Lai, Yen-Chun; Chen, Chang-Chih; Chang, Wen-Han; Su, Yu-Jang

    2008-06-01

    During summer, near drowning is a common accident in Taiwan. It may lead to multiple organ damages in cases where severe hypothermia and hypoxemia occur. We present a case of myocardial infarction after near drowning. The patient was sent to our ED by the emergency medical services called by the witness. On arrival to our ED, hypothermia and hypoxemia overcame him. Endotracheal intubation and warm intravenous fluid were applied at once owing to drowsy consciousness, respiratory distress, and hypothermia. Electrocardiogram showed diffuse ST-segment elevation over the precordial leads V2-V6. The initial level of cardiac enzymes was within normal limit but elevated in troponin I on the second day after hospitalization. We presumed that the possibility of myocardial infarction resulted from near drowning-related hypoxemia. To our knowledge, this is the first case describing myocardial injury with electrocardiogram changes after near drowning.

  9. Dynamic CT myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Caruso, Damiano; Eid, Marwen; Schoepf, U. Joseph; Jin, Kwang Nam; Varga-Szemes, Akos; Tesche, Christian; Mangold, Stefanie

    2016-01-01

    Highlights: • CT myocardial perfusion provides functional assessment of the myocardium. • CCTA is limited in determining the hemodynamic significance of coronary stenosis. • CT-MPI can accurately detect hemodynamically significant coronary artery stenosis. - Abstract: Non-invasive cardiac imaging has rapidly evolved during the last decade due to advancements in CT based technologies. Coronary CT angiography has been shown to reliably assess coronary anatomy and detect high risk coronary artery disease. However, this technique is limited to anatomical assessment, thus non-invasive techniques for functional assessment of the heart are necessary. CT myocardial perfusion is a new CT based technique that provides functional assessment of the myocardium and allows for a comprehensive assessment of coronary artery disease with a single modality when combined with CTA. This review aims to discuss dynamic CT myocardial perfusion as a new technique in the assessment of CAD.

  10. Dynamic CT myocardial perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Caruso, Damiano [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiological Sciences, Oncological and Pathological Sciences, University of Rome “Sapienza”, Latina (Italy); Eid, Marwen [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC (United States); Jin, Kwang Nam [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul (Korea, Republic of); Varga-Szemes, Akos [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Tesche, Christian [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich (Germany); Mangold, Stefanie [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Diagnostic and Interventional Radiology, University Hospital of Tuebingen, Tuebingen (Germany); and others

    2016-10-15

    Highlights: • CT myocardial perfusion provides functional assessment of the myocardium. • CCTA is limited in determining the hemodynamic significance of coronary stenosis. • CT-MPI can accurately detect hemodynamically significant coronary artery stenosis. - Abstract: Non-invasive cardiac imaging has rapidly evolved during the last decade due to advancements in CT based technologies. Coronary CT angiography has been shown to reliably assess coronary anatomy and detect high risk coronary artery disease. However, this technique is limited to anatomical assessment, thus non-invasive techniques for functional assessment of the heart are necessary. CT myocardial perfusion is a new CT based technique that provides functional assessment of the myocardium and allows for a comprehensive assessment of coronary artery disease with a single modality when combined with CTA. This review aims to discuss dynamic CT myocardial perfusion as a new technique in the assessment of CAD.

  11. Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor

    Science.gov (United States)

    Sikavitsas, Vassilios I.; Bancroft, Gregory N.; Mikos, Antonios G.; McIntire, L. V. (Principal Investigator)

    2002-01-01

    The aim of this study is to investigate the effect of the cell culture conditions of three-dimensional polymer scaffolds seeded with rat marrow stromal cells (MSCs) cultured in different bioreactors concerning the ability of these cells to proliferate, differentiate towards the osteoblastic lineage, and generate mineralized extracellular matrix. MSCs harvested from male Sprague-Dawley rats were culture expanded, seeded on three-dimensional porous 75:25 poly(D,L-lactic-co-glycolic acid) biodegradable scaffolds, and cultured for 21 days under static conditions or in two model bioreactors (a spinner flask and a rotating wall vessel) that enhance mixing of the media and provide better nutrient transport to the seeded cells. The spinner flask culture demonstrated a 60% enhanced proliferation at the end of the first week when compared to static culture. On day 14, all cell/polymer constructs exhibited their maximum alkaline phosphatase activity (AP). Cell/polymer constructs cultured in the spinner flask had 2.4 times higher AP activity than constructs cultured under static conditions on day 14. The total osteocalcin (OC) secretion in the spinner flask culture was 3.5 times higher than the static culture, with a peak OC secretion occurring on day 18. No considerable AP activity and OC secretion were detected in the rotating wall vessel culture throughout the 21-day culture period. The spinner flask culture had the highest calcium content at day 14. On day 21, the calcium deposition in the spinner flask culture was 6.6 times higher than the static cultured constructs and over 30 times higher than the rotating wall vessel culture. Histological sections showed concentration of cells and mineralization at the exterior of the foams at day 21. This phenomenon may arise from the potential existence of nutrient concentration gradients at the interior of the scaffolds. The better mixing provided in the spinner flask, external to the outer surface of the scaffolds, may explain the

  12. Different Causes of Death in Patients with Myocardial Infarction Type 1, Type 2, and Myocardial Injury.

    Science.gov (United States)

    Lambrecht, Sascha; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Hosbond, Susanne; Diederichsen, Axel C P; Thygesen, Kristian; Mickley, Hans

    2018-05-01

    Data outlining the mortality and the causes of death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and those with myocardial injury are limited. During a 1-year period from January 2010 to January 2011, all hospitalized patients who had cardiac troponin I measured on clinical indication were prospectively studied. Patients with at least one cardiac troponin I value >30 ng/L underwent case ascertainment and individual evaluation by an experienced adjudication committee. Patients were classified as having type 1 myocardial infarction, type 2 myocardial infarction, or myocardial injury according to the criteria of the universal definition of myocardial infarction. Follow-up was ensured until December 31, 2014. Data on mortality and causes of death were obtained from the Danish Civil Registration System and the Danish Register of Causes of Death. Overall, 3762 consecutive patients were followed for a mean of 3.2 years (interquartile range 1.3-3.6 years). All-cause mortality differed significantly among categories: Type 1 myocardial infarction 31.7%, type 2 myocardial infarction 62.2%, myocardial injury 58.7%, and 22.2% in patients with nonelevated troponin values (log-rank test; P causes, vs 42.6% in patients with type 2 myocardial infarction (P = .015) and 41.2% in those with myocardial injury (P causes of death did not differ substantially between patients with type 2 myocardial infarction and those with myocardial injury. Patients with type 2 myocardial infarction and myocardial injury exhibit a significantly higher long-term mortality compared with patients with type 1 myocardial infarction . However, most patients with type 1 myocardial infarction die from cardiovascular causes in contrast to patients with type 2 myocardial infarction and myocardial injury, in whom noncardiovascular causes of death predominate. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Myocardial abscess as a complication of an infected arteriovenous fistula: autopsy report

    Directory of Open Access Journals (Sweden)

    Cristiane Rúbia Ferreira

    2011-09-01

    Full Text Available Myocardial abscess is a severe and life-threatening infectious complication thatis commonly but not exclusively associated with infective endocarditis. It mayalso be developed in necrotic myocardial tissue, post trauma, in septic burnpatients, in transplanted heart, in ventricular aneurysm and post angioplasty.Patients on hemodialysis are prone to bacteremia, and infectious complicationsoccur in 48-73% of cases. Myocardial abscess is a rare complication of aninfected arteriovenous fistula. We present an autopsy report of a hemodialysispatient who had an arteriovenous fistula with a polytetrafluoroethylene graftwhere a local infection developed. The patient presented with fever and toxemia.On post-admission day 2, he unexpectedly suffered sudden cardiopulmonaryarrest and died. The autopsy revealed a myocardial abscess, near a branch ofthe left coronary artery, with septic embolism.

  14. Dobutamine cine magnetic resonance imaging after myocardial infarction

    International Nuclear Information System (INIS)

    Giovagnoni, A.; Ligabue, G.; Romagnoli, R.; Reggio Emilia Univ., Reggio Emilia; Rossi, R.; Muia, N.; Modena, M.G.; Reggio Emilia Univ.

    1999-01-01

    Dobutamine Cine MRI is a new diagnostic imaging technique in the pretreatment (revascularization) assessment of myocardial infarction patients. In this issue are reported the result of a comparative study of the diagnostic yield of dobutamine Cine MRI with that of stress echocardiography in the assessment of viable myocardium. A new method for analysis of Cine MR images, employing digital subtraction, aimed at decreasing subjectivity in the quantitative assessment of myocardial wall thickening. Twenty-six patients (21 men and 5 women) with a history of myocardial infarction who were scheduled for revascularization were submitted to stress echocardiography and dobutamine Cine MRI to evaluate contractile recovery of the segments considered akinetic or hypo kinetic at baseline echocardiography. Dobutamine was administered in growing doses (5, 10, 15γ/kg/min). 16 segments of the left ventricle in each patient were considered. In the 416 segments studied, it was found that 307 normo kinetic, 64 scarred and 45 viable segments with stress echocardiography, versus 302 normo kinetic, 83 scarred and 31 viable segments with dobutamine MRI. Three months after revascularization 15 patients were examined to check contractile recovery of the segments considered as viable. Echocardiography had 79% sensitivity and 97% specificity, while Cine MRI had 96% and 86%, respectively. In patients with anteroseptal wall myocardial infarction stress echocardiography had 75% sensitivity and 97% specificity. Echocardiography permits to distinguish viable myocardium and scarred myocardial tissue with good sensitivity and specificity, but Cine MRI performs better. Cine MRI has much higher sensitivity than stress echocardiography and thus makes the technique of choice to evaluate viable myocardium in these sites. The digital subtraction technique is as accurate as manual measurements, but reduces the error rate and permits quicker evaluation, particularly in subendocardial thickening [it

  15. Imaging techniques for myocardial inflammation

    International Nuclear Information System (INIS)

    O'Connell, J.B.; Henkin, R.E.; Robinson, J.A.

    1986-01-01

    Dilated cardiomyopathy (DC) represents a heterogeneous group of disorders which results in morbidity and mortality in young individuals. Recent evidence suggests that a subset of these patients have histologic evidence of myocarditis which is potentially treatable with immunosuppression. The identification of myocardial inflammation may therefore lead to development of therapeutic regimens designed to treat the cause rather than the effect of the myocardial disease. Ultimately, this may result in improvement in the abysmal prognosis of DC. The currently accepted technique for identification of active myocardial inflammation is endomyocardial biopsy. This technique is not perfect, however, since pathologic standards for the diagnosis of myocarditis have not been established. Furthermore, focal inflammation may give rise to sampling error. The inflammation-avid radioisotope gallium-67 citrate has been used as an adjunct to biopsy improving the yield of myocarditis from 7 percent to 36 percent. Serial imaging correlates well to biopsy results. Future studies are designed to study the applicability of lymphocyte labelling techniques to myocardial inflammatory disease

  16. Myocardial contusion following nonfatal blunt chest trauma

    International Nuclear Information System (INIS)

    Kumar, S.A.; Puri, V.K.; Mittal, V.K.; Cortez, J.

    1983-01-01

    Currently available diagnostic techniques for myocardial contusion following blunt chest trauma were evaluated. We investigated 30 patients prospectively over a period of 1 year for the presence of myocardial contusion. Among the 30 patients, eight were found to have myocardial contusion on the basis of abnormal electrocardiograms, elevated creatine phosphokinase MB fraction (CPK-MB), and positive myocardial scan. Myocardial scan was positive in seven of eight patients (87.5%). CPK-MB fraction was elevated in four of eight patients (50%). Definitive electrocardiographic changes were seen in only two of eight patients (25%). It appears that myocardial scan using technetium pyrophosphate and CPK-MB fraction determinations are the most reliable aids in diagnosis of myocardial contusion following blunt chest trauma

  17. Myocardial protection in heart surgery.

    Science.gov (United States)

    Mentzer, Robert M

    2011-01-01

    One of the unmet clinical needs in heart surgery is the prevention of myocardial stunning and necrosis that occurs as a result of ischemia-reperfusion. Myocardial stunning, a frequent consequence after heart surgery, is characterized by a requirement for postoperative inotropic support despite a technically satisfactory heart operation. In high-risk patients with marginal cardiac reserve, stunning is a major cause of prolonged critical care and may be associated with as much as a 5-fold increase in mortality. In contrast, the frequency of myocardial necrosis (myocardial infarction [MI]) after cardiac surgery is less appreciated and its consequences are much more subtle. The consequences may not be apparent for months to years. While we now have a much better understanding of the molecular mechanisms underlying myocardial stunning and MI, we still have no effective way to prevent these complications, nor a consistently effective means to engage the well-studied endogenous mechanisms of cardioprotection. The failure to develop clinically effective interventions is multifactorial and can be attributed to reliance on findings obtained from subcellular and cellular studies, to drawing conclusions from preclinical large animal studies that have been conducted in a disease-free state, and to accepting less than robust surrogate markers of injury in phase II clinical trials. These factors also explain the disappointing failure to identify effective adjuvant therapy in the setting of percutaneous coronary revascularization for acute MI (AMI) and reperfusion injury. These issues have contributed to the disappointing outcomes of large and costly phase III trials, resulting in a lack of enthusiasm on the part of the pharmaceutical industry to engage in further drug development for this indication. The purpose of this review is to (1) define the scope of the clinical problem; (2) summarize the outcomes of selected phases II and III clinical trials; and (3) identify the gap that

  18. Myocardial ischemia in Kawasaki disease

    International Nuclear Information System (INIS)

    Fukuda, Tsuyoshi

    1993-01-01

    The detection of myocardial ischemia is essential for evaluation of patients with Kawasaki disease, especially who have had coronary artery lesions. To evaluate the clinical efficacy of Tl-201 single photon emission computed tomography (SPECT) after dipyridamole infusion (maximum dose 0.70 mg/kg) for detecting myocardial ischemia, 44 patients with Kawasaki disease aged 7.7±4.8 years at the study and 10 age matched controls were observed. In the Kawasaki disease group, significant coronary artery stenosis was observed in 14, coronary aneurysm without stenosis in 18, the regression of the coronary aneurysms in 2 and without coronary lesions in 10 patients. In 24 of 44 patients, treadmill exercise stress test was also performed at the same period. Myocardial ischemic changes were observed in 11 patients, all combined with significant coronary artery stenosis. The sensitivity of SPECT for detection of overall coronary stenosis was 79%, coronary that of treadmill exercise test was only 33% (p<0.001). Furthermore, among the patients having significant coronary stenosis, the severity score was significantly elevated in patients who had electrocardiographic abnormal Q wave compared to those without abnormal Q wave (51.0±38.8 versus 20.0±12.1, p<0.05). These data suggest that the pharmacological stress scintigraphy using dipyridamole injection provides not only the accurate detection but quantitative evaluation of myocardial ischemia in these patients. This noninvasive technique may become one of the most useful index for detection and follow-up of myocardial ischemia in Kawasaki disease. (author)

  19. Myocardial ischemia and angina pectoris

    International Nuclear Information System (INIS)

    Selwyn, A.P.; Fox, K.M.; Jonathan, A.; Lavender, P.; Watson, I.

    1981-01-01

    Ambulatory monitoring of ST segment changes was performed in 60 patients presenting with angina, positive ECG stress tests and coronary artery disease, 85% of ischemic ECG events were asymptomatic, 37% occurred with no increase in heart rate and 15% of episodes either lasted 20 minutes or more or fluctuated in severity. A controlled pilot study in ten patients showed depression. Radionuclide studies in 50 patients with angina and coronary artery disease have shown that stress (i.e., atrial pacing) produced different patterns of disturbed regional myocardial perfusion related to the patient's exercise capacity and eventually leading to a decrease in regional myocardial perfusion during the ischemic episode. ST segment depression appeared only after the decrease in regional myocardial perfusion. These findings combined with past research suggest that patients with angina and coronary artery disease can suffer frequent asymptomatic disturbances of the regional myocardial perfusion. The frequency of these episodes and the time course for the recovery of the metabolic consequences mean that segments of ventricular myocardium may be constantly abnormal. The relative importance of changes in coronary tone and malfunction of platelets in the diseased coronary tree needs to be examined in clinical research. Pilot studies of antiplatelet agents have shown a significant beneficial effect on episodes of ischemia occurring at night and those occurring without any increase in heart rate. The techniques and observations in these patients with coronary artery disease all suggest that acute transient regional myocardial ischemia is caused by a variety of mechnisms. Further research using objective methods is required to discover the causes of ischemia and to rationalize treatment. (orig./MG) [de

  20. Radioiodinated tracers for myocardial imaging

    International Nuclear Information System (INIS)

    Kulkarni, P.V.; Corbett, J.R.

    1990-01-01

    Recent advances in the efficient production of high purity radioiodine (123I) and new efficient radiolabeling techniques have allowed the development of new classes of cardiovascular radiopharmaceuticals. These include 123I-labeled fatty acids to assess myocardial metabolism, 123I-metaiodobenzylguanidine (MIBG) for myocardial neuronal activity, labeled monoclonal antibodies for myocardial necrosis, and labeled lipoproteins for receptor concentration. 123I-labeled fatty acids and MIBG are under clinical investigation with encouraging results. 123I- and 111In-labeled fragments of monoclonal antibodies to myosin have been used for imaging myocardial necrosis in humans. The development of radiotracers for imaging of cholinergic and adrenergic receptors is still in the experimental stage. Recent advances in imaging instrumentation and radiopharmaceuticals have resulted in cardiac imaging applications beyond blood pool ventriculography, perfusion, and infarct-avid imaging. Developments of radioiodine (123I)-labeled agents promise to play an important role in the assessment of myocardial metabolism, neuronal activity, and receptor concentration. The chemistry of iodine is well defined compared with that of 99mTc; therefore, iodine isotopes are well suited for labeling biologically important molecules. Among the iodine isotopes, 123I has nearly ideal nuclear properties for nuclear medical applications with a 13.3-hour half-life (T1/2) and 159 keV gamma emission (83%). Despite the nearly ideal chemical and nuclear properties of 123I, the widespread application of 123I-based radiopharmaceuticals in clinical practice has been limited by high production costs (123I is produced in a cyclotron), relatively limited availability, and the presence of undesirable radionuclidic impurities (124I, T1/2 = 4.2 days; 125I, T1/2 = 60 days; 126I, T1/2 = 13.1 days). 77 references

  1. CURRENT REPERFUSION THERAPY POSSIBILITIES IN MYOCARDIAL INFARCTION AND ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    E. V. Konstantinova

    2015-01-01

    Full Text Available Myocardial infarction and ischemic stroke remain to be of the greatest medical and social importance because of their high prevalence, disability, and mortality rates. Intractable thrombotic occlusion of the respective artery leads to the formation of an ischemic lesion focus in the tissue of the heart or brain. Emergency reperfusion serves to decrease a necrotic focus, makes its formation reversible, and reduces patient death rates. The paper considers main reperfusion therapy lines: medical (with thrombolytic drugs and mechanical (with primary interventions one and their combination in treating patients with acute myocardial and cerebral ischemia. Each reperfusion procedure is discussed in view of its advantages, disadvantages, available guidelines, and possibilities of real clinical practice. Tenecteplase is assessed in terms of its efficacy, safety, and capacities for bolus administration, which allows its use at any hospital and at the pre-hospital stage. Prehospital thrombolysis permits reperfusion therapy to bring much closer to the patient and therefore aids in reducing time to reperfusion and in salvaging as much the myocardial volume as possible. The rapidest recovery of myocardial and cerebral perfusion results in a decreased necrotic area and both improved immediate and late prognosis. The results of randomized clinical trials studying the possibilities of the medical and mechanical methods to restore blood flow are analyzed in the context of evidence-based medicine. The reason why despite the available contraindications, limited efficiency, and the risk of hemorrhagic complications, thrombolytic therapy remains the method of choice for prehospital reperfusion, an alternative to primary percutaneous coronary intervention (PCI if it cannot be carried out in patients with myocardial infarction at the stated time, and the only treatment ischemic stroke treatment that has proven its efficiency and safety in clinical trials is under

  2. Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

    Science.gov (United States)

    Wang, Li; Lu, Min-Jie; Feng, Lei; Wang, Juan; Fang, Wei; He, Zuo-Xiang; Dou, Ke-Fei; Zhao, Shi-Hua; Yang, Min-Fu

    2018-03-07

    The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18 F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99m Tc-sestamibi and 18 F-FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18 F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.

  3. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Larissa Ferraz [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Mataveli, Fábio D’Aguiar [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva [Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2015-07-01

    Evaluate the effects of VEGF{sub 165} gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF{sub 165} treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF{sub 165}. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF{sub 165}, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF{sub 165} seems to provide a protective effect in the treatment of acute myocardial infarct.

  4. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    International Nuclear Information System (INIS)

    Garcia, Larissa Ferraz; Mataveli, Fábio D’Aguiar; Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell; Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva

    2015-01-01

    Evaluate the effects of VEGF_1_6_5 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF_1_6_5 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF_1_6_5. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF_1_6_5, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF_1_6_5 seems to provide a protective effect in the treatment of acute myocardial infarct

  5. Study progress of cardiac MRI technology in assessment of myocardial viability after myocardial infarction

    International Nuclear Information System (INIS)

    Wang Jing; Zhang Hao

    2013-01-01

    Acute myocardial infarction (AMI) is one of the most common diseases that cause disability and death around the world. Correctly and effectively assessing the myocardial viability after myocardial infarction can reduce the disabled rate and mortality rate. At present, many methods could be used to assess myocardial viability. The cardiac magnetic resonance imaging (CMR) technology has a lot of advantages compared to other methods. In this paper, we reviewed the research progress of CMR in assessment of myocardial viability after myocardial infarction, and compared CMR with other technologies. (authors)

  6. Evaluation of left ventricular function in patient with old myocardial infarction by 201-thallium myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Kanji; Shimohara, Yasuaki; Ito, Misao; Okada, Keisei [Kure Kyosai Hospital, Hiroshima (Japan); Kodama, Kazunori

    1984-08-01

    Correlation between the ratio of myocardial defect calculated by 201-thallium myocardial scintigraphy and the left ventricular ejection fraction (LVEF) obtained by gated blood pool scintigraphy and the maximum level of creatine phosphokinase (CPK) was studied in 70 patients with old myocardial infarction. There was a significant correlation between the defect ratio and the LVEF or CPK level in patients with anterior or septal myocardial infarction. In all patients with inferior myocardial infarction in whom no defect was seen, the LVEF was more than 40%. However, no distinct correlation between the defect ratio and the LVEF or CPK level was obtained in cases of inferior myocardial infarction.

  7. Diffusion chamber system for testing of collagen-based cell migration barriers for separation of ligament enthesis zones in tissue-engineered ACL constructs.

    Science.gov (United States)

    Hahner, J; Hoyer, M; Hillig, S; Schulze-Tanzil, G; Meyer, M; Schröpfer, M; Lohan, A; Garbe, L-A; Heinrich, G; Breier, A

    2015-01-01

    A temporary barrier separating scaffold zones seeded with different cell types prevents faster growing cells from overgrowing co-cultured cells within the same construct. This barrier should allow sufficient nutrient diffusion through the scaffold. The aim of this study was to test the effect of two variants of collagen-based barriers on macromolecule diffusion, viability, and the spreading efficiency of primary ligament cells on embroidered scaffolds. Two collagen barriers, a thread consisting of a twisted film tape and a sponge, were integrated into embroidered poly(lactic-co-caprolactone) and polypropylene scaffolds, which had the dimension of lapine anterior cruciate ligaments (ACL). A diffusion chamber system was designed and established to monitor nutrient diffusion using fluorescein isothiocyanate-labeled dextran of different molecular weights (20, 40, 150, 500 kDa). Vitality of primary lapine ACL cells was tested at days 7 and 14 after seeding using fluorescein diacetate and ethidium bromide staining. Cell spreading on the scaffold surface was measured using histomorphometry. Nuclei staining of the cross-sectioned scaffolds revealed the penetration of ligament cells through both barrier types. The diffusion chamber was suitable to characterize the diffusivity of dextran molecules through embroidered scaffolds with or without integrated collagen barriers. The diffusion coefficients were generally significantly lower in scaffolds with barriers compared to those without barriers. No significant differences between diffusion coefficients of both barrier types were detected. Both barriers were cyto-compatible and prevented most of the ACL cells from crossing the barrier, whereby the collagen thread was easier to handle and allowed a higher rate of cell spreading.

  8. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    Science.gov (United States)

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production. © 2013 Wiley Periodicals, Inc.

  9. Correlation of the myocardial perfusion corrected by attenuation with the coronariography. Preliminary results; Correlacion de la perfusion miocardica corregida por atenuacion con la coronariografia

    Energy Technology Data Exchange (ETDEWEB)

    Garcia C, S.E.; Garcia O, R. [Servicio de Medicina Nuclear, Centro Medico ABC, Campis Observatorio, IAP (Mexico)

    2005-07-01

    The attenuation that suffers the radiation in the soft tissues of the hinders the appropriate interpretation of the myocardial perfusion studies, for what have been implemented attenuation correction systems to reduce the attenuation for soft tissues and to provide myocardial perfusion images more accurate in the diagnosis of coronary illness. The objective was to evaluate the utility of an attenuation correction system (with source of Gadolinium 153) to minimize the devices that look like true defects of myocardial perfusion, caused by soft tissues (mammary tissue, thoracic wall, abdomen, left hemi diaphragm), and to compare those interpretations of the studies with the interpretations of the corresponding coronariographies. The method consists of 95 electronic files which were revised with the concept of heart catheterization, being identified 20 patients from the masculine sex to those that underwent coronariography among May 1999 and December 2002, and that they had study of myocardial perfusion in a maximum period of 3 months foresaw to the invasive procedure. (Author)

  10. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Hasan Ali Kiraz

    2015-12-01

    Full Text Available Objective: Ischemia/reperfusion (I/R injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg were randomly divided into three equal groups as follows: the diabetic I/R group (DIR in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL, which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC which underwent sham operations without tightening of the coronary sutures. As a control group (C, six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p=0.008. Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively. Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001. Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively. Also, myocardial tissue edema was significantly different among groups (p=0.006. The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively. Conclusion: Taken together, our data

  11. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    Science.gov (United States)

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  12. Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure

    Directory of Open Access Journals (Sweden)

    Julia Pohl

    2017-10-01

    Full Text Available Macrophage migration inhibitory factor (MIF is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF-1α. We here report on MIF expression in the failing human heart and assess myocardial MIF in different types of cardiomyopathy. Myocardial tissue samples from n = 30 patients were analyzed by quantitative Real-Time PCR. MIF and HIF-1α mRNA expression was analyzed in myocardial samples from patients with ischemic (ICM and non-ischemic cardiomyopathy (NICM and from patients after heart transplantation (HTX. MIF expression was elevated in myocardial samples from patients with ICM compared to NICM. Transplanted hearts showed lower MIF levels compared to hearts from patients with ICM. Expression of HIF-1α was analyzed and was shown to be significantly increased in ICM patients compared to patients with NICM. MIF and HIF-1α mRNA is expressed in the human heart. MIF and HIF-1α expression depends on the underlying type of cardiomyopathy. Patients with ICM show increased myocardial MIF and HIF-1α expression.

  13. Catecholamine stimulation, substrate competition, and myocardial glucose uptake in conscious dogs assessed with positron emission tomography

    International Nuclear Information System (INIS)

    Merhige, M.E.; Ekas, R.; Mossberg, K.; Taegtmeyer, H.; Gould, K.L.

    1987-01-01

    Uptake of radiolabelled deoxyglucose out of proportion to reduced coronary flow demonstrated by positron emission tomography has been used to identify reversibly ischemic, viable myocardium. For this concept to be applied reliably in the clinical setting, factors that may depress glucose availability independent of tissue viability, such as adrenergic stimulation and substrate competition, must be examined. Accordingly, we studied the effect of catecholamine stimulation by dopamine on myocardial glucose uptake in vivo using chronically instrumented, intact dogs and positron emission tomography. We measured myocardial activity of [2- 18 F]-2-deoxyglucose (FDG) and 82 Rb in glucose-loaded animals randomly studied during dopamine infusion, during insulin infusion, and then during their combined infusion. Myocardial FDG uptake was significantly decreased when animals were treated with dopamine, compared with treatment in the same animals with insulin. When insulin was added to the dopamine infusion, myocardial FDG uptake was restored. In contrast, myocardial activity of 82 Rb, which is taken up in proportion to coronary flow, was similar under all three experimental conditions. Plasma glucose, free fatty acid, and lactate concentrations were determined before and during each infusion. The depression of myocardial FDG activity seen during dopamine infusion and its reversal with addition of insulin can be explained on the basis of effects of these hormones on substrate availability and competition

  14. Effect of methylprednisolone upon technetium-99m pyrophosphate assessment of myocardial necrosis in the canine countershock model

    International Nuclear Information System (INIS)

    Schneider, R.M.; Hayslett, J.P.; Downing, S.E.; Berger, H.J.; Donabedian, R.K.; Zaret, B.L.

    1977-01-01

    RRepeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-/sup 99m/ pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P < 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in MP dogs, resulting in accelerated urinary excretion of PYP (46.9 +- 3.6 vs 35.8 +- 2.4 percent injected dose in one hour, P < 0.01), and reduced blood PYP. Thus, MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data

  15. Construction of collagen II/hyaluronate/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering and preliminary analysis of its physico-chemical properties and biocompatibility.

    Science.gov (United States)

    Li, Chang-Qing; Huang, Bo; Luo, Gang; Zhang, Chuan-Zhi; Zhuang, Ying; Zhou, Yue

    2010-02-01

    To construct a novel scaffold for nucleus pulposus (NP) tissue engineering, The porous type II collagen (CII)/hyaluronate (HyA)-chondroitin-6-sulfate (6-CS) scaffold was prepared using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross-linking system. The physico-chemical properties and biocompatibility of CII/HyA-CS scaffolds were evaluated. The results suggested CII/HyA-CS scaffolds have a highly porous structure (porosity: 94.8 +/- 1.5%), high water-binding capacity (79.2 +/- 2.8%) and significantly improved mechanical stability by EDC/NHS crosslinking (denaturation temperature: 74.6 +/- 1.8 and 58.1 +/- 2.6 degrees C, respectively, for the crosslinked scaffolds and the non-crosslinked; collagenase degradation rate: 39.5 +/- 3.4 and 63.5 +/- 2.0%, respectively, for the crosslinked scaffolds and the non-crosslinked). The CII/HyA-CS scaffolds also showed satisfactory cytocompatibility and histocompatibility as well as low immunogenicity. These results indicate CII/HyA-CS scaffolds may be an alternative material for NP tissue engineering due to the similarity of its composition and physico-chemical properties to those of the extracellular matrices (ECM) of native NP.

  16. Imaging techniques in nuclear cardiology for the assessment of myocardial viability

    NARCIS (Netherlands)

    Slart, RHJA; Bax, JJ; van Veldhuisen, DJ; van der Wall, EE; Dierckx, RAJO; Jager, PL

    The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with sufficient viable myocardium, patients with predominantly scar tissue should be

  17. Diagnosis of early human myocardial ischemic damage with electron probe microanalysis

    International Nuclear Information System (INIS)

    Singh, S.; Abraham, J.L.; Raasch, F.; Wolf, P.; Bloor, C.M.

    1983-01-01

    We determined the Na/K x-ray intensity ratio in frozen sections of myocardial tissues obtained at autopsy from patients who died from various causes, using electron probe analysis. We have been able to distinguish between the ischemically injured and normal cells. The method is simple, fast, and dependable even when the duration of ischemia is only 30 minutes

  18. Method for preparing 99mTc-labelled radiopharmaceuticals for myocardial scintigraphy

    International Nuclear Information System (INIS)

    Seifert, S.; Syhre, R.; Muenze, R.

    1987-01-01

    Radiopharmaceuticals which preferably concentrate in myocardial tissue are prepared, in particular technetium compounds with the reducing ligand molecule DMPE. A method is introduced to convert pertechnetate in one step into the proposed compound by means of a saline, slow-oxidizing and lyophilized form of the reducing ligand DMPE, preferably DMPE x 2HCl

  19. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction

    NARCIS (Netherlands)

    M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert); F.J.J. van de Werf (Frans); P.W. Armstrong (Paul); P.E. Aylward (Philip Edmund); G.I. Barbash; E.R. Bates (Eric); A. Betriu; J.H. Chesebro (James); J.J. Col (Jacques); D.P. de Bono (David); J.M. Gore (Joel); A.D. Guerci (Alan); J.R. Hampton (John)

    1993-01-01

    textabstractBACKGROUND: The relative efficacy of streptokinase and tissue plasminogen activator and the roles of intravenous as compared with subcutaneous heparin as adjunctive therapy in acute myocardial infarction are unresolved questions. The current trial was designed to compare new, aggressive

  20. Myocardial perfusion modeling using MRI

    DEFF Research Database (Denmark)

    Larsson, H B; Fritz-Hansen, T; Rostrup, Egill

    1996-01-01

    In the present study, it is shown that it is possible to quantify myocardial perfusion using magnetic resonance imaging in combination with gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA). Previously, a simple model and method for measuring myocardial perfusion using an inversion recovery...... turbo-FLASH (fast low-angle shot) sequence and Gd-DTPA has been presented. Here, an extension of the model is presented taking into account fast and slow water exchange between the compartments, enabling the calculation of the unidirectional influx constant (Ki) for Gd-DTPA, the distribution volume...... of Gd-DTPA (lambda), the vascular blood volume (Vb), and the time delay through the coronary arteries (delta T). The model was evaluated by computer simulation and used on experimental results from seven healthy subjects. The results in the healthy volunteers for a region of interest placed...

  1. Use of ultrafast computed tomography to quantitate regional myocardial perfusion: a preliminary report

    International Nuclear Information System (INIS)

    Rumberger, J.A.; Feiring, A.J.; Lipton, M.J.; Higgins, C.B.; Ell, S.R.; Marcus, M.L.

    1987-01-01

    The purpose of this study was to assess the potential for rapid acquisition computed axial tomography (Imatron C-100) to quantify regional myocardial perfusion. Myocardial and left ventricular cavity contrast clearance curves were constructed after injecting nonionic contrast (1 ml/kg over 2 to 3 seconds) into the inferior vena cava of six anesthetized, closed chest dogs (n = 14). Independent myocardial perfusion measurements were obtained by coincident injection of radiolabeled microspheres into the left atrium during control, intermediate and maximal myocardial vasodilation with adenosine (0.5 to 1.0 mg/kg per min, intravenously, respectively). At each flow state, 40 serial short-axis scans of the left ventricle were taken near end-diastole at the midpapillary muscle level. Contrast clearance curves were generated and analyzed from the left ventricular cavity and posterior papillary muscle regions after excluding contrast recirculation and minimizing partial volume effects. The area under the curve (gamma variate function) was determined for a region of interest placed within the left ventricular cavity. Characteristics of contrast clearance data from the posterior papillary muscle region that were evaluated included the peak myocardial opacification, area under the contrast clearance curve and a contrast clearance time defined by the full width/half maximal extent of the clearance curve. Myocardial perfusion (microspheres) ranged from 35 to 450 ml/100 g per min (mean 167 +/- 125)

  2. Myocardial delayed contrast enhancement in patients with arterial hypertension: Initial results of cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Kjel [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: kjel_andersen@web.de; Hennersdorf, Marcus [Department of Cardiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: hennersdorf@med.uni-duesseldorf.de; Cohnen, Mathias [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: cohnen@med.uni-duesseldorf.de; Blondin, Dirk [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: blondin@med.uni-duesseldorf.de; Moedder, Ulrich [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: moedder@uni-duesseldorf.de; Poll, Ludger W. [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: poll@gmx.de

    2009-07-15

    Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

  3. Exercise training prior to myocardial infarction attenuates cardiac deterioration and cardiomyocyte dysfunction in rats

    Directory of Open Access Journals (Sweden)

    Luiz Henrique Marchesi Bozi

    2013-04-01

    Full Text Available OBJECTIVES: The present study was performed to investigate 1 whether aerobic exercise training prior to myocardial infarction would prevent cardiac dysfunction and structural deterioration and 2 whether the potential cardiac benefits of aerobic exercise training would be associated with preserved morphological and contractile properties of cardiomyocytes in post-infarct remodeled myocardium. METHODS: Male Wistar rats underwent an aerobic exercise training protocol for eight weeks. The rats were then assigned to sham surgery (SHAM, sedentary lifestyle and myocardial infarction or exercise training and myocardial infarction groups and were evaluated 15 days after the surgery. Left ventricular tissue was analyzed histologically, and the contractile function of isolated myocytes was measured. Student's t-test was used to analyze infarct size and ventricular wall thickness, and the other parameters were analyzed by the Kruskal-Wallis test followed by Dunn's test or a one-way analysis of variance followed by Tukey's test (p<0.05. RESULTS: Myocardial infarctions in exercise-trained animals resulted in a smaller myocardial infarction extension, a thicker infarcted wall and less collagen accumulation as compared to myocardial infarctions in sedentary animals. Myocardial infarction-induced left ventricular dilation and cardiac dysfunction, as evaluated by +dP/dt and -dP/dt, were both prevented by previous aerobic exercise training. Moreover, aerobic exercise training preserved cardiac myocyte shortening, improved the maximum shortening and relengthening velocities in infarcted hearts and enhanced responsiveness to calcium. CONCLUSION: Previous aerobic exercise training attenuated the cardiac dysfunction and structural deterioration promoted by myocardial infarction, and such benefits were associated with preserved cardiomyocyte morphological and contractile properties.

  4. [Effect of edaravone on oxidative stress and myocardial fibrosis induced by isoproterenol in rats].

    Science.gov (United States)

    Wang, Shixiang; Lu, Zhifeng; Xu, Wei; Chen, Youquan; Chen, Ximing

    2015-11-01

    To investigate the effect of edaravone on oxidative stress and myocardial fibrosis induced by isoproterenol in rats. Fifty male SD rats were randomly divided into 5 groups, including a control group, a myocardial fibrosis model (established by injections of isopropyl adrenaline for 10 days) group, and 3 edaravone groups with edaravone treatment at low, medium, or high doses for 14 days. After the treatments, the rats were examined for the degree of myocardial fibrosis, left ventricular mass index (LVMI), collagen volume fraction (CVF), and myocardial contents of collagen I (Col I), collage III (Col III), hydroxyproline (Hyp), superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO); The expression of transforming growth factor-β1 (TGF-β1) in the myocardial tissues was examined by immunofluorescence assay and Western blotting. Compared with the control rats, the rat models of myocardial fibrosis showed significantly increased CVF and LVMI (P=0.000), which were lowered by edaravone treatments in a dose-dependent manner (Pedaravone; the contents of MDA was higher (P=0.000) and SOD and NO were lower in the model group (P=0.000), and edaravone treatments obviously increased SOD and NO contents (Pedaravone treatments (P=0.000). The myocardial content of MDA was positively correlated while SOD and NO were negatively with LVMI, CVF, Col I, Col III and Hyp; TGF-β1 was positively correlated with LVMI, CVF, Col I, Col III, Hyp and MDA but negatively with SOD and NO. Edaravone can relieve oxidative stress and inhibit TGF-β1 activation to ameliorate myocardial fibrosis in rats.

  5. Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs.

    Science.gov (United States)

    Ford, Jordan; McEndaffer, Laura; Renshaw, Randall; Molesan, Alex; Kelly, Kathleen

    2017-11-01

    Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%-45%) and 2 of 41 controls (5%; 95% CI, 0.1%-16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

  6. Myocardial delayed contrast enhancement in patients with arterial hypertension: Initial results of cardiac MRI

    International Nuclear Information System (INIS)

    Andersen, Kjel; Hennersdorf, Marcus; Cohnen, Mathias; Blondin, Dirk; Moedder, Ulrich; Poll, Ludger W.

    2009-01-01

    Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

  7. Functional tests for myocardial ischemia

    International Nuclear Information System (INIS)

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A.

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references

  8. [Myocardial microcirculation in humans--new approaches using MRI].

    Science.gov (United States)

    Wacker, Christian M; Bauer, Wolfgang R

    2003-03-01

    One crucial goal of magnetic resonance imaging (MRI) in patients with coronary artery disease (CAD) is the characterization of myocardial microcirculation that reflects tissue supply much better than detection and quantification of a stenosis itself. PERFUSION: Myocardial perfusion is one important parameter of microcirculation and it is commonly detected by first-pass techniques using contrast agents (CA). Despite the quantification of perfusion it is an indispensable component of a comprehensive diagnosis to determine the perfusion reserve, which is believed a good indicator for viability of myocardium. However, most MRI techniques for perfusion imaging are Ca based and this implies a restricted reproducibility in humans. Beyond it, most first-pass techniques are qualitative and not quantitative. REGIONAL BLOOD VOLUME: Another parameter of microcirculation is the regional intracapillary myocardial blood volume (RBV) that almost represents the whole intramyocardial blood volume due to its dominating volume fraction. The RBV reflects the autoregulatory adaptation of microvessels, e.g., a severe stenosis may lead to an increase of the RBV by capillary recruitment, and the RBV is reduced in scar areas. The RBV may be quantified by first-pass techniques; however, this demands a definite relation between signal intensity and concentration of the CA, which is difficult to find for the range of concentrations present during the first pass. Until recently, no techniques existed for the exact and noninvasive assessment of the RBV. CAPILLARY RECRUITMENT: The evaluation of the relevance of a coronary artery stenosis is of paramount interest for the therapeutic decision. A severe stenosis implies the activation of compensation mechanisms, which includes poststenotic dilation of the microvascular system. This lowering of the vascular resistance aims to maintain sufficient blood supply at least under resting conditions. However, many obstacles hamper the noninvasive assessment

  9. Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

    Science.gov (United States)

    Sun, Hongyu; Zhou, Jing; Huang, Zhu; Qu, Linlin; Lin, Ning; Liang, Chengxiao; Dai, Ruiwu; Tang, Lijun; Tian, Fuzhou

    2017-01-01

    Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. PMID:28450785

  10. Cardiac MRI for myocardial ischemia.

    LENUS (Irish Health Repository)

    Daly, Caroline

    2013-01-01

    Proper assessment of the physiologic impact of coronary artery stenosis on the LV myocardium can affect patient prognosis and treatment decisions. Cardiac magnetic resonance imaging (CMR) assesses myocardial perfusion by imaging the myocardium during a first-pass transit of an intravenous gadolinium bolus, with spatial and temporal resolution substantially higher than nuclear myocardial perfusion imaging. Coupled with late gadolinium enhancement (LGE) imaging for infarction during the same imaging session, CMR with vasodilating stress perfusion imaging can qualitatively and quantitatively assess the myocardial extent of hypoperfusion from coronary stenosis independent of infarcted myocardium. This approach has been validated experimentally, and multiple clinical trials have established its diagnostic robustness when compared to stress single-photon emission computed tomography. In specialized centers, dobutamine stress CMR has been shown to have incremental diagnostic value above stress echocardiography due to its high imaging quality and ability to image the heart with no restriction of imaging window. This paper reviews the technical aspects, diagnostic utility, prognostic values, challenges to clinical adaptation, and future developments of stress CMR imaging.

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

    Science.gov (United States)

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

    2016-07-01

    Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Fluorine-18 heart dosimetry in myocardial perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Toledo, Janine M.; Trindade, Bruno; Campos, Tarcísio P.R., E-mail: janine.toledo@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Programa de Pós-Graduação em Ciências e Técnicas Nucleares

    2017-07-01

    This paper conducts a recalling in myocardial perfusion imaging (MPI) followed by a spatial dosimetric investigation of the Fluorine-18 distributed at the myocardium by self-absorption of the heart uptake. Methods and Results: Radiological data manipulation was prepared and a computational heart voxelized model was assembled. A set of images from the abdominal aorta and angiotomography of the thorax was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of fluorine-18 was assumed into the heart myocardial wall. MCNP – Monte Carlo Code was used to provide the photon transport into the heart model taken in consideration the interactions into the tissues. The spatial dose distribution and histogram dose versus volume are presented. An analytical alternative model was addressed to the data validation. The present developed tools can produce spatial dose distribution in MPI at heart. Specially, the dosimetry performed elucidates imparted dose in the myocardial muscle per unit of injected Fluorine-18 activity by self-absorption of the heart uptake, which can contribute to future deterministic effect investigations. (author)

  13. Tc99m-sestamibi dosimetry in myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Toledo, Janine M.; Trindade, Bruno M.; Campos, Tarcisio P.R.

    2015-01-01

    This paper addressed myocardial perfusion imaging providing a spatial dosimetric investigation of the 99m Tc-radiopharmaceutical dose distribution at the myocardium. Radiological data manipulation was performed in order to create a computational voxel model of the heart. A set of images obtained by thoracic angiotomography and abdominal aorta was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of 99m Tc was assumed into the cardiac muscle. Simulations of the transport of particles through the voxel and the interaction with the heart tissues were performed on the MCNP - Monte Carlo Code. The spatial dose distribution in the heart model is displayed as well as the dose versus volume histogram of the heart muscle. The present computational tools can generate spatial doses distribution in myocardial perfusion imaging. Specially, the dosimetry performed elucidates imparted dose distribution in the myocardial muscle per unit of injected 99m Tc activity, which can contribute to future deterministic effect investigations. (author)

  14. Myocardial Perfusion: Characteristics of Distal Intramyocardial Arteriolar Trees.

    Science.gov (United States)

    Zamir, Mair; Vercnocke, Andrew J; Edwards, Phillip K; Anderson, Jill L; Jorgensen, Steven M; Ritman, Erik L

    2015-11-01

    A combination of experimental, theoretical, and imaging methodologies is used to examine the hierarchical structure and function of intramyocardial arteriolar trees in porcine hearts to provide a window onto a region of myocardial microvasculature which has been difficult to fully explore so far. A total of 66 microvascular trees from 6 isolated myocardial specimens were analyzed, with a cumulative number of 2438 arteriolar branches greater than or equal to 40 μm lumen diameter. The distribution of flow rates within each tree was derived from an assumed power law relationship for that tree between the diameter of vessel segments and flow rates that are consistent with that power law and subject to conservation of mass along hierarchical structure of the tree. The results indicate that the power law index increases at levels of arteriolar vasculature closer to the capillary level, consistent with a concomitant decrease in shear stress acting on endothelial tissue. These results resolve a long standing predicament which could not be resolved previously because of lack of data about the 3D, interconnected, arterioles. In the context of myocardial perfusion, the results indicate that the coefficient of variation of flow rate in pre-capillary distal arterioles is high, suggesting that heterogeneity of flow rate in these arterioles is not entirely random but may be due at least in part to active control.

  15. Fluorine-18 heart dosimetry in myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Toledo, Janine M.; Trindade, Bruno; Campos, Tarcísio P.R.

    2017-01-01

    This paper conducts a recalling in myocardial perfusion imaging (MPI) followed by a spatial dosimetric investigation of the Fluorine-18 distributed at the myocardium by self-absorption of the heart uptake. Methods and Results: Radiological data manipulation was prepared and a computational heart voxelized model was assembled. A set of images from the abdominal aorta and angiotomography of the thorax was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of fluorine-18 was assumed into the heart myocardial wall. MCNP – Monte Carlo Code was used to provide the photon transport into the heart model taken in consideration the interactions into the tissues. The spatial dose distribution and histogram dose versus volume are presented. An analytical alternative model was addressed to the data validation. The present developed tools can produce spatial dose distribution in MPI at heart. Specially, the dosimetry performed elucidates imparted dose in the myocardial muscle per unit of injected Fluorine-18 activity by self-absorption of the heart uptake, which can contribute to future deterministic effect investigations. (author)

  16. MYOCARDIAL DEFORMATION AND COMPLETE LEFT BUNDLE BRANCH BLOCK

    Directory of Open Access Journals (Sweden)

    E. N. Pavlyukova

    2015-12-01

    Full Text Available Tissue Doppler imaging is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular systolic and diastolic function. Over the last 10 years, myocardial deformation imaging has become possible initially with tissue Doppler , and more recently with myocardial speckle-tracking using 2D echocardiography. Unlike simple tissue velocity measurements, deformation measurements are specific for the region of interest. Strain rate or strain measurements have been used as sensitive indicators for subclinical diseases, and it is the most widely used tool to assess mechanical dyssynchrony. Left bundle branch block is a frequent, etiologically heterogeneous, clinically hostile and diagnostically challenging entity. About 2% of patients underwent cardiac stress testing show stable or intermittent left bundle branch block. Presence of left bundle branch block is associated with a lower and slower diastolic coronary flow velocity especially during hyperemia. Stress echocardiography is the best option for the diagnosis of ischemic heart disease, albeit specificity and sensitivity reduce in patients with left bundle branch block in the territory of left anterior descending artery in presence of initial septum dyskinesia.

  17. Effect of limb ischemic preconditioning on myocardial apoptosis-related proteins in ischemia-reperfusion injury

    Science.gov (United States)

    GAO, JIANZHI; ZHAO, LINJING; WANG, YONGLING; TENG, QINGLEI; LIANG, LIDONG; ZHANG, JINYING

    2013-01-01

    The aim of this study was to investigate the effect of limb ischemic preconditioning (LIPC) on myocardial apoptosis in myocardial ischemia-reperfusion injury (MIRI), as well as the regulation of caspase-3 and the B cell lymphoma 2 (Bcl-2) gene in LIPC. A total of 50 rats were divided randomly into 5 groups (n=10). Four rats in each group were drawn out for detection of apoptosis. The sham, MIRI and LIPC groups underwent surgery without additional treatment. In the LY294002 group, LY294002 preconditioning was administered 15 min before reperfusion. In the LY294002+LIPC group, following LIPC, LY294002 was administered 15 min before reperfusion. The relative expression of myocardial Bcl-2 and caspase-3 mRNA and the apoptotic index for each group were determined by reverse transcription-polymerase chain reaction (RT-PCR) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. The ultrastructure of the cardiac muscle tissues was observed by election microscopy. Compared with the sham group, the expression of caspase-3 mRNA in the MIRI group significantly increased (P<0.05) and the expression of Bcl-2 mRNA clearly decreased. Compared with the MIRI group, LIPC reduced the expression of caspase-3 and increased the expression of Bcl-2 mRNA (P<0.05). There were no significant differences between the LY294002+LIPC group and the MIRI group. Compared with the sham group, the apoptotic index of myocardial cells in the MIRI group significantly increased (P<0.05). Compared with the MIRI group, LIPC significantly decreased the apoptotic index of myocardial cells (P<0.05) and LY294002 increased the apoptotic index of myocardial cells. Compared with the LIPC group, LY294002+LIPC significantly increased the apoptotic index of myocardial cells (P<0.05). There were no significant differences between the LY294002+LIPC and MIRI groups. In conclusion, LIPC increased the expression of Bcl-2 and decreased caspase-3 mRNA and

  18. [Effects and mechanisms of ursodeoxycholic acid on isoprenaline-Induced myocardial fibrosis in mice].

    Science.gov (United States)

    Li, X; Han, K Q; Shi, Y N; Men, S Z; Li, S; Sun, M H; Dong, H; Lu, J J; Ma, L J; Zhao, M; Li, D; Liu, W

    2017-02-07

    Objective: To investigate the effects and possible mechanisms of ursodeoxycholic acid (UDCA) on myocardial fibrosis in mice. Method: To observe the expression of transforming growth factor(TGF) -β1, CTGF, MMPs and the degree of myocardial fibrosis, 61 male Kunming mice were randomly divided into normal group, low dose UDCA group, high dose of UDCA group, spironolactone group, and the control group.Isoproterenol (ISO) injection was given subcutaneously (30 d) to make the model of myocardial fibrosis.Corresponding anti-fibrosis drugs (UDCA or spironolactone) were given by gavage.HE staining and Masson staining were performed to explore the inflammation and fibrosis in the myocardium.The expression of collagen Ⅰ and collagen Ⅲ protein was detected by immunohistochemistry to evaluate the degree of fibrosis among the groups.Western blot was used to detect the expression of transforming growth factor, (TGF)-β1, connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2, -9, tissue inhibitor of metalloproteinase (TIMP)-4, -1 and anti-phospho-NFKBIA (p-IκB-α) inhibitor of NF-κB (IκB) protein in myocardium. Results: HE and Masson staining results showed that in the normal group, myocardial fibrosis is less, while the control group showed a large amount of fibrotic tissue ( P 0.05). UDCA decrease p-IκB-α expression and increase IκB protein expression dose-dependently. Conclusions: UDCA can relieve isoproterenol induced myocardial fibrosis and reduce the myocardial collagen Ⅰ and collagen Ⅲ deposition in a dose dependent manner.Down-regulating of TGFβ-1 protein expression through the inhibition of TGR5-NF-κB signal transduction pathway might be a potential mechanism underlying UDCA's effects.

  19. Assessment of myocardial fibrosis with T1 mapping MRI

    International Nuclear Information System (INIS)

    Everett, R.J.; Stirrat, C.G.; Semple, S.I.R.; Newby, D.E.; Dweck, M.R.; Mirsadraee, S.

    2016-01-01

    Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson–Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present.

  20. Assessment of myocardial fibrosis with T1 mapping MRI.

    Science.gov (United States)

    Everett, R J; Stirrat, C G; Semple, S I R; Newby, D E; Dweck, M R; Mirsadraee, S

    2016-08-01

    Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present. Copyright © 2016 The Royal College

  1. Constructed Wetlands

    Science.gov (United States)

    these systems can improve water quality, engineers and scientists construct systems that replicate the functions of natural wetlands. Constructed wetlands are treatment systems that use natural processes

  2. Severe acute myocardial infarction and peripheral thrombosis in patient with bladder cancer

    Directory of Open Access Journals (Sweden)

    Ahmet Seyfeddin Gürbüz

    2017-12-01

    Full Text Available Cancer-associated thrombosis worsens the lives of patients substantially. Venous manifestations of cancer-associated thrombosis include deep vein thrombosis and pulmonary embolism. Arterial events include stroke and myocardial infarction. In this patient, myocardial infarction and cardiogenic shock are associated with diffuse coronary thrombosis together with peripheral thrombosis. He had surgery because of bladder carcinoma. Severe hypercoagulable condition probably facilitated by cancer itself and surgery caused multivessel coronary and peripheral intense thrombus burden. Intracoronary 10 mcg/kg tirofiban bolus and 15 mg tissue plasminogen activator (tPA were administered respectively before revascularization and thrombectomy operation was performed. Complete revascularization was achieved.

  3. Screening for silent myocardial ischemia caseof diabetics : interest of myocardial perfusion scintigraphy

    International Nuclear Information System (INIS)

    Bahri, Haifa

    2007-01-01

    Silent myocardial ischemia is a major cause of morbidity and mortality in diabetic patients. Its diagnosis by noninvasive means such as myocardial SPECT would improve the management of these patients. The purpose of this study is to assess the frequency of silent myocardial ischemia in asymptomatic diabetics and their evolution. As a result, the myocardial SPECT is a reliable tool for screening for silent myocardial ischemia in diabetic patients. Its prognostic value allows to stratify the cardiac risk and guide therapeutic management. Its integration into a screening strategy in Tunisia seems limited by its low availability and cost. The latter could be reduced by better patient selection.

  4. Microgel Technology to Advance Modular Tissue Engineering

    NARCIS (Netherlands)

    Kamperman, Tom

    2018-01-01

    The field of tissue engineering aims to restore the function of damaged or missing tissues by combining cells and/or a supportive biomaterial scaffold into an engineered tissue construct. The construct’s design requirements are typically set by native tissues – the gold standard for tissue

  5. The Role of Sulfur Dioxide in the Regulation of Mitochondrion-Related Cardiomyocyte Apoptosis in Rats with Isopropylarterenol-Induced Myocardial Injury

    Directory of Open Access Journals (Sweden)

    Junbao Du

    2013-05-01

    Full Text Available The authors investigated the regulatory effects of sulfur dioxide (SO2 on myocardial injury induced by isopropylarterenol (ISO hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO2 group, and SO2 only group. Cardiac function was measured and cardiomyocyte apoptosis was detected. Bcl-2, bax and cytochrome c (cytc expressions, and caspase-9 and caspase-3 activities in the left ventricular tissues were examined in the rats. The opening status of myocardial mitochondrial permeability transition pore (MPTP and membrane potential were analyzed. The results showed that ISO-treated rats developed heart dysfunction and cardiac injury. Furthermore, cardiomyocyte apoptosis in the left ventricular tissues was augmented, left ventricular tissue bcl-2 expression was down-regulated, bax expression was up-regulated, mitochondrial membrane potential was significantly reduced, MPTP opened, cytc release from mitochondrion into cytoplasm was significantly increased, and both caspase-9 and caspase-3 activities were increased. Administration of an SO2 donor, however, markedly improved heart function and relieved myocardial injury of the ISO-treated rats; it lessened cardiomyocyte apoptosis, up-regulated myocardial bcl-2, down-regulated bax expression, stimulated mitochondrial membrane potential, closed MPTP, and reduced cytc release as well as caspase-9 and caspase-3 activities in the left ventricular tissue. Hence, SO2 attenuated myocardial injury in association with the inhibition of apoptosis in myocardial tissues, and the bcl-2/cytc/caspase-9/caspase-3 pathway was possibly involved in this process.

  6. Myocardial viability assessment using nuclear imaging

    International Nuclear Information System (INIS)

    Matsunari, Ichiro; Hisada, Kinichi; Taki, Junichi; Nakajima, Kenichi; Tonami, Norihisa

    2003-01-01

    Myocardial assessment continues to be an issue in patients with coronary artery disease and left ventricular dysfunction. Nuclear imaging has long played an important role in this field. In particular, PET imaging using 18 F-fluorodeoxyglucose is regarded as the metabolic gold standard of tissue viability, which has been supported by a wide clinical experience. Viability assessment using SPECT techniques has gained more wide-spread clinical acceptance than PET, because it is more widely available at lower cost. Moreover, technical advances in SPECT technology such as gated-SPECT further improve the diagnostic accuracy of the test. However, other imaging techniques such as dobutamine echocardiography have recently emerged as competitors to nuclear imaging. It is also important to note that they sometimes may work in a complementary fashion to nuclear imaging, indicating that an appropriate use of these techniques may significantly improve their overall accuracy. In keeping these circumstances in mind, further efforts are necessary to further improve the diagnostic performance of nuclear imaging as a reliable viability test. (author) 107 refs

  7. Myocardial contusion in patients with blunt chest trauma as evaluated by thallium 201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Bodin, L.; Rouby, J.J.; Viars, P.

    1988-01-01

    Fifty five patients suffering from blunt chest trauma were studied to assess the diagnosis of myocardial contusion using thallium 201 myocardial scintigraphy. Thirty-eight patients had consistent scintigraphic defects and were considered to have a myocardial contusion. All patients with scintigraphic defects had paroxysmal arrhythmias and/or ECG abnormalities. Of 38 patients, 32 had localized ST-T segment abnormalities; 29, ST-T segment abnormalities suggesting involvement of the same cardiac area as scintigraphic defects; 21, echocardiographic abnormalities. Sixteen patients had segmental hypokinesia involving the same cardiac area as the scintigraphic defects. Fifteen patients had clinical signs suggestive of myocardial contusion and scintigraphic defects. Almost 70 percent of patients with blunt chest trauma had scintigraphic defects related to areas of myocardial contusion. When thallium 201 myocardial scintigraphy directly showed myocardial lesion, two-dimensional echocardiography and standard ECG detected related functional consequences of cardiac trauma

  8. Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins

    DEFF Research Database (Denmark)

    Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S

    2016-01-01

    BACKGROUND: Cardiac troponins have emerged as the preferred biomarkers for detecting myocardial necrosis and diagnosing myocardial infarction. However, current cardiac troponin assays do not discriminate between ischemic and nonischemic causes of myocardial cell death. Thus, when an increased...... troponin value is encountered in the absence of obvious myocardial ischemia, a careful search for other clinical conditions is crucial. METHODS: In 2010 to 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. An acute myocardial infarction...... was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak...

  9. Nifedipine for angina and acute myocardial ischemia

    NARCIS (Netherlands)

    P.G. Hugenholtz (Paul); J.W. de Jong (Jan Willem); P.D. Verdouw (Pieter); P.W.J.C. Serruys (Patrick)

    1983-01-01

    textabstractThis paper reviews the mechanisms believed to be responsible for myocardial ischaemia and the mode of action of calcium antagonist drugs. The clinical management of patients with myocardial ischaemia is discussed in the context of current knowledge about patho-physiology and drug action.

  10. The end of the unique myocardial band

    DEFF Research Database (Denmark)

    MacIver, David H; Partridge, John B; Agger, Peter

    2018-01-01

    Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour th...

  11. When is 201Tl myocardial scintigraphy indicated?

    International Nuclear Information System (INIS)

    Klepzig, H. Jr.; Kaltenbach, M.

    1987-01-01

    Myocardial scintigraphy with thallium-201 has met with good acceptance in cardiology and has proven its value. The method implies only low risk and yields diagnostic results that allow verification or disqualification of suspected myocardial ischemia in those cases where there is only reduced accuracy of the exercise electrocardiogram. (TRV) [de

  12. Do episodes of anger trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Möller, J; Hallqvist, J; Diderichsen, Finn

    1999-01-01

    Our objectives were to study anger as a trigger of acute myocardial infarction (MI) and to explore potential effect modification by usual behavioral patterns related to hostility.......Our objectives were to study anger as a trigger of acute myocardial infarction (MI) and to explore potential effect modification by usual behavioral patterns related to hostility....

  13. Monitoring of myocardial edema following acute myocardial infarction

    International Nuclear Information System (INIS)

    Tahir, E.; Sinn, M.; Avanesov, M.; Wien, J.; Saering, D.; Stehning, C.; Radunski, U. K.; Muellerleile, K.; Adam, G.; Lund, G. K.

    2015-01-01

    Full text: Currently, myocardial edema monitoring after acute myocardial infarction (AMI) is based on visualization of the region with increased signal-intensity on T2-weighted images. Native T1 and T2 mapping are promising novel MRI techniques to quantitatively assess myocardial edema. The purpose of the study was to quantitatively evaluate resorption of myocardial edema following AMI by native T1 and T2 -mapping cardiac magnetic resonance imaging (CMR). CMR (1.5 Tesla Philips Achieva) was performed in 30 patients four times after reperfused AMI at baseline (BL) at 9±6 days after infarction and at 7±1 weeks (follow-up 1, FU1), 3.6±0.5 months (FU2) and 6.5±0.7 months (FU3), respectively. Edema sensitive black-blood T2-weighted (T2w) STIR CMR was performed on end-diastolic LV short-axes. A free-breathing, navigatorgated multi-echo sequence was used for short-axis T2 mapping. T1 mapping was performed using the modified look-locker inversion recovery (MOLLI) sequence. T2 maps were calculated from nine and T1 maps from eight echoes using a dedicated plug-in written for OsiriX software. Two experienced observers independently evaluated T2w-CMR as well as T1 and T2 mapping using the HeAT-Software applying a threshold method. Size of edema and prolongation of the native T1- or T2-time was measured using a cutoff >2SD of remote normal myocardium. Edema size continuously decreased from BL with 32.8 %LV to 24.6 %LV at FU1, to 19.1 %LV at FU2 and to 16.4 %LV at FU3 using T2w-CMR. An almost identical decrease of edema size was observed using native T1 and T2 - mapping. T2 times only decreased between BL from 79±5 ms to 73±2 ms at FU1 (P<0.05), but no further change was observed at later time points with 70±5 ms at FU2 and 70±6 ms at FU3. At all time points the T2 times of remote normal myocardium were about 50±2 ms and significantly lower compared to the edema zone. Also native T1 time within the edema was with 1253 ±103 ms significantly increased compared to remote

  14. Construction management

    CERN Document Server

    Pellicer, Eugenio; Teixeira, José C; Moura, Helder P; Catalá, Joaquín

    2014-01-01

    The management of construction projects is a wide ranging and challenging discipline in an increasingly international industry, facing continual challenges and demands for improvements in safety, in quality and cost control, and in the avoidance of contractual disputes. Construction Management grew out of a Leonardo da Vinci project to develop a series of Common Learning Outcomes for European Managers in Construction. Financed by the European Union, the project aimed to develop a library of basic materials for developing construction management skills for use in a pan-European context. Focused exclusively on the management of the construction phase of a building project from the contractor's point of view, Construction Management covers the complete range of topics of which mastery is required by the construction management professional for the effective delivery of new construction projects. With the continued internationalisation of the construction industry, Construction Management will be required rea...

  15. Xylan polysaccharides fabricated into nanofibrous substrate for myocardial infarction

    International Nuclear Information System (INIS)

    Venugopal, J.; Rajeswari, R.; Shayanti, M.; Sridhar, R.; Sundarrajan, S.; Balamurugan, R.; Ramakrishna, S.

    2013-01-01

    Myocardial infarction, a main cause of heart failure, leads to loss of cardiac tissue impairment of left ventricular function. Repair of diseased myocardium with in vitro engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for myocardial infarction. We attempted to solve these problems by in vitro study by selecting a plant based polysaccharides beech wood Xylan for the normal functioning of infarcted myocardium. The present study fabricated Xylan based nanofibrous scaffolds cross-linked with glutaraldehyde (Glu) vapors for 24 h, 48 h and 1% Glu blended fibers for the culture of neonatal rat cardiac cells for myocardial infarction. These nanofibers were characterized by SEM, FT-IR, tensile testing and cell culture studies for the normal expression of cardiac proteins. The observed results showed that the Xylan/polyvinyl alcohol (PVA) 24 h Glu vapor cross-linked nanofibers (427 nm) having mechanical strength of 2.43 MPa and Young modulus of 3.74 MPa are suitable for the culture of cardiac cells. Cardiac cells proliferation increased only by 11% in Xylan/PVA 24 h Glu cross-linked nanofibers compared to control tissue culture plate (TCP). The normal cardiac cell morphology was observed in 24 h cross-linked Xylan/PVA nanofibers but 48 h cross-linked fibers cell morphology was changed to flattened and elongated on the fibrous surfaces. Confocal analysis for cardiac expression proteins actinin, connexin 43 was observed normally in 24 h Glu cross-linked nanofibers compared to all other nanofibrous scaffolds. The fabricated Xylan/PVA nanofibrous scaffold may have good potential for the normal functioning of infarcted myocardium. - Highlights: ► Fabrication of polysaccharides Xylan/PVA nanofibers for cardiac tissue engineering ► Nanofibers characterized by SEM, FT-IR, tensile testing and cell culture studies ► Isolation of cardiac cells and cultured on Xylan/PVA nanofibrous scaffolds ► Cultured cells on 24 h Glu cross

  16. Quantitative myocardial perfusion from static cardiac and dynamic arterial CT

    Science.gov (United States)

    Bindschadler, Michael; Branch, Kelley R.; Alessio, Adam M.

    2018-05-01

    Quantitative myocardial blood flow (MBF) estimation by dynamic contrast enhanced cardiac computed tomography (CT) requires multi-frame acquisition of contrast transit through the blood pool and myocardium to inform the arterial input and tissue response functions. Both the input and the tissue response functions for the entire myocardium are sampled with each acquisition. However, the long breath holds and frequent sampling can result in significant motion artifacts and relatively high radiation dose. To address these limitations, we propose and evaluate a new static cardiac and dynamic arterial (SCDA) quantitative MBF approach where (1) the input function is well sampled using either prediction from pre-scan timing bolus data or measured from dynamic thin slice ‘bolus tracking’ acquisitions, and (2) the whole-heart tissue response data is limited to one contrast enhanced CT acquisition. A perfusion model uses the dynamic arterial input function to generate a family of possible myocardial contrast enhancement curves corresponding to a range of MBF values. Combined with the timing of the single whole-heart acquisition, these curves generate a lookup table relating myocardial contrast enhancement to quantitative MBF. We tested the SCDA approach in 28 patients that underwent a full dynamic CT protocol both at rest and vasodilator stress conditions. Using measured input function plus single (enhanced CT only) or plus double (enhanced and contrast free baseline CT’s) myocardial acquisitions yielded MBF estimates with root mean square (RMS) error of 1.2 ml/min/g and 0.35 ml/min/g, and radiation dose reductions of 90% and 83%, respectively. The prediction of the input function based on timing bolus data and the static acquisition had an RMS error compared to the measured input function of 26.0% which led to MBF estimation errors greater than threefold higher than using the measured input function. SCDA presents a new, simplified approach for quantitative

  17. Xylan polysaccharides fabricated into nanofibrous substrate for myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Venugopal, J., E-mail: nnijrv@nus.edu.sg; Rajeswari, R.; Shayanti, M.; Sridhar, R.; Sundarrajan, S.; Balamurugan, R.; Ramakrishna, S.

    2013-04-01

    Myocardial infarction, a main cause of heart failure, leads to loss of cardiac tissue impairment of left ventricular function. Repair of diseased myocardium with in vitro engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for myocardial infarction. We attempted to solve these problems by in vitro study by selecting a plant based polysaccharides beech wood Xylan for the normal functioning of infarcted myocardium. The present study fabricated Xylan based nanofibrous scaffolds cross-linked with glutaraldehyde (Glu) vapors for 24 h, 48 h and 1% Glu blended fibers for the culture of neonatal rat cardiac cells for myocardial infarction. These nanofibers were characterized by SEM, FT-IR, tensile testing and cell culture studies for the normal expression of cardiac proteins. The observed results showed that the Xylan/polyvinyl alcohol (PVA) 24 h Glu vapor cross-linked nanofibers (427 nm) having mechanical strength of 2.43 MPa and Young modulus of 3.74 MPa are suitable for the culture of cardiac cells. Cardiac cells proliferation increased only by 11% in Xylan/PVA 24 h Glu cross-linked nanofibers compared to control tissue culture plate (TCP). The normal cardiac cell morphology was observed in 24 h cross-linked Xylan/PVA nanofibers but 48 h cross-linked fibers cell morphology was changed to flattened and elongated on the fibrous surfaces. Confocal analysis for cardiac expression proteins actinin, connexin 43 was observed normally in 24 h Glu cross-linked nanofibers compared to all other nanofibrous scaffolds. The fabricated Xylan/PVA nanofibrous scaffold may have good potential for the normal functioning of infarcted myocardium. - Highlights: ► Fabrication of polysaccharides Xylan/PVA nanofibers for cardiac tissue engineering ► Nanofibers characterized by SEM, FT-IR, tensile testing and cell culture studies ► Isolation of cardiac cells and cultured on Xylan/PVA nanofibrous scaffolds ► Cultured cells on 24 h Glu cross

  18. Ventricular and myocardial scintiscanning: Methodical fundamentals

    International Nuclear Information System (INIS)

    Standke, R.; Hoer, G.; Maul, F.D.

    1984-01-01

    Nuclear cardiology is concerned with non invasive procedures to quantitate global and regional left ventricular function (Radionuclide ventriculography), also the imaging of vitally perfused myocardium (Myocardial scintigraphy) is achieved. A gammacamera and a minicomputer are necessary. Radionuclide ventriculography enables the analysis of global and regional time dependent left ventricular volume curves and hence the evaluation of contraction and contractility of the heart muscle. The basis is a sequence of scans covering an average heartcycle. This sequence may be produced either by first pass or equilibrium technique. Myocardial scintigraphy at rest images vital myocardium, scans immediately after exercise represent the interference of myocardial perfusion and muscle mass. The regional difference (Redistribution) between normalized exercise- and rest scans provide quantitative parameters to detect impairment of exercise-induced myocardial perfusion anomalies. The procedures of sectorial analysis of left ventricular function and myocardial perfusion are presented. (orig.) [de

  19. Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Margaret E McCormick

    Full Text Available A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.

  20. Extraction of left ventricular myocardial mass from dynamic 11C-acetate PET

    DEFF Research Database (Denmark)

    Harms, Hans; Tolbod, Lars Poulsen; Hansson, Nils Henrik

    Background: Dynamic 11C-acetate PET is used to quantify oxygen metabolism, which is used to calculate left ventricular (LV) myocardial efficiency, an early marker of heart failure. This requires estimation of LV myocardial mass and is typically derived from a separate cardiovascular magnetic...... resonance (CMR) scan. The aim of this study was to explore the feasibility of estimating myocardial mass directly from a dynamic 11C-acetate PET scan. Methods: 21 subjects underwent a 27-min 11C-acetate PET scan on a Siemens Biograph TruePoint 64 PET/CT scanner. In addition, 10 subjects underwent a dynamic...... 11C-acetate 27-min PET scan on a GE Discovery ST PET/CT scanner. Parametric images of uptake rate K1 and both arterial (VA) and venous (VV) spillover fractions were generated using a basis function implementation of the standard single tissue compartment model using non-gated dynamic data. The LV...

  1. Lingual Haematoma due to Tenecteplase in a Patient with Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Muhlis Bal

    2013-01-01

    Full Text Available The use of intravenous thrombolytic agents has revolutionised the treatment of acute myocardial infarction. However, the improvement in mortality rate achieved with these drugs is tempered by the risk of serious bleeding complications, including intracranial haemorrhage. Tenecteplase is a genetically engineered mutant tissue plasminogen activator. Haemorrhagic complications of tissue plasminogen activator (tPA are well known. Compared to other tPAs, tenecteplase use leads to lower rates of bleeding complications. Here, we report a case of unusual site of spontaneous bleeding, intralingual haematoma during tenecteplase therapy following acute myocardial infarction, which caused significant upper airway obstruction and required tracheotomy to maintain the patient’s airway. Clinical dilemmas related to securing the airway or reversing the effects of tissue plasminogen activator are discussed.

  2. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Science.gov (United States)

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  3. Three-dimension structure of ventricular myocardial fibers after myocardial infarction

    Directory of Open Access Journals (Sweden)

    Li Libin

    2010-11-01

    Full Text Available Abstract Background To explore the pathological changes of three-dimension structure of ventricular myocardial fibers after anterior myocardial infarction in dog heart. Methods Fourteen acute anterior myocardial infarction models were made from healthy dogs (mean weight 17.6 ± 2.5 kg. Six out of 14 dogs with old myocardial infarction were sacrificed, and their hearts were harvested after they survived the acute anterior myocardial infarction for 3 months. Each heart was dissected into ventricular myocardial band (VMB, morphological characters in infarction region were observed, and infarct size percents in descending segment and ascending segment were calculated. Results Six dog hearts were successfully dissected into VMB. Uncorresponding damages in myocardial fibers of descending segment and ascending segment were found in apical circle in anterior wall infarction. Infarct size percent in the ascending segment was significantly larger than that in the descending segment (23.36 ± 3.15 (SD vs 30.69 ± 2.40%, P = 0.0033; the long axis of infarction area was perpendicular to the orientation of myocardial fibers in ascending segment; however, the long axis of the infarction area was parallel with the orientation of myocardial fibers in descending segment. Conclusions We found that damages were different in both morphology and size in ascending segment and descending segment in heart with myocardial infarction. This may provide an important insight for us to understand the mechanism of heart failure following coronary artery diseases.

  4. Diagnostic value of exercise induced 18F-FDG myocardial metabolism scintigraphy in myocardial ischemia

    International Nuclear Information System (INIS)

    Shen Rui; He Zuoxiang; Shi Rongfang; Liu Xiujie; Tian Yueqin; Guo Feng; Wei Hongxing; Wu Yongjian; Qin Xuewen; Gao Runlin

    2006-01-01

    Objective: To evaluate the feasibility and diagnostic accuracy of exercise induced myocardial imaging with 18 F-fluorodeoxyglucose (FDG) in myocardial ischemia. Methods: Twenty-six patients with known or suspected coronary artery, disease (CAD) and with no prior myocardial infarction underwent simultaneous myocardial perfusion and metabolism imaging following intravenous injection of 99 Tc m -methoxy-isobutylisonitrile ( 99 Tc m -sestamibi) and 18 F-FDG at peak exercise. Subsequently rest perfusion imaging and coronary angiography (CAG) were performed in all patients. Exercise 18 F-FDG myocardial imaging was compared with 99 Tc m -sestamibi imaging and CAG. Results: In 22 patients with ≥50% narrowing over l coronary artery, 18 had perfusion abnormalities (sensitivity 82%), whereas 20 had abnormal myocardial 18 F-FDG uptake (sensitivity 91%, P>0.05). Patients with reversible (12 cases) or partial reversible (3 cases) perfusion abnormalities had increased myocardial 18 F-FDG uptake in abnormal perfusion segments. Compared with CAG, perfusion defect was seen in myocardial segments corresponding to 25 vascular territories of 51 vessels with ≥50% narrowing in 22 patients in 99 Tc m -sestamibi imaging (sensitivity 49%), whereas increased 18 F-FDG uptake was seen in 34 vascular territories (sensitivity 67%, P=0.008). Conclusions: Exercise induced myocardial ischemia can be imaged directly with 18 F-FDG. Combined exercise 18 F-FDG and 99 Tc m -sestamibi imaging provides a better assessment of exercise-induced myocardial ischemia as compared with exercise-rest perfusion imaging. (authors)

  5. Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

    Science.gov (United States)

    Shin, Su Ryon; Jung, Sung Mi; Zalabany, Momen; Kim, Keekyoung; Zorlutuna, Pinar; Kim, Sang bok; Nikkhah, Mehdi; Khabiry, Masoud; Azize, Mohamed; Kong, Jing; Wan, Kai-tak; Palacios, Tomas; Dokmeci, Mehmet R.; Bae, Hojae; Tang, Xiaowu (Shirley); Khademhosseini, Ali

    2013-01-01

    We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT) incorporated photocrosslinkable gelatin methacrylate (GelMA) hydrogel. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework is the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity. PMID:23363247

  6. An experimental study of 99Tcm-HL91 in detection of myocardial viability

    International Nuclear Information System (INIS)

    Xu Tao; Liu Baoping; Meng Yubao; Sun Bingqi; Niu Guangjun; Han Xingmin; Yuan Qiao

    2005-01-01

    Objective: To investigate whether 99 Tc m -4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (HL91) can be used to distinguish ischemic myocardium segments from infarction segments. Methods: Twenty-five acute myocardial infarction patients (≤6 weeks) and 5 old myocardial infarction patients (> 6 weeks) were included in the study. All the study patients underwent 99 Tc m -HL91 and 99 Tc m -methoxyisobutylisonitrile (MIBI) imaging intervented and unintervented with nitroglycerin, and the myocardium segments were divided into three groups according to 99 Tc m -MIBI imaging results: normal, ischemic, and infarction myocardium segments. The difference of the radial counts of 99 Tc m -HL91 in three groups were analyzed after the imaging with 99 Tc m -HL91. Results: 1) In acute myocardial infarction patients, the accumulation rates of 99 Tc m -HL91 was 95% in normal segment group, 157% in ischemic group, 93% in infarction group. The accumulation rates of 99 Tc m -HL91 in the ischemic group was higher than that in the normal group and infarction group. 2)In old myocardial infarction patients, the accumulation rates of 99 Tc m -HL91 were of no difference among the normal, ischemic, and infarction groups. Conclusion: 99 Tc m -HL91 is a potential marker for detecting the ischemic myocardial tissue. (authors)

  7. Postmortem MR quantification of the heart for characterization and differentiation of ischaemic myocardial lesions

    Energy Technology Data Exchange (ETDEWEB)

    Zech, Wolf-Dieter; Schwendener, Nicole; Jackowski, Christian [University of Bern, Institute of Forensic Medicine, Bern (Switzerland); Persson, Anders; Warntjes, Marcel J. [University of Linkoeping, Center for Medical Image Science and Visualization (CMIV), Linkoeping (Sweden)

    2015-07-15

    Recently, an MRI quantification sequence has been developed which can be used to acquire T1- and T2-relaxation times as well as proton density (PD) values. Those three quantitative values can be used to describe soft tissue in an objective manner. The purpose of this study was to investigate the applicability of quantitative cardiac MRI for characterization and differentiation of ischaemic myocardial lesions of different age. Fifty post-mortem short axis cardiac 3 T MR examinations have been quantified using a quantification sequence. Myocardial lesions were identified according to histology and appearance in MRI images. Ischaemic lesions were assessed for mean T1-, T2- and proton density values. Quantitative values were plotted in a 3D-coordinate system to investigate the clustering of ischaemic myocardial lesions. A total of 16 myocardial lesions detected in MRI images were histologically characterized as acute lesions (n = 8) with perifocal oedema (n = 8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising the combined quantitative values of T1, T2 and PD, the clusters of all investigated lesions could be well differentiated from each other. Post-mortem quantitative cardiac MRI is feasible for characterization and discrimination of different age stages of myocardial infarction. (orig.)

  8. Postmortem MR quantification of the heart for characterization and differentiation of ischaemic myocardial lesions

    International Nuclear Information System (INIS)

    Zech, Wolf-Dieter; Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J.

    2015-01-01

    Recently, an MRI quantification sequence has been developed which can be used to acquire T1- and T2-relaxation times as well as proton density (PD) values. Those three quantitative values can be used to describe soft tissue in an objective manner. The purpose of this study was to investigate the applicability of quantitative cardiac MRI for characterization and differentiation of ischaemic myocardial lesions of different age. Fifty post-mortem short axis cardiac 3 T MR examinations have been quantified using a quantification sequence. Myocardial lesions were identified according to histology and appearance in MRI images. Ischaemic lesions were assessed for mean T1-, T2- and proton density values. Quantitative values were plotted in a 3D-coordinate system to investigate the clustering of ischaemic myocardial lesions. A total of 16 myocardial lesions detected in MRI images were histologically characterized as acute lesions (n = 8) with perifocal oedema (n = 8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising the combined quantitative values of T1, T2 and PD, the clusters of all investigated lesions could be well differentiated from each other. Post-mortem quantitative cardiac MRI is feasible for characterization and discrimination of different age stages of myocardial infarction. (orig.)

  9. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-03-03

    Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.

  10. Bioeffects of albumin-encapsulated microbubbles and real-time myocardial contrast echocardiography in an experimental canine model

    Directory of Open Access Journals (Sweden)

    P.M.M. Dourado

    2006-06-01

    Full Text Available Myocardial contrast echocardiography has been used for assessing myocardial perfusion. Some concerns regarding its safety still remain, mainly regarding the induction of microvascular alterations. We sought to determine the bioeffects of microbubbles and real-time myocardial contrast echocardiography (RTMCE in a closed-chest canine model. Eighteen mongrel dogs were randomly assigned to two groups. Nine were submitted to continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA plus continuous imaging using power pulse inversion RTMCE for 180 min, associated with manually deflagrated high-mechanical index impulses. The control group consisted of 3 dogs submitted to continuous imaging using RTMCE without PESDA, 3 dogs received PESDA alone, and 3 dogs were sham-operated. Hemodynamics and cardiac rhythm were monitored continuously. Histological analysis was performed on cardiac and pulmonary tissues. No hemodynamic changes or cardiac arrhythmias were observed in any group. Normal left ventricular ejection fraction and myocardial perfusion were maintained throughout the protocol. Frequency of mild and focal microhemorrhage areas in myocardial and pulmonary tissue was similar in PESDA plus RTMCE and control groups. The percentages of positive microscopical fields in the myocardium were 0.4 and 0.7% (P = NS in the PESDA plus RTMCE and control groups, respectively, and in the lungs they were 2.1 and 1.1%, respectively (P = NS. In this canine model, myocardial perfusion imaging obtained with PESDA and RTMCE was safe, with no alteration in cardiac rhythm or left ventricular function. Mild and focal myocardial and pulmonary microhemorrhages were observed in both groups, and may be attributed to surgical tissue manipulation.

  11. Myocardial perfusion imaging with dual energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Kwang Nam [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); De Cecco, Carlo N. [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Caruso, Damiano [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiological Sciences, Oncology and Pathology, University of Rome “Sapienza”, Rome (Italy); Tesche, Christian [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich (Germany); Spandorfer, Adam; Varga-Szemes, Akos [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC (United States)

    2016-10-15

    Highlights: • Stress dual-energy sCTMPI offers the possibility to directly detect the presence of myocardial perfusion defects. • Stress dual-energy sCTMPI allows differentiating between reversible and fixed myocardial perfusion defects. • The combination of coronary CT angiography and dual-energy sCTMPI can improve the ability of CT to detect hemodynamically relevant coronary artery disease. - Abstract: Dual-energy CT (DECT) enables simultaneous use of two different tube voltages, thus different x-ray absorption characteristics are acquired in the same anatomic location with two different X-ray spectra. The various DECT techniques allow material decomposition and mapping of the iodine distribution within the myocardium. Static dual-energy myocardial perfusion imaging (sCTMPI) using pharmacological stress agents demonstrate myocardial ischemia by single snapshot images of myocardial iodine distribution. sCTMPI gives incremental values to coronary artery stenosis detected on coronary CT angiography (CCTA) by showing consequent reversible or fixed myocardial perfusion defects. The comprehensive acquisition of CCTA and sCTMPI offers extensive morphological and functional evaluation of coronary artery disease. Recent studies have revealed that dual-energy sCTMPI shows promising diagnostic accuracy for the detection of hemodynamically significant coronary artery disease compared to single-photon emission computed tomography, invasive coronary angiography, and cardiac MRI. The aim of this review is to present currently available DECT techniques for static myocardial perfusion imaging and recent clinical applications and ongoing investigations.

  12. Electrochemical construction

    Science.gov (United States)

    Einstein, Harry; Grimes, Patrick G.

    1983-08-23

    An electrochemical cell construction features a novel co-extruded plastic electrode in an interleaved construction with a novel integral separator-spacer. Also featured is a leak and impact resistant construction for preventing the spill of corrosive materials in the event of rupture.

  13. Usability Constructs

    DEFF Research Database (Denmark)

    Hertzum, Morten; Clemmesen, Torkil; Hornbæk, Kasper Anders Søren

    2007-01-01

    Whereas research on usability predominantly employs universal definitions of the aspects that comprise usability, people experience their use of information systems through personal constructs. Based on 48 repertory-grid interviews, this study investigates how such personal constructs are affected...... use of constructs traditionally associated with usability (e.g., easy-to-use, intuitive, and liked). Further analysis of the data is ongoing...

  14. Myocardial infarction, androgen and the skin.

    Science.gov (United States)

    Halim, M M; Meyrick, G; Jeans, W D; Murphy, D; Burton, J L

    1978-01-01

    Various indices of masculinity were compared in 48 men who had recovered from myocardial infarction and in their age-matched controls. We found little evidence to support the idea that myocardial infarction is related to increased androgenic stimulation. The patients with myocardial infarction had no increase in plasma testosterone, muscle thickness, sebum excretion rate, maximal sweat secretion rate, male pattern alopecia or density of terminal body hair, but as a group they had a slight increase in skin and bone thickness compared with the controls.

  15. Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

    Science.gov (United States)

    Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

    2013-01-01

    Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA) have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress). These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage. PMID:23936799

  16. Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Ramón Rodrigo

    2013-01-01

    Full Text Available Acute myocardial infarction (AMI is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress. These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage.

  17. Extraction and myocardial distribution of IPBDA potentials of lipophylic cations for use as thallium substitutes

    International Nuclear Information System (INIS)

    Rigo, P.; Woo, D.V.; Tanaka, T.; Wong, D.F.; Dannals, R.; Wagner, H.N. Jr.; Becker, L.C.

    1984-01-01

    Potassium analogs have been used for several years as clinical indicators of myocardial blood flow, but the value of thallium is limited by its long half life and low energy photons. We have tested 4-iodiphenylbenzyldimethylammonium (IPBDA) a radio-iodinated cation as a potential thallium substitute in a series of 7 mongrel dogs. First pass myocardial and systemic extraction were determined using the double tracer technique, with technetium albumin as reference. Tissue iodine 125 IPBDA distributions were compared to microspheres under a variety of pathophysiological conditions (control, myocardial infarction, coronary artery stenosis, Dipyridamole infusion). First pass extraction averaged 73% in normal controls (3 determinations), 66.1% in dogs with LAD occlusion (4 determination) and 40.1% in dogs receiving persantine (with or without coronary stenosis or occlusion) (5 determinations). Tissue microspheres and IPBDA distribution correlated in each dog (r=.75, to .85) but the relationship was not linear, IPBDA underestimating myocardial blood flow at high flow. Iodinated IPBDA is a potential thallium substitute due to the better physical characteristics of iodine 123. It shares however the biological limitations of potassium and analogs: a variable extraction and a non linear relation to flow. (Author)

  18. Utility of Cardiac Magnetic Resonance to assess association between admission hyperglycemia and myocardial damage in patients with reperfused ST-Segment Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Wolf Jean-Eric

    2008-01-01

    Full Text Available Abstract Aims to investigate the association between admission hyperglycemia and myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI using Cardiac Magnetic Resonance (CMR. Methods We analyzed 113 patients with STEMI treated with successful primary percutaneous coronary intervention. Admission hyperglycemia was defined as a glucose level ≥ 7.8 mmol/l. Contrast-enhanced CMR was performed between 3 and 7 days after reperfusion to evaluate left ventricular function and perfusion data after injection of gadolinium-DTPA. First-pass images (FP, providing assessment of microvascular obstruction and Late Gadolinium Enhanced images (DE, reflecting the extent of infarction, were investigated and the extent of transmural tissue damage was determined by visual scores. Results Patients with a supramedian FP and DE scores more frequently had left anterior descending culprit artery (p = 0.02 and 1c (p = 0.01 and 0.04, peak plasma Creatine Kinase (p In a multivariate model, admission hyperglycemia remains independently associated with increased FP and DE scores. Conclusion Our results show the existence of a strong relationship between glucose metabolism impairment and myocardial damage in patients with STEMI. Further studies are needed to show if aggressive glucose control improves myocardial perfusion, which could be assessed using CMR.

  19. SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

    Science.gov (United States)

    Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

    2016-01-01

    Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

  20. The clinical application value of myocardial perfusion imaging in evaluating coronary artery myocardial bridge patients with symptoms

    International Nuclear Information System (INIS)

    Wang Yuetao; Fu Ning; Ding Xuemei; Lu Cunzhi; Zhu Feng; Wang Guanmin; Huang Yijie; Wang Linguang

    2008-01-01

    Objective: Myocardial bridge is a common inborn coronary artery anomaly, myocardial bridge may be associated with myocardial ischemia. Only a few patients with coronary artery myocardial bridge were evaluated with nuclear medicine techniques. The aim of this study was to investigate the role of nuclear cardiology with myocardial perfusion technique in symptomatic myocardial bridge patients. Methods Nineteen myocardial bridge patients with the symptoms of chest pain and chest distress were analyzed retrospectively. 99 Tc m -methoxyisobutylisonitrile (MIBI) myocardial perfusion images (both exercise and rest) were performed in all. Imaging results were compared with the results of movement electrocardiogram (ECG) and coronary arteriography. The t test or χ 2 test was used to statistically analyze the data with Stata 7.0 software. Results: Of the 19 patients, 18 patients had myocardial bridge locating at the left anterior descending artery, 1 patient at the left anterior descending and left circumflex artery, the mean angiographic systolic occlusion within the myocardial bridge was (65.4 ± 22.1)%. Of these 19 patients, Exercise-rest 99 Tc m -MIBI myocardial perfusion imaging defined positive myocardial ischemia in 10 and negative in 9 patients. Of the 10 patients with 99 Tc m -MIBI myocardial perfusion imaging defined myocardial ischemia, 8 had reversible radioactive defect of partial anterior wall and (or) apex, 1 had reversible defect of post lateral wall and post septal wall, and 1 had reversible defect of inferior wall. The positive predictive value of myocardial perfusion imaging was 52.6% (10/19), which was higher than movement ECG [21.1% (4/19), χ 2 = 4.07, P 99 Tc m -MIBI myocardial periusion imaging defined myocardial ischemia. Six cases with Grade II stenosis, two were 99 Tc m -MIBI myocardial perfusion imaging defined myocardial ischemia. Eight cases with Grade III stenosis, seven were 99 Tc m -MIBI myocardial perfusion imaging defined myocardial

  1. Association of Exercise Training with Tobacco Smoking Prevents Fibrosis but has Adverse Impact on Myocardial Mechanics.

    Science.gov (United States)

    Reis Junior, Dermeval; Antonio, Ednei Luiz; de Franco, Marcello Fabiano; de Oliveira, Helenita Antonia; Tucci, Paulo José Ferreira; Serra, Andrey Jorge

    2016-12-01

    There was no data for cardiac repercussion of exercise training associated with tobacco smoking. This issue is interesting because some smoking people can be enrolled in an exercise-training program. Thus, we evaluated swimming training effects on the function and structural myocardial in rats exposed to tobacco smoking. Male Wistar rats were assigned to one of four groups: C, untrained rats without exposure to tobacco smoking; E, exercised rats without exposure to tobacco smoking; CS, untrained rats exposed to tobacco smoking; ECS, exercised rats exposed to tobacco smoking. Rats swam five times a week twice daily (60min per session) for 8 weeks. Before each bout exercise, rats breathed smoke from 20 cigarettes for 60min. Twenty-four hours after the last day of the protocol, papillary muscles were isolated for in vitro analysis of myocardial mechanics. The myocardial mass and nuclear cardiomyocyte volume were used as hypertrophy markers, and collagen content was determined by picrosirius red staining. There was a well-pronounced myocardial hypertrophic effect for two interventions. The exercise blunted myocardial collagen increases induced by tobacco smoking. However, exercise and tobacco-smoking association was deleterious to myocardial performance. Thereby, in vitro experiments with papillary muscles contracting in isometric showed impairment myocardial inotropism in exercised rats exposed to tobacco smoking. This work presents novel findings on the role of exercise training on cardiac remodeling induced by tobacco smoking. Although exercise has mitigated tissue fibrosis, their association with tobacco smoking exacerbated hypertrophy and in vitro myocardial dysfunction. This is first study to show that the association of an aerobic exercise training with tobacco smoking intensifies the phenotype of pathological cardiac hypertrophy. Therefore, the combination of interventions resulted in exacerbated myocardial hypertrophy and contractility dysfunction. These

  2. Quantitative aspects of myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Vogel, R.A.

    1980-01-01

    Myocardial perfusion measurements have traditionally been performed in a quantitative fashion using application of the Sapirstein, Fick, Kety-Schmidt, or compartmental analysis principles. Although global myocardial blood flow measurements have not proven clinically useful, regional determinations have substantially advanced our understanding of and ability to detect myocardial ischemia. With the introduction of thallium-201, such studies have become widely available, although these have generally undergone qualitative evaluation. Using computer-digitized data, several methods for the quantification of myocardial perfusion images have been introduced. These include orthogonal and polar coordinate systems and anatomically oriented region of interest segmentation. Statistical ranges of normal and time-activity analyses have been applied to these data, resulting in objective and reproducible means of data evaluation

  3. Myocardial perfusion scintigraphy - possibilities of diagnosing CAD

    International Nuclear Information System (INIS)

    Tsonevska, A.

    1998-01-01

    A reviewing the diagnostic methods used in the intricate process of evaluating CAD patients in a attempt to establish the role played by radionuclide methods in the diagnostic strategy is done. The perfusion cardiotropic radiopharmaceuticals used and the various methods of evaluating myocardial are discussed. Although 210 Tl-chloride is the most widely used myocardial perfusion agent, recently 99m Tc-MIBI is proposed as an alternative because of its advantages. Myocardial perfusion assessment is done by various techniques depending on the specific aim, each of them having its proper advantages and shortcomings. The inference is reached that regardless of the routine practical implementation of myocardial perfusion scintigraphy and comprehensive studies along this line in course, there are problems still not well enough clarified awaiting solution

  4. The Pathogenesis of Human Myocardial Infarction

    Science.gov (United States)

    Rona, George

    1966-01-01

    Coronary arteriography, dissection of the coronary arteries and histopathological examination of the heart were carried out in 150 autopsies to study the effect of coronary narrowing and occlusion, of the presence of collaterals, and of coronary artery predominance on the development of myocardial infarction. The thrombosis rate was related to the severity of coronary sclerosis. The development of collaterals was not enhanced by coronary sclerosis and occlusion, and collaterals did not protect the myocardium against reinfarction. Coronary occlusion was regularly demonstrable in recent myocardial infarct cases. The association of atrial and posterior ventricular infarcts was explained by occlusion of their common arterial branch. The interdependence between coronary sclerosis, thrombosis and myocardial infarction in human autopsy material emphasizes the importance of mural coronary artery disease in the genesis of coronary occlusion and myocardial infarction, and it is at variance with statistical data and experimental results. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:5924947

  5. DEPRESSIVE DISORDERS IN PATIENTS AFTER MYOCARDIAL INFARCTION

    OpenAIRE

    MUXAMADIYEVA NIGINA BAKHODIROVNA

    2016-01-01

    In article the depressions arising at patients after a myocardial infarction (MI) are shined, necessity of overcoming stigma concerning weight of the transferred MI, rational under-standing of illness especially in early period of the post infraction is defined.

  6. Echocardiography diagnosis of myocardial infarction complications

    Directory of Open Access Journals (Sweden)

    N.D. Oryshchyn

    2016-03-01

    Full Text Available Diagnosis and management of myocardial infarction complications are discussed in this article. These complications are associated with high level of mortality and surgery is a main treatment method. High level of suspicion and early diagnosis are essential for appropriate treatment and improvement of prognosis. Echocardiography is a main diagnostic method. Analysis of literature about contemporary management of mechanical complications of myocardial infarction has been performed, case reports are presented.

  7. Acute myocardial infarction: 'telomerasing' for cardioprotection

    OpenAIRE

    Sanchís-Gomar, Fabián; Lucía Mulas, Alejandro

    2015-01-01

    Reactivating the telomerase gene through gene therapy after acute myocardial infarction (AMI) has been recently reported to improve survival in mice. Given that regular physical exercise also activates this gene, therapeutic and lifestyle interventions targeting telomerase need to be explored as possible additions to the current armamentarium for myocardial regeneration. 9.292 JCR (2015) Q1, 17/289 Biochemistry & mollecular biology, 17/187 Cell biology, 8/124 Medicine, research & experimen...

  8. Improved exercise myocardial perfusion during lidoflazine therapy

    International Nuclear Information System (INIS)

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-01-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise

  9. Measurement of myocardial perfusion using magnetic resonance

    DEFF Research Database (Denmark)

    Fritz-Hansen, T.; Jensen, L.T.; Larsson, H.B.

    2008-01-01

    Cardiac magnetic resonance imaging (MRI) has evolved rapidly. Recent developments have made non-invasive quantitative myocardial perfusion measurements possible. MRI is particularly attractive due to its high spatial resolution and because it does not involve ionising radiation. This paper reviews...... myocardial perfusion imaging with MR contrast agents: methods, validation and experiences from clinical studies. Unresolved issues still restrict the use of these techniques to research although clinical applications are within reach Udgivelsesdato: 2008/12/8...

  10. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)

    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  11. Automated quantitative coronary computed tomography correlates of myocardial ischaemia on gated myocardial perfusion SPECT

    International Nuclear Information System (INIS)

    Graaf, Michiel A. de; Boogers, Mark J.; Veltman, Caroline E.; El-Naggar, Heba M.; Bax, Jeroen J.; Delgado, Victoria; Broersen, Alexander; Kitslaar, Pieter H.; Dijkstra, Jouke; Kroft, Lucia J.; Younis, Imad Al; Reiber, Johan H.; Scholte, Arthur J.

    2013-01-01

    Automated software tools have permitted more comprehensive, robust and reproducible quantification of coronary stenosis, plaque burden and plaque location of coronary computed tomography angiography (CTA) data. The association between these quantitative CTA (QCT) parameters and the presence of myocardial ischaemia has not been explored. The aim of the present investigation was to evaluate the association between QCT parameters of coronary artery lesions and the presence of myocardial ischaemia on gated myocardial perfusion single-photon emission CT (SPECT). Included in the study were 40 patients (mean age 58.2 ± 10.9 years, 27 men) with known or suspected coronary artery disease (CAD) who had undergone multidetector row CTA and gated myocardial perfusion SPECT within 6 months. From the CTA datasets, vessel-based and lesion-based visual analyses were performed. Consecutively, lesion-based QCT was performed to assess plaque length, plaque burden, percentage lumen area stenosis and remodelling index. Subsequently, the presence of myocardial ischaemia was assessed using the summed difference score (SDS ≥2) on gated myocardial perfusion SPECT. Myocardial ischaemia was seen in 25 patients (62.5 %) in 37 vascular territories. Quantitatively assessed significant stenosis and quantitatively assessed lesion length were independently associated with myocardial ischaemia (OR 7.72, 95 % CI 2.41-24.7, p 2 = 20.7) and lesion length (χ 2 = 26.0) to the clinical variables and the visual assessment (χ 2 = 5.9) had incremental value in the association with myocardial ischaemia. Coronary lesion length and quantitatively assessed significant stenosis were independently associated with myocardial ischaemia. Both quantitative parameters have incremental value over baseline variables and visually assessed significant stenosis. Potentially, QCT can refine assessment of CAD, which may be of potential use for identification of patients with myocardial ischaemia. (orig.)

  12. Effect of eating on thallium myocardial imaging

    International Nuclear Information System (INIS)

    Wilson, R.A.; Sullivan, P.J.; Okada, R.D.; Boucher, C.A.; Morris, C.; Pohost, G.M.; Strauss, H.W.

    1986-01-01

    To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The 201 Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of 201 Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed 201 Tl images causes increased 201 Tl myocardial clearance rates and may alter 201 Tl myocardial redistribution over time

  13. Myocardial infarction in Swedish subway drivers.

    Science.gov (United States)

    Bigert, Carolina; Klerdal, Kristina; Hammar, Niklas; Gustavsson, Per

    2007-08-01

    Particulate matter in urban air is associated with the risk of myocardial infarction in the general population. Very high levels of airborne particles have been detected in the subway system of Stockholm, as well as in several other large cities. This situation has caused concern for negative health effects among subway staff. The aim of this study was to investigate whether there is an increased incidence of myocardial infarction among subway drivers. Data from a population-based case-control study of men aged 40-69 in Stockholm County in 1976-1996 were used. The study included all first events of myocardial infarction in registers of hospital discharges and deaths. The controls were selected randomly from the general population. National censuses were used for information on occupation. Altogether, 22 311 cases and 131 496 controls were included. Among these, 54 cases and 250 controls had worked as subway drivers. The relative risk of myocardial infarction among subway drivers was not increased. It was 0.92 [95% confidence interval (95% CI) 0.68-1.25] when the subway drivers were compared with other manual workers and 1.06 (95% CI 0.78-1.43) when the subway drivers were compared with all other gainfully employed men. Subgroup analyses indicated no influence on the risk of myocardial infarction from the duration of employment, latency time, or time since employment stopped. Subway drivers in Stockholm do not have a higher incidence of myocardial infarction than other employed persons.

  14. Construction mathematics

    CERN Document Server

    Virdi, Surinder; Virdi, Narinder Kaur

    2014-01-01

    Construction Mathematics is an introductory level mathematics text, written specifically for students of construction and related disciplines. Learn by tackling exercises based on real-life construction maths. Examples include: costing calculations, labour costs, cost of materials and setting out of building components. Suitable for beginners and easy to follow throughout. Learn the essential basic theory along with the practical necessities. The second edition of this popular textbook is fully updated to match new curricula, and expanded to include even more learning exercises. End of chapter exercises cover a range of theoretical as well as practical problems commonly found in construction practice, and three detailed assignments based on practical tasks give students the opportunity to apply all the knowledge they have gained. Construction Mathematics addresses all the mathematical requirements of Level 2 construction NVQs from City & Guilds/CITB and Edexcel courses, including the BTEC First Diploma in...

  15. Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning

    NARCIS (Netherlands)

    J.A. Cabrera (Jesús); E.A. Ziemba (Elizabeth); L.H. Colbert (Lisa); L.B. Anderson (Lorraine); W.J. Sluiter (Wim); D.J.G.M. Duncker (Dirk); T.A. Butterick (Tammy); J. Sikora (Joseph); H.B. Ward (Herbert B.); R.F. Kelly (Rosemary); E.O. McFalls (Edward)

    2012-01-01

    textabstractAltered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated

  16. Myocardial oxygen extraction fraction measured using bolus inhalation of 15O-oxygen gas and dynamic PET

    NARCIS (Netherlands)

    Lubberink, Mark; Wong, YY; Raijmakers, P. G.; Huisman, Marc C.; Schuit, Robert C.; Luurtsema, Geert; Boellaard, Ronald; Knaapen, P; Vonk-Noordegraaf, Anton; Lammertsma, Adriaan A.

    Abstract The aim of this study was to determine the accuracy of oxygen extraction fraction (OEF) measurements using a dynamic scan protocol after bolus inhalation of 15O2. The method of analysis was optimized by investigating potential reuse of myocardial blood flow (MBF), perfusable tissue

  17. FFTF constructibility

    International Nuclear Information System (INIS)

    Weber, S.A.; Hulbert, D.I.

    1975-01-01

    The influence of the design criteria on the constructibility of the Fast Flux Test Facility is described. Specifically, the effects of requirements due to maintenance accessibility, inerting of cells, seismicity, codes, and standards are addressed. The design and construction techniques developed to minimize the impact of the design criteria on cost and schedule are presented with particular emphasis on the cleanliness and humidity controls imposed during construction of the sodium systems. (U.S.)

  18. Quantitative myocardial blood flow with Rubidium-82 PET

    DEFF Research Database (Denmark)

    Hagemann, Christoffer E; Ghotbi, Adam A; Kjær, Andreas

    2015-01-01

    Positron emission tomography (PET) allows assessment of myocardial blood flow in absolute terms (ml/min/g). Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) extend the scope of conventional semi-quantitative myocardial perfusion imaging (MPI): e.g. in 1) identificat......Positron emission tomography (PET) allows assessment of myocardial blood flow in absolute terms (ml/min/g). Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) extend the scope of conventional semi-quantitative myocardial perfusion imaging (MPI): e.g. in 1...... global MFR and major adverse cardiovascular events (MACE), and together with new diagnostic possibilities from measuring the longitudinal myocardial perfusion gradient, cardiac (82)Rb PET faces a promising clinical future. This article reviews current evidence on quantitative (82)Rb PET's ability...

  19. Myocardial adrenergic nerve activity in valvular diseases assessed by iodine-123-metaiodobenzylguanidine myocardial scintigraphy

    International Nuclear Information System (INIS)

    Imamura, Yoshihiro; Fukuyama, Takaya

    1997-01-01

    Iodine-123-metaiodobenzylguanidine (MIBG) imaging was used to assess myocardial adrenergic nerve activity in patients with heart failure. MIBG planar images were obtained in 94 patients. The uptake of MIBG, calculated as the heart-to-mediastinum activity ratio in the immediate image (15 min), showed a significant decrease only in patients with severe heart failure due to cardiomyopathy, but was not changed in those with valvular diseases. Storage and release of MIBG, calculated as the percentage myocardial MIBG washout from 15 min to 4 hours after isotope injection, was substantially accelerated in both patients with cardiomyopathy and valvular diseases in proportion to the severity of heart failure. These data suggest that, in severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. Also, myocardial adrenergic nerve activity is accelerated in proportion to the severity of heart failure independent of the underlying cause. MIBG images were analyzed in 20 patients with mitral stenosis with the same methods to clarify whether myocardial adrenergic nerve activity is different in patients with heart failure without left ventricular volume or pressure overload. Myocardial uptake of MIBG did not show any significant difference. The percentage myocardial MIBG washout was increased in patients with severe heart failure. The closest correlation was between myocardial washout and cardiac output. In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. Decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification. (author)

  20. The diagnosis of silent myocardial ischemia. Motion-Frozen (or morphing) myocardial perfusion imaging.

    Science.gov (United States)

    Chang, Cheng; Ye, Bo; Xie, Wenhui; Zhang, Daoliang; Lei, Bei; Ye, Xiaodan

    2016-01-01

    Silent myocardial ischemia is typically defined as objective evidence of myocardial ischemia in patients without subjective ischemia symptoms. Currently, coronary artery angiography is the gold standard for diagnosis of asymptomatic coronary artery disease (CAD). Computed tomography coronary angiography (CTCA) can visually demonstrate the morphology, trend and extent of coronary stenosis and is commonly used in clinical screening of CAD. Myocardial perfusion imaging can be used not only to identify whether anatomical stenosis causes myocardial dysfunction, but to also assess the risk stratification and prognosis of myocardial disease (MD). Myocardial perfusion imaging using morphing combined with CTCA can simultaneously show the relationship between CAD and myocardial ischemia from an anatomical and functional aspect. This allows earlier diagnosis of asymptomatic CAD myocardial ischemia, accurate identification of the culprit vessels, and could prevent unnecessary interventional therapy. The 1-day dobutamine stress/resting met-hod is also one of the methods used. The combination of CTCA and the morphing technique can provide anatomical and functional information on coronary arteries at the same time, significantly improving the diagnostic sensitivity, specificity, and accuracy of MD.

  1. Value of the Doppler index of myocardial performance in the early phase of acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Jensen, S E; Tei, C

    2000-01-01

    Prospective assessment of a nongeometric Doppler-derived index of combined systolic and diastolic myocardial performance was performed in 64 patients with acute myocardial infarction (MI) within 1 hour after their arrival to the hospital and in 39 age-matched healthy subjects. The index is defined...

  2. Myocardial imaging with a radioiodinated norepinephrine storage analog

    International Nuclear Information System (INIS)

    Wieland, D.M.; Brown, L.E.; Rogers, W.L.; Worthington, K.C.; Wu, J.L.; Clinthorne, N.H.; Otto, C.A.; Swanson, D.P.; Beierwaltes, W.H.