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Sample records for adult human hearts

  1. Adult human heart slices are a multicellular system suitable for electrophysiological and pharmacological studies.

    PubMed

    Camelliti, Patrizia; Al-Saud, Sara Abou; Smolenski, Ryszard T; Al-Ayoubi, Samha; Bussek, Alexandra; Wettwer, Erich; Banner, Nicholas R; Bowles, Christopher T; Yacoub, Magdi H; Terracciano, Cesare M

    2011-09-01

    Electrophysiological and pharmacological data from the human heart are limited due to the absence of simple but representative experimental model systems of human myocardium. The aim of this study was to establish and characterise adult human myocardial slices from small patients' heart biopsies as a simple, reproducible and relevant preparation suitable for the study of human cardiac tissue at the multicellular level. Vibratome-cut myocardial slices were prepared from left ventricular biopsies obtained from end-stage heart failure patients undergoing heart transplant or ventricular assist device implantation, and from hearts of normal dogs. Multiple slices were prepared from each biopsy. Regular contractility was observed at a range of stimulation frequencies (0.1-2 Hz), and stable electrical activity, monitored using multi-electrode arrays (MEA), was maintained for at least 8 h from slice preparation. ATP/ADP and phosphocreatine/creatine ratios were comparable to intact organ values, and morphology and gap junction distribution were representative of native myocardium. MEA recordings showed that field potential duration (FPD) and conduction velocity (CV) in human and dog slices were similar to the values previously reported for papillary muscles, ventricular wedges and whole hearts. Longitudinal CV was significantly faster than transversal CV, with an anisotropic ratio of 3:1 for human and 2.3:1 for dog slices. Importantly, slices responded to the application of E-4031, chromanol and 4-aminopyridine, three potassium channel blockers known to affect action potential duration, with an increase in FPD. We conclude that viable myocardial slices with preserved structural, biochemical and electrophysiological properties can be prepared from adult human and canine heart biopsies and offer a novel preparation suitable for the study of heart failure and drug screening.

  2. Main tributaries of the coronary sinus in the adult human heart.

    PubMed

    Duda, B; Grzybiak, M

    1998-01-01

    The coronary sinus collects blood from the heart walls. It is a structure which presently plays a very important clinical role in invasive cardology. In this study, the occurrence of the main tributaries of the coronary sinus was examined as wall as the topography of their outlet portions. Material consistied of 150 adult human hearts of both sexes from aged 18 to 85 years. In the examined material, the graet and middle cardiac veins as well as the posterior vein of the left ventricle were always obserwed. The remaining tributaries of the coronary sinus were less stable. The outlet portions of the main veins of the heart were characterized by significant variability.

  3. Congenital Heart Disease in Adults

    MedlinePlus

    ... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...

  4. Human fetal cardiac progenitors: The role of stem cells and progenitors in the fetal and adult heart.

    PubMed

    Bulatovic, Ivana; Månsson-Broberg, Agneta; Sylvén, Christer; Grinnemo, Karl-Henrik

    2016-02-01

    The human fetal heart is formed early during embryogenesis as a result of cell migrations, differentiation, and formative blood flow. It begins to beat around gestation day 22. Progenitor cells are derived from mesoderm (endocardium and myocardium), proepicardium (epicardium and coronary vessels), and neural crest (heart valves, outflow tract septation, and parasympathetic innervation). A variety of molecular disturbances in the factors regulating the specification and differentiation of these cells can cause congenital heart disease. This review explores the contribution of different cardiac progenitors to the embryonic heart development; the pathways and transcription factors guiding their expansion, migration, and functional differentiation; and the endogenous regenerative capacity of the adult heart including the plasticity of cardiomyocytes. Unfolding these mechanisms will become the basis for understanding the dynamics of specific congenital heart disease as well as a means to develop therapy for fetal as well as postnatal cardiac defects and heart failure.

  5. Hybrid Mathematical Model of Cardiomyocyte Turnover in the Adult Human Heart

    PubMed Central

    Elser, Jeremy A.; Margulies, Kenneth B.

    2012-01-01

    Rationale The capacity for cardiomyocyte regeneration in the healthy adult human heart is fundamentally relevant for both myocardial homeostasis and cardiomyopathy therapeutics. However, estimates of cardiomyocyte turnover rates conflict greatly, with a study employing C14 pulse-chase methodology concluding 1% annual turnover in youth declining to 0.5% with aging and another using cell population dynamics indicating substantial, age-increasing turnover (4% increasing to 20%). Objective Create a hybrid mathematical model to critically examine rates of cardiomyocyte turnover derived from alternative methodologies. Methods and Results Examined in isolation, the cell population analysis exhibited severe sensitivity to a stem cell expansion exponent (20% variation causing 2-fold turnover change) and apoptosis rate. Similarly, the pulse-chase model was acutely sensitive to assumptions of instantaneous incorporation of atmospheric C14 into the body (4-fold impact on turnover in young subjects) while numerical restrictions precluded otherwise viable solutions. Incorporating considerations of primary variable sensitivity and controversial model assumptions, an unbiased numerical solver identified a scenario of significant, age-increasing turnover (4–6% increasing to 15–22% with age) that was compatible with data from both studies, provided that successive generations of cardiomyocytes experienced higher attrition rates than predecessors. Conclusions Assignment of histologically-observed stem/progenitor cells into discrete regenerative phenotypes in the cell population model strongly influenced turnover dynamics without being directly testable. Alternatively, C14 trafficking assumptions and restrictive models in the pulse-chase model artificially eliminated high-turnover solutions. Nevertheless, discrepancies among recent cell turnover estimates can be explained and reconciled. The hybrid mathematical model provided herein permits further examination of these and

  6. Heart transplantation in adult congenital heart disease.

    PubMed

    Burchill, Luke J

    2016-12-01

    Heart failure (HF) in adult congenital heart disease (ACHD) is vastly different to that observed in acquired heart disease. Unlike acquired HF in which pharmacological strategies are the cornerstone for protecting and improving ventricular function, ACHD-related HF relies heavily upon structural and other interventions to achieve these aims. patients with ACHD constitute a small percentage of the total adult heart transplant population (∼3%), although the number of ACHD heart transplant recipients is growing rapidly with a 40% increase over the last two decades. The worldwide experience to date has confirmed heart transplantation as an effective life-extending treatment option in carefully selected patients with ACHD with end-stage cardiac disease. Opportunities for improving outcomes in patients with ACHD-related HF include (i) earlier recognition and referral to centres with combined expertise in ACHD and HF, (ii) increased awareness of arrhythmia and sudden cardiac death risk in this population, (iii) greater collaboration between HF and ACHD specialists at the time of heart transplant assessment, (iv) expert surgical planning to reduce ischaemic time and bleeding risk at the time of transplant, (v) tailored immunosuppression in the post-transplant period and (vi) development and validation of ACHD-specific risk scores to predict mortality and guide patient selection. The purpose of this article is to review current approaches to diagnosing and treating advanced HF in patients with ACHD including indications, contraindications and clinical outcomes after heart transplantation.

  7. Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves.

    PubMed

    van Geemen, Daphne; Soares, Ana L F; Oomen, Pim J A; Driessen-Mol, Anita; Janssen-van den Broek, Marloes W J T; van den Bogaerdt, Antoon J; Bogers, Ad J J C; Goumans, Marie-José T H; Baaijens, Frank P T; Bouten, Carlijn V C

    2016-01-01

    There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation-but more pronounced in aortic valves-the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age.

  8. Effects of Moxa (Folium Artemisiae argyi) Smoke Exposure on Heart Rate and Heart Rate Variability in Healthy Young Adults: A Randomized, Controlled Human Study

    PubMed Central

    Cui, Yingxue; Zhao, Baixiao; Huang, Yuhai; Chen, Zhanghuang; Liu, Ping; Huang, Jian; Lao, Lixing

    2013-01-01

    Objective. To determine the effects of the moxa smoke on human heart rate (HR) and heart rate variability (HRV). Methods. Fifty-five healthy young adults were randomly divided into experimental (n = 28) and control (n = 27) groups. Experimental subjects were exposed to moxa smoke (2.5 ± 0.5 mg/m3) twice for 25 minutes in one week. ECG monitoring was performed before, during, and after exposure. Control subjects were exposed to normal indoor air in a similar environment and similarly monitored. Followup was performed the following week. Short-term (5 min) HRV parameters were analyzed with HRV analysis software. SPSS software was used for statistical analysis. Results. During and after the first exposure, comparison of percentage changes or changes in all parameters between groups showed no significant differences. During the second exposure, percentage decrease in HR, percentage increases in lnTP, lnHF, lnLF, and RMSSD, and increase in PNN50 were significantly greater in the experimental group than in control. Conclusion. No significant adverse HRV effects were associated with this clinically routine 25-minute exposure to moxa smoke, and the data suggests that short-term exposure to moxa smoke might have positive regulating effects on human autonomic function. Further studies are warranted to confirm these findings. PMID:23762143

  9. Adult Congenital Heart Association

    MedlinePlus

    ... my congenital heart … Read More Let's Talk About Love... BY Kelly DiMaggio Being in love and in a relationship is one of the ... are born they have … Read More Learning to Love the Scar BY Clare Almand I wrote about ...

  10. TGFβ-Dependent Epithelial-to-Mesenchymal Transition Is Required to Generate Cardiospheres from Human Adult Heart Biopsies

    PubMed Central

    Forte, Elvira; Miraldi, Fabio; Chimenti, Isotta; Angelini, Francesco; Zeuner, Ann; Giacomello, Alessandro; Mercola, Mark

    2012-01-01

    Autologous cardiac progenitor cells (CPCs) isolated as cardiospheres (CSps) represent a promising candidate for cardiac regenerative therapy. A better understanding of the origin and mechanisms underlying human CSps formation and maturation is undoubtedly required to enhance their cardiomyogenic potential. Epithelial-to-mesenchymal transition (EMT) is a key morphogenetic process that is implicated in the acquisition of stem cell-like properties in different adult tissues, and it is activated in the epicardium after ischemic injury to the heart. We investigated whether EMT is involved in the formation and differentiation of human CSps, revealing that an up-regulation of the expression of EMT-related genes accompanies CSps formation that is relative to primary explant-derived cells and CSp-derived cells grown in a monolayer. EMT and CSps formation is enhanced in the presence of transforming growth factor β1 (TGFβ1) and drastically blocked by the type I TGFβ-receptor inhibitor SB431452, indicating that TGFβ-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFβ is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs. PMID:22765842

  11. Human heart by art.

    PubMed

    Tamir, Abraham

    2012-11-01

    Heart is of great importance in maintaining the life of the body. Enough to stop working for a few minutes to cause death, and hence the great importance in physiology, medicine, and research. This fact was already emphasized in the Bible in the Book of Proverbs, chapter 4 verse 23: "Keep your heart with all diligence, for out of it is the wellspring of life." Art was able to demonstrate the heart from various aspects; realistically, as done by Leonardo de Vinci who demonstrated the halves of the heart and its blood vessels. Symbolically, as a source of life, the heart was demonstrated by the artist Mrs. Erlondeiel, as a caricature by Salvador Dali, as an open heart by Sawaya, etc. Finally, it should be emphasized that different demonstrations of the human heart by many artworks make this most important organ of our body (that cannot be seen from outside) more familiar and clearer to us. And this is the purpose of this article-to demonstrate the heart through a large number of artworks of different kinds.

  12. Heart transplantation in adults with congenital heart disease.

    PubMed

    Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien

    2017-02-22

    With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes.

  13. Cardiac fibroblast-derived extracellular matrix (biomatrix) as a model for the studies of cardiac primitive cell biological properties in normal and pathological adult human heart.

    PubMed

    Castaldo, Clotilde; Di Meglio, Franca; Miraglia, Rita; Sacco, Anna Maria; Romano, Veronica; Bancone, Ciro; Della Corte, Alessandro; Montagnani, Stefania; Nurzynska, Daria

    2013-01-01

    Cardiac tissue regeneration is guided by stem cells and their microenvironment. It has been recently described that both cardiac stem/primitive cells and extracellular matrix (ECM) change in pathological conditions. This study describes the method for the production of ECM typical of adult human heart in the normal and pathological conditions (ischemic heart disease) and highlights the potential use of cardiac fibroblast-derived ECM for in vitro studies of the interactions between ECM components and cardiac primitive cells responsible for tissue regeneration. Fibroblasts isolated from adult human normal and pathological heart with ischemic cardiomyopathy were cultured to obtain extracellular matrix (biomatrix), composed of typical extracellular matrix proteins, such as collagen and fibronectin, and matricellular proteins, laminin, and tenascin. After decellularization, this substrate was used to assess biological properties of cardiac primitive cells: proliferation and migration were stimulated by biomatrix from normal heart, while both types of biomatrix protected cardiac primitive cells from apoptosis. Our model can be used for studies of cell-matrix interactions and help to determine the biochemical cues that regulate cardiac primitive cell biological properties and guide cardiac tissue regeneration.

  14. Heart transplantation in adults with congenital heart disease.

    PubMed

    Stewart, Garrick C; Mayer, John E

    2014-01-01

    Heart transplantation has become an increasingly common and effective therapy for adults with end-stage congenital heart disease (CHD) because of advances in patient selection and surgical technique. Indications for transplantation in CHD are similar to other forms of heart failure. Pretransplant assessment of CHD patients emphasizes evaluation of cardiac anatomy, pulmonary vascular disease, allosensitization, hepatic dysfunction, and neuropsychiatric status. CHD patients experience longer waitlist times and higher waitlist mortality than other transplant candidates. Adult CHD patients undergoing transplantation carry an early hazard for mortality compared with non-CHD recipients, but by 10 years posttransplant, CHD patients have a slight actuarial survival advantage.

  15. Heart Failure in Older Adults.

    PubMed

    Butrous, Hoda; Hummel, Scott L

    2016-09-01

    Heart failure (HF) is a leading cause of morbidity, hospitalization, and mortality in older adults and a growing public health problem placing a huge financial burden on the health care system. Many challenges exist in the assessment and management of HF in geriatric patients, who often have coexisting multimorbidity, polypharmacy, cognitive impairment, and frailty. These complex "geriatric domains" greatly affect physical and functional status as well as long-term clinical outcomes. Geriatric patients have been under-represented in major HF clinical trials. Nonetheless, available data suggest that guideline-based medical and device therapies improve morbidity and mortality. Nonpharmacologic strategies, such as exercise training and dietary interventions, are an active area of research. Targeted geriatric evaluation, including functional and cognitive assessment, can improve risk stratification and guide management in older patients with HF. Clinical trials that enroll older patients with multiple morbidities and HF and evaluate functional status and quality of life in addition to mortality and cardiovascular morbidity should be encouraged to guide management of this age group.

  16. [Evaluation of congenital heart disease in adults].

    PubMed

    Oliver Ruiz, José María; Mateos García, Marta; Bret Zurita, Montserrat

    2003-06-01

    Improvements in the diagnosis and surgical treatment of congenital heart disease during infancy and childhood have resulted in an outstanding increase in the prevalence of these entities during adulthood. Congenital heart disease in the adult represents a new diagnostic challenge to the consultant cardiologist, unfamiliar with the anatomical and functional complexities of cardiac malformations. Assessment of adult congenital heart disease with imaging techniques can be as accurate as in children. However, these techniques cannot substitute for a detailed clinical assessment. Physical examination, electrocardiography and chest x-rays remain the three main pillars of bedside diagnosis. Transthoracic echocardiography is undoubtedly the imaging technique which provides most information, and in many situations no additional studies are needed. Nevertheless, ultrasound imaging properties in adults are not as favorable as in children, and prior surgical procedures further impair image quality. Despite recent advances in ultrasound technologies such as harmonic or contrast imaging, other diagnostic procedures are sometimes required. Fortunately, transesophageal echocardiography and magnetic resonance imaging are easily performed in the adult, and do not require anaesthetic support, in contrast to pediatric patients. These techniques, together with nuclear cardiology and cardiac catheterization, complete the second tier of diagnostic techniques for congenital heart disease. To avoid unnecessary repetition of diagnostic procedures, the attending cardiologist should choose the sequence of diagnostic techniques carefully; although the information this yields is often redundant, it is also frequently complementary. This article aims to compare the diagnostic utility of different imaging techniques in adult patients with congenital heart disease, both with and without prior surgical repair.

  17. Adults with Congenital Heart Defects

    MedlinePlus

    ... Heart area Search By Zipcode Search by State SELECT YOUR LANGUAGE Español (Spanish) 简体中文 (Traditional Chinese) 繁体中文 ( ... in the Young and Council on Clinical Cardiology. Select a topic from the list below to learn ...

  18. Hypoxia induces heart regeneration in adult mice.

    PubMed

    Nakada, Yuji; Canseco, Diana C; Thet, SuWannee; Abdisalaam, Salim; Asaithamby, Aroumougame; Santos, Celio X; Shah, Ajay M; Zhang, Hua; Faber, James E; Kinter, Michael T; Szweda, Luke I; Xing, Chao; Hu, Zeping; Deberardinis, Ralph J; Schiattarella, Gabriele; Hill, Joseph A; Oz, Orhan; Lu, Zhigang; Zhang, Cheng Cheng; Kimura, Wataru; Sadek, Hesham A

    2017-01-12

    The adult mammalian heart is incapable of regeneration following cardiomyocyte loss, which underpins the lasting and severe effects of cardiomyopathy. Recently, it has become clear that the mammalian heart is not a post-mitotic organ. For example, the neonatal heart is capable of regenerating lost myocardium, and the adult heart is capable of modest self-renewal. In both of these scenarios, cardiomyocyte renewal occurs via the proliferation of pre-existing cardiomyocytes, and is regulated by aerobic-respiration-mediated oxidative DNA damage. Therefore, we reasoned that inhibiting aerobic respiration by inducing systemic hypoxaemia would alleviate oxidative DNA damage, thereby inducing cardiomyocyte proliferation in adult mammals. Here we report that, in mice, gradual exposure to severe systemic hypoxaemia, in which inspired oxygen is gradually decreased by 1% and maintained at 7% for 2 weeks, results in inhibition of oxidative metabolism, decreased reactive oxygen species production and oxidative DNA damage, and reactivation of cardiomyocyte mitosis. Notably, we find that exposure to hypoxaemia 1 week after induction of myocardial infarction induces a robust regenerative response with decreased myocardial fibrosis and improvement of left ventricular systolic function. Genetic fate-mapping analysis confirms that the newly formed myocardium is derived from pre-existing cardiomyocytes. These results demonstrate that the endogenous regenerative properties of the adult mammalian heart can be reactivated by exposure to gradual systemic hypoxaemia, and highlight the potential therapeutic role of hypoxia in regenerative medicine.

  19. Large-scale discovery of enhancers from human heart tissue.

    PubMed

    May, Dalit; Blow, Matthew J; Kaplan, Tommy; McCulley, David J; Jensen, Brian C; Akiyama, Jennifer A; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Afzal, Veena; Simpson, Paul C; Rubin, Edward M; Black, Brian L; Bristow, James; Pennacchio, Len A; Visel, Axel

    2011-12-04

    Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.

  20. Morphology and biomechanics of human heart

    NASA Astrophysics Data System (ADS)

    Chelnokova, Natalia O.; Golyadkina, Anastasiya A.; Kirillova, Irina V.; Polienko, Asel V.; Ivanov, Dmitry V.

    2016-03-01

    Object of study: A study of the biomechanical characteristics of the human heart ventricles was performed. 80 hearts were extracted during autopsy of 80 corpses of adults (40 women and 40 men) aged 31-70 years. The samples were investigated in compliance with the recommendations of the ethics committee. Methods: Tension and compression tests were performed with help of the uniaxial testing machine Instron 5944. Cardiometry was also performed. Results: In this work, techniques for human heart ventricle wall biomechanical properties estimation were developed. Regularities of age and gender variability in deformative and strength properties of the right and left ventricle walls were found. These properties were characterized by a smooth growth of myocardial tissue stiffness and resistivity at a relatively low strain against reduction in their strength and elasticity from 31-40 to 61-70 years. It was found that tissue of the left ventricle at 61-70 years had a lower stretchability and strength compared with tissues of the right ventricle and septum. These data expands understanding of the morphological organization of the heart ventricles, which is very important for the development of personalized medicine. Taking into account individual, age and gender differences of the heart ventricle tissue biomechanical characteristics allows to rationally choosing the type of patching materials during reconstructive operations on heart.

  1. miRNA Expression in Pediatric Failing Human Heart

    PubMed Central

    Stauffer, Brian L.; Russell, Gloria; Nunley, Karin; Miyamoto, Shelley D.; Sucharov, Carmen C.

    2013-01-01

    miRNAs are short regulatory RNAs that can regulate gene expression through interacting with the 3'UTR of target mRNAs. Although the role of miRNAs has been extensively studied in adult human and animal models of heart disease, nothing is known about their expression in pediatric heart failure patients. Different than adults with heart failure, pediatric patients respond well to phosphodiesterase inhibitor (PDEi) treatment, which is safe in the outpatient setting, results in fewer heart failure emergency department visits, fewer cardiac hospital admissions and improved NYHA classification. We have recently shown that the pediatric heart failure patients display a unique molecular profile that is different from adults with heart failure. In this study we show for the first time that pediatric heart failure patients display a unique miRNA profile, and that expression of some miRNAs correlate with response to PDEi treatment. Moreover, we show that expression of Smad4, a potential target for PDEi-regulated miRNAs, is normalized in PDEi-treated patients. Since miRNAs may be used as therapy for human heart failure, our results underscore the importance of defining the molecular characteristics of pediatric heart failure patients, so age-appropriate therapy can be designed for this population. PMID:23333438

  2. Epidemiology, Pathophysiology, and Prognosis of Heart Failure in Older Adults

    PubMed Central

    Rich, Michael W.

    2017-01-01

    Synopsis Heart failure is the quintessential cardiovascular syndrome of aging that results from common cardiovascular conditions in older adults in conjunction with age-associated changes in cardiovascular structure and function. To a large extent, heart failure is a geriatric syndrome in much the same way that dementia, falls, and frailty are geriatric syndromes. The incidence and prevalence of heart failure increase strikingly with age and make heart failure the most common reason for hospitalization among older adults. While outcomes for older adults with heart failure have improved over time, mortality, hospitalization, and rehospitalization rates remain high. PMID:17905375

  3. Evaluation of Adults With Congenital Heart Disease.

    PubMed

    Graziani, Francesca; Delogu, Angelica Bibiana

    2016-03-01

    The clinical approach to adults with congenital heart diseases (ACHDs) is unique in cardiovascular medicine because these patients encompass a broad range of presentations. Each patient, despite having similar diagnosis, will be anatomically and physiologically unlike others within ACHD population, in relation to the type of repair, age at repair, associated defects, with specific long-term risk factors and complications. Furthermore, as many patients will not complain of symptoms, clinical evaluation and diagnostic testing must also be based on the underlying main diagnostic category, with complete standardized lesion-specific clinical protocols, investigating all known risk factors specific for each congenital heart disease and performed as part of screening for significant long-term complications. The first part of this review will focus on clinical history, physical examination, and the most important diagnostic testing in ACHD population. The second part of the article will focus on some clinical issues we have to face in our daily practice, such as heart failure, cyanosis, and pulmonary hypertension. Furthermore, as survival rates of ACHD population continue to improve and patients with this condition live longer, we will briefly report on a new clinical concern regarding the impact of acquired morbidities like coronary artery disease that appear to be of greater importance in defining outcome in older patients with ACHD.

  4. Medical therapy in adults with congenital heart disease.

    PubMed

    Book, Wendy M; Shaddy, Robert E

    2014-01-01

    Heart failure is a common late complication in adults with congenital heart defects, both repaired and unrepaired. The onset of clinical heart failure is associated with increased morbidity and mortality. Some patients with congenital heart disease may benefit from medications shown to improve survival in the population with acquired heart failure, but these same therapies may be of no benefit to other patients. Further studies are needed to better guide the choice of medical therapies.

  5. Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

    MedlinePlus

    ... Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  6. Towards defining heart failure in adults with congenital heart disease.

    PubMed

    Bolger, Aidan P; Gatzoulis, Michael A

    2004-12-01

    Injury to the myocardium disrupts geometric integrity and results in changes to intracardiac pressure, wall stress and tension, and the pattern of blood flow through the heart. Significant disruption to pump function results in heart failure which is defined in terms of symptoms: breathlessness and fatigue, signs of salt and water retention, and neurohormonal activation. This syndrome most commonly occurs in the context of injury due to ischaemic heart disease and dilated cardiomyopathy but because patients with congenital heart disease (CHD) are born with sometimes gross distortions of cardiac anatomy they too are subject to the forces that drive heart failure. This paper explores the available data relating to the clinical and neurohormonal manifestations of heart failure in patients with congenital heart disease and describes how, by additionally exploring events at a cellular level, we may be able to arrive at a definition of heart failure relevant to this population.

  7. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair.

    PubMed

    Xin, Mei; Olson, Eric N; Bassel-Duby, Rhonda

    2013-08-01

    As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through 'reawakening' pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure.

  8. Acquired heart conditions in adults with congenital heart disease: a growing problem.

    PubMed

    Tutarel, Oktay

    2014-09-01

    The number of adults with congenital heart disease is increasing due to the great achievements in the field of paediatric cardiology, congenital heart surgery and intensive care medicine over the last decades. Mortality has shifted away from the infant and childhood period towards adulthood. As congenital heart disease patients get older, a high prevalence of cardiovascular risk factors is encountered similar to the general population. Consequently, the contribution of acquired morbidities, especially acquired heart conditions to patient outcome, is becoming increasingly important. Therefore, to continue the success story of the last decades in the treatment of congenital heart disease and to further improve the outcome of these patients, more attention has to be given to the prevention, detection and adequate therapy of acquired heart conditions. The aim of this review is to give an overview about acquired heart conditions that may be encountered in adults with congenital heart disease.

  9. Genome-wide analysis of alternative splicing during human heart development

    NASA Astrophysics Data System (ADS)

    Wang, He; Chen, Yanmei; Li, Xinzhong; Chen, Guojun; Zhong, Lintao; Chen, Gangbing; Liao, Yulin; Liao, Wangjun; Bin, Jianping

    2016-10-01

    Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.

  10. A review of the economics of adult congenital heart disease.

    PubMed

    Seckeler, Michael D; Thomas, Ian D; Andrews, Jennifer; Joiner, Keith; Klewer, Scott E

    2016-01-01

    Adults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.

  11. Adult Congenital Heart Disease in Pregnancy.

    PubMed

    Lindley, Kathryn J; Conner, Shayna N; Cahill, Alison G

    2015-06-01

    With the success of modern surgical techniques for congenital heart disease, the population of women of childbearing age with congenital heart disease is growing. Because of the significant hemodynamic load of pregnancy, labor, and delivery, women with congenital heart disease require preconceptual risk assessment and expert multidisciplinary care throughout pregnancy. The aim of this review is to discuss the management of cardiovascular, obstetric, and fetal care issues that are commonly encountered during pregnancy in women with congenital heart disease.

  12. Adult Congenital Heart Disease: Scope of the Problem.

    PubMed

    Mazor Dray, Efrat; Marelli, Ariane J

    2015-11-01

    This article reviews the changing epidemiology of congenital heart disease summarizing its impact on the demographics of the congenital heart disease population and the progress made in order to improve outcomes in this patient population. Birth prevalence of congenital heart disease can be modified by many factors. As a result of decreasing mortality and increasing survival in all forms of congenital heart disease, the median age of patients has increased and adults now compose two-thirds of patients with congenital heart disease. Disease burden and resulting health services utilization increase significantly across the lifespan. Bridging the gap between policy and quality of care can be improved by referral to specialized adult congenital heart disease centers and planning delivery of specialized services that are commensurate with population needs, program accreditation criteria and certified training of designated workforce.

  13. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-08

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.

  14. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  15. Computer Simulation of the Beating Human Heart

    NASA Astrophysics Data System (ADS)

    Peskin, Charles S.; McQueen, David M.

    2001-06-01

    The mechanical function of the human heart couples together the fluid mechanics of blood and the soft tissue mechanics of the muscular heart walls and flexible heart valve leaflets. We discuss a unified mathematical formulation of this problem in which the soft tissue looks like a specialized part of the fluid in which additional forces are applied. This leads to a computational scheme known as the Immersed Boundary (IB) method for solving the coupled equations of motion of the whole system. The IB method is used to construct a three-dimensional Virtual Heart, including representations of all four chambers of the heart and all four valves, in addition to the large arteries and veins that connect the heart to the rest of the circulation. The chambers, valves, and vessels are all modeled as collections of elastic (and where appropriate, actively contractile) fibers immersed in viscous incompressible fluid. Results are shown as a computer-generated video animation of the beating heart.

  16. Data from acellular human heart matrix.

    PubMed

    Sánchez, Pedro L; Fernández-Santos, M Eugenia; Espinosa, M Angeles; González-Nicolas, M Angeles; Acebes, Judith R; Costanza, Salvatore; Moscoso, Isabel; Rodríguez, Hugo; García, Julio; Romero, Jesús; Kren, Stefan M; Bermejo, Javier; Yotti, Raquel; Del Villar, Candelas Pérez; Sanz-Ruiz, Ricardo; Elizaga, Jaime; Taylor, Doris A; Fernández-Avilés, Francisco

    2016-09-01

    Perfusion decellularization of cadaveric hearts removes cells and generates a cell-free extracellular matrix scaffold containing acellular vascular conduits, which are theoretically sufficient to perfuse and support tissue-engineered heart constructs. This article contains additional data of our experience decellularizing and testing structural integrity and composition of a large series of human hearts, "Acellular human heart matrix: a critical step toward whole heat grafts" (Sanchez et al., 2015) [1]. Here we provide the information about the heart decellularization technique, the valve competence evaluation of the decellularized scaffolds, the integrity evaluation of epicardial and myocardial coronary circulation, the pressure volume measurements, the primers used to assess cardiac muscle gene expression and, the characteristics of donors, donor hearts, scaffolds and perfusion decellularization process.

  17. Adult heart transplant: indications and outcomes.

    PubMed

    Alraies, M Chadi; Eckman, Peter

    2014-08-01

    Cardiac transplantation is the treatment of choice for many patients with end-stage heart failure (HF) who remain symptomatic despite optimal medical therapy. For carefully selected patients, heart transplantation offers markedly improved survival and quality of life. Risk stratification of the large group of patients with end-stage HF is essential for identifying patients who are most likely to benefit, particularly as the number of suitable donors is insufficient to meet demand. The indications for heart transplant and review components of the pre-transplant evaluation, including the role for exercise testing and risk scores such as the Heart Failure Survival Score (HFSS) and Seattle Heart Failure Model (SHFM) are summarized. Common contraindications are also discussed. Outcomes, including survival and common complications such as coronary allograft vasculopathy are reviewed.

  18. Adult heart transplant: indications and outcomes

    PubMed Central

    Alraies, M. Chadi

    2014-01-01

    Cardiac transplantation is the treatment of choice for many patients with end-stage heart failure (HF) who remain symptomatic despite optimal medical therapy. For carefully selected patients, heart transplantation offers markedly improved survival and quality of life. Risk stratification of the large group of patients with end-stage HF is essential for identifying patients who are most likely to benefit, particularly as the number of suitable donors is insufficient to meet demand. The indications for heart transplant and review components of the pre-transplant evaluation, including the role for exercise testing and risk scores such as the Heart Failure Survival Score (HFSS) and Seattle Heart Failure Model (SHFM) are summarized. Common contraindications are also discussed. Outcomes, including survival and common complications such as coronary allograft vasculopathy are reviewed. PMID:25132979

  19. More Than Just the Heart: Transition and Psychosocial Issues in Adult Congenital Heart Disease.

    PubMed

    Kovacs, Adrienne H; Utens, Elisabeth M

    2015-11-01

    Most infants born with congenital heart disease (CHD) are now expected to reach adulthood. However, adults with CHD of moderate or great complexity remain at elevated risk of heart failure, arrhythmias, additional surgeries and interventional procedures, and premature mortality. This creates a need for lifelong specialized cardiac care and leads to 2 sets of potential challenges: (1) the transition from pediatric to adult care and (2) the psychosocial implications of coping with a chronic and often life-shortening medical condition. Many adolescents struggle with the transition to adult care, and mood and anxiety disorders are not uncommon in the adult setting.

  20. Intensive care of the adult patient with congenital heart disease.

    PubMed

    Allan, Catherine K

    2011-01-01

    Prevalence of congenital heart disease in the adult population has increased out of proportion to that of the pediatric population as survival has improved, and adult congenital heart disease patients make up a growing percentage of pediatric and adult cardiac intensive care unit admissions. These patients often develop complex multiorgan system disease as a result of long-standing altered cardiac physiology, and many require reoperation during adulthood. Practitioners who care for these patients in the cardiac intensive care unit must have a strong working knowledge of the pathophysiology of complex congenital heart disease, and a full team of specialists must be available to assist in the care of these patients. This chapter will review some of the common multiorgan system effects of long-standing congenital heart disease (eg, renal and hepatic dysfunction, coagulation abnormalities, arrhythmias) as well as some of the unique cardiopulmonary physiology of this patient population.

  1. Hope in elderly adults with chronic heart failure. Concept analysis.

    PubMed

    Caboral, Meriam F; Evangelista, Lorraine S; Whetsell, Martha V

    2012-01-01

    This topic review employed Walker and Avant's method of concept analysis to explore the construct of hope in elderly adults with chronic heart failure. The articles analyzed revealed that hope, as the belief of the occurrence of a positive result without any guarantee that it will be produced, is necessary for the survival and wellbeing of the elderly adults enduring this disease.

  2. Development of the human heart.

    PubMed

    Sylva, Marc; van den Hoff, Maurice J B; Moorman, Antoon F M

    2014-06-01

    Molecular and genetic studies around the turn of this century have revolutionized the field of cardiac development. We now know that the primary heart tube, as seen in the early embryo contains little more than the precursors for the left ventricle, whereas the precursor cells for the remainder of the cardiac components are continuously added, to both the venous and arterial pole of the heart tube, from a single center of growth outside the heart. While the primary heart tube is growing by addition of cells, it does not show significant cell proliferation, until chamber differentiation and expansion starts locally in the tube, by which the chambers balloon from the primary heart tube. The transcriptional repressors Tbx2 and Tbx3 locally repress the chamber-specific program of gene expression, by which these regions are allowed to differentiate into the distinct components of the conduction system. Molecular genetic lineage analyses have been extremely valuable to assess the distinct developmental origin of the various component parts of the heart, which currently can be unambiguously identified by their unique molecular phenotype. Despite the enormous advances in our knowledge on cardiac development, even the most common congenital cardiac malformations are only poorly understood. The challenge of the newly developed molecular genetic techniques is to unveil the basic gene regulatory networks underlying cardiac morphogenesis.

  3. Pregnancy and Adult Congenital Heart Disease.

    PubMed

    Bhatt, Ami B; DeFaria Yeh, Doreen

    2015-11-01

    Most women with known congenital heart disease can have successful pregnancy, labor, and delivery. Preconception assessment is essential in understanding anatomy, repairs, and current physiology, all of which can influence risk in pregnancy. With that foundation, a multidisciplinary cardio-obstetric team can predict and prepare for complications that may occur with superimposed hemodynamic changes of pregnancy. Individuals with Eisenmenger syndrome, pulmonary hypertension, cyanosis, significant left heart obstruction, ventricular dysfunction, or prior major cardiac event are among the highest risk for complications.

  4. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair

    PubMed Central

    Xin, Mei; Olson, Eric N.; Bassel-Duby, Rhonda

    2013-01-01

    As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through ‘reawakening’ pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure. PMID:23839576

  5. Hope in elderly adults with chronic heart failure. Concept analysis

    PubMed Central

    Caboral, Meriam F.; Evangelista, Lorraine S.; Whetsell, Martha V.

    2015-01-01

    This topic review employed Walker and Avant’s method of concept analysis to explore the construct of hope in elderly adults with chronic heart failure. The articles analyzed revealed that hope, as the belief of the occurrence of a positive result without any guarantee that it will be produced, is necessary for the survival and wellbeing of the elderly adults enduring this disease. PMID:26321777

  6. Percutaneous options for heart failure in adults with congenital heart disease.

    PubMed

    Mylotte, Darren; Martucci, Giuseppe; Piazza, Nicolo; McElhinney, Doff

    2014-01-01

    In the context of congenital heart disease (CHD), the complex biochemical and physiologic response to the pressure- or volume-loaded ventricle can be induced by stenotic and shunt/regurgitant lesions, respectively. A range of transcatheter therapies have recently emerged to expand the therapeutic potential of the more traditional surgical and medical interventions for heart failure in patients with CHD. Together, these complementary interventions aim to treat the growing patient population with adult CHD (ACHD). In this article, the most commonly used transcatheter interventions for heart failure in patients with ACHD are reviewed.

  7. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family

    PubMed Central

    Porrello, Enzo R.; Mahmoud, Ahmed I.; Simpson, Emma; Johnson, Brett A.; Grinsfelder, David; Canseco, Diana; Mammen, Pradeep P.; Rothermel, Beverly A.; Olson, Eric N.; Sadek, Hesham A.

    2013-01-01

    We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity. PMID:23248315

  8. Oxygen consumption of human heart cells in monolayer culture.

    PubMed

    Sekine, Kaori; Kagawa, Yuki; Maeyama, Erina; Ota, Hiroki; Haraguchi, Yuji; Matsuura, Katsuhisa; Shimizu, Tatsuya

    2014-09-26

    Tissue engineering in cardiovascular regenerative therapy requires the development of an efficient oxygen supply system for cell cultures. However, there are few studies which have examined human cardiomyocytes in terms of oxygen consumption and metabolism in culture. We developed an oxygen measurement system equipped with an oxygen microelectrode sensor and estimated the oxygen consumption rates (OCRs) by using the oxygen concentration profiles in culture medium. The heart is largely made up of cardiomyocytes, cardiac fibroblasts, and cardiac endothelial cells. Therefore, we measured the oxygen consumption of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), cardiac fibroblasts, human cardiac microvascular endothelial cell and aortic smooth muscle cells. Then we made correlations with their metabolisms. In hiPSC-CMs, the value of the OCR was 0.71±0.38pmol/h/cell, whereas the glucose consumption rate and lactate production rate were 0.77±0.32pmol/h/cell and 1.61±0.70pmol/h/cell, respectively. These values differed significantly from those of the other cells in human heart. The metabolism of the cells that constitute human heart showed the molar ratio of lactate production to glucose consumption (L/G ratio) that ranged between 1.97 and 2.2. Although the energy metabolism in adult heart in vivo is reported to be aerobic, our data demonstrated a dominance of anaerobic glycolysis in an in vitro environment. With our measuring system, we clearly showed the differences in the metabolism of cells between in vivo and in vitro monolayer culture. Our results regarding cell OCRs and metabolism may be useful for future tissue engineering of human heart.

  9. Programming and reprogramming a human heart cell.

    PubMed

    Sahara, Makoto; Santoro, Federica; Chien, Kenneth R

    2015-03-12

    The latest discoveries and advanced knowledge in the fields of stem cell biology and developmental cardiology hold great promise for cardiac regenerative medicine, enabling researchers to design novel therapeutic tools and approaches to regenerate cardiac muscle for diseased hearts. However, progress in this arena has been hampered by a lack of reproducible and convincing evidence, which at best has yielded modest outcomes and is still far from clinical practice. To address current controversies and move cardiac regenerative therapeutics forward, it is crucial to gain a deeper understanding of the key cellular and molecular programs involved in human cardiogenesis and cardiac regeneration. In this review, we consider the fundamental principles that govern the "programming" and "reprogramming" of a human heart cell and discuss updated therapeutic strategies to regenerate a damaged heart.

  10. [Pediatric cardiology and congenital heart disease: from fetus to adult].

    PubMed

    Subirana, M Teresa; Oliver, José M; Sáez, José M; Zunzunegui, José L

    2012-01-01

    This article contains a review of some of the most important publications on congenital heart disease and pediatric cardiology that appeared in 2010 and up until September 2011. Of particular interest were studies on demographic changes reported in this patient population and on the need to manage the patients' transition from the pediatric to the adult cardiology department. This transition has given rise to the appearance of new areas of interest: for example, pregnancy in women with congenital heart disease, and the effect of genetic factors on the etiology and transmission of particular anomalies. In addition, this review considers some publications on fetal cardiology from the perspective of early diagnosis and, if possible, treatment. There follows a discussion on new contributions to Eisenmenger's syndrome and arrhythmias, as well as on imaging techniques, interventional catheterization and heart transplantation. Finally, there is an overview of the new version of clinical practice guidelines on the management of adult patients with congenital heart disease and of recently published guidelines on pregnancy in women with heart disease, both produced by the European Society of Cardiology.

  11. Telocytes and putative stem cells in ageing human heart.

    PubMed

    Popescu, Laurentiu M; Curici, Antoanela; Wang, Enshi; Zhang, Hao; Hu, Shengshou; Gherghiceanu, Mihaela

    2015-01-01

    Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days-1 year), children (6-17 years) and adults (34-60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm(2) ) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52-62%; vascular smooth muscle cells and pericytes 22-28%, Schwann cells with nerve endings 6-7%, fibroblasts 3-10%, macrophages 1-8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults).

  12. Arts & Humanities in Adult Education.

    ERIC Educational Resources Information Center

    Word's Worth: A Quarterly Newsletter of the Lifelong Learning Network, 1998

    1998-01-01

    This issue of a quarterly newsletter on lifelong learning focuses on the theme of the arts and humanities in adult literacy education. The following articles are included: (1) "In Defense of a Practical Education" (Earl Shorris); (2) "From the Program Director" (Elizabeth Bryant McCrary); (3) "Vermont Council on the Humanities: Book Discussion…

  13. Resting Heart Rate and Aortic Stiffness in Normotensive Adults

    PubMed Central

    Logan, Jeongok G.

    2016-01-01

    Background and Objectives Large-artery stiffness is an independent predictor of cardiovascular disease (CVD), and carotid-femoral pulse wave velocity (cfPWV) is considered the gold standard measure of arterial stiffness. A resting heart rate is an easily measured vital sign that is also associated with CVD morbidity and mortality. Previous studies have reported the significant relationship of a resting heart rate with arterial stiffness as measured by cfPWV only in hypertensive subjects; their relationship in nonhypertensive subjects remains unknown. The present study, therefore, examined their relationship in normotensive subjects. Subjects and Methods In 102 healthy Korean Americans between ages 20 and 60 years, their resting heart rate was measured by an automated blood pressure measuring device after a 10 minute rest in the supine position. Arterial stiffness was measured by cfPWV using the SphygmoCor device. Results The mean resting heart rate of participants (mean age, 39.64 years; 59% women) was 61.91 bpm (standard deviation [SD], 9.62 bpm) and mean the cfPWV was 6.99 (SD, 1.14) m/s. A multiple regression analysis showed that a resting heart rate is a significant predictor of cfPWV after controlling for age, body mass index, and mean arterial pressure. For one bpm increase of resting heart rate, cfPWV increased approximately 0.02 m/s. Conclusion Our results suggest that a higher resting heart rate is independently associated with increased arterial stiffness as measured by cfPWV in normotensive adults. Arterial stiffness may explain the prognostic role of an individual's heart rate in cardiovascular morbidity and mortality. PMID:27826343

  14. Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue.

    PubMed

    Asp, Julia; Steel, Daniella; Jonsson, Marianne; Améen, Caroline; Dahlenborg, Kerstin; Jeppsson, Anders; Lindahl, Anders; Sartipy, Peter

    2010-10-01

    Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.

  15. Ghrelin signaling in heart remodeling of adult obese mice.

    PubMed

    Lacerda-Miranda, Glauciane; Soares, Vivian M; Vieira, Anatalia K G; Lessa, Juliana G; Rodrigues-Cunha, Alessandra C S; Cortez, Erika; Garcia-Souza, Erica P; Moura, Anibal S

    2012-05-01

    Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), has been suggested to be associated to obesity, insulin secretion, cardiovascular growth and homeostasis. GHS-R has been found in most of the tissues, and among the hormone action it is included the regulation of heart energy metabolism. Therefore, hypernutrition during early life leads to obesity, induces cardiac hypertrophy, compromises myocardial function, inducing heart failure in adulthood. We examined ghrelin signaling process in cardiac remodeling in these obese adult mice. The cardiomyocytes (cmy) of left ventricle were analyzed by light microscopy and stereology, content and phosphorilation of cardiac proteins: ghrelin receptor (growth hormone secretagogue receptor 1a, GHSR-1a), protein kinase B (AKT and pAKT), phosphatidil inositol 3 kinase (PI3K), AMP-activated protein kinase (AMPK and pAMPK) and actin were achieved by Western blotting. GHSR-1a gene expression was analyzed by Real Time-PCR. We observed hyperglycemia and higher liver and visceral fat weight in obese when compared to control group. Obese mice presented a marked increase in heart weight/tibia length, indicating an enlarged heart size or a remodeling process. Obese mice had increased GHSR-1a content and expression in the heart associated to PI3K content and increased AKT content and phosphorylation. In contrast, AMPK content and phosphorylation in heart was not different between experimental groups. Ghrelin plasma levels in obese group were decreased when compared to control group. Our data suggest that remodeled myocardial in adult obese mice overnourished in early life are associated with higher phosphorylation of GHSR-1a, PI3K and AKT but not with AMPK.

  16. Myocardial bridges of the coronary arteries in the human fetal heart.

    PubMed

    Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

    2010-09-01

    During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

  17. Angiopoietin-2 in Adults with Congenital Heart Disease and Heart Failure

    PubMed Central

    Kümpers, Philipp; Denecke, Agnieszka; Westhoff-Bleck, Mechthild; Schieffer, Bernhard; Bauersachs, Johann; Kielstein, Jan T.; Tutarel, Oktay

    2013-01-01

    Background Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its application in ACHD has limitations. The angiogenic factors Angiopoietin-1 and -2 (Ang-1, Ang-2), vascular endothelial growth factor (VEGF), and soluble receptor tyrosine kinase of the Tie family (sTie2) correlate with disease severity in heart failure of non-congenital origin. Their role in ACHD has not been studied. Methods In 91 patients Ang-2 and NT-proBNP were measured and related to New York Heart Association class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Ang-1, VEGF, and sTie2 were also measured. Results Ang-2 correlates with NYHA class and ventricular dysfunction comparable to NT-proBNP. Further, Ang-2 showed a good correlation with parameters of cardiopulmonary exercise testing. Both, Ang-2 and NT-proBNP identified patients with severely limited cardiopulmonary exercise capacity. Additionally, Ang-2 is elevated in patients with a single ventricle physiology in contrast to NT-proBNP. VEGF, Ang-1, and sTie2 were not correlated with any clinical parameter. Conclusion The performance of Ang-2 as a biomarker for heart failure in ACHD is comparable to NT-proBNP. Its significant elevation in patients with single ventricle physiology indicates potential in this patient group and warrants further studies. PMID:23826161

  18. Transfer to Adult Care--Experiences of Young Adults with Congenital Heart Disease.

    PubMed

    Asp, Ann; Bratt, Ewa-Lena; Bramhagen, Ann-Cathrine

    2015-01-01

    More than 90% of children born with congenital heart disease survive into adulthood due to successes of cardiac surgery and medical management. Interviews with 16 young adults with congenital heart disease to explore their experiences of transfer from pediatric to adult care were performed. The analysis identified five themes; Feeling secure during the transfer process, Experiencing trust in the care, Expecting to be involved, Assuming responsibility for one's health is a process and Lack of knowledge leads to uncertainty. In conclusion; a structured and gradual transfer process was necessary to enable the informants to shoulder the responsibility for self-care.

  19. Heart failure treatment in adults with congenital heart disease: where do we stand in 2014?

    PubMed

    Krieger, Eric V; Valente, Anne Marie

    2014-09-01

    Heart failure (HF) is the leading cause of death in adults with repaired congenital heart disease (CHD). However there is currently little evidence to guide treatment strategies in this growing group of patients. Unlike the majority of HF, which is usually caused by LV systolic or diastolic dysfunction, CHD-HF is more often a consequence of RV disease, valve dysfunction, shunting or pulmonary hypertension. It is therefore not appropriate to extrapolate from the acquired HF literature and apply it to this heterogeneous population of CHD patients. Additionally, patients with CHD have been excluded from most large trials of medical or device therapy of HF, which has resulted in small retrospective and underpowered studies in the CHD population. This article critically reviews the current knowledge about CHD-HF, paying particular attention to medical therapy in different CHD populations, cardiac resynchronisation therapy and implantable cardiac defibrillators, and the challenges of heart transplantation and mechanical circulatory support in CHD patients.

  20. Orthotropic heart transplantation for adult congenital heart disease: a case with heterotaxy and dextrocardia.

    PubMed

    Matsuda, Hikaru; Fukushima, Norihide; Ichikawa, Hajime; Sawa, Yoshiki

    2017-01-01

    A 41-year-old male with heterotaxy (left isomerism) and dextrocardia composed by single ventricle, absent inferior vena cava, bilateral superior vena cava (SVC), common atrioventricular valve has received orthotopic heart transplantation (HTx) after long waiting period as Status-1. Reconstructions of bilateral SVC and hepatic vein route were successful without use of prosthetic material, and the donor heart was placed in the left mediastinum. In spite of satisfactory early recovery, the patient expired 4 months after transplantation mainly from fungal infection which developed following humoral rejection. HTx for adult patients with complex congenital heart disease is demanding in technical as well as pre- and post-transplant management, and indication should be critically determined.

  1. Preconditioning boosts regenerative programmes in the adult zebrafish heart

    PubMed Central

    de Preux Charles, Anne-Sophie; Bise, Thomas; Baier, Felix; Sallin, Pauline; Jaźwińska, Anna

    2016-01-01

    During preconditioning, exposure to a non-lethal harmful stimulus triggers a body-wide increase of survival and pro-regenerative programmes that enable the organism to better withstand the deleterious effects of subsequent injuries. This phenomenon has first been described in the mammalian heart, where it leads to a reduction of infarct size and limits the dysfunction of the injured organ. Despite its important clinical outcome, the actual mechanisms underlying preconditioning-induced cardioprotection remain unclear. Here, we describe two independent models of cardiac preconditioning in the adult zebrafish. As noxious stimuli, we used either a thoracotomy procedure or an induction of sterile inflammation by intraperitoneal injection of immunogenic particles. Similar to mammalian preconditioning, the zebrafish heart displayed increased expression of cardioprotective genes in response to these stimuli. As zebrafish cardiomyocytes have an endogenous proliferative capacity, preconditioning further elevated the re-entry into the cell cycle in the intact heart. This enhanced cycling activity led to a long-term modification of the myocardium architecture. Importantly, the protected phenotype brought beneficial effects for heart regeneration within one week after cryoinjury, such as a more effective cell-cycle reentry, enhanced reactivation of embryonic gene expression at the injury border, and improved cell survival shortly after injury. This study reveals that exposure to antecedent stimuli induces adaptive responses that render the fish more efficient in the activation of the regenerative programmes following heart damage. Our results open a new field of research by providing the adult zebrafish as a model system to study remote cardiac preconditioning. PMID:27440423

  2. Antenatal architecture and activity of the human heart

    PubMed Central

    Pervolaraki, Eleftheria; Anderson, Richard A.; Benson, Alan P.; Hayes-Gill, Barrie; Holden, Arun V.; Moore, Benjamin J. R.; Paley, Martyn N.; Zhang, Henggui

    2013-01-01

    We construct the components for a family of computational models of the electrophysiology of the human foetal heart from 60 days gestational age (DGA) to full term. This requires both cell excitation models that reconstruct the myocyte action potentials, and datasets of cardiac geometry and architecture. Fast low-angle shot and diffusion tensor magnetic resonance imaging (DT-MRI) of foetal hearts provides cardiac geometry with voxel resolution of approximately 100 µm. DT-MRI measures the relative diffusion of protons and provides a measure of the average intravoxel myocyte orientation, and the orientation of any higher order orthotropic organization of the tissue. Such orthotropic organization in the adult mammalian heart has been identified with myocardial sheets and cleavage planes between them. During gestation, the architecture of the human ventricular wall changes from being irregular and isotropic at 100 DGA to an anisotropic and orthotropic architecture by 140 DGA, when it has the smooth, approximately 120° transmural change in myocyte orientation that is characteristic of the adult mammalian ventricle. The DT obtained from DT-MRI provides the conductivity tensor that determines the spread of potential within computational models of cardiac tissue electrophysiology. The foetal electrocardiogram (fECG) can be recorded from approximately 60 DGA, and RR, PR and QT intervals between the P, R, Q and T waves of the fECG can be extracted by averaging from approximately 90 DGA. The RR intervals provide a measure of the pacemaker rate, the QT intervals an index of ventricular action potential duration, and its rate-dependence, and so these intervals constrain and inform models of cell electrophysiology. The parameters of models of adult human sinostrial node and ventricular cells that are based on adult cell electrophysiology and tissue molecular mapping have been modified to construct preliminary models of foetal cell electrophysiology, which reproduce these

  3. Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells.

    PubMed

    van den Berg, Cathelijne W; Okawa, Satoshi; Chuva de Sousa Lopes, Susana M; van Iperen, Liesbeth; Passier, Robert; Braam, Stefan R; Tertoolen, Leon G; del Sol, Antonio; Davis, Richard P; Mummery, Christine L

    2015-09-15

    Differentiated derivatives of human pluripotent stem cells (hPSCs) are often considered immature because they resemble foetal cells more than adult, with hPSC-derived cardiomyocytes (hPSC-CMs) being no exception. Many functional features of these cardiomyocytes, such as their cell morphology, electrophysiological characteristics, sarcomere organization and contraction force, are underdeveloped compared with adult cardiomyocytes. However, relatively little is known about how their gene expression profiles compare with the human foetal heart, in part because of the paucity of data on the human foetal heart at different stages of development. Here, we collected samples of matched ventricles and atria from human foetuses during the first and second trimester of development. This presented a rare opportunity to perform gene expression analysis on the individual chambers of the heart at various stages of development, allowing us to identify not only genes involved in the formation of the heart, but also specific genes upregulated in each of the four chambers and at different stages of development. The data showed that hPSC-CMs had a gene expression profile similar to first trimester foetal heart, but after culture in conditions shown previously to induce maturation, they cluster closer to the second trimester foetal heart samples. In summary, we demonstrate how the gene expression profiles of human foetal heart samples can be used for benchmarking hPSC-CMs and also contribute to determining their equivalent stage of development.

  4. Management of the sensitized adult heart transplant candidate.

    PubMed

    Eckman, Peter M; Hanna, Mazen; Taylor, David O; Starling, Randall C; Gonzalez-Stawinski, Gonzalo V

    2010-01-01

    Heart transplant recipients sensitized to human leukocyte antigens comprise a challenging subgroup of patients. Sensitization has been associated with a variety of effects that determine short-term and long-term outcomes. These include a higher rate of acute rejection and graft loss, and a heightened risk for developing cardiac allograft vasculopathy. Because of improvements in both tissue typing and immunomodulatory therapies coupled with the growing population receiving mechanical circulatory support/LVAD, the percent of sensitized patients listed for heart transplantation has increased, inflicting a greater burden to the already scarce donor pool. Despite these potentially adverse developments, pre-transplant immunologic management has resulted in decreased waiting times and outcomes that were not possible over 10 yr ago. The following review will focus on the contemporary management of the sensitized heart transplant candidate and highlight therapies that have allowed the successful transplantation of this growing and challenging patient population, including several approaches in development.

  5. Contractile force measured in unskinned isolated adult rat heart fibres.

    PubMed

    Brady, A J; Tan, S T; Ricchiuti, N V

    1979-12-13

    A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.

  6. Clinical Research Priorities in Adult Congenital Heart Disease

    PubMed Central

    Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R.; John, Anitha S.; Valente, Anne Marie; Zaidi, Ali N.; Cook, Stephen C.; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J.; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S.

    2014-01-01

    Background Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. Methods A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. Results The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. Conclusions The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. PMID:24411207

  7. [Pulmonary arterial hypertension in adult patients with congenital heart disease].

    PubMed

    Serino, G; Giacomazzi, F

    2010-01-01

    Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.

  8. [Cardiac magnetic resonance imaging of congenital heart defects in adults].

    PubMed

    Bastarrika Alemañ, G; Gavira Gómez, J J; Zudaire Díaz-Tejeiro, B; Castaño Rodríguez, S; Romero Ibarra, C; Sáenz de Buruaga, J D

    2007-01-01

    The study of congenital cardiopathies (CC) is one of the most clearly established indications of cardiac magnetic resonance imaging (CMRI). Different sequences, including anatomic, functional, flow (phase contrast), and 3D angiographic sequences, enable the diagnosis, treatment planning, and follow-up of these conditions. CMRI allows the anatomy, function, and alterations of flow in these cardiopathies to be evaluated in a single examination. Three-dimensional MR angiography enables the study of the great vessels and the anomalies associated to congenital heart defects in adults. This article describes an examination protocol and provides examples of MR images of the most common CC in adults: atrial septal defect, interventricular communication, atrioventricular canal, tetralogy of Fallot, transposition of the great arteries, congenitally corrected transposition of the great arteries, bicuspid aortic valve, subaortic stenosis, aortic coarctation, and Ebstein's anomaly.

  9. Sodium MRI in human heart: a review.

    PubMed

    Bottomley, Paul A

    2016-02-01

    This paper offers a critical review of the properties, methods and potential clinical application of sodium ((23)Na) MRI in human heart. Because the tissue sodium concentration (TSC) in heart is about ~40 µmol/g wet weight, and the (23)Na gyromagnetic ratio and sensitivity are respectively about one-quarter and one-11th of that of hydrogen ((1)H), the signal-to-noise ratio of (23)Na MRI in the heart is about one-6000th of that of conventional cardiac (1)H MRI. In addition, as a quadrupolar nucleus, (23)Na exhibits ultra-short and multi-component relaxation behavior (T1 ~ 30 ms; T2 ~ 0.5-4 ms and 12-20 ms), which requires fast, specialized, ultra-short echo-time MRI sequences, especially for quantifying TSC. Cardiac (23)Na MRI studies from 1.5 to 7 T measure a volume-weighted sum of intra- and extra-cellular components present at cytosolic concentrations of 10-15 mM and 135-150 mM in healthy tissue, respectively, at a spatial resolution of about 0.1-1 ml in 10 min or so. Currently, intra- and extra-cellular sodium cannot be unambiguously resolved without the use of potentially toxic shift reagents. Nevertheless, increases in TSC attributable to an influx of intra-cellular sodium and/or increased extra-cellular volume have been demonstrated in human myocardial infarction consistent with prior animal studies, and arguably might also be seen in future studies of ischemia and cardiomyopathies--especially those involving defects in sodium transport. While technical implementation remains a hurdle, a central question for clinical use is whether cardiac (23)Na MRI can deliver useful information unobtainable by other more convenient methods, including (1)H MRI.

  10. Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult Xenopus

    PubMed Central

    Girardot, Fabrice; Péricard, Louise; Demeneix, Barbara A.; Coen, Laurent; Chai, Norin

    2017-01-01

    Models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. Such studies are currently dominated by the use of zebrafish and mice. Remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. Amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowledge. We thus developed an endoscopy-based resection method to explore the consequences of cardiac injury in adult Xenopus laevis. This method allowed in situ live heart observation, standardised tissue amputation size and reproducibility. During the first week following amputation, gene expression of cell proliferation markers remained unchanged, whereas those relating to sarcomere organisation decreased and markers of inflammation, fibrosis and hypertrophy increased. One-month post-amputation, fibrosis and hypertrophy were evident at the injury site, persisting through 11 months. Moreover, cardiomyocyte sarcomere organisation deteriorated early following amputation, and was not completely recovered as far as 11 months later. We conclude that the adult Xenopus heart is unable to regenerate, displaying cellular and molecular marks of scarring. Our work suggests that, contrary to urodeles and teleosts, with the exception of medaka, adult anurans share a cardiac injury outcome similar to adult mammals. This observation is at odds with current hypotheses that link loss of cardiac regenerative capacity with acquisition of homeothermy. PMID:28278282

  11. Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult Xenopus.

    PubMed

    Marshall, Lindsey; Vivien, Céline; Girardot, Fabrice; Péricard, Louise; Demeneix, Barbara A; Coen, Laurent; Chai, Norin

    2017-01-01

    Models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. Such studies are currently dominated by the use of zebrafish and mice. Remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. Amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowledge. We thus developed an endoscopy-based resection method to explore the consequences of cardiac injury in adult Xenopus laevis. This method allowed in situ live heart observation, standardised tissue amputation size and reproducibility. During the first week following amputation, gene expression of cell proliferation markers remained unchanged, whereas those relating to sarcomere organisation decreased and markers of inflammation, fibrosis and hypertrophy increased. One-month post-amputation, fibrosis and hypertrophy were evident at the injury site, persisting through 11 months. Moreover, cardiomyocyte sarcomere organisation deteriorated early following amputation, and was not completely recovered as far as 11 months later. We conclude that the adult Xenopus heart is unable to regenerate, displaying cellular and molecular marks of scarring. Our work suggests that, contrary to urodeles and teleosts, with the exception of medaka, adult anurans share a cardiac injury outcome similar to adult mammals. This observation is at odds with current hypotheses that link loss of cardiac regenerative capacity with acquisition of homeothermy.

  12. Affecting Rhomboid-3 Function Causes a Dilated Heart in Adult Drosophila

    PubMed Central

    Yu, Lin; Lee, Teresa; Lin, Na; Wolf, Matthew J.

    2010-01-01

    Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT) can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF)–like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz–EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest that an

  13. Imaging of congenital heart disease in adults: choice of modalities.

    PubMed

    Orwat, Stefan; Diller, Gerhard-Paul; Baumgartner, Helmut

    2014-01-01

    Major advances in noninvasive imaging of adult congenital heart disease have been accomplished. These tools play now a key role in comprehensive diagnostic work-up, decision for intervention, evaluation for the suitability of specific therapeutic options, monitoring of interventions and regular follow-up. Besides echocardiography, magnetic resonance (CMR) and computed tomography (CT) have gained particular importance. The choice of imaging modality has thus become a critical issue. This review summarizes strengths and limitations of the different imaging modalities and how they may be used in a complementary fashion. Echocardiography obviously remains the workhorse of imaging routinely used in all patients. However, in complex disease and after surgery echocardiography alone frequently remains insufficient. CMR is particularly useful in this setting and allows reproducible and accurate quantification of ventricular function and comprehensive assessment of cardiac anatomy, aorta, pulmonary arteries and venous return including complex flow measurements. CT is preferred when CMR is contraindicated, when superior spatial resolution is required or when "metallic" artefacts limit CMR imaging. In conclusion, the use of currently available imaging modalities in adult congenital heart disease needs to be complementary. Echocardiography remains the basis tool, CMR and CT should be added considering specific open questions and the ability to answer them, availability and economic issues.

  14. Zebrafish heart as a model for human cardiac electrophysiology.

    PubMed

    Vornanen, Matti; Hassinen, Minna

    2016-01-01

    The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non-orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart.

  15. Echocardiographic image of an active human heart

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Echocardiographic images provide quick, safe images of the heart as it beats. While a state-of-the art echocardiograph unit is part of the Human Research Facility on International Space Station, quick transmission of images and data to Earth is a challenge. NASA is developing techniques to improve the echocardiography available to diagnose sick astronauts as well as study the long-term effects of space travel on their health. Echocardiography uses ultrasound, generated in a sensor head placed against the patient's chest, to produce images of the structure of the heart walls and valves. However, ultrasonic imaging creates an enormous volume of data, up to 220 million bits per second. This can challenge ISS communications as well as Earth-based providers. Compressing data for rapid transmission back to Earth can degrade the quality of the images. Researchers at the Cleveland Clinic Foundation are working with NASA to develop compression techniques that meet imaging standards now used on the Internet and by the medical community, and that ensure that physicians receive quality diagnostic images.

  16. How to mend a broken heart: adult and induced pluripotent stem cell therapy for heart repair and regeneration.

    PubMed

    Wegener, Marie; Bader, Augustinus; Giri, Shibashish

    2015-06-01

    The recently developed ability to differentiate primary adult stem cells and induced pluripotent stem cells (iPSCs) into cardiomyocytes is providing unprecedented opportunities to produce an unlimited supply of cardiomyocytes for use in patients with heart disease. Here, we examine the evidence for the preclinical use of such cells for successful heart regeneration. We also describe advances in the identification of new cardiac molecular and cellular targets to induce proliferation of cardiomyocytes for heart regeneration. Such new advances are paving the way for a new innovative drug development process for the treatment of heart disease.

  17. 3D Printing to Guide Ventricular Assist Device Placement in Adults With Congenital Heart Disease and Heart Failure.

    PubMed

    Farooqi, Kanwal M; Saeed, Omar; Zaidi, Ali; Sanz, Javier; Nielsen, James C; Hsu, Daphne T; Jorde, Ulrich P

    2016-04-01

    As the population of adults with congenital heart disease continues to grow, so does the number of these patients with heart failure. Ventricular assist devices are underutilized in adults with congenital heart disease due to their complex anatomic arrangements and physiology. Advanced imaging techniques that may increase the utilization of mechanical circulatory support in this population must be explored. Three-dimensional printing offers individualized structural models that would enable pre-surgical planning of cannula and device placement in adults with congenital cardiac disease and heart failure who are candidates for such therapies. We present a review of relevant cardiac anomalies, cases in which such models could be utilized, and some background on the cost and procedure associated with this process.

  18. Perspectives of Puerto Rican Adults about Heart Health and a Potential Community Program

    ERIC Educational Resources Information Center

    Todorova, Irina L. G.; Tejada, Shirley; Castaneda-Sceppa, Carmen

    2014-01-01

    Background: Puerto Ricans are the second largest Hispanic group in the United States, and older adults have significant health disparities. Educational programs that address heart disease risk for this population have rarely been developed and implemented. Purpose: To address this gap, the Heart Healthy Initiative for Puerto Rican adults is being…

  19. Social burden and lifestyle in adults with congenital heart disease.

    PubMed

    Zomer, A Carla; Vaartjes, Ilonca; Uiterwaal, Cuno S P; van der Velde, Enno T; Sieswerda, Gert-Jan T; Wajon, Elly M C; Plomp, Koos; van Bergen, Paul F M; Verheugt, Carianne L; Krivka, Eva; de Vries, Cees J; Lok, Dirk J A; Grobbee, Diederick E; Mulder, Barbara J M

    2012-06-01

    We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group.

  20. Pain in adults post surgical repair of congenital heart defects.

    PubMed

    Jensen, Louise; Rebeyka, Darlene; Urquhart, Gayle; Roschkov, Sylvia

    2004-01-01

    The purpose of this study was to describe pain in adults post surgical repair for congenital heart defects. What is the intensity, sensory, and affective dimensions of pain experienced post-operatively? What is the trend in pain experienced post-operatively over time? What is the effectiveness of post-operative pain management strategies? What factors influence the dimensions of post-operative pain experienced? A descriptive prospective repeated measures design was used with 30 adult congenital heart (ACH) post-operative patients. Pain assessments using the McGill Short Form Questionnaire (MSFQ), a visual analogue pain scale (VAP), and recordings of other variables (analgesic, anxiety, activity level, non-pharmacologic intervention) were performed three times daily until hospital discharge. Mean pain intensity scores ranged from 2.44 +/- 1.31 following extubation to 1.30 +/- 0.66 on post-operative day (POD) five (scale, 0-5). Mean MSFQ scores ranged from 9.26 +/- 7.21 following extubation to 4.40 +/- 5.22 on POD five (scale, 0-45). Mean VAP scores ranged from 50.77 +/- 25.79 following extubation to 18.76 +/- 18.50 on POD five (scale, 0-100). Mean number of narcotic doses per day ranged from 4.61 +/- 2.01 to 1.88 +/- 1.98 on PODs one and five, respectively. Anxiety predicted VAP and MSFQ scores on PODs one and two; anxiety and analgesia doses predicted VAP and MSFQ scores on POD three; analgesia doses predicted MSFQ scores, analgesia and anxiety predicted VAP scores on POD four; analgesia doses and anxiety predicted VAP and MSFQ scores on POD five. No relationships were found among pain and other demographic, treatment, or clinical variables. Overall, pain was reported as mild to moderate intensity, variable in sensations, decreased over time, and adequately managed.

  1. Identification of cardiac progenitors that survive in the ischemic human heart after ventricular myocyte death

    PubMed Central

    Omatsu-Kanbe, Mariko; Nozuchi, Nozomi; Nishino, Yuka; Mukaisho, Ken-ichi; Sugihara, Hiroyuki; Matsuura, Hiroshi

    2017-01-01

    Atypically-shaped cardiomyocytes (ACMs) are beating heart cells identified in the cultures of cardiomyocyte-removed fractions obtained from adult mouse hearts. Since ACMs spontaneously develop into beating cells in the absence of hormones or chemicals, these cells are likely to be a type of cardiac progenitors rather than stem cells. “Native ACMs” are found as small interstitial cells among ventricular myocytes that co-express cellular prion protein (PrP) and cardiac troponin T (cTnT) in mouse and human heart tissues. However, the endogenous behavior of human ACMs is unclear. In the present study, we demonstrate that PrP+ cTnT+ cells are present in the human heart tissue with myocardial infarction (MI). These cells were mainly found in the border of necrotic cardiomyocytes caused by infarcts and also in the hibernating myocardium subjected to the chronic ischemia. The ratio of PrP+ cTnT+ cells to the total cells observed in the normal heart tissue section of mouse and human was estimated to range from 0.3–0.8%. Notably, living human PrP+ cTnT+ cells were identified in the cultures obtained at pathological autopsy despite exposure to lethal ischemic conditions for hours after death. These findings suggest that ACMs could survive in the ischemic human heart and develop into a sub-population of cardiac myocytes. PMID:28120944

  2. On the conscious control of the human heart.

    PubMed

    Pokrovskii, Vladimir M; Polischuk, Lily V

    2012-06-01

    This study describes methods of volitional management of heart rhythms and proves that it is possible by means of management of its operations, subject to arbitrary control, which also has a strong functional connection to the center of the heart rhythm formation in the brain. Experiments demonstrate that it is possible for arbitrary changes in the heart rhythm to be made through conscious control of the breathing rhythm, and even a short-term cardiac arrest by means of contracting abdominal muscles. We postulate that the management of human heart rhythm is indirectly regulated through arbitrary controlled operations. The present article describes and analyzes ways that enable a human to consciously and purposefully manage the frequency of heart contractions. Common principles of arbitrary management of the heart rhythm in humans are uncovered through analysis.

  3. Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

    PubMed

    Stennard, Fiona A; Costa, Mauro W; Lai, Donna; Biben, Christine; Furtado, Milena B; Solloway, Mark J; McCulley, David J; Leimena, Christiana; Preis, Jost I; Dunwoodie, Sally L; Elliott, David E; Prall, Owen W J; Black, Brian L; Fatkin, Diane; Harvey, Richard P

    2005-05-01

    The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

  4. Evolutionary anticipation of the human heart.

    PubMed

    Victor, S; Nayak, V M

    2000-09-01

    We have studied the comparative anatomy of hearts from fish, frog, turtle, snake, crocodile, birds (duck, chicken, quail), mammals (elephant, dolphin, sheep, goat, ox, baboon, wallaby, mouse, rabbit, possum, echidna) and man. The findings were analysed with respect to the mechanism of evolution of the heart.

  5. [Perspectives in the management of congenital heart defects in adult patients].

    PubMed

    Hartyánszky, István; Varga, Sándor; Havasi, Kálmán; Babik, Barna; Katona, Márta; Bogáts, Gábor

    2015-01-18

    Due to improving results in congenital heart surgery, the number of adult patients with congenital heart defect is increasing. The question is: what kind of problems can be managed in this patient-group? The authors review the different problems of management of congenital heart defects in adults based on national and international literature data. Simple defects recognised in adults, postoperative residual problems, changing of small grafts and valves, correction of primary or operated coarctation aortae can be usually managed without problems. A very close follow-up is necessary to establish the correct period for heart transplantation in patients with transposition of great arteries with Senning/Mustard operation, and univentricular heart corrected with "Fontan-circulation" type surgical procedure. The authors conclude that although the number of patients increases, only a few congenital heart diseases may cause problems. It seems important (1) to monitor asymptomatic patient who underwent operation (Fallot-IV, Ross procedure, etc.), (2) follow up regularly patients who underwent Senning/Mustard procedure (magnetic resonance imaging, echocardiography, brain natriuretic peptide measurement), (3) define the proper period of preparation for heart transplantation of patients with a univentricular heart, with special attention to the possibility of multiorgan (lung, liver, etc.) failure. Due to the improvement of foetal diagnosis of congenital heart defects, the number of patients with complex congenital heart defects is decreasing. The standard management of these patients could be primary heart transplantation in infancy.

  6. Matrix metalloproteinases as candidate biomarkers in adults with congenital heart disease.

    PubMed

    Baggen, Vivan J M; Eindhoven, Jannet A; van den Bosch, Annemien E; Witsenburg, Maarten; Cuypers, Judith A A E; Langstraat, Jannette S; Boersma, Eric; Roos-Hesselink, Jolien W

    2016-07-01

    Context Matrix metalloproteinases (MMPs) are associated with diastolic dysfunction and heart failure in acquired heart disease. Objective To investigate the role of MMPs as novel biomarkers in clinically stable adults with congenital heart disease. Methods We measured serum MMP-2, -3, -9 and tissue inhibitor of matrix metalloproteinase-1 in 425 patients and analysed the association with cardiac function and exercise capacity. Results MMP-2 was significantly associated with exercise capacity, ventilatory efficiency and left ventricular deceleration time, independently of age, sex, body surface area and NT-proBNP. Conclusion MMP-2 may provide new information in the clinical evaluation of adults with congenital heart disease.

  7. Modeling heart rate variability in healthy humans: a turbulence analogy.

    PubMed

    Lin, D C; Hughson, R L

    2001-02-19

    Many complex systems share similar statistical characteristics. In this Letter, a turbulence analogy is proposed for the long-term heart rate variability of healthy humans. Based on such an analogy, the equivalence of an inertial range is found and a cascade model, which captures the statistical properties of the heart rate data, is given.

  8. Risks and Benefits of Exercise Training in Adults With Congenital Heart Disease.

    PubMed

    Chaix, Marie-A; Marcotte, François; Dore, Annie; Mongeon, François-Pierre; Mondésert, Blandine; Mercier, Lise-Andrée; Khairy, Paul

    2016-04-01

    Exercise capacity in adults with various forms of congenital heart disease is substantially lower than that of the general population. Although the underlying congenital heart defect, and its sequelae, certainly contribute to observed exercise limitations, there is evidence suggesting that deconditioning and a sedentary lifestyle are important implicated factors. The prevalence of acquired cardiovascular comorbidities is on the increase in the aging population with congenital heart disease, such that obesity and a sedentary lifestyle confer increased risk. Health fears and misconceptions are common barriers to regular physical activity in adults with congenital heart disease, despite evidence linking lower functional capacity to poor outcomes, and data supporting the safety and efficacy of exercise in bestowing numerous physical and psychosocial rewards. With few exceptions, adults with congenital heart disease should be counselled to exercise regularly. In this contemporary review, we provide a practical approach to assessing adults with congenital heart disease before exercise training. We examine available evidence supporting the safety and benefits of exercise training. Risks associated with exercise training in adults with congenital heart disease are discussed, particularly with regard to sudden cardiac death. Finally, recommendations for exercise training are provided, with consideration for the type of congenital heart disease, the nature (ie, static vs dynamic) and intensity (ie, low, medium, high) of the physical activity, and associated factors such as systemic ventricular dysfunction and residual defects. Further research is required to determine optimal exercise regimens and to identify effective strategies to implement exercise training as a key determinant of healthy living.

  9. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Bui, Albert D; Sprague, Lisanne; D'Souza, Manoranjan S

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart.

  10. Placing Advocacy at the Heart of Adult Education

    ERIC Educational Resources Information Center

    Taylor, Jackie

    2016-01-01

    Adult educators know that adults and families change their lives through adult education. Adult education also positively impacts a host of social and economic issues. Yet this fact is largely unknown or misunderstood by the general public. Resources have become increasingly scarce, while at the same time adult educators are asked to do more with…

  11. Phase Transition in a Healthy Human Heart Rate

    NASA Astrophysics Data System (ADS)

    Kiyono, Ken; Struzik, Zbigniew R.; Aoyagi, Naoko; Togo, Fumiharu; Yamamoto, Yoshiharu

    2005-07-01

    A healthy human heart rate displays complex fluctuations which share characteristics of physical systems in a critical state. We demonstrate that the human heart rate in healthy individuals undergoes a dramatic breakdown of criticality characteristics, reminiscent of continuous second order phase transitions. By studying the germane determinants, we show that the hallmark of criticality—highly correlated fluctuations—is observed only during usual daily activity, and a breakdown of these characteristics occurs in prolonged, strenuous exercise and sleep. This finding is the first reported discovery of the dynamical phase transition phenomenon in a biological control system and will be a key to understanding the heart rate control system in health and disease.

  12. Treatment of congenital heart disease: risk-reducing measures in young adults.

    PubMed

    van der Bom, Teun; Luijendijk, Paul; Bouma, Berto J; Koolbergen, Dave R; de Groot, Joris R; Mulder, Barbara J M; Mulder, Barbara B J

    2011-03-01

    Adults with congenital heart disease form a new and relatively young population, since surgical treatment of heart defects became available three to four decades ago. Owing to improved survival this population is steadily growing in number and age. Little is known regarding long-term survival; however, late complications occur frequently. During adulthood, almost half of the patients have one or more complication, such as endocarditis, stroke, systemic or pulmonary hypertension, aortic aneurysm or dissection and arrhythmias. Heart failure and sudden cardiac death are the main causes of death. Treatment of adults with congenital heart disease is aimed at the reduction of symptoms, but also at minimizing the risk and severity of late complications. In this article the most recent advances in the treatment of congenital heart disease will be discussed. The main focus of the article will be on pharmacological, interventional and surgical interventions that reduce the risk of heart failure, arrhythmias, vascular complications, pulmonary hypertension and endocarditis.

  13. Anticoagulation in adults with congenital heart disease: The who, the when and the how?

    PubMed

    Jensen, A S; Idorn, L; Nørager, B; Vejlstrup, N; Sondergaard, L

    2015-03-01

    Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events. It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts. Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable recommendations for which patients are likely to benefit from which anticoagulation treatments, when they should be considered and how these would be carried out.

  14. Heart Rate Change When Standing Up Might Predict Older Adult's Death Risk

    MedlinePlus

    ... Change When Standing Up Might Predict Older Adult's Death Risk People with slower heart rate recovery had ... they stand up might reveal their risk of death over the next several years, a new study ...

  15. Moxifloxacin Increases Heart Rate in Humans

    PubMed Central

    Mason, Jay W.; Moon, Thomas E.

    2017-01-01

    (1) Background: We assessed the effect of moxifloxacin on heart rate, and reviewed the heart rate effects of other antibiotics; (2) Methods: A total of 335 normal volunteers had 12-lead electrocardiograms recorded at multiple time points before and during treatment with moxifloxacin and with placebo in seven consecutive, thorough QT studies of crossover design; (3) Results: The average baseline heart rate across the seven studies was 61.5 bpm. The heart rate after moxifloxacin dosing was analyzed at five time points shared by all seven studies (hours 1, 2, 3, 12 and 24). The maximum mean heart rate (HR) increase for the seven studies combined was 2.4 bpm (95% CI 1.6, 3.3) at hour 2. The range of mean maximum increases among the seven studies was 2.1 to 4.3 bpm. For the seven studies combined, the increase was statistically significant at all but the 24 h time point. The maximum observed individual increase in HR was 36 bpm and the mean maximum increase was 30 ± 4.1 bpm by time point and 8 ± 6.9 bpm by subject. Many antibiotics increase HR, some several-fold more than moxifloxacin. However, clinicians and clinical investigators give little attention to this potential adverse effect in the medical literature; (4) Conclusions: The observed moxifloxacin-induced increase in HR is large enough to be clinically relevant, and it is a potentially important confounder in thorough QT studies using moxifloxacin as an active control. More attention to heart rate effects of antibiotics is warranted. PMID:28165431

  16. Zebrafish heart as a model for human cardiac electrophysiology

    PubMed Central

    Vornanen, Matti; Hassinen, Minna

    2016-01-01

    ABSTRACT The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non-orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart. PMID:26671745

  17. Variability in heart rate recovery measurements over 1 year in healthy, middle-aged adults.

    PubMed

    Mellis, M G; Ingle, L; Carroll, S

    2014-02-01

    This study assessed the longer-term (12-month) variability in post-exercise heart rate recovery following a submaximal exercise test. Longitudinal data was analysed for 97 healthy middle-aged adults (74 male, 23 female) from 2 occasions, 12 months apart. Participants were retrospectively selected if they had stable physical activity habits, submaximal treadmill fitness and anthropometric measurements between the 2 assessment visits. A submaximal Bruce treadmill test was performed to at least 85% age-predicted maximum heart rate. Absolute heart rate and Δ heart rate recovery (change from peak exercise heart rate) were recorded for 1 and 2 min post-exercise in an immediate supine position. Heart rate recovery at both time-points was shown to be reliable with intra-class correlation coefficient values ≥ 0.714. Absolute heart rate 1-min post-exercise showed the strongest agreement between repeat tests (r = 0.867, P < 0.001). Lower coefficient of variation (≤ 10.2%) and narrower limits of agreement were found for actual heart rate values rather than Δ heart rate recovery, and for 1-min rather than 2-min post-exercise recovery time points. Log-transformed values generated better variability with acceptable coefficient of variation for all measures (2.2-10%). Overall, 1 min post-exercise heart rate recovery data had least variability over the 12-month period in apparently healthy middle-aged adults.

  18. Prevalence and correlates of heart disease among adults in Singapore.

    PubMed

    Picco, Louisa; Subramaniam, Mythily; Abdin, Edimansyah; Vaingankar, Janhavi Ajit; Chong, Siow Ann

    2016-02-01

    Heart disease is one of the leading causes of morbidity and mortality worldwide and it has been well established that it is associated with both mental and physical conditions. This paper describes the prevalence of heart disease with mental disorders and other chronic physical conditions among the Singapore resident population. Data were from the Singapore Mental Health Study which was a representative, cross-sectional epidemiological survey undertaken with 6616 Singapore residents, between December 2009 and December 2010. The Composite International Diagnostic Interview Version 3.0 was used to establish the diagnosis of mental disorders, while a chronic medical conditions checklist was used to gather information on 15 physical conditions, including various forms of heart disease. Health-related quality of life was measured using the Euro-Quality of Life Scale (EQ-5D). The lifetime prevalence of heart disease was 2.8%. Socio-demographic correlates of heart disease included older age, Indian ethnicity, secondary education (vs. tertiary) and being economically inactive. After adjusting for socio-demographic variables and other comorbid physical and mental disorders, the prevalence of major depressive disorder and bipolar disorder were significantly higher among those with heart disease, as were diabetes, arthritis, kidney failure and lung disease. These findings highlight important associations between heart disease and various socio-demographic correlates, mental disorders and physical conditions. Given the high prevalence of mood disorders among heart disease patients, timely and appropriate screening and treatment of mental disorders among this group is essential.

  19. Asymmetrical Dimethylarginine - More Sensitive than NT-proBNP to Diagnose Heart Failure in Adults with Congenital Heart Disease

    PubMed Central

    Bode-Böger, Stefanie M.; Martens-Lobenhoffer, Jens; Lovric, Svjetlana; Bauersachs, Johann; Schieffer, Bernhard; Westhoff-Bleck, Mechthild; Kielstein, Jan T.

    2012-01-01

    Background Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its value in ACHD has limitations. Asymmetrical dimethylarginine (ADMA) correlates with disease severity and independently predicts adverse clinical events in heart failure of non-congenital origin. Its role in ACHD has not been investigated. Methods In 102 patients ADMA and NT-proBNP were measured and related to NYHA class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Results In contrast to NT-proBNP ADMA differentiated between NYHA classes I-III. Both, ADMA and NT-proBNP showed a good correlation with parameters of cardiopulmonary exercise testing with comparable receiver-operating characteristic curves for identifying patients with severely limited cardiopulmonary exercise capacity. Conclusion ADMA seems to be a better biomarker than NT-proBNP for the assessment of NYHA class and as a good as NT-proBNP for the estimation of maximum exercise capacity in adults with congenital heart disease. Its use in clinical routine should be evaluated. PMID:22470476

  20. Acellular human heart matrix: A critical step toward whole heart grafts.

    PubMed

    Sánchez, Pedro L; Fernández-Santos, M Eugenia; Costanza, Salvatore; Climent, Andreu M; Moscoso, Isabel; Gonzalez-Nicolas, M Angeles; Sanz-Ruiz, Ricardo; Rodríguez, Hugo; Kren, Stefan M; Garrido, Gregorio; Escalante, Jose L; Bermejo, Javier; Elizaga, Jaime; Menarguez, Javier; Yotti, Raquel; Pérez del Villar, Candelas; Espinosa, M Angeles; Guillem, María S; Willerson, James T; Bernad, Antonio; Matesanz, Rafael; Taylor, Doris A; Fernández-Avilés, Francisco

    2015-08-01

    The best definitive treatment option for end-stage heart failure currently is transplantation, which is limited by donor availability and immunorejection. Generating an autologous bioartificial heart could overcome these limitations. Here, we have decellularized a human heart, preserving its 3-dimensional architecture and vascularity, and recellularized the decellularized extracellular matrix (dECM). We decellularized 39 human hearts with sodium-dodecyl-sulfate for 4-8 days. Cell removal and architectural integrity were determined anatomically, functionally, and histologically. To assess cytocompatibility, we cultured human cardiac-progenitor cells (hCPC), bone-marrow mesenchymal cells (hMSCs), human endothelial cells (HUVECs), and H9c1 and HL-1 cardiomyocytes in vitro on dECM ventricles up to 21 days. Cell survival, gene expression, organization and/or electrical coupling were analyzed and compared to conventional 2-dimensional cultures. Decellularization removed cells but preserved the 3-dimensional cardiac macro and microstructure and the native vascular network in a perfusable state. Cell survival was observed on dECM for 21 days. hCPCs and hMSCs expressed cardiocyte genes but did not adopt cardiocyte morphology or organization; HUVECs formed a lining of endocardium and vasculature; differentiated cardiomyocytes organized into nascent muscle bundles and displayed mature calcium dynamics and electrical coupling in recellularized dECM. In summary, decellularization of human hearts provides a biocompatible scaffold that retains 3-dimensional architecture and vascularity and that can be recellularized with parenchymal and vascular cells. dECM promotes cardiocyte gene expression in stem cells and organizes existing cardiomyocytes into nascent muscle showing electrical coupling. These findings represent a first step toward manufacturing human heart grafts or matrix components for treating cardiovascular disease.

  1. Best Practice BioBanking of Human Heart Tissue.

    PubMed

    Lal, Sean; Li, Amy; Allen, David; Allen, Paul D; Bannon, Paul; Cartmill, Tim; Cooke, Roger; Farnsworth, Alan; Keogh, Anne; Dos Remedios, Cristobal

    2015-12-01

    This review provides a guide to researchers who wish to establish a biobank. It also gives practical advice to investigators seeking access to samples of healthy or diseased human hearts. We begin with a brief history of the Sydney Heart Bank (SHB) from when it began in 1989, including the pivotal role played by the late Victor Chang. We discuss our standard operating procedures for tissue collection which include cryopreservation and the quality assurance needed to maintain the long-term molecular and cellular integrity of the samples. The SHB now contains about 16,000 heart samples derived from over 450 patients who underwent isotopic heart transplant procedures and from over 100 healthy organ donors. These enable us to provide samples from a wide range of categories of heart failure. So far, we have delivered heart samples to more than 50 laboratories over two decades, and we answer their most frequently asked questions. Other SHB services include the development of tissue microarrays (TMA). These enable end users to perform preliminary examinations of the expression and localisation of target molecules in diseased or aging donor hearts, all in a single section of the TMA. Finally, the processes involved in managing tissue requests from external users and logistics considerations for the shipment of human tissue are discussed in detail.

  2. Best Practice BioBanking of Human Heart Tissue

    PubMed Central

    Lal, Sean; Li, Amy; Allen, David; Allen, Paul D; Bannon, Paul; Cartmill, Tim; Cooke, Roger; Farnsworth, Alan; Keogh, Anne; dos Remedios, Cristobal

    2015-01-01

    This review provides a guide to researchers who wish to establish a biobank. It also gives practical advice to investigators seeking access to samples of healthy or diseased human hearts. We begin with a brief history of the Sydney Heart Bank (SHB) from when it began in 1989, including the pivotal role played by the late Victor Chang. We discuss our standard operating procedures for tissue collection which include cryopreservation and the quality assurance needed to maintain the long-term molecular and cellular integrity of the samples. The SHB now contains about 16,000 heart samples derived from over 450 patients who underwent isotopic heart transplant procedures and from over 100 healthy organ donors. These enable us to provide samples from a wide range of categories of heart failure. So far, we have delivered heart samples to more than 50 laboratories over two decades, and we answer their most frequently asked questions. Other SHB services include the development of tissue microarrays (TMA). These enable end users to perform preliminary examinations of the expression and localisation of target molecules in diseased or aging donor hearts, all in a single section of the TMA. Finally, the processes involved in managing tissue requests from external users and logistics considerations for the shipment of human tissue are discussed in detail. PMID:26998172

  3. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed

    Liao, Song-Yan; Tse, Hung-Fat

    2013-12-24

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed.

  4. Key issues of daily life in adults with congenital heart disease.

    PubMed

    Ladouceur, Magalie; Iserin, Laurence; Cohen, Sarah; Legendre, Antoine; Boudjemline, Younes; Bonnet, Damien

    2013-01-01

    Increasing survival rates of patients with congenital heart disease have resulted in a new and growing patient population of adults with operated congenital heart disease. Medical professionals face the specific medical needs of these patients but must also deal with their daily life issues. Adult patients with congenital heart disease report difficulties in several areas of daily life, such as sport, employment, insurability and travel or driving. Moreover, they must have a healthy lifestyle to prevent cardiovascular complications. All these issues can be addressed in a specific educational program. In this review, we discuss the different daily life issues of adults with congenital heart disease and the preventive measures that can be proposed to improve their quality of life.

  5. Overweight Status, Obesity, and Risk Factors for Coronary Heart Disease in Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Henderson, C. Michael; Robinson, Laura M.; Davidson, Philip W.; Haveman, Meindert; Janicki, Matthew P.; Albertini, Giorgio

    2008-01-01

    Research indicates that adults with intellectual disabilities (ID) have high rates of overweight status/obesity (OSO). OSO is associated with several important risk factors for coronary heart disease (CHD). This study focused on assessing whether such risk factors are being identified in adults with ID who are receiving their healthcare in…

  6. How Live Performance Moves the Human Heart

    PubMed Central

    Shoda, Haruka; Adachi, Mayumi; Umeda, Tomohiro

    2016-01-01

    We investigated how the audience member’s physiological reactions differ as a function of listening context (i.e., live versus recorded music contexts). Thirty-seven audience members were assigned to one of seven pianists’ performances and listened to his/her live performances of six pieces (fast and slow pieces by Bach, Schumann, and Debussy). Approximately 10 weeks after the live performance, each of the audience members returned to the same room and listened to the recorded performances of the same pianists’ via speakers. We recorded the audience members’ electrocardiograms in listening to the performances in both conditions, and analyzed their heart rates and the spectral features of the heart-rate variability (i.e., HF/TF, LF/HF). Results showed that the audience’s heart rate was higher for the faster than the slower piece only in the live condition. As compared with the recorded condition, the audience’s sympathovagal balance (LF/HF) was less while their vagal nervous system (HF/TF) was activated more in the live condition, which appears to suggest that sharing the ongoing musical moments with the pianist reduces the audience’s physiological stress. The results are discussed in terms of the audience’s superior attention and temporal entrainment to live performance. PMID:27104377

  7. How Live Performance Moves the Human Heart.

    PubMed

    Shoda, Haruka; Adachi, Mayumi; Umeda, Tomohiro

    2016-01-01

    We investigated how the audience member's physiological reactions differ as a function of listening context (i.e., live versus recorded music contexts). Thirty-seven audience members were assigned to one of seven pianists' performances and listened to his/her live performances of six pieces (fast and slow pieces by Bach, Schumann, and Debussy). Approximately 10 weeks after the live performance, each of the audience members returned to the same room and listened to the recorded performances of the same pianists' via speakers. We recorded the audience members' electrocardiograms in listening to the performances in both conditions, and analyzed their heart rates and the spectral features of the heart-rate variability (i.e., HF/TF, LF/HF). Results showed that the audience's heart rate was higher for the faster than the slower piece only in the live condition. As compared with the recorded condition, the audience's sympathovagal balance (LF/HF) was less while their vagal nervous system (HF/TF) was activated more in the live condition, which appears to suggest that sharing the ongoing musical moments with the pianist reduces the audience's physiological stress. The results are discussed in terms of the audience's superior attention and temporal entrainment to live performance.

  8. Significance of Anti-HLA Antibodies on Adult and Pediatric Heart Allograft Outcomes

    PubMed Central

    Mangiola, Massimo; Marrari, Marilyn; Feingold, Brian; Zeevi, Adriana

    2017-01-01

    As methods for human leukocyte antigens (HLA) antibody detection have evolved and newer solid phase assays are much more sensitive, the last 15 years has seen a renewed focus on the importance of HLA antibodies in solid organ transplant rejection. However, there is still much controversy regarding the clinical significance of antibody level as depicted by the mean fluorescence intensity of a patient’s neat serum. Emerging techniques, including those that identify antibody level and function, show promise for the detection of individuals at risk of allograft rejection, determination of the effectiveness of desensitization prior to transplant, and for monitoring treatment of rejection. Here, we review current publications regarding the relevance of donor-specific HLA antibodies (DSA) in adult and pediatric heart transplantation (HT) with graft survival, development of antibody-mediated rejection and cardiac allograft vasculopathy (CAV). The negative impact of DSA on patient and allograft survival is evident in adult and pediatric HT recipients. Many questions remain regarding the most appropriate frequency of assessment of pre- and posttransplant DSA as well as the phenotype of DSA memory vs. true de novo antibody using large multicenter adult and pediatric cohorts and state-of-the-art methodologies for DSA detection and characterization. PMID:28191005

  9. The epidemiology of heart failure in adults with congenital heart disease.

    PubMed

    Rodriguez, Fred H; Marelli, Ariane J

    2014-01-01

    The impact of lifelong exposure to myocardial dysfunction in populations with congenital heart disease (CHD) is becoming increasingly recognized. Most children born with CHD now reach adulthood and the long-term sequelae of treatment are contributing to substantial comorbidity. The combination of structural changes present at birth with changes resulting from cardiac surgery can result in heart failure. This article reports on the current state of knowledge on the epidemiology of heart failure in this patient population.

  10. The Living Heart Project: A robust and integrative simulator for human heart function.

    PubMed

    Baillargeon, Brian; Rebelo, Nuno; Fox, David D; Taylor, Robert L; Kuhl, Ellen

    2014-11-01

    The heart is not only our most vital, but also our most complex organ: Precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. While numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. Here we present a proof-of-concept simulator for a four-chamber human heart model created from computer topography and magnetic resonance images. We illustrate the governing equations of excitation-contraction coupling and discretize them using a single, unified finite element environment. To illustrate the basic features of our model, we visualize the electrical potential and the mechanical deformation across the human heart throughout its cardiac cycle. To compare our simulation against common metrics of cardiac function, we extract the pressure-volume relationship and show that it agrees well with clinical observations. Our prototype model allows us to explore and understand the key features, physics, and technologies to create an integrative, predictive model of the living human heart. Ultimately, our simulator will open opportunities to probe landscapes of clinical parameters, and guide device design and treatment planning in cardiac diseases such as stenosis, regurgitation, or prolapse of the aortic, pulmonary, tricuspid, or mitral valve.

  11. The Living Heart Project: A robust and integrative simulator for human heart function

    PubMed Central

    Baillargeon, Brian; Rebelo, Nuno; Fox, David D.; Taylor, Robert L.; Kuhl, Ellen

    2014-01-01

    The heart is not only our most vital, but also our most complex organ: Precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. While numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. Here we present a proof-of-concept simulator for a four-chamber human heart model created from computer topography and magnetic resonance images. We illustrate the governing equations of excitation-contraction coupling and discretize them using a single, unified finite element environment. To illustrate the basic features of our model, we visualize the electrical potential and the mechanical deformation across the human heart throughout its cardiac cycle. To compare our simulation against common metrics of cardiac function, we extract the pressure-volume relationship and show that it agrees well with clinical observations. Our prototype model allows us to explore and understand the key features, physics, and technologies to create an integrative, predictive model of the living human heart. Ultimately, our simulator will open opportunities to probe landscapes of clinical parameters, and guide device design and treatment planning in cardiac diseases such as stenosis, regurgitation, or prolapse of the aortic, pulmonary, tricuspid, or mitral valve. PMID:25267880

  12. Genomics, proteomics and bioinformatics of human heart failure

    PubMed Central

    DOS REMEDIOS, C.G.; LIEW, C.C.; ALLEN, P.D.; WINSLOW, R.L.; VAN EYK, J.E.; DUNN, M.J.

    2005-01-01

    Unraveling the molecular complexities of human heart failure, particularly end-stage failure, can be achieved by combining multiple investigative approaches. There are several parts to the problem. Each patient is the product of a complex set of genetic variations, different degrees of influence of diets and lifestyles, and usually heart transplantation patients are treated with multiple drugs. The genomic status of the myocardium of any one transplant patient can be analysed using gene arrays (cDNA- or oligonucleotide-based) each with its own strengths and weaknesses. The proteins expressed by these failing hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2DGE) which promised to resolve several thousand proteins in a single sample of failing heart. However, while 2DGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. Highly focused first dimension separations combined with recent advances in mass spectrometry now provide new hope for solving this difficulty. Protein arrays are a more recent form of proteomics that hold great promise but, like the above methods, they have their own drawbacks. Our approach to solving the problems inherent in the genomics and proteomics of heart failure is to provide experts in each analytical method with a sample from the same human failing heart. This requires a sufficiently large number of samples from a sufficiently large pool of heart transplant patients as well as a large pool of non-diseased, non-failing human hearts. We have collected more than 200 hearts from patients undergoing heart transplantations and a further 50 non-failing hearts. By combining our expertise we expect to reduce and possibly eliminate the inherent difficulties of each analytical approach. Finally, we recognise the need for bioinformatics to make sense of the large quantities of data that will

  13. Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells.

    PubMed

    Oh, Hidemasa; Chi, Xuan; Bradfute, Steven B; Mishina, Yuji; Pocius, Jennifer; Michael, Lloyd H; Behringer, Richard R; Schwartz, Robert J; Entman, Mark L; Schneider, Michael D

    2004-05-01

    The evidence of cardiomyocyte proliferation in damaged heart implied cardiac regeneration might occur by resident or extra cardiac stem cells. However, the specification and origin of these cells remain unknown. Here, we report using fluorescence-activated cell sorting that cardiac progenitor cells resided in adult heart and colocalized with small capillary vessels, within the stem cell antigen (Sca-1) population expressing high telomerase activity. Notably, hematopoietic stem cells capable of efflux Hoechst 33342, termed side population cells, also were identified within the heart-derived cells. The cardiac progenitor cells (CD45(-)/CD34(-)) express neither cardiac muscle nor endothelial cell markers at an undifferentiated stage. The exposure of 5-azacytidine induced cardiac differentiation, which depends, in part, on Bmpr1a, a type IA receptor for bone morphogenetic protein (BMP). The capability of adult Sca1(+) cells to adopt a cardiac muscle in embryogenesis was substantiated by blastocyst injection, using progenitors from the adult hearts of transgenic mice that harbor a bacterial artificial chromosome expressing GFP via the Nkx-2.5 locus. Intravenously injected progenitors, shortly after ischemic/reperfusion, homed and functionally differentiated 3.5% of total left ventricle in the host myocardium. Differentiation included both fusion-independent and fusion-associated components, proved by the Cre/loxP donor/recipient system. Our studies suggest that endogenous cardiac progenitors reside in the adult heart, regenerate cardiomyocytes functionally, and integrate into the existing heart circuitry.

  14. Problems in the organization of care for patients with adult congenital heart disease.

    PubMed

    Meijboom, Folkert; Mulder, Barbara

    2010-01-01

    The prevalence of congenital heart disease among adults in Europe, or in any country in Europe, is not known. This is due to a lack of agreement on the incidence of congenital heart disease, with estimations varying from four per 1000 births to 50 per 1000 births, and it is not known how many patients with congenital heart disease have died. Based on several studies that estimated and calculated the number of adult patients with congenital heart disease, the number of patients should be much higher than the number of patients that are actually seen in specialized centres throughout Europe. This implies that either a large proportion of adult patients with congenital heart disease do not receive appropriate medical care, or that the calculations and estimations are grossly wrong. A combination of the two is also possible. A substantial expansion of the number and size of specialized centres for adult congenital heart disease is advocated, but since setting up (and running) a service for this disease is a costly affair, and because uncertainty remains about the actual number of patients needing specialized care, this has been difficult to realize in most European countries in the past few years.

  15. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    SciTech Connect

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  16. Metabolic gene profile in early human fetal heart development.

    PubMed

    Iruretagoyena, J I; Davis, W; Bird, C; Olsen, J; Radue, R; Teo Broman, A; Kendziorski, C; Splinter BonDurant, S; Golos, T; Bird, I; Shah, D

    2014-07-01

    The primitive cardiac tube starts beating 6-8 weeks post fertilization in the developing embryo. In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database. Fourteen fetal hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were prospectively collected at the time of elective termination of pregnancy. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cutoff to determine differential gene expression for individual genes. Test for enrichment to identify functional groups was carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. Single transcript and Ontology analysis showed first trimester heart expression of myosin-related genes to be up-regulated >5-fold compared with second trimester heart. In contrast the second trimester hearts showed further gestation-related increases in many genes involved in energy production and cardiac remodeling. In conclusion, fetal heart development during the first trimester was dominated by heart-specific genes coding for myocardial development and differentiation. During the second trimester, transcripts related to energy generation and cardiomyocyte communication for contractile coordination/proliferation were more dominant. Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and clearly increase as the heart matures. Retinol

  17. Reorganized PKA-AKAP associations in the failing human heart.

    PubMed

    Aye, Thin-Thin; Soni, Siddarth; van Veen, Toon A B; van der Heyden, Marcel A G; Cappadona, Salvatore; Varro, Andras; de Weger, Roel A; de Jonge, Nicolaas; Vos, Marc A; Heck, Albert J R; Scholten, Arjen

    2012-02-01

    Here we reveal that the characterization of large-scale re-arrangements of signaling scaffolds induced by heart failure can serve as a novel concept to identify more specific therapeutic targets. In the mammalian heart, the cAMP pathway, with the cAMP-dependent protein kinase (PKA) in a central role, acts directly downstream of adrenergic receptors to mediate cardiac contractility and rhythm. Heart failure, characterized by severe alterations in adrenergic stimulation is, amongst other interventions, often treated with β-blockers. Contrasting results, however, have shown both beneficial and detrimental effects of decreased cAMP levels in failing hearts. We hypothesize that the origin of this behavior lies in the complex spatiotemporal organization of the regulatory subunit of PKA (PKA-R), which associates tightly with various A-kinase anchoring proteins (AKAPs) to specifically localize PKA's activity. Using chemical proteomics directly applied to human patient and control heart tissue we demonstrate that the association profile of PKA-R with several AKAPs is severely altered in the failing heart, for instance effecting the interaction between PKA and the novel AKAP SPHKAP was 6-fold upregulated upon failing heart conditions. Also a significant increase in captured cGMP-dependent protein kinase (PKG) and phosphodiesterase 2 (PDE2) was observed. The observed altered profiles can already explain many aspects of the aberrant cAMP-response in the failing human heart, validating that this dataset may provide a resource for several novel, more specific, treatment options. This article is part of a Special Issue entitled "Local Signaling in Myocytes".

  18. FISH CONSUMPTION, METHYLMERCURY, AND HUMAN HEART DISEASE.

    SciTech Connect

    LIPFERT, F.W.; SULLIVAN, T.M.

    2005-09-21

    Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased mortality risks in the highest fish-consuming group ({approx}3 times

  19. Notch-independent RBPJ controls angiogenesis in the adult heart

    PubMed Central

    Díaz-Trelles, Ramón; Scimia, Maria Cecilia; Bushway, Paul; Tran, Danh; Monosov, Anna; Monosov, Edward; Peterson, Kirk; Rentschler, Stacey; Cabrales, Pedro; Ruiz-Lozano, Pilar; Mercola, Mark

    2016-01-01

    Increasing angiogenesis has long been considered a therapeutic target for improving heart function after injury such as acute myocardial infarction. However, gene, protein and cell therapies to increase microvascularization have not been successful, most likely because the studies failed to achieve regulated and concerted expression of pro-angiogenic and angiostatic factors needed to produce functional microvasculature. Here, we report that the transcription factor RBPJ is a homoeostatic repressor of multiple pro-angiogenic and angiostatic factor genes in cardiomyocytes. RBPJ controls angiogenic factor gene expression independently of Notch by antagonizing the activity of hypoxia-inducible factors (HIFs). In contrast to previous strategies, the cardiomyocyte-specific deletion of Rbpj increased microvascularization of the heart without adversely affecting cardiac structure or function even into old age. Furthermore, the loss of RBPJ in cardiomyocytes increased hypoxia tolerance, improved heart function and decreased pathological remodelling after myocardial infarction, suggesting that inhibiting RBPJ might be therapeutic for ischaemic injury. PMID:27357444

  20. Theory of mind deficit in adult patients with congenital heart disease.

    PubMed

    Chiavarino, Claudia; Bianchino, Claudia; Brach-Prever, Silvia; Riggi, Chiara; Palumbo, Luigi; Bara, Bruno G; Bosco, Francesca M

    2015-10-01

    This article provides the first assessment of theory of mind, that is, the ability to reason about mental states, in adult patients with congenital heart disease. Patients with congenital heart disease and matched healthy controls were administered classical theory of mind tasks and a semi-structured interview which provides a multidimensional evaluation of theory of mind (Theory of Mind Assessment Scale). The patients with congenital heart disease performed worse than the controls on the Theory of Mind Assessment Scale, whereas they did as well as the control group on the classical theory-of-mind tasks. These findings provide the first evidence that adults with congenital heart disease may display specific impairments in theory of mind.

  1. Programming and reprogramming a human heart cell

    PubMed Central

    Sahara, Makoto; Santoro, Federica; Chien, Kenneth R

    2015-01-01

    The latest discoveries and advanced knowledge in the fields of stem cell biology and developmental cardiology hold great promise for cardiac regenerative medicine, enabling researchers to design novel therapeutic tools and approaches to regenerate cardiac muscle for diseased hearts. However, progress in this arena has been hampered by a lack of reproducible and convincing evidence, which at best has yielded modest outcomes and is still far from clinical practice. To address current controversies and move cardiac regenerative therapeutics forward, it is crucial to gain a deeper understanding of the key cellular and molecular programs involved in human cardiogenesis and cardiac regeneration. In this review, we consider the fundamental principles that govern the “programming” and “reprogramming” of a human heart cell and discuss updated therapeutic strategies to regenerate a damaged heart. PMID:25712211

  2. Advances in MR imaging assessment of adults with congenital heart disease.

    PubMed

    Kathiria, Nazima N; Higgins, Charles B; Ordovas, Karen G

    2015-02-01

    Many novel cardiac MR sequences can be used for assessment of adult patients with congenital heart disease. Although most of these techniques are still primarily used in the research arena, there are many potential applications in clinical practice. Advanced cardiac MR assessment of myocardial tissue characterization, flow hemodynamics, and myocardial strain are promising tools for diagnostic and prognostic assessment late after repair of congenital heart diseases.

  3. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    SciTech Connect

    Weinberger, Florian Mehrkens, Dennis Starbatty, Jutta Nicol, Philipp Eschenhagen, Thomas

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  4. Influence of heart failure on nucleolar organization and protein expression in human hearts

    SciTech Connect

    Rosello-Lleti, Esther; Rivera, Miguel; Cortes, Raquel; Azorin, Inmaculada; Sirera, Rafael; Martinez-Dolz, Luis; Hove, Leif; Cinca, Juan; Lago, Francisca; Gonzalez-Juanatey, Jose R.; Salvador, Antonio; Portoles, Manuel

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Heart failure alters nucleolar morphology and organization. Black-Right-Pointing-Pointer Nucleolin expression is significant increased in ischemic and dilated cardiomyopathy. Black-Right-Pointing-Pointer Ventricular function of heart failure patients was related with nucleolin levels. -- Abstract: We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n = 38) and DCM (n = 27) patients, undergoing heart transplantation and control donors (n = 6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p < 0.05) and DCM (141%, p < 0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p < 0.05) and DCM (1.70-fold, p < 0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p < 0.0001), and it was increased in pathological hearts (p < 0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p < 0.05 and 131%, p < 0.001) and DCM (56%, p < 0.01 and 69%, p < 0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p < 0.001), perinucleolar chromatin (p < 0.01) and dense fibrillar components (p < 0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p < 0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.

  5. Hear the beat: decellularized mouse heart regenerated with human induced pluripotent stem cells.

    PubMed

    Lin, Bo; Lu, Tung-Ying; Yang, Lei

    2014-02-01

    Heart tissue engineering holds a great potential for human heart disease therapy. Regeneration of whole biofunctional human heart is the ultimate goal of tissue engineering. Recent advances take the first step towards whole heart regeneration. However, a substantial amount of challenges have to be overcome.

  6. Immunohistochemical distribution of desmin in the human fetal heart.

    PubMed

    Yamamoto, Masahito; Abe, Shin-ichi; Rodríguez-Vázquez, José Francisco; Fujimiya, Mineko; Murakami, Gen; Ide, Yoshinobu

    2011-08-01

    Desmin is a member of the intermediate filaments, which play crucial roles in the maturation, maintenance and recovery of muscle fibers. Its expression has been examined in human cardiac muscle, rat and chicken, but its spatial distribution in the human fetal heart has not been described. The present study investigated desmin expression in the human fetal heart and associated great vessels in 14 mid-term fetuses from 9 to 18 weeks of gestation. Immunoreactivity for myosin heavy chain (MHC) and alpha smooth muscle actin (α-SMA), as well as neuron-specific enolase (NSE), was also examined. Increased expression of desmin from 9 to 18 weeks was clearly localized in the atrial wall, the proximal portions of the pulmonary vein and vena cava, and around the atrioventricular node. Desmin-positive structures were also positive for MHC. Meanwhile, the great vessels were also positive for α-SMA. The distribution of desmin exhibited a pattern quite different from that described in previous studies of rat and chicken. Thus, desmin in the human fetal heart does not seem to play a general role in myocardial differentiation but rather a specific role closely related to the maturation of the α-isozyme of MHC. Desmin expression in the developing fetal heart also appeared to be induced by mechanical stress due to the involvement of venous walls against the atrium.

  7. Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure

    PubMed Central

    Gupte, Anisha A.; Hamilton, Dale J.; Cordero-Reyes, Andrea M.; Youker, Keith A.; Yin, Zheng; Estep, Jerry D.; Stevens, Robert D.; Wenner, Brett; Ilkayeva, Olga; Loebe, Matthias; Peterson, Leif E.; Lyon, Christopher J.; Wong, Stephen T.C.; Newgard, Christopher B.; Torre-Amione, Guillermo; Taegtmeyer, Heinrich; Hsueh, Willa A.

    2015-01-01

    Background Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood. Methods and Results We compared metabolomic, gene transcript, and protein data from six paired failing human left ventricular (LV) tissue samples obtained during left ventricular assist device (LVAD) insertion (heart failure (HF) samples) and at heart transplant (post-LVAD samples). Non-failing left ventricular (NFLV) wall samples procured from explanted hearts of patients with right HF served as novel comparison samples. Metabolomic analyses uncovered a distinct pattern in HF tissue: 2.6 fold increased pyruvate concentrations coupled with reduced Krebs cycle intermediates and short-chain acylcarnitines, suggesting a global reduction in substrate oxidation. These findings were associated with decreased transcript levels for enzymes that catalyze fatty acid oxidation and pyruvate metabolism and for key transcriptional regulators of mitochondrial metabolism and biogenesis, peroxisome proliferator-activated receptor gamma co-activator1α (PGC1A, 1.3 fold) and estrogen-related receptor α (ERRA, 1.2 fold) and γ (ERRG, 2.2 fold). Thus, parallel decreases in key transcription factors and their target metabolic enzyme genes can explain the decreases in associated metabolic intermediates. Mechanical support with LVAD improved all of these metabolic and transcriptional defects. Conclusions These observations underscore an important pathophysiologic role for severely defective metabolism in HF, while the reversibility of these defects by LVAD suggests metabolic resilience of the human heart. PMID:24825877

  8. The human heart: application of the golden ratio and angle.

    PubMed

    Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per

    2011-08-04

    The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality.

  9. Re-employment of developmental transcription factors in adult heart disease

    PubMed Central

    Oka, Toru; Xu, Jian; Molkentin, Jeffery D.

    2007-01-01

    A finite number of transcription factors constitute a combinatorial code that orchestrates cardiac development and the specification and differentiation of myocytes. Many, if not all of these same transcription factors are re-employed in the adult heart in response to disease stimuli that promote hypertrophic enlargement and/or dilated cardiomyopathy, as part of the so called “fetal gene program”. This review will discuss the transcription factors that regulate the hypertrophic growth response of the adult heart, with a special emphasis on those regulators that participate in cardiac development. PMID:17161634

  10. Comparative gene expression profiling in human-induced pluripotent stem cell--derived cardiocytes and human and cynomolgus heart tissue.

    PubMed

    Puppala, Dinesh; Collis, Leon P; Sun, Sunny Z; Bonato, Vinicius; Chen, Xian; Anson, Blake; Pletcher, Mathew; Fermini, Bernard; Engle, Sandra J

    2013-01-01

    Cardiotoxicity is one of the leading causes of drug attrition. Current in vitro models insufficiently predict cardiotoxicity, and there is a need for alternative physiologically relevant models. Here we describe the gene expression profile of human-induced pluripotent stem cell-derived cardiocytes (iCC) postthaw over a period of 42 days in culture and compare this profile to human fetal and adult as well as adult cynomolgus nonhuman primate (NHP, Macaca fascicularis) heart tissue. Our results indicate that iCC express relevant cardiac markers such as ion channels (SCN5A, KCNJ2, CACNA1C, KCNQ1, and KCNH2), tissue-specific structural markers (MYH6, MYLPF, MYBPC3, DES, TNNT2, and TNNI3), and transcription factors (NKX2.5, GATA4, and GATA6) and lack the expression of stem cell markers (FOXD3, GBX2, NANOG, POU5F1, SOX2, and ZFP42). Furthermore, we performed a functional evaluation of contractility of the iCC and showed functional and pharmacological correlations with myocytes isolated from adult NHP hearts. These results suggest that stem cell-derived cardiocytes may represent a novel in vitro model to study human cardiac toxicity with potential ex vivo and in vivo translation.

  11. Heart research advances using database search engines, Human Protein Atlas and the Sydney Heart Bank.

    PubMed

    Li, Amy; Estigoy, Colleen; Raftery, Mark; Cameron, Darryl; Odeberg, Jacob; Pontén, Fredrik; Lal, Sean; Dos Remedios, Cristobal G

    2013-10-01

    This Methodological Review is intended as a guide for research students who may have just discovered a human "novel" cardiac protein, but it may also help hard-pressed reviewers of journal submissions on a "novel" protein reported in an animal model of human heart failure. Whether you are an expert or not, you may know little or nothing about this particular protein of interest. In this review we provide a strategic guide on how to proceed. We ask: How do you discover what has been published (even in an abstract or research report) about this protein? Everyone knows how to undertake literature searches using PubMed and Medline but these are usually encyclopaedic, often producing long lists of papers, most of which are either irrelevant or only vaguely relevant to your query. Relatively few will be aware of more advanced search engines such as Google Scholar and even fewer will know about Quertle. Next, we provide a strategy for discovering if your "novel" protein is expressed in the normal, healthy human heart, and if it is, we show you how to investigate its subcellular location. This can usually be achieved by visiting the website "Human Protein Atlas" without doing a single experiment. Finally, we provide a pathway to discovering if your protein of interest changes its expression level with heart failure/disease or with ageing.

  12. The Effects of Various Comfort Food on Heart Coherence in Adults

    PubMed Central

    Joseph, Madeline Matar; McIntosh, Mark S.; Joseph, Christine Marie

    2014-01-01

    Background: Some of the nutrients in food are precursors to neurotransmitters, accounting for its effects on mood. Heart coherence (HC), which relates to the optimal psycho-physiological conditions for human body functions, is affected by a person's emotional status. Objectives: (1) To determine the effects of various comfort food on HC and heart rate (HR) in adult females 20 to 50 years of age and (2) to evaluate if body mass index (BMI) has an effect on HC and HR when eating various comfort foods. Methods: The researcher obtained consent from participants after explaining the project. The subjects' height and weight were measured using standardized methods to calculate their BMI. Participants sat in a comfortable chair in a quiet area with a clipped earpiece to measure their heart rate variability (HRV), HR, and HC. Each participant was asked about their favorite comfort food (sweet vs salty). First, the participant imagined eating her favorite comfort food (IFCF) and then was asked to imagine her non-favorite comfort food (INFCF). Finally, the participant ate her favorite comfort food (EFCF) and then ate her non-favorite comfort food (ENFCF). HC scores were recorded in three categories (low, medium, and high) in these four settings. Results: A total of 20 participants completed the study. Paired student's t-tests were used to assess whether the means of the compared groups were statistically different. The data demonstrated that there was a higher HC when participants ate their favorite comfort food than when they ate the non-favorite comfort food (t=−2.912, P<.01) and a higher HC when eating a favorite comfort food than when imaging eating a favorite comfort food (t=−.2408, P<.01). The participants' BMI had a positive correlation between the BMI and low HC (when one increases, the other increases as well) when imagining eating a favorite comfort food (r =.475, P<.05). There was a negative correlation between BMI and medium HC (when one increases, the other

  13. Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology.

    PubMed

    Sommer, Paula

    2013-06-01

    The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury. Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue. This review is a summary of the recent research into all these avenues, discussing the reasons for the limited successes of clinical trials using stem cells after cardiac injury and explaining new advances in basic science. It concludes with a reiteration that chances of successful regeneration would be improved by understanding and implementing the basics of heart development and stem cell biology.

  14. A new look at the comparative physiology of insect and human hearts.

    PubMed

    Sláma, Karel

    2012-08-01

    Recent electrocardiographic (ECG) studies of insect hearts revealed the presence of human-like, involuntary and purely myogenic hearts. Certain insects, like a small light-weight species of hoverfly (Episyrphus balteatus), have evolved a very efficient cardiac system comprised of a compact heart ventricle and a narrow tube of aorta, which evolved as an adaptation to sustained hovering flights. Application of thermocardiographic and optocardiographic ECG methods revealed that adult flies of this species use the compact muscular heart chamber (heart ventricle) for intensive pumping of insect "blood" (haemolymph) into the head and thorax which is ringed all over with indirect flight musculature. The recordings of these hearts revealed extremely high, record rates of forward-directed, anterograde heartbeat (up to 10Hz), associated with extremely enhanced synchronic (not peristaltic) propagation of systolic myocardial contractions (32.2mm/s at room temperature). The relatively slow, backward-directed or retrograde cardiac contractions occurred only sporadically in the form of individual or twinned pulses replacing occasionally the resting periods. The compact heart ventricle contained bi-directional lateral apertures, whose opening and closure diverted the intracardiac anterograde "blood" streams between the abdominal haemocoelic cavity and the aortan artery, respectively. The visceral organs of this flying machine (crop, midgut) exhibited myogenic, extracardiac peristaltic pulsations similar to heartbeat, including the periodically reversed forward and backward direction of the peristaltic waves. The tubular crop contracted with a periodicity of 1Hz, both forwards and backwards, with propagation of the peristaltic waves at 4.4mm/s. The air-inflated and blindly ended midgut contracted at 0.2Hz, with a 0.9mm/s propagation of the peristaltic contraction waves. The neurogenic system of extracardiac haemocoelic pulsations, widely engaged in the regulation of circulatory and

  15. Dynamics of Cell Generation and Turnover in the Human Heart.

    PubMed

    Bergmann, Olaf; Zdunek, Sofia; Felker, Anastasia; Salehpour, Mehran; Alkass, Kanar; Bernard, Samuel; Sjostrom, Staffan L; Szewczykowska, Mirosława; Jackowska, Teresa; Dos Remedios, Cris; Malm, Torsten; Andrä, Michaela; Jashari, Ramadan; Nyengaard, Jens R; Possnert, Göran; Jovinge, Stefan; Druid, Henrik; Frisén, Jonas

    2015-06-18

    The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart.

  16. Distinct effects of inflammation on preconditioning and regeneration of the adult zebrafish heart

    PubMed Central

    de Preux Charles, Anne-Sophie; Bise, Thomas; Baier, Felix; Marro, Jan; Jaźwińska, Anna

    2016-01-01

    The adult heart is able to activate cardioprotective programmes and modifies its architecture in response to physiological or pathological changes. While mammalian cardiac remodelling often involves hypertrophic expansion, the adult zebrafish heart exploits hyperplastic growth. This capacity depends on the responsiveness of zebrafish cardiomyocytes to mitogenic signals throughout their entire life. Here, we have examined the role of inflammation on the stimulation of cell cycle activity in the context of heart preconditioning and regeneration. We used thoracotomy as a cardiac preconditioning model and cryoinjury as a model of cardiac infarction in the adult zebrafish. First, we performed a spatio-temporal characterization of leucocytes and cycling cardiac cells after thoracotomy. This analysis revealed a concomitance between the infiltration of inflammatory cells and the stimulation of the mitotic activity. However, decreasing the immune response using clodronate liposome injection, PLX3397 treatment or anti-inflammatory drugs surprisingly had no effect on the re-entry of cardiac cells into the cell cycle. In contrast, reducing inflammation using the same strategies after cryoinjury strongly impaired cardiac cell mitotic activity and the regenerative process. Taken together, our results show that, while the immune response is not necessary to induce cell-cycle activity in intact preconditioned hearts, inflammation is required for the regeneration of injured hearts in zebrafish. PMID:27440424

  17. Early life permethrin insecticide treatment leads to heart damage in adult rats.

    PubMed

    Vadhana, M S Dhivya; Carloni, Manuel; Nasuti, Cinzia; Fedeli, Donatella; Gabbianelli, Rosita

    2011-09-01

    Early life environmental exposure to xenobiotics could represent a critical period for the onset of permanent alterations in the structure and function of different organs. Cardiovascular diseases can be related to various factors including environmental toxicants. The aim of the present study was to evaluate the effect of early life permethrin treatment (1/50 LD(50), from 6th to 21st day of life) on heart of adult rats. Increased DNA damage, decreased heart cell membrane fluidity, increased cholesterol content, protein and lipid oxidation were measured in heart cells from adult rats treated with permethrin during the neonatal period with respect to control rats. Moreover, the same group showed higher levels of cholesterol, IL-1β, IL-2, IFN-γ, rat-Rantes and IL-10 cytokines and decreased albumin content in plasma. Lower cholesterol levels and perturbation in the phospholipid lateral diffusion together with decreased GSH levels and increased GPx activity were measured in heart mitochondria of the treated group. Our findings support the evidence that the neonatal period has a critical role in the development of heart disease in adulthood. We hypothesize that the alterations observed in adult rats could depend on epigenetic changes that occurred during this period which influence gene expression throughout the rat's life, leading to alterations of certain parameters related to cardiac function.

  18. Functional and pharmacological characteristics of permeability transition in isolated human heart mitochondria.

    PubMed

    Morota, Saori; Manolopoulos, Theodor; Eyjolfsson, Atli; Kimblad, Per-Ola; Wierup, Per; Metzsch, Carsten; Blomquist, Sten; Hansson, Magnus J

    2013-01-01

    The objective of the present study was to validate the presence and explore the characteristics of mitochondrial permeability transition (mPT) in isolated mitochondria from human heart tissue in order to investigate if previous findings in animal models of cardiac disorders are translatable to human disease. Mitochondria were rapidly isolated from fresh atrial tissue samples obtained from 14 patients undergoing Maze surgery due to atrial fibrillation. Human heart mitochondria exhibited typical mPT characteristics upon calcium overload such as swelling, evaluated by changes in light scattering, inhibition of respiration and loss of respiratory coupling. Swelling was a morphologically reversible event following transient calcium challenge. Calcium retention capacity (CRC), a quantitative measure of mPT sensitivity assayed by following extramitochondrial [Ca(2+)] and changes in respiration during a continuous calcium infusion, was significantly increased by cyclophilin D (CypD) inhibitors. The thiol-reactive oxidant phenylarsine oxide sensitized mitochondria to calcium-induced mPT. Release of the pro-apoptotic intermembrane protein cytochrome c was increased after, but not before, calcium discharge and respiratory inhibition in the CRC assay. From the present study, we conclude that adult viable heart mitochondria have a CypD- and oxidant-regulated mPT. The findings support that inhibition of mPT may be a relevant pharmacological target in human cardiac disease and may underlie the beneficial effect of cyclosporin A in reperfusion injury.

  19. Metabolic Syndrome and Short-Term Heart Rate Variability in Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Chang, Yaw-Wen; Lin, Jin-Ding; Chen, Wei-Liang; Yen, Chia-Feng; Loh, Ching-Hui; Fang, Wen-Hui; Wu, Li-Wei

    2012-01-01

    Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV…

  20. Understanding age-based transition needs: Perspectives from adolescents and adults with congenital heart disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to explore the transition process in congenital heart disease (CHD) care through the perceived needs and concerns of adolescents (pretransition) and the experiential insight from adults (post-transition), in order to inform future transition initiatives and information ...

  1. Employability and career counseling for adolescents and adults with congenital heart disease.

    PubMed

    McGrath, K A; Truesdell, S C

    1994-06-01

    Employability is an important issue for adolescents and young adults with congenital heart disease. This article provides an overview of specific federal laws that protect these individuals and information about state vocational rehabilitation programs. Guidelines are provided to help health care providers counsel their patients more effectively.

  2. Attributing heart attack and stroke to "Old Age": Implications for subsequent health outcomes among older adults.

    PubMed

    Stewart, Tara L; Chipperfield, Judith G; Perry, Raymond P; Hamm, Jeremy M

    2016-01-01

    This study assessed the extent to which older adults attribute a recent heart attack/stroke to "old age," and examined consequences for subsequent lifestyle behavior and health-care service utilization. Community-dwelling adults (N = 57, ages 73-98 years) were interviewed about their heart attack/stroke, and an objective health registry provided data on health-care utilization over a 3-year period. Endorsement of "old age" as a cause of heart attack/stroke negatively predicted lifestyle behavior change, and positively predicted frequency of physician visits and likelihood of hospitalization over the subsequent 3 years. Findings suggest the importance of considering "old age" attributions in the context of cardiovascular health events.

  3. General anesthesia suppresses normal heart rate variability in humans

    NASA Astrophysics Data System (ADS)

    Matchett, Gerald; Wood, Philip

    2014-06-01

    The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

  4. Pharmacology and inotropic potential of forskolin in the human heart.

    PubMed Central

    Bristow, M R; Ginsburg, R; Strosberg, A; Montgomery, W; Minobe, W

    1984-01-01

    We evaluated the effects of the diterpene compound forskolin in human myocardial adenylate cyclase preparations, isolated trabeculae and papillary muscles derived from failing human hearts, and acutely instrumented dogs. Forskolin was a potent, powerful activator of human myocardial adenylate cyclase and produced maximal effects that were 4.82 (normally functioning left ventricle) and 6.13 (failing left ventricle) fold greater than isoproterenol. In contrast to isoproterenol, forskolin retained full activity in membrane preparations derived from failing hearts. In cyclase preparations, forskolin demonstrated unique substrate and Mg2+ kinetic properties that could be distinguished from hormone receptor-coupled agonists or fluoride ion. The adenylate cyclase stimulatory effect of forskolin was synergistic with isoproterenol, apparently due to the location of forskolin activation being beyond the level of hormone receptor-agonist in the receptor-cyclase complex. Forskolin was a potent positive inotrope in failing human myocardium, producing a stimulation of contraction that was similar to isoproterenol. Finally, in open chest dogs forskolin was a positive inotropic agent that reduced preload and afterload. We conclude that forskolin belongs to a class of agents that may have therapeutic potential in the treatment of congestive heart failure. Images PMID:6330174

  5. Second heart field and the development of the outflow tract in human embryonic heart.

    PubMed

    Yang, Yan-Ping; Li, Hai-Rong; Cao, Xi-Mei; Wang, Qin-Xue; Qiao, Cong-Jin; Ya, Jing

    2013-04-01

    The second heart field (SHF) is indicated to contribute to the embryonic heart development. However, less knowledge is available about SHF development of human embryo due to the difficulty of collecting embryos. In this study, serial sections of human embryos from Carnegie stage 10 (CS10) to CS16 were stained with antibodies against Islet-1 (Isl-1), Nkx2.5, GATA4, myosin heavy chain (MHC) and α-smooth muscle actin (α-SMA) to observe spatiotemporal distribution of SHF and its contribution to the development of the arterial pole of cardiac tube. Our findings suggest that during CS10 to CS12, SHF of the human embryo is composed of the bilateral pharyngeal mesenchyme, the central mesenchyme of the branchial arch and splanchnic mesoderm of the pericardial cavity dorsal wall. With development, SHF translocates and consists of ventral pharyngeal mesenchyme and dorsal wall of the pericardial cavity. Hence, the SHF of human embryo shows a dynamic spatiotemporal distribution pattern. The formation of the Isl-1 positive condense cell prongs provides an explanation for the saddle structure formation at the distal pole of the outflow tract. In human embryo, the Isl-1 positive cells of SHF may contribute to the formation of myocardial outflow tract (OFT) and the septum during different development stages.

  6. gamma. sub 2 -MSH immunoreactivity in the human heart

    SciTech Connect

    Ekman, R.; Bjartell, A.; Lisander, J.; Edvinsson, L. )

    1989-01-01

    In patients undergoing aorto-coronary by-pass surgery, we found a 26% arterial-venous difference of immunoreactive {gamma}{sub 2}-melanocytostimulating hormone (MSH), a proopiomelanocortin (POMC) derived peptide known to possess profound hemodynamic effects. These results prompted an investigation of the presence of {gamma}{sub 2}-MSH in the human heart. Using a two-step extraction procedure, regions of human hearts were examined by sensitive and specific radioimmunoassays to determine their {gamma}{sub 2}-MSH content. Mean ({plus minus} SEM) concentrations of 0.14 {plus minus} 0.023 pmol/g and 0.12 {plus minus} 0.017 were found in right atrium and right ventricle, respectively. High performance liquid chromatography indicated that 80-90 % of the total immunoreactivity eluted in a single sharp peak in a position identical to that of synthetic {gamma}{sub 2}-MSH.

  7. Influence of heart rate at rest for predicting the metabolic syndrome in older Chinese adults.

    PubMed

    O'Hartaigh, Bríain; Jiang, Chao Qiang; Bosch, Jos A; Zhang, Wei Sen; Cheng, Kar Keung; Lam, Tai Hing; Thomas, G Neil

    2013-06-01

    The aim of this study was to examine the relationship between seated resting heart rate and the metabolic syndrome (MetS) among older residents of Guangzhou, South China. A total of 30,519 older participants (≥50 years) from the Guangzhou Biobank Cohort Study were stratified into quartiles based on seated resting heart rate. The associations between each quartile and the MetS were assessed using multivariable logistic regression. A total of 6,907 (22.8 %) individuals were diagnosed as having the MetS, which was significantly associated with increasing heart rate quartiles (P < 0.001). Participants in the uppermost quartile (mean resting heart rate 91 ± 8 beats/min) of this cardiovascular proxy had an almost twofold increased adjusted risk (odds ratio (95 % CI) = 1.94 (1.79, 2.11), P < 0.001) for the MetS, as compared to those in the lowest quartile (mean resting heart rate, 63 ± 4 beats/min). Heart rate, which is an inexpensive and simple clinical measure, was independently associated with the MetS in older Chinese adults. We hope these observations will spur further studies to examine the usefulness of resting heart rate as a means of risk stratification in such populations, for which targeted interventions should be implemented.

  8. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo.

    PubMed

    Herrmann, Julia E; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L; Vickers, Alison E M

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24h. In this in vivo rat study (0.5mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices.

  9. Human Heart Failure: Is Cell Therapy a Valid Option?

    PubMed Central

    Rota, Marcello; Leri, Annarosa; Anversa, Piero

    2014-01-01

    The concept of the heart as a terminally differentiated organ incapable of replacing damaged myocytes has been at the center of cardiovascular research and therapeutic development for the last fifty years. The progressive decline in myocyte number with aging and the formation of scarred tissue following myocardial infarction have been interpreted as irrefutable proofs of the post-mitotic characteristics of the adult heart. However, emerging evidence supports a more dynamic view of the myocardium in which cell death and cell restoration are vital components of the remodeling process that governs organ homeostasis, aging and disease. The identification of dividing myocytes throughout the life span of the organisms and the recognition that undifferentiated primitive cells regulate myocyte turnover and tissue regeneration indicate that the heart is a self-renewing organ controlled by a compartment of resident stem cells. Moreover, exogenous progenitors of bone marrow origin transdifferentiate and acquire the cardiomyocyte and vascular lineages. This new reality constitutes the foundation of the numerous cell-based clinical trials that have been conducted in the last decade for the treatment of ischemic and non-ischemic cardiomyopathies. PMID:24239645

  10. Angiogenic properties of adult human thymus fat.

    PubMed

    Salas, Julián; Montiel, Mercedes; Jiménez, Eugenio; Valenzuela, Miguel; Valderrama, José Francisco; Castillo, Rafael; González, Sergio; El Bekay, Rajaa

    2009-11-01

    The endogenous proangiogenic properties of adipose tissue are well recognized. Although the adult human thymus has long been known to degenerate into fat tissue, it has never been considered as a potential source of angiogenic factors. We have investigated the expression of diverse angiogenic factors, including vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein kinase receptor-2 (an angiopoietin receptor), and then analyzed their physiological role on endothelial cell migration and proliferation, two relevant events in angiogenesis. The detection of the gene and protein expression of the various proteins has been performed by immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction. We show, for the first time, that adult thymus fat produces a variety of angiogenic factors and induces the proliferation and migration of human umbilical cord endothelial cells. Based on these findings, we suggest that this fat has a potential angiogenic function that might affect thymic function and ongoing adipogenesis within the thymus.

  11. Usefulness of the Seattle Heart Failure Model to identify adults with congenital heart disease at high risk of poor outcome.

    PubMed

    Stefanescu, Ada; Macklin, Eric A; Lin, Elaine; Dudzinski, David M; Johnson, Jacob; Kennedy, Kevin F; Jacoby, Daniel; DeFaria Yeh, Doreen; Lewis, Gregory D; Yeh, Robert W; Liberthson, Richard; Lui, George; Bhatt, Ami B

    2014-03-01

    Our objective was to determine whether the Seattle Heart Failure Model (SHFM) differentiates patients with adult congenital heart disease (ACHD) at high versus low risk for cardiovascular outcomes and poor exercise capacity. The ACHD population is growing and presents increasingly for care in the community and at tertiary centers. Few strategies exist to identify the patients with ACHD at high risk for heart failure and mortality.We studied 153 adults with transposition of the great arteries, Ebstein anomaly, tetralogy of Fallot, double outlet right ventricle, and single ventricle from 2 ACHD centers. The primary outcome was cardiovascular death, with a secondary composite outcome of death, transplant, ventricular assist device, cardiovascular admission, and treatment for arrhythmia. We defined risk groups based on SHFM 5-year predicted survival: high (predicted survival <70%), intermediate (70% to 85%), and low risk (>85%). Ten patients had the primary outcome of death, and 46 the combined end point. The hazard of death in the SHFM high- versus the intermediate-risk group was 7.09 (95% confidence interval 1.5 to 33.4, p = 0.01; no deaths in the low-risk group) and the hazard of the composite outcome between the high- versus low-risk group was 6.64 (95% confidence interval 2.5 to 17.6, p = 0.0001). Kaplan-Meier survival analysis showed greater probability of all-cause mortality (p = 0.003) in the high-risk group. In conclusion, the SHFM can help identify subjects with ACHD at risk for adverse outcome and poor cardiopulmonary efficiency. This may add to the care of patients with ACHD in the community and streamline care at tertiary centers.

  12. Awareness of heart attack and stroke symptoms among Hispanic male adults living in the United States.

    PubMed

    Lutfiyya, May Nawal; Bardales, Ricardo; Bales, Robert; Aguero, Carlos; Brady, Shelly; Tobar, Adriana; McGrath, Cynthia; Zaiser, Julia; Lipsky, Martin S

    2010-10-01

    There is evidence that Hispanic men are a high risk group for treatment delay for both heart attack and stroke. More targeted research is needed to elucidate this specific population's knowledge of warning signs for these acute events. This study sought to describe within-group disparities in Hispanic men's knowledge of heart attack and stroke symptomology. Multivariate techniques were used to analyze a multi-year Behavioral Risk Factor Surveillance Heart and Stroke module database. The data were cross-sectional and focused on health risk factors and behaviors. The research participants were U.S. male Hispanic adults aged 18-99. The main outcome measure for the study was heart attack and stroke symptom knowledge score. Multivariate logistic regression analysis yielded that Hispanic men aged >or=18 years who earned low scores on the composite heart attack and stroke knowledge questions (range 0-8 points) were more likely to: have less than a high school education, have deferred medical care because of cost, not have an identified health care provider, and be uninsured. There were significant within-group differences. Targeting educational efforts toward older (>or=55 years) Hispanic men with less than high school education, those who do not have an identified health care provider or health insurance, and who defer health care because of cost could be ways to improve the outcome of acute vascular events among the U.S. Hispanic adult male population.

  13. Disparities in adult awareness of heart attack warning signs and symptoms--14 states, 2005.

    PubMed

    2008-02-22

    In 2005, approximately 920,000 persons in the United States had a myocardial infarction (i.e., heart attack); in 2004, approximately 157,000 heart attacks were fatal. One study indicated that approximately half of cardiac deaths occur within 1 hour of symptom onset, before patients reach a hospital. Timely access to emergency cardiac care, receipt of advanced treatment, and potential for surviving a heart attack all depend on 1) early recognition of warning signs and symptoms of a heart attack by persons who are having a heart attack and bystanders and 2) immediately calling 9-1-1. Healthy People 2010 includes an objective to increase from 46% to 50% the proportion of adults aged > or =20 years who are aware of the early warning signs and symptoms of a heart attack and the importance of accessing rapid emergency care by calling 9-1-1 (objective 12-2). To update estimates of public awareness of heart attack warning signs and symptoms and knowledge of the importance of calling 9-1-1, CDC analyzed 2005 Behavioral Risk Factor Surveillance System (BRFSS) data from the 14 states that included questions on signs and symptoms of a heart attack. This report describes the results of that analysis, which indicated that although the awareness of certain individual warning signs was as high as 93% (i.e., for shortness of breath), awareness of all five warning signs was 31%, underscoring the need for public health measures to increase public awareness of heart attack warning signs and symptoms. In addition, disparities in awareness were observed by race/ethnicity, sex, and level of education, suggesting that new public health measures should target populations with the lowest levels of awareness.

  14. Emerging Research Directions in Adult Congenital Heart Disease: A Report From an NHLBI/ACHA Working Group.

    PubMed

    Gurvitz, Michelle; Burns, Kristin M; Brindis, Ralph; Broberg, Craig S; Daniels, Curt J; Fuller, Stephanie M P N; Honein, Margaret A; Khairy, Paul; Kuehl, Karen S; Landzberg, Michael J; Mahle, William T; Mann, Douglas L; Marelli, Ariane; Newburger, Jane W; Pearson, Gail D; Starling, Randall C; Tringali, Glenn R; Valente, Anne Marie; Wu, Joseph C; Califf, Robert M

    2016-04-26

    Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy.

  15. High Contrast Ultrafast Imaging of the Human Heart

    PubMed Central

    Papadacci, Clement; Pernot, Mathieu; Couade, Mathieu; Fink, Mathias; Tanter, Mickael

    2014-01-01

    Non-invasive ultrafast imaging for human cardiac applications is a big challenge to image intrinsic waves such as electromechanical waves or remotely induced shear waves in elastography imaging techniques. In this paper we propose to perform ultrafast imaging of the heart with adapted sector size by using diverging waves emitted from a classical transthoracic cardiac phased array probe. As in ultrafast imaging with plane wave coherent compounding, diverging waves can be summed coherently to obtain high-quality images of the entire heart at high frame rate in a full field-of-view. To image shear waves propagation at high SNR, the field-of-view can be adapted by changing the angular aperture of the transmitted wave. Backscattered echoes from successive circular wave acquisitions are coherently summed at every location in the image to improve the image quality while maintaining very high frame rates. The transmitted diverging waves, angular apertures and subapertures size are tested in simulation and ultrafast coherent compounding is implemented on a commercial scanner. The improvement of the imaging quality is quantified in phantom and in vivo on human heart. Imaging shear wave propagation at 2500 frame/s using 5 diverging waves provides a strong increase of the Signal to noise ratio of the tissue velocity estimates while maintaining a high frame rate. Finally, ultrafast imaging with a 1 to 5 diverging waves is used to image the human heart at a frame rate of 900 frames/s over an entire cardiac cycle. Thanks to spatial coherent compounding, a strong improvement of imaging quality is obtained with a small number of transmitted diverging waves and a high frame rate, which allows imaging the propagation of electromechanical and shear waves with good image quality. PMID:24474135

  16. Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure.

    PubMed

    Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming; Creighton, Chad J; Yang, Jin; Donti, Taraka R; Harmancey, Romain; Vasquez, Hernan G; Graham, Brett H; Bellen, Hugo J; Taegtmeyer, Heinrich; Chang, Ching-Pin; Tsai, Ming-Jer; Tsai, Sophia Y

    2015-09-10

    Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy.

  17. Human care system for heart-rate and human-movement trajectory in home and its application to detect mental disease

    NASA Astrophysics Data System (ADS)

    Hata, Yutaka; Kanazawa, Seigo; Endo, Maki; Tsuchiya, Naoki; Nakajima, Hiroshi

    2012-06-01

    This paper proposes a heart rate monitoring system for detecting autonomic nervous system by the heart rate variability using an air pressure sensor to diagnose mental disease. Moreover, we propose a human behavior monitoring system for detecting the human trajectory in home by an infrared camera. In day and night times, the human behavior monitoring system detects the human movement in home. The heart rate monitoring system detects the heart rate in bed in night time. The air pressure sensor consists of a rubber tube, cushion cover and pressure sensor, and it detects the heart rate by setting it to bed. It unconstraintly detects the RR-intervals; thereby the autonomic nervous system can be assessed. The autonomic nervous system analysis can examine the mental disease. While, the human behavior monitoring system obtains distance distribution image by an infrared camera. It classifies adult, child and the other object from distance distribution obtained by the camera, and records their trajectories. This behavior, i.e., trajectory in home, strongly corresponds to cognitive disorders. Thus, the total system can detect mental disease and cognitive disorders by uncontacted sensors to human body.

  18. Sertraline exposure leads to small left heart syndrome in adult mice

    PubMed Central

    Haskell, Sarah E.; Hermann, Gregory M.; Reinking, Benjamin E.; Volk, Kenneth A.; Peotta, Veronica A.; Zhu, Vivian; Roghair, Robert D.

    2013-01-01

    Background Sertraline, a selective serotonin reuptake inhibitor (SSRI), is the most commonly prescribed therapy for maternal depression. Epidemiologic studies have linked SSRI exposure with decreased fetal growth, altered autonomic regulation, and cardiac malformations. We hypothesized SSRI exposure decreases left ventricular volumes and increases adult sympathetic nervous system activation, resulting in increased adult heart rates. Methods C57BL/6 mice received saline or sertraline (5 or 15 mg/kg/day i.p.) on postnatal days 1–14. Adult phenotypes were assessed at 5 months. Results Sertraline-exposed mice had smaller left ventricular internal diameters in diastole (control 4.0 ± 0.1 mm, SSRI 3.7 ± 0.1 mm, p < 0.05), decreased stroke volumes (control 46 ± 2.6 μL, SSRI 37 ± 2.3 μL, p < 0.05), higher heart rates (control 530 ± 13 beats per minute (bpm), SSRI 567 ± 6 bpm, p <0.05) and increased urinary excretion of noradrenaline (control 174 ± 29.4 ng/mL, SSRI 276 ± 35.1 ng/mL, p<0.05). These changes were associated with increased cerebral serotonin transporter (5-HTT) expression. Conclusion Neonatal sertraline exposure causes long term changes in cardiac morphology and physiology. We speculate that early life SSRI exposure impairs cardiomyocyte growth and central serotonin signaling, leading to a small left heart syndrome in adult mice. PMID:23232669

  19. Human Mesenchymal Stem Cells Reendothelialize Porcine Heart Valve Scaffolds: Novel Perspectives in Heart Valve Tissue Engineering

    PubMed Central

    Lanuti, Paola; Serafini, Francesco; Pierdomenico, Laura; Simeone, Pasquale; Bologna, Giuseppina; Ercolino, Eva; Di Silvestre, Sara; Guarnieri, Simone; Canosa, Carlo; Impicciatore, Gianna Gabriella; Chiarini, Stella; Magnacca, Francesco; Mariggiò, Maria Addolorata; Pandolfi, Assunta; Marchisio, Marco; Di Giammarco, Gabriele; Miscia, Sebastiano

    2015-01-01

    Abstract Heart valve diseases are usually treated by surgical intervention addressed for the replacement of the damaged valve with a biosynthetic or mechanical prosthesis. Although this approach guarantees a good quality of life for patients, it is not free from drawbacks (structural deterioration, nonstructural dysfunction, and reintervention). To overcome these limitations, the heart valve tissue engineering (HVTE) is developing new strategies to synthesize novel types of valve substitutes, by identifying efficient sources of both ideal scaffolds and cells. In particular, a natural matrix, able to interact with cellular components, appears to be a suitable solution. On the other hand, the well-known Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative abilities, and their immunomodulatory capacities make them highly promising for HVTE applications. In the present study, we investigated the possibility to use porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs differentiated along the endothelial lineage, paralleled with human umbilical vein endothelial cells (HUVECs), used as positive control. Here, we were able to successfully decellularize porcine heart valves, which were then recellularized with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell types were able to reconstitute a cellular monolayer. Cells were able to positively interact with the natural matrix and demonstrated the surface expression of typical endothelial markers. Altogether, these data suggest that the interaction between a biological scaffold and WJ-MSCs allows the regeneration of a morphologically well-structured endothelium, opening new perspectives in the field of HVTE. PMID:26309804

  20. Myocardial factor revisited: The importance of myocardial fibrosis in adults with congenital heart disease.

    PubMed

    Broberg, Craig S; Burchill, Luke J

    2015-06-15

    Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a "myocardial factor" playing a role. They conjectured that residual alterations in myocardial function would be significant for patients' long-term outlook. In fulfillment of their early observations, today's adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the 'myocardial factor' was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor--myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment.

  1. Myocardial Factor Revisited: The Importance of Myocardial Fibrosis in Adults with Congenital Heart Disease

    PubMed Central

    Broberg, Craig S.; Burchill, Luke J.

    2015-01-01

    Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a “myocardial factor” playing a role. They conjectured that residual alterations in myocardial function would be significant for patients’ long-term outlook. In fulfillment of their early observations, today’s adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the ‘myocardial factor’ was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor – myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment. PMID:25897907

  2. Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart.

    PubMed

    Zhang, Yuan; Sivakumaran, Priyadharshini; Newcomb, Andrew E; Hernandez, Damián; Harris, Nicole; Khanabdali, Ramin; Liu, Guei-Sheung; Kelly, Darren J; Pébay, Alice; Hewitt, Alex W; Boyle, Andrew; Harvey, Richard; Morrison, Wayne A; Elliott, David A; Dusting, Gregory J; Lim, Shiang Y

    2015-10-01

    Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2(+) CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2(+) CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2(+) CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRα, ISL1, or WT1. W8B2(+) CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2(+) CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2(+) CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (∼40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2(+) CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67(+) cTnT(+) cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163(+) cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2(+) CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction.

  3. Uniquely hominid features of adult human astrocytes.

    PubMed

    Oberheim, Nancy Ann; Takano, Takahiro; Han, Xiaoning; He, Wei; Lin, Jane H C; Wang, Fushun; Xu, Qiwu; Wyatt, Jeffrey D; Pilcher, Webster; Ojemann, Jeffrey G; Ransom, Bruce R; Goldman, Steven A; Nedergaard, Maiken

    2009-03-11

    Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca(2+) waves with a speed of 36 microm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca(2+) in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5-6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.

  4. Arrhythmogenic remodelling of activation and repolarization in the failing human heart.

    PubMed

    Holzem, Katherine M; Efimov, Igor R

    2012-11-01

    Heart failure is a major cause of disability and death worldwide, and approximately half of heart failure-related deaths are sudden and presumably due to ventricular arrhythmias. Patients with heart failure have been shown to be at 6- to 9-fold increased risk of sudden cardiac death compared to the general population. (AHA. Heart Disease and Stroke Statistics-2003 Update. Heart and Stroke Facts. Dallas, TX: American Heart Association; 2002) Thus, electrophysiological remodelling associated with heart failure is a leading cause of disease mortality and has been a major investigational focus examined using many animal models of heart failure. While these studies have provided an important foundation for understanding the arrhythmogenic pathophysiology of heart failure, the need for corroborating studies conducted on human heart tissue has been increasingly recognized. Many human heart studies of conduction and repolarization remodelling have now been published and shed some light on important, potentially arrhythmogenic, changes in human heart failure. These studies are being conducted at multiple experimental scales from isolated cells to whole-tissue preparations and have provided insight into regulatory mechanisms such as decreased protein expression, alternative mRNA splicing of ion channel genes, and defective cellular trafficking. Further investigations of heart failure in the human myocardium will be essential for determining possible therapeutic targets to prevent arrhythmia in heart failure and for facilitating the translation of basic research findings to the clinical realm.

  5. Interventional and surgical treatment of cardiac arrhythmias in adults with congenital heart disease.

    PubMed

    Koyak, Zeliha; de Groot, Joris R; Mulder, Barbara J M

    2010-12-01

    Arrhythmias are a major cause of morbidity, mortality and hospital admission in adults with congenital heart disease (CHD). The etiology of arrhythmias in this population is often multifactorial and includes electrical disturbances as part of the underlying defect, surgical intervention or hemodynamic abnormalities. Despite the numerous existing arrhythmia management tools including drug therapy, pacing and ablation, management of arrhythmias in adults with CHD remains difficult and challenging. Owing to improvement in mapping and ablation techniques, ablation and arrhythmia surgery are being performed more frequently in adults with CHD. However, there is little information on the long-term results of these treatment strategies. The purpose of this article is therefore to review the available data on nonpharmacological treatment of cardiac arrhythmias in adult patients with CHD and to give an overview of the available data on the early and late outcomes of these treatment strategies.

  6. MyHEART: A Non Randomized Feasibility Study of a Young Adult Hypertension Intervention

    PubMed Central

    Johnson, Heather M; LaMantia, Jamie N; Warner, Ryan C; Pandhi, Nancy; Bartels, Christie M; Smith, Maureen A; Lauver, Diane R

    2016-01-01

    Background In the United States, young adults (18–39 year-olds) have the lowest hypertension control rates (35%) compared to middle-aged (58%) and older (54%) adults. Ambulatory care for hypertension management often focuses on medication with little time for self-management and behavioral counseling. This study was designed to evaluate the feasibility of MyHEART, a telephone-based health coach self-management intervention for young adults. The goals were to determine the intervention’s ability to: 1) recruit young adults with uncontrolled hypertension, 2) maintain ongoing communication between the coach and participants, 3) increase participants’ engagement in self-management, 4) document coach-patient communication in the electronic health record, and 5) assess patient acceptability. Methods Eligible participants were identified through the electronic health record. Inclusion criteria included 18–39 year-olds, with ICD-9 hypertension diagnoses and uncontrolled hypertension (≥ 140/90 mmHg), receiving regular primary care at a large multispecialty group practice. The intervention consisted of 6 telephone self-management sessions by a health coach targeting lifestyle modifications. Patients completed an open-ended acceptability survey. Results Study uptake was 47% (9 enrolled/19 eligible). Mean (SD) age was 35.8 (2.6) years, 78% male, and 33% Black. Over 85% of enrolled young adults maintained communication with their health coach. At baseline, 11% reported checking their blood pressure outside of clinic; 44% reported blood pressure monitoring after the study. All coach-patient encounters were successfully documented in the electronic health record for primary care provider review. Open-ended responses from all surveys indicated that participants had a positive experience with the MyHEART intervention. Conclusions This study demonstrated that MyHEART was feasible and acceptable to young adults with uncontrolled hypertension. Health coaches can effectively

  7. Hyperpolarized 13C Metabolic MRI of the Human Heart

    PubMed Central

    Lau, Justin Y.C.; Chen, Albert P.; Geraghty, Benjamin J.; Perks, William J.; Roifman, Idan; Wright, Graham A.; Connelly, Kim A.

    2016-01-01

    Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. Objective: To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart. Methods and Results: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1-13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1-13C]lactate. Conclusions: These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1-13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009. PMID:27635086

  8. Point mutations in murine Nkx2-5 phenocopy human congenital heart disease and induce pathogenic Wnt signaling

    PubMed Central

    Furtado, Milena B.; Wilmanns, Julia C.; Chandran, Anjana; Perera, Joelle; Hon, Olivia; Biben, Christine; Willow, Taylor J.; Nim, Hieu T.; Kaur, Gurpreet; Simonds, Stephanie; Willians, David; Salimova, Ekaterina; Plachta, Nicolas; Denegre, James M.; Murray, Stephen A.; Cowley, Michael; Pearson, James T.; Kaye, David; Ramialison, Mirana; Rosenthal, Nadia A.; Costa, Mauro W.

    2017-01-01

    Mutations in the Nkx2-5 gene are a main cause of congenital heart disease. Several studies have addressed the phenotypic consequences of disrupting the Nkx2-5 gene locus, although animal models to date failed to recapitulate the full spectrum of the human disease. Here, we describe a new Nkx2-5 point mutation murine model, akin to its human counterpart disease–generating mutation. Our model fully reproduces the morphological and physiological clinical presentations of the disease and reveals an understudied aspect of Nkx2-5–driven pathology, a primary right ventricular dysfunction. We further describe the molecular consequences of disrupting the transcriptional network regulated by Nkx2-5 in the heart and show that Nkx2-5–dependent perturbation of the Wnt signaling pathway promotes heart dysfunction through alteration of cardiomyocyte metabolism. Our data provide mechanistic insights on how Nkx2-5 regulates heart function and metabolism, a link in the study of congenital heart disease, and confirms that our models are the first murine genetic models to our knowledge to present all spectra of clinically relevant adult congenital heart disease phenotypes generated by NKX2-5 mutations in patients. PMID:28352650

  9. Point mutations in murine Nkx2-5 phenocopy human congenital heart disease and induce pathogenic Wnt signaling.

    PubMed

    Furtado, Milena B; Wilmanns, Julia C; Chandran, Anjana; Perera, Joelle; Hon, Olivia; Biben, Christine; Willow, Taylor J; Nim, Hieu T; Kaur, Gurpreet; Simonds, Stephanie; Wu, Qizhu; Willians, David; Salimova, Ekaterina; Plachta, Nicolas; Denegre, James M; Murray, Stephen A; Fatkin, Diane; Cowley, Michael; Pearson, James T; Kaye, David; Ramialison, Mirana; Harvey, Richard P; Rosenthal, Nadia A; Costa, Mauro W

    2017-03-23

    Mutations in the Nkx2-5 gene are a main cause of congenital heart disease. Several studies have addressed the phenotypic consequences of disrupting the Nkx2-5 gene locus, although animal models to date failed to recapitulate the full spectrum of the human disease. Here, we describe a new Nkx2-5 point mutation murine model, akin to its human counterpart disease-generating mutation. Our model fully reproduces the morphological and physiological clinical presentations of the disease and reveals an understudied aspect of Nkx2-5-driven pathology, a primary right ventricular dysfunction. We further describe the molecular consequences of disrupting the transcriptional network regulated by Nkx2-5 in the heart and show that Nkx2-5-dependent perturbation of the Wnt signaling pathway promotes heart dysfunction through alteration of cardiomyocyte metabolism. Our data provide mechanistic insights on how Nkx2-5 regulates heart function and metabolism, a link in the study of congenital heart disease, and confirms that our models are the first murine genetic models to our knowledge to present all spectra of clinically relevant adult congenital heart disease phenotypes generated by NKX2-5 mutations in patients.

  10. THERP and HEART integrated methodology for human error assessment

    NASA Astrophysics Data System (ADS)

    Castiglia, Francesco; Giardina, Mariarosa; Tomarchio, Elio

    2015-11-01

    THERP and HEART integrated methodology is proposed to investigate accident scenarios that involve operator errors during high-dose-rate (HDR) treatments. The new approach has been modified on the basis of fuzzy set concept with the aim of prioritizing an exhaustive list of erroneous tasks that can lead to patient radiological overexposures. The results allow for the identification of human errors that are necessary to achieve a better understanding of health hazards in the radiotherapy treatment process, so that it can be properly monitored and appropriately managed.

  11. Are urinary polyaromatic hydrocarbons associated with adult hypertension, heart attack, and cancer? USA NHANES, 2011-2012.

    PubMed

    Shiue, Ivy

    2015-11-01

    Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols and pesticides. Therefore, it was aimed to study the relationships of urinary polyaromatic hydrocarbons and adult cardiovascular disease and cancer using human sample in a national and population-based study in recent years. Data was retrieved from US National Health and Nutrition Examination Surveys, 2011-2012, including demographics, self-reported health conditions and urinary polyaromatic hydrocarbons. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling and population attributable risk (PAR) estimation. Of 5560 American adults aged 20-80 and included in the statistical analysis, urinary polyaromatic hydrocarbons (representatively in one-third sample) were observed to be higher in people with cardiovascular disease and total cancer. In particular, urinary 4-hydroxyphenanthrene was associated with hypertension (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.00-1.76, P = 0.048, PAR 5.1%), urinary 1-hydroxypyrene was significantly associated with heart attack (OR 1.47, 95%CI 1.05-2.06, P = 0.027, PAR 1.7%), and urinary 2-hydroxynapthalene (2-naphthol) was associated with cancer (OR 1.46, 95%CI 1.12-1.90, P = 0.008, PAR 3.9%). Urinary polyaromatic hydrocarbons were associated with adult hypertension, heart attack and cancer, although the causality cannot be established. From the research perspective, future studies with a longitudinal or experimental approach would be suggested. From the law and public health perspectives, regulation on minimizing exposure to polyaromatic hydrocarbons might need to be considered in future health and environmental policies and intervention programs.

  12. Effect of Rotating Acoustic Stimulus on Heart Rate Variability in Healthy Adults

    PubMed Central

    Roy, Bhaskar; Choudhuri, Raghabendra; Pandey, Ambarish; Bandopadhyay, Sajal; Sarangi, Sasmit; Kumar Ghatak, Sobhendu

    2012-01-01

    Acoustic stimulus can modulate the Autonomic Nervous System. However, previous reports on this topic are conflicting and inconclusive. In this study we have shown, how rotating acoustic stimulus, a novel auditory binaural stimulus, can change the autonomic balance of the cardiac system. We have used Heart rate Variability (HRV), an indicator of autonomic modulation of heart, both in time and frequency domain to analyze the effect of stimulus on 31 healthy adults. A decrease in the heart rate accompanied with an increase in SD and RMSSD indices on linear analysis was observed post-stimulation. In the Poincaré Plot, Minor Axis (SD1), Major Axis (SD2) and the ratio SD12 (SD1/SD2) increased after the stimulation. Post stimulus greater increment of SD12 with higher lag numbers of (M) beat to beat intervals, when compared to pre stimulus values, resulted in increased curvilinearity in the SD12 vs. Lag number plot. After stimulation,value of exponent alpha of Dretended Flactuation Analysis of HRV was found to be decreased. From these characteristic responses of the heart after the stimulus, it appears that rotating acoustic stimulus may be beneficial for the sympathovagal balance of the heart. PMID:23091566

  13. Heart failure in older adults. Providing nursing care to improve outcomes.

    PubMed

    Konick-McMahan, Joanne; Bixby, Brian; McKenna, Catherine

    2003-12-01

    Heart failure continues to be a challenge for older patients and their health care providers. This article is based on work by advanced practice nurses in a nursing study funded by the National Institute of Nursing Research of the National Institute of Health. Mary Naylor, RN, PhD at the University of Pennsylvania School of Nursing through grant #1RO1-NR04315 is using a transitional care model to provide advance practice nurse intervention for older adults with heart failure in a randomized controlled trial. Effects of the intervention being addressed include quality of life, functional status, rehospitalizations, and costs of care. Working with the patient in the acute hospital setting and following patients to the home care setting for 3 months, the advance practice nurse develops a visit pattern and intervention plan individual to the patient's needs. Key to a successful intervention plan is the right treatment for systolic versus diastolic failure. Although the patient's symptoms and some physical findings may be similar, the drugs used to treat systolic versus diastolic heart failure are different. Thus the nursing interventions to promote symptom management and avoid rehospitalizations have a different approach. In this article, care of elderly individuals with systolic versus diastolic heart failure is compared and contrasted using physical examination and diagnostic techniques, medication management, and nursing intervention. Case studies of a typical patient with systolic and diastolic heart failure will be used to illustrate the differences in approach to this common group of patients with complex needs.

  14. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts

    PubMed Central

    Chong, James J.H.; Yang, Xiulan; Don, Creighton W.; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M.; Van Biber, Benjamin; Cook, Savannah M.; Palpant, Nathan J; Gantz, Jay; Fugate, James A.; Muskheli, Veronica; Gough, G. Michael; Vogel, Keith W.; Astley, Cliff A.; Hotchkiss, Charlotte E.; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A.; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A.; Murry, Charles E.

    2014-01-01

    Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure 1 by providing human cardiomyocytes to support heart regeneration 2. Studies of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in small animal models have shown favorable effects of this treatment 3–7. It remains unknown, however, whether clinical scale hESC-CMs transplantation is feasible, safe or can provide large-scale myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (>1 billion cells/batch) and cryopreserved with good viability. Using a non-human primate (NHP) model of myocardial ischemia-reperfusion, we show that that cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs generates significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a three-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small animal models 7, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome. PMID:24776797

  15. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.

    PubMed

    Chong, James J H; Yang, Xiulan; Don, Creighton W; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M; Van Biber, Benjamin; Cook, Savannah M; Palpant, Nathan J; Gantz, Jay A; Fugate, James A; Muskheli, Veronica; Gough, G Michael; Vogel, Keith W; Astley, Cliff A; Hotchkiss, Charlotte E; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A; Murry, Charles E

    2014-06-12

    Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure by providing human cardiomyocytes to support heart regeneration. Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment. However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (more than one billion cells per batch) and cryopreserved with good viability. Using a non-human primate model of myocardial ischaemia followed by reperfusion, we show that cryopreservation and intra-myocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a 3-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small-animal models, non-fatal ventricular arrhythmias were observed in hESC-CM-engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome.

  16. Improving Medication Knowledge among Older Adults with Heart Failure: A Patient-Centered Approach to Instruction Design

    ERIC Educational Resources Information Center

    Morrow, Daniel G.; Weiner, Michael; Young, James; Steinley, Douglas; Deer, Melissa; Murray, Michael D.

    2005-01-01

    Purpose: We investigated whether patient-centered instructions for chronic heart failure medications increase comprehension and memory for medication information in older adults diagnosed with chronic heart failure. Design and Methods: Patient-centered instructions for familiar and unfamiliar medications were compared with instructions for the…

  17. Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts.

    PubMed

    Garreta, Elena; de Oñate, Lorena; Fernández-Santos, M Eugenia; Oria, Roger; Tarantino, Carolina; Climent, Andreu M; Marco, Andrés; Samitier, Mireia; Martínez, Elena; Valls-Margarit, Maria; Matesanz, Rafael; Taylor, Doris A; Fernández-Avilés, Francisco; Izpisua Belmonte, Juan Carlos; Montserrat, Nuria

    2016-08-01

    Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting.

  18. Improving outcomes for older adults with heart failure: a randomized trial using a theory-guided nursing intervention.

    PubMed

    Duffy, Joanne R; Hoskins, Lois M; Dudley-Brown, Sharon

    2010-01-01

    Newly discharged older adults with heart failure continue to experience frequent hospital readmissions, lower quality of life, and decreased satisfaction with health services. A theory-guided intervention delivered by home health nurses via the telephone was studied using a randomized controlled trial to assess its feasibility and inform further studies. Findings generated a profile of older adults with heart failure, utilization by patients and nurses, operational issues, and preliminary data on intended outcomes. Implications for further study are presented.

  19. The cardiac glycoside-receptor system in the human heart.

    PubMed

    Erdmann, E; Brown, L

    1983-01-01

    Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta-blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity: half-maximal receptor binding occurs at approximately 2 nM (approximately 1.5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na+ + K+)-ATPase activity--which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains approximately 1.5 x 10(14) binding sites/g wet weight, right ventricle approximately 0.9 x 10(14). In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.

  20. Innate Immunity in the Adult Mammalian Heart: For Whom the Cell Tolls

    PubMed Central

    Mann, Douglas L.; Topkara, Veli K.; Evans, Sarah; Barger, Philip M.

    2010-01-01

    Recent studies suggest that the heart possesses an intrinsic system that is intended to delimit tissue injury, as well as orchestrate homoeostatic responses within the heart. The extant literature suggests that this intrinsic stress response is mediated, at least in part, by a family of pattern recognition receptors that belong to the innate immune system, including CD14, the soluble pattern recognition receptor for lipopolysaccharide, and Toll like receptors-2, 3, 4, and 6. Although this intrinsic stress response system provides a short-term adaptive response to tissue injury, the beneficial effects of this phylogenetically ancient system may be lost if myocardial expression of these molecules either becomes sustained and/or excessive, in which case the salutary effects of activation of these pathways may be contravened by the known deleterious effects of inflammatory signaling. Herein we present new information with regard to activation of innate immune gene expression in the failing human heart. Taken together, these new observations provide provisional evidence that the innate immune system is activated in human heart failure, raising the interesting possibility that this pathway may represent a target for the development of novel heart failure therapeutics. PMID:20697548

  1. Dietary Interventions for Heart Failure in Older Adults: Re-emergence of the Hedonic Shift

    PubMed Central

    Wessler, Jeffrey D.; Hummel, Scott L.; Maurer, Mathew S.

    2014-01-01

    Dietary non-adherence to sodium restriction is an important contribution to heart failure (HF) symptom burden, particularly in older adults. While knowledge, skills, and attitudes towards sodium restriction are important, sodium intake is closely linked to the ability to taste salt. The ‘hedonic shift’ occurs when sodium restriction induces changes in an individual’s salt taste that lower subsequent salt affinity. Older adults often have compromised salt taste and higher dietary salt affinity due to age-related changes. Older HF patients may have additional loss of salt taste and elevated salt appetite due to comorbid conditions, medication use, and micronutrient or electrolyte abnormalities, creating a significant barrier to dietary adherence. Induction of the hedonic shift has the potential to improve long-term dietary sodium restriction and significantly impact HF outcomes in older adults. PMID:25216615

  2. Generation of pluripotent stem cells from adult human testis.

    PubMed

    Conrad, Sabine; Renninger, Markus; Hennenlotter, Jörg; Wiesner, Tina; Just, Lothar; Bonin, Michael; Aicher, Wilhelm; Bühring, Hans-Jörg; Mattheus, Ulrich; Mack, Andreas; Wagner, Hans-Joachim; Minger, Stephen; Matzkies, Matthias; Reppel, Michael; Hescheler, Jürgen; Sievert, Karl-Dietrich; Stenzl, Arnulf; Skutella, Thomas

    2008-11-20

    Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

  3. Anesthesia for the adult patient with an unrepaired congenital cyanotic heart defect: a case report.

    PubMed

    Cosgrove, Marianne S

    2012-06-01

    Adult congenital heart disease, previously considered a rare comorbidity, is increasingly becoming a reality for today's anesthesia providers. Improvements in prenatal diagnosis, sophisticated surgical techniques and equipment, advances in pediatric critical care, enhanced efficacy of cardiovascular pharmacologic agents, and an overall increase in postrepair survival rates have resulted in an estimated population of approximately 800,000 adults with congenital heart disease. Despite successful surgical repair or palliation, these individuals present the anesthesia provider with a multitude of challenges. Individualized care of these fragile patients should be approached with a keen understanding of the patient's underlying cardiac anomaly. This case report chronicles the anesthetic care of a 36-year-old woman presenting for left-sided ureteroscopy with laser lithotripsy and stent placement. Her medical history was remarkable for the presence of complex congenital heart disease consisting of multiple anomalies: a double-outlet right ventricle, transposition of the great arteries, pulmonary stenosis, atrial septal defect, and a hypoplastic left ventricle with concomitant mitral valve atresia. General anesthesia was successfully administered, with meticulous attention given to maintenance of systemic vascular resistance to minimize shunting, oxygenation, administration of preprocedure antibiotics, and judicious replacement of intravenous fluids via air-filtered tubing.

  4. Abcg2-Labeled Cells Contribute to Different Cell Populations in the Embryonic and Adult Heart.

    PubMed

    Doyle, Michelle J; Maher, Travis J; Li, Qinglu; Garry, Mary G; Sorrentino, Brian P; Martin, Cindy M

    2016-02-01

    ATP-binding cassette transporter subfamily G member 2 (Abcg2)-expressing cardiac-side population cells have been identified in the developing and adult heart, although the role they play in mammalian heart growth and regeneration remains unclear. In this study, we use genetic lineage tracing to follow the cell fate of Abcg2-expressing cells in the embryonic and adult heart. During cardiac embryogenesis, the Abcg2 lineage gives rise to multiple cardiovascular cell types, including cardiomyocytes, endothelial cells, and vascular smooth muscle cells. This capacity for Abcg2-expressing cells to contribute to cardiomyocytes decreases rapidly during the postnatal period. We further tested the role of the Abcg2 lineage following myocardial injury. One month following ischemia reperfusion injury, Abcg2-expressing cells contributed significantly to the endothelial cell lineage, however, there was no contribution to regenerated cardiomyocytes. Furthermore, consistent with previous results showing that Abcg2 plays an important cytoprotective role during oxidative stress, we show an increase in Abcg2 labeling of the vasculature, a decrease in the scar area, and a moderate improvement in cardiac function following myocardial injury. We have uncovered a difference in the capacity of Abcg2-expressing cells to generate the cardiovascular lineages during embryogenesis, postnatal growth, and cardiac regeneration.

  5. Baseline heart rate, sensation seeking, and aggression in young adult women: a two-sample examination.

    PubMed

    Wilson, Laura C; Scarpa, Angela

    2013-01-01

    Although substantial literature discusses sensation seeking as playing a role in the relationship between baseline heart rate and aggression, few published studies have tested the relationships among these variables. Furthermore, most prior studies have focused on risk factors of aggression in men and have largely ignored this issue in women. Two samples (n = 104; n = 99) of young adult women completed measures of resting heart rate, sensation seeking, and aggression. Across the two samples of females there was no evidence for the relationships of baseline heart rate with sensation seeking or with aggression that has been consistently shown in males. Boredom susceptibility and disinhibition subscales of sensation seeking were consistently significantly correlated with aggression. The lack of significance and the small effect sizes indicate that other mechanisms are also at work in affecting aggression in young adult women. Finally, it is important to consider the type of sensation seeking in relation to aggression, as only boredom susceptibility and disinhibition were consistently replicated across samples.

  6. Hierarchical Structure of Heart Rate Variability in Humans

    NASA Astrophysics Data System (ADS)

    Gao, X. Z.; Ching, E. S. C.; Lin, D. C.

    2004-03-01

    We show a hierarchical structure (HS) of the She-Leveque form in the beat-to-beat RR intervals of heart rate variability (HRV) in humans. This structure, first found as an empirical law in turbulent fluid flows, implies further details in the HRV multifractal scaling. We tested HS using daytime RRi data from healthy subjects and heart diseased patients with congestive heart failure and found a universal law C(b) where b characterizes the multifractality of HRV and C is related to a co-dimension parameter of the most violent events in the fluctuation. The potential of diagnosis is discussed based on the characteristics of this finding. To model the HRV phenomenology, we propose a local-feedback-global-cascade (LFGC) model based on the She-Waymire (SW) cascade solution to the HS in fluid turbulence. This model extends from the previous work in that it integrates additive law multiplicatively into the cascade structure. It is an attempt to relate to the cardiovascular physiology which consists of numerous feedback controls that function primarily on the principle of additive law. In particular, the model is based on the same philosophy as the SW cascade that its multifractal dynamics consists of a singular and a modulating component. In the LFGC model, we introduce local feedback to model the dynamics of the modulating effect. The novelty of our model is to incorporate the cascade structure in the scheduling for the feedback control. This model also represents an alternative solution to the HS. We will present the simulation results by the LFGC model and discuss its implication in physiology terms.

  7. Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts.

    PubMed

    Iribarren, Carlos; Tolstykh, Irina V; Miller, Mary K; Sobel, Erica; Eisner, Mark D

    2012-12-01

    Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.

  8. Blood is thicker than water: the management of hyperviscosity in adults with cyanotic heart disease.

    PubMed

    DeFilippis, Andrew Paul; Law, Karen; Curtin, Sarah; Eckman, James R

    2007-01-01

    Complications of chronic hypoxia, including erythrocytosis, hyperviscosity, abnormalities of hemostasis, cerebral abscesses, stroke, and endocarditis, are among the most common consequences of cyanotic heart disease in adults. The compensatory erythrocytosis of cyanotic heart disease can become pathologic by causing an increase in blood viscosity, thereby decreasing perfusion and resulting in decreased total oxygen delivery and increased risk of venoocclusive/hyperviscosity syndrome. Treatment of hyperviscosity secondary to erythrocytosis in cyanotic heart disease is controversial. Data is limited but suggest that phlebotomy has the potential to increase exercise capacity, reduce the symptoms of hyperviscosity, and reduce the potential risk of vasoocclusive disease in selected patients with polycythemia secondary to cyanotic heart disease. Unfortunately, repeated phlebotomy can quickly lead to iron deficiency, resulting in microcytic erythrocytes that induce higher viscosity than normocytic erythrocytes, which may increase the risk for venoocclusive events. There are limited data on the use of hydroxyurea to suppress erythrocytosis in this patient population. The authors conclude that until newer approaches to decreasing hematocrit without inducing iron deficiency are shown to be safe and efficacious, phlebotomy should only be used for the acute resolution of hyperviscosity symptoms. In addition, the use of hydroxyurea should be limited to patients with recurrent symptoms.

  9. The Relationship Between Nurse Staffing and 30-Day Readmission for Adults With Heart Failure

    PubMed Central

    Giuliano, Karen K.; Danesh, Valerie; Funk, Marjorie

    2016-01-01

    OBJECTIVE The purpose of this study was to better understand the relationship between nurse staffing and 30-day excess readmission ratios for patients with heart failure in the top US adult cardiology and heart surgery hospitals. BACKGROUND Heart failure is the most common cause of hospitalization for patients older than 65 years and is the most frequent diagnosis associated with 30-day hospital readmission in the United States. METHODS A secondary data analysis was conducted using nurse staffing data from 661 cardiology and heart surgery hospitals from the 2013 US News & World Report “Best Hospitals” survey. These data were combined with excess readmission ratios from the Centers for Medicare & Medicaid Services Hospital Compare database from 2013. An independent-samples t test was used to compare staffing (low/high) and excess hospital readmissions rates. RESULTS A significant difference (P = .021) was found between the low nurse staffing group (n = 358) and the high nurse staffing group (n = 303). Hospitals with a lower nurse staffing index had a significantly higher excess readmission rate. CONCLUSION These data provide further support to the body of research showing a positive relationship between nurse staffing and positive outcomes. PMID:26579974

  10. Early life exposures and the occurrence and timing of heart disease among the older adult Puerto Rican population.

    PubMed

    McEnry, Mry; Palloni, Alberto

    2010-02-01

    Few studies have examined the effects of early life conditions on the timing of the onset of heart disease. We use the remarkable example of a representative sample of the population of older Puerto Ricans aged 60-74 who lived in the countryside during childhood (n = 1,438) to examine the effects ofseasonal exposures to poor nutrition and infectious diseases during late gestation on the timing of the onset and the probability of ever experiencing adult heart disease. Cox and log logistic hazard models controlling for childhood conditions (self-reported childhood health status and socioeconomic status [SES], rheumatic fever, and knee height) and adult risk factors (adult SES, obesity, smoking, exercise, and self-reported diabetes) showed that the risk of onset of heart disease was 65% higher among those born during high-exposure periods compared with unexposed individuals. However, there were no significant differences in median time of onset for those ever experiencing heart disease. As a comparison, we found that there were no significant seasonality effects for those who lived in urban areas during childhood. We conclude that early exposures in utero have important ramifications for adult heart disease among the older Puerto Rican population. We show, however, that while exposure is associated with the probability of ever experiencing adult heart disease, it is not associated with the timing of onset among those who do experience it.

  11. Age-related differences in biomedical and folk beliefs as causes for diabetes and heart disease among Mexican origin adults.

    PubMed

    Palmquist, Aunchalee E L; Wilkinson, Anna V; Sandoval, Juan-Miguel; Koehly, Laura M

    2012-08-01

    An understanding of health beliefs is key to creating culturally appropriate health services for Hispanic populations in the US. In this study we explore age-based variations in causal beliefs for heart disease and diabetes among Mexican origin adults in Houston, TX. This cross-sectional study included 497 adults of Mexican origin. Participants were asked to indicate the importance of biomedically defined and folk illness-related risk factors as causes for heart disease and diabetes. Biomedical risk factors were ranked highest as causes of diabetes and heart disease among all participants. Folk illness-related factors were ranked below biomedical factors as causes of heart disease among all age groups. Susto was ranked above the median as a risk factor for diabetes among older participants. Age-related differences in causal beliefs may have implications for designing culturally appropriate health services, such as tailored diabetes interventions for older Mexican origin adults.

  12. Epigenomic Landscape of Human Fetal Brain, Heart, and Liver*

    PubMed Central

    Yan, Liying; Guo, Hongshan; Hu, Boqiang; Li, Rong; Yong, Jun; Zhao, Yangyu; Zhi, Xu; Fan, Xiaoying; Guo, Fan; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Wang, Yan; Wen, Lu; Qiao, Jie; Tang, Fuchou

    2016-01-01

    The epigenetic regulation of spatiotemporal gene expression is crucial for human development. Here, we present whole-genome chromatin immunoprecipitation followed by high throughput DNA sequencing (ChIP-seq) analyses of a wide variety of histone markers in the brain, heart, and liver of early human embryos shortly after their formation. We identified 40,181 active enhancers, with a large portion showing tissue-specific and developmental stage-specific patterns, pointing to their roles in controlling the ordered spatiotemporal expression of the developmental genes in early human embryos. Moreover, using sequential ChIP-seq, we showed that all three organs have hundreds to thousands of bivalent domains that are marked by both H3K4me3 and H3K27me3, probably to keep the progenitor cells in these organs ready for immediate differentiation into diverse cell types during subsequent developmental processes. Our work illustrates the potentially critical roles of tissue-specific and developmental stage-specific epigenomes in regulating the spatiotemporal expression of developmental genes during early human embryonic development. PMID:26719341

  13. Epigenomic Landscape of Human Fetal Brain, Heart, and Liver.

    PubMed

    Yan, Liying; Guo, Hongshan; Hu, Boqiang; Li, Rong; Yong, Jun; Zhao, Yangyu; Zhi, Xu; Fan, Xiaoying; Guo, Fan; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Wang, Yan; Wen, Lu; Qiao, Jie; Tang, Fuchou

    2016-02-26

    The epigenetic regulation of spatiotemporal gene expression is crucial for human development. Here, we present whole-genome chromatin immunoprecipitation followed by high throughput DNA sequencing (ChIP-seq) analyses of a wide variety of histone markers in the brain, heart, and liver of early human embryos shortly after their formation. We identified 40,181 active enhancers, with a large portion showing tissue-specific and developmental stage-specific patterns, pointing to their roles in controlling the ordered spatiotemporal expression of the developmental genes in early human embryos. Moreover, using sequential ChIP-seq, we showed that all three organs have hundreds to thousands of bivalent domains that are marked by both H3K4me3 and H3K27me3, probably to keep the progenitor cells in these organs ready for immediate differentiation into diverse cell types during subsequent developmental processes. Our work illustrates the potentially critical roles of tissue-specific and developmental stage-specific epigenomes in regulating the spatiotemporal expression of developmental genes during early human embryonic development.

  14. Statistical Properties of the Interbeat Interval Cascade in Human Hearts

    NASA Astrophysics Data System (ADS)

    Ghasemi, Fatemeh; Peinke, J.; Reza Rahimi Tabar, M.; Sahimi, Muhammad

    Statistical properties of interbeat intervals cascade in human hearts are evaluated by considering the joint probability distribution P (Δx2, τ2 Δx1, τ1) for two interbeat increments Δx1 and Δx2 of different time scales τ1 and τ2. We present evidence that the conditional probability distribution P (Δx2, τ2 | Δx1, τ1) may be described by a Chapman-Kolmogorov equation. The corresponding Kramers-Moyal (KM) coefficients are evaluated. The analysis indicates that while the first and second KM coefficients take on well-defined and significant values, the higher-order coefficients in the KM expansion are small. As a result, the joint probability distributions of the increments in the interbeat intervals are described by a Fokker-Planck equation, with the first two KM coefficients acting as the drift and diffusion coefficients. The method provides a novel technique for distinguishing two classes of subjects, namely, healthy ones and those with congestive heart failure, in terms of the drift and diffusion coefficients which behave differently for two classes of the subjects.

  15. Human heart rate variability relation is unchanged during motion sickness

    NASA Technical Reports Server (NTRS)

    Mullen, T. J.; Berger, R. D.; Oman, C. M.; Cohen, R. J.

    1998-01-01

    In a study of 18 human subjects, we applied a new technique, estimation of the transfer function between instantaneous lung volume (ILV) and instantaneous heart rate (HR), to assess autonomic activity during motion sickness. Two control recordings of ILV and electrocardiogram (ECG) were made prior to the development of motion sickness. During the first, subjects were seated motionless, and during the second they were seated rotating sinusoidally about an earth vertical axis. Subjects then wore prism goggles that reverse the left-right visual field and performed manual tasks until they developed moderate motion sickness. Finally, ILV and ECG were recorded while subjects maintained a relatively constant level of sickness by intermittent eye closure during rotation with the goggles. Based on analyses of ILV to HR transfer functions from the three conditions, we were unable to demonstrate a change in autonomic control of heart rate due to rotation alone or due to motion sickness. These findings do not support the notion that moderate motion sickness is manifested as a generalized autonomic response.

  16. Latent inhibition in human adults without masking.

    PubMed

    Escobar, Martha; Arcediano, Francisco; Miller, Ralph R

    2003-09-01

    Latent inhibition refers to attenuated responding to Cue X observed when the X-outcome pairings are preceded by X-alone presentations. It has proven difficult to obtain in human adults unless the preexposure (X-alone) presentations are embedded within a masking (i.e., distracting) task. The authors hypothesized that the difficulty in obtaining latent inhibition with unmasked tasks is related to the usual training procedures, in which the preexposure and conditioning experiences are separated by a set of instructions. Experiment 1 reports latent inhibition without masking in a task in which preexposure and conditioning occur without interruption. Experiments 2 and 3 demonstrate that this attenuation in responding to target Cue X does not pass a summation test for conditioned inhibition and is context specific, thereby confirming that it is latent inhibition. Experiments 3 and 4 confirm that introducing instructions between preexposure and conditioning disrupts latent inhibition.

  17. What is the Best Measure of Daytime Sleepiness in Adults with Heart Failure?

    PubMed Central

    Riegel, Barbara; Hanlon, Alexandra L.; Zhang, Xuemei; Fleck, Desiree; Sayers, Steven L.; Goldberg, Lee R.; Weintraub, William S.

    2014-01-01

    Purpose To identify the best screening measure of daytime sleepiness in adults with heart failure (HF). Data sources 280 adults with HF completed the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, and a single Likert item measuring daytime sleepiness. The sensitivity and specificity of these self-report measures were assessed in relation to a measure of daytime dysfunction from poor sleep quality. Conclusions Only 16% of the sample reported significant daytime dysfunction due to poor sleep quality. Those reporting daytime dysfunction were likely to be younger (p<0.001), to be unmarried (p=0.002), to have New York Heart Association (NYHA) functional class IV HF (p=0.015), and to report low income (p=0.006) and fewer hours of sleep (p=0.015). The measure of daytime sleepiness that was most sensitive to daytime dysfunction was a single Likert item measured on a 10-point (1–10) scale. Patients with a score ≥ 4 were 2.4 times more likely to have daytime dysfunction than those with a score <4. Implications for practice Complaints of daytime dysfunction due to poor sleep are not common in adults with HF. Routine use of a single question about daytime sleepiness can help nurse practitioners to identify those HF patients with significant sleep issues that may require further screening. PMID:24170569

  18. Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-aged and Older Adults

    PubMed Central

    Hvidtfeldt, Ulla A.; Tolstrup, Janne S.; Jakobsen, Marianne U.; Heitmann, Berit L.; Grønbæk, Morten; O’Reilly, Eilis; Bälter, Katarina; Goldbourt, Uri; Hallmans, Göran; Knekt, Paul; Liu, Simin; Pereira, Mark; Pietinen, Pirjo; Spiegelman, Donna; Stevens, June; Virtamo, Jarmo; Willett, Walter C.; Rimm, Eric B.; Ascherio, Alberto

    2011-01-01

    Background Light-to-moderate alcohol consumption is associated with a reduced risk of coronary heart disease (CHD). This protective effect of alcohol, however, may be confined to middle-aged or older individuals. CHD Incidence is low in men younger than 40 and in women younger than 50 years and for this reason, study cohorts rarely have the power to investigate effects of alcohol on CHD risk in younger adults. This study examined whether the beneficial effect of alcohol on CHD depends on age. Methods and results A pooled analysis of eight prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline. Average daily alcohol intake was assessed at baseline using a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups: hazard ratios among moderately drinking men (5.0–29.9 g/day) aged 39–50, 50–59, and 60+ years were 0.58 (95% C.I. 0.36 to 0.93), 0.72 (95% C.I. 0.60–0.86), and 0.85 (95% C.I. 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference (IRD) between abstainers and moderate consumers in younger adults (IRD=45 per 100,000; 90% C.I. 8 to 84), than in middle-aged (IRD=64 per 100,000; 90% C.I. 24 to 102) and older adults (IRD=89 per 100,000; 90% C.I. 44 to 140). Similar results were observed in women. Conclusions Alcohol is also associated with a decreased risk of CHD in younger adults; however, the absolute risk was small compared with middle-aged and older adults. PMID:20351238

  19. Embryonic even skipped-Dependent Muscle and Heart Cell Fates Are Required for Normal Adult Activity, Heart Function, and Lifespan

    PubMed Central

    Fujioka, Miki; Wessells, Robert J.; Han, Zhe; Liu, Jiandong; Fitzgerald, Kerry; Yusibova, Galina L.; Zamora, Monica; Ruiz-Lozano, Pilar; Bodmer, Rolf; Jaynes, James B.

    2009-01-01

    The Drosophila pair-rule gene even skipped (eve) is required for embryonic segmentation and later in specific cell lineages in both the nervous system and the mesoderm. We previously generated eve mesoderm-specific mutants by combining an eve null mutant with a rescuing transgene that includes the entire locus, but with the mesodermal enhancer removed. This allowed us to analyze in detail the defects that result from a precisely targeted elimination of mesodermal eve expression in the context of an otherwise normal embryo. Absence of mesodermal eve causes a highly selective loss of the entire eve-expressing lineage in this germ layer, including those progeny that do not continue to express eve, suggesting that mesodermal eve precursor specification is not implemented. Despite the resulting absence of a subset of muscles and pericardial cells, mesoderm-specific eve mutants survive to fertile adulthood, providing an opportunity to examine the effects of these developmental abnormalities on adult fitness and heart function. We find that in these mutants, flying ability, myocardial performance under normal and stressed conditions, and lifespan are severely reduced. These data imply a nonautonomous role of the affected pericardial cells and body wall muscles in developing and/or maintaining cardiac performance and possibly other functions contributing to normal lifespan. Given the similarities of molecular-genetic control between Drosophila and vertebrates, these findings suggest that peri/epicardial influences may well be important for proper myocardial function. PMID:16239588

  20. Healthy Heart Quizzes

    MedlinePlus

    ... Cholesterol Tools & Resources Congenital Defects Children & Adults About Congenital Heart Defects The Impact of Congenital Heart Defects Understand Your Risk for Congenital Heart Defects Symptoms & ...

  1. Astrocitary niches in human adult medulla oblongata.

    PubMed

    Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

    2013-04-01

    Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density.

  2. A Simple Dissection Method for the Conduction System of the Human Heart

    ERIC Educational Resources Information Center

    Yanagawa, Nariaki; Nakajima, Yuji

    2009-01-01

    A simple dissection guide for the conduction system of the human heart is shown. The atrioventricular (AV) node, AV bundle, and right bundle branch were identified in a formaldehyde-fixed human heart. The sinu-atrial (SA) node could not be found, but the region in which SA node was contained was identified using the SA nodal artery. Gross…

  3. Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

    NASA Technical Reports Server (NTRS)

    Alexander, Tiffaney Miller

    2017-01-01

    Research results have shown that more than half of aviation, aerospace and aeronautics mishaps incidents are attributed to human error. As a part of Quality within space exploration ground processing operations, the identification and or classification of underlying contributors and causes of human error must be identified, in order to manage human error.This presentation will provide a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

  4. Have you got any cholesterol? Adults' views of human nutrition

    NASA Astrophysics Data System (ADS)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  5. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation.

    PubMed

    Hirt, Marc N; Boeddinghaus, Jasper; Mitchell, Alice; Schaaf, Sebastian; Börnchen, Christian; Müller, Christian; Schulz, Herbert; Hubner, Norbert; Stenzig, Justus; Stoehr, Andrea; Neuber, Christiane; Eder, Alexandra; Luther, Pradeep K; Hansen, Arne; Eschenhagen, Thomas

    2014-09-01

    Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

  6. Encephalitis-Associated Human Metapneumovirus Pneumonia in Adult, Australia.

    PubMed

    Fok, Anthony; Mateevici, Cristina; Lin, Belinda; Chandra, Ronil V; Chong, Victor H T

    2015-11-01

    Human metapneumovirus pneumonia, most commonly found in children, was diagnosed in an adult with encephalitis. This case suggests that testing for human metapneumovirus RNA in nasopharyngeal aspirate and cerebrospinal fluid samples should be considered in adults with encephalitis who have a preceding respiratory infection.

  7. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    ERIC Educational Resources Information Center

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  8. Toxoplasma gondii Myocarditis after Adult Heart Transplantation: Successful Prophylaxis with Pyrimethamine

    PubMed Central

    Strabelli, Tania Mara V.; Siciliano, Rinaldo Focaccia; Vidal Campos, Silvia; Bianchi Castelli, Jussara; Bacal, Fernando; Bocchi, Edimar A.; Uip, David E.

    2012-01-01

    Toxoplasma gondii primary infection/reactivation after solid organ transplantation is a serious complication, due to the high mortality rate following disseminated disease. We performed a retrospective study of all cases of T. gondii infections in 436 adult patients who had received an orthotopic cardiac transplant at our Institution from May 1968 to January 2011. Six patients (1.3%) developed T. gondii infection/reactivation in the post-operative period. All infections/reactivations occurred before 1996, when no standardized toxoplasmosis prophylactic regimen or co-trimoxazole prophylaxis was used. Starting with the 112th heart transplant, oral pyrimethamine 75 mg/day was used for seronegative transplant recipients whose donors were seropositive or unknown. Two patients (33.3%) presented with disseminated toxoplasmosis infection, and all patients (100%) had myocarditis. Five patients (83.3%) were seronegative before transplant and one patient did not have pre-transplant serology available. Median time for infection onset was 131 days following transplantation. Three patients (50%) died due to toxoplasmosis infection. After 1996, we did not observe any additional cases of T. gondii infection/reactivation. In conclusion, toxoplasmosis in heart allographs was more frequent among seronegative heart recipients, and oral pyrimethamine was highly effective for the prevention of T. gondii infection in this population. PMID:23209479

  9. Extracorporeal life support in lung and heart-lung transplantation for pulmonary hypertension in adults.

    PubMed

    Kortchinsky, Talna; Mussot, Sacha; Rezaiguia, Saïda; Artiguenave, Margaux; Fadel, Elie; Stephan, François

    2016-09-01

    After bilateral lung and heart-lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life-threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30-day and 1-year survival rates in patients managed with vs without post-operative venoarterial ECLS in 2008-2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart-lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0-6] hours after surgery completion and for a median of 3.0 [2.0-8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart-lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding.

  10. Neonatal Diesel Exhaust Particulate Exposure Does Not Predispose Mice to Adult Cardiac Hypertrophy or Heart Failure

    PubMed Central

    Liu, Yonggang; Weldy, Chad S.; Chin, Michael T.

    2016-01-01

    Background: We have previously reported that in utero and early life exposure to diesel exhaust particulates predisposes mice to adult heart failure, and that in utero exposure alone is sufficient to confer this predisposition. This follow up study addresses whether neonatal exposure alone can also confer this predisposition. Methods: Newborn male C57BL/6 mice were exposed to diesel exhaust (DE) particulates immediately after birth until weaning at 21 days of age, whereupon they were transferred to filtered air (FA) conditions. At the age of 12 weeks, transverse aortic constriction (TAC) was performed followed by weekly echocardiography for three weeks. After the last echocardiogram, mice were euthanized for organ harvest, gravimetry and histology. Results: Neonatal exposure to DE particulates did not increase susceptibility to cardiac hypertrophy or heart failure after TAC when compared to FA exposed controls (ventricular weight/body weight ratio 7.505 vs. 7.517 mg/g, p = Not Significant (NS)). The left ventricular ejection fraction after TAC was similar between groups at one week, two weeks, and three weeks after procedure. Histological analysis showed no difference in the degree of cardiac hypertrophy or fibrosis. Conclusions: Neonatal exposure to DE particulates does not predispose mice to TAC-induced cardiac hypertrophy and heart failure in adulthood, in contrast to previously published results showing susceptibility due to in utero exposure. PMID:27886143

  11. Evaluation of right ventricular function in adults with congenital heart defects.

    PubMed

    Bussadori, Claudio; Di Salvo, Giovanni; Pluchinotta, Francesca R; Piazza, Luciane; Gaio, Giampiero; Russo, Maria Giovanna; Carminati, Mario

    2015-01-01

    The right ventricle (RV) is of lesser importance in acquired heart disease, but its role is of increasing importance in congenital heart disease (CHD). Despite major progress being made, precise measurements of the RV are challenging because of its peculiar anatomical structure that is not adaptable to any planar geometrical assumption. This is particularly true in adult patients with CHD where the RV shape eludes any standardization, it may assume various morphologies, and its modality of contraction depends on previous surgical treatment and/or pathophysiological conditions. However, reliable and repeatable quantification of RV dimensions and function for these patients are essential to provide appropriate timing for intervention to optimize outcomes. In this population, echocardiographic evaluation should not be limited to an observational and subjective functional assessment of the RV but must provide quantitative values repeatable and clinically reliable to help the decision-making process. The aim of this review was to discuss the echocardiographic approach to the RV in adult patients with CHD in general and in specific cases of pressure or volume overload.

  12. Adult human brain cell culture for neuroscience research.

    PubMed

    Gibbons, Hannah M; Dragunow, Mike

    2010-06-01

    Studies of the brain have progressed enormously through the use of in vivo and in vitro non-human models. However, it is unlikely such studies alone will unravel the complexities of the human brain and so far no neuroprotective treatment developed in animals has worked in humans. In this review we discuss the use of adult human brain cell culture methods in brain research to unravel the biology of the normal and diseased human brain. The advantages of using adult human brain cells as tools to study human brain function from both historical and future perspectives are discussed. In particular, studies using dissociated cultures of adult human microglia, astrocytes, oligodendrocytes and neurons are described and the applications of these types of study are evaluated. Alternative sources of human brain cells such as adult neural stem cells, induced pluripotent stem cells and slice cultures of adult human brain tissue are also reviewed. These adult human brain cell culture methods could benefit basic research and more importantly, facilitate the translation of basic neuroscience research to the clinic for the treatment of brain disorders.

  13. Structure and function relationship of human heart from DENSE MRI

    NASA Astrophysics Data System (ADS)

    Moghaddam, Abbas N.; Gharib, Morteza

    2007-03-01

    The study here, suggests a macroscopic structure for the Left Ventricle (LV), based on the heart kinematics which is obtained through imaging. The measurement of the heart muscle deformation using the Displacement ENcoding with Stimulated Echoes (DENSE) MRI, which describes the heart kinematics in the Lagrangian frame work, is used to determine the high resolution patterns of true myocardial strain. Subsequently, the tangential Shortening Index (SI) and the thickening of the LV wall are calculated for each data point. Considering the heart as a positive-displacement pump, the contribution of each segment of LV in the heart function, can be determined by the SI and thickening of the wall in the same portion. Hence the SI isosurfaces show the extent and spatial distribution of the heart activity and reveals its macro structure. The structure and function of the heart are, therefore, related which in turn results in a macroscopic model for the LV. In particular, it was observed that the heart functionality is not uniformly distributed in the LV, and the regions with greater effect on the pumping process, form a band which wraps around the heart. These results, which are supported by the established histological evidence, may be considered as a landmark in connecting the structure and function of the heart through imaging. Furthermore, the compatibility of this model with microscopic observations about the fiber direction is investigated. This method may be used for planning as well as post evaluation of the ventriculoplasty.

  14. The dynamics of adult neurogenesis in human hippocampus

    PubMed Central

    Ihunwo, Amadi O.; Tembo, Lackson H.; Dzamalala, Charles

    2016-01-01

    The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis in humans and makes comparison to animal data. PMID:28197172

  15. Outpatient clinics for adults with congenital heart disease: increasing workload and evolving patterns of referral

    PubMed Central

    Gatzoulis, M; Hechter, S; Siu, S; Webb, G

    1999-01-01

    Objective—To examine the evolving role of specialised outpatient services for adult patients with congenital heart disease.
Design—A retrospective analysis of all patients attending the Toronto Congenital Cardiac Centre for Adults over three corresponding three month periods in 1987, 1992, and 1997.
Setting—A tertiary referral centre.
Main outcome measures—Patient demographics, residence, medical and surgical history, type and source of referral, and investigations performed.
Results—In all, 570 patients were seen at the clinic during these three periods. There was a 44% and a 269% increase in workload between 1987 to 1992 and 1992 to 1997, respectively. There was a steady fall in mean age of patients seen at the clinic with time (38.5, 33.6, and 31.7 years in 1987, 1992, and 1997, respectively, p < 0.001). New referrals from community cardiologists and family physicians increased more in relative terms than did referrals from the Hospital for Sick Children, Toronto (6.7%, 15%, and 37.5%, p = 0.02). There was a steady increase in patients with previous reparative surgery (48.9%, 59.2%, and 69.2%, p < 0.002). The proportion of patients with previous reoperations also increased (2.3%, 10%, and 9.2%, p < 0.01). Echocardiography remained the predominant method of diagnosis. The diagnostic mix did not change with time.
Conclusions—Over the past 10 years there has been a large increase in adults with congenital heart disease requiring and seeking specialised care in a tertiary health centre, with a concomitant evolution of referral patterns. These data may be helpful in planning of similar paediatric and adult cardiac services for this expanding population.

 Keywords: congenital heart disease;  ambulatory clinics PMID:10220546

  16. Cardioprotective stress response in the human fetal heart

    PubMed Central

    Coles, John G.; Boscarino, Cathy; Takahashi, Mark; Grant, Diane; Chang, Astra; Ritter, Julia; Dai, Xiaojing; Du, Changqing; Musso, Gabriel; Yamabi, Hideaki; Goncalves, Jason; Kumar, Ashu Sunny; Woodgett, James; Lu, Huanzhang; Hannigan, Gregory

    2016-01-01

    Objective We propose that the fetal heart is highly resilient to hypoxic stress. Our objective was to elucidate the human fetal gene expression profile in response to simulated ischemia and reperfusion to identify molecular targets that account for the innate cardioprotection exhibited by the fetal phenotype. Methods Primary cultures of human fetal cardiac myocytes (gestational age, 15–20 weeks) were exposed to simulated ischemia and reperfusion in vitro by using a simulated ischemic buffer under anoxic conditions. Total RNA from treated and baseline cells were isolated, reverse transcribed, and labeled with Cy3 or Cy5 and hybridized to a human cDNA microarray for expression analysis. This analysis revealed a highly significant (false discovery rate, <3%) suppression of interleukin 6 transcript levels during the reperfusion phase confirmed by means of quantitative polymerase chain reaction (0.25 ± 0.11-fold). Interleukin 6 signaling during ischemia and reperfusion was assessed at the protein expression level by means of Western measurements of interleukin 6 receptor, the signaling subunit of the interleukin 6 receptor complex (gp130), and signal transducer of activated transcription 3. Posttranslational changes in the protein kinase B signaling pathway were determined on the basis of the phosphorylation status of protein kinase B, mitogen-activated protein kinase, and glycogen synthase kinase 3β. The effect of suppression of a prohypertrophic kinase, integrin-linked kinase, with short-interfering RNA was determined in an ischemia and reperfusion–stressed neonatal rat cardiac myocyte model. Endogenous secretion of interleukin 6 protein in culture supernatants was measured by enzyme-linked immunosorbent assay. Results Human fetal cardiac myocytes exhibited a significantly lower rate of apoptosis induction during ischemia and reperfusion and after exposure to staurosporine and recombinant interleukin 6 compared with that observed in neonatal rat cardiac myocytes

  17. Proteome-wide protein concentrations in the human heart.

    PubMed

    Aye, Thin Thin; Scholten, Arjen; Taouatas, Nadia; Varro, Andras; Van Veen, Toon A B; Vos, Marc A; Heck, Albert J R

    2010-10-01

    The largest component of the human heart, the left ventricle (LV), plays a major role in delivering blood throughout the body. Therefore, an in-depth detailed quantitative proteome analysis of the human LV is a valuable resource. For this purpose, a multifaceted proteomics approach combining differential sample fractionations (gel, strong cation exchange (SCX)), enzymatic digestions (trypsin, chymotrypsin, LysN), and peptide fragmentation techniques (CID and ETcaD) was used to enhance protein sequence coverage, identification confidence and quantitative abundance determination. Using stringent criteria, 3584 distinct proteins could be identified from the latest well-annotated Swissprot database (23,000 entries). Commutatively, the over 130,000 identified MS/MS spectra were used to assess concentrations of each identified LV protein through a combination of spectral counting methods. Among the most concentrated proteins, many currently used biomarkers for detection of myocardial infarction reside. These cardiac leakage markers have a good diagnostic power, but their prognostic potential seems limited. Discovery of markers that represent etiological determinants of cardiac disease require a shift of focus towards the signaling proteome. Therefore, a protein-class centered quantitative analysis of kinases, phosphatases and GTPases was adopted. These comparative analyses revealed many cardiac involved kinases (PKA, CaMKII, ERK) to reside among the most abundant signaling proteins, and also to mediate many observed in vivo phosphorylation sites. The abundance chart of signaling proteins may assist in identifying novel functional pathways, for instance through the abundant, but relatively little known, kinases STK38L and OXSR1. The obtained quantitative protein library of the human left ventricle is a valuable resource to isolate signaling based, putative biomarkers with concentrations likely to be detectable in plasma.

  18. Lung function and heart disease in American Indian adults with high frequency of metabolic abnormalities (from the Strong Heart Study).

    PubMed

    Yeh, Fawn; Dixon, Anne E; Best, Lyle G; Marion, Susan M; Lee, Elisa T; Ali, Tauqeer; Yeh, Jeunliang; Rhoades, Everett R; Howard, Barbara V; Devereux, Richard B

    2014-07-15

    The associations of pulmonary function with cardiovascular disease (CVD) independent of diabetes mellitus (DM) and metabolic syndrome have not been examined in a population-based setting. We examined prevalence and incidence CVD in relation to lower pulmonary function in the Strong Heart Study second examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung disease (mean age 60 years). Lung function was assessed by standard spirometry. Participants with metabolic syndrome or DM with or without CVD had lower pulmonary function than participants without these conditions after adjustment for hypertension, age, gender, abdominal obesity, smoking, physical activity index, and study field center. CVD participants with DM had significantly lower forced vital capacity than participants with CVD alone. Significant associations were observed between reduced pulmonary function, preclinical CVD, and prevalent CVD after adjustment for multiple CVD risk factors. During follow-up (median 13.3 years), pulmonary function did not predict CVD incidence, it predicted CVD mortality. Among 3,225 participants, 412 (298 without baseline CVD) died from CVD by the end of 2008. In models adjusted for multiple CVD risk factors, DM, metabolic syndrome, and baseline CVD, compared with highest quartile of lung function, lower lung function predicted CVD mortality (relative risk up to 1.5, 95% confidence interval 1.1 to 2.0, p<0.05). In conclusion, a population with a high prevalence of DM and metabolic syndrome and lower lung function was independently associated with prevalent clinical and preclinical CVD, and its impairment predicted CVD mortality. Additional research is needed to identify mechanisms linking metabolic abnormalities, low lung function, and CVD.

  19. Muscarinic M3 receptor subtype gene expression in the human heart.

    PubMed

    Hellgren, I; Mustafa, A; Riazi, M; Suliman, I; Sylvén, C; Adem, A

    2000-01-20

    The heart is an important target organ for cholinergic function. In this study, muscarinic receptor subtype(s) in the human heart were determined using reverse transcription-polymerase chain reaction. Our results demonstrated muscarinic receptor M2 and M3 subtype RNA in left/right atria/ventricles of donor hearts. Receptor autoradiography analysis using selective muscarinic ligands indicated an absence of M1 receptor subtype in the human heart. The level of muscarinic receptor binding in atria was two to three times greater than in ventricles. Our results suggest that muscarinic receptors in the human heart are of the M2 and M3 subtypes. This is the first report of M3 receptors in the human myocardium.

  20. Inhibitors of human heart chymase based on a peptide library.

    PubMed Central

    Bastos, M; Maeji, N J; Abeles, R H

    1995-01-01

    We have synthesized two sets of noncleavable peptide-inhibitor libraries to map the S and S' subsites of human heart chymase. Human heart chymase is a chymotrypsin-like enzyme that converts angiotensin I to angiotensin II. The first library consists of peptides with 3-fluorobenzylpyruvamides in the P1 position. (Amino acid residues of substrates numbered P1, P2, etc., are toward the N-terminal direction, and P'1, P'2, etc., are toward the C-terminal direction from the scissile bond.) The P'1 and P'2 positions were varied to contain each one of the 20 naturally occurring amino acids and P'3 was kept constant as an arginine. The second library consists of peptides with phenylalanine keto-amides at P1, glycine in P'1, and benzyloxycarbonyl (Z)-isoleucine in P4. The P2 and P3 positions were varied to contain each of the naturally occurring amino acids, except for cysteine and methionine. The peptides of both libraries are attached to a solid support (pins). The peptides are evaluated by immersing the pins in a solution of the target enzyme and evaluating the amount of enzyme absorbed. The pins with the best inhibitors will absorb most enzyme. The libraries select the best and worst inhibitors within each group of peptides and provide an approximate ranking of the remaining peptides according to Ki. Through this library, we determined that Z-Ile-Glu-Pro-Phe-CO2Me and (F)-Phe-CO-Glu-Asp-ArgOMe should be the best inhibitors of chymase in this collection of peptide inhibitors. We synthesized the peptides and found Ki values were 1 nM and 1 microM, respectively. The corresponding Ki values for chymotrypsin were 10 nM and 100 microM. The use of libraries of inhibitors has advantages over the classical method of synthesis of potential inhibitors in solution: the libraries are reusable, the same libraries can be used with a variety of different serine proteases, and the method allows the screening of hundreds of compounds in short periods of time. Images Fig. 1 PMID:7624313

  1. Trends in Heart Disease Mortality among Mississippi Adults over Three Decades, 1980-2013

    PubMed Central

    2016-01-01

    Heart disease (HD) remains the leading cause of death among Mississippians; however, despite the importance of the condition, trends in HD mortality in Mississippi have not been adequately explored. This study examined trends in HD mortality among adults in Mississippi from 1980 through 2013 and further examined these trends by race and sex. We used data from Mississippi Vital Statistics (1980–2013) to calculate age-adjusted HD mortality rates for Mississippians age 25 or older. Cases were identified using underlying cause of death codes from the International Classification of Diseases, Ninth Revision (ICD-9: 390–398, 402, 404–429) and Tenth Revision (ICD-10), including I00-I09, I11, I13, and I20-I51. Joinpoint software was used to calculate the average annual percent change in HD mortality rates for the overall population and by race and sex. Overall, the age-adjusted HD mortality rate among Mississippi adults decreased by 36.5% between 1980 and 2013, with an average annual percent change of -1.60% (95% CI -2.00 to -1.30). This trend varied across subgroups: HD mortality rates experienced an average annual change of -1.34% (95% CI -1.98 to -0.69) for black adults; -1.60% (95% CI -1.74 to -1.46) for white adults; -1.30% (95% CI -1.50 to -1.10) for all women, and -1.90% (95% -2.20 to -1.50) for all men. From 1980 to 2013, there was a continuous decrease in HD mortality among adult Mississippians. However, the magnitude of this reduction differed by race and sex. PMID:27518895

  2. Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

    PubMed Central

    Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

  3. Adult human neurogenesis: from microscopy to magnetic resonance imaging.

    PubMed

    Sierra, Amanda; Encinas, Juan M; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

  4. Time-lapse imaging of human heart motion with switched array UWB radar.

    PubMed

    Brovoll, Sverre; Berger, Tor; Paichard, Yoann; Aardal, Øyvind; Lande, Tor Sverre; Hamran, Svein-Erik

    2014-10-01

    Radar systems for detection of human heartbeats have mostly been single-channel systems with limited spatial resolution. In this paper, a radar system for ultra-wideband (UWB) imaging of the human heart is presented. To make the radar waves penetrate the human tissue the antenna is placed very close to the body. The antenna is an array with eight elements, and an antenna switch system connects the radar to the individual elements in sequence to form an image. Successive images are used to build up time-lapse movies of the beating heart. Measurements on a human test subject are presented and the heart motion is estimated at different locations inside the body. The movies show rhythmic motion consistent with the beating heart, and the location and shape of the reflections correspond well with the expected response form the heart wall. The spatial dependent heart motion is compared to ECG recordings, and it is confirmed that heartbeat modulations are seen in the radar data. This work shows that radar imaging of the human heart may provide valuable information on the mechanical movement of the heart.

  5. Characteristic parameters of electromagnetic signals from a human heart system

    NASA Astrophysics Data System (ADS)

    Liu, Xin-Yuan; Pei, Liu-Qing; Wang, Yin; Zhang, Su-Ming; Gao, Hong-Lei; Dai, Yuan-Dong

    2011-04-01

    The electromagnetic field of a human heart system is a bioelectromagnetic field. Electrocardiography (ECG) and magnetocardiography (MCG) are both carriers of electromagnetic information about the cardiac system, and they are nonstationary signals. In this study, ECG and MCG data from healthy subjects are acquired; the MCG data are captured using a high-Tc radio frequency superconducting quantum interference device (HTc rf SQUIDs) and the QRS complexes in these data are analysed by the evolutionary spectrum analysis method. The results show that the quality factor Q and the central frequency fz of the QRS complex evolutionary spectrum are the characteristic parameters (CHPs) of ECG and MCG in the time—frequency domain. The confidence intervals of the mean values of the CHPs are estimated by the Student t distribution method in mathematical statistics. We believe that there are threshold ranges of the mean values of Q and fz for healthy subjects. We have postulated the following criterion: if the mean values of CHPs are in the proper ranges, the cardiac system is in a normal condition and it possesses the capability of homeostasis. In contrast, if the mean values of the CHPs do not lie in the proper ranges, the homeostasis of the cardiac system is lacking and some cardiac disease may follow. The results and procedure of MCG CHPs in the study afford a technological route for the application of HTc rf SQUIDs in cardiology.

  6. Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure

    PubMed Central

    Lou, Qing; Fedorov, Vadim V.; Glukhov, Alexey V.; Moazami, Nader; Fast, Vladimir G.; Efimov, Igor R.

    2011-01-01

    Background Excitation-contraction (EC) coupling is altered in the end-stage heart failure (HF). However, spatial heterogeneity of this remodeling has not been established at the tissue level in failing human heart. The objective is to study functional remodeling of EC coupling and calcium handling in failing and nonfailing human hearts. Methods and Results We simultaneously optically mapped action potentials (AP) and calcium transients (CaT) in coronary-perfused left ventricular wedge preparations from nonfailing (n = 6) and failing (n = 5) human hearts. Our major findings are: (1) CaT duration minus AP duration was longer at sub-endocardium in failing compared to nonfailing hearts during bradycardia (40 beats/min). (2) The transmural gradient of CaT duration was significantly smaller in failing hearts compared with nonfailing hearts at fast pacing rates (100 beats/min). (3) CaT in failing hearts had a flattened plateau at the midmyocardium; and exhibited a “two-component” slow rise at sub-endocardium in three failing hearts. (4) CaT relaxation was slower at sub-endocardium than that at sub-epicardium in both groups. Protein expression of sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) was lower at sub-endocardium than that at sub-epicardium in both nonfailing and failing hearts. SERCA2a protein expression at sub-endocardium was lower in hearts with ischemic cardiomyopathy compared with nonischemic cardiomyopathy. Conclusions For the first time, we present direct experimental evidence of transmural heterogeneity of EC coupling and calcium handling in human hearts. End-stage HF is associated with the heterogeneous remodeling of EC coupling and calcium handling. PMID:21502574

  7. In Utero Caffeine Exposure Induces Transgenerational Effects on the Adult Heart

    PubMed Central

    Fang, Xiefan; Poulsen, Ryan R.; Rivkees, Scott A.; Wendler, Christopher C.

    2016-01-01

    Each year millions of pregnant woman are exposed to caffeine, which acts to antagonize adenosine action. The long-term consequences of this exposure on the developing fetus are largely unknown, although in animal models we have found adverse effects on cardiac function. To assess if these effects are transmitted transgenerationally, we exposed pregnant mice to caffeine equivalent to 2–4 cups of coffee at two embryonic stages. Embryos (F1 generation) exposed to caffeine early from embryonic (E) day 6.5–9.5 developed a phenotype similar to dilated cardiomyopathy by 1 year of age. Embryos exposed to caffeine later (E10.5–13.5) were not affected. We next examined the F2 generation and F3 generation of mice exposed to caffeine from E10.5–13.5, as this coincides with germ cell development. These F2 generation adult mice developed a cardiac phenotype similar to hypertrophic cardiomyopathy. The F3 generation exhibited morphological changes in adult hearts, including increased mass. This report shows that in utero caffeine exposure has long-term effects into adulthood and that prenatal caffeine exposure can exert adverse transgenerational effects on adult cardiac function. PMID:27677355

  8. Radiologic evaluation of coronary artery disease in adults with congenital heart disease.

    PubMed

    Valenzuela, David M; Ordovas, Karen G

    2016-01-01

    Improved surgical and medical therapy have prolonged survival in patients with congenital heart disease (CHD) such that general medical conditions like coronary artery disease (CAD) are now the main determinants of mortality. A summary of the association of CAD with CHD, as well as a discussion of the radiologic evaluation of the coronary arteries in adults with CHD is described herein. Cross sectional imaging to evaluate CAD in adults with CHD should follow the same appropriateness criteria as gender and aged matched patients without CHD. Coronary CT imaging may be particularly valuable in evaluating the coronary arteries in this patient population as invasive coronary angiography may prove challenging secondary to complicated or unconventional anatomy of the coronary arteries. Further, typical methods for evaluating CAD such as stress or echocardiography may be impractical in adults with CHD. Finally, delineating the anatomic relationship of the coronary arteries and their relationship with the sternum, chest wall, conduits, grafts, and valves is highly recommended in patients with CHD prior to reintervention to avoid iatrogenic complications.

  9. Human heart conjugate cooling simulation: Unsteady thermo-fluid-stress analysis

    PubMed Central

    Abdoli, Abas; Dulikravich, George S.; Bajaj, Chandrajit; Stowe, David F.; Jahania, M. Salik

    2015-01-01

    The main objective of this work was to demonstrate computationally that realistic human hearts can be cooled much faster by performing conjugate heat transfer consisting of pumping a cold liquid through the cardiac chambers and major veins while keeping the heart submerged in cold gelatin filling a cooling container. The human heart geometry used for simulations was obtained from three-dimensional, high resolution MRI scans. Two fluid flow domains for the right (pulmonic) and left (systemic) heart circulations, and two solid domains for the heart tissue and gelatin solution were defined for multi-domain numerical simulation. Detailed unsteady temperature fields within the heart tissue were calculated during the conjugate cooling process. A linear thermoelasticity analysis was performed to assess the stresses applied on the heart due to the coolant fluid shear and normal forces and to examine the thermal stress caused by temperature variation inside the heart. It was demonstrated that a conjugate cooling effort with coolant temperature at +4°C is capable of reducing the average heart temperature from +37°C to +8°C in 25 minutes for cases in which the coolant was steadily pumped only through major heart inlet veins and cavities. PMID:25045006

  10. Human heart conjugate cooling simulation: unsteady thermo-fluid-stress analysis.

    PubMed

    Abdoli, Abas; Dulikravich, George S; Bajaj, Chandrajit; Stowe, David F; Jahania, M Salik

    2014-11-01

    The main objective of this work was to demonstrate computationally that realistic human hearts can be cooled much faster by performing conjugate heat transfer consisting of pumping a cold liquid through the cardiac chambers and major veins while keeping the heart submerged in cold gelatin filling a cooling container. The human heart geometry used for simulations was obtained from three-dimensional, high resolution CT-angio scans. Two fluid flow domains for the right (pulmonic) and left (systemic) heart circulations, and two solid domains for the heart tissue and gelatin solution were defined for multi-domain numerical simulation. Detailed unsteady temperature fields within the heart tissue were calculated during the conjugate cooling process. A linear thermoelasticity analysis was performed to assess the stresses applied on the heart due to the coolant fluid shear and normal forces and to examine the thermal stress caused by temperature variation inside the heart. It was demonstrated that a conjugate cooling effort with coolant temperature at +4°C is capable of reducing the average heart temperature from +37°C to +8°C in 25 minutes for cases in which the coolant was steadily pumped only through major heart inlet veins and cavities.

  11. Developing Resourceful Humans. Adult Education within the Economic Context.

    ERIC Educational Resources Information Center

    Burton, Lynn Elen, Ed.

    This book, which explores the shifting paradigm from human resource development to developing resourceful humans, establishes the historical position of adult education within the economic context, discusses human capital propositions, and examines the learning dimensions of economic and educational change. The following chapters are included:…

  12. Desensitization strategies in adult heart transplantation-Will persistence pay off?

    PubMed

    Chih, Sharon; Patel, Jignesh

    2016-08-01

    Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation.

  13. Change in heart rate variability after the adult attachment interview in dissociative patients.

    PubMed

    Farina, Benedetto; Speranza, Anna Maria; Imperatori, Claudio; Quintiliani, Maria Isabella; Della Marca, Giacomo

    2015-01-01

    The aim of this study was to assess heart rate variability (HRV) in individuals with dissociative disorders (DD) before and after the Adult Attachment Interview (AAI). Electrocardiograms were recorded before, during, and after the AAI in 13 individuals with DD and 13 healthy participants matched for age and gender. Significant change in HRV was observed only in the DD group. After the AAI, those with DD showed significant increases in the low frequency/high frequency ratio (pre-AAI = 1.91 ± 1.19; post-AAI = 4.03 ± 2.40; Wilcoxon test = -2.76, p = .005). Our results suggest that the retrieval of childhood attachment experiences in individuals with DD is associated with a change in HRV patterns that could reflect the emotion dysregulation of dissociative psychopathological processes.

  14. Social isolation, C-reactive protein, and coronary heart disease mortality among community-dwelling adults.

    PubMed

    Heffner, Kathi L; Waring, Molly E; Roberts, Mary B; Eaton, Charles B; Gramling, Robert

    2011-05-01

    Social isolation confers increased risk for coronary heart disease (CHD) events and mortality. In two recent studies, low levels of social integration among older adults were related to higher levels of C-reactive protein (CRP), a marker of inflammation, suggesting a possible biological link between social isolation and CHD. The current study examined relationships among social isolation, CRP, and 15-year CHD death in a community sample of US adults aged 40 years and older without a prior history of myocardial infarction. A nested case-cohort study was conducted from a parent cohort of community-dwelling adults from the southeastern New England region of the United States (N = 2321) who were interviewed in 1989 and 1990. CRP levels were measured from stored sera provided by the nested case-cohort (n = 370), which included all cases of CHD death observed through 2005 (n = 48), and a random sample of non-cases. We found that the most socially isolated individuals had two-and-a-half times the odds of elevated CRP levels compared to the most socially integrated. In separate logistic regression models, both social isolation and CRP predicted later CHD death. The most socially isolated continued to have more than twice the odds of CHD death compared to the most socially integrated in a model adjusting for CRP and more traditional CHD risk factors. The current findings support social isolation as an independent risk factor of both high levels of CRP and CHD death in middle-aged adults without a prior history of myocardial infarction. Prospective study of inflammatory pathways related to social isolation and mortality are needed to fully delineate whether and how CRP or other inflammatory markers contribute to mechanisms linking social isolation to CVD health.

  15. Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease.

    PubMed

    Rosenblum, Omer; Katz, Uriel; Reuveny, Ronen; Williams, Craig A; Dubnov-Raz, Gal

    2015-12-01

    Few previous studies have addressed exercise capacity in patients with corrected congenital heart disease (CHD) and significant anatomical residua. The aim of this study was to determine the aerobic fitness and peak cardiac function of patients with corrected CHD with complete or incomplete repairs, as determined by resting echocardiography. Children, adolescents and young adults (<40 years) with CHD from both sexes, who had previously undergone biventricular corrective therapeutic interventions (n = 73), and non-CHD control participants (n = 76) underwent cardiopulmonary exercise testing. The CHD group was further divided according to the absence/presence of significant anatomical residua on a resting echocardiogram ("complete"/"incomplete" repair groups). Aerobic fitness and cardiac function were compared between groups using linear regression and analysis of covariance. Peak oxygen consumption, O2 pulse and ventilatory threshold were significantly lower in CHD patients compared with controls (all p < 0.01). Compared with the complete repair group, the incomplete repair group had a significantly lower mean peak work rate, age-adjusted O2 pulse (expressed as % predicted) and a higher VE/VCO2 ratio (all p ≤ 0.05). Peak oxygen consumption was comparable between the subgroups. Patients after corrected CHD have lower peak and submaximal exercise parameters. Patients with incomplete repair of their heart defect had decreased aerobic fitness, with evidence of impaired peak cardiac function and lower pulmonary perfusion. Patients that had undergone a complete repair had decreased aerobic fitness attributed only to deconditioning. These newly identified differences explain why in previous studies, the lowest fitness was seen in patients with the most hemodynamically significant heart malformations.

  16. Prevalence and Correlates of Post-traumatic Stress Disorder in Adults With Congenital Heart Disease.

    PubMed

    Deng, Lisa X; Khan, Abigail May; Drajpuch, David; Fuller, Stephanie; Ludmir, Jonathan; Mascio, Christopher E; Partington, Sara L; Qadeer, Ayesha; Tobin, Lynda; Kovacs, Adrienne H; Kim, Yuli Y

    2016-03-01

    Post-traumatic stress disorder (PTSD) is associated with adverse outcomes and increased mortality in cardiac patients. No studies have examined PTSD in the adult congenital heart disease (ACHD) population. The objectives of this study were to assess the prevalence of self-reported symptoms of PTSD in patients with ACHD and explore potential associated factors. Patients were enrolled from an outpatient ACHD clinic and completed several validated measures including the Impact of Event Scale-Revised, PTSD Checklist-Civilian Version, and the Hospital Anxiety and Depression Scale. Clinical data were abstracted through medical data review. A total of 134 participants (mean age 34.6 ± 10.6; 46% men) were enrolled. Of the 127 participants who completed the Impact of Event Scale-Revised, 14 (11%) met criteria for elevated PTSD symptoms specifically related to their congenital heart disease or treatment. Of the 134 patients who completed PTSD Checklist-Civilian Version, 27 (21%) met criteria for global PTSD symptoms. In univariate analyses, patients with congenital heart disease-specific PTSD had their most recent cardiac surgery at an earlier year (p = 0.008), were less likely to have attended college (p = 0.04), had higher rates of stroke or transient ischemic attack (p = 0.03), and reported greater depressive symptoms on the Hospital Anxiety and Depression Scale (7 vs 2, p <0.001). In multivariable analysis, the 2 factors most strongly associated with PTSD were depressive symptoms (p <0.001) and year of most recent cardiac surgery (p <0.03). In conclusion, PTSD is present in 11% to 21% of subjects seen at a tertiary referral center for ACHD. The high prevalence of PTSD in this complex group of patients has important implications for the medical and psychosocial management of this growing population.

  17. Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

    PubMed

    Elder, Robert W; George, Roshan P; McCabe, Nancy M; Rodriguez, Fred H; Book, Wendy M; Mahle, William T; Kirk, Allan D

    2015-10-01

    Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.

  18. Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults.

    PubMed

    Bianchim, M S; Sperandio, E F; Martinhão, G S; Matheus, A C; Lauria, V T; da Silva, R P; Spadari, R C; Gagliardi, A R T; Arantes, R L; Romiti, M; Dourado, V Z

    2016-03-01

    The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders.

  19. Adult stem cell therapy and heart failure, 2000 to 2016: a systematic review

    PubMed Central

    Nguyen, Patricia K.; Rhee, June-Wha; Wu, Joseph C.

    2017-01-01

    Importance Stem cell therapy is a promising treatment strategy for patients with heart failure, which accounts for over 10% of deaths in the U.S. annually. Despite over a decade of research, further investigation is still needed to determine whether stem cell regenerative therapy is clinically effective and can be routinely implemented in clinical practice. Objective The purpose of this review is to describe the current progress in cardiac stem cell regenerative therapy using adult stem cells and highlight the merits and limitations of clinical trials performed to date. Evidence Review Information for this review was obtained through a search of PubMed and the Cochrane database for English language studies published between January 1, 2000 and April 20, 2016. Twenty-nine randomized clinical trials and 7 systematic reviews and meta-analyses were included in this review. Findings Although adult stem cells were once believed to have the ability to create new heart tissue or grow blood vessels, preclinical studies suggest instead that these cells release cardio-protective paracrine factors that activate endogenous pathways, leading to myocardial repair. Subsequent randomized controlled clinical trials, the majority of which used autologous bone marrow mononuclear cells, have found only a modest benefit in patients receiving stem cell therapy. The lack of a significant benefit may result from variations in trial methodology, discrepancies in reporting, and an over-reliance on surrogate endpoints. Conclusions and Relevance Although stem cell therapy for cardiovascular disease is not yet ready for routine clinical application, significant progress continues to be made. Physicians should be aware of the current status of this treatment so that they can better inform their patients who may be in search of alternative therapies. PMID:27557438

  20. Adult Literacy Education and Human Rights: A View from Afghanistan

    ERIC Educational Resources Information Center

    Andersen, Susan M.; Kooij, Christina S.

    2007-01-01

    In this article, we argue that adult literacy as part of international development is an issue of both human rights and women's rights. We explore this by presenting a case study of the effects of one innovative adult literacy program in Afghanistan that places men and women, as well as various ethnicities, together in the same classroom as…

  1. Twelve-hour reanimation of a human heart following donation after circulatory death.

    PubMed

    Rosenfeldt, Franklin; Ou, Ruchong; Woodard, John; Esmore, Donald; Marasco, Silvana

    2014-01-01

    Despite increasing use of donation after cardiac death (DCD) and encouraging results for non-cardiac transplants, DCD cardiac transplantation has not been widely adopted because, (1) the DCD heart sustains warm ischaemic injury during the death process and (2) conventional static cold storage significantly adds to the ischaemic injury. We have developed a simple system for perfusion of the DCD heart with cold crystalloid solution using gravity-feed that can reduce ischaemic injury and potentially render the heart suitable for transplantation. This report describes the first application of this technique to a human DCD heart with good functional metabolic recovery over 12h on an ex vivo rig.

  2. Implementation of the American College of Cardiology/American Heart Association 2008 Guidelines for the Management of Adults With Congenital Heart Disease.

    PubMed

    Goossens, Eva; Fernandes, Susan M; Landzberg, Michael J; Moons, Philip

    2015-08-01

    Although different guidelines on adult congenital heart disease (ACHD) care advocate for lifetime cardiac follow-up, a critical appraisal of the guideline implementation is lacking. We investigated the implementation of the American College of Cardiology/American Heart Association 2008 guidelines for ACHD follow-up by investigating the type of health care professional, care setting, and frequency of outpatient visits in young adults with CHD. Furthermore, correlates for care in line with the recommendations or untraceability were investigated. A cross-sectional observational study was conducted, including 306 patients with CHD who had a documented outpatient visit at pediatric cardiology before age 18 years. In all, 210 patients (68.6%) were in cardiac follow-up; 20 (6.5%) withdrew from follow-up and 76 (24.9%) were untraceable. Overall, 198 patients were followed up in tertiary care, 1/4 (n = 52) of which were seen at a formalized ACHD care program and 3/4 (n = 146) remained at pediatric cardiology. Of those followed in formalized ACHD and pediatric cardiology care, the recommended frequency was implemented in 94.2% and 89%, respectively (p = 0.412). No predictors for the implementation of the guidelines were identified. Risk factors for becoming untraceable were none or lower number of heart surgeries, health insurance issues, and nonwhite ethnicity. In conclusion, a significant number of adults continue to be cared for by pediatric cardiologists, indicating that transfer to adult-oriented care was not standard practice. Frequency of follow-up for most patients was in line with the ACC/AHA 2008 guidelines. A considerable proportion of young adults were untraceable in the system, which makes them vulnerable for discontinuation of care.

  3. Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations.

    PubMed

    Pastore, Robert L; Brooks, Judith T; Carbone, John W

    2015-06-01

    Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P < .001) HDL, independent of changes in body weight, relative to both baseline and the traditional heart-healthy diet. Paleolithic nutrition offers promising potential for nutritional management of hyperlipidemia in adults whose lipid profiles have not improved after following more traditional heart-healthy dietary recommendations.

  4. The human subject: an integrative animal model for 21st century heart failure research

    PubMed Central

    Chandrasekera, P Charukeshi; Pippin, John J

    2015-01-01

    Heart failure remains a leading cause of death and it is a major cause of morbidity and mortality affecting tens of millions of people worldwide. Despite decades of extensive research conducted at enormous expense, only a handful of interventions have significantly impacted survival in heart failure. Even the most widely prescribed treatments act primarily to slow disease progression, do not provide sustained survival advantage, and have adverse side effects. Since mortality remains about 50% within five years of diagnosis, the need to increase our understanding of heart failure disease mechanisms and development of preventive and reparative therapies remains critical. Currently, the vast majority of basic science heart failure research is conducted using animal models ranging from fruit flies to primates; however, insights gleaned from decades of animal-based research efforts have not been proportional to research success in terms of deciphering human heart failure and developing effective therapeutics for human patients. Here we discuss the reasons for this translational discrepancy which can be equally attributed to the use of erroneous animal models and the lack of widespread use of human-based research methodologies and address why and how we must position our own species at center stage as the quintessential animal model for 21st century heart failure research. If the ultimate goal of the scientific community is to tackle the epidemic status of heart failure, the best way to achieve that goal is through prioritizing human-based, human-relevant research. PMID:26550463

  5. Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.

    PubMed

    Ardehali, Reza; Ali, Shah R; Inlay, Matthew A; Abilez, Oscar J; Chen, Michael Q; Blauwkamp, Timothy A; Yazawa, Masayuki; Gong, Yongquan; Nusse, Roeland; Drukker, Micha; Weissman, Irving L

    2013-02-26

    A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2(+) cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart.

  6. Systems approach to understanding electromechanical activity in the human heart: a national heart, lung, and blood institute workshop summary.

    PubMed

    Rudy, Yoram; Ackerman, Michael J; Bers, Donald M; Clancy, Colleen E; Houser, Steven R; London, Barry; McCulloch, Andrew D; Przywara, Dennis A; Rasmusson, Randall L; Solaro, R John; Trayanova, Natalia A; Van Wagoner, David R; Varró, András; Weiss, James N; Lathrop, David A

    2008-09-09

    The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation-contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm.

  7. Altered protein levels in the isolated extracellular matrix of failing human hearts with dilated cardiomyopathy.

    PubMed

    DeAguero, Joshua L; McKown, Elizabeth N; Zhang, Liwen; Keirsey, Jeremy; Fischer, Edgar G; Samedi, Von G; Canan, Benjamin D; Kilic, Ahmet; Janssen, Paul M L; Delfín, Dawn A

    Dilated cardiomyopathy (DCM) is associated with extensive pathological cardiac remodeling and involves numerous changes in the protein expression profile of the extracellular matrix of the heart. We obtained seven human, end-stage, failing hearts with DCM (DCM-failing) and nine human, nonfailing donor hearts and compared their extracellular matrix protein profiles. We first showed that the DCM-failing hearts had indeed undergone extensive remodeling of the left ventricle myocardium relative to nonfailing hearts. We then isolated the extracellular matrix from a subset of these hearts and performed a proteomic analysis on the isolated matrices. We found that the levels of 26 structural proteins were altered in the DCM-failing isolated cardiac extracellular matrix compared to nonfailing isolated cardiac extracellular matrix. Overall, most of the extracellular matrix proteins showed reduced levels in the DCM-failing hearts, while all of the contractile proteins showed increased levels. There was a mixture of increased and decreased levels of cytoskeletal and nuclear transport proteins. Using immunoprobing, we verified that collagen IV (α2 and α6 isoforms), zyxin, and myomesin protein levels were reduced in the DCM-failing hearts. We expect that these data will add to the understanding of the pathology associated with heart failure with DCM.

  8. Human gene copy number spectra analysis in congenital heart malformations

    PubMed Central

    Mahnke, Donna K.; Struble, Craig A.; Tuffnell, Maureen E.; Stamm, Karl D.; Hidestrand, Mats; Harris, Susan E.; Goetsch, Mary A.; Simpson, Pippa M.; Bick, David P.; Broeckel, Ulrich; Pelech, Andrew N.; Tweddell, James S.; Mitchell, Michael E.

    2012-01-01

    The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways. PMID:22318994

  9. Outcomes of a Telehealth Intervention for Homebound Older Adults with Heart or Chronic Respiratory Failure: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Gellis, Zvi D.; Kenaley, Bonnie; McGinty, Jean; Bardelli, Ellen; Davitt, Joan; Ten Have, Thomas

    2012-01-01

    Purpose: Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management. Design and Methods: We report on a randomized controlled trial examining the impact of a multifaceted…

  10. Hyperoxia Induces Inflammation and Cytotoxicity in Human Adult Cardiac Myocytes.

    PubMed

    Hafner, Christina; Wu, Jing; Tiboldi, Akos; Hess, Moritz; Mitulovic, Goran; Kaun, Christoph; Krychtiuk, Konstantin Alexander; Wojta, Johann; Ullrich, Roman; Tretter, Eva Verena; Markstaller, Klaus; Klein, Klaus Ulrich

    2017-04-01

    Supplemental oxygen (O2) is used as adjunct therapy in anesthesia, emergency, and intensive care medicine. We hypothesized that excessive O2 levels (hyperoxia) can directly injure human adult cardiac myocytes (HACMs). HACMs obtained from the explanted hearts of transplantation patients were exposed to constant hyperoxia (95% O2), intermittent hyperoxia (alternating 10 min exposures to 5% and 95% O2), constant normoxia (21% O2), or constant mild hypoxia (5% O2) using a bioreactor. Changes in cell morphology, viability as assessed by lactate dehydrogenase (LDH) release and trypan blue (TB) staining, and secretion of vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), and various pro-inflammatory cytokines (interleukin, IL; chemokine C-X-C motif ligand, CXC; granulocyte-colony stimulating factor, G-CSF; intercellular adhesion molecule, ICAM; chemokine C-C motif ligand, CCL) were compared among treatment groups at baseline (0 h) and after 8, 24, and 72 h of treatment. Changes in HACM protein expression were determined by quantitative proteomic analysis after 48 h of exposure. Compared with constant normoxia and mild hypoxia, constant hyperoxia resulted in a higher TB-positive cell count, greater release of LDH, and elevated secretion of VEGF, MIF, IL-1β, IL-6, IL-8, CXCL-1, CXCL-10, G-CSF, ICAM-1, CCL-3, and CCL-5. Cellular inflammation and cytotoxicity gradually increased and was highest after 72 h of constant and intermittent hyperoxia. Quantitative proteomic analysis revealed that hypoxic and hyperoxic O2 exposure differently altered the expression levels of proteins involved in cell-cycle regulation, energy metabolism, and cell signaling. In conclusion, constant and intermittent hyperoxia induced inflammation and cytotoxicity in HACMs. Cell injury occurred earliest and was greatest after constant hyperoxia, but even relatively brief repeating hyperoxic episodes induced a substantial inflammatory response.

  11. Metabolic syndrome and short-term heart rate variability in adults with intellectual disabilities.

    PubMed

    Chang, Yaw-Wen; Lin, Jin-Ding; Chen, Wei-Liang; Yen, Chia-Feng; Loh, Ching-Hui; Fang, Wen-Hui; Wu, Li-Wei

    2012-01-01

    Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV between the healthy and ID population, and the association of short-term HRV with MetS. In this study, we analyzed 129 ID subjects who participated in routine health check-ups in October 2010. We measured their metabolic components and evaluated the relationships of MetS with short-term HRV indices. The study found that MetS and obesity are common in persons with ID. ID subjects have significantly lower HRV than healthy adults, and persons with ID persons with MetS have significantly lower HRV than ID subjects without MetS. The individual components of MetS are differentially associated with HRV in ID men and women. Metabolic syndrome adversely affects autonomic cardiac control, and reduced autonomic cardiac control could contribute to an increased risk of subsequent cardiovascular events in individuals who exhibit metabolic syndrome. Sex differences in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in ID women compared with ID men.

  12. Medication Management: The Macrocognitive Workflow of Older Adults With Heart Failure

    PubMed Central

    2016-01-01

    Background Older adults with chronic disease struggle to manage complex medication regimens. Health information technology has the potential to improve medication management, but only if it is based on a thorough understanding of the complexity of medication management workflow as it occurs in natural settings. Prior research reveals that patient work related to medication management is complex, cognitive, and collaborative. Macrocognitive processes are theorized as how people individually and collaboratively think in complex, adaptive, and messy nonlaboratory settings supported by artifacts. Objective The objective of this research was to describe and analyze the work of medication management by older adults with heart failure, using a macrocognitive workflow framework. Methods We interviewed and observed 61 older patients along with 30 informal caregivers about self-care practices including medication management. Descriptive qualitative content analysis methods were used to develop categories, subcategories, and themes about macrocognitive processes used in medication management workflow. Results We identified 5 high-level macrocognitive processes affecting medication management—sensemaking, planning, coordination, monitoring, and decision making—and 15 subprocesses. Data revealed workflow as occurring in a highly collaborative, fragile system of interacting people, artifacts, time, and space. Process breakdowns were common and patients had little support for macrocognitive workflow from current tools. Conclusions Macrocognitive processes affected medication management performance. Describing and analyzing this performance produced recommendations for technology supporting collaboration and sensemaking, decision making and problem detection, and planning and implementation. PMID:27733331

  13. Medication problems occurring at hospital discharge among older adults with heart failure.

    PubMed

    Foust, Janice B; Naylor, Mary D; Bixby, M Brian; Ratcliffe, Sarah J

    2012-01-01

    Medication reconciliation problems are common among older adults at hospital discharge and lead to adverse events. The purpose of this study was to examine the rates and types of medication reconciliation problems among older adults hospitalized for acute episodes of heart failure who were discharged home. This secondary analysis of data generated from a transitional care intervention included 198 hospital discharge medical records, representing 162 patients. A retrospective chart review comparing medication lists between hospital discharge summaries and patient discharge instructions was completed to identify medication reconciliation problems. Most hospital discharges (71.2%) had at least one type of reconciliation problem and frequently involved a high-risk medication (76.6%). Discrepancies were the most common problem (58.9%), followed by incomplete discharge summaries (52.5%) and partial patient discharge instructions (48.9%). More attention needs to be given to the quality of discharge instructions, and the problem of vague phrases (e.g., "take as directed") can be addressed by adding it to "do not use" lists to promote safer transitions in care.

  14. A comparative study of bifidobacteria in human babies and adults

    PubMed Central

    KHONSARI, Shadi; SUGANTHY, Mayuran; BURCZYNSKA, Beata; DANG, Vu; CHOUDHURY, Manika; PACHENARI, Azra

    2015-01-01

    The composition and diversity of the gut microbiota are known to be different between babies and adults. The aim of this project was to compare the level of bifidobacteria between babies and adults and to investigate the influence of lifestyle factors on the level of this bacterium in the gut. During this study, the levels of bifidobacteria in 10 human babies below 2 years of age were compared with that of 10 human adults above 40 years. The level of bifidobacteria proved to be significantly higher in babies in comparison with adults. This investigation concluded that a combination of several factors, such as age, diet, and BMI, has an important effect on the level of bifidobacteria in adults, while in babies, a combination of diet and age may influence the level of intestinal bifidobacteria. PMID:27200263

  15. Hospitalizations and mortality in the United States for adults with Down syndrome and congenital heart disease.

    PubMed

    Baraona, Fernando; Gurvitz, Michelle; Landzberg, Michael J; Opotowsky, Alexander R

    2013-04-01

    Congenital heart disease (CHD) is common in patients with Down syndrome (DS), and these patients are living longer lives. The aim of this study was to describe the epidemiology of hospitalizations in adults with DS and CHD in the United States. Hospitalizations from 1998 to 2009 for adults aged 18 to 64 years with and without DS with CHD diagnoses associated with DS (atrioventricular canal defect, ventricular septal defect, tetralogy of Fallot, and patent ductus arteriosus) were analyzed using the Nationwide Inpatient Sample. Outcomes of interest were (1) in-hospital mortality, (2) common co-morbidities, (3) cardiac procedures, (4) hospital charges, and (5) length of stay. Multivariate modeling adjusted for age, gender, CHD diagnosis, and co-morbidities. There were 78,793 ± 2,653 CHD admissions, 9,088 ± 351 (11.5%) of which were associated with diagnoses of DS. The proportion of admissions associated with DS (DS/CHD) decreased from 15.2 ± 1.3% to 8.5 ± 0.9%. DS was associated with higher in-hospital mortality (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.4 to 2.4), especially in women (OR 2.4, 95% CI 1.7 to 3.4). DS/CHD admissions were more commonly associated with hypothyroidism (OR 7.7, 95% CI 6.6 to 9.0), dementia (OR 82.0, 95% CI 32 to 213), heart failure (OR 2.2, 95% CI 1.9 to 2.5), pulmonary hypertension (OR 2.5, 95% CI 2.2 to 2.9), and cyanosis or secondary polycythemia (OR 4.6, 95% CI 3.8 to 5.6). Conversely, DS/CHD hospitalizations were less likely to include cardiac procedures or surgery (OR 0.3, 95% CI 0.2 to 0.4) and were associated with lower charges ($23,789 ± $1,177 vs $39,464 ± $1,371, p <0.0001) compared to non-DS/CHD admissions. In conclusion, DS/CHD hospitalizations represent a decreasing proportion of admissions for adults with CHD typical of DS; patients with DS/CHD are more likely to die during hospitalization but less likely to undergo a cardiac procedure.

  16. Visualization of Fiber Structurein the Left and Right Ventricleof a Human Heart

    SciTech Connect

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-07-12

    The human heart is composed of a helical network of musclefibers. Anisotropic least squares filtering followed by fiber trackingtechniques were applied to Diffusion Tensor Magnetic Resonance Imaging(DTMRI) data of the excised human heart. The fiber configuration wasvisualized by using thin tubes to increase 3-dimensional visualperception of the complex structure. All visualizations were performedusing the high-quality ray-tracing software POV-Ray. The fibers are shownwithin the left and right ventricles. Both ventricles exhibit similarfiber architecture and some bundles of fibers are shown linking right andleft ventricles on the posterior region of the heart.

  17. Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: complex congenital cardiac lesions.

    PubMed

    Silversides, Candice K; Salehian, Omid; Oechslin, Erwin; Schwerzmann, Markus; Vonder Muhll, Isabelle; Khairy, Paul; Horlick, Eric; Landzberg, Mike; Meijboom, Folkert; Warnes, Carole; Therrien, Judith

    2010-03-01

    With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death. Medical aspects that need to be considered relate to the long-term and multisystemic effects of single ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part III of the guidelines includes recommendations for the care of patients with complete transposition of the great arteries, congenitally corrected transposition of the great arteries, Fontan operations and single ventricles, Eisenmenger's syndrome, and cyanotic heart disease. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts, which are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.

  18. Minimal changes in heart rate of incubating American Oystercatchers (Haematopus palliatus) in response to human activity

    USGS Publications Warehouse

    Borneman, Tracy E.; Rose, Eli T.; Simons, Theodore R.

    2014-01-01

    An organism's heart rate is commonly used as an indicator of physiological stress due to environmental stimuli. We used heart rate to monitor the physiological response of American Oystercatchers (Haematopus palliatus) to human activity in their nesting environment. We placed artificial eggs with embedded microphones in 42 oystercatcher nests to record the heart rate of incubating oystercatchers continuously for up to 27 days. We used continuous video and audio recordings collected simultaneously at the nests to relate physiological response of birds (heart rate) to various types of human activity. We observed military and civilian aircraft, off-road vehicles, and pedestrians around nests. With the exception of high-speed, low-altitude military overflights, we found little evidence that oystercatcher heart rates were influenced by most types of human activity. The low-altitude flights were the only human activity to significantly increase average heart rates of incubating oystercatchers (12% above baseline). Although statistically significant, we do not consider the increase in heart rate during high-speed, low-altitude military overflights to be of biological significance. This noninvasive technique may be appropriate for other studies of stress in nesting birds.

  19. [Heart rhythm indices during human solving of arithmetic tasks].

    PubMed

    Danilova, N N; Korshunova, S G; Sokolov, E N

    1994-01-01

    Heart rate and respiration were recorded in a group of 90 subjects (25 males and 65 females) aged 17-19 during rest and under informational load (arithmetical tasks) lasting 3 min each. Off-line spectral analysis was performed for all the subjects. Anxiety according to Spilberger and strength of excitation-inhibition according to Strelau were also tested. It was shown that heart rate increased significantly in the group as a whole, however, variability of RR-intervals remained unchanged. Then two subgroups of subjects who responded to information load by a decrease and increase of RR-interval variability were distinguished. These subgroups were characterized respectively by the high and low levels of personal anxiety. The decrease of RR-interval variability in the high-anxiety subgroup was associated with a decrease of power in all frequency bands of the rate spectrum. The increase of RR-interval variability in the low-anxiety subground was due to an increase of heart rate modulation in a low-frequency band of the heart rate spectrum. Fatigue is regarded as a cause of such heart rate modulation.

  20. The care of adults with congenital heart disease across the globe: Current assessment and future perspective: A position statement from the International Society for Adult Congenital Heart Disease (ISACHD).

    PubMed

    Webb, Gary; Mulder, Barbara J; Aboulhosn, Jamil; Daniels, Curt J; Elizari, Maria Amalia; Hong, Gu; Horlick, Eric; Landzberg, Michael J; Marelli, Ariane J; O'Donnell, Clare P; Oechslin, Erwin N; Pearson, Dorothy D; Pieper, Els P G; Saxena, Anita; Schwerzmann, Markus; Stout, Karen K; Warnes, Carole A; Khairy, Paul

    2015-09-15

    The number of adults with congenital heart disease (CHD) has increased markedly over the past few decades as a result of astounding successes in pediatric cardiac care. Nevertheless, it is now well understood that CHD is not cured but palliated, such that life-long expert care is required to optimize outcomes. All countries in the world that experience improved survival in CHD must face new challenges inherent to the emergence of a growing and aging CHD population with changing needs and medical and psychosocial issues. Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with CHD worldwide. Recognizing the unique and varied issues involved in caring for adults with CHD, ISACHD established a task force to assess the current status of care for adults with CHD across the globe, highlight major challenges and priorities, and provide future direction. The writing committee consisted of experts from North America, South America, Europe, South Asia, East Asia, and Oceania. The committee was divided into subgroups to review key aspects of adult CHD (ACHD) care. Regional representatives were tasked with investigating and reporting on relevant local issues as accurately as possible, within the constraints of available data. The resulting ISACHD position statement addresses changing patterns of worldwide epidemiology, models of care and organization of care, education and training, and the global research landscape in ACHD.

  1. Intact Imaging of Human Heart Structure Using X-ray Phase-Contrast Tomography.

    PubMed

    Kaneko, Yukihiro; Shinohara, Gen; Hoshino, Masato; Morishita, Hiroyuki; Morita, Kiyozo; Oshima, Yoshihiro; Takahashi, Masashi; Yagi, Naoto; Okita, Yutaka; Tsukube, Takuro

    2017-02-01

    Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases.

  2. Total lymphatic irradiation and bone marrow in human heart transplantation

    SciTech Connect

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  3. Humanities and the Adult Learner in an Information Society.

    ERIC Educational Resources Information Center

    Myers, Dale; Kamholtz, Jonathan

    Humanities courses have often been given little attention in continuing education for adults, possibly because they have been viewed as not "practical" or not "job-oriented" enough in our career-oriented, technologically advanced society. However, the humanities should be an integral part of our culture and of the lives of…

  4. Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling.

    PubMed

    Lou, Qing; Janks, Deborah L; Holzem, Katherine M; Lang, Di; Onal, Birce; Ambrosi, Christina M; Fedorov, Vadim V; Wang, I-Wen; Efimov, Igor R

    2012-12-15

    Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ∼6.3 × 6.3 cm(2) field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF.

  5. Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling

    PubMed Central

    Lou, Qing; Janks, Deborah L.; Holzem, Katherine M.; Lang, Di; Onal, Birce; Ambrosi, Christina M.; Fedorov, Vadim V.; Wang, I-Wen

    2012-01-01

    Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ∼6.3 × 6.3 cm2 field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF. PMID:23042951

  6. A deep sequencing approach to uncover the miRNOME in the human heart.

    PubMed

    Leptidis, Stefanos; El Azzouzi, Hamid; Lok, Sjoukje I; de Weger, Roel; Olieslagers, Servé; Olieslagers, Serv; Kisters, Natasja; Silva, Gustavo J; Heymans, Stephane; Cuppen, Edwin; Berezikov, Eugene; De Windt, Leon J; da Costa Martins, Paula

    2013-01-01

    MicroRNAs (miRNAs) are a class of non-coding RNAs of ∼22 nucleotides in length, and constitute a novel class of gene regulators by imperfect base-pairing to the 3'UTR of protein encoding messenger RNAs. Growing evidence indicates that miRNAs are implicated in several pathological processes in myocardial disease. The past years, we have witnessed several profiling attempts using high-density oligonucleotide array-based approaches to identify the complete miRNA content (miRNOME) in the healthy and diseased mammalian heart. These efforts have demonstrated that the failing heart displays differential expression of several dozens of miRNAs. While the total number of experimentally validated human miRNAs is roughly two thousand, the number of expressed miRNAs in the human myocardium remains elusive. Our objective was to perform an unbiased assay to identify the miRNOME of the human heart, both under physiological and pathophysiological conditions. We used deep sequencing and bioinformatics to annotate and quantify microRNA expression in healthy and diseased human heart (heart failure secondary to hypertrophic or dilated cardiomyopathy). Our results indicate that the human heart expresses >800 miRNAs, the majority of which not being annotated nor described so far and some of which being unique to primate species. Furthermore, >250 miRNAs show differential and etiology-dependent expression in human dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM). The human cardiac miRNOME still possesses a large number of miRNAs that remain virtually unexplored. The current study provides a starting point for a more comprehensive understanding of the role of miRNAs in regulating human heart disease.

  7. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  8. Heart rate recovery after the 10-m incremental shuttle walking test in older adults with intellectual disabilities.

    PubMed

    Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Evenhuis, Heleen M

    2014-03-01

    Heart rate recovery (HRR) after exercise is an independent predictor for cardiovascular and all-cause mortality. To investigate the usefulness of HRR in cardiorespiratory exercise testing in older adults with intellectual disabilities (ID), the aims of this study were (a) to assess HRR in older adults with ID after the 10-m incremental shuttle walking test (ISWT) and (b) its association with personal characteristics (gender, age, distance walked on the ISWT, level of ID, genetic syndrome causing ID, autism, behavioral problems, and peak heart rate (HRpeak)). HRR was assessed after the 10-m incremental shuttle walking test in 300 older adults (>50 years) with borderline to profound ID. HRR was defined as the change from HRpeak during the ISWT to heart rate measured after 1, 2, 3, 4, and 5 min of passive recovery. The largest decrease in heart rate was in the first minute of recovery leveling off toward the fifth minute of recovery. An abnormal HHR (≤12 bpm) was seen in 36.1% of the participants with Down syndrome (DS) and in 30.7% of the participants with ID by other causes. After the fifth minute the heart rates of 69.4% of the participants with DS and of 61.4% of the participants with ID by other causes returned to resting levels. HRpeak and distance walked on the ISWT were positively related to all HRR measures. More severe ID was negatively related and having DS positively related to HRR after 3-5 min of recovery. The other characteristics were not significantly associated to HRR. HRR is a potentially useful outcome measure in cardiorespiratory fitness testing of older adults with ID with a direct, objective, and non-invasive measurement. Further research is needed to identify the relation between HRR and adverse health outcomes in this population.

  9. Heart Rate and Heart Rate Variability in Dairy Cows with Different Temperament and Behavioural Reactivity to Humans.

    PubMed

    Kovács, Levente; Kézér, Fruzsina Luca; Tőzsér, János; Szenci, Ottó; Póti, Péter; Pajor, Ferenc

    2015-01-01

    From the 1990s, extensive research was started on the physiological aspects of individual traits in animals. Previous research has established two extreme (proactive and reactive) coping styles in several animal species, but the means of reactivity with the autonomic nervous system (ANS) activity has not yet been investigated in cattle. The aim of this study was the characterization of cardiac autonomic activity under different conditions in cows with different individual characteristics. For this purpose, we investigated heart rate and ANS-related heart rate variability (HRV) parameters of dairy cows (N = 282) on smaller- and larger-scale farms grouped by (1) temperament and (2) behavioural reactivity to humans (BRH). Animals with high BRH scores were defined as impulsive, while animals with low BRH scores were defined as reserved. Cardiac parameters were calculated for undisturbed lying (baseline) and for milking bouts, the latter with the presence of an unfamiliar person (stressful situation). Sympathetic tone was higher, while vagal activity was lower in temperamental cows than in calm animals during rest both on smaller- and larger-scale farms. During milking, HRV parameters were indicative of a higher sympathetic and a lower vagal activity of temperamental cows as compared to calm ones in farms of both sizes. Basal heart rate did not differ between BRH groups either on smaller- or larger-scale farms. Differences between basal ANS activity of impulsive and reserved cows reflected a higher resting vagal and lower sympathetic activity of reserved animals compared to impulsive ones both on smaller- and larger-scale farms. There was no difference either in heart rate or in HRV parameters between groups during milking neither in smaller- nor in larger-scale farms. These two groupings allowed to draw possible parallels between personality and cardiac autonomic activity during both rest and milking in dairy cows. Heart rate and HRV seem to be useful for

  10. Structural brain correlates of heart rate variability in a healthy young adult population.

    PubMed

    Winkelmann, Tobias; Thayer, Julian F; Pohlack, Sebastian; Nees, Frauke; Grimm, Oliver; Flor, Herta

    2017-03-01

    The high frequency component of heart rate variability (HRV) has reliably been shown to serve as an index of autonomic inhibitory control and is increasingly considered as a biomarker of adaptability and health. While several functional neuroimaging studies identified associations between regional cerebral blood flow and HRV, studies on structural brain correlates of HRV are scarce. We investigated whether interindividual differences in HRV are related to brain morphology in healthy humans. Thirty participants underwent HRV recording at rest subsequent to structural magnetic resonance imaging. Cortical reconstruction and subcortical volumetry were performed with the Freesurfer image analysis suite. The amount of resting HRV was positively correlated with the cortical thickness of an area within the right anterior midcingulate cortex (aMCC). Consistent with existing studies implicating forebrain regions in cardiac regulation, our findings show that the thickness of the right aMCC is associated with the degree of parasympathetic regulation of heart rate. Evidence for the neural correlates of interindividual differences in HRV may complement our understanding of the mechanisms underlying the association between HRV and self-regulatory capacity.

  11. Encounters with the Human Heart: An Interview with John Stone.

    ERIC Educational Resources Information Center

    Flynn, Dale Bachman

    1995-01-01

    Interviews Dale Bachman Flynn, professor of cardiology and dean of admissions and student affairs at Emory University School of Medicine, about his "In the Country of Hearts," a collection of stories about his medical practice. Discusses Flynn's personal life; his life-long practice of writing; and his interest in the intersections among medicine,…

  12. Infrequency of cytomegalovirus genome in coronary arteriopathy of human heart allografts.

    PubMed Central

    Gulizia, J. M.; Kandolf, R.; Kendall, T. J.; Thieszen, S. L.; Wilson, J. E.; Radio, S. J.; Costanzo, M. R.; Winters, G. L.; Miller, L. L.; McManus, B. M.

    1995-01-01

    In heart transplantation, long-term engraftment success is severely limited by the rapid development of obliterative disease of the coronary arteries. Data from various groups have been suggestive of a pathogenetic role of herpesviruses, particularly human cytomegalovirus, in accelerated allograft coronary artery disease; however, results are not yet conclusive. This study examines the hypothesis that human cytomegalovirus infection of allograft tissues is related pathogenetically and directly to accelerated coronary artery disease. Using in situ DNA hybridization and polymerase chain reaction, we examined particular coronary artery segments from 41 human heart allografts (ranging from 4 days to greater than 4 years after transplantation; mean, 457 days) and 22 donor age- and gender-comparable, coronary site-matched trauma victims for presence of human cytomegalovirus DNA. Human cytomegalovirus genome was detected in 8 of 41 (19.5%) allografts and in 1 of 22 (4.5%) control hearts. This difference in positivity was not statistically significant (P = 0.10). In the human cytomegalovirus-positive hearts, viral genome was localized to perivascular myocardium or coronary artery media or adventitia. Human cytomegalovirus genome was not detected in arterial intima of any allograft or control heart, although human cytomegalovirus genome was readily identified within intima of small pulmonary arteries from lung tissue with human cytomegalovirus pneumonitis. By statistical analyses, the presence of human cytomegalovirus genome was not associated with the nature or digitized extent of transplant arteriopathy, evidence of rejection, allograft recipient or donor serological data suggestive of human cytomegalovirus infection, duration of allograft implantation, or causes of death or retransplantation. Thus, our data indicate a low frequency of detectable human cytomegalovirus genome in accelerated coronary artery disease and do not support a direct role for human cytomegalovirus

  13. Restrictive lung disease is an independent predictor of exercise intolerance in the adult with congenital heart disease

    PubMed Central

    Ginde, Salil; Bartz, Peter J.; Hill, Garick D.; Danduran, Michael J.; Biller, Julie; Sowinski, Jane; Tweddell, James S.; Earing, Michael G.

    2016-01-01

    Background/Objectives Following repair of congenital heart disease (CHD), adult patients are at risk for reduced exercise capacity. Restrictive lung disease (RLD) may contribute to reduced exercise capacity in this population. The aim of this study was to determine the prevalence of RLD and its impact on exercise tolerance in the adult with congenital heart disease. Methods One hundred consecutive adult patients with CHD, who underwent routine cardiopulmonary exercise testing with spirometry, were evaluated. Clinical data was obtained by retrospective chart review. Results Patients from 10 major diagnostic groups were identified. The median age for the cohort was 31 years (range 18–63) and included 43 males and 57 females. Most patients, 79%, had at least one previous surgical procedure. Based on spirometry and flow/volume loops, 50 patients were classified as normal pulmonary function, 44 patients had patterns suggestive of RLD, 4 suggestive of mixed (obstructive and restrictive), and 2 indeterminate. Risk factors associated with RLD include history of multiple thoracotomies (odds ratio=9.01, p=0.05) and history of atrial arrhythmias (odd ratio=4.25, p=0.05). Overall, 56% of the patients had abnormal exercise capacity. Spirometry suggestive of RLD was a significant risk factor for decreased exercise capacity (odds ratio=3.65, p=0.03). Patients with spirometry suggesting RLD also had lower exercise duration (p=0.004) and a higher New York Heart Association Functional Class (p=0.02). History of previous surgery and decreased heart rate reserve were also significant risk factors for decreased exercise capacity. Conclusion Abnormal spirometry suggestive of RLD is common in the adult with CHD and is a significant risk factor for decreased exercise tolerance in this population. Further studies, are needed to evaluate the relationship between RLD and exercise intolerance and its relationship to mortality in the adult with CHD. PMID:23075089

  14. Risks for Heart Valve Problems

    MedlinePlus

    ... Cholesterol Tools & Resources Congenital Defects Children & Adults About Congenital Heart Defects The Impact of Congenital Heart Defects Understand Your Risk for Congenital Heart Defects Symptoms & ...

  15. Proteomic analysis of membrane microdomains derived from both failing and non-failing human hearts.

    PubMed

    Banfi, Cristina; Brioschi, Maura; Wait, Robin; Begum, Shajna; Gianazza, Elisabetta; Fratto, Pasquale; Polvani, Gianluca; Vitali, Ettore; Parolari, Alessandro; Mussoni, Luciana; Tremoli, Elena

    2006-03-01

    Eukaryotic cells plasma membranes are organized into microdomains of specialized function such as lipid rafts and caveolae, with a specific lipid composition highly enriched in cholesterol and glycosphingolipids. In addition to their role in regulating signal transduction, multiple functions have been proposed, such as anchorage of receptors, trafficking of cholesterol, and regulation of permeability. However, an extensive understanding of their protein composition in human heart, both in failing and non-failing conditions, is not yet available. Membrane microdomains were isolated from left ventricular tissue of both failing (n = 15) and non-failing (n = 15) human hearts. Protein composition and differential protein expression was explored by comparing series of 2-D maps and subsequent identification by LC-MS/MS analysis. Data indicated that heart membrane microdomains are enriched in chaperones, cytoskeletal-associated proteins, enzymes and protein involved in signal transduction pathway. In addition, differential protein expression profile revealed that 30 proteins were specifically up- or down-regulated in human heart failure membrane microdomains. This study resulted in the identification of human heart membrane microdomain protein composition, which was not previously available. Moreover, it allowed the identification of multiple proteins whose expression is altered in heart failure, thus opening new perspectives to determine which role they may play in this disease.

  16. Efficacy and safety of bosentan for pulmonary arterial hypertension in adults with congenital heart disease.

    PubMed

    Monfredi, Oliver; Griffiths, Linda; Clarke, Bernard; Mahadevan, Vaikom S

    2011-11-15

    The dual endothelin receptor antagonist, bosentan, has been shown to be well tolerated and effective in improving pulmonary arterial hypertension (PAH) symptoms in patients with Eisenmenger syndrome but data from longer-term studies are lacking. The aim of this study was to retrospectively analyze the long-term efficacy and safety of bosentan in adults with PAH secondary to congenital heart disease (PAH-CHD). Prospectively collected data from adult patients with PAH-CHD (with and without Down syndrome) initiated on bosentan from October 2007 through June 2010 were analyzed. Parameters measured before bosentan initiation (62.5 mg 2 times/day for 4 weeks titrated to 125 mg 2 times/day) and at each follow-up (1 month and 3, 6, 9, 12, 18, and 24 months) included exercise capacity (6-minute walk distance [6MWD]), pretest oxygen saturation, liver enzymes, and hemoglobin. Data were analyzed from 39 patients with PAH-CHD (10 with Down syndrome) who had received ≥ 1 dose of bosentan (mean duration of therapy 2.1 ± 1.5 years). A significant (p < 0.0001) average improvement in 6MWD of 54 m over a 2-year period in patients with PAH-CHD without Down syndrome was observed. Men patients had a 6MWD of 33 m greater than women (p < 0.01). In all patients, oxygen saturation, liver enzymes, and hemoglobin levels remained stable. There were no discontinuations from bosentan owing to adverse events. In conclusion, patients with PAH-CHD without Down syndrome gain long-term symptomatic benefits in exercise capacity after bosentan treatment. Men seem to benefit more on bosentan treatment. Bosentan appears to be well tolerated in patients with PAH-CHD with or without Down syndrome.

  17. Adoption of American Heart Association 2020 ideal healthy diet recommendations prevents weight gain in young adults.

    PubMed

    Forget, Geneviève; Doyon, Myriam; Lacerte, Guillaume; Labonté, Mélissa; Brown, Christine; Carpentier, André C; Langlois, Marie-France; Hivert, Marie-France

    2013-11-01

    In 2010, the American Heart Association established the concept of ideal cardiovascular health. Nationally representative data estimated that <1% of Americans meet the seven health metrics required for achieving ideal cardiovascular health, with the main challenge residing in meeting the criteria for an ideal Healthy Diet Score. In a cohort of young adults (N=196), we aimed to investigate the prevalence of ideal cardiovascular health and ideal Healthy Diet Score and its association to weight gain over a 4-year follow-up period. Anthropometric measures, blood pressure, and blood samples were taken according to standardized procedures. Dietary intake was measured by a 3-day food diary and verified by a registered dietitian. We observed that only 0.5% of our sample met the criteria for ideal cardiovascular health and only 4.1% met the criteria for an ideal Healthy Diet Score. The components of the Healthy Diet Score with the lowest observance were consumption of fruits and vegetables (9.7%) and whole grains (14.8%). Meeting zero or one out of five of the Healthy Diet Score components was associated with increased risk of weight gain over 4 years compared with meeting at least two components (P=0.03). With the exception of dietary criteria, prevalence was high for achieving ideal levels of the remaining six cardiovascular health metrics. In conclusion, in this sample of young adults, a very low prevalence of ideal overall cardiovascular health was observed, mainly driven by poor dietary habits, and a poor Healthy Diet Score was associated with increased weight gain.

  18. Perceptions of Older Adults with Heart Failure on Playing an Interactive Digital e-Health Game (IDEG) for Learning About Heart Failure (HF): Prototype Development and Usability Testing.

    PubMed

    Radhakrishnan, Kavita; Toprac, Paul; O'Hair, Matt; Bias, Randolph; Mackert, Mike; Xie, Bo; Kim, Miyong; Bradley, Paul

    2016-01-01

    Effective self-management can decrease up to 50% of heart failure (HF) hospitalizations. However, self-management by patients with HF remains poor. We describe the development and usability testing of an interactive digital e-health game (IDEG) for older patients with HF in Central Texas, USA. Majority of the participants (5 out of 6) who participated in the usability testing found the game interesting, enjoyable and helpful to play. Developing an IDEG that is satisfying and acceptable to older adults with HF is feasible.

  19. Heart rate variability is reduced in underweight and overweight healthy adult women.

    PubMed

    Triggiani, Antonio Ivano; Valenzano, Anna; Ciliberti, Michela Anna Pia; Moscatelli, Fiorenzo; Villani, Stefano; Monda, Marcellino; Messina, Giovanni; Federici, Antonio; Babiloni, Claudio; Cibelli, Giuseppe

    2017-03-01

    Heart rate variability (HRV) is altered in obese subjects, but whether this is true also in underweight (UW) subjects is still under debate. We investigated the HRV profile in a sample of healthy adult women and its association with adiposity. Five-minute resting state electrocardiographic activity was recorded in 69 subjects grouped according to their body mass index, [23 normal weight (NW), 23 overweight/obese (OW) and 23 UW). Body fat mass (FM) was measured by bio-impedance. Frequency- and time-domain analyses were performed. Compared to NW, UW and OW subjects showed a significant decrease in HRV indices, as revealed by spectral analysis. No differences were observed between UW and OW subjects. A second-order polynomial regression unveiled an inverted U-shaped relationship between FM extent and HRV indices. A decrease of HRV indices was associated with changes in FM extent, proving that in UW and OW subjects, the adaptive flexibility of autonomic cardiac function was reduced. These findings provide important clues to guide future studies addressed to determine how changes in adiposity and autonomic cardiac function may contribute to health risk.

  20. Heart rate and blood pressure response in adult men and women during exercise and sexual activity.

    PubMed

    Palmeri, Sebastian T; Kostis, John B; Casazza, Laurie; Sleeper, Lynn A; Lu, Minmin; Nezgoda, Joseph; Rosen, Raymond S

    2007-12-15

    The purpose of this study was to assess the heart rate (HR) and blood pressure (BP) response of sexual activity compared with treadmill exercise in adult men and women. Nineteen men, 55 +/- 8 years, and 13 women, 51 +/- 7 years, underwent a maximal Bruce protocol treadmill stress test followed by home-monitored sexual activity using noninvasive HR and BP recording devices. The mean treadmill times were significantly shorter than the mean times of sexual activity for men and women (p <0.001 and p = 0.002, respectively). For the men, average maximum HR, systolic BP, and HR-BP product during sexual activity were 72%, 80%, and 57% of respective measurements during treadmill exercise. For the women, maximum HR, systolic BP, and HR-BP product during sexual activity were 64%, 75%, and 48% of respective measurements during treadmill exercise. Age correlated inversely with duration of treadmill exercise (a 9-second decrease in duration per increasing year of age; p = 0.036), and with the duration of sexual activity (a 1-minute decrease in duration per increasing year of age; p = 0.024). Treadmill exercise duration predicted sexual activity duration (a 2.3-minute increase in sexual activity duration per each minute treadmill duration; p = 0.026). In conclusion, sexual activity provides modest physical stress comparable with stage II of the standard multistage Bruce treadmill protocol for men and stage I for women.

  1. MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes.

    PubMed

    Zhang, Xiaomin; Azhar, Gohar; Williams, Emmanuel D; Rogers, Steven C; Wei, Jeanne Y

    2015-01-01

    The microRNAs and microRNA clusters have been implicated in normal cardiac development and also disease, including cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens of microRNAs, the expression of a microRNA cluster could have a substantial impact on its target genes. In the present study, the configuration and distribution of microRNA clusters in the mouse genome were examined at various inter-microRNA distances. Three important microRNA clusters that are significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363, and miR-106b-25, were also examined in terms of their genomic location, RNA transcript character, sequence homology, and their relationship with the corresponding microRNA families. Multiple microRNAs derived from the three clusters potentially target various protein components of the cdc42-SRF signaling pathway, which regulates cytoskeleton dynamics associated with cardiac structure and function. The data indicate that aging impacted the expression of both guide and passenger strands of the microRNA clusters; nutrient stress also affected the expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR-106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby affect cardiac morphology and function during pathological conditions and the aging process.

  2. Anatomy of the Heart

    MedlinePlus

    ... picture of the outside of a normal, healthy, human heart. Heart Exterior Figure A shows the location of ... picture of the inside of a normal, healthy, human heart. Heart Interior Figure A shows the location of ...

  3. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    SciTech Connect

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalen; Palmqvist, Lars; Jeppsson, Anders; Hulten, Lillemor Mattsson

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We found a 17-fold upregulation of ALOX15 in the ischemic heart. Black-Right-Pointing-Pointer Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. Black-Right-Pointing-Pointer We observed increased levels of proinflammatory markers in ischemic heart tissue. Black-Right-Pointing-Pointer Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1{alpha} (HIF-1{alpha}) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1{alpha} mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield

  4. "Young at heart": Regenerative potential linked to immature cardiac phenotypes.

    PubMed

    Gomes, Renata S M; Skroblin, Philipp; Munster, Alex B; Tomlins, Hannah; Langley, Sarah R; Zampetaki, Anna; Yin, Xiaoke; Wardle, Fiona C; Mayr, Manuel

    2016-03-01

    The adult human myocardium is incapable of regeneration; yet, the zebrafish (Danio rerio) can regenerate damaged myocardium. Similar to the zebrafish heart, hearts of neonatal, but not adult mice are capable of myocardial regeneration. We performed a proteomics analysis of adult zebrafish hearts and compared their protein expression profile to hearts from neonatal and adult mice. Using difference in-gel electrophoresis (DIGE), there was little overlap between the proteome from adult mouse (>8weeks old) and adult zebrafish (18months old) hearts. Similarly, there was a significant degree of mismatch between the protein expression in neonatal and adult mouse hearts. Enrichment analysis of the selected proteins revealed over-expression of DNA synthesis-related proteins in the cardiac proteome of the adult zebrafish heart similar to neonatal and 4days old mice, whereas in hearts of adult mice there was a mitochondria-related predominance in protein expression. Importantly, we noted pronounced differences in the myofilament composition: the adult zebrafish heart lacks many of the myofilament proteins of differentiated adult cardiomyocytes such as the ventricular isoforms of myosin light chains and nebulette. Instead, troponin I and myozenin 1 were expressed as skeletal isoforms rather than cardiac isoforms. The relative immaturity of the adult zebrafish heart was further supported by cardiac microRNA data. Our assessment of zebrafish and mammalian hearts challenges the assertions on the translational potential of cardiac regeneration in the zebrafish model. The immature myofilament composition of the fish heart may explain why adult mouse and human cardiomyocytes lack this endogenous repair mechanism.

  5. Differentiated human stem cells resemble fetal, not adult, β cells.

    PubMed

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.

  6. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models.

    PubMed

    Wang, Louis W; Huttner, Inken G; Santiago, Celine F; Kesteven, Scott H; Yu, Ze-Yan; Feneley, Michael P; Fatkin, Diane

    2017-01-01

    The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l(-1) having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high frequency

  7. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models

    PubMed Central

    Wang, Louis W.; Huttner, Inken G.; Santiago, Celine F.; Kesteven, Scott H.; Yu, Ze-Yan; Feneley, Michael P.

    2017-01-01

    ABSTRACT The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l−1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high

  8. Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations

    PubMed Central

    Boyle, Patrick M.; Vogt, Christoph C.; Karathanos, Thomas V.; Arevalo, Hermenegild J.; Fleischmann, Bernd K.; Trayanova, Natalia A.

    2016-01-01

    Ventricular arrhythmias are among the most severe complications of heart disease and can result in sudden cardiac death. Patients at risk currently receive implantable defibrillators that deliver electrical shocks to terminate arrhythmias on demand. However, strong electrical shocks can damage the heart and cause severe pain. Therefore, we have tested optogenetic defibrillation using expression of the light-sensitive channel channelrhodopsin-2 (ChR2) in cardiac tissue. Epicardial illumination effectively terminated ventricular arrhythmias in hearts from transgenic mice and from WT mice after adeno-associated virus–based gene transfer of ChR2. We also explored optogenetic defibrillation for human hearts, taking advantage of a recently developed, clinically validated in silico approach for simulating infarct-related ventricular tachycardia (VT). Our analysis revealed that illumination with red light effectively terminates VT in diseased, ChR2-expressing human hearts. Mechanistically, we determined that the observed VT termination is due to ChR2-mediated transmural depolarization of the myocardium, which causes a block of voltage-dependent Na+ channels throughout the myocardial wall and interrupts wavefront propagation into illuminated tissue. Thus, our results demonstrate that optogenetic defibrillation is highly effective in the mouse heart and could potentially be translated into humans to achieve nondamaging and pain-free termination of ventricular arrhythmia. PMID:27617859

  9. Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: executive summary.

    PubMed

    Silversides, Candice K; Marelli, Ariane; Beauchesne, Luc; Dore, Annie; Kiess, Marla; Salehian, Omid; Bradley, Timothy; Colman, Jack; Connelly, Michael; Harris, Louise; Khairy, Paul; Mital, Seema; Niwa, Koichiro; Oechslin, Erwin; Poirier, Nancy; Schwerzmann, Markus; Taylor, Dylan; Vonder Muhll, Isabelle; Baumgartner, Helmut; Benson, Lee; Celermajer, David; Greutmann, Matthias; Horlick, Eric; Landzberg, Mike; Meijboom, Folkert; Mulder, Barbara; Warnes, Carole; Webb, Gary; Therrien, Judith

    2010-03-01

    With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure, and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death.Medical aspects that need to be considered relate to the long-term and multisystemic effects of single-ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the understanding of the late outcomes, genetics, medical therapy and interventional approaches in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. The present executive summary is a brief overview of the new guidelines and includes the recommendations for interventions. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology, including sections on genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy and contraception risks, and follow-up requirements. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.

  10. Differential expression of embryonic epicardial progenitor markers and localization of cardiac fibrosis in adult ischemic injury and hypertensive heart disease.

    PubMed

    Braitsch, Caitlin M; Kanisicak, Onur; van Berlo, Jop H; Molkentin, Jeffery D; Yutzey, Katherine E

    2013-12-01

    During embryonic heart development, the transcription factors Tcf21, Wt1, and Tbx18 regulate activation and differentiation of epicardium-derived cells, including fibroblast lineages. Expression of these epicardial progenitor factors and localization of cardiac fibrosis were examined in mouse models of cardiovascular disease and in human diseased hearts. Following ischemic injury in mice, epicardial fibrosis is apparent in the thickened layer of subepicardial cells that express Wt1, Tbx18, and Tcf21. Perivascular fibrosis with predominant expression of Tcf21, but not Wt1 or Tbx18, occurs in mouse models of pressure overload or hypertensive heart disease, but not following ischemic injury. Areas of interstitial fibrosis in ischemic and hypertensive hearts actively express Tcf21, Wt1, and Tbx18. In all areas of fibrosis, cells that express epicardial progenitor factors are distinct from CD45-positive immune cells. In human diseased hearts, differential expression of Tcf21, Wt1, and Tbx18 also is detected with epicardial, perivascular, and interstitial fibrosis, indicating conservation of reactivated developmental mechanisms in cardiac fibrosis in mice and humans. Together, these data provide evidence for distinct fibrogenic mechanisms that include Tcf21, separate from Wt1 and Tbx18, in different fibroblast populations in response to specific types of cardiac injury.

  11. Grown-up congenital heart (GUCH) disease: current needs and provision of service for adolescents and adults with congenital heart disease in the UK

    PubMed Central

    2002-01-01

    The size of the national population of patients with grown-up congenital heart disease (GUCH) is uncertain, but since 80–85% of patients born with congenital heart disease now survive to adulthood (age 16 years), an annual increase of 2500 can be anticipated according to birth rate. Organisation of medical care is haphazard with only three of 18 cardiac surgical centres operating on over 30 cases per annum and only two established specialised units fully equipped and staffed. Not all grown-ups with congenital heart disease require the same level of expertise; 20–25% are complex, rare, etc, and require life long expert supervision and/or intervention; a further 35–40% require access to expert consultation. The rest, about 40%, have simple or cured diseases and need little or no specialist expertise. The size of the population needing expertise is small in comparison to coronary and hypertensive disease, aging, and increasing in complexity. It requires expert cardiac surgery and specialised medical cardiology, intensive care, electrophysiology, imaging and interventions, "at risk" pregnancy services, connection to transplant services familiar with their basic problem, clinical nurse specialist advisors, and trained nurses. An integrated national service is described with 4–6 specialist units established within adult cardiology, ideally in relation or proximity to university hospital/departments in appropriate geographic location, based in association with established paediatric cardiac surgical centres with designated inpatient and outpatient facilities for grown-up patients with congenital heart disease. Specialist units should accept responsibility for educating the profession, training the specialists, cooperative research, receiving patients "out of region", sharing particular skills between each other, and they must liaise with other services and trusts in the health service, particularly specified outpatient clinics in district and regional centres. Not

  12. Late Pleistocene adult mortality patterns and modern human establishment

    PubMed Central

    Trinkaus, Erik

    2011-01-01

    The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20–40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans. PMID:21220336

  13. Relationships between QT interval and heart rate variability at rest and the covariates in healthy young adults.

    PubMed

    Arai, Kaori; Nakagawa, Yui; Iwata, Toyoto; Horiguchi, Hyogo; Murata, Katsuyuki

    2013-01-01

    To clarify the links between ECG QT-related parameters and heart rate variability (HRV) and the covariates possibly distorting them, the averaged RR and QT intervals in a single lead ECG were measured for 64 male and 86 female subjects aged 18-26. The QT index, defined by Rautaharju et al., in the young adults was not significantly related to any HRV parameters nor heart rate, but the Bazett's corrected QT (QTc) interval was associated negatively with the parasympathetic activity and positively with heart rate. No significant differences in the QTc interval, QT index or heart rate were seen between the men and women, but they significantly differed between both sexes after adjustment for possible covariates such as age and body mass index (BMI). Significant sex differences in parasympathetic parameters of the HRV were unchanged before and after the adjustment, but significant differences observed in the unadjusted sympathetic parameters disappeared after adjusting for covariates. Age, BMI and body fat percentage also were significant covariates affecting these ECG parameters. Consequently, QT index, unaffected by heart rate and HRV parameters, appears to be a more useful indicator than the QTc interval. Instead, the QT index and HRV parameters are recommended to be simultaneously measured in epidemiological research because they are probably complementary in assessing autonomic nervous function. Also, these parameters should be analyzed in men and women separately.

  14. Linking adult hippocampal neurogenesis with human physiology and disease.

    PubMed

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc.

  15. Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart.

    PubMed

    Caracausi, Maria; Piovesan, Allison; Vitale, Lorenza; Pelleri, Maria Chiara

    2017-04-01

    A systematic meta-analysis of the available gene expression profiling datasets for the whole normal human heart generated a quantitative transcriptome reference map of this organ. Transcriptome Mapper (TRAM) software integrated 32 gene expression profile datasets from different sources returning a reference value of expression for each of the 43,360 known, mapped transcripts assayed by any of the experimental platforms used in this regard. Main findings include the visualization at the gene and chromosomal levels of the classical description of the basic histology and physiology of the heart, the identification of suitable housekeeping reference genes, the analysis of stoichiometry of gene products, and the focusing on chromosome 21 genes, which are present in one excess copy in Down syndrome subjects, presenting cardiovascular defects in 30-40% of cases. Independent in vitro validation showed an excellent correlation coefficient (r = 0.98) with the in silico data. Remarkably, heart/non-cardiac tissue expression ratio may also be used to anticipate that effects of mutations will most probably affect or not the heart. The quantitative reference global portrait of gene expression in the whole normal human heart illustrates the structural and functional aspects of the whole organ and is a general model to understand the mechanisms underlying heart pathophysiology. J. Cell. Physiol. 232: 759-770, 2017. © 2016 Wiley Periodicals, Inc.

  16. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  17. Maps of the adult human hypothalamus

    PubMed Central

    Lemaire, Jean-Jacques; Nezzar, Hachemi; Sakka, Laurent; Boirie, Yves; Fontaine, Denys; Coste, Aurélien; Coll, Guillaume; Sontheimer, Anna; Sarret, Catherine; Gabrillargues, Jean; De Salles, Antonio

    2013-01-01

    The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents. PMID:23682342

  18. Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves

    PubMed Central

    Miller, Jordan D.; Chu, Yi; Heistad, Donald D.

    2009-01-01

    Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2·−) was measured in heart valves from explanted human hearts that were not used for transplantation. O2·− levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in O2·−. Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased O2·− levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in O2·− during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated O2·−, and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine. PMID:19666839

  19. Computational modelling of electrocardiograms: repolarisation and T-wave polarity in the human heart.

    PubMed

    Hurtado, Daniel E; Kuhl, Ellen

    2014-01-01

    For more than a century, electrophysiologists, cardiologists and engineers have studied the electrical activity of the human heart to better understand rhythm disorders and possible treatment options. Although the depolarisation sequence of the heart is relatively well characterised, the repolarisation sequence remains a subject of great controversy. Here, we study regional and temporal variations in both depolarisation and repolarisation using a finite element approach. We discretise the governing equations in time using an unconditionally stable implicit Euler backward scheme and in space using a consistently linearised Newton-Raphson-based finite element solver. Through systematic parameter-sensitivity studies, we establish a direct relation between a normal positive T-wave and the non-uniform distribution of the controlling parameter, which we have termed refractoriness. To establish a healthy baseline model, we calibrate the refractoriness using clinically measured action potential durations at different locations in the human heart. We demonstrate the potential of our model by comparing the computationally predicted and clinically measured depolarisation and repolarisation profiles across the left ventricle. The proposed framework allows us to explore how local action potential durations on the microscopic scale translate into global repolarisation sequences on the macroscopic scale. We anticipate that our calibrated human heart model can be widely used to explore cardiac excitation in health and disease. For example, our model can serve to identify optimal pacing sites in patients with heart failure and to localise optimal ablation sites in patients with cardiac fibrillation.

  20. The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue.

    PubMed

    Sobanski, Piotr; Krajnik, Malgorzata; Shaqura, Mohammed; Bloch-Boguslawska, Elzbieta; Schäfer, Michael; Mousa, Shaaban A

    2014-11-01

    Functional evidence suggests that the stimulation of peripheral and central opioid receptors (ORs) is able to modulate heart function. Moreover, selective stimulation of either cardiac or central ORs evokes preconditioning and, therefore, protects the heart against ischemic injury. However, anatomic evidence for OR subtypes in the human heart is scarce. Human heart tissue obtained during autopsy after sudden death was examined immunohistochemically for mu- (MOR), kappa- (KOR), and delta- (DOR) OR subtypes. MOR and DOR immunoreactivity was found mainly in myocardial cells, as well as on sparse individual nerve fibers. KOR immunoreactivity was identified predominantly in myocardial cells and on intrinsic cardiac adrenergic (ICA) cell-like structures. Double immunofluorescence confocal microscopy revealed that DOR colocalized with the neuronal marker PGP9.5, as well as with the sensory neuron marker calcitonin gene-related peptide (CGRP). CGRP-immunoreactive (IR) fibers were detected either in nerve bundles or as sparse individual fibers containing varicose-like structures. Our findings offer the first hint of an anatomic basis for the existence of OR subtypes in the human heart by demonstrating their presence in CGRP-IR sensory nerve fibers, small cells with an eccentric nucleus resembling ICA cells, and myocardial cells. Taken together, this suggests the role of opioids in both the neural transmission and regulation of myocardial cell function.

  1. Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types.

    PubMed

    Loh, Kyle M; Chen, Angela; Koh, Pang Wei; Deng, Tianda Z; Sinha, Rahul; Tsai, Jonathan M; Barkal, Amira A; Shen, Kimberle Y; Jain, Rajan; Morganti, Rachel M; Shyh-Chang, Ng; Fernhoff, Nathaniel B; George, Benson M; Wernig, Gerlinde; Salomon, Rachel E A; Chen, Zhenghao; Vogel, Hannes; Epstein, Jonathan A; Kundaje, Anshul; Talbot, William S; Beachy, Philip A; Ang, Lay Teng; Weissman, Irving L

    2016-07-14

    Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT.

  2. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  3. Cardiac myosin-Th17 responses promote heart failure in human myocarditis

    PubMed Central

    Myers, Jennifer M.; Cooper, Leslie T.; Kem, David C.; Stavrakis, Stavros; Kosanke, Stanley D.; Shevach, Ethan M.; Fairweather, DeLisa; Stoner, Julie A.; Cox, Carol J.; Cunningham, Madeleine W.

    2016-01-01

    In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4+IL17+ T cells and Th17-promoting cytokines IL-6, TGF-β, and IL-23 as well as GM-CSF–secreting CD4+ T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14+ monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17–producing T cells and IL-17–promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3+ Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-β, IL-6, and IL-23 from myocarditic CD14+ monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option. PMID:27366791

  4. Adenosine reduces postbypass transfusion requirements in humans after heart surgery.

    PubMed Central

    Mentzer, R M; Rahko, P S; Canver, C C; Chopra, P S; Love, R B; Cook, T D; Hegge, M O; Lasley, R D

    1996-01-01

    OBJECTIVE: The objective of this study was to determine the effect, if any, of adenosine blood cardioplegia on blood component usage after heart surgery. SUMMARY BACKGROUND DATA: The most common cause of nonsurgical postcardiopulmonary bypass bleeding is platelet dysfunction. For this reason, pharmacologic agents are under investigation in an effort to reduce the need for transfusion in this setting. METHODS: A posthoc analysis of blood product usage was performed in data obtained from a Phase I, single center, open label, randomized study performed in 63 patients. The trial was designed to test the safety and tolerance of adenosine when added to blood cardioplegia in increasing doses to enhance myocardial protection. The database provided information regarding the effect of adenosine cardioplegia on venous plasma adenosine concentrations, the amount of platelets, fresh frozen plasma and packed erythrocytes used, and the association between the adenosine dose and postoperative thoracic drainage. RESULTS: The postoperative thoracic drainage at 6 hours, 24 hours, and at the time of chest tube removal in the high-dose adenosine cardioplegia group was 68%, 76%, and 75% of the placebo and low-dose adenosine cardioplegia group (p < 0.05). The highest dose of adenosine studied increased baseline adenosine venous plasma levels 360-fold, from 0.17 +/- 0.09 mumol/L to 42.30 +/- 11.20 mumol/L (p < 0.05). This marked increase was associated with a 68%, 56%, and 58% reduction in platelet, fresh frozen plasma, and packed erythrocyte usage, respectively (p < 0.05). CONCLUSIONS: In addition to enhancing the heart's tolerance to ischemia, adenosine-supplemented cardioplegic solution also may reduce bleeding after cardiopulmonary bypass. PMID:8857856

  5. Contrary microRNA Expression Pattern Between Fetal and Adult Cardiac Remodeling: Therapeutic Value for Heart Failure.

    PubMed

    Yan, Hualin; Li, Yifei; Wang, Chuan; Zhang, Yi; Liu, Cong; Zhou, Kaiyu; Hua, Yimin

    2016-08-10

    microRNAs (miRNAs) belong to a class of non-coding RNAs that regulate post-transcriptional gene expression during development and disease. Growing evidence indicates abundant miRNA expression changes and their important role in cardiac hypertrophy and failure. However, the role of miRNAs in fetal cardiac remodeling is little known. Here, we investigated the altered expression of fifteen miRNAs in rat fetal cardiac remodeling compared with adult cardiac remodeling. Among fifteen tested miRNAs, eleven and five miRNAs (miR-199a-5p, miR-214-3p, miR-155-3p, miR-155-5p and miR-499-5p) are significantly differentially expressed in fetal and adult cardiac remodeling, respectively. After comparison of miRNA expression in fetal and adult cardiac remodeling, we find that miRNA expression returns to the fetal level in adult cardiac failure and is activated in advance of the adult level in fetal failure. The current study highlights the contrary expression pattern between fetal and adult cardiac remodeling and that supports a novel potential therapeutic approach to treating heart failure.

  6. Transmural heterogeneity of cellular level power output is reduced in human heart failure

    PubMed Central

    Haynes, Premi; Nava, Kristofer E.; Lawson, Benjamin A.; Chung, Charles S.; Mitov, Mihail I.; Campbell, Stuart G.; Stromberg, Arnold J.; Sadayappan, Sakthivel; Bonnell, Mark R.; Hoopes, Charles W.; Campbell, Kenneth S.

    2014-01-01

    Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces transmural region-specific changes in contractile function. Permeabilized samples were prepared from the sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricular free wall of non-failing (n=6) and failing (n=10) human hearts. Power, an in vitro index of systolic function, was higher in non-failing mid-myocardial samples (0.59±0.06 μW mg−1) than in samples from the sub-epicardium (p=0.021) and the sub-endocardium (p=0.015). Non-failing mid-myocardial samples also produced more isometric force (14.3±1.33 kN m−2) than samples from the sub-epicardium (p=0.008) and the sub-endocardium (p=0.026). Heart failure reduced power (p=0.009) and force (p=0.042) but affected the mid-myocardium more than the other transmural regions. Fibrosis increased with heart failure (p=0.021) and mid-myocardial tissue from failing hearts contained more collagen than matched sub-epicardial (p<0.001) and sub-endocardial (p=0.043) samples. Power output was correlated with the relative content of actin and troponin I, and was also statistically linked to the relative content and phosphorylation of desmin and myosin light chain- 1. Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in the mid-myocardium. Targeting fibrosis and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure. PMID:24560668

  7. Sleep Stage Dependence of Invariance Characteristics in Fluctuations of Healthy Human Heart Rate

    NASA Astrophysics Data System (ADS)

    Togo, Fumiharu; Kiyono, Ken; Struzik, Zbigniew R.; Yamamoto, Yoshiharu

    2005-08-01

    The outstanding feature of healthy human heart rate is the robust scale invariance in the non-Gaussian probability density function (PDF), which is preserved not only in a quiescent condition, but also in a dynamic state during waking hours [K. Kiyono et al. Phys. Rev. Lett. 93 (2004)]. Together with 1/f like scaling, this characteristic is a strong indication of far-from-equilibrium, critical-like dynamics of heart rate regulation. Our results suggest that healthy human heart rate departs from a critical state-like operation during sleeping hours, at a rate which is heterogeneous with respect to sleep stages annotated according to traditional techniques. We study specific contributions of sleep stages to the relative departure from criticality through the analysis of sleep stage dependence of the root mean square of multiscale local energy and the multiscale PDF. There is a possibility that the involvement of cortical activity may be important for a critical state-like operation.

  8. Holt-Oram Syndrome in Adult Presenting with Heart Failure: A Rare Presentation

    PubMed Central

    Kumar, Rupesh; Mahapatra, Subhendu Sekhar; Datta, Monalisa; Hoque, Amanul; Datta, Swarnendu; Ghosh, Soumyajit; Datta, Santanu; Bhattacharjee, Subhankar

    2014-01-01

    Holt-Oram syndrome is a rare inherited disorder involving the hands, arms, and the heart. The defects involve carpal bones of the wrist and the thumb and the associated cardiac anomalies like atrial or ventricular septal defects. Congenital cardiac and upper-limb malformations frequently occur together and are classified as heart-hand syndromes. The most common amongst the heart-hand disorders is the Holt-Oram syndrome, which is characterized by septal defects of the heart and preaxial radial ray abnormalities. Its incidence is one in 100,000 live births. Approximately three out of four patients have some cardiac abnormality with common associations being either an atrial septal defect or ventricular septal defect. Herein, we report a rare sporadic case of Holt-Oram syndrome with atrial septal defect with symptoms of heart failure in a forty-five-year-old lady who underwent emergency cardiac surgery for the symptoms. PMID:24826304

  9. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    PubMed

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  10. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds

    PubMed Central

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J.

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a ‘wildlife photographer’, resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds. PMID:27293597

  11. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    PubMed

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

  12. Evidence for differential sympathetic and parasympathetic reinnervation after heart transplantation in humans.

    PubMed

    Tio, R A; Reyners, A K; van Veldhuisen, D J; van den Berg, M P; Brouwer, R M; Haaksma, J; Smit, A J; Crijns, H J

    1997-12-11

    During heart transplantation (HTX) all neural connections are severed. In humans, signs of autonomic reinnervation have been found. In this study non-invasive tests were used to compare signs of sympathetic and parasympathetic reinnervation. Non-invasive autonomic function tests and heart rate variability parameters (HRV; 24 h electrocardiographic registration) were used to investigate signs of reinnervation. 16 HTX patients (14 males) were compared with age-and sex-matched controls. Parasympathetic heart rate changes in HTX compared to controls were attenuated during the diving test, deep breathing, the Valsalva maneuver and standing up but not during carotid sinus massage. Sympathetic heart rate increases were lower during the cold pressor test and mental stress. The blood pressure responses were comparable to the control group, but not during active standing and tilting. This finding suggests an obligatory 'blood pressure' role for the innervated heart in these two tests. All HRV parameters were lower in HTX. One or more normal parasympathetic responses were found in 13 out of 16 patients versus 4 out of 16 with normal sympathetic responses (p < 0.05). Heart rate variations were less in case of a higher donor age, and higher in case of a longer time after HTX. Parasympathetic signs of reinnervation are more common than sympathetic signs of reinnervation. A higher donor age reduces signs of reinnervation. If the sympatho-vagal balance is a prognostic factor in HTX patients as it is in other cardiac diseases these findings are clinically relevant.

  13. Optimized Three Dimensional Sodium Imaging of the Human Heart on a Clinical 3T scanner

    PubMed Central

    Gai, Neville D.; Rochitte, Carlos; Nacif, Marcelo S.; Bluemke, David A.

    2014-01-01

    Purpose Optimization of sequence and sequence parameters to allow 3D sodium imaging of the entire human heart in-vivo in a clinically reasonable time. Theory and Methods A stack of spirals pulse sequence was optimized for cardiac imaging by considering factors such as spoiling, nutation angles, repetition time, echo time, T1/T2 relaxation, off-resonance, data acquisition window, motion and segmented k-space acquisition. Simulations based on Bloch equations as well as the exact trajectory used for data acquisition provided the basis for choice of parameter combinations for sodium imaging. Sodium phantom scanning was used to validate the choice of parameters and for corroboration with simulations. In-vivo cardiac imaging in six volunteers was also done with an optimized sequence. Results Phantom studies showed good correlation with simulation results. Images obtained from human volunteers showed that the heart can be imaged with a nominal resolution of 5 × 5 × 10 mm3 and with SNR>15 (in the septum) in about 6-10 minutes. Long axis views of the reformatted human heart show true 3D imaging capability. Conclusion Optimization of the sequence and its parameters allowed in-vivo 3D sodium imaging of the entire human heart in a clinically reasonable time. PMID:24639022

  14. Visualization of human heart conduction system by means of fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Venius, Jonas; Bagdonas, Saulius; Žurauskas, Edvardas; Rotomskis, Ricardas

    2011-10-01

    The conduction system of the heart is a specific muscular tissue, where a heartbeat signal originates and initiates the depolarization of the ventricles. The muscular origin makes it complicated to distinguish the conduction system from the surrounding tissues. A surgical intervention can lead to the accidental harm of the conduction system, which may eventually result in a dangerous obstruction of the heart functionality. Therefore, there is an immense necessity for developing a helpful method to visualize the conduction system during the operation time. The specimens for the spectroscopic studies were taken from nine diverse human hearts. The localization of distinct types of the tissue was preliminary marked by the pathologist and approved histologically after the spectral measurements. Variations in intensity, as well as in shape, were detected in autofluorescence spectra of different heart tissues. The most distinct differences were observed between the heart conduction system and the surrounding tissues under 330 and 380 nm excitation. The spectral region around 460 nm appeared to be the most suitable for an unambiguous differentiation of the human conduction system avoiding the absorption peak of blood. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, was also demonstrated.

  15. [Human factors and heart surgery: a Cartesian dream].

    PubMed

    de Leval, M R

    1996-01-01

    It is postulated that high technology medicine can be assimilated to complex socio-technical systems such as the aviation industry, nuclear power or chemical plants etc. It is proposed to apply to cardiac surgery the techniques of human reliability and human error analysis that have been acquired over the past two decades to enhance safety in those areas of high technology. It is now widely accepted that in complex socio-technical systems accidents are due to human factors in 60-80% of the cases. Accident theories and, in particular theories of organisational accidents, have been applied prospectively to negative surgical outcomes in an attempt to understand their causation ad to establish defence mechanisms to prevent them or at least mitigate their consequences. The philosophical issues raised by this endeavour will be outlined.

  16. Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity.

    PubMed

    Gordon, C J; Johnstone, A F; Aydin, C; Phillips, P M; MacPhail, R C; Kodavanti, U P; Ledbetter, A D; Jarema, K A

    2014-06-01

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats.

  17. Effect of Fasting Blood Glucose Level on Heart Rate Variability of Healthy Young Adults

    PubMed Central

    Lutfi, Mohamed Faisal; Elhakeem, Ramaze Farouke

    2016-01-01

    Background Previous studies reported increased risk of cardiac events in subjects with fasting blood glucose (FBG) levels lower than the diagnostic threshold of diabetes mellitus. However, whether increased cardiac events in those with upper normal FBG is secondary to the shift of their cardiac sympathovagal balance towards sympathetic predominance is unknown. Aims To assess the association between FBG levels and cardiac autonomic modulation (CAM) in euglycaemic healthy subjects based on heart rate variability (HRV) derived indices. Subjects and Methods The study enrolled 42 healthy young adults. Following sociodemographic and clinical assessment, blood samples were collected to measure FBG levels. Five minutes ECG recordings were performed to all participants to obtain frequency domain HRV measurements, namely the natural logarithm (Ln) of total power (LnTP), very low frequency (LnVLF), low frequency (LnLF) and high frequency (LnHF), low frequency/ high frequency ratio (LnLF/HF), normalized low frequency (LF Norm) and high frequency (HF Norm). Results FBG levels correlated positively with LnHF (r = 0.33, P = 0.031) and HF Norm (r = 0.35, P = 0.025) and negatively with LF Norm (r = -0.35, P = 0.025) and LnLF/HF (r = -0.33, P = 0.035). LnHF and HF Norm were significantly decreased in subjects with the lower (4.00 (1.34) ms2/Hz and 33.12 (11.94) n.u) compared to those with the upper FBG quartile (5.64 (1.63) ms2/Hz and 49.43 (17.73) n.u, P = 0.013 and 0.032 respectively). LF Norm and LnLF/HF were significantly increased in subjects with the lower (66.88 (11.94) n.u and 0.73 (0.53)) compared to those with the higher FBG quartile (50.58 (17.83) n.u and 0.03 (0.79), P = 0.032 and 0.038 respectively). Conclusion The present study is the first to demonstrate that rise of blood glucose concentration, within physiological range, is associated with higher parasympathetic, but lower sympathetic CAM. Further researches are needed to set out the glycemic threshold beyond which

  18. Bacteriology of moderate (chronic) periodontitis in mature adult humans.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Ranney, R R

    1983-01-01

    A total of 171 taxa was represented among 1,900 bacterial isolates from 60 samples of sites affected with moderate periodontitis in 22 mature adult humans. The composition of the subgingival sulcus flora was statistically significantly different from that of the adjacent supragingival flora and the subgingival flora of 14 people with healthy gingiva, but was not significantly different from that of sulci affected with severe periodontitis in 21 young human adults. The sulcus floras of moderate periodontitis and severe periodontitis shared many of their predominant bacterial species, but there were differences in the relative proportions of some of these species. Similar relationships were found for seven taxa of treponemes that were cultured from the samples. PMID:6642641

  19. Common multifractality in the heart rate variability and brain activity of healthy humans

    NASA Astrophysics Data System (ADS)

    Lin, D. C.; Sharif, A.

    2010-06-01

    The influence from the central nervous system on the human multifractal heart rate variability (HRV) is examined under the autonomic nervous system perturbation induced by the head-up-tilt body maneuver. We conducted the multifractal factorization analysis to factor out the common multifractal factor in the joint fluctuation of the beat-to-beat heart rate and electroencephalography data. Evidence of a central link in the multifractal HRV was found, where the transition towards increased (decreased) HRV multifractal complexity is associated with a stronger (weaker) multifractal correlation between the central and autonomic nervous systems.

  20. [Congenital heart disease in adults: residua, sequelae, and complications of cardiac defects repaired at an early age].

    PubMed

    Oliver Ruiz, José María

    2003-01-01

    Nowadays, it is estimated that 85% of the infants born with congenital heart disease (CHD) will survive to adulthood, thanks mainly to surgical or therapeutic procedures performed during infancy or childhood. The clinical profile and disease pattern of adults with CHD is changing. The prevalence of certain adult CHDs, such as tetralogy of Fallot, transposition of the great arteries or univentricular heart, is rising, but these conditions have practically become new diseases as a result of therapy. Most surviving patients present residua, sequelae, or complications, which can progress during adult life. These disorders can present electrophysiological disturbances, valvular disease, persistent shunts, myocardial dysfunction, pulmonary or systemic vascular disease, problems caused by prosthetic materials, infectious complications, thromboembolic events, or extravascular disorders involving multiple organs or systems. In tetralogy of Fallot, the most striking problems that affect long-term prognosis are pulmonary valve regurgitation, right ventricle dysfunction, and atrial or ventricular arrhythmias. The main problems appearing after physiological atrial repair of transposition of the great arteries are related to right ventricular function, since it is structurally unprepared for systemic circulation, and atrial arrhythmias. Surgical repair of univentricular heart using Fontan techniques should be considered a palliative procedure that does not modify the underlying structural disorder and exposes the postoperative patient to severe complications and problems. The increase in the number of patients with CHD who will reach adulthood in the coming decades makes it necessary to carefully consider the new healthcare demands that are being generated, who should be responsible for them, and how and where solutions can be found.

  1. Lymphatic Stomata in the Adult Human Pulmonary Ligament

    PubMed Central

    Miura, Masahiro; Iobe, Hiroaki; Kudo, Tomoo; Shimazu, Yoshihito; Aoba, Takaaki; Okudela, Koji; Nagahama, Kiyotaka; Sakamaki, Kentaro; Yoshida, Maki; Nagao, Toshitaka; Nakaya, Takeo; Kurata, Atsushi; Ohtani, Osamu

    2015-01-01

    Abstract Background: Lymphatic stomata are small lymphatic openings in the serosal membrane that communicate with the serosal cavity. Although these stomata have primarily been studied in experimental mammals, little is known concerning the presence and properties of lymphatic stomata in the adult human pleura. Thus, adult human pleurae were examined for the presence or absence of lymphatic stomata. Methods and Results: A total of 26 pulmonary ligaments (13 left and 13 right) were obtained from 15 adult human autopsy cases and examined using electron and light microscopy. The microscopic studies revealed the presence of apertures fringed with D2-40-positive, CD31-positive, and cytokeratin-negative endothelial cells directly communicating with submesothelial lymphatics in all of the pulmonary ligaments. The apertures' sizes and densities varied from case to case according to the serial tissue section. The medians of these aperture sizes ranged from 2.25 to 8.75 μm in the left pulmonary ligaments and from 2.50 to 12.50 μm in the right pulmonary ligaments. The densities of the apertures ranged from 2 to 9 per mm2 in the left pulmonary ligaments and from 2 to 18 per mm2 in the right pulmonary ligaments. However, no significant differences were found regarding the aperture size (p=0.359) and density (p=0.438) between the left and the right pulmonary ligaments. Conclusions: Our study revealed that apertures exhibit structural adequacy as lymphatic stomata on the surface of the pulmonary ligament, thereby providing evidence that lymphatic stomata are present in the adult human pleura. PMID:25526320

  2. The Physiological Effect of Human Grooming on the Heart Rate and the Heart Rate Variability of Laboratory Non-Human Primates: A Pilot Study in Male Rhesus Monkeys

    PubMed Central

    Grandi, Laura Clara; Ishida, Hiroaki

    2015-01-01

    Grooming is a widespread, essential, and complex behavior with social and affiliative valence in the non-human primate world. Its impact at the autonomous nervous system level has been studied during allogrooming among monkeys living in a semi-naturalistic environment. For the first time, we investigated the effect of human grooming to monkey in a typical experimental situation inside laboratory. We analyzed the autonomic response of male monkeys groomed by a familiar human (experimenter), in terms of the heart rate (HR) and heart rate variability (HRV) at different body parts. We considered the HRV in both the time (SDNN, RMSSD, and RMSSD/SDNN) and the frequency domain (HF, LF, and LF/HF). For this purpose, we recorded the electrocardiogram of two male rhesus monkeys seated in a primate chair while the experimenter groomed their mouth, chest, or arm. We demonstrated that (1) the grooming carried out by a familiar human determined a decrement of the HR and an increment of the HRV; (2) there was a difference in relation to the groomed body part. In particular, during grooming the mouth the HRV was higher than during grooming the arm and the chest. Taken together, the results represent the first evidence that grooming carried out by a familiar human on experimental monkeys has the comparable positive physiological effect of allogrooming between conspecifics. Moreover, since the results underlined the positive modulation of both HR and HRV, the present study could be a starting point to improve the well-being of non-human primates in experimental condition by means of grooming by a familiar person. PMID:26664977

  3. Doublecortin expression in the normal and epileptic adult human brain.

    PubMed

    Liu, Y W J; Curtis, M A; Gibbons, H M; Mee, E W; Bergin, P S; Teoh, H H; Connor, B; Dragunow, M; Faull, R L M

    2008-12-01

    Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

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

    PubMed

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

    2015-08-01

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

  5. Guided tissue regeneration in heart valve replacement: from preclinical research to first-in-human trials.

    PubMed

    Iop, L; Gerosa, G

    2015-01-01

    Heart valve tissue-guided regeneration aims to offer a functional and viable alternative to current prosthetic replacements. Not requiring previous cell seeding and conditioning in bioreactors, such exceptional tissue engineering approach is a very fascinating translational regenerative strategy. After in vivo implantation, decellularized heart valve scaffolds drive their same repopulation by recipient's cells for a prospective autologous-like tissue reconstruction, remodeling, and adaptation to the somatic growth of the patient. With such a viability, tissue-guided regenerated conduits can be delivered as off-the-shelf biodevices and possess all the potentialities for a long-lasting resolution of the dramatic inconvenience of heart valve diseases, both in children and in the elderly. A review on preclinical and clinical investigations of this therapeutic concept is provided with evaluation of the issues still to be well deliberated for an effective and safe in-human application.

  6. Sarcoplasmic reticulum-associated cyclic adenosine 5'-monophosphate phosphodiesterase activity in normal and failing human hearts.

    PubMed Central

    Movsesian, M A; Smith, C J; Krall, J; Bristow, M R; Manganiello, V C

    1991-01-01

    Sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was examined in microsomes prepared from the left ventricular myocardium of eight heart transplant recipients with end-stage idiopathic dilated cardiomyopathy and six unmatched organ donors with normal cardiac function. At cAMP concentrations less than or equal to 1.0 microM, sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was functionally homogeneous. cAMP phosphodiesterase activity was inhibited competitively by cGMP (Ki = 0.031 +/- 0.008 microM) and the cilostamide derivative OPC 3911 (Ki = 0.018 +/- 0.004 microM), but was essentially insensitive to rolipram. Vmax and Km were 781.7 +/- 109.2 nmol/mg per min and 0.188 +/- 0.031 microM, respectively, in microsomes prepared from nonfailing hearts and 793.9 +/- 68.9 nmol/mg per min and 0.150 +/- 0.027 microM in microsomes prepared from failing hearts. Microsomes prepared from nonfailing and failing hearts did not differ with respect to either the ratio of cAMP phosphodiesterase activity to ATP-dependent Ca2+ accumulation activity or the sensitivity of cAMP phosphodiesterase activity to inhibition by OPC 3911. These data suggest that the diminished inotropic efficacy of phosphodiesterase inhibitors in failing human hearts does not result from changes in the level, kinetic properties, or pharmacologic sensitivity of sarcoplasmic reticulum-associated cAMP phosphodiesterase activity. PMID:1647414

  7. Stretchable, multiplexed pH sensors with demonstrations on rabbit and human hearts undergoing ischemia.

    PubMed

    Chung, Hyun-Joong; Sulkin, Matthew S; Kim, Jong-Seon; Goudeseune, Camille; Chao, Hsin-Yun; Song, Joseph W; Yang, Sang Yoon; Hsu, Yung-Yu; Ghaffari, Roozbeh; Efimov, Igor R; Rogers, John A

    2014-01-01

    Stable pH is an established biomarker of health, relevant to all tissues of the body, including the heart. Clinical monitoring of pH in a practical manner, with high spatiotemporal resolution, is particularly difficult in organs such as the heart due to its soft mechanics, curvilinear geometry, heterogeneous surfaces, and continuous, complex rhythmic motion. The results presented here illustrate that advanced strategies in materials assembly and electrochemical growth can yield interconnected arrays of miniaturized IrOx pH sensors encapsulated in thin, low-modulus elastomers to yield conformal monitoring systems capable of noninvasive measurements on the surface of the beating heart. A thirty channel custom data acquisition system enables spatiotemporal pH mapping with a single potentiostat. In vitro testing reveals super-Nernstian sensitivity with excellent uniformity (69.9 ± 2.2 mV/pH), linear response to temperature (-1.6 mV °C(-1) ), and minimal influence of extracellular ions (<3.5 mV). Device examples include sensor arrays on balloon catheters and on skin-like stretchable membranes. Real-time measurement of pH on the surfaces of explanted rabbit hearts and a donated human heart during protocols of ischemia-reperfusion illustrate some of the capabilities. Envisioned applications range from devices for biological research, to surgical tools and long-term implants.

  8. Parallel computing simulation of electrical excitation and conduction in the 3D human heart.

    PubMed

    Di Yu; Dongping Du; Hui Yang; Yicheng Tu

    2014-01-01

    A correctly beating heart is important to ensure adequate circulation of blood throughout the body. Normal heart rhythm is produced by the orchestrated conduction of electrical signals throughout the heart. Cardiac electrical activity is the resulted function of a series of complex biochemical-mechanical reactions, which involves transportation and bio-distribution of ionic flows through a variety of biological ion channels. Cardiac arrhythmias are caused by the direct alteration of ion channel activity that results in changes in the AP waveform. In this work, we developed a whole-heart simulation model with the use of massive parallel computing with GPGPU and OpenGL. The simulation algorithm was implemented under several different versions for the purpose of comparisons, including one conventional CPU version and two GPU versions based on Nvidia CUDA platform. OpenGL was utilized for the visualization / interaction platform because it is open source, light weight and universally supported by various operating systems. The experimental results show that the GPU-based simulation outperforms the conventional CPU-based approach and significantly improves the speed of simulation. By adopting modern computer architecture, this present investigation enables real-time simulation and visualization of electrical excitation and conduction in the large and complicated 3D geometry of a real-world human heart.

  9. A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells.

    PubMed

    Später, Daniela; Abramczuk, Monika K; Buac, Kristina; Zangi, Lior; Stachel, Maxine W; Clarke, Jonathan; Sahara, Makoto; Ludwig, Andreas; Chien, Kenneth R

    2013-09-01

    Most of the mammalian heart is formed from mesodermal progenitors in the first and second heart fields (FHF and SHF), whereby the FHF gives rise to the left ventricle and parts of the atria and the SHF to the right ventricle, outflow tract and parts of the atria. Whereas SHF progenitors have been characterized in detail, using specific molecular markers, comprehensive studies on the FHF have been hampered by the lack of exclusive markers. Here, we present Hcn4 (hyperpolarization-activated cyclic nucleotide-gated channel 4) as an FHF marker. Lineage-traced Hcn4+/FHF cells delineate FHF-derived structures in the heart and primarily contribute to cardiomyogenic cell lineages, thereby identifying an early cardiomyogenic progenitor pool. As a surface marker, HCN4 also allowed the isolation of cardiomyogenic Hcn4+/FHF progenitors from human embryonic stem cells. We conclude that a primary purpose of the FHF is to generate cardiac muscle and support the contractile activity of the primitive heart tube, whereas SHF-derived progenitors contribute to heart cell lineage diversification.

  10. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    PubMed

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  11. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model for Heart Development and Congenital Heart Disease.

    PubMed

    Doyle, Michelle J; Lohr, Jamie L; Chapman, Christopher S; Koyano-Nakagawa, Naoko; Garry, Mary G; Garry, Daniel J

    2015-10-01

    Congenital heart disease (CHD) remains a significant health problem, with a growing population of survivors with chronic disease. Despite intense efforts to understand the genetic basis of CHD in humans, the etiology of most CHD is unknown. Furthermore, new models of CHD are required to better understand the development of CHD and to explore novel therapies for this patient population. In this review, we highlight the role that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes can serve to enhance our understanding of the development, pathophysiology and potential therapeutic targets for CHD. We highlight the use of hiPSC-derived cardiomyocytes to model gene regulatory interactions, cell-cell interactions and tissue interactions contributing to CHD. We further emphasize the importance of using hiPSC-derived cardiomyocytes as personalized research models. The use of hiPSCs presents an unprecedented opportunity to generate disease-specific cellular models, investigate the underlying molecular mechanisms of disease and uncover new therapeutic targets for CHD.

  12. Human heart valve-derived scaffold improves cardiac repair in a murine model of myocardial infarction

    PubMed Central

    Wan, Long; Chen, Yao; Wang, Zhenhua; Wang, Weijun; Schmull, Sebastian; Dong, Jun; Xue, Song; Imboden, Hans; Li, Jun

    2017-01-01

    Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction. PMID:28051180

  13. Insights into the genetic structure of congenital heart disease from human and murine studies on monogenic disorders.

    PubMed

    Prendiville, Terence; Jay, Patrick Y; Pu, William T

    2014-10-01

    Study of monogenic congenital heart disease (CHD) has provided entry points to gain new understanding of heart development and the molecular pathogenesis of CHD. In this review, we discuss monogenic CHD caused by mutations of the cardiac transcription factor genes NKX2-5 and GATA4. Detailed investigation of these genes in mice and humans has expanded our understanding of heart development, shedding light on the complex genetic and environmental factors that influence expression and penetrance of CHD gene mutations.

  14. Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

    PubMed Central

    Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

    2016-01-01

    Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF. PMID:27594875

  15. Association of heart rate recovery after exercise with indices of obesity in healthy, non-obese adults.

    PubMed

    Dimkpa, Uchechukwu; Oji, Jude O

    2010-03-01

    We aimed at determining whether body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) are associated with heart rate recovery (HRR) and to demonstrate which of the three indices of obesity, is the strongest predictor of HRR in apparently healthy non-obese adults. Three hundred and twenty-five subjects aged 18-66 years participated in the study. Anthropometric indices were measured, and subjects performed cycle ergometer exercise at 75-85% maximum heart rate. Heart rate (HR) was measured during the last minute of exercise and in the first minute of post-exercise recovery. A partial correlation test and a multiple linear regression analysis, after adjusting for age and peak oxygen uptake indicated that the best predictors of HRR were BMI in males and WHR in females. The present data suggest that, HRR is independently related to indices of obesity-BMI, WC, and WHR and strengthen the usefulness of these anthropometric indices in predicting cardiovascular risks. In addition, the findings suggest that BMI in men and WHR in women best express the relationship between obesity and cardiovascular risks.

  16. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus-Seropositive Patients.

    PubMed

    Conte, Antonio Hernandez; Kittleson, Michelle M; Dilibero, Deanna; Hardy, W David; Kobashigawa, Jon A; Esmailian, Fardad

    2016-02-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus-accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation.

  17. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus–Seropositive Patients

    PubMed Central

    Kittleson, Michelle M.; Dilibero, Deanna; Hardy, W. David; Kobashigawa, Jon A.; Esmailian, Fardad

    2016-01-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus—accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation. PMID:27047290

  18. Covert spatial attention is functionally intact in amblyopic human adults

    PubMed Central

    Roberts, Mariel; Cymerman, Rachel; Smith, R. Theodore; Kiorpes, Lynne; Carrasco, Marisa

    2016-01-01

    Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attention's role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from covert spatial attention—the selective processing of visual information in the absence of eye movements—to the same degree as neurotypical observers. We manipulated both involuntary (Experiment 1) and voluntary (Experiment 2) attention during an orientation discrimination task for which the effects of covert spatial attention have been well established in neurotypical and special populations. In both experiments, attention significantly improved accuracy and decreased reaction times to a similar extent (a) between the eyes of the amblyopic adults and (b) between the amblyopes and their age- and gender-matched controls. Moreover, deployment of voluntary attention away from the target location significantly impaired task performance (Experiment 2). The magnitudes of the involuntary and voluntary attention benefits did not correlate with amblyopic depth or severity. Both groups of observers showed canonical performance fields (better performance along the horizontal than vertical meridian and at the lower than upper vertical meridian) and similar effects of attention across locations. Despite their characteristic low-level vision impairments, covert spatial attention remains functionally intact in human amblyopic adults. PMID:28033433

  19. The nutrition intervention improved adult human capital and economic productivity.

    PubMed

    Martorell, Reynaldo; Melgar, Paul; Maluccio, John A; Stein, Aryeh D; Rivera, Juan A

    2010-02-01

    This article reviews key findings about the long-term impact of a nutrition intervention carried out by the Institute of Nutrition of Central America and Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04 show substantial impact on adult human capital and economic productivity. The 1988-89 study showed that adult body size and work capacity increased for those provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed that schooling was increased for women and reading comprehension and intelligence increased in both men and women. Participants were 26-42 y of age at the time of the 2002-04 follow-up, facilitating the assessment of economic productivity. Wages of men increased by 46% in those provided with improved nutrition through age 2 y. Findings for cardiovascular disease risk factors were heterogeneous; however, they suggest that improved nutrition in early life is unlikely to increase cardiovascular disease risk later in life and may indeed lower risk. In conclusion, the substantial improvement in adult human capital and economic productivity resulting from the nutrition intervention provides a powerful argument for promoting improvements in nutrition in pregnant women and young children.

  20. Prediction of heart rate and oxygen uptake during incremental and maximal exercise in healthy adults.

    PubMed

    Fairbarn, M S; Blackie, S P; McElvaney, N G; Wiggs, B R; Paré, P D; Pardy, R L

    1994-05-01

    Measurement of heart rate and oxygen uptake during incremental exercise and at maximal exercise is useful in evaluating mechanisms responsible for exercise limitation in patients with cardiopulmonary disease. Presently used prediction equations are based on relatively small groups of subjects in whom there was an uneven distribution of subjects with regard to age and sex or based on equations that were from extrapolated data. Our prediction equations are based on data from 231 men and women equally divided within decades between 20 and 80 years. Patients exercised to a symptom-limited maximum on a cycle ergometer while measurements of heart rate and oxygen uptake were recorded. The relationship between heart rate and oxygen uptake throughout exercise (HR:VO2) was determined using a statistical technique that included each data point from each subject. The HR:VO2 throughout incremental exercise was best described by separate equations for women younger than 50 years and older than 50 years and for men younger than 70 years and older than 70 years. Prediction equations for maximal heart rate (HRmax) and maximal oxygen uptake (VO2max) were developed by linear regression and were selected from all possible combinations of parameters. The HRmax was most accurately predicted by age alone for both sexes. Unlike the HR:VO2 relationship, the slope of the line relating heart rate to age was not different for the older women compared with the younger women so that a single equation was derived to predict HRmax. A single equation for the men was also sufficient since the slope of heart rate to age was the same for all ages. To most accurately predict VO2max, a separate equation was required for both the women and men that included age, height, and weight.

  1. Decentralization of Care for Adults with Congenital Heart Disease in the United States: A Geographic Analysis of Outpatient Surgery

    PubMed Central

    Maxwell, Bryan G.; Maxwell, Thane G.; Wong, Jim K.

    2014-01-01

    Background Guidelines recommend that adults with congenital heart disease (CHD) undergo noncardiac surgery in regionalized centers of expertise, but no studies have assessed whether this occurs in the United States. We hypothesized that adults with CHD are less likely than children to receive care at specialized CHD centers. Methods Using a comprehensive state ambulatory surgical registry (California Ambulatory Surgery Database, 2005–2011), we calculated the proportion of adult and pediatric patients with CHD who had surgery at a CHD center, distance to the nearest CHD center, and distance to the facility where surgery was performed. Results Patients with CHD accounted for a larger proportion of the pediatric population (n = 11,254, 1.0%) than the adult population (n = 10,547, 0.07%). Only 2,741 (26.0%) adults with CHD had surgery in a CHD center compared to 6,403 (56.9%) children (p<0.0001). Adult CHD patients who had surgery at a non-specialty center (11.9±15.4 miles away) lived farther from the nearest CHD center (37.9±43.0 miles) than adult CHD patients who had surgery at a CHD center (23.2±28.4 miles; p<0.0001). Pediatric CHD patients who had surgery at a non-specialty center (18.0±20.7 miles away) lived farther from the nearest CHD center (35.7±45.2 miles) than pediatric CHD patients who had surgery at a CHD center (22.4±26.0 miles; p<0.0001). Conclusions Unlike children with CHD, most adults with CHD (74%) do not have outpatient surgery at a CHD center. For both adults and children with CHD, greater distance from a CHD center is associated with having surgery at a non-specialty center. These results have significant public health implications in that they suggest a failing to achieve adequate regional access to specialized ACHD care. Further studies will be required to evaluate potential strategies to more reliably direct this vulnerable population to centers of expertise. PMID:25247694

  2. Epidemiologic burden of hospitalisation for congestive heart failure among adults aged ≥19 years in the Philippines

    PubMed Central

    Tumanan-Mendoza, Bernadette A; Mendoza, Victor L; Bermudez–Delos Santos, April Ann A; Punzalan, Felix Eduardo R; Pestaño, Noemi S; Natividad, Rudy Boy; Shiu, Louie Alfred; Macabeo, Renelene

    2017-01-01

    Objectives The study determined the prevalence of hospitalisation due to congestive heart failure (CHF) among adult patients aged 19 years and above in the Philippines and its 17 regions in 2014. It also determined the demographic profile of these patients, aetiology and type of CHF, comorbidities, duration of hospitalisation and the overall in-hospital mortality rate. Methods Data collection was done using the hospitalisation claims database of the Philippine Health Insurance Corporation (PhilHealth). All patient claims for CHF, that is, patients who were admitted from 1 January to 31 December 2014, were included. Descriptive statistics were utilised to obtain the results. Results The prevalence rate was 1.6% or 1648 cases of CHF for every 100 000 patient claims for medical conditions in 2014. The mean age was 52.6±15.1 years. There was no sex predilection. Only 22.67% of the hospitalisation claims for CHF listed possible specific aetiologies, the most common of which was hypertensive heart disease (86.7%). There were more cases of systolic compared to diastolic heart failure. The mean length of hospital stay was 5.9 days (+8.2) days (median 4 days), with an overall in-hospital mortality rate of 8.2%. Conclusions There were 16 cases of heart failure for every 1000 Filipino patients admitted due to a medical condition in 2014. Hypertension was possibly the most common aetiologic factor. Compared to western and Asia-Pacific countries, the local mortality rate was relatively higher.

  3. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats

    PubMed Central

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-01-01

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×106 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters. PMID:27956912

  4. Human Immunodeficiency Virus and Heart Failure in Low- and Middle-Income Countries.

    PubMed

    Bloomfield, Gerald S; Alenezi, Fawaz; Barasa, Felix A; Lumsden, Rebecca; Mayosi, Bongani M; Velazquez, Eric J

    2015-08-01

    Successful combination therapy for human immunodeficiency virus (HIV) has transformed this disease from a short-lived infection with high mortality to a chronic disease associated with increasing life expectancy. This is true for high- as well as low- and middle-income countries. As a result of this increased life expectancy, people living with HIV are now at risk of developing other chronic diseases associated with aging. Heart failure has been common among people living with HIV in the eras of pre- and post- availability of antiretroviral therapy; however, our current understanding of the pathogenesis and approaches to management have not been systematically addressed. HIV may cause heart failure through direct (e.g., viral replication, mitochondrial dysfunction, cardiac autoimmunity, autonomic dysfunction) and indirect (e.g., opportunistic infections, antiretroviral therapy, alcohol abuse, micronutrient deficiency, tobacco use) pathways. In low- and middle-income countries, 2 large observational studies have recently reported clinical characteristics and outcomes in these patients. HIV-associated heart failure remains a common cardiac diagnosis in people living with heart failure, yet a unifying set of diagnostic criteria is lacking. Treatment patterns for heart failure fall short of society guidelines. Although there may be promise in cardiac glycosides for treating heart failure in people living with HIV, clinical studies are needed to validate in vitro findings. Owing to the burden of HIV in low- and middle-income countries and the concurrent rise of traditional cardiovascular risk factors, strategic and concerted efforts in this area are likely to impact the care of people living with HIV around the globe.

  5. Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

    PubMed Central

    Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

    2016-01-01

    Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents. PMID:27898071

  6. Interactions between heart rate variability and pulmonary gas exchange efficiency in humans.

    PubMed

    Sin, Peter Y W; Webber, Matthew R; Galletly, Duncan C; Ainslie, Philip N; Brown, Stephen J; Willie, Chris K; Sasse, Alexander; Larsen, Peter D; Tzeng, Yu-Chieh

    2010-07-01

    The respiratory component of heart rate variability (respiratory sinus arrhythmia, RSA) has been associated with improved pulmonary gas exchange efficiency in humans via the apparent clustering and scattering of heart beats in time with the inspiratory and expiratory phases of alveolar ventilation, respectively. However, since human RSA causes only marginal redistribution of heart beats to inspiration, we tested the hypothesis that any association between RSA amplitude and pulmonary gas exchange efficiency may be indirect. In 11 patients with fixed-rate cardiac pacemakers and 10 healthy control subjects, we recorded R-R intervals, respiratory flow, end-tidal gas tension and the ventilatory equivalents for carbon dioxide and oxygen during 'fast' (0.25 Hz) and 'slow' paced breathing (0.10 Hz). Mean heart rate, mean arterial blood pressure, mean arterial pressure fluctuations, tidal volume, end-tidal CO(2), and were similar between pacemaker and control groups in both the fast and slow breathing conditions. Although pacemaker patients had no RSA and slow breathing was associated with a 2.5-fold RSA amplitude increase in control subjects (39 +/- 21 versus 97 +/- 45 ms, P < 0.001), comparable (main effect for breathing frequency, F(1,19) = 76.54, P < 0.001) and reductions (main effect for breathing frequency, F(1,19) = 23.90, P < 0.001) were observed for both cohorts during slow breathing. In addition, the degree of (r = 0.36, P = 0.32) and reductions (r = 0.29, P = 0.43) from fast to slow breathing were not correlated to the degree of associated RSA amplitude enhancements in control subjects. These findings suggest that the association between RSA amplitude and pulmonary gas exchange efficiency during variable-frequency paced breathing observed in prior human work is not contingent on RSA being present. Therefore, whether RSA serves an intrinsic physiological function in optimizing pulmonary gas exchange efficiency in humans requires further experimental validation.

  7. CCM2 expression during prenatal development and adult human neocortex.

    PubMed

    Tanriover, Gamze; Sozen, Berna; Gunel, Murat; Demir, Necdet

    2011-08-01

    Cerebral cavernous malformation (CCM) is one of the most common types of vascular malformations of the central nervous system, affecting nearly one in 200 people. CCM lesions are characterized by grossly dilated vascular channels lined by a single layer of endothelium. Genetic linkage analyses have mapped three CCM loci to CCM1, CCM2 and CCM3. All three causative genes have now been identified allowing new insights into CCM pathophysiology. We focused on the CCM2 protein that might take place in blood vessel formation; we report here the expression patterns of CCM2 in prenatal development and adult human neocortex by means of immunohistochemistry and Western blot analysis. CCM2 was obviously detected in vascular endothelium and neuroglial precursor cells during development and also observed in arterial endothelium, neurons, some of the glial cells in adult neocortex. The expression patterns suggest that it could be one of the arterial markers whether this is a cause or a consequence of an altered vascular identity. CCM2 might play a role during vasculogenesis and angiogenesis during human brain development. Furthermore, with this study, CCM2 have been described for the first time in developing human neocortex.

  8. Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.

    PubMed Central

    Studer, R; Reinecke, H; Müller, B; Holtz, J; Just, H; Drexler, H

    1994-01-01

    Local activation of the components of the renin angiotensin system in the heart is regarded as an important modulator of cardiac phenotype and function; however, little is known about their presence, regulation, and potential activation in the human heart. To investigate the gene expression of major angiotensin-II-forming enzymes in left ventricles of normal (n = 9) and failing human hearts (n = 20), we established a competitive RNA-polymerase chain reaction (PCR) for mRNA quantification of angiotensin-I converting enzyme (ACE) and human heart chymase. For each gene, competitor RNA targets with small internal deletions were used as internal standards to quantify the original number of transcripts and to control reverse transcription and PCR. In PCR, each target and the corresponding competitor were amplified by competing for the same primer oligonucleotides. The variability of ACE RNA-PCR was 11% indicating a high reproducibility of this method. In addition, ACE mRNA levels obtained by competitive RNA-PCR correlated favorably with traditional slot blot hybridization (r = 0.69, n = 10; P < 0.05). Compared with nonfailing hearts, the number of ACE transcripts referred to 100 ng of total RNA was increased threefold in patients with chronic heart failure (4.2 +/- 2.5 vs. 12.8 +/- 6 x 10(5); P < 0.0005). In contrast, no significant difference was found in chymase gene expression between normal and failing hearts. Thus, the expression of the cardiac ACE but not of human heart chymase is upregulated in failing human heart indicating an activation of the cardiac renin-angiotensin system in patients with advanced heart failure. Images PMID:8040271

  9. Mouse heart rate in a human: diagnostic mystery of an extreme tachyarrhythmia.

    PubMed

    Chhabra, Lovely; Goel, Narender; Prajapat, Laxman; Spodick, David H; Goyal, Sanjeev

    2012-01-01

    We report telemetry recording of an extreme non-fatal tachyarrhythmia noted in a hospitalized quadriplegic male with history of atrial fibrillation where the average ventricular conduction rate was found to be about 600 beats per minute and was associated with transient syncope. A medical literature review suggests that the fastest human ventricular conduction rate reported to date in a tachyarrhythmia is 480 beats per minute. We therefore report the fastest human heart rate noted in a tachyarrhythmia and the most probable mechanism of this arrhythmia being a rapid atrial fibrillation with 1:1 conduction in the setting of probable co-existing multiple bypass tracts.

  10. Ontogeny of morningness-eveningness across the adult human lifespan

    NASA Astrophysics Data System (ADS)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  11. Heart Failure Induces Significant Changes in Nuclear Pore Complex of Human Cardiomyocytes

    PubMed Central

    Tarazón, Estefanía; Rivera, Miguel; Roselló-Lletí, Esther; Molina-Navarro, Maria Micaela; Sánchez-Lázaro, Ignacio José; España, Francisco; Montero, José Anastasio; Lago, Francisca; González-Juanatey, José Ramón; Portolés, Manuel

    2012-01-01

    Aims The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function. Methods and Results A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = −0382, p = 0.004; r = −0.290, p = 0.033; respectively). Conclusions This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management. PMID:23152829

  12. Comparison at Necropsy of Heart Weight in Women Aged 20 to 29 Years With Fatal Trauma or Chemical Intoxication Versus Fatal Natural Cause (A Search for the Normal Adult Heart Weight).

    PubMed

    Blackbourne, Brian D; Vasudevan, Anupama; Roberts, William C

    2017-03-01

    The present obesity epidemic makes determining the normal heart weight in adults difficult. This study examines the heart weight at autopsy in 104 women aged 20 to 29 years who died in 1978 to 1980 before the overweight epidemic ensued. Of the 104 cases, the hearts weighed ≤300 g in 86 (83%) and >300 g in 18 (17%). Of the 67 cases dying from an unnatural cause (trauma or chemical intoxication), only 3 (4%) had hearts weighing >300 g; of the 37 patients dying from a variety of natural causes, 15 (41%) had hearts weighing >300 g (p <0.001). The body mass index (BMI) was ≤25 kg/m(2) in 82 cases (79%) and the hearts in them ranged from 120 to 400 g (mean 262 ± 51; median 257 g); of the 22 cases (21%) in whom the BMI was >25 kg/m(2), the hearts ranged from 230 to 850 g (mean 351 ± 142; median 300 g). In conclusion, the cases dying from an unnatural cause had smaller mean heart weights than those women dying from a natural cause and those with a normal BMI (≤25 kg/m(2)) had smaller mean heart weights than those with a BMI >25 kg/m(2). The normal heart weight in young women dying from an unnatural cause with few exceptions is <300 g.

  13. Surgery for an adult with tetralogy of Fallot and acquired heart disease.

    PubMed

    Hamamoto, Masaki; Morifuji, Kiyohiko

    2014-06-01

    We experienced the rare case of an elderly woman with uncorrected tetralogy of Fallot. She also had significant mitral and tricuspid regurgitation with deteriorated ventricular function and ischemic coronary artery disease. We performed a radical repair of the tetralogy of Fallot, valvular operations for the mitral and tricuspid regurgitation, and coronary artery bypass grafting. Although mechanical circulatory support was required postoperatively, she recovered well to New York Heart Association functional class II.

  14. Genetics of valvular heart disease.

    PubMed

    LaHaye, Stephanie; Lincoln, Joy; Garg, Vidu

    2014-01-01

    Valvular heart disease is associated with significant morbidity and mortality and often the result of congenital malformations. However, the prevalence is increasing in adults not only because of the growing aging population, but also because of improvements in the medical and surgical care of children with congenital heart valve defects. The success of the Human Genome Project and major advances in genetic technologies, in combination with our increased understanding of heart valve development, has led to the discovery of numerous genetic contributors to heart valve disease. These have been uncovered using a variety of approaches including the examination of familial valve disease and genome-wide association studies to investigate sporadic cases. This review will discuss these findings and their implications in the treatment of valvular heart disease.

  15. Distribution of Tight Junction Proteins in Adult Human Salivary Glands

    PubMed Central

    Maria, Ola M.; Kim, Jung-Wan Martin; Gerstenhaber, Jonathan A.; Baum, Bruce J.; Tran, Simon D.

    2008-01-01

    Tight junctions (TJs) are an essential structure of fluid-secreting cells, such as those in salivary glands. Three major families of integral membrane proteins have been identified as components of the TJ: claudins, occludin, and junctional adhesion molecules (JAMs), plus the cytosolic protein zonula occludens (ZO). We have been working to develop an orally implantable artificial salivary gland that would be suitable for treating patients lacking salivary parenchymal tissue. To date, little is known about the distribution of TJ proteins in adult human salivary cells and thus what key molecular components might be desirable for the cellular component of an artificial salivary gland device. Therefore, the aim of this study was to determine the distribution of TJ proteins in human salivary glands. Salivary gland samples were obtained from 10 patients. Frozen and formalin-fixed paraffin-embedded sections were stained using IHC methods. Claudin-1 was expressed in ductal, endothelial, and ∼25% of serous cells. Claudins-2, -3, and -4 and JAM-A were expressed in both ductal and acinar cells, whereas claudin-5 was expressed only in endothelial cells. Occludin and ZO-1 were expressed in acinar, ductal, and endothelial cells. These results provide new information on TJ proteins in two major human salivary glands and should serve as a reference for future studies to assess the presence of appropriate TJ proteins in a tissue-engineered human salivary gland. (J Histochem Cytochem 56:1093–1098, 2008) PMID:18765838

  16. Combined use of autogenic therapy and biofeedback in training effective control of heart rate by humans

    NASA Technical Reports Server (NTRS)

    Cowings, P. S.

    1977-01-01

    Experiments were performed on 24 men and women (aged 20-27 yr) in three equal groups who were taught to control their own heart rates by autogenic training and biofeedback under dark and sound-isolated conditions. Group I was parasympathetic dominant, group II was sympathetic dominant, and group III consisted of parasympathetic-dominant subjects and controls who received only biofeedback of their own heart rates. The results corroborate three hypotheses: (1) subjects with para-sympathetic-dominant autonomic profiles perform in a way that is both qualitatively and quantitatively different from subjects with sympathetic-dominant autonomic profiles; (2) tests of interindividual variability yield data relevant to individual performance in visceral learning tasks; and (3) the combined use of autogenic training, biofeedback, and verbal feedback is suitable for conditioning large stable autonomic responses in humans.

  17. Heart rate variability of human in hypoxic oxygen-argon environment

    NASA Astrophysics Data System (ADS)

    Khayrullina, Rezeda; Smoleevskiy, Alexandr; Bubeev, Yuri

    Human adaptive capacity, reliability and stability in extreme environments depend primarily on the individual resistance to stresses, includes both innate and acquired components. We have conducted studies in six healthy subjects - men aged between 24 to 42 years who psychophysiological indicators acterizing the severity of stress reactions studied directly during an emergency situation, before and after it. The subjects were in a hypoxic oxygen-argon atmosphere 10 days. Cardiovascular system is one of the first to respond to stressful reaction. The method of heart rate variability (HRV) allows us to estimate balance of sympathetic and parasympathetic parts of vegetative nervous system. In the course of the baseline study it was found that resting heart rate (HR) in the examined individuals is within normal limits. During the experiment in all subjects there was a trend towards more frequent heartbeat. Each subject at one stage or another stay in a hypoxic oxygen-argon environment heart rate go beyond the group norm, but the extent and duration of these abnormalities were significantly different. Marked increase in middle heart rate during of subjects experiment, fluctuating within a wide range (from 2.3% to 29.1%). Marked increase in middle heart rate during of subjects experiment, fluctuating within a wide range (from 2.3% to 29.1%). This suggests that the ability to adapt to living in the investigated gas environment have marked individual differences. SDNN (mean square deviation of all R-R intervals) is the integral indicator of the total effect of the sinus node to the sympathetic and parasympathetic parts of vegetative nervous system, as well as indicating the higher functional reserves of the cardiovascular systems. Increase in heart rate in the majority of subject was accompanied by an increase in individual SDNN. This suggests that the parasympathetic system is able to balance the increase in activity of the sympathetic system, and functional reserves are

  18. Tumor Necrosis Factor Receptor Associated Factor 2 Signaling Provokes Adverse Cardiac Remodeling in the Adult Mammalian Heart

    PubMed Central

    Divakaran, Vijay G.; Evans, Sarah; Topkara, Veli K.; Diwan, Abhinav; Burchfield, Jana; Gao, Feng; Dong, Jianwen; Tzeng, Huei-Ping; Sivasubramanian, Natarajan; Barger, Philip M.; Mann, Douglas L.

    2013-01-01

    Background Tumor necrosis factor (TNF) superfamily ligands that provoke a dilated cardiac phenotype signal through a common scaffolding protein termed TNF receptor associated factor 2 (TRAF2); however, virtually nothing is known with regard to TRAF2 signaling in the adult mammalian heart. Methods and Results We generated multiple founder lines of mice with cardiac restricted overexpression of TRAF2 and characterized the phenotype of mice with higher expression levels of TRAF2 (MHC-TRAF2HC). MHC-TRAF2HC transgenic mice developed a time-dependent increase in cardiac hypertrophy, LV dilation and adverse LV remodeling, and a significant decrease in LV +dP/dt and −dP/dt when compared to littermate (LM) controls (p < 0.05 compared to LM). During the early phases of LV remodeling there was a significant increase in total matrix metalloproteinase (MMP) activity that corresponded with a decrease in total myocardial fibrillar collagen content. As the MHC-TRAF2HC mice aged, there was a significant decrease in total MMP activity accompanied by an increase in total fibrillar collagen content and an increase in myocardial tissue inhibitor of metalloproteinase-1 levels. There was a significant increase in NF-κB activation at 4 – 12 weeks and JNK activation at 4 weeks in the MHCs TRAF2HC mice. Transciptional profiling revealed that > 95% of the hypertrophic/dilated cardiomyopathy-related genes that were significantly upregulated genes in the MHC-TRAF2HC hearts contained κB elements in their promoters. Conclusions These results show for the first time that targeted overexpression of TRAF2 is sufficient to mediate adverse cardiac remodeling in the heart. PMID:23493088

  19. Rapid manufacturing techniques for the tissue engineering of human heart valves.

    PubMed

    Lueders, Cora; Jastram, Ben; Hetzer, Roland; Schwandt, Hartmut

    2014-10-01

    Three-dimensional (3D) printing technologies have reached a level of quality that justifies considering rapid manufacturing for medical applications. Herein, we introduce a new approach using 3D printing to simplify and improve the fabrication of human heart valve scaffolds by tissue engineering (TE). Custom-made human heart valve scaffolds are to be fabricated on a selective laser-sintering 3D printer for subsequent seeding with vascular cells from human umbilical cords. The scaffolds will be produced from resorbable polymers that must feature a number of specific properties: the structure, i.e. particle granularity and shape, and thermic properties must be feasible for the printing process. They must be suitable for the cell-seeding process and at the same time should be resorbable. They must be applicable for implementation in the human body and flexible enough to support the full functionality of the valve. The research focuses mainly on the search for a suitable scaffold material that allows the implementation of both the printing process to produce the scaffolds and the cell-seeding process, while meeting all of the above requirements. Computer tomographic data from patients were transformed into a 3D data model suitable for the 3D printer. Our current activities involve various aspects of the printing process, material research and the implementation of the cell-seeding process. Different resorbable polymeric materials have been examined and used to fabricate heart valve scaffolds by rapid manufacturing. Human vascular cells attached to the scaffold surface should migrate additionally into the inner structure of the polymeric samples. The ultimate intention of our approach is to establish a heart valve fabrication process based on 3D rapid manufacturing and TE. Based on the computer tomographic data of a patient, a custom-made scaffold for a valve will be produced on a 3D printer and populated preferably by autologous cells. The long-term goal is to support

  20. Electrophysiological properties under heart failure conditions in a human ventricular cell: a modeling study.

    PubMed

    Elshrif, Mohamed M; Pengcheng Shi; Cherry, Elizabeth M

    2014-01-01

    Heart failure (HF) is one of the major diseases across the world. During HF the electrophysiology of the failing heart is remodeled, which renders the heart more susceptible to ventricular arrhythmias. In this study, we quantitatively analyze the effects of electrophysiological remodeling of the major currents of human ventricular myocytes on the dynamics of the failing heart. We develop a HF model using a modified version of a recently published model of the human ventricular action potential, the O'Hara-Virag-Varro-Rudy (OVVR) model. The proposed HF model incorporates recently available HF clinical data. It can reproduce most of the action potential (AP) properties of failing myocytes, including action potential duration (APD), amplitude (APA), notch (APN), plateau (APP), resting membrane potential (RMP), and maximum upstroke velocity (dV/dtmax). In addition, the model reproduces the behavior of the [Na+], concentration and [Ca(2)+]i dynamics. Moreover, the HF model exhibits alternans with a fast pacing frequency and can induce early afterdepolarizations (EADs). Additionally, blocking the late sodium current shortens the APD and suppresses EADs, in agreement with experimental findings. The dynamics of the proposed model are assessed through investigating the rate dependence of the AP and the dynamics of the major currents. The steady-state (S-S) and S1-S2 restitution curves along with accommodation to an abrupt change in cycle length were evaluated. Our study should help to elucidate the roles of alterations in electrophysiological properties during HF. Also, this HF cellular model could be used to study HF in a realistic geometry and could be embedded into a model of HF electromechanics to investigate electrical and mechanical properties simultaneously during HF.

  1. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

    SciTech Connect

    Schwaiger, M.; Kalff, V.; Rosenspire, K.; Haka, M.S.; Molina, E.; Hutchins, G.D.; Deeb, M.; Wolfe, E. Jr.; Wieland, D.M. )

    1990-08-01

    The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi (11C)hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial (11C)hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, (11C)hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart.

  2. Reference gene alternatives to Gapdh in rodent and human heart failure gene expression studies

    PubMed Central

    2010-01-01

    Background Quantitative real-time RT-PCR (RT-qPCR) is a highly sensitive method for mRNA quantification, but requires invariant expression of the chosen reference gene(s). In pathological myocardium, there is limited information on suitable reference genes other than the commonly used Gapdh mRNA and 18S ribosomal RNA. Our aim was to evaluate and identify suitable reference genes in human failing myocardium, in rat and mouse post-myocardial infarction (post-MI) heart failure and across developmental stages in fetal and neonatal rat myocardium. Results The abundance of Arbp, Rpl32, Rpl4, Tbp, Polr2a, Hprt1, Pgk1, Ppia and Gapdh mRNA and 18S ribosomal RNA in myocardial samples was quantified by RT-qPCR. The expression variability of these transcripts was evaluated by the geNorm and Normfinder algorithms and by a variance component analysis method. Biological variability was a greater contributor to sample variability than either repeated reverse transcription or PCR reactions. Conclusions The most stable reference genes were Rpl32, Gapdh and Polr2a in mouse post-infarction heart failure, Polr2a, Rpl32 and Tbp in rat post-infarction heart failure and Rpl32 and Pgk1 in human heart failure (ischemic disease and cardiomyopathy). The overall most stable reference genes across all three species was Rpl32 and Polr2a. In rat myocardium, all reference genes tested showed substantial variation with developmental stage, with Rpl4 as was most stable among the tested genes. PMID:20331858

  3. Characterisation of the human embryonic and foetal epicardium during heart development.

    PubMed

    Risebro, Catherine A; Vieira, Joaquim Miguel; Klotz, Linda; Riley, Paul R

    2015-11-01

    The epicardium is essential for mammalian heart development. At present, our understanding of the timing and morphogenetic events leading to the formation of the human epicardium has essentially been extrapolated from model organisms. Here, we studied primary tissue samples to characterise human epicardium development. We reveal that the epicardium begins to envelop the myocardial surface at Carnegie stage (CS) 11 and this process is completed by CS15, earlier than previously inferred from avian studies. Contrary to prevailing dogma, the formed human epicardium is not a simple squamous epithelium and we reveal evidence of more complex structure, including novel spatial differences aligned to the developing chambers. Specifically, the ventricular, but not atrial, epicardium exhibited areas of expanded epithelium, preferential cell alignment and spindle-like morphology. Likewise, we reveal distinct properties ex vivo, such that ventricular cells spontaneously differentiate and lose epicardial identity, whereas atrial-derived cells remained 'epithelial-like'. These data provide insight into the developing human epicardium that may contribute to our understanding of congenital heart disease and have implications for the development of strategies for endogenous cell-based cardiac repair.

  4. The roadmap of WT1 protein expression in the human fetal heart.

    PubMed

    Duim, Sjoerd N; Smits, Anke M; Kruithof, Boudewijn P T; Goumans, Marie-José

    2016-01-01

    The transcription factor Wilms' Tumor-1 (WT1) is essential for cardiac development. Deletion of Wt1 in mice results in disturbed epicardial and myocardial formation and lack of cardiac vasculature, causing embryonic lethality. Little is known about the role of WT1 in the human fetal heart. Therefore, as a first step, we analyzed the expression pattern of WT1 protein during human cardiac development from week 4 till week 20. WT1 expression was apparent in epicardial, endothelial and endocardial cells in a spatiotemporal manner. The expression of WT1 follows a pattern starting at the epicardium and extending towards the lumen of the heart, with differences in timing and expression levels between the atria and ventricles. The expression of WT1 in cardiac arterial endothelial cells reduces in time, whereas WT1 expression in the endothelial cells of cardiac veins and capillaries remains present at all stages studied. This study provides for the first time a detailed description of the expression of WT1 protein during human cardiac development, which indicates an important role for WT1 also in human cardiogenesis.

  5. Apoptosis in Heart Failure: Release of Cytochrome c from Mitochondria and Activation of Caspase-3 in Human Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Narula, Jagat; Pandey, Pramod; Arbustini, Eloisa; Haider, Nezam; Narula, Navneet; Kolodgie, Frank D.; dal Bello, Barbara; Semigran, Marc J.; Bielsa-Masdeu, Anna; Dec, G. William; Israels, Sara; Ballester, Manel; Virmani, Renu; Saxena, Satya; Kharbanda, Surender

    1999-07-01

    Apoptosis has been shown to contribute to loss of cardiomyocytes in cardiomyopathy, progressive decline in left ventricular function, and congestive heart failure. Because the molecular mechanisms involved in apoptosis of cardiocytes are not completely understood, we studied the biochemical and ultrastructural characteristics of upstream regulators of apoptosis in hearts explanted from patients undergoing transplantation. Sixteen explanted hearts from patients undergoing heart transplantation were studied by electron microscopy or immunoblotting to detect release of mitochondrial cytochrome c and activation of caspase-3. The hearts explanted from five victims of motor vehicle accidents or myocardial ventricular tissues from three donor hearts were used as controls. Evidence of apoptosis was observed only in endstage cardiomyopathy. There was significant accumulation of cytochrome c in the cytosol, over myofibrils, and near intercalated discs of cardiomyocytes in failing hearts. The release of mitochondrial cytochrome c was associated with activation of caspase-3 and cleavage of its substrate protein kinase C δ but not poly(ADP-ribose) polymerase. By contrast, there was no apparent accumulation of cytosolic cytochrome c or caspase-3 activation in the hearts used as controls. The present study provides in vivo evidence of cytochrome c-dependent activation of cysteine proteases in human cardiomyopathy. Activation of proteases supports the phenomenon of apoptosis in myopathic process. Because loss of myocytes contributes to myocardial dysfunction and is a predictor of adverse outcomes in the patients with congestive heart failure, the present demonstration of an activated apoptotic cascade in cardiomyopathy could provide the basis for novel interventional strategies.

  6. Eating Patterns and Overweight Status in Young Adults: The Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies have focused on the association between eating patterns and obesity. However, the findings have not been consistent. The goal of the present study was to identify the eating patterns associated with overweight among young adults aged 19-28 years (n = 504) in Bogalusa, Louisiana. Fo...

  7. Dietary & health predictors associated with overweight & obesity in young adults: the Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined independent associations between diet and lifestyle behaviors; differences in markers of cardiovascular disease (CVD), and type 2 diabetes mellitus (T2DM); and self-reported health problems among normal weight (NW); overweight (OW), and obese (OB) young adults. Cross-sectional data on pa...

  8. Dietary, lifestyle, and health correlates of overweight and obesity in adults 19 to 39 years of age: The Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet and lifestyle factors of young adults and their relationship to health risk factors are understudied. Data from the Bogalusa Heart Study population (n = 1214; 19-39 years; 74.1% white; 60.8% female) were used to study associations of lifestyle, health risk factors, and reported health problems ...

  9. Heart regeneration.

    PubMed

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  10. Neuropeptide Y in the adult and fetal human pineal gland.

    PubMed

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  11. Association between Vitamin D Status and Coronary Heart Disease among Adults in Saudi Arabia: A Case-Control Study

    PubMed Central

    Aljefree, Najlaa M.; Lee, Patricia; Alsaqqaf, Jamal M.; Ahmed, Faruk

    2016-01-01

    Recent evidence has pointed out an association between vitamin D deficiency and coronary heart disease (CHD). Due to the growing epidemic of CHD and vitamin D deficiency in Saudi Arabia, exploring the role of vitamin D in the prevention of CHD is crucial. The aim of this study was to examine the association between vitamin D status and CHD in Saudi Arabian adults. This case-control study included 130 CHD cases and 195 age-sex matched controls. Study subjects were recruited from three hospitals in the western region of Saudi Arabia. Study participants were interviewed face-to-face to collect data on their socio-demographic characteristics and family history of CHD. Fasting blood samples were collected, and serum levels of vitamin D, glucose, and total cholesterol were measured. Body weight, height, and blood pressure measurements were also recorded. Severe vitamin D deficiency (25(OH)D < 10 ng/mL) was much more prevalent in CHD cases than in controls (46% and 3%, respectively). The results of multivariate logistic regression showed that vitamin D deficiency (25(OH)D < 20 ng/mL) was associated with CHD, with an odds ratio of 6.5 (95% CI: 2.7–15, p < 0.001). The current study revealed that vitamin D deficiency is independently associated with CHD, suggesting an important predictor of CHD among Saudi adults. PMID:27763496

  12. Association between Vitamin D Status and Coronary Heart Disease among Adults in Saudi Arabia: A Case-Control Study.

    PubMed

    Aljefree, Najlaa M; Lee, Patricia; Alsaqqaf, Jamal M; Ahmed, Faruk

    2016-10-17

    Recent evidence has pointed out an association between vitamin D deficiency and coronary heart disease (CHD). Due to the growing epidemic of CHD and vitamin D deficiency in Saudi Arabia, exploring the role of vitamin D in the prevention of CHD is crucial. The aim of this study was to examine the association between vitamin D status and CHD in Saudi Arabian adults. This case-control study included 130 CHD cases and 195 age-sex matched controls. Study subjects were recruited from three hospitals in the western region of Saudi Arabia. Study participants were interviewed face-to-face to collect data on their socio-demographic characteristics and family history of CHD. Fasting blood samples were collected, and serum levels of vitamin D, glucose, and total cholesterol were measured. Body weight, height, and blood pressure measurements were also recorded. Severe vitamin D deficiency (25(OH)D < 10 ng/mL) was much more prevalent in CHD cases than in controls (46% and 3%, respectively). The results of multivariate logistic regression showed that vitamin D deficiency (25(OH)D < 20 ng/mL) was associated with CHD, with an odds ratio of 6.5 (95% CI: 2.7-15, p < 0.001). The current study revealed that vitamin D deficiency is independently associated with CHD, suggesting an important predictor of CHD among Saudi adults.

  13. The impact of human rhinovirus infection in pediatric patients undergoing heart surgery.

    PubMed

    Delgado-Corcoran, Claudia; Witte, Madolin K; Ampofo, Krow; Castillo, Ramon; Bodily, Stephanie; Bratton, Susan L

    2014-12-01

    Human rhinovirus (HRV), the most common cause of upper respiratory infection in children, can present as bronchiolitis, pneumonia, or asthma exacerbations. The impact of HRV in infants and toddlers with congenital heart disease is poorly defined. A case-control study was performed to compare the clinical course for 19 young children with respiratory symptoms who tested positive for rhinovirus after heart surgery with that of 56 matched control subjects. The control subjects were matched by surgical repair, age, weight, and time of the year. Patients with known HRVs before surgery and control subjects with respiratory symptoms or positive test results for viruses were excluded from the study. Human rhinovirus infection was associated with more than a tenfold increase in the odds of noninvasive ventilation after extubation (odds ratio [OR] 11.45; 95 % confidence interval [CI] 3.97-38.67), a 12-fold increase in the probability of extubation failure (OR 12.84; 95 % CI 2.93-56.29), and increased use of pulmonary medications including bronchodilator and nitric oxide (p < 0.001). As a result, the hospital length of stay (HLOS) was two times longer than for the control subjects (p < 0.001), and the cardiac intensive care unit (CICU) length of stay (CICU LOS) was three times longer (p < 0.0001). The intubation time was significantly longer (p < 0.001), and the CICU respiratory charges were significantly greater (p = 0.001) for the infected patients. Human rhinovirus increases resource use and prolongs postoperative recovery after pediatric heart surgery. Surgery timing should be delayed for patients with rhinovirus if possible.

  14. Do Lambs Perceive Regular Human Stroking as Pleasant? Behavior and Heart Rate Variability Analyses

    PubMed Central

    Coulon, Marjorie; Nowak, Raymond; Peyrat, Julie; Chandèze, Hervé; Boissy, Alain; Boivin, Xavier

    2015-01-01

    Stroking by humans is beneficial to the human-animal relationship and improves welfare in many species that express intraspecific allogrooming, but very few studies have looked at species like sheep that do not express such contact except around parturition. This study investigated the way lambs perceive regular human tactile contact using behavioral and physiological responses. Twenty-four lambs were reared and bucket-fed in groups of four. All were stroked daily by their familiar caregiver. At 8 weeks of age, the lambs were individually tested in their home pen but in a 1×1m open-barred pen after a 15h period of habituation to physical separation from peers while remaining in visual and auditory contact. Half of the lambs received stroking by their caregiver for 8min and half were exposed to their caregiver’s immobile presence. Heart rate and heart rate variability were recorded and analyzed by 2-min slots over the same interval based on three measures: mean heart rate value (HR), root mean square of successive differences (RMSSD) and standard deviation of all intervals measured between consecutive sinus beats (SDNN). Behavioral responses (ear postures of the lamb and time spent in contact with the familiar caregiver, on the knees of the familiar caregiver, and moving) were recorded throughout the test. Lamb HR decreased continuously while in the presence of their caregiver. Lambs being stroked showed slower HR and higher RMSSD which reflected positive emotional states compared to lambs left unstroked. All behavioral variables were highly correlated with the main component axis of the PCA analyses: the more the animals stayed in contact with their caregiver, the less they moved and the more their ears were hanging. This first component clearly differentiates lambs being stroked or not. Behavioral and physiological observations support the hypothesis that gentle physical contact with the caregiver is perceived positively by lambs. PMID:25714604

  15. Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes

    PubMed Central

    Funakoshi, Shunsuke; Miki, Kenji; Takaki, Tadashi; Okubo, Chikako; Hatani, Takeshi; Chonabayashi, Kazuhisa; Nishikawa, Misato; Takei, Ikue; Oishi, Akiko; Narita, Megumi; Hoshijima, Masahiko; Kimura, Takeshi; Yamanaka, Shinya; Yoshida, Yoshinori

    2016-01-01

    Human pluripotent stem cell-derived cardiomyocytes (CMs) are a promising tool for cardiac cell therapy. Although transplantation of induced pluripotent stem cell (iPSC)-derived CMs have been reported in several animal models, the treatment effect was limited, probably due to poor optimization of the injected cells. To optimize graft cells for cardiac reconstruction, we compared the engraftment efficiency of intramyocardially-injected undifferentiated-iPSCs, day4 mesodermal cells, and day8, day20, and day30 purified iPSC-CMs after initial differentiation by tracing the engraftment ratio (ER) using in vivo bioluminescence imaging. This analysis revealed the ER of day20 CMs was significantly higher compared to other cells. Transplantation of day20 CMs into the infarcted hearts of immunodeficient mice showed good engraftment, and echocardiography showed significant functional improvement by cell therapy. Moreover, the imaging signal and ratio of Ki67-positive CMs at 3 months post injection indicated engrafted CMs proliferated in the host heart. Although this graft growth reached a plateau at 3 months, histological analysis confirmed progressive maturation from 3 to 6 months. These results suggested that day20 CMs had very high engraftment, proliferation, and therapeutic potential in host mouse hearts. They also demonstrate this model can be used to track the fate of transplanted cells over a long time. PMID:26743035

  16. Redox proteomics identification of oxidatively modified myocardial proteins in human heart failure: implications for protein function.

    PubMed

    Brioschi, Maura; Polvani, Gianluca; Fratto, Pasquale; Parolari, Alessandro; Agostoni, Piergiuseppe; Tremoli, Elena; Banfi, Cristina

    2012-01-01

    Increased oxidative stress in a failing heart may contribute to the pathogenesis of heart failure (HF). The aim of this study was to identify the oxidised proteins in the myocardium of HF patients and analyse the consequences of oxidation on protein function. The carbonylated proteins in left ventricular tissue from failing (n = 14) and non-failing human hearts (n = 13) were measured by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated in the presence of stimuli relevant for HF in order to assess the generation of reactive oxygen species (ROS), the induction of protein carbonylation, and its consequences on protein function. The levels of carbonylated proteins were significantly higher in the HF patients than in the controls (p<0.01). We identified two proteins that mainly underwent carbonylation: M-type creatine kinase (M-CK), whose activity is impaired, and, to a lesser extent, α-cardiac actin. Exposure of cardiomyocytes to angiotensin II and norepinephrine led to ROS generation and M-CK carbonylation with loss of its enzymatic activity. Our findings indicate that protein carbonylation is increased in the myocardium during HF and that these oxidative changes may help to explain the decreased CK activity and consequent defects in energy metabolism observed in HF.

  17. Redox Proteomics Identification of Oxidatively Modified Myocardial Proteins in Human Heart Failure: Implications for Protein Function

    PubMed Central

    Brioschi, Maura; Polvani, Gianluca; Fratto, Pasquale; Parolari, Alessandro; Agostoni, Piergiuseppe; Tremoli, Elena; Banfi, Cristina

    2012-01-01

    Increased oxidative stress in a failing heart may contribute to the pathogenesis of heart failure (HF). The aim of this study was to identify the oxidised proteins in the myocardium of HF patients and analyse the consequences of oxidation on protein function. The carbonylated proteins in left ventricular tissue from failing (n = 14) and non-failing human hearts (n = 13) were measured by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated in the presence of stimuli relevant for HF in order to assess the generation of reactive oxygen species (ROS), the induction of protein carbonylation, and its consequences on protein function. The levels of carbonylated proteins were significantly higher in the HF patients than in the controls (p<0.01). We identified two proteins that mainly underwent carbonylation: M-type creatine kinase (M-CK), whose activity is impaired, and, to a lesser extent, α-cardiac actin. Exposure of cardiomyocytes to angiotensin II and norepinephrine led to ROS generation and M-CK carbonylation with loss of its enzymatic activity. Our findings indicate that protein carbonylation is increased in the myocardium during HF and that these oxidative changes may help to explain the decreased CK activity and consequent defects in energy metabolism observed in HF. PMID:22606238

  18. Verapamil as an antiarrhythmic agent in congestive heart failure: hopping from rabbit to human?

    PubMed Central

    Stams, Thom RG; Bourgonje, Vincent JA; Vos, Marc A; van der Heyden, Marcel AG

    2012-01-01

    Repolarization-dependent cardiac arrhythmias only arise in hearts facing multiple ‘challenges’ affecting its so-called repolarization reserve. Congestive heart failure (CHF) is one such challenge frequently observed in humans and is accompanied by altered calcium handling within the contractile heart cell. This raises the question as to whether or not the well-known calcium channel antagonist verapamil acts as an antiarrhythmic drug in this setting, as seen in arrhythmia models without CHF. According to the study of Milberg et al. in this issue of BJP, the answer is yes. The results of this study, using a rabbit CHF model, raise important questions. First, given that the model combines CHF with a number of other interventions that predispose towards arrhythmia, will similar conclusions be reached in a setting where CHF is a more prominent proarrhythmic challenge; second, what is the extent to which other effects of calcium channel block would limit the clinical viability of this pharmacological approach in CHF? In vivo studies in large animal CHF models are now required to further explore this interesting, but complex, approach to the treatment of arrhythmia. LINKED ARTICLE This article is a commentary on Milberg et al., pp. 557–568 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01721.x PMID:22188337

  19. PTH-receptors regulate norepinephrine release in human heart and kidney.

    PubMed

    Potthoff, S A; Janus, A; Hoch, H; Frahnert, M; Tossios, P; Reber, D; Giessing, M; Klein, H M; Schwertfeger, E; Quack, I; Rump, L C; Vonend, O

    2011-11-10

    Recent data suggests that chronic renal failure and hyperparathyroidism are associated with sympathetic overactivity. Since peptide hormones are known to modulate norepinephrine (NE) release by activating prejunctional receptors, this study investigates whether parathyroid hormone fragment (1-34) (hPTH(1-34)) increases neuronal NE release in human heart and kidney. Using specific PTH-receptor agonists and antagonists, this study furthermore highlights functional differences between PTH1 and PTH2 receptors. Human atrial and renal tissues were incubated with [(3)H]-NE and superfused. Three electrical stimulations (5Hz, 1min) induced a stable [(3)H]-NE release which was taken as an index of endogenous NE release. RT-PCR with specific primers for PTH1- and PTH2-receptor was performed in heart and kidney. hPTH(1-34) (0.01-0.1μmol/L) and a stable analog of its second messenger cAMP (8-bromo-cAMP) increased [(3)H]-NE release in human atria. This facilitatory effect of PTH was also observed in human renal cortex. The PTH1-receptor antagonist (D-Trp(12), Tyr(34))-pTH-(7-34) (0.5μmol/L) abolished the effect of hPTH(1-34). This data was verified using isolated perfused mouse kidneys. Tuberoinfundibular peptide of 39 residues (TIP-39) (0.1nmol/L-0.1μmol/L) decreased [(3)H]-NE release in atria. PTH1- and PTH2-receptor expressions were demonstrated in human heart and kidney. Moreover, a splice variant of the PTH2-receptor was detected in human kidney. In conclusion, PTH is able to facilitate NE release in human atria and renal cortex by activation of PTH1-receptors. The highly increased PTH levels that can be observed in chronic renal failure might be one contributor for the elevated sympathetic nerve activity and the associated cardiovascular mortality in patients with end stage renal disease.

  20. Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure.

    PubMed

    Bell, David; Gordon, Brian J; Lavery, Anita; Megaw, Katie; Kinney, Michael O; Harbinson, Mark T

    2016-02-01

    Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%). In healthy subjects, plasma levels (mean+SE) of IMD (6.3+0.6 pg ml(-1)) were lower than, but correlated with those of AM (25.8+1.8 pg ml(-1); r=0.49, p<0.001). Plasma preproIMD(25-56) (39.6+3.1 pg ml(-1)), preproIMD(57-92) (25.9+3.8 pg ml(-1)) and MRproAM(45-92) (200.2+6.7 pg ml(-1)) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8+1.3 pg ml(-1), p<0.05), similarly to MRproAM(45-92) (329.5+41.9 pg ml(-1), p<0.001) and AM (56.8+10.9 pg ml(-1), p<0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3+1.8 pg ml(-1)) than those without (6.5+1.0 pg ml(-1); p<0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.

  1. Sex Determination of Adult Human Maxillary Sinuses on Panoramic Radiographs.

    PubMed

    Leao de Queiroz, Cristhiane; Terada, Andrea Sayuri Silveira Dias; Dezem, Thais Uenoyama; Gomes de Araújo, Lais; Galo, Rodrigo; Oliveira-Santos, Christiano; Alves da Silva, Ricardo Henrique

    2016-09-01

    The purpose of this study was to evaluate dimensions of adult human maxillary sinuses on panoramic radiographs and their possible application on the sex determination for forensic purposes. The sample comprised 64 database panoramic radiographs from individuals aged 20 years or older (32 male and 32 female subjects), with complete permanent dentition (or absence of third molars). One examiner measured the width and height of the right and left maxillary sinuses using the software Image J 1.47v (National Institutes of Health, Bethesda, USA). Measurements were repeated to calculate intra-observer agreement. Chi-Square test, Kappa, ANOVA and T-Student were used for results analysis for p≤ 0.05. Intra-observer agreement with correlation Kappa ranged between 0.38 and 0.96. For female subjects, the mean height and width of the left maxillary sinus were 28.7856mm and 44.6178mm, respectively. And right maxillary sinus was 27.7163mm for height and 45.1850mm for width. Male subjects were found to have the mean height and width of the left maxillary sinus 30.9981mm and 48.7753mm, respectively. And right maxillary sinus was 30.7403mm for height and 48.5753mm for width. There was a statistically significant difference in the height and width of maxillary sinuses between males and females. It can be concluded that maxillary sinuses height and width on panoramic radiographs can be used to determine the gender of adult human subjects.

  2. The adult human pubic symphysis: a systematic review

    PubMed Central

    Becker, Ines; Woodley, Stephanie J; Stringer, Mark D

    2010-01-01

    The pubic symphysis is a unique joint consisting of a fibrocartilaginous disc sandwiched between the articular surfaces of the pubic bones. It resists tensile, shearing and compressive forces and is capable of a small amount of movement under physiological conditions in most adults (up to 2 mm shift and 1° rotation). During pregnancy, circulating hormones such as relaxin induce resorption of the symphyseal margins and structural changes in the fibrocartilaginous disc, increasing symphyseal width and mobility. This systematic review of the English, German and French literature focuses on the normal anatomy of the adult human pubic symphysis. Although scientific studies of the joint have yielded useful descriptive data, comparison of results is hampered by imprecise methodology and/or poorly controlled studies. Several aspects of the anatomy of the pubic symphysis remain unknown or unclear: the precise attachments of surrounding ligaments and muscles; the arrangement of connective tissue fibres within the interpubic disc and the origin, structure and function of its associated interpubic cleft; the biomechanical consequences of sexual dimorphism; potential ethnic variations in morphology; and its precise innervation and blood supply. These deficiencies hinder our understanding of the normal form and function of the joint, which is particularly relevant when attempting to understand the mechanisms underlying pregnancy-related pubic symphyseal pain, a neglected and relatively common cause of pubic pain. A better understanding of the normal anatomy of the human pubic symphysis should improve our understanding of such problems and contribute to better treatments for patients suffering from symphyseal pain and dysfunction. PMID:20840351

  3. Sex Determination of Adult Human Maxillary Sinuses on Panoramic Radiographs

    PubMed Central

    Leao de Queiroz, Cristhiane; Terada, Andrea Sayuri Silveira Dias; Dezem, Thais Uenoyama; Gomes de Araújo, Lais; Galo, Rodrigo; Oliveira-Santos, Christiano

    2016-01-01

    Absract The purpose of this study was to evaluate dimensions of adult human maxillary sinuses on panoramic radiographs and their possible application on the sex determination for forensic purposes. The sample comprised 64 database panoramic radiographs from individuals aged 20 years or older (32 male and 32 female subjects), with complete permanent dentition (or absence of third molars). One examiner measured the width and height of the right and left maxillary sinuses using the software Image J 1.47v (National Institutes of Health, Bethesda, USA). Measurements were repeated to calculate intra-observer agreement. Chi-Square test, Kappa, ANOVA and T-Student were used for results analysis for p≤ 0.05. Intra-observer agreement with correlation Kappa ranged between 0.38 and 0.96. For female subjects, the mean height and width of the left maxillary sinus were 28.7856mm and 44.6178mm, respectively. And right maxillary sinus was 27.7163mm for height and 45.1850mm for width. Male subjects were found to have the mean height and width of the left maxillary sinus 30.9981mm and 48.7753mm, respectively. And right maxillary sinus was 30.7403mm for height and 48.5753mm for width. There was a statistically significant difference in the height and width of maxillary sinuses between males and females. It can be concluded that maxillary sinuses height and width on panoramic radiographs can be used to determine the gender of adult human subjects. PMID:27847394

  4. An image-based model of the whole human heart with detailed anatomical structure and fiber orientation.

    PubMed

    Deng, Dongdong; Jiao, Peifeng; Ye, Xuesong; Xia, Ling

    2012-01-01

    Many heart anatomy models have been developed to study the electrophysiological properties of the human heart. However, none of them includes the geometry of the whole human heart. In this study, an anatomically detailed mathematical model of the human heart was firstly reconstructed from the computed tomography images. In the reconstructed model, the atria consisted of atrial muscles, sinoatrial node, crista terminalis, pectinate muscles, Bachmann's bundle, intercaval bundles, and limbus of the fossa ovalis. The atrioventricular junction included the atrioventricular node and atrioventricular ring, and the ventricles had ventricular muscles, His bundle, bundle branches, and Purkinje network. The epicardial and endocardial myofiber orientations of the ventricles and one layer of atrial myofiber orientation were then measured. They were calculated using linear interpolation technique and minimum distance algorithm, respectively. To the best of our knowledge, this is the first anatomically-detailed human heart model with corresponding experimentally measured fibers orientation. In addition, the whole heart excitation propagation was simulated using a monodomain model. The simulated normal activation sequence agreed well with the published experimental findings.

  5. Myocardial infarction in an adult with cystic fibrosis and heart and lung transplant

    PubMed Central

    2013-01-01

    We present a case of myocardial infarction in a 19 year old female with cystic fibrosis who had a heart and lung transplant performed at the age of four years old. She presented atypically with a one day history of severe, intermittent, central, sharp chest pain, radiating to her back and down her left arm. A coronary angiogram showed proximal stenosis of the left anterior descending artery and right coronary artery. She was treated with percutaneous coronary intervention, involving drug eluting stents to the left anterior descending artery (LAD) and the right coronary artery (RCA). In this study we discuss the pathophysiology, investigations and treatment of cardiac transplant vasculopathy. Although complete reversal of LAD and RCA stenosis was achieved, routine follow-up with coronary angiography and careful control of cardiac risk factors will be important to identify and reduce future restenosis and adverse cardiac events. PMID:23759073

  6. The Lived Experience of African American Caregivers Caring for Adult African American Patients With Heart Failure.

    PubMed

    Hamilton, Heather

    2016-04-01

    Assistance from informal caregivers such as family members, friends, or neighbors is crucial to adequately managing the complex care of heart failure (HF) patients. This study examined the lived experience of African American caregivers caring for African American patients with HF. Purposive sampling was used to recruit 10 participants who were formally interviewed. The interviews, analyzed using Colaizzi's steps, revealed six themes: layers of support, realization of self-neglect, experiencing the "blues," connecting with healthcare providers, unmet financial needs, and perception of nonadherence. The information regarding the experience of African American caregivers of HF patients obtained through this research will inform the delivery of culturally competent support to caregivers, thereby improving quality of life for both the HF patients and their caregivers.

  7. Morphological description of great cardiac vein in pigs compared to human hearts

    PubMed Central

    Alejandro Gómez, Fabian; Ballesteros, Luis Ernesto; Stella Cortés, Luz

    2015-01-01

    Introduction In spite of its importance as an experimental model, the information on the great cardiac vein in pigs is sparse. Objective To determine the morphologic characteristics of the great cardiac vein and its tributaries in pigs. Methods 120 hearts extracted from pigs destined to the slaughterhouse with stunning method were studied. This descriptive cross-over study evaluated continuous variables with T test and discrete variables with Pearson χ square test. A level of significance P<0.05 was used. The great cardiac vein and its tributaries were perfused with polyester resin (85% Palatal and 15% Styrene) and then subjected to potassium hydroxide infusion to release the subepicardial fat. Calibers were measured, and trajectories and relations with adjacent arterial structures were evaluated. Results The origin of the great cardiac vein was observed at the heart apex in 91 (76%) hearts. The arterio-venous trigone was present in 117 (97.5%) specimens, corresponding to the open expression in its lower segment and to the closed expression in the upper segment in the majority of the cases (65%). The caliber of the great cardiac vein at the upper segment of the paraconal interventricular sulcus was 3.73±0.79 mm. An anastomosis between the great cardiac vein and the middle cardiac vein was found in 59 (49%) specimens. Conclusion The morphological and biometric characteristics of the great cardiac vein and its tributaries had not been reported in prior studies, and due to their similitude with those of the human heart, allows us to propose the pig model for procedural and hemodynamic applications. PMID:25859869

  8. Heart Surgery Terms

    MedlinePlus

    ... the hearts of humans who have died (cadavers). Angina pectoris The discomfort experienced by individuals when their heart ... performed during symptoms suggestive of coronary artery disease angina pectoris , abnormalities may confirm the diagnosis of ischemic heart ...

  9. Ultrastructural evidence of exosome secretion by progenitor cells in adult mouse myocardium and adult human cardiospheres.

    PubMed

    Barile, Lucio; Gherghiceanu, Mihaela; Popescu, Laurentiu M; Moccetti, Tiziano; Vassalli, Giuseppe

    2012-01-01

    The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres) that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34⁺ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an "off-the-shelf" product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.

  10. Preparing Children for Heart Surgery

    MedlinePlus

    ... Physical Activity Recommendations for Heart Health • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

  11. Developing a novel comprehensive framework for the investigation of cellular and whole heart electrophysiology in the in situ human heart: historical perspectives, current progress and future prospects.

    PubMed

    Taggart, Peter; Orini, Michele; Hanson, Ben; Hayward, Martin; Clayton, Richard; Dobrzynski, Halina; Yanni, Joseph; Boyett, Mark; Lambiase, Pier D

    2014-08-01

    Understanding the mechanisms of fatal ventricular arrhythmias is of great importance. In view of the many electrophysiological differences that exist between animal species and humans, the acquisition of basic electrophysiological data in the intact human heart is essential to drive and complement experimental work in animal and in-silico models. Over the years techniques have been developed to obtain basic electrophysiological signals directly from the patients by incorporating these measurements into routine clinical procedures which access the heart such as cardiac catheterisation and cardiac surgery. Early recordings with monophasic action potentials provided valuable information including normal values for the in vivo human heart, cycle length dependent properties, the effect of ischaemia, autonomic nervous system activity, and mechano-electric interaction. Transmural recordings addressed the controversial issue of the mid myocardial "M" cell. More recently, the technique of multielectrode mapping (256 electrodes) developed in animal models has been extended to humans, enabling mapping of activation and repolarisation on the entire left and right ventricular epicardium in patients during cardiac surgery. Studies have examined the issue of whether ventricular fibrillation was driven by a "mother" rotor with inhomogeneous and fragmented conduction as in some animal models, or by multiple wavelets as in other animal studies; results showed that both mechanisms are operative in humans. The simpler spatial organisation of human VF has important implications for treatment and prevention. To link in-vivo human electrophysiological mapping with cellular biophysics, multielectrode mapping is now being combined with myocardial biopsies. This technique enables region-specific electrophysiology changes to be related to underlying cellular biology, for example: APD alternans, which is a precursor of VF and sudden death. The mechanism is incompletely understood but related

  12. Building and re-building the heart by cardiomyocyte proliferation

    PubMed Central

    Foglia, Matthew J.; Poss, Kenneth D.

    2016-01-01

    The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most-cited basis of this ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes. However, mammalian cardiomyocytes can avidly proliferate during fetal and neonatal development, and both adult zebrafish and neonatal mice can regenerate cardiac muscle after injury, suggesting that latent regenerative potential exists. Dissecting the cellular and molecular mechanisms that promote cardiomyocyte proliferation throughout life, deciphering why proliferative capacity normally dissipates in adult mammals, and deriving means to boost this capacity are primary goals in cardiovascular research. Here, we review our current understanding of how cardiomyocyte proliferation is regulated during heart development and regeneration. PMID:26932668

  13. The Effect of Body Mass on Outdoor Adult Human Decomposition.

    PubMed

    Roberts, Lindsey G; Spencer, Jessica R; Dabbs, Gretchen R

    2017-02-23

    Forensic taphonomy explores factors impacting human decomposition. This study investigated the effect of body mass on the rate and pattern of adult human decomposition. Nine males and three females aged 49-95 years ranging in mass from 73 to 159 kg who were donated to the Complex for Forensic Anthropology Research between December 2012 and September 2015 were included in this study. Kelvin accumulated degree days (KADD) were used to assess the thermal energy required for subjects to reach several total body score (TBS) thresholds: early decomposition (TBS ≥6.0), TBS ≥12.5, advanced decomposition (TBS ≥19.0), TBS ≥23.0, and skeletonization (TBS ≥27.0). Results indicate no significant correlation between body mass and KADD at any TBS threshold. Body mass accounted for up to 24.0% of variation in decomposition rate depending on stage, and minor differences in decomposition pattern were observed. Body mass likely has a minimal impact on postmortem interval estimation.

  14. Adult human liver mesenchymal progenitor cells express phenylalanine hydroxylase.

    PubMed

    Baruteau, Julien; Nyabi, Omar; Najimi, Mustapha; Fauvart, Maarten; Sokal, Etienne

    2014-09-01

    Phenylketonuria (PKU) is one of the most prevalent inherited metabolic diseases and is accountable for a severe encephalopathy by progressive intoxication of the brain by phenylalanine. This results from an ineffective L-phenylalanine hydroxylase enzyme (PAH) due to a mutated phenylalanine hydroxylase (PAH) gene. Neonatal screening programs allow an early dietetic treatment with restrictive phenylalanine intake. This diet prevents most of the neuropsychological disabilities but remains challenging for lifelong compliance. Adult-derived human liver progenitor cells (ADHLPC) are a pool of precursors that can differentiate into hepatocytes. We aim to study PAH expression and PAH activity in a differenciated ADHLPC. ADHLPC were isolated from human hepatocyte primary culture of two different donors and differenciated under specific culture conditions. We demonstrated the high expression of PAH and a large increase of PAH activity in differenciated LPC. The age of the donor, the cellular viability after liver digestion and cryopreservation affects PAH activity. ADHLPC might therefore be considered as a suitable source for cell therapy in PKU.

  15. Ossified Ligamentum Longitudinale Anterius in Adult Human Dry Vertebrae

    PubMed Central

    Venumadhav, Nelluri; KS, Siddaraju

    2014-01-01

    Background: The ligamentum longitudinale anterius is a broad and strong band of fibrous tissue that runs along the anterior surfaces of the bodies of the vertebrae. Aim: The study was undertaken to evaluate the incidence of ossified ligamentum longitudinale anterius in adult dry human vertebra. Materials and Methods: This study was carried out on 95 sets of dry human vertebral columns irrespective of age and sex at Mayo Institute of Medical Sciences- Barabanki,-UP, Melaka Manipal Medical College-Manipal University and Department of Anatomy, KMCT Medical College, Manassery- Calicut, India. All the sets of vertebral columns were macroscopically inspected for the ossified ligamentum longitudinale anterius. Results: It was observed that out of 95 sets of vertebral columns, 27 (28.42%) vertebral columns showed ossification. Out of 27 vertebral columns, 17 (17.89%) vertebral columns showed segmental type of ossification, 2 (2.11%) vertebral columns showed continuous type of ossification and 8 (8.42%) vertebral columns showed mixed type of ossification at different vertebral level. Conclusion: Such type of ossification will affect the biomechanics of the spine and may result in stiff neck, low back pain, dysphagia, odynophagia, compression of the brachial plexus, aphonia, immobility or mucosal thickening of larynx. Hence, knowledge of such abnormalities should be kept in mind to minimise serious complications in any surgical intervention or investigative procedures in the region. PMID:25302180

  16. A biokinetic model for systemic technetium in adult humans

    SciTech Connect

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  17. A biokinetic model for systemic technetium in adult humans

    DOE PAGES

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection.more » Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

  18. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  19. Purpose in life and reduced risk of myocardial infarction among older U.S. adults with coronary heart disease: a two-year follow-up.

    PubMed

    Kim, Eric S; Sun, Jennifer K; Park, Nansook; Kubzansky, Laura D; Peterson, Christopher

    2013-04-01

    This study examined whether purpose in life was associated with myocardial infarction among a sample of older adults with coronary heart disease after adjusting for relevant sociodemographic, behavioral, biological, and psychological factors. Prospective data from the Health and Retirement Study-a nationally representative panel study of American adults over the age of 50-were used. Analyses were conducted on the subset of 1,546 individuals who had coronary heart disease at baseline. Greater baseline purpose in life was associated with lower odds of having a myocardial infarction during the 2-year follow-up period. On a six-point purpose in life measure, each unit increase was associated with a multivariate-adjusted odds ratio of 0.73 for myocardial infarction (95% CI, 0.57-0.93, P = .01). The association remained significant after controlling for coronary heart disease severity, self-rated health, and a comprehensive set of possible confounds. Higher purpose in life may play an important role in protecting against myocardial infarction among older American adults with coronary heart disease.

  20. Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome).

    PubMed

    Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika

    2016-12-01

    Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

  1. Modelling sarcomeric cardiomyopathies in the dish: from human heart samples to iPSC cardiomyocytes.

    PubMed

    Eschenhagen, Thomas; Mummery, Christine; Knollmann, Bjorn C

    2015-04-01

    One of the obstacles to a better understanding of the pathogenesis of human cardiomyopathies has been poor availability of heart-tissue samples at early stages of disease development. This has possibly changed by the advent of patient-derived induced pluripotent stem cell (hiPSC) from which cardiomyocytes can be derived in vitro. The main promise of hiPSC technology is that by capturing the effects of thousands of individual gene variants, the phenotype of differentiated derivatives of these cells will provide more information on a particular disease than simple genotyping. This article summarizes what is known about the 'human cardiomyopathy or heart failure phenotype in vitro', which constitutes the reference for modelling sarcomeric cardiomyopathies in hiPSC-derived cardiomyocytes. The current techniques for hiPSC generation and cardiac myocyte differentiation are briefly reviewed and the few published reports of hiPSC models of sarcomeric cardiomyopathies described. A discussion of promises and challenges of hiPSC-modelling of sarcomeric cardiomyopathies and individualized approaches is followed by a number of questions that, in the view of the authors, need to be answered before the true potential of this technology can be evaluated.

  2. Ultrasensitive cardiac troponin I antibody based nanohybrid sensor for rapid detection of human heart attack.

    PubMed

    Bhatnagar, Deepika; Kaur, Inderpreet; Kumar, Ashok

    2017-02-01

    An ultrasensitive cardiac troponin I antibody conjugated with graphene quantum dots (GQD) and polyamidoamine (PAMAM) nanohybrid modified gold electrode based sensor was developed for the rapid detection of heart attack (myocardial infarction) in human. Screen printed gold (Au) electrode was decorated with 4-aminothiophenol for amine functionalization of the Au surface. These amino groups were further coupled with carboxyl functionalities of GQD with EDC-NHS reaction. In order to enhance the sensitivity of the sensor, PAMAM dendrimer was successively embedded on GQD through carbodiimide coupling to provide ultra-high surface area for antibody immobilization. The activated cardiac troponin I (cTnI) monoclonal antibody was immobilized on PAMAM to form nanoprobe for sensing specific heart attack marker cTnI. Various concentrations of cardiac marker, cTnI were electrochemically measured using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in human blood serum. The modifications on sensor surface were characterized by FTIR and AFM techniques. The sensor is highly specific to cTnI and showed negligible response to non-specific antigens. The sensitivity of the sensor was 109.23μAcm(-2)μg(-1) and lower limit of detection of cTnI was found 20fgmL(-1).

  3. Modelling sarcomeric cardiomyopathies in the dish: from human heart samples to iPSC cardiomyocytes

    PubMed Central

    Eschenhagen, Thomas; Mummery, Christine; Knollmann, Bjorn C.

    2015-01-01

    One of the obstacles to a better understanding of the pathogenesis of human cardiomyopathies has been poor availability of heart-tissue samples at early stages of disease development. This has possibly changed by the advent of patient-derived induced pluripotent stem cell (hiPSC) from which cardiomyocytes can be derived in vitro. The main promise of hiPSC technology is that by capturing the effects of thousands of individual gene variants, the phenotype of differentiated derivatives of these cells will provide more information on a particular disease than simple genotyping. This article summarizes what is known about the ‘human cardiomyopathy or heart failure phenotype in vitro’, which constitutes the reference for modelling sarcomeric cardiomyopathies in hiPSC-derived cardiomyocytes. The current techniques for hiPSC generation and cardiac myocyte differentiation are briefly reviewed and the few published reports of hiPSC models of sarcomeric cardiomyopathies described. A discussion of promises and challenges of hiPSC-modelling of sarcomeric cardiomyopathies and individualized approaches is followed by a number of questions that, in the view of the authors, need to be answered before the true potential of this technology can be evaluated. PMID:25618410

  4. Socioeconomic and air pollution correlates of adult asthma, heart attack, and stroke risks in the United States, 2010-2013.

    PubMed

    Cox, Louis Anthony Tony

    2017-05-01

    Asthma in the United States has become an important public health issue, with many physicians, regulators, and scientists elsewhere expressing concern that criterion air pollutants have contributed to a rising tide of asthma cases and symptoms. This paper studies recent associations (from 2008 to 2012) between self-reported asthma experiences and potential predictors, including age, sex, income, education, smoking, and county-level average annual ambient concentrations of ozone (O3) and fine particulate matter (PM2.5) levels recorded by the U.S. Environmental Protection Agency, for adults 50 years old or older for whom survey data are available from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System (BRFSS). We also examine associations between these variables and self-reported heart attack and stroke experience; all three health outcomes are positively associated with each other. Young divorced women with low incomes are at greatest risk of asthma, especially if they are ever-smokers. Income is an important confounder of other relations. For example, in logistic regression modeling, PM2.5 is positively associated (p<0.06) with both stroke risk and heart attack risk when these are regressed only against PM2.5, sex, age, and ever-smoking status, but not when they are regressed against these variables and income. In this data set, PM2.5 is significantly negatively associated with asthma risk in regression models, with a 10μg/m(3) decrease in PM2.5 corresponding to about a 6% increase in the probability of asthma, possibly because of confounding by smoking, which is negatively associated with PM2.5 and positively associated with asthma risk. A variety of non-parametric methods are used to quantify these associations and to explore potential causal interpretations.

  5. A phenotypic in vitro model for the main determinants of human whole heart function

    PubMed Central

    Stancescu, Maria; Molnar, Peter; McAleer, Christopher W.; McLamb, William; Long, Christopher J.; Oleaga, Carlota; Prot, Jean-Matthieu; Hickman, James J.

    2015-01-01

    This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model featured a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems. PMID:25978005

  6. Atrioventricular valves development in human heart: the Paris embryological collection revisited.

    PubMed

    Mandarim-de-Lacerda, C A

    1989-01-01

    29 human embryos staging from stage 15 to stage 23 (post-somitic period, collection of the UER Biomedicale des Saints-Péres, Université René Descartes Paris V) have been studied. The most important morphological events of the atrioventricular valves development have been reinvestigated and photographed. This is a complementary information about cardiac development analysing this french collection of human embryos (Mandarim-de-Lacerda, in press). At stage 15, we can observe the gelatinous reticulum well organized when cardiac valves will become established; progressively the fused endocardial cushions and right and left lateral cushions encircle the atrioventricular channels indicating the site of the tricuspid valves. These cushions, however, have a temporary influence being replaced gradually by atrial and ventricular myocardium. At stage 23, the heart presents a complete atrioventricular valvular structure.

  7. A phenotypic in vitro model for the main determinants of human whole heart function.

    PubMed

    Stancescu, Maria; Molnar, Peter; McAleer, Christopher W; McLamb, William; Long, Christopher J; Oleaga, Carlota; Prot, Jean-Matthieu; Hickman, James J

    2015-08-01

    This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems.

  8. The Independent Association of Hypertension with Cognitive Function Among Older Adults with Heart Failure

    PubMed Central

    Alosco, Michael L.; Brickman, Adam M.; Spitznagel, Mary Beth; van Dulmen, Manfred; Raz, Naftali; Cohen, Ronald; Sweet, Lawrence H.; Colbert, Lisa H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2012-01-01

    Objective Hypertension is the most common comorbidity among heart failure (HF) patients and has been independently linked with cognitive impairment. Cognitive impairment is prevalent among HF patients, though the extent to which hypertension contributes to cognitive function in this population is unclear. Methods 116 HF patients (31.0% women, 67.68 ± 11.16 years) completed neuropsychological testing and impedance cardiography. History of physician diagnosed hypertension, along with other medical characteristics, was ascertained through a review of participants’ medical charts. Results 69.8% of the HF patients had a diagnostic history of hypertension. After adjustment for demographic and medical characteristics (i.e., cardiac index, medication status, and resting blood pressure), hypertension was independently associated with attention/executive function/psychomotor speed (ΔF(1,103) = 10.85, ΔR2 = .07, p < .01) and motor functioning (ΔF(1,103) = 4.46, ΔR2 = .04, p < .05). HF patients with a diagnosed history of hypertension performed worse in these domains than those without such history. Conclusion The current findings indicate that diagnostic history of hypertension is an important contributor to cognitive impairment in HF. Hypertension frequently precedes HF and future studies should examine whether sustained hypertension compromises cerebral autoregulatory mechanisms to produce brain damage and exacerbate cognitive impairment in this population. PMID:23026535

  9. Tai Chi Chuan modulates heart rate variability during abdominal breathing in elderly adults.

    PubMed

    Wei, Gao-Xia; Li, You-Fa; Yue, Xiao-Lin; Ma, Xiao; Chang, Yu-Kai; Yi, Long-Yan; Li, Jing-Cheng; Zuo, Xi-Nian

    2016-03-01

    Tai Chi Chuan (TCC) practice is currently intentionally applied in clinical populations, especially those with cardiovascular diseases because of its potential benefits on the autonomic nervous system. The long-term effect of TCC practice on heart rate variability (HRV) remains largely unknown. In this study, we recruited 23 TCC practitioners whose experience averaged approximately 21 years and 19 controls matched by age, sex and education to examine the effect of TCC practice on the autonomic nervous system during a resting state and during an abdominal breathing state. HRV was measured by traditional electrocardiogram (ECG) recording. The results showed that the low frequency, total power frequency, and normalized low frequency components and the low-frequency/high-frequency ratio were significantly higher, whereas the normalized high frequency was significantly lower in the TCC practitioners relative to controls during the abdominal breathing state. However, we did not detect any significant difference in the HRV measures during the resting state between the two groups. Additionally, TCC experience did not correlate with HRV components either in the abdominal state or the resting state in the TCC group. Considering all of these findings, we suggest that TCC improves vagal activity and the balance between sympathetic and parasympathetic activity during the relaxation state. This study also provides direct physiological evidence for the role of TCC practice in relaxation.

  10. Dietary Patterns, Alcohol Consumption and Risk of Coronary Heart Disease in Adults: A Meta-Analysis.

    PubMed

    Zhang, Xiao-Yan; Shu, Long; Si, Cai-Juan; Yu, Xiao-Long; Liao, Dan; Gao, Wei; Zhang, Lun; Zheng, Pei-Fen

    2015-08-07

    Previous studies reported the potential associations between dietary patterns and the risk of coronary heart disease (CHD) in adulthood, however a consistent perspective has not been established to date. Herein, we carried out this meta-analysis to evaluate the associations between dietary patterns and the risk of CHD. MEDLINE and EBSCO were searched for relevant articles published up to April 2015. A total of 35 articles (reporting 37 original studies) met the inclusion criteria and were included in the present meta-analysis. The decreased risk of CHD was shown for the highest compared with the lowest categories of healthy/prudent dietary patterns (odds ratio (OR) = 0.67; 95% confidence interval (CI): 0.60, 0.75; p < 0.00001) and alcohol consumption (OR = 0.68; 95% CI: 0.59, 0.78; p < 0.00001). There was evidence of an increased risk of CHD in the highest compared with the lowest categories of the unhealthy/Western-type dietary patterns (OR = 1.45; 95% CI: 1.05, 2.01; p = 0.02). The results of this meta-analysis indicate that different dietary patterns may be associated with the risk of CHD.

  11. Pulmonary hypertension in adults with congenital heart disease and Eisenmenger syndrome: current advanced management strategies.

    PubMed

    D'Alto, Michele; Diller, Gerhard-Paul

    2014-09-01

    The presence of pulmonary arterial hypertension (PAH) increases morbidity and reduces survival in patients with congenital heart disease (CHD). PAH-CHD is a heterogeneous condition, depending on the type of the underlying defect and previous repair strategies. There is growing evidence of the benefits of PAH-specific therapy in the PAH-CHD population, but despite recent advances mortality rates remain relatively high. In the last years, an increasing focus has been placed on patients with PAH-CHD and net left-to-right shunt. Currently, there are limited data to guide the management of these patients and uncertainty on the cut-off values for eventual defect closure. Pregnancy conveys significant risks in PAH-CHD patients: appropriate counselling and care, including psychological support and a multidisciplinary team, should be part of the routine management of women with PAH-CHD of reproductive age. Some subgroups, such as patients with Down's syndrome, Fontan circulation and 'segmental' pulmonary hypertension, present particular challenges in terms of management and therapy. The current review focuses on contemporary treatment strategies in PAH-CHD patients with particular emphasis on challenging patient groups and conditions.

  12. Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

    PubMed

    Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

    2016-02-01

    Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of

  13. Anatomic Localization and Autonomic Modulation of AV Junctional Rhythm in Failing Human Hearts

    PubMed Central

    Fedorov, Vadim V.; Ambrosi, Christina M.; Kostecki, Geran; Hucker, William J.; Glukhov, Alexey V.; Wuskell, Joseph P.; Loew, Leslie M.; Moazami, Nader; Efimov, Igor R.

    2011-01-01

    Background The structure-function relationship in the atrioventricular junction (AVJ) of various animal species has been investigated in detail, however less is known about the human AVJ. In this study, we performed high-resolution optical mapping of the human AVJ (n=6) to define its pacemaker properties and response to autonomic stimulation. Methods and Results Isolated, coronary-perfused AVJ preparations from failing human hearts (n=6, 53±6 years) were optically mapped using the near-infrared, voltage-sensitive dye, di-4-ANBDQBS, with isoproterenol (Iso, 1 μM) and acetylcholine (ACh, 1μM). An algorithm detecting multiple components of optical action potentials was used to reconstruct multi-layered intramural AVJ activation and to identify specialized slow and fast conduction pathways (SP and FP). The anatomical origin and propagation of pacemaker activity was verified via histology. Spontaneous AVJ rhythms of 29±11 bpm (n=6) originated in the nodal-His region (NH, n=3) and/or the proximal His bundle (H, n=4). Iso accelerated the AVJ rhythm to 69±12 bpm (n=5); shifted the leading pacemaker to the transitional cell (TC) regions near the FP and SP (n=4) and/or coronary sinus (n=2); and triggered reentrant arrhythmias (n=2). ACh (n=4) decreased the AVJ rhythm to 18±4 bpm; slowed FP/SP conduction leading to block between the AVJ and atrium; and shifted the pacemaker to either the TC or TC/NH (bifocal activation). Conclusions We have demonstrated that the AVJ pacemaker in failing human hearts is located in the NH or H-regions and can be modified with autonomic stimulation. Moreover, we found that both the FP and SP are involved in anterograde and retrograde conduction. PMID:21646375

  14. Cor triatriatum dexter versus prominent Eustachian valve in an adult congenital heart disease patient.

    PubMed

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna; Marrero-Santiago, Hector; Santana-Montesdeoca, Jose; López-Gude, María Jesús

    2013-01-01

    An eustachian valve (EV) remnant, if present, is usually noted by the presence of a thin ridge or a crescent-shaped fold of endocardium arising from the anterior rim of the inferior vena cava orifice due to the persistence of the right sinus venosus valve. Though the embryologic explanation of cor triatriatum dexter (CTD) is the same as that of the normal formation of the EV--lack of regression of the right sinus venosus valve--it is usually called CTD or divided right atrium when there are attachments on the atrial septum giving the appearance of a divided atrium. However, it's called prominent eustachian valve when the right sinus venosus valve has partly regressed, with no remaining septal attachments and without the appearance of a divided atrium. We present the case of an adult patient with an atrial septal defect with a high insertion of a giant EV, which mimics the echocardiographic appearance of divided right atrium.

  15. Dietary patterns and bone mineral status in young adults: the Northern Ireland Young Hearts Project.

    PubMed

    Whittle, Claire R; Woodside, Jayne V; Cardwell, Chris R; McCourt, Hannah J; Young, Ian S; Murray, Liam J; Boreham, Colin A; Gallagher, Alison M; Neville, Charlotte E; McKinley, Michelle C

    2012-10-28

    Studies of individual nutrients or foods have revealed much about dietary influences on bone. Multiple food or nutrient approaches, such as dietary pattern analysis, could offer further insight but research is limited and largely confined to older adults. We examined the relationship between dietary patterns, obtained by a posteriori and a priori methods, and bone mineral status (BMS; collective term for bone mineral content (BMC) and bone mineral density (BMD)) in young adults (20-25 years; n 489). Diet was assessed by 7 d diet history and BMD and BMC were determined at the lumbar spine and femoral neck (FN). A posteriori dietary patterns were derived using principal component analysis (PCA) and three a priori dietary quality scores were applied (dietary diversity score (DDS), nutritional risk score and Mediterranean diet score). For the PCA-derived dietary patterns, women in the top compared to the bottom fifth of the 'Nuts and Meat' pattern had greater FN BMD by 0·074 g/cm(2) (P = 0·049) and FN BMC by 0·40 g (P = 0·034) after adjustment for confounders. Similarly, men in the top compared to the bottom fifth of the 'Refined' pattern had lower FN BMC by 0·41 g (P = 0·049). For the a priori DDS, women in the top compared to the bottom third had lower FN BMD by 0·05 g/cm(2) after adjustments (P = 0·052), but no other relationships with BMS were identified. In conclusion, adherence to a 'Nuts and Meat' dietary pattern may be associated with greater BMS in young women and a 'Refined' dietary pattern may be detrimental for bone health in young men.

  16. The Adult Göttingen Minipig as a Model for Chronic Heart Failure After Myocardial Infarction: Focus on Cardiovascular Imaging and Regenerative Therapies

    PubMed Central

    Schuleri, Karl H; Boyle, Andrew J; Centola, Marco; Amado, Luciano C; Evers, Robert; Zimmet, Jeffrey M; Evers, Kristine S; Ostbye, Katherine M; Scorpio, Diana G; Hare, Joshua M; Lardo, Albert C

    2008-01-01

    Porcine models have become increasingly popular in cardiovascular research. The standard farm pig rapidly increases in body weight and size, potentially confounding serial measurements of cardiac function and morphology. We developed an adult porcine model that does not show physiologic increases in heart mass during the study period and is suitable for long-term study. We compared adult minipigs with the commonly used adolescent Yorkshire swine. Myocardial infarction was induced in adult Göttingen minipigs and adolescent Yorkshire swine by occlusion of the left anterior descending coronary artery followed by reperfusion. At 8 wk after infarction, the left ventricular ejection fraction was 34.1 ± 2.3% in minipigs and 30.7 ± 2.0% in Yorkshire swine. The left ventricular end-diastolic mass in Yorkshire pigs assessed by magnetic resonance imaging increased 17 ± 5 g, from 42.6 ± 4.3 g at week 1 after infarction to 52.8 ± 6.6 g at week 8, whereas it remained unchanged in minipigs. Cardiac anatomy and physiology in adult minipigs were evaluated invasively by angiography and noninvasively by Multidetector Computed Tomography and by Magnetic Resonance Imaging at 1.5 T and 3 T prior to myocardial infarction and during folow-up. This porcine heart failure model is reproducible, mimics the pathophysiology in patients who have experienced myocardial infarction, and is suitable for imaging studies. New heart failure therapies and devices can be tested preclinically in this adult animal model of chronic heart failure. PMID:19149414

  17. Experiences and Outcomes of Transition from Pediatric to Adult Health Care Services for Young People with Congenital Heart Disease: A Systematic Review.

    PubMed

    Heery, Emily; Sheehan, Aisling M; While, Alison E; Coyne, Imelda

    2015-01-01

    This review synthesizes the empirical literature on outcomes and experiences of transfer and transition from pediatric to adult care for young people with congenital heart disease. A systematic review of papers published between January 2001 and May 2013 that examined outcomes or experiences of transfer and transition among young people with congenital heart disease was conducted. Data were extracted by two independent reviewers with the outcomes data combined using narrative synthesis and the experiences data integrated using thematic synthesis. Thirteen papers were included in the review: six reported outcomes following transfer, six reported experiences of transfer and transition, and one reported both outcomes and experiences. The review data indicate that high proportions of young people were lost to follow-up or experienced long gaps in care after leaving pediatric cardiology. Factors that protected against loss to follow-up or lapse in care included: beliefs that specialized adult care was necessary; poorer health status; attendance at pediatric appointments without parents; and pediatric referral to an adult congenital heart disease center. Data on experiences highlighted that many young people were unconcerned about transition, but lacked knowledge about their condition and were insufficiently prepared for transfer. In terms of adult services, many young people desired continuity in the quality of care, youth-oriented facilities, a personalized approach, and for their parents to remain involved in their care, but in a secondary, supportive capacity. In conclusion, the high proportions of young people lost to follow-up highlight the need for formal transition programs, which ensure a planned and coordinated transfer. Patients with congenital heart disease need education throughout adolescence about the implications of their condition, the differences between pediatric and adult services, and self-care management.

  18. Left heart bypass support with the Rotaflow Centrifugal Pump® as a bridge to decision and recovery in an adult.

    PubMed

    Kashiwa, Koichi; Nishimura, Takashi; Saito, Aya; Kubo, Hitoshi; Fukaya, Aoi; Tamai, Hisayoshi; Yambe, Tomoyuki; Kyo, Shunei; Ono, Minoru

    2012-06-01

    Since left heart bypass or biventricular circulatory assist with an extracorporeal centrifugal pump as a bridge to decision or recovery sometimes requires long-time support, the long-term durability of extracorporeal centrifugal pumps is crucial. The Rotaflow Centrifugal Pump(®) (MAQUET Cardiopulmonary AG, Hirrlingen, Germany) is one of the centrifugal pumps available for long-term use in Japan. However, there have been few reports of left heart bypass or biventricular circulatory support over the mid-term. This is a case report of left heart bypass support with the Rotaflow Centrifugal Pump(®) as a bridge to decision and recovery for an adult patient who could not be weaned from cardiopulmonary bypass and percutaneous cardiopulmonary support after cardiac surgery. We could confirm that the patient's consciousness level was normal; however, the patient could not be weaned from the left heart bypass support lasting 1 month. Therefore, the circulatory assist device was switched to the extracorporeal Nipro ventricular assist device (VAD). This time, left heart bypass support could be maintained for 30 days using a single Rotaflow Centrifugal Pump(®). There were no signs of hemolysis during left heart bypass support. The Rotaflow Centrifugal Pump(®) itself may be used as a device for a bridge to decision or recovery before using a VAD in cardiogenic shock patients.

  19. Associations of Heart Rate With Inflammatory Markers Are Modulated by Gender and Obesity in Older Adults

    PubMed Central

    Bandinelli, Stefania; Gemma, Antonella; Ferrucci, Luigi; Incalzi, Raffaele Antonelli

    2015-01-01

    Background. Faster resting heart rate (HR), which is associated with inflammation and elevated cortisol levels, is a risk factor for excess cardiovascular morbidity and mortality. Obesity is associated with increased cardiovascular morbidity and mortality, inflammation, and elevated cortisol levels. The aim of the present study was to evaluate the interaction of Body Mass Index (BMI) with inflammation and cortisol in modulating HR in older subjects. Methods. We analyzed data of 895 participants aged 65+ enrolled in the “InCHIANTI” study, in sinus rhythm, and not taking beta blockers or digoxin. Linear regression was performed to assess the adjusted association between HR, IL-6, and cortisol levels. The model was also analyzed stratifying for BMI tertiles. Logistic regression was adopted for evaluating the association of HR exceeding the mean value with Il-6 and serum cortisol. Results. According to multivariable linear regression, IL-6 and cortisol levels were associated with HR (B = 1.42, 95% CI = 0.43–2.42; p = .005 and B = .34, 95% CI = 0.17–.51; p < .0001, respectively). The association was significant only among women in the highest BMI tertile (B = 4.16, 95% CI = 1.40–6.91; p = .003 for IL-6 and B = .57, 95% CI = 0.14–1.01; p = .010 for cortisol). Logistic regression confirmed that IL-6 and cortisol levels were associated with HR above the mean value in the highest BMI tertile (OR = 2.13, 95% CI = 1.15–3.97; p = .009 and OR = 1.14, 95% CI = 1.03–1.25; p = .009, respectively). Conclusions. Faster HR is associated with proinflammatory state in elderly patients; this association seems to be limited to women with higher BMI. PMID:25429009

  20. Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study

    PubMed Central

    Saito, Isao; Hitsumoto, Shinichi; Maruyama, Koutatsu; Nishida, Wataru; Eguchi, Eri; Kato, Tadahiro; Kawamura, Ryoichi; Takata, Yasunori; Onuma, Hiroshi; Osawa, Haruhiko; Tanigawa, Takeshi

    2015-01-01

    Background Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. Methods Between 2009–2012, the Toon Health Study recruited 1899 individuals aged 30–79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR) and Gutt’s insulin sensitivity index (ISI). Pulse was recorded for 5 min, and time-domain heart rate variability (HRV) indices were calculated: the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive difference (RMSSD). Power spectral analysis provided frequency domain measures of HRV: high frequency (HF) power, low frequency (LF) power, and the LF:HF ratio. Results Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41–3.10). Conclusions Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals. PMID:26277879

  1. Heart Anatomy

    MedlinePlus

    ... español An Incredible Machine Bonus poster (PDF) The Human Heart Anatomy Blood The Conduction System The Coronary Arteries The Heart Valves The Heartbeat Vasculature of the Arm Vasculature of the Head Vasculature of the Leg Vasculature of the Torso ...

  2. Simple Dispersion Equation Based on Lamb-Wave Model for Propagating Pulsive Waves in Human Heart Wall

    NASA Astrophysics Data System (ADS)

    Bekki, Naoaki; Shintani, Seine A.

    2015-12-01

    We consider the Rayleigh-Lamb-type equation for propagating pulsive waves excited by aortic-valve closure at end-systole in the human heart wall. We theoretically investigate the transcendental dispersion equation of pulsive waves for the asymmetrical zero-order mode of the Lamb wave. We analytically find a simple dispersion equation with a universal constant for a small Lamb wavenumber. We show that the simple dispersion equation can qualitatively explain the myocardial noninvasive measurements in vivo of pulsive waves in the human heart wall. We can also consistently estimate the viscoelastic constant of the myocardium in the human heart wall using the simple dispersion equation for a small Lamb wavenumber instead of using a complex nonlinear optimization.

  3. Hybrid Surgery Options for Complex Clinical Scenarios in Adult Patients with Congenital Heart Disease: Three Case Reports

    PubMed Central

    Rapetto, Filippo; Kenny, Damien; Turner, Mark; Parry, Andrew; Stoica, Serban; Uzun, Orhan; Caputo, Massimo

    2017-01-01

    The strategy for the management of adult patients with congenital heart disease (CHD) often represents a challenge for cardiac surgeons and cardiologists due to complex anatomy, wide range of clinical presentations, and a high-risk profile. However, hybrid approach may represent an attractive solution. We report three cases of adult patients previously operated for CHD and recently treated with a hybrid approach in our institution. Case 1: a 76-year-old woman with permanent atrial fibrillation, lung disease, chronic kidney disease, microcytic anemia, and type II diabetes mellitus, previously operated for atrial septal defect closure and pulmonary valvotomy, presented with severe pulmonary regurgitation and advanced right ventricular failure. In order to minimize the surgical risk, a hybrid approach was used: an extensive right ventricular outflow tract (RVOT) plication was followed by implantation of an Edwards Sapien XT prosthesis in the RVOT through the right ventricular apex, without cardiopulmonary bypass. Case 2: a 64-year-old man with previous atrial septum excision and pericardial baffle for partial anomalous pulmonary venous drainage with intact interatrial septum, presented with worsening dyspnea, right ventricular failure, and pulmonary hypertension caused by baffle stenosis. His comorbidities included coronary artery disease, atrial flutter, and previous left pneumonectomy. After performing a redo longitudinal median sternotomy, a 20-mm stent was implanted in the baffle with access through the superior vena cava. Case 3: a 50-year-old man, with previous atrioventricular septal defect repair, followed by mitral valve replacement with a mechanical prosthesis, subsequently developed a paravalvular leak (PVL) with severe mitral regurgitation and severe left ventricular dysfunction. He underwent a transapical PVL device closure with two Amplatzer Vascular Plugs. In our opinion, hybrid surgery is a promising therapeutic modality that increases the available

  4. Prevalence of Major Cardiovascular Risk Factors and Coronary Heart Disease in a Sample of Greek Adults: The Saronikos Study

    PubMed Central

    Gikas, Aristofanis; Lambadiari, Vaia; Sotiropoulos, Alexios; Panagiotakos, Demosthenes; Pappas, Stavros

    2016-01-01

    Background: Comprehensive data regarding prevalence of coronary heart disease (CHD) and associated factors in different geographical regions are very important to our understanding of global distribution and evolution of CHD. The aim of this study was to assess the current prevalence of self-reported risk factors and CHD in Greek adult population. Methods: A community-based cross-sectional study was conducted in May 2014, during an election day, among residents of Saronikos municipality (Attica region). Data were collected from face-to-face interviews. The study sample included 2636 subjects (men, 49.5%; mean age, 50.5; range 20-95 years), with similar age and sex distribution to the target population. Results: The age-standardized prevalence rates of five major risk factors were as follows: type 2 diabetes 11.1%, hypercholesterolemia (cholesterol>240 mg/dl or using cholesterol-lowering medication) 23.8%, hypertension 27.2%, current smoking 38.9% and physical inactivity 43%. Of the participants, only 21% were free of any of these factors. Clustering of two to five risk factors was more frequent among persons aged 50 years and older as compared with younger ones (60% vs 27%, P=0.000). The age-adjusted prevalence of CHD was 6.3% (in men, 8.9%; in women, 3.8%) and that of myocardial infarction was 3.6% (in men, 5.2%; in women, 2.1%). According to multivariate analysis age, gender, education level, obesity, diabetes, hypercholesterolemia, hypertension and ever smoking were strongly associated with CHD. Conclusion: Classic risk factors are highly prevalent and frequently clustered, especially in adults aged 50 years and older. These findings raise concerns about future trends of already increased rates of CHD. Multifactorial and integrated population-based interventions need to be applied to reduce the burden of cardiovascular conditions. PMID:27429668

  5. A quantitative systematic review of normal values for short-term heart rate variability in healthy adults.

    PubMed

    Nunan, David; Sandercock, Gavin R H; Brodie, David A

    2010-11-01

    Heart rate variability (HRV) is a known risk factor for mortality in both healthy and patient populations. There are currently no normative data for short-term measures of HRV. A thorough review of short-term HRV data published since 1996 was therefore performed. Data from studies published after the 1996 Task Force report (i.e., between January 1997 and September 2008) and reporting short-term measures of HRV obtained in normally healthy individuals were collated and factors underlying discrepant values were identified. Forty-four studies met the pre-set inclusion criteria involving 21,438 participants. Values for short-term HRV measures from the literature were lower than Task Force norms. A degree of homogeneity for common measures of HRV in healthy adults was shown across studies. A number of studies demonstrate large interindividual variations (up to 260,000%), particularly for spectral measures. A number of methodological discrepancies underlined disparate values. These include a systematic failure within the literature (a) to recognize the importance of RR data recognition/editing procedures and (b) to question disparate HRV values observed in normally healthy individuals. A need for large-scale population studies and a review of the Task Force recommendations for short-term HRV that covers the full-age spectrum were identified. Data presented should be used to quantify reference ranges for short-term measures of HRV in healthy adult populations but should be undertaken with reference to methodological factors underlying disparate values. Recommendations for the measurement of HRV require updating to include current technologies.

  6. Differentiation of Overweight from Normal Weight Young Adults by Postprandial Heart Rate Variability and Systolic Blood Pressure

    PubMed Central

    Taffe, Lauren; Stancil, Kimani; Bond, Vernon; Pemminati, Sudhakar; Gorantla, Vasavi Rakesh; Kadur, Kishan

    2016-01-01

    Introduction Obesity and cardiovascular disease are inextricably linked and the health community’s response to the current epidemic of adolescent obesity may be improved by the ability to target adolescents at highest risk for developing cardiovascular disease in the future. Overweight manifests early as autonomic dysregulation and current methods do not permit differentiation of overweight adolescents or young adults at highest risk for developing cardiovascular disease. Aim This study was designed to test the hypothesis that scaling exponents motivated by nonlinear fractal analyses of Heart Rate Variability (HRV) differentiate overweight, otherwise healthy adolescent/young adult subjects at risk for developing prehypertension, the primary forerunner of cardiovascular disease. Materials and Methods The subjects were 18-20year old males with Body Mass Index (BMI) 20.1-42.5kg/m2. Electrocardiographic inter-beat (RR) intervals were measured during 3h periods of bed rest after overnight fasting and ingestion of 900Cal high-carbohydrate and high-fat test beverages on separate days. Detrended Fluctuation Analysis (DFA), k-means cluster and ANOVA analyses of scaling coefficients α, α1, and α2, showed dependencies on hourly measurements of systolic blood pressure and on premeasured BMI. Results It was observed that α value increased during the caloric challenge, appears to represent metabolically-induced changes in HRV across the participants. An ancillary analysis was performed to determine the dependency on BMI without BMI as a parameter. Cluster analysis of the high-carbohydrate test beverage treatment and the high-fat treatment produced grouping with very little overlap. ANOVA on both clusters demonstrated significance at p<0.001. We were able to demonstrate increased sympathetic modulation of our study group during ingestion and metabolism of isocaloric high-carbohydrate and high-fat test beverages. Conclusion These findings demonstrate significantly different

  7. Absence of sex differences in systolic blood pressure and heart rate responses to exercise in healthy young adults.

    PubMed

    Maruf, F A; Ogochukwu, U N; Dim, P A; Alada, A Ra

    2012-06-07

    The influence of sex on systolic blood pressure (SBP) and heart rate (HR) responses associated with cardiovascular morbidity, in healthy young adults was determined in ninety healthy young adults (47 females and 43 males) exercised using Bruce protocol. SBP and HR were measured pre- and post-exercise, and during recovery. SBPresponse (peak minus pre-exercise SBP), %SBPresponse [(peak minus pre-exercise SBP)÷pre-exercise SBP]x100, SBP3 (SBP 3 minutes into recovery), SBP4 (SBP 4 minutes into recovery), SBP3:peak (SBP3÷peak SBP), %SBPd3 [(peak SBP minus SBP 3 minutes into recovery)x peak SBP]x100, %SBPd4 [(peak SBP minus SBP 4 minutes into recovery)x peak SBP]X100, HRresponse (Peak HR minus pre-exercise HR), %HRresponse [(peak HR minus pre-exercise HR)÷pre-exercise HR]x 100, HR3 (HR 3 minutes into recovery), HR4 (HR 4 minutes into recovery), %HRd3 [(peak HR minus HR 3 minutes into recovery)÷peak HR]x100, %HRd4 [(peak HR minus HR 4 minutes into recovery)÷peak HR]X100, and HR50-70 (HR between 50th and 70th seconds into recovery) were derived from SBP and HR measurements. SBPpeak, HRresponse and %HRresponse were higher in males than in females whereas, SBPresponse, %SBPresponse and HRpeak were not different. There were no significant differences in the post-exercise SBP and HR responses of males and females except for SBP3, SBP4, HR3 and HR4. After adjusting for exercise duration, body mass index (BMI), and resting SBP and HR, these variables became similar. Sex differences in some SBP and HR responses to exercise, become nonexistent after adjusting for BMI, exercise duration, and resting SBP and HR.

  8. A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart

    PubMed Central

    Thomas, R. Croft; Singh, Abhishek; Cowley, Patrick; Myagmar, Bat-Erdene; Montgomery, Megan D.; Swigart, Philip M.; De Marco, Teresa; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    Background Translation of preclinical findings could benefit from a simple, reproducible, high throughput human model to study myocardial signaling. Alpha-1A-adrenergic receptors (ARs) are expressed at very low levels in the human heart, and it is unknown if they function. Objectives To develop a high throughput human myocardial slice culture model, and to test the hypothesis that alpha-1A- ARs are functional in the human heart. Methods Cores of LV free wall 8 mm diameter were taken from 52 hearts (18 failing and 34 nonfailing). Slices 250 μm thick were cut with a Krumdieck apparatus and cultured using a rotating incubation unit. Results About 60 slices were cut from each LV core, and a typical study could use 96 slices. Myocyte morphology was maintained, and diffusion into the slice center was rapid. Slice viability was stable for at least 3 days in culture by ATP and MTT assays. The beta-AR agonist isoproterenol stimulated phospholamban phosphorylation, and the alpha-1A-AR agonist A61603 stimulated ERK phosphorylation, with nanomolar EC50 values in slices from both failing and nonfailing hearts. Strips cut from the slices were used to quantify activation of contraction by isoproterenol, A61603, and phenylephrine. The slices supported transduction by adenovirus. Conclusions We have developed a simple, high throughput LV myocardial slice culture model to study signaling in the human heart. This model can be useful for translational studies, and we show for the first time that the alpha-1A-AR is functional in signaling and contraction in the human heart. PMID:27453955

  9. Linking Gene Expression and Functional Network Data in Human Heart Failure

    PubMed Central

    Camargo, Anyela; Azuaje, Francisco

    2007-01-01

    Background Gene expression profiling and the analysis of protein-protein interaction (PPI) networks may support the identification of disease bio-markers and potential drug targets. Thus, a step forward in the development of systems approaches to medicine is the integrative analysis of these data sources in specific pathological conditions. We report such an integrative bioinformatics analysis in human heart failure (HF). A global PPI network in HF was assembled, which by itself represents a useful compendium of the current status of human HF-relevant interactions. This provided the basis for the analysis of interaction connectivity patterns in relation to a HF gene expression data set. Results Relationships between the significance of the differentiation of gene expression and connectivity degrees in the PPI network were established. In addition, relationships between gene co-expression and PPI network connectivity were analysed. Highly-connected proteins are not necessarily encoded by genes significantly differentially expressed. Genes that are not significantly differentially expressed may encode proteins that exhibit diverse network connectivity patterns. Furthermore, genes that were not defined as significantly differentially expressed may encode proteins with many interacting partners. Genes encoding network hubs may exhibit weak co-expression with the genes encoding their interacting protein partners. We also found that hubs and superhubs display a significant diversity of co-expression patterns in comparison to peripheral nodes. Gene Ontology (GO) analysis established that highly-connected proteins are likely to be engaged in higher level GO biological process terms, while low-connectivity proteins tend to be engaged in more specific disease-related processes. Conclusion This investigation supports the hypothesis that the integrative analysis of differential gene expression and PPI network analysis may facilitate a better understanding of functional roles

  10. Features of hand-foot crawling behavior in human adults.

    PubMed

    Maclellan, M J; Ivanenko, Y P; Cappellini, G; Sylos Labini, F; Lacquaniti, F

    2012-01-01

    Interlimb coordination of crawling kinematics in humans shares features with other primates and nonprimate quadrupeds, and it has been suggested that this is due to a similar organization of the locomotor pattern generators (CPGs). To extend the previous findings and to further explore the neural control of bipedal vs. quadrupedal locomotion, we used a crawling paradigm in which healthy adults crawled on their hands and feet at different speeds and at different surface inclinations (13°, 27°, and 35°). Ground reaction forces, limb kinematics, and electromyographic (EMG) activity from 26 upper and lower limb muscles on the right side of the body were collected. The EMG activity was mapped onto the spinal cord in approximate rostrocaudal locations of the motoneuron pools to characterize the general features of cervical and lumbosacral spinal cord activation. The spatiotemporal pattern of spinal cord activity significantly differed between quadrupedal and bipedal gaits. In addition, participants exhibited a large range of kinematic coordination styles (diagonal vs. lateral patterns), which is in contrast to the stereotypical kinematics of upright bipedal walking, suggesting flexible coupling of cervical and lumbosacral pattern generators. Results showed strikingly dissimilar directional horizontal forces for the arms and legs, considerably retracted average leg orientation, and substantially smaller sacral vs. lumbar motoneuron activity compared with quadrupedal gait in animals. A gradual transition to a more vertical body orientation (increasing the inclination of the treadmill) led to the appearance of more prominent sacral activity (related to activation of ankle plantar flexors), typical of bipedal walking. The findings highlight the reorganization and adaptation of CPG networks involved in the control of quadrupedal human locomotion and a high specialization of the musculoskeletal apparatus to specific gaits.

  11. Evaluation of Adult Chronic Chagas' Heart Disease Diagnosis by Molecular and Serological Methods ▿

    PubMed Central

    Ramírez, Juan David; Guhl, Felipe; Umezawa, Eufrosina Setsu; Morillo, Carlos A.; Rosas, Fernando; Marin-Neto, Jose A.; Restrepo, Silvia

    2009-01-01

    Chagas' disease caused by Trypanosoma cruzi is endemic in Latin America. T. cruzi presents heterogeneous populations and comprises two main genetic lineages, named T. cruzi I and T. cruzi II. Diagnosis in the chronic phase is based on conventional serological tests, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), and diagnosis in the acute phase based on parasitological methods, including hemoculture. The objective of this study was to evaluate the diagnostic procedures of Chagas' disease in adult patients in the chronic phase by using a PCR assay and conventional serological tests, including TESA-blot as the gold standard. Samples were obtained from 240 clinical chronic chagasic patients. The sensitivities, compared to that of TESA-blot, were 70% for PCR using the kinetoplast region, 75% for PCR using the nuclear repetitive region, 99% for IIF, and 95% for ELISA. According to the serological tests results, we recommend that researchers assess the reliability and sensitivity of the commercial kit Chagatest ELISA recombinant, version 3.0 (Chagatest Rec v3.0; Wiener Lab, Rosario, Argentina), due to the lack of sensitivity. Based on our analysis, we concluded that PCR cannot be validated as a conventional diagnostic technique for Chagas' disease. These data have been corroborated by low levels of concordance with serology test results. It is recommended that PCR be used only for alternative diagnostic support. Using the nuclear repetitive region of T. cruzi, PCR could also be applicable for monitoring patients receiving etiologic treatment. PMID:19846646

  12. Hemodynamic Correlates of Blood Pressure Across the Adult Age Spectrum: Noninvasive Evaluation in the Framingham Heart Study

    PubMed Central

    Mitchell, Gary F.; Wang, Na; Palmisano, Joseph N.; Larson, Martin G.; Hamburg, Naomi M.; Vita, Joseph A.; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.

    2010-01-01

    Background Systolic blood pressure and pulse pressure are substantially higher in older adults. The relative contributions of increased forward versus reflected pressure wave amplitude or earlier arrival of the reflected wave to elevated pulse pressure remain controversial. Methods and Results We measured proximal aortic pressure and flow, forward pressure wave amplitude, global wave reflection, reflected wave timing and pulse wave velocity noninvasively in 6417 (age range, 19 to 90 years; 53% women) Framingham Heart Study Third Generation and Offspring participants. Variation in forward wave amplitude paralleled pulse pressure throughout adulthood. In contrast, wave reflection and pulse pressure were divergent across adulthood: in younger participants, pulse pressure was lower and wave reflection higher with advancing age whereas in older participants, pulse pressure was higher and wave reflection lower with age. Reflected wave timing differed modestly across age groups despite considerable differences in pulse wave velocity. Forward wave amplitude explained 80% (central) and 66% (peripheral) of the variance in pulse pressure in younger participants (<50 years) and 90% and 84% in the older participants (≥50 years, all P<0.0001). In a stepwise model that evaluated age-pulse pressure relations in the full sample, the late accelerated increases in central and peripheral pulse pressure were markedly attenuated when variation in forward wave amplitude was considered. Conclusions Higher pulse pressure at any age and higher pulse pressure with advancing age is predominantly associated with a larger forward pressure wave. The influence of wave reflection on age-related differences in pulse pressure was minor. PMID:20855656

  13. Metric analysis of basal sphenoid angle in adult human skulls

    PubMed Central

    Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

    2014-01-01

    Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

  14. Body mass index, waist-circumference and cardiovascular disease risk factors in Iranian adults: Isfahan healthy heart program.

    PubMed

    Mohammadifard, Noushin; Nazem, Masoud; Sarrafzadegan, Nizal; Nouri, Fatemeh; Sajjadi, Firouzeh; Maghroun, Maryam; Alikhasi, Hassan

    2013-09-01

    Considering the main effect of obesity on chronic non-communicable diseases, this study was performed to assess the association between body mass index (BMI), waist-circumference (WC), cardio-metabolic risk factors and to corroborate whether either or both BMI and WC are independently associated with the risk factors in a sample of Iranian adults. This cross-sectional study was performed on data from baseline survey of Isfahan Healthy Heart Program (IHHP). The study was done on 12,514 randomly-selected adults in Isfahan, Najafabad and Arak counties in 2000-2001. Ages of the subjects were recorded. Fasting blood glucose (FBG), 2-hour post-load glucose (2hpp), serum lipids, systolic and diastolic blood pressure (SBP and DBP), BMI, WC, smoking status, and total daily physical activity were determined. Increase in BMI and WC had a significant positive relation with the mean of FBG, 2hpp, SBP, DBP, serum lipids, except for HDL-C (p<0.001 for all). After adjustment for age, smoking, physical activity, socioeconomic status (SES), and BMI, the highest odds ratio (OR) (95% CI) for diabetes mellitus (DM) according to WC was 3.13 (1.93-5.08) and 1.99 (1.15-3.44) in women and men respectively. Moreover, the highest ORs based on BMI with adjustment for age, smoking, physical activity, SES, and WC were for dyslipidaemia (DLP) [1.97 (1.58-2.45) in women and 2.96 (2.41-3.63) in men]. The use of BMI or WC alone in the models caused to enhance all ORs. When both BMI and WC were entered in the model, the ORs for all risk factors, in men, according to BMI, were more compared to WC. However, in women, ORs for DM and hypertension (HTN) in WC quartiles were more than in BMI quartiles. BMI is the better predictor of DM, HTN, and DLP in men compared to WC. Conversely, in women, WC is a superior predictor than BMI, particularly for DM and HTN. Furthermore, the measurement of both WC and BMI in Iranian adults may be a better predictor of traditional risk factors of CVDs compared to BMI or WC

  15. Mutations in NTRK3 suggest a novel signaling pathway in human congenital heart disease

    PubMed Central

    Werner, Petra; Paluru, Prasuna; Simpson, Anisha M.; Latney, Brande; Iyer, Radhika; Brodeur, Garrett M.; Goldmuntz, Elizabeth

    2014-01-01

    Congenital heart defects (CHDs) are the most common major birth defects and the leading cause of death from congenital malformations. The etiology remains largely unknown, though genetic variants clearly contribute. In a previous study, we identified a large copy number variant (CNV) that deleted 46 genes in a patient with a malalignment type ventricular septal defect (VSD). The CNV included the gene NTRK3 encoding neurotrophic tyrosine kinase receptor C (TrkC), which is essential for normal cardiogenesis in animal models. To evaluate the role of NTRK3 in human CHDs, we studied 467 patients with related heart defects for NTRK3 mutations. We identified four missense mutations in four patients with VSDs that were not found in ethnically matched controls and were predicted to be functionally deleterious. Functional analysis using neuroblastoma cell lines expressing mutant TrkC demonstrated that one of the mutations (c.278C>T, p.T93M) significantly reduced autophosphorylation of TrkC in response to ligand binding, subsequently decreasing phosphorylation of downstream target proteins. In addition compared to WT, three of the four cell lines expressing mutant TrkC showed altered cell growth in low-serum conditions without supplemental NT-3. These findings suggest a novel pathophysiological mechanism involving NTRK3 in the development of VSDs. PMID:25196463

  16. [The function of the heart changes in implementation of the diving reactions in humans].

    PubMed

    Baranova, T I; Berlov, D N; Zavarina, L B; Minigalin, A D; Smith, N Y; Xu, S; Yanvareva, I N

    2015-03-01

    The changes of chronotropic function of the heart and of the myocardium in the implementation of the diving response in humans were studied by the electrocardiographic method. The study involved 80 students aged 18-20 years. Diving simulation was performed by immersing the face in cold water during breath-hold exhale. When the water temperature was 12.3 +/- 2.3 degrees C, average duration of apnea was 31 +/- 11 s. The oxygen content in the exhaled air after apnea was 98.8 +/- 8.7 mm Hg, carbon dioxide--49.1 +/- 3.5 mm Hg. It was observed slowing of the heart rate, mainly due to the increasing of diastole in 41 of the 80 surveyed during simulating diving. But it also can be observed symptoms of conduction deterioration: atrioventricular block type I (22% of reactive type and 29% of the highly reactive type subjects), and exceeds standards QTc-interval prolongation (at 7.5% of the subjects). These responses are adaptive in nature and disappear in the recovery process. But the fact abnormalities of conduction in the myocardium must be considered when using the diving reflex in medical practice, as may be due to a predisposition to a certain pathology of the cardiovascular system.

  17. Perturbations of heart development and function in cardiomyocytes from human embryonic stem cells with trisomy 21.

    PubMed

    Bosman, Alexis; Letourneau, Audrey; Sartiani, Laura; Del Lungo, Martina; Ronzoni, Flavio; Kuziakiv, Rostyslav; Tohonen, Virpi; Zucchelli, Marco; Santoni, Federico; Guipponi, Michel; Dumevska, Biljana; Hovatta, Outi; Antonarakis, Stylianos E; Jaconi, Marisa E

    2015-05-01

    Congenital heart defects (CHD) occur in approximately 50% of patients with Down syndrome (DS); the mechanisms for this occurrence however remain unknown. In order to understand how these defects evolve in early development in DS, we focused on the earliest stages of cardiogenesis to ascertain perturbations in development leading to CHD. Using a trisomy 21 (T21) sibling human embryonic stem cell (hESC) model of DS, we show that T21-hESC display many significant differences in expression of genes and cell populations associated with mesodermal, and more notably, secondary heart field (SHF) development, in particular a reduced number of ISL1(+) progenitor cells. Furthermore, we provide evidence for two candidate genes located on chromosome 21, ETS2 and ERG, whose overexpression during cardiac commitment likely account for the disruption of SHF development, as revealed by downregulation or overexpression experiments. Additionally, we uncover an abnormal electrophysiological phenotype in functional T21 cardiomyocytes, a result further supported by mRNA expression data acquired using RNA-Seq. These data, in combination, revealed a cardiomyocyte-specific phenotype in T21 cardiomyocytes, likely due to the overexpression of genes such as RYR2, NCX, and L-type Ca(2+) channel. These results contribute to the understanding of the mechanisms involved in the development of CHD. Stem Cells 2015;33:1434-1446.

  18. P2 receptors in human heart: upregulation of P2X6 in patients undergoing heart transplantation, interaction with TNFalpha and potential role in myocardial cell death.

    PubMed

    Banfi, Cristina; Ferrario, Silvia; De Vincenti, Ombretta; Ceruti, Stefania; Fumagalli, Marta; Mazzola, Alessia; D' Ambrosi, Nadia; Volontè, Cinzia; Fratto, Pasquale; Vitali, Ettore; Burnstock, Geoffrey; Beltrami, Elena; Parolari, Alessandro; Polvani, GianLuca; Biglioli, Paolo; Tremoli, Elena; Abbracchio, Maria P

    2005-12-01

    ATP acts as a neurotransmitter via seven P2X receptor-channels for Na(+) and Ca(2+), and eight G-protein-coupled P2Y receptors. Despite evidence suggesting roles in human heart, the map of myocardial P2 receptors is incomplete, and their involvement in chronic heart failure (CHF) has never received adequate attention. In left myocardia from five to nine control and 5-12 CHF subjects undergoing heart transplantation, we analyzed the full repertoire of P2 receptors and of 10 "orphan" P2Y-like receptors. All known P2Y receptors (i.e. P2Y(1,2,4,6,11,12,13,14)) and two P2Y-like receptors (GPR91 and GPR17) were detected in all subjects. All known P2X(1-7) receptors were also detected; of these, only P2X(6) was upregulated in CHF, as confirmed by quantitative real time-PCR. The potential significance of this change was studied in primary cardiac fibroblasts freshly isolated from young pigs. Exposure of cardiac fibroblasts to ATP or its hydrolysis-resistant-analog benzoylATP induced apoptosis. TNFalpha (a cytokine implicated in CHF progression) exacerbated cell death. Similar effects were induced by ATP and TNFalpha in a murine cardiomyocytic cell line. In cardiac fibroblasts, TNFalpha inhibited the downregulation of P2X(6) mRNA associated to prolonged agonist exposure, suggesting that, by preventing ATP-induced P2X(6) desensitization, TNFalpha may abolish a defense mechanism meant at avoiding Ca(2+) overload and, ultimately, Ca(2+)-dependent cell death. This may provide a basis for P2X(6) upregulation in CHF. In conclusion, we provide the first characterization of P2 receptors in the human heart and suggest that the interaction between TNFalpha and the upregulated P2X(6) receptor may represent a novel pathogenic mechanism in CHF.

  19. Catheter Ablation to Treat Supraventricular Arrhythmia in Children and Adults With Congenital Heart Disease: What We Know and Where We Are Going

    PubMed Central

    Thomas, Patricia E.; Macicek, Scott L.

    2016-01-01

    Background: Catheter ablation has been used to manage supraventricular arrhythmia in children since 1990. This article reviews the history of catheter ablation used to treat arrhythmia in children and discusses new frontiers in the field. We also address ablation in adult patients with a history of congenital heart disease (CHD) that was diagnosed and initially treated in childhood. Methods: We conducted an evidence-based literature review to gather available data on ablation for supraventricular tachycardia in children and adult patients with CHD. Results: Ablations can be performed safely and effectively in children. Complication rates are higher in children <4 years and <15 kg. In one study, the overall success rate of radiofrequency ablation in pediatrics was 95.7%, with the highest success rate in left free wall pathways (97.8%). Recurrence was higher in septal pathways. Cryoablation has been reported to have a 93% acute success rate for atrioventricular (AV) nodal reentrant tachycardia and septal pathways with no risk of AV block and a 5%-9% risk of recurrence. Three-dimensional mapping, intracardiac echocardiography, remote magnetic navigation, and irrigated catheter ablation are new technologies used to treat pediatric and adult patients with CHD. The population of adult patients with CHD is growing, and these patients are at particularly high risk for arrhythmia. A paucity of data is available on ablation in adult patients with CHD. Conclusion: Electrophysiology for pediatric and adult patients with CHD is a rapidly growing and progressing field. We benefit from continuous development of ablation techniques for adults with structurally normal hearts and have the unique challenge and responsibility to ensure the safe and effective application of these techniques in the vulnerable population of pediatric and adult patients with CHD. PMID:27660579

  20. Integrated Central-Autonomic Multifractal Complexity in the Heart Rate Variability of Healthy Humans

    PubMed Central

    Lin, D. C.; Sharif, A.

    2012-01-01

    Purpose of Study: The aim of this study was to characterize the central-autonomic interaction underlying the multifractality in heart rate variability (HRV) of healthy humans. Materials and Methods: Eleven young healthy subjects participated in two separate ~40 min experimental sessions, one in supine (SUP) and one in, head-up-tilt (HUT), upright (UPR) body positions. Surface scalp electroencephalography (EEG) and electrocardiogram (ECG) were collected and fractal correlation of brain and heart rate data was analyzed based on the idea of relative multifractality. The fractal correlation was further examined with the EEG, HRV spectral measures using linear regression of two variables and principal component analysis (PCA) to find clues for the physiological processing underlying the central influence in fractal HRV. Results: We report evidence of a central-autonomic fractal correlation (CAFC) where the HRV multifractal complexity varies significantly with the fractal correlation between the heart rate and brain data (P = 0.003). The linear regression shows significant correlation between CAFC measure and EEG Beta band spectral component (P = 0.01 for SUP and P = 0.002 for UPR positions). There is significant correlation between CAFC measure and HRV LF component in the SUP position (P = 0.04), whereas the correlation with the HRV HF component approaches significance (P = 0.07). The correlation between CAFC measure and HRV spectral measures in the UPR position is weak. The PCA results confirm these findings and further imply multiple physiological processes underlying CAFC, highlighting the importance of the EEG Alpha, Beta band, and the HRV LF, HF spectral measures in the supine position. Discussion and Conclusion: The findings of this work can be summarized into three points: (i) Similar fractal characteristics exist in the brain and heart rate fluctuation and the change toward stronger fractal correlation implies the change toward more complex

  1. Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart

    PubMed Central

    Hansen, Katrina J.; Favreau, John T.; Guyette, Jacques P.; Tao, Ze-Wei; Coffin, Spencer T.; Cunha-Gavidia, Anny; D'Amore, Brian; Perreault, Luke R.; Fitzpatrick, John P.; DeMartino, Angelica; Gaudette, Glenn R.

    2016-01-01

    Abstract Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW) and systolic area of contraction (SAC) and global parameters derived from the pressure waveform. MI (n = 6) significantly decreased RSW (0.026 ± 0.011) and SAC (0.022 ± 0.015) when compared with sham operation (RSW: 0.141 ± 0.009; SAC: 0.166 ± 0.005, n = 6) (p < 0.05). The delivery of unseeded biological sutures to the infarcted hearts did not change regional mechanical function compared with the infarcted hearts (RSW: 0.032 ± 0.004, SAC: 0.037 ± 0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend toward increase of regional mechanical function compared with the infarcted heart (RSW: 0.057 ± 0.011; SAC: 0.051 ± 0.014, n = 6). Global function showed no significant differences between any group (p > 0.05); however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0% ± 2.2%), where unseeded (3.8% ± 0.6%) and hMSC-seeded (3.7% ± 0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining suture area

  2. Direct hydrogel encapsulation of pluripotent stem cells enables ontomimetic differentiation and growth of engineered human heart tissues.

    PubMed

    Kerscher, Petra; Turnbull, Irene C; Hodge, Alexander J; Kim, Joonyul; Seliktar, Dror; Easley, Christopher J; Costa, Kevin D; Lipke, Elizabeth A

    2016-03-01

    Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. We demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue.

  3. Direct Hydrogel Encapsulation of Pluripotent Stem Cells Enables Ontomimetic Differentiation and Growth of Engineered Human Heart Tissues

    PubMed Central

    Kerscher, Petra; Turnbull, Irene C; Hodge, Alexander J; Kim, Joonyul; Seliktar, Dror; Easley, Christopher J; Costa, Kevin D; Lipke, Elizabeth A

    2016-01-01

    Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. Here we demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue. PMID:26826618

  4. Knowledge Gaps in Cardiovascular Care of Older Adults: A Scientific Statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society: Executive Summary.

    PubMed

    Rich, Michael W; Chyun, Deborah A; Skolnick, Adam H; Alexander, Karen P; Forman, Daniel E; Kitzman, Dalane W; Maurer, Mathew S; McClurken, James B; Resnick, Barbara M; Shen, Win K; Tirschwell, David L

    2016-11-01

    The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease (CVD) is the leading cause of death and major disability in adults aged 75 and older. Despite the effect of CVD on quality of life, morbidity, and mortality in older adults, individuals aged 75 and older have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older adults with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in nursing homes and assisted living facilities. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older adults typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision-making, and recommend future research to close existing knowledge gaps. To achieve these objectives, a detailed review was conducted of current American College of Cardiology/American Heart Association (ACC/AHA) and American Stroke Association (ASA) guidelines to identify content and recommendations that explicitly targeted older adults. A pervasive lack of evidence to guide clinical decision-making in older adults with CVD was found, as well as a paucity of data on the effect of diagnostic and therapeutic interventions on outcomes that are particularly important to older adults, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older adults representative of those seen in clinical practice and that incorporate relevant outcomes important to older adults in the study design. The results of these studies will provide the foundation for

  5. Two pacemaker channels from human heart with profoundly different activation kinetics.

    PubMed Central

    Ludwig, A; Zong, X; Stieber, J; Hullin, R; Hofmann, F; Biel, M

    1999-01-01

    Cardiac pacemaking is produced by the slow diastolic depolarization phase of the action potential. The hyperpolarization-activated cation current (If) forms an important part of the pacemaker depolarization and consists of two kinetic components (fast and slow). Recently, three full-length cDNAs encoding hyperpolarization-activated and cyclic nucleotide-gated cation channels (HCN1-3) have been cloned from mouse brain. To elucidate the molecular identity of cardiac pacemaker channels, we screened a human heart cDNA library using a highly conserved neuronal HCN channel segment and identified two cDNAs encoding HCN channels. The hHCN2 cDNA codes for a protein of 889 amino acids. The HCN2 gene is localized on human chromosome 19p13.3 and contains eight exons spanning approximately 27 kb. The second cDNA, designated hHCN4, codes for a protein of 1203 amino acids. Northern blot and PCR analyses showed that both hHCN2 and hHCN4 are expressed in heart ventricle and atrium. When expressed in HEK 293 cells, either cDNA gives rise to hyperpolarization-activated cation currents with the hallmark features of native If. hHCN2 and hHCN4 currents differ profoundly from each other in their activation kinetics, being fast and slow, respectively. We thus conclude that hHCN2 and hHCN4 may underlie the fast and slow component of cardiac If, respectively. PMID:10228147

  6. Autonomic control of heart rate by metabolically sensitive skeletal muscle afferents in humans.

    PubMed

    Fisher, James P; Seifert, Thomas; Hartwich, Doreen; Young, Colin N; Secher, Niels H; Fadel, Paul J

    2010-04-01

    Isolated activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) using post-exercise ischaemia (PEI) following handgrip partially maintains exercise-induced increases in arterial blood pressure (BP) and muscle sympathetic nerve activity (SNA), while heart rate (HR) declines towards resting values. Although masking of metaboreflex-mediated increases in cardiac SNA by parasympathetic reactivation during PEI has been suggested, this has not been directly tested in humans. In nine male subjects (23 +/- 5 years) the muscle metaboreflex was activated by PEI following moderate (PEI-M) and high (PEI-H) intensity isometric handgrip performed at 25% and 40% maximum voluntary contraction, under control (no drug), parasympathetic blockade (glycopyrrolate) and beta-adrenergic blockade (metoprolol or propranalol) conditions, while beat-to-beat HR and BP were continuously measured. During control PEI-M, HR was slightly elevated from rest (+3 +/- 2 beats min(-1)); however, this HR elevation was abolished with beta-adrenergic blockade (P < 0.05 vs. control) but augmented with parasympathetic blockade (+8 +/- 2 beats min(-1), P < 0.05 vs. control and beta-adrenergic blockade). The HR elevation during control PEI-H (+9 +/- 3 beats min(-1)) was greater than with PEI-M (P < 0.05), and was also attenuated with beta-adrenergic blockade (+4 +/- 2 beats min(-1), P < 0.05 vs. control), but was unchanged with parasympathetic blockade (+9 +/- 2 beats min(-1), P > 0.05 vs. control). BP was similarly increased from rest during PEI-M and further elevated during PEI-H (P < 0.05) in all conditions. Collectively, these findings suggest that the muscle metaboreflex increases cardiac SNA during PEI in humans; however, it requires a robust muscle metaboreflex activation to offset the influence of cardiac parasympathetic reactivation on heart rate.

  7. Genome-wide compendium and functional assessment of in vivo heart enhancers

    PubMed Central

    Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; Fukuda-Yuzawa, Yoko; Osterwalder, Marco; Mannion, Brandon J.; May, Dalit; Spurrell, Cailyn H.; Plajzer-Frick, Ingrid; Pickle, Catherine S.; Lee, Elizabeth; Garvin, Tyler H.; Kato, Momoe; Akiyama, Jennifer A.; Afzal, Veena; Lee, Ah Young; Gorkin, David U.; Ren, Bing; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

    2016-01-01

    Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function. PMID:27703156

  8. Immunoreactivity of thymosin beta 4 in human foetal and adult genitourinary tract

    PubMed Central

    Nemolato, S.; Cabras, T.; Fanari, M.U.; Cau, F.; Fanni, D.; Gerosa, C.; Manconi, B.; Messana, I.; Castagnola, M.; Faa, G.

    2010-01-01

    Thymosin beta 4 (Tβ4) is a member of the beta-thymosins family, a family of peptides playing essential roles in many cellular functions. Our recent studies suggested Tβ4 plays a key role in the development of human salivary glands and the gastrointestinal tract. The aim of this study was to analyse the presence of Tβ4 in the human adult and foetal genitourinary tract. Immunolocalization of Tβ4 was studied in autoptic samples of kidney, bladder, uterus, ovary, testicle and prostate obtained from four human foetuses and four adults. Presence of the peptide was observed in cells of different origin: in surface epithelium, in gland epithelial cells and in the interstitial cells. Tβ4 was mainly found in adult and foetal bladder in the transitional epithelial cells; in the adult endometrium, glands and stromal cells were immunoreactive for the peptide; Tβ4 was mainly localized in the glands of foetal prostate while, in the adults a weak Tβ4 reactivity was restricted to the stroma. In adult and foetal kidney, Tβ4 reactivity was restricted to ducts and tubules with completely spared glomeruli; a weak positivity was observed in adult and foetal oocytes; immunoreactivity was mainly localized in the interstitial cells of foetal and adult testis. In this study, we confirm that Tβ4 could play a relevant role during human development, even in the genitourinary tract, and reveal that immunoreactivity for this peptide may change during postnatal and adult life. PMID:21263742

  9. Functional identification of histamine H3-receptors in the human heart.

    PubMed

    Imamura, M; Seyedi, N; Lander, H M; Levi, R

    1995-07-01

    Norepinephrine release contributes to ischemic cardiac dysfunction and arrhythmias. Because activation of histamine H3-receptors inhibits norepinephrine release, we searched for the presence of H3-receptors directly in sympathetic nerve endings (cardiac synaptosomes) isolated from surgical specimens of human atria. Norepinephrine was released by depolarization with K+. The presence of H3-receptors was ascertained because the selective H3-receptor agonists (R) alpha-methylhistamine and imetit reduced norepinephrine release, and the specific H3-receptor antagonist thioperamide blocked this effect. Norepinephrine release was exocytotic, since it was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220. Functional relevance of these H3-receptors was obtained by showing that transmural electrical stimulation of sympathetic nerve endings in human atrial tissue increased contractility, an effect blocked by propranolol and attenuated in a concentration-dependent manner by (R) alpha-methylhistamine. Also, thioperamide antagonized the effect of (R) alpha-methylhistamine. Our findings are the first demonstration that H3-receptors are present in sympathetic nerve endings in the human heart, where they modulate adrenergic responses by inhibiting norepinephrine release. Since myocardial ischemia causes intracardiac histamine release, H3-receptor-induced attenuation of sympathetic neurotransmission may be clinically relevant.

  10. Prevalence and determinants of anemia in adults with complex congenital heart disease and ventricular dysfunction (subaortic right ventricle and single ventricle physiology).

    PubMed

    Collins, Nicholas; Piran, Sanaz; Harrison, Jeanine; Azevedo, Eduardo; Oechslin, Erwin; Silversides, Candice K

    2008-09-01

    Anemia is well recognized as a marker of poor prognosis in patients with acquired heart disease and heart failure. Adults with complex congenital heart disease and ventricular dysfunction (subaortic right ventricle or single-ventricle physiology) represent a different population, because they are typically much younger and have less co-morbidity compared with patients with acquired forms of heart disease. The purpose of this study was to evaluate the prevalence and determinants of anemia in this population. Baseline hemoglobin levels were recorded at the time of the initial clinic visit, and final hemoglobin levels were those recorded before death or transplantation or at study completion. Anemia was defined as hemoglobin <135 g/L in men and <120 g/L in women. One hundred sixty-seven patients (100 men, mean age 34 +/- 8 years, mean ejection fraction 35 +/- 9%) were included, 66 with atrial switch operations, 42 with congenitally corrected transposition of the great arteries, and 59 with Fontan physiology. The mean hemoglobin level at baseline was 149 +/- 22 g/L and at follow-up was 139 +/- 29 g/L. The overall prevalence of anemia was 29% at completion. Hyponatremia, decreased renal function, and the use of warfarin were independent predictors of anemia. In conclusion, anemia is common in patients with complex congenital heart disease and ventricular dysfunction, in particular those with Fontan physiology.

  11. Perceived physical health and heart-focused anxiety among daily adult cigarette smokers: associations with affect-relevant smoking motives and outcome expectancies.

    PubMed

    Leyro, Teresa M; Zvolensky, Michael J; Vujanovic, Anka A; Johnson, Kirsten; Gregor, Kristin

    2010-01-01

    The present investigation examined heart-focused anxiety and perceived physical health in terms of affect-relevant cigarette smoking motives and outcome expectancies. Participants were a community sample of 140 adult daily smokers (81 women, mean age = 29.60 years, SD = 11.98). In terms of smoking motives, both heart-focused anxiety and perceived physical health incrementally predicted smoking for negative affect reduction motives above and beyond relevant covariates (gender, weekly alcohol consumption, daily smoking rate). Yet heart-focused anxiety, but not perceived physical health, was incrementally predictive of habitual motives, relative to the same covariates. With regard to smoking outcome expectancies, heart-focused anxiety was incrementally predictive of negative reinforcement outcome expectancies, whereas perceived physical health was not. Alternatively, perceived physical health was incrementally predictive of negative personal consequence outcome expectancies, but heart-focused anxiety was not. Findings are discussed in relation to the role of perceived health vulnerabilities in clarifying affect-oriented smoking motives and expectancies.

  12. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expande