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  1. Exposure to Concentrated Ambient Particles Does Not Affect Vascular Function in Patients with Coronary Heart Disease

    PubMed Central

    Mills, Nicholas L.; Robinson, Simon D.; Fokkens, Paul H. B.; Leseman, Daan L. A. C.; Miller, Mark R.; Anderson, David; Freney, Evelyn J.; Heal, Mathew R.; Donovan, Robert J.; Blomberg, Anders; Sandström, Thomas; MacNee, William; Boon, Nicholas A.; Donaldson, Ken; Newby, David E.; Cassee, Flemming R.

    2008-01-01

    Background Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans. Objectives We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. Methods Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures. Results Particulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 μg/m3) were higher than ambient levels (31 ± 8 μg/m3) and levels in filtered air (0.5 ± 0.4 μg/m3; p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group. Conclusions Despite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans. PMID:18560524

  2. How Do Cognitive Function and Knowledge Affect Heart Failure Self-Care?

    ERIC Educational Resources Information Center

    Dickson, Victoria Vaughan; Lee, Christopher S.; Riegel, Barbara

    2011-01-01

    Despite extensive patient education, few heart failure (HF) patients master self-care. Impaired cognitive function may explain why patient education is ineffective. A concurrent triangulation mixed methods design was used to explore how knowledge and cognitive function influence HF self-care. A total of 41 adults with HF participated in interviews…

  3. Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ.

    PubMed

    Baldwin, H S; Lloyd, T R; Solursh, M

    1994-02-01

    Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular matrix or "cardiac jelly," yet little is known about its role in the ontogeny of early ventricular performance. To investigate the in situ effect of hyaluronate degradation on ventricular function, whole rat embryos were cultured in rat serum alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase (treatment embryos) from gestational day 9.5 (before formation of the heart tube) through initial looping of the heart. Cardiac function was measured before looping (24 hours in culture) and immediately after looping (36 hours in culture) by video motion analysis of the external wall motion of the bulbus cordis and primitive ventricle. Degradation of hyaluronic acid in the treated embryos was confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate, circumferential shortening fraction, maximum velocity of circumferential contraction, and maximum velocity of circumferential relaxation were observed with looping in both control and treatment embryos. Although there was minimal difference in ventricular performance between control and treatment embryos before looping, there was a significant increase in all parameters of ventricular performance in the hyaluronidase-treated embryos immediately after looping of the heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an additional group of embryos cultured in the presence of Streptomyces hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These experiments are the first to (1) document a quantifiable increase in ventricular performance during early cardiac looping and (2) demonstrate that hyaluronate degradation results in abnormal endocardial cushion formation and altered ventricular performance of the postlooped heart.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. 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

  5. Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

    PubMed

    Wang, Dong; Gladysheva, Inna P; Fan, Tai-Hwang M; Sullivan, Ryan; Houng, Aiilyan K; Reed, Guy L

    2014-03-01

    Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

  6. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter 2007 Table ... of this page please turn Javascript on. Young Women: Lifestyle-related factors that increase heart disease risk ...

  7. Diastolic function in heart failure.

    PubMed

    Kovács, Sándor J

    2015-01-01

    Heart failure has reached epidemic proportions, and diastolic heart failure or heart failure with preserved ejection fraction (HFpEF) constitutes about 50% of all heart failure admissions. Long-term prognosis of both reduced ejection fraction heart failure and HFpEF are similarly dismal. No pharmacologic agent has been developed that actually treats or repairs the physiologic deficit(s) responsible for HFpEF. Because the physiology of diastole is both subtle and counterintuitive, its role in heart failure has received insufficient attention. In this review, the focus is on the physiology of diastole in heart failure, the dominant physiologic laws that govern the process in all hearts, how all hearts work as a suction pump, and, therefore, the elucidation and characterization of what actually is meant by "diastolic function". The intent is for the reader to understand what diastolic function actually is, what it is not, and how to measure it. Proper measurement of diastolic function requires one to go beyond the usual E/A, E/E', etc. phenomenological metrics and employ more rigorous causality (mathematical modeling) based parameters of diastolic function. The method simultaneously provides new physiologic insight into the meaning of in vivo "equilibrium volume" of the left ventricle (LV), longitudinal versus transverse volume accommodation of the chamber, diastatic "ringing" of the mitral annulus, and the mechanism of L-wave generation, as well as availability of a load-independent index of diastolic function (LIIDF). One important consequence of understanding what diastolic function is, is the recognition that all that current therapies can do is basically alter the load, rather than actually "repair" the functional components (chamber stiffness, chamber relaxation). If beneficial (biological/structural/metabolic) remodeling due to therapy does manifest ultimately as improved diastolic function, it is due to resumption of normal physiology (as in alleviation of

  8. Diastolic Function in Heart Failure

    PubMed Central

    Kovács, Sándor J

    2015-01-01

    Heart failure has reached epidemic proportions, and diastolic heart failure or heart failure with preserved ejection fraction (HFpEF) constitutes about 50% of all heart failure admissions. Long-term prognosis of both reduced ejection fraction heart failure and HFpEF are similarly dismal. No pharmacologic agent has been developed that actually treats or repairs the physiologic deficit(s) responsible for HFpEF. Because the physiology of diastole is both subtle and counterintuitive, its role in heart failure has received insufficient attention. In this review, the focus is on the physiology of diastole in heart failure, the dominant physiologic laws that govern the process in all hearts, how all hearts work as a suction pump, and, therefore, the elucidation and characterization of what actually is meant by “diastolic function”. The intent is for the reader to understand what diastolic function actually is, what it is not, and how to measure it. Proper measurement of diastolic function requires one to go beyond the usual E/A, E/E′, etc. phenomenological metrics and employ more rigorous causality (mathematical modeling) based parameters of diastolic function. The method simultaneously provides new physiologic insight into the meaning of in vivo “equilibrium volume” of the left ventricle (LV), longitudinal versus transverse volume accommodation of the chamber, diastatic “ringing” of the mitral annulus, and the mechanism of L-wave generation, as well as availability of a load-independent index of diastolic function (LIIDF). One important consequence of understanding what diastolic function is, is the recognition that all that current therapies can do is basically alter the load, rather than actually “repair” the functional components (chamber stiffness, chamber relaxation). If beneficial (biological/structural/metabolic) remodeling due to therapy does manifest ultimately as improved diastolic function, it is due to resumption of normal physiology (as in

  9. Chamber identity programs drive early functional partitioning of the heart.

    PubMed

    Mosimann, Christian; Panáková, Daniela; Werdich, Andreas A; Musso, Gabriel; Burger, Alexa; Lawson, Katy L; Carr, Logan A; Nevis, Kathleen R; Sabeh, M Khaled; Zhou, Yi; Davidson, Alan J; DiBiase, Anthony; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Zon, Leonard I

    2015-08-26

    The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.

  10. How Does Smoking Affect the Heart and Blood Vessels?

    MedlinePlus

    ... heart disease, heart attack, and stroke . Smoking and Atherosclerosis The image shows how smoking can affect arteries ... a detailed view of a leg artery with atherosclerosis—plaque buildup that's partially blocking blood flow. Figure ...

  11. Assessment of Diastolic Function in Congenital Heart Disease

    PubMed Central

    Panesar, Dilveer Kaur; Burch, Michael

    2017-01-01

    Diastolic function is an important component of left ventricular (LV) function which is often overlooked. It can cause symptoms of heart failure in patients even in the presence of normal systolic function. The parameters used to assess diastolic function often measure flow and are affected by the loading conditions of the heart. The interpretation of diastolic function in the context of congenital heart disease requires some understanding of the effects of the lesions themselves on these parameters. Individual congenital lesions will be discussed in this paper. Recently, load-independent techniques have led to more accurate measurements of ventricular compliance and remodeling in heart disease. The combination of inflow velocities and tissue Doppler measurements can be used to estimate diastolic function and LV filling pressures. This review focuses on diastolic function and assessment in congenital heart disease. PMID:28261582

  12. Renal function assessment in heart failure.

    PubMed

    Pérez Calvo, J I; Josa Laorden, C; Giménez López, I

    2017-03-01

    Renal function is one of the most consistent prognostic determinants in heart failure. The prognostic information it provides is independent of the ejection fraction and functional status. This article reviews the various renal function assessment measures, with special emphasis on the fact that the patient's clinical situation and response to the heart failure treatment should be considered for the correct interpretation of the results. Finally, we review the literature on the performance of tubular damage biomarkers.

  13. Regenerating functional heart tissue for myocardial repair

    PubMed Central

    Alcon, Andre; Bozkulak, Esra Cagavi; Qyang, Yibing

    2012-01-01

    Heart disease is one of the leading causes of death worldwide and the number of patients with the disease is likely to grow with the continual decline in health for most of the developed world. Heart transplantation is one of the only treatment options for heart failure due to an acute myocardial infarction, but limited donor supply and organ rejection limit its widespread use. Cellular cardiomyoplasty, or cellular implantation, combined with various tissue-engineering methods aims to regenerate functional heart tissue. This review highlights the numerous cell sources that have been used to regenerate the heart as well as cover the wide range of tissue-engineering strategies that have been devised to optimize the delivery of these cells. It will probably be a long time before an effective regenerative therapy can make a serious impact at the bedside. PMID:22388688

  14. ON THE BIOMECHANICS OF HEART VALVE FUNCTION

    PubMed Central

    Sacks, Michael S.; Merryman, W. David; Schmidt, David E.

    2009-01-01

    Heart valves (HVs) are fluidic control components of the heart that ensure unidirectional blood flow during the cardiac cycle. However, this description does not adequately describe the biomechanical ramifications of their function in that their mechanics are multi-modal. Moreover, they must replicate their cyclic function over an entire lifetime, with an estimated total functional demand of least 3×109 cycles. The focus of the present review is on the functional biomechanics of heart valves. Thus, the focus of the present review is on functional biomechanics, referring primarily to biosolid as well as several key biofluid mechanical aspects underlying heart valve physiological function. Specifically, we refer to the mechanical behaviors of the extra-cellular matrix structural proteins, underlying cellular function, and their integrated relation to the major aspects of valvular hemodynamic function. While we focus on the work from the author’s laboratories, relevant works of other investigators have been included whenever appropriate. We conclude with a summary of important future trends. PMID:19540499

  15. Renal function in cyanotic congenital heart disease.

    PubMed

    Burlet, A; Drukker, A; Guignard, J P

    1999-01-01

    We performed renal function tests in 18 young patients, 1.8-14.6 years of age, with cyanotic congenital heart disease (CCHD). Glomerular filtration rate was normal (116 +/- 4.5 ml/min/1.73 m2), and renal plasma flow was decreased (410 +/- 25 ml/min/1.73 m2) with a rise in the filtration fraction (29 +/- 1.1%). The suggested pathophysiologic explanation of these findings is that the blood hyperviscosity seen in patients with CCHD causes an overall increase in renal vascular resistance with a rise in intraglomerular blood pressure. Despite a sluggish flow of blood in the glomerular capillary bed, the effective filtration pressure was adjusted to conserve the glomerular filtration rate. In addition to these renal hemodynamic parameters, we also studied renal acidification and tubular sodium and water handling during a forced water diuresis. Our data indicate that children with CCHD have a mild to moderate normal ion gap metabolic acidosis due to a low proximal tubular threshold for bicarbonate. Proximal tubular sodium and water reabsorption under these conditions were somewhat increased, though not significantly, probably due to intrarenal hydrostatic forces, in particular the rise in the oncotic pressure in the postglomerular capillaries in patients with high hematocrit values. The distal tubular functions such as sodium handling and acidification were not affected.

  16. Hypothyroidism and renal function in patients with systolic heart failure.

    PubMed

    Merla, Ramanna; Martinez, Juan D; Martinez, Milagros A; Khalife, Wissam; Bionat, Susan; Bionat, Joanne; Barbagelata, Alejandro

    2010-01-01

    The extent to which hypothyroidism affects renal function in patients with heart failure remains incompletely explored, despite the known adverse prognostic implications of renal dysfunction in these patients.In a pilot retrospective study, we evaluated 75 patients (age, >or=18 yr) with left ventricular ejection fractions <0.40. Forty-five patients had normal thyroid function (thyroid-stimulating hormone [TSH], 0.35-5.5 micro IU/mL) and 30 had hypothyroidism. The group with hypothyroidism was subdivided into 17 patients who had controlled hypothyroidism (TSH, 0.35-5.5 micro IU/mL) and 13 who had uncontrolled hypothyroidism (TSH, >5.5 micro IU/mL). Renal function, measured in terms of glomerular filtration rate, was analyzed once in each patient, and the populations were statistically compared, with P <0.05 conferring statistical significance.Baseline characteristics in all groups were similar. Mean glomerular filtration rate was better in patients with normal thyroid function than those with hypothyroidism (75.45 +/- 31.48 vs 63.95 +/- 21.43 mL/min/1.73 m2; P=0.032). There was no significant difference between patients with controlled hypothyroidism (66.89 +/- 24.18 mL/min/1.73 m2) and those with normal thyroid function (P=0.131). In patients with uncontrolled hypothyroidism, mean glomerular filtration rate (60.2 +/- 17.4 mL/min/1.73 m2) was significantly worse than in patients with normal thyroid function (P=0.015).We found that heart-failure patients with insufficiently treated hypothyroidism have worse renal function than do patients whose thyroid function is normal or whose hypothyroidism is effectively treated. Larger studies will be needed in order to evaluate this conclusion further. We recommend that hypothyroidism in heart-failure patients be strictly controlled, lest it affect prognosis adversely.

  17. The Impact of Family Functioning on Caregiver Burden among Caregivers of Veterans with Congestive Heart Failure

    ERIC Educational Resources Information Center

    Moore, Crystal Dea

    2010-01-01

    A cross-sectional study of 76 family caregivers of older veterans with congestive heart failure utilized the McMaster model of family functioning to examine the impact of family functioning variables (problem solving, communication, roles, affective responsiveness, and affective involvement) on caregiver burden dimensions (relationship burden,…

  18. Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate.

    PubMed

    Nakahara, T; Kawada, T; Sugimachi, M; Miyano, H; Sato, T; Shishido, T; Yoshimura, R; Miyashita, H; Sunagawa, K

    1998-08-01

    Recent investigations in our laboratory using a Gaussian white noise technique showed that the transfer function representing the dynamic properties of transduction from vagus nerve activity to heart rate had characteristics of a first-order low-pass filter. However, the physiological determinants of those characteristics remain to be elucidated. In this study, we stimulated the vagus nerve according to a Gaussian white noise pattern to estimate the transfer function from vagal stimulation to the heart rate response in anesthetized rabbits and examined how changes in acetylcholine kinetics affected the transfer function. We found that although increases in the mean frequency of vagal stimulation from 5 to 10 Hz did not change the characteristics of the transfer function, administration of neostigmine (30 microg . kg-1 . h-1 iv), a cholinesterase inhibitor, increased the dynamic gain from 8.19 +/- 3.66 to 11.7 +/- 4.88 beats . min-1 . Hz-1 (P < 0.05), decreased the corner frequency from 0.12 +/- 0.05 to 0.04 +/- 0.01 Hz (P < 0.01), and increased the lag time from 0.17 +/- 0.12 to 0.27 +/- 0.08 s (P < 0.05). These results suggest that the rate of acetylcholine degradation at the neuroeffector junction, rather than the amount of available acetylcholine, plays a key role in determining the dynamic properties of transduction from vagus nerve activity to heart rate.

  19. 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.

  20. Placebo Sleep Affects Cognitive Functioning

    ERIC Educational Resources Information Center

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  1. Mitochondrial function as a therapeutic target in heart failure

    PubMed Central

    Brown, David A.; Perry, Justin B.; Allen, Mitchell E.; Sabbah, Hani N.; Stauffer, Brian L.; Shaikh, Saame Raza; Cleland, John G. F.; Colucci, Wilson S.; Butler, Javed; Voors, Adriaan A.; Anker, Stefan D.; Pitt, Bertram; Pieske, Burkert; Filippatos, Gerasimos; Greene, Stephen J.; Gheorghiade, Mihai

    2017-01-01

    Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible. Although the pathophysiology of heart failure is complex, mitochondrial dysfunction seems to be an important target for therapy to improve cardiac function directly. Mitochondrial abnormalities include impaired mitochondrial electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria. PMID:28004807

  2. Subclinical hypothyroidism affects mitochondrial function.

    PubMed

    Kvetny, J; Wilms, L; Pedersen, P L; Larsen, J

    2010-05-01

    The aim of the present study was to examine mitochondrial function in cells from persons with subclinical hypothyroidism and euthyroid controls. The participating persons were examined clinically and had basal oxygen consumption (VO(2)) determined. The concentrations of thyroid hormones and thyrotropine stimulating hormone were determined, and mitochondrial function in isolated mononuclear blood cells was examined by enzymatic methods [citrate synthase activity (CS)] and by flow cytometry (mitochondrial membrane potential by TMRM fluorescence and mitochondrial mass by MTG fluorescence). The ratio of T(4)/T(3) was lowered in subclinical hypothyroidism patients compared to controls (2.5+/-0.5 vs. 2.9+/-0.4, p=0.005). VO(2) was increased in persons with subclinical hypothyroidism compared to controls (adolescents: 134+/-27 ml O(2)/min*m(2) vs. 119+/-27 ml O(2)/min*m(2), p=0.006, adults: 139+/-14 ml O(2)/min*m(2) vs. 121+/-17 ml O(2)/min*m(2), p=0.001). The mitochondrial function, represented by citrate synthase activity, MTG, and TMRM fluorescence were all increased (CS in subclinical hypothyroidism vs. controls: 0.074+/-0.044 nmol/mg*min vs. 0.056+/-0.021 nmol/mg*min, p=0.005; MTG fluorescence in subclinical hypothyroidism vs. controls: 7,482+/-1,733 a.u. vs. 6,391+/-2,171 a.u., p=0.027; TMRM fluorescence in subclinical hypothyroidism vs. controls: 13,449+/-3,807 a.u. vs. 11,733+/-4,473 a.u, p=0.04). Our results indicate an increased mitochondrial stimulation, eventually caused by increased deiodination of T(4) to intracellular bioactive iodothyronines in adults and adolescents with subclinical hypothyroidism.

  3. A family with a dystrophin gene mutation specifically affecting dystrophin expression in the heart

    SciTech Connect

    Muntoni, F.; Davies, K.; Dubowitz, V.

    1994-09-01

    We recently described a family with X-linked dilated cardiomyopathy where a large deletion in the muscle promoter region of the dystrophin gene was associated with a severe dilated cardiomyopathy in absence of clinical skeletal muscle involvement. The deletion removed the entire muscle promoter region, the first muscle exon and part of intron 1. The brain and Purkinje cell promoters were not affected by the deletion. Despite the lack of both the muscle promoter and the first muscle exon, dystrophin was detected immunocytochemically in relative high levels in the skeletal muscle of the affected males. We have now found that both the brain and Purkinje cell promoters were transcribed at high levels in the skeletal muscle of these individuals. This phenomenon, that does not occur in normal skeletal muscle, indicates that these two isoforms, physiologically expressed mainly in the central nervous system, can be transcribed and be functionally active in skeletal muscle under specific circumstances. Contrary to what is observed in skeletal muscle, dystrophin was not detected in the heart of one affected male using immunocytochemistry and an entire panel of anti-dystrophin antibodies. This was most likely the cause for the pronounced cardiac fibrosis observed and eventually responsible for the severe cardiac involvement invariably seen in seven affected males. In conclusion, the mutation of the muscle promoter, first muscle exon and part of intron 1 specifically affected expression of dystrophin in the heart. We believe that this deletion removes sequences involved in regulation of dystrophin expression in the heart and are at the moment characterizing other families with X-linked cardiomyopathy secondary to a dystrophinopathy.

  4. Right heart function and haemodynamics in pulmonary hypertension.

    PubMed

    Hemnes, A R; Champion, H C

    2008-07-01

    The primary challenge in the care of the patient with advanced pulmonary arterial hypertension (PAH) is right ventricular dysfunction with concomitant right heart failure. Right heart function is closely tied to survival in this disease, and there is a growing interest in the study of this unique structure. While echocardiography and cardiac magnetic resonance (CMR) have augmented our ability to image the right ventricle (RV), the primary means of assessing right heart function remains right heart catheterisation. Several of the currently available treatments for PAH have been shown to have effects on the RV, not just the pulmonary vasculature, and, in future, therapies aimed at optimizing right ventricular function may allow better outcomes in this challenging disease. New directions in right ventricular assessment including measurement of pulmonary vascular impedance and more widespread availability of CMR may allow greater knowledge about this little studied, yet highly important, right side of the heart.

  5. Structure and function of the hearts of lizards and snakes.

    PubMed

    Jensen, Bjarke; Moorman, Antoon F M; Wang, Tobias

    2014-05-01

    With approximately 7000 species, snakes and lizards, collectively known as squamates, are by far the most species-rich group of reptiles. It was from reptile-like ancestors that mammals and birds evolved and squamates can be viewed as phylogenetically positioned between them and fishes. Hence, their hearts have been studied for more than a century yielding insights into the group itself and into the independent evolution of the fully divided four-chambered hearts of mammals and birds. Structurally the heart is complex and debates persist on rudimentary issues such as identifying structures critical to understanding ventricle function. In seeking to resolve these controversies we have generated three-dimensional (3D) models in portable digital format (pdf) of the anaconda and anole lizard hearts ('typical' squamate hearts) and the uniquely specialized python heart with comprehensive annotations of structures and cavities. We review the anatomy and physiology of squamate hearts in general and emphasize the unique features of pythonid and varanid lizard hearts that endow them with mammal-like blood pressures. Excluding pythons and varanid lizards it is concluded that the squamate heart has a highly consistent design including a disproportionately large right side (systemic venous) probably due to prevailing pulmonary bypass (intraventricular shunting). Unfortunately, investigations on rudimentary features are sparse. We therefore point out gaps in our knowledge, such as the size and functional importance of the coronary vasculature and of the first cardiac chamber, the sinus venosus, and highlight areas with implications for vertebrate cardiac evolution.

  6. Other Factors That Affect Heart Disease: Birth Control Pills

    MedlinePlus

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  7. Resveratrol Reverses Functional Chagas Heart Disease in Mice

    PubMed Central

    Mata-Santos, Hilton; Vicentino, Amanda R. R.; Feijó, Daniel F.; Meyer-Fernandes, José R.; Paula-Neto, Heitor A.; Medei, Emiliano; Bozza, Marcelo T.; Lannes-Vieira, Joseli; Paiva, Claudia N.

    2016-01-01

    Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol’s actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC. PMID:27788262

  8. Resveratrol Reverses Functional Chagas Heart Disease in Mice.

    PubMed

    Vilar-Pereira, Glaucia; Carneiro, Vitor C; Mata-Santos, Hilton; Vicentino, Amanda R R; Ramos, Isalira P; Giarola, Naira L L; Feijó, Daniel F; Meyer-Fernandes, José R; Paula-Neto, Heitor A; Medei, Emiliano; Bozza, Marcelo T; Lannes-Vieira, Joseli; Paiva, Claudia N

    2016-10-01

    Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol's actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC.

  9. [Heart functions in monkeys during a 2-week antiorthostatic hypokinesia

    NASA Technical Reports Server (NTRS)

    Krotov, V. P.; Convertino, V.; Korol'kov, V. I.; Latham, R.; Trambovetskii, E. V.; Fanton, J.; Crisman, R.; Truzhennikov, A. N.; Evert, D.; Nosovskii, A. M.; Conolly, J.

    1996-01-01

    Dynamics of the left heart ventricular muscle contractility and compliance was studied in 4 monkeys in the head down position (antiorthostatic hypokinesia) with the body angle 10 during 2 weeks. Functional tests on a tilt table and under two conditions of centrifuge rotation were performed prior to and after the antiorthostatic hypokinesia. No changes in the left heart ventricular muscle contractility was found. However, the sensitivity level of the baroreflex control decreased. Compliance of the left heart myocardial fibre increased in the first hours and days of the antiorthostatic hypokinesia.

  10. Notes on the Heart: Affective Issues in the Writing Classroom.

    ERIC Educational Resources Information Center

    McLeod, Susan H.

    The most used model for empirical research on the writing process is based on cognitive psychology and does not take into account affective phenomena, although it has long been recognized that affect (that is, the noncognitive aspects of mental activity) plays a large role in writing and learning to write. To understand the complete picture, it is…

  11. Heart autonomic function in overweight adolescents.

    PubMed

    Guízar, Juan-Manuel; Ahuatzin, Rosalía; Amador, Norma; Sánchez, Guillermo; Romer, Gustavo

    2005-05-01

    We compared factors associated with sympathetic cardiac activity in 70 male adolescents (34 obese and 36 with appropriate weight). In fasting we measured insulin, leptin, glucose, blood pressure, and heart rate variability by power spectral analysis. Obese adolescents had higher values for systolic blood pressure, insulin, leptin, low frequency/high frequency index (LF/HF); and lower for standard deviation of all the normal RR intervals, and total power. In the multiple regression analysis, factors associated with LF/HF index were leptin and systolic blood pressure (R2 = 0.18; P = 0.004 for the model). We concluded that higher sympathetic activity in obese adolescents is related to higher leptin and systolic blood pressure levels..

  12. A Methodology for Quantifying Heart Function in the Embryonic Zebrafish

    NASA Astrophysics Data System (ADS)

    Johnson, Brennan; Garrity, Deborah; Dasi, Lakshmi

    2012-11-01

    Several studies have linked epigenetic factors such as blood flow dynamics and cardiac function to proper heart development. To better understand this process, it is essential to develop robust quantitative methods to investigate the blood dynamics and wall kinematics in vivo. Here, we develop a methodology that can be used throughout the early stages of development which requires no specialized equipment other than a bright field microscope and high-speed camera. We use the embryonic zebrafish as our model due to its superb optical access and widespread acceptance as a powerful model for human heart development. Using these methods, we quantify blood flow rates, stroke volume, cardiac output, ejection fraction, and other important parameters related to heart function. We also investigate the pumping mechanics from heart tube to looped configuration. We show that although the mechanism changes fundamentally, it does so in a continuous fashion that can incorporate combined pumping mechanisms at intermediate stages. This work provides a basis for quantitatively comparing normal and abnormal heart development, and may help us gain a better understanding of congenital heart defects. Funded by NSF.

  13. Chronic Ischemic Heart Disease Affects Health Related Quality of Life

    PubMed Central

    Goreishi, Abolfazl; Shajari, Zahra; Mohammadi, Zeinab

    2012-01-01

    Background Chronic diseases endanger not only physical health but also psychological and social health of patient. Thus, evaluation of such patients for psychological treatment decisions is very important. Method This is a descriptive study that was performed with 50 chronic patients (ischemic heart disease) selected from Valiasr and Mousavi at cardiac wards in Zanjan Province. They were given three types of questionnaire: demographic, WHOQOL, and Zung depression and anxiety index. The information was statically analyzed by frequency chart, central indexes, dispersion, Chi-Square and t tests, Pearson’s correlation index (P < 0.05). Results The average of quality of life in all patients were calculated as was respectively 12.19, 11.98, 12.08, and 12.4 in physical, psychological, social and environmental domains respectively, 68 percent of total number of the patients had various degrees of anxiety and 78 percent of them had various degrees of depression. There was a significant relationship between the life quality average in all domains and anxiety intensity and depression intensity (P < 0.05) and there was a significant relationship between life quality average in all domains and income (P < 0.05). Conclusion As the level of depression and anxiety goes up, quality of life decreases pointing out that they have a reverse relationship. Depression and anxiety are one of the most significant factors of quality of life among other variables. Regarding specific conditions of the treatment, it is necessary to pay special attention to psychological aspects.

  14. 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.

  15. 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

  16. Endomorphins and β-Endorphin Do Not Affect Heart Tolerance to the Pathogenic Effect of Reperfusion.

    PubMed

    Mukhomedzyanov, A V; Maslov, L N; Tsibulnikov, S Yu; Pei, J M

    2016-11-01

    Selective agonists of μ1- and μ2-opioid receptors endomorphin-2 and endomorphin-1 injected intravenously in a dose of 4500 nmol/kg in 5 min before coronary blood flow resumption had no effect on cardiac reperfusion damage. Consequently, μ1- and μ2-opioid receptors are not involved in the regulation of heart tolerance to reperfusion injury. Nonselective opioid receptor agonist β-endorphin (100 nmol/kg) also did not affect heart tolerance to the pathogenic effect of reperfusion.

  17. Heart failure: when form fails to follow function.

    PubMed

    Katz, Arnold M; Rolett, Ellis L

    2016-02-01

    Cardiac performance is normally determined by architectural, cellular, and molecular structures that determine the heart's form, and by physiological and biochemical mechanisms that regulate the function of these structures. Impaired adaptation of form to function in failing hearts contributes to two syndromes initially called systolic heart failure (SHF) and diastolic heart failure (DHF). In SHF, characterized by high end-diastolic volume (EDV), the left ventricle (LV) cannot eject a normal stroke volume (SV); in DHF, with normal or low EDV, the LV cannot accept a normal venous return. These syndromes are now generally defined in terms of ejection fraction (EF): SHF became 'heart failure with reduced ejection fraction' (HFrEF) while DHF became 'heart failure with normal or preserved ejection fraction' (HFnEF or HFpEF). However, EF is a chimeric index because it is the ratio between SV--which measures function, and EDV--which measures form. In SHF the LV dilates when sarcomere addition in series increases cardiac myocyte length, whereas sarcomere addition in parallel can cause concentric hypertrophy in DHF by increasing myocyte thickness. Although dilatation in SHF allows the LV to accept a greater venous return, it increases the energy cost of ejection and initiates a vicious cycle that contributes to progressive dilatation. In contrast, concentric hypertrophy in DHF facilitates ejection but impairs filling and can cause heart muscle to deteriorate. Differences in the molecular signals that initiate dilatation and concentric hypertrophy can explain why many drugs that improve prognosis in SHF have little if any benefit in DHF.

  18. Do Bells Affect Behaviour and Heart Rate Variability in Grazing Dairy Cows?

    PubMed Central

    Johns, Julia; Patt, Antonia; Hillmann, Edna

    2015-01-01

    In alpine regions cows are often equipped with bells. The present study investigated the impact of wearing a bell on behaviour and heart rate variability in dairy cows. Nineteen non-lactating Brown-Swiss cows with bell experience were assigned to three different treatments. For 3 days each, cows were equipped with no bell (control), with a bell with inactivated clapper (silent bell) or with a functional bell (functional bell). The bells weighed 5.5 kg and had frequencies between 532 Hz and 2.8 kHz and amplitudes between 90 and 113 dB at a distance of 20 cm. Data were collected on either the first and third or on all 3 days of each treatment. Whereas duration of rumination was reduced with a functional bell and a silent bell compared with no bell, feeding duration was reduced with a silent bell and was intermediate with a functional bell. Head movements were reduced when wearing a silent bell compared with no bell and tended to be reduced when wearing a functional compared to no bell. With a functional bell, lying duration was reduced by almost 4 hours on the third day of treatment compared with the first day with a functional bell and compared with no bell or a silent bell. All additional behavioural measures are consistent with the hypothesis of a restriction in the behaviour of the cows wearing bells, although this pattern did not reach significance. There was no treatment effect on heart rate variability, suggesting that the bells did not affect vago-sympathetic balance. An effect of experimental day was found for only 1 out of 10 behavioural parameters, as shown by a decrease in lying with a functional bell on day 3. The results indicate behavioural changes in the cows wearing a bell over 3 days, without indication of habituation to the bell. Altogether, the behavioural changes suggest that the behaviour of the cows was disturbed by wearing a bell. If long-lasting, these effects may have implications for animal welfare. PMID:26110277

  19. Risk factors for coronary heart disease and platelet functions.

    PubMed

    Renaud, S

    1984-01-01

    Epidemiologic studies have shown that several environmental factors are associated with coronary heart disease (CHD). Most of them are predisposing factors known also as risk factors. Other factors appear to have preventive effects. Blood lipids have been considered the main blood mediator between most of these factors and CHD. In recent years, this concept has been challenged since many of these factors did not affect serum lipids. By contrast blood platelets, involved in both thrombosis and atherosclerosis, appear to have their functions markedly changed by most of the factors associated with CHD. To determine whether saturated fats would affect platelet functions as shown in animals and in pilot studies in man, groups of male farmers (40-45 years) from 2 regions of France (Var and Moselle) in which the mortality rate from CHD differed markedly were studied, particularly regarding their platelet functions in relation to the intake of saturated fats. No difference could be observed in blood between the 2 regions concerning total cholesterol, HDL cholesterol, or triglycerides, the coagulation was markedly accelerated, as well as the platelet clotting activity in farmers from Moselle. The response of platelets mostly to thrombin but also to adenosine diphosphate (ADP), epinephrine, and collagen was more elevated in Moselle farmers. In Moselle farmers, there was significantly higher intake of saturated fats (16% of the calories) as compared to Var (12%). To determine whether the abnormal platelet response in Moselle farmers was really due to the diet or whether a genetic factor might be involved, a group of 50 Moselle farmers were persuaded to change their dietary habits in order to lower their intake of saturated fats to 10% of the calories and that of polyunsaturated to approximately 12%. 1 year after diet modification, the clotting time (PCT) and clotting activity of platelets were considerably prolonged and the response to thrombin drastically reduced. These

  20. Relationship between obesity, negative affect and basal heart rate in predicting heart rate reactivity to psychological stress among adolescents.

    PubMed

    Park, Andres E; Huynh, Pauline; Schell, Anne M; Baker, Laura A

    2015-08-01

    Reduced cardiovascular responses to psychological stressors have been found to be associated with both obesity and negative affect in adults, but have been less well studied in children and adolescent populations. These findings have most often been interpreted as reflecting reduced sympathetic nervous system response, perhaps associated with heightened baseline sympathetic activation among the obese and those manifesting negative affect. However, obesity and negative affect may themselves be correlated, raising the question of whether they both independently affect cardiovascular reactivity. The present study thus examined the separate effects of obesity and negative affect on both cardiovascular and skin conductance responses to stress (e.g., during a serial subtraction math task) in adolescents, while controlling for baseline levels of autonomic activity during rest. Both obesity and negative affect had independent and negative associations with cardiovascular reactivity, such that reduced stress responses were apparent for obese adolescents and those with high levels of negative affect. In contrast, neither obesity nor negative affect was related to skin conductance responses to stress, implicating specifically noradrenergic mechanisms rather than sympathetic mechanisms generally as being deficient. Moreover, baseline heart rate was unrelated to obesity in this sample, which suggests that heightened baseline of sympathetic activity is not necessary for the reduced cardiovascular reactivity to stress.

  1. Pulmonary Function and Arterial Stiffness in Chronic Heart Failure

    PubMed Central

    Hu, Bangchuan; Gong, Shijin; Yu, Yihua; Dai, Haiwen

    2016-01-01

    Arterial stiffness contributes to heart failure and is decreased by angiotensin receptor blockers (ARBs). This cross-sectional study aimed to assess associations of lung function and ARB with arterial stiffness in patients with chronic heart failure. 354 outpatients (168 males; 186 females; 68.2 ± 7.2 years old) with chronic heart failure were evaluated. Lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1 to FVC ratio (FEV1/FVC), were assessed. The cardio-ankle vascular index (CAVI) was used to estimate arterial stiffness. Unadjusted correlation analyses revealed a positive association of CAVI with ARB but not ACEI, and a negative correlation with FEV1 (r = −0.2987, p < 0.0001). Multiple stepwise regression analyses showed that ARB and FEV1 (p < 0.0001) were independent predicting factors for CAVI. These findings suggest that reduced pulmonary function is associated with increased CAVI. Pulmonary function protection could be used to improve the prognosis in heart failure, but additional studies are necessary. PMID:28097138

  2. Neuronal uptake affects dynamic characteristics of heart rate response to sympathetic stimulation.

    PubMed

    Nakahara, T; Kawada, T; Sugimachi, M; Miyano, H; Sato, T; Shishido, T; Yoshimura, R; Miyashita, H; Inagaki, M; Alexander, J; Sunagawa, K

    1999-07-01

    Recently, studies in our laboratory involving the use of a Gaussian white noise technique demonstrated that the transfer function from sympathetic stimulation frequency to heart rate (HR) response showed dynamic characteristics of a second-order low-pass filter. However, determinants for the characteristics remain to be established. We examined the effect of an increase in mean sympathetic stimulation frequency and that of a blockade of the neuronal uptake mechanism on the transfer function in anesthetized rabbits. We found that increasing mean sympathetic stimulation frequency from 1 to 4 Hz significantly (P < 0.01) decreased the dynamic gain of the transfer function without affecting other parameters, such as the natural frequency, lag time, or damping coefficient. In contrast, the administration of desipramine (0.3 mg/kg iv), a neuronal uptake blocking agent, significantly (P < 0.01) decreased both the dynamic gain and the natural frequency and prolonged the lag time. These results suggest that the removal rate of norepinephrine at the neuroeffector junction, rather than the amount of available norepinephrine, plays an important role in determining the low-pass filter characteristics of the HR response to sympathetic stimulation.

  3. Level of Mercury Manometer With Respect to Heart: Does it Affect Blood Pressure Measurement?

    PubMed

    Kapoor, Raj; Roy, V K; Manna, S; Bhattacharjee, M

    2015-01-01

    Measurement of blood pressure is an integral part of clinical examination. Over the years various types of instruments have been used to measure blood pressure but till date the mercury sphygmomanometer is regarded as the gold standard. However, there is a myth prevalent among health professionals regarding the level of the manometer in relation to heart at the time of measuring of blood pressure. Many professionals insist that it has to be placed at the level of the heart. We argue that the limb from which pressure is measured must be at the heart level rather than the manometer. We conducted a study in which we measured the blood pressure in adults by placing the manometer at three different levels with respect to the heart. The values of blood pressure obtained at all levels were similar and did not show any statistically significant difference. We therefore conclude that the level of sphygmomanometer per se does not affect blood pressure measurement.

  4. The Effects of Heart Failure on Renal Function

    PubMed Central

    Udani, Suneel M; Koyner, Jay L

    2010-01-01

    Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250

  5. Exploring Heart and Lung Function in Space: ARMS Experiments

    NASA Technical Reports Server (NTRS)

    Kuipers, Andre; Cork, Michael; LeGouic, Marine

    2002-01-01

    The Advanced Respiratory Monitoring System (ARMS) is a suite of monitoring instruments and supplies used to study the heart, lungs, and metabolism. Many experiments sponsored by the European Space Agency (ESA) will be conducted using ARMS during STS-107. The near-weightless environment of space causes the body to undergo many physiological adaptations, and the regulation of blood pressure is no exception. Astronauts also experience a decrease in blood volume as an adaptation to microgravity. Reduced blood volume may not provide enough blood pressure to the head during entry or landing. As a result, astronauts often experience light-headedness, and sometimes even fainting, when they stand shortly after returning to Earth. To help regulate blood pressure and heart rate, baroreceptors, sensors located in artery walls in the neck and near the heart, control blood pressure by sending information to the brain and ensuring blood flow to organs. These mechanisms work properly in Earth's gravity but must adapt in the microgravity environment of space. However, upon return to Earth during entry and landing, the cardiovascular system must readjust itself to gravity, which can cause fluctuation in the control of blood pressure and heart rate. Although the system recovers in hours or days, these occurrences are not easily predicted or understood - a puzzle investigators will study with the ARMS equipment. In space, researchers can focus on aspects of the cardiovascular system normally masked by gravity. The STS-107 experiments using ARMS will provide data on how the heart and lungs function in space, as well as how the nervous system controls them. Exercise will also be combined with breath holding and straining (the Valsalva maneuver) to test how heart rate and blood pressure react to different stresses. This understanding will improve astronauts' cardiopulmonary function after return to Earth, and may well help Earthbound patients who experience similar effects after long

  6. 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.

  7. Heart Rate Variability – a Tool to Differentiate Positive and Negative Affective States in Pigs?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The causal neurophysiological processes, such as autonomic nervous system activity, that mediate behavioral and physiological reactivity to an environment have largely been ignored. Heart rate variability (HRV) analysis is a clinical diagnostic tool used to assess affective states (stressful and ple...

  8. The eel heart: multilevel insights into functional organ plasticity.

    PubMed

    Imbrogno, Sandra

    2013-10-01

    The remarkable functional homogeneity of the heart as an organ requires a well-coordinated myocardial heterogeneity. An example is represented by the selective sensitivity of the different cardiac cells to physical (i.e. shear stress and/or stretch) or chemical stimuli (e.g. catecholamines, angiotensin II, natriuretic peptides, etc.), and the cell-specific synthesis and release of these substances. The biological significance of the cardiac heterogeneity has recently received great attention in attempts to dissect the complexity of the mechanisms that control the cardiac form and function. A useful approach in this regard is to identify natural models of cardiac plasticity. Among fishes, eels (genus Anguilla), for their adaptive and acclimatory abilities, represent a group of animals so far largely used to explore the structural and ultrastructural myoarchitecture organization, as well as the complex molecular networks involved in the modulation of the heart function, such as those converting environmental signals into physiological responses. However, an overview on the existing current knowledge of eel cardiac form and function is not yet available. In this context, this review will illustrate major features of eel cardiac organization and pumping performance. Aspects of autocrine-paracrine modulation and the influence of factors such as body growth, exercise, hypoxia and temperature will highlight the power of the eel heart as an experimental model useful to decipher how the cardiac morpho-functional heterogeneities may support the uniformity of the whole-organ mechanics.

  9. Structural remodeling and mechanical function in heart failure.

    PubMed

    Leonard, Bridget Louise; Smaill, Bruce Henry; LeGrice, Ian John

    2012-02-01

    The cardiac extracellular matrix (ECM) is the three-dimensional scaffold that defines the geometry and muscular architecture of the cardiac chambers and transmits forces produced during the cardiac cycle throughout the heart wall. The cardiac ECM is an active system that responds to the stresses to which it is exposed and in the normal heart is adapted to facilitate efficient mechanical function. There are marked differences in the short- and medium-term changes in ventricular geometry and cardiac ECM that occur as a result of volume overload, hypertension, and ischemic cardiomyopathy. Despite this, there is a widespread view that a common remodeling "phenotype" governs the final progression to end-stage heart failure in different forms of heart disease. In this review article, we make the case that this interpretation is not consistent with the clinical and experimental data on the topic. We argue that there is a need for new theoretical and experimental models that will enable stresses acting on the ECM and resultant deformations to be estimated more accurately and provide better spatial resolution of local signaling mechanisms that are activated as a result. These developments are necessary to link the effects of structural remodeling with altered cardiac mechanical function.

  10. Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

    PubMed

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Peterson, Lindsy M; Mai, Katherine; McHale, Quinn; Jenkins, Michael W; Linask, Kersti K; Rollins, Andrew M; Watanabe, Michiko

    2014-02-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.

  11. Ganglionic GFAP (+) glial Gq-GPCR signaling enhances heart functions in vivo.

    PubMed

    Xie, Alison Xiaoqiao; Lee, Jakovin J; McCarthy, Ken D

    2017-01-26

    The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein-coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein-expressing (GFAP(+)) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP(+) glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions. In this study, we investigated whether Gq-GPCR activation in GFAP(+) glia modulates the regulatory effect of the SNS on the heart; transgenic mice expressing Gq-coupled DREADD (designer receptors exclusively activated by designer drugs) (hM3Dq) selectively in GFAP(+) glia were used to address this question in vivo. We found that acute Gq-GPCR activation in peripheral GFAP(+) glia significantly accelerated heart rate and increased left ventricle contraction. Pharmacological experiments suggest that the glial-induced cardiac changes were due to Gq-GPCR activation in satellite glial cells within the sympathetic ganglion; this activation led to increased norepinephrine (NE) release and beta-1 adrenergic receptor activation within the heart. Chronic glial Gq-GPCR activation led to hypotension in female Gfap-hM3Dq mice. This study provides direct evidence that Gq-GPCR activation in peripheral GFAP(+) glia regulates cardiovascular functions in vivo.

  12. Ganglionic GFAP+ glial Gq-GPCR signaling enhances heart functions in vivo

    PubMed Central

    Lee, Jakovin J.; McCarthy, Ken D.

    2017-01-01

    The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein–coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein–expressing (GFAP+) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP+ glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions. In this study, we investigated whether Gq-GPCR activation in GFAP+ glia modulates the regulatory effect of the SNS on the heart; transgenic mice expressing Gq-coupled DREADD (designer receptors exclusively activated by designer drugs) (hM3Dq) selectively in GFAP+ glia were used to address this question in vivo. We found that acute Gq-GPCR activation in peripheral GFAP+ glia significantly accelerated heart rate and increased left ventricle contraction. Pharmacological experiments suggest that the glial-induced cardiac changes were due to Gq-GPCR activation in satellite glial cells within the sympathetic ganglion; this activation led to increased norepinephrine (NE) release and beta-1 adrenergic receptor activation within the heart. Chronic glial Gq-GPCR activation led to hypotension in female Gfap-hM3Dq mice. This study provides direct evidence that Gq-GPCR activation in peripheral GFAP+ glia regulates cardiovascular functions in vivo. PMID:28138563

  13. The Study of Cognitive Function and Related Factors in Patients With Heart Failure

    PubMed Central

    Ghanbari, Atefeh; Moaddab, Fatemeh; Salari, Arsalan; Kazemnezhad Leyli, Ehsan; Sedghi Sabet, Mitra; Paryad, Ezzat

    2013-01-01

    Background: Cognitive impairment is increasingly recognized as a common adverse consequence of heart failure. Both Heart failure and cognitive impairment are associated with frequent hospitalization and increased mortality, particularly when they occur simultaneously. Objectives: To determine cognitive function and related factors in patients with heart failure. Materials and Methods: In this descriptive cross-sectional study, we assessed 239 patients with heart failure. Data were collected by Mini Mental status Examination, Charlson comorbidity index and NYHA classification system. Data were analyzed using descriptive statistics, Kolmogorov-Smirnov test, chi-square test, t-test and logistic regression analysis. Results: The mean score of cognitive function was 21.68 ± 4.51. In total, 155 patients (64.9%) had cognitive impairment. Significant associations were found between the status of cognitive impairment and gender (P < 0.002), education level (P < 0.000), living location (P < 0.000), marital status (P < 0.03), living arrangement (P < 0.001 ), employment status (P < 0.000), income (P < 0.02), being the head of family (P < 0.03), the family size (P < 0.02), having a supplemental insurance (P < 0.003) and the patient’s comorbidities (P < 0.02). However, in logistic regression analysis, only education and supplementary insurance could predict cognitive status which indicates that patients with supplementary insurance and higher education levels were more likely to maintain optimal cognitive function. Conclusions: More than a half of the subjects had cognitive impairment. As the level of patients cognitive functioning affects their behaviors and daily living activities, it is recommended that patients with heart failure should be assessed for their cognitive functioning. PMID:25414874

  14. Affective Instability in Daily Life Is Predicted by Resting Heart Rate Variability

    PubMed Central

    Kuppens, Peter; Van den Bergh, Omer; Tuerlinckx, Francis; Sütterlin, Stefan

    2013-01-01

    Previous research has shown that being affectively unstable is an indicator of several forms of psychological maladjustment. However, little is known about the mechanisms underlying affective instability. Our research aims to examine the possibility that being prone to extreme fluctuations in one’s feelings is related to maladaptive emotion regulation. We investigated this hypothesis by relating affective instability, assessed in daily life using the experience sampling method, to self-reported emotion regulation strategies and to parasympathetically mediated heart rate variability (HRV), a physiological indicator of emotion regulation capacity. Results showed that HRV was negatively related to instability of positive affect (as measured by mean square successive differences), indicating that individuals with lower parasympathetic tone are emotionally less stable, particularly for positive affect. PMID:24312315

  15. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

  16. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    PubMed

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

  17. Drug effects on functional structures in isolated perfused pig heart

    NASA Astrophysics Data System (ADS)

    Trinks, Tobias; Rauh, Robert; Hiller, Michael; Kessler, Manfred D.

    2002-06-01

    Until today monitoring of immediate drug tissue interaction in living organs is an unsolved problem. However, for the development of new drugs and the improvement of medical therapy outcome it would be helpful to get new tools to visualize drug effects on tissue directly. With the EMPHO II SSK and a 3D-scanning device we detected changes of functional structures in an isolated perfused pig heart model after adding commonly used drugs like verapamil, nitroglycerin and salviae miltiorrhizae (Chinese herbal drug). In the paper the results are presented.

  18. Facets of psychopathy, heart rate variability and cognitive function.

    PubMed

    Hansen, Anita Lill; Johnsen, Bjørn Helge; Thornton, David; Waage, Leif; Thayer, Julian F

    2007-10-01

    The aim of the present study was to investigate whether the four facets of Hare's Psychopathy Checklist-Revised (PCL-R; Hare, 1991; Bolt, Hare, Vitale, & Newman, 2004) were related to physiological and cognitive mechanisms. Fifty-three male prisoners participated in this study. Physiological responses were measured as heart rate variability (HRV) and heart rate (HR). Cognitive functions were measured using a continuous performance test (CPT; California Computerized Assessment Package, Abbreviated version) and a working memory test (WMT); based on Baddeley & Hitch (1974). The regression analysis of the HRV revealed that the interpersonal facet explained most of the variance during baseline (28%), CPT (16%), and WMT (12%). This was also true for the HR data during baseline (28%), CPT (20%), WMT (10%), and recovery (13%). The antisocial facet explained 10% of the variance only during baseline. Subjects scoring high compared to low on the interpersonal facet also showed better cognitive functioning. The study suggests that the different facets were differently associated with both physiological and cognitive functions.

  19. The heart's ‘little brain’ controlling cardiac function in the rabbit

    PubMed Central

    Brack, Kieran E

    2015-01-01

    New Findings •What is the topic of this review? The topic of the review is the intrinsic cardiac nervous system in the rabbit. •What advances does it highlight? The anatomy of rabbit intrinsic ganglia is similar to that of other species, including humans. Immunohistochemistry confirms the presence of cholinergic and adrenergic neurones, with a striking arrangement of neuronal nitric oxide synthase-positive cell bodies. Activation of atrial ganglia produces effects on local and remote regions. Heart disease is a primary cause of mortality in the developed world, and it is well recognized that neural mechanisms play an important role in many cardiac pathologies. The role of extrinsic autonomic nerves has traditionally attracted the most attention. However, there is a rich intrinsic innervation of the heart, including numerous cardiac ganglia (ganglionic plexuses), that has the potential to affect cardiac function independently as well as to influence the actions of the extrinsic nerves. To investigate this, an isolated, perfused, innervated rabbit Langendorff heart preparation was considered the best option. Although ganglionic plexuses have been well described for several species, there was no full description of the anatomy and histochemistry of rabbit hearts. To this end, rabbit intrinsic ganglia were located using acetylcholinesterase histology (n = 33 hearts). This revealed six generalized ganglionic regions, defined as a left neuronal complex above the left pulmonary vein, a right neuronal complex around the base of right cranial vein, three scattered in the dorsal right atrium and a region containing numerous ventricular ganglia located on the conus arteriosus. Using immunohistochemistry, neurons were found to contain choline acetyltransferase or tyrosine hydroxylase and/or neuronal nitric oxide synthase in differing amounts (choline acetyltransferase > tyrosine hydroxylase > neuronal nitric oxide synthase). The function of rabbit intrinsic ganglia

  20. Executive function moderates the relationship between depressive symptoms and resting heart rate variability in heart failure.

    PubMed

    Gathright, Emily C; Walter, Fawn A; Hawkins, Misty A W; Spitznagel, Mary Beth; Hughes, Joel W; Gunstad, John

    2016-04-01

    Heart failure (HF) is associated with high rates of depression. In turn, depression is associated with reduced heart rate variability (HRV), a marker of parasympathetic dysfunction and poorer cardiac outcomes. Cognitive impairment--especially executive dysfunction--is also highly prevalent in HF, but it is unknown whether executive function (EF) impacts the depression-HRV relationship. The primary objective of this paper is to examine whether EF moderates the relationship between depression and HRV in HF. Participants were 109 HF patients. Depressive symptoms were measured using the Beck Depression Inventory-II. EF was assessed using a composite of age-adjusted T scores on the Frontal Assessment Battery, Trail Making Test B, and Stroop Color Word subtest. Parasympathetic function was assessed using resting high frequency HRV (HF-HRV). Multiple hierarchical regression was used to conduct BDI × EF moderation analyses. BDI scores were associated with reduced resting HF-HRV (p < .05). No main effects were detected between EF and resting HF-HRV (p > .05). However, EF moderated the relationship between BDI scores and resting HF-HRV (β = 0.59, p < .01). Simple slope analyses revealed that among participants with poorer EF, higher BDI scores were associated with lower resting HF-HRV (p < .001). Structural brain changes common in HF may contribute to lower EF, increased depression, and poorer autonomic functioning. Alternatively, the results may indicate that individuals with intact EF engage in self-care strategies that negate the detrimental impact of depression on autonomic function. Additional work is needed to clarify these possibilities and the potential benefits of treating depression in HF patients with different cognitive abilities.

  1. Integrating affective and cognitive correlates of heart rate variability: A structural equation modeling approach.

    PubMed

    Mann, Sarah L; Selby, Edward A; Bates, Marsha E; Contrada, Richard J

    2015-10-01

    High frequency heart rate variability (HRV) is a measure of neurocardiac communication thought to reflect predominantly parasympathetic cardiac regulation. Low HRV has been associated empirically with clinical and subclinical levels of anxiety and depression and, more recently, high levels of HRV have been associated with better performance on some measures of executive functioning (EF). These findings have offered support for theories proposing HRV as an index measure of a broad, self-regulatory capacity underlying aspects of emotion regulation and executive control. This study sought to test that proposition by using a structural equation modeling approach to examine the relationships of HRV to negative affect (NA) and EF in a large sample of U.S. adults ages 30s-80s. HRV was modeled as a predictor of an NA factor (self-reported trait anxiety and depression symptoms) and an EF factor (performance on three neuropsychological tests tapping facets of executive abilities). Alternative models also were tested to determine the utility of HRV for predicting NA and EF, with and without statistical control of demographic and health-related covariates. In the initial structural model, HRV showed a significant positive relationship to EF and a nonsignificant relationship to NA. In a covariate-adjusted model, HRV's associations with both constructs were nonsignificant. Age emerged as the only significant predictor of NA and EF in the final model, showing inverse relationships to both. Findings may reflect population and methodological differences from prior research; they also suggest refinements to the interpretations of earlier findings and theoretical claims regarding HRV.

  2. Cybersickness provoked by head-mounted display affects cutaneous vascular tone, heart rate and reaction time.

    PubMed

    Nalivaiko, Eugene; Davis, Simon L; Blackmore, Karen L; Vakulin, Andrew; Nesbitt, Keith V

    2015-11-01

    Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n=8) having values of 23-29 °C, and high-temperature group (n=18) having values of 32-36 °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4 °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2 °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50 ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology.

  3. Evaluation of Heart Function in Patients With Hemophilia.

    PubMed

    Amoozgar, Hamid; Fath, Maedeh; Jooya, Parisa; Karimi, Mehran

    2015-11-04

    There are conflicting reports about the protective effect of hemophilia on the occurrence of ischemic heart disease. This study focuses on evaluation of heart function in patients with hemophilia. Cross-sectional, case-control study was done on all patients with hemophilia A or B who came to hemophilia center, and data were compared to controls. The data were collected from their charts, and heart function was evaluated by 2-dimensional, Doppler and pulse tissue Doppler. The serum troponin I level was measured in all patients as a marker of myocardial damage. Fifty patients with hemophilia took part in this study. All of them were male with mean age 29.1 years. Systolic blood pressure (mean = 121.52 ± 11 vs 115.61 ± 9.81, P = .038) and diastolic (mean = 81.94 ± 4.51 vs 75.21 ± 3.95, P = .042) blood pressure were higher in the patients. Five (10%) patients had systolic hypertension and 7 (14%) patients had diastolic hypertension. The M-mode echocardiography results showed that interventricular septum in diastole in patients with hemophilia (mean 1.143 ± 0.29) was significantly thicker than the control group (mean 0.828 ± 0.22, P < .001). Tissue Doppler echocardiography showed that late diastolic velocity of septum (Aa; P = .030), systolic velocity (S) of lateral mitral valve (P = .006), late diastolic velocity of lateral mitral (Aa) annulus (P = .038), and late velocity of (Aa) tricuspid (P = .004) had significant difference compared with the control group (P < .05). Troponin enzyme level was < 0.1 in all patients. Patients with hemophilia had higher blood pressure and more hypertension. Echocardiographic study of patients with hemophilia showed some increase in septal thickness and changes in diastolic dysfunction.

  4. Physiological Arousal and Juvenile Psychopathy: Is Low Resting Heart Rate Associated with Affective Dimensions?

    PubMed

    Kavish, Nicholas; Vaughn, Michael G; Cho, Eunsoo; Barth, Amy; Boutwell, Brian; Vaughn, Sharon; Capin, Philip; Stillman, Stephanie; Martinez, Leticia

    2017-03-01

    A wealth of past research has examined the relationship between low physiological arousal and violence or antisocial behavior. Relatively little research; however, has examined the relationship between low physiological arousal and psychopathic traits, with even less having been conducted with juveniles. The current study attempts to fill this gap by evaluating juveniles' physiological arousal using resting heart rate and their levels of psychopathic traits. Results suggest that there is indeed an inverse relationship between resting heart rate and the affective traits of psychopathy (Uncaring, Callousness, and Unemotionality) as well as Thrill or Sensation Seeking in males. No significant relationship was found in females. Implications of the findings as well as study limitations and future directions are discussed.

  5. Functional Tricuspid Regurgitation Model in a Beating Heart Platform.

    PubMed

    Jaworek, Michal; Piola, Marco; Lucherini, Federico; Gelpi, Guido; Castagna, Marco; Lentini, Giuliana; Antona, Carlo; Fiore, Gianfranco B; Vismara, Riccardo

    2017-01-03

    Currently, clinicians are seeking new, minimally invasive treatment options for functional tricuspid regurgitation (FTR). Challenging tricuspid complexity requires the evaluation of the treatment techniques in adequate and realistic preclinical scenario. The purpose of this paper is to describe the design and functional assessment of a novel passive beating heart model of the pulmonary circulation with the possibility to tightly control FTR.The model housed porcine hearts actuated by a volumetric pump that cyclically pressurized the right ventricle. The in-vitro FTR model exploited the tendency of the ventricle to dilate under pressure. The dilation entailed papillary muscles displacement and valve annulus enlargement, thus inducing tricuspid valve insufficiency. Employment of constraint bands allowed to restore valve competency.The system provided consistent replication of the main determinants of the pulmonary hemodynamics in a wide range of working conditions. The experimental model of FTR was reliable, easily controllable and showed good stability over time. Echocardiography and fiberscope imaging provided a unique opportunity to investigate valve dynamics. These features make the platform suitable for realistic training purposes and testing of the upcoming FTR therapies.

  6. Treadmill performance and cardiac function in selected patients with coronary heart disease

    SciTech Connect

    McKirnan, M.D.; Sullivan, M.; Jensen, D.; Froelicher, V.F.

    1984-02-01

    To investigate the cardiac determinants of treadmill performance in patients able to exercise to volitional fatigue, 88 patients with coronary heart disease free of angina pectoris were tested. The exercise tests included supine bicycle radionuclide ventriculography, thallium scintigraphy and treadmill testing with expired gas analysis. The number of abnormal Q wave locations, ejection fraction, end-diastolic volume, cardiac output, exercise-induced ST segment depression and thallium scar and ischemia scores were the cardiac variables considered. Rest and exercise ejection fractions were highly correlated to thallium scar score (r . -0.72 to -0.75, p less than 0.001), but not to maximal oxygen consumption (r . 0.19 to 0.25, p less than 0.05). Fifty-five percent of the variability in predicting treadmill time or estimated maximal oxygen consumption was explained by treadmill test-induced change in heart rate (39%), thallium ischemia score (12%) and cardiac output at rest (4%). The change in heart rate induced by the treadmill test explained only 27% of the variability in measured maximal oxygen consumption. Myocardial damage predicted ejection fraction at rest and the ability to increase heart rate with treadmill exercise appeared as an essential component of exercise capacity. Exercise capacity was only minimally affected by asymptomatic ischemia and was relatively independent of ventricular function.

  7. Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen

    PubMed Central

    Hatayama, Naoyuki; Inubushi, Masayuki; Naito, Munekazu; Hirai, Shuichi; Jin, Yong-Nan; Tsuji, Atsushi B.; Seki, Kunihiro; Itoh, Masahiro; Saga, Tsuneo; Li, Xiao-Kang

    2016-01-01

    We recently succeeded in resuscitating an extracted rat heart following 24–48 hours of preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O2). This study aimed to examine the function of rat hearts transplanted after being preserved in the high-pressure CO and O2 gas mixture. The hearts of donor rats were preserved in a chamber filled with CO and O2 under high pressure for 24 h (CO24h) or 48 h at 4 °C. For the positive control (PC) group, hearts immediately extracted from donor rats were used for transplantation. The preserved hearts were transplanted into recipient rats by heterotopic cervical heart transplantation. CO toxicity does not affect the grafts or the recipients. Light microscopy and [18F]-fluorodeoxyglucose positron emission tomography revealed that there were no significant differences in the size of the myocardial infarction or apoptosis of myocardial cells in post-transplant hearts between the PC and CO24h groups. Furthermore, at 100 days after the transplantation, the heart rate, weight and histological staining of the post-transplanted hearts did not differ significantly between the PC and CO24h groups. These results indicate that the function of rat hearts is well preserved after 24 hours of high-pressure preservation in a CO and O2 gas mixture. Therefore, high-pressure preservation in a gas mixture can be a useful method for organ preservation. PMID:27562456

  8. The Ubiquitin-Like SUMO System and Heart Function: From Development to Disease.

    PubMed

    Mendler, Luca; Braun, Thomas; Müller, Stefan

    2016-01-08

    SUMOylation is a ubiquitin-related transient posttranslational modification pathway catalyzing the conjugation of small ubiquitin-like modifier (SUMO) proteins (SUMO1, SUMO2, and SUMO3) to lysine residues of proteins. SUMOylation targets a wide variety of cellular regulators and thereby affects a multitude of different cellular processes. SUMO/sentrin-specific proteases are able to remove SUMOs from targets, contributing to a tight control of SUMOylated proteins. Genetic and cell biological experiments indicate a critical role of balanced SUMOylation/deSUMOylation for proper cardiac development, metabolism, and stress adaptation. Here, we review the current knowledge about SUMOylation/deSUMOylation in the heart and provide an integrated picture of cardiac functions of the SUMO system under physiologic or pathologic conditions. We also describe potential therapeutic approaches targeting the SUMO machinery to combat heart disease.

  9. Attachment Status Affects Heart Rate Responses to Experimental Ostracism in Inpatients with Depression

    PubMed Central

    De Rubeis, Jannika; Sütterlin, Stefan; Lange, Diane; Pawelzik, Markus; van Randenborgh, Annette; Victor, Daniela; Vögele, Claus

    2016-01-01

    Depression is assumed to be both a risk factor for rejection and a result of it, and as such constitutes an important factor in rejection research. Attachment theory has been applied to understand psychological disorders, such as depression, and can explain individual differences in responses to rejection. Research on autonomic nervous system activity to rejection experiences has been contradictory, with opposing strings of argumentation (activating vs. numbing). We investigated autonomic nervous system-mediated peripheral physiological responses (heart rate) to experimentally manipulated ostracism (Cyberball) in 97 depressed patients with organized (n = 52) and disorganized attachment status (n = 45). Controlling for baseline mean heart rate levels, depressed patients with disorganized attachment status responded to ostracism with significantly higher increases in heart rate than depressed patients with organized attachment status (p = .029; ηp2 = .051). These results suggest that attachment status may be a useful indicator of autonomic responses to perceived social threat, which in turn may affect the therapeutic process and the patient-therapist relationship. PMID:26943924

  10. Attachment Status Affects Heart Rate Responses to Experimental Ostracism in Inpatients with Depression.

    PubMed

    De Rubeis, Jannika; Sütterlin, Stefan; Lange, Diane; Pawelzik, Markus; van Randenborgh, Annette; Victor, Daniela; Vögele, Claus

    2016-01-01

    Depression is assumed to be both a risk factor for rejection and a result of it, and as such constitutes an important factor in rejection research. Attachment theory has been applied to understand psychological disorders, such as depression, and can explain individual differences in responses to rejection. Research on autonomic nervous system activity to rejection experiences has been contradictory, with opposing strings of argumentation (activating vs. numbing). We investigated autonomic nervous system-mediated peripheral physiological responses (heart rate) to experimentally manipulated ostracism (Cyberball) in 97 depressed patients with organized (n = 52) and disorganized attachment status (n = 45). Controlling for baseline mean heart rate levels, depressed patients with disorganized attachment status responded to ostracism with significantly higher increases in heart rate than depressed patients with organized attachment status (p = .029; ηp2 = .051). These results suggest that attachment status may be a useful indicator of autonomic responses to perceived social threat, which in turn may affect the therapeutic process and the patient-therapist relationship.

  11. 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

  12. Does iron deficiency anemia affect olfactory function?

    PubMed

    Dinc, Mehmet Emre; Dalgic, Abdullah; Ulusoy, Seckin; Dizdar, Denizhan; Develioglu, Omer; Topak, Murat

    2016-07-01

    Conclusion This study found a negative effect of IDA on olfactory function. IDA leads to a reduction in olfactory function, and decreases in hemoglobin levels result in further reduction in olfactory function. Objective This study examined the effects of iron-deficiency anemia (IDA) on olfactory function. Method The study enrolled 50 IDA patients and 50 healthy subjects. Olfactory function was evaluated using the Sniffin' Sticks olfactory test. The diagnosis of IDA was made according to World Health Organization (WHO) criteria. Results Patients with IDA had a significantly lower threshold, discrimination, and identification (TDI) value, and a lower threshold compared with the control group. However, there were no significant differences between the groups in terms of smell selectivity values.

  13. Can Particulate Pollution Affect Lung Function in Healthy Adults?

    EPA Science Inventory

    Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

  14. Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm.

    PubMed

    Chetaille, Philippe; Preuss, Christoph; Burkhard, Silja; Côté, Jean-Marc; Houde, Christine; Castilloux, Julie; Piché, Jessica; Gosset, Natacha; Leclerc, Séverine; Wünnemann, Florian; Thibeault, Maryse; Gagnon, Carmen; Galli, Antonella; Tuck, Elizabeth; Hickson, Gilles R; El Amine, Nour; Boufaied, Ines; Lemyre, Emmanuelle; de Santa Barbara, Pascal; Faure, Sandrine; Jonzon, Anders; Cameron, Michel; Dietz, Harry C; Gallo-McFarlane, Elena; Benson, D Woodrow; Moreau, Claudia; Labuda, Damian; Zhan, Shing H; Shen, Yaoqing; Jomphe, Michèle; Jones, Steven J M; Bakkers, Jeroen; Andelfinger, Gregor

    2014-11-01

    The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-β signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.

  15. Effect of Right Heart Systolic Function on Outcomes in Patients with Constrictive Pericarditis Undergoing Pericardiectomy

    PubMed Central

    Lin, Xue; Xu, Rui-Yi; Liu, Jian-Zhou; Chen, Wei; Chen, Lian-Feng; Yang, Peng-Hua; Fang, Li-Gang

    2016-01-01

    Background: To determine the influence of right ventricular function in patients with constrictive pericarditis (CP) undergoing surgery and to compare the outcomes of patients who received surgery with those managed medically. Methods: Patients with the diagnosis of CP and healthy volunteers were recruited from January 2006 to November 2011. Patients with CP chose to either receive pericardiectomy or medical management. Echocardiographic measurements were performed to evaluate heart function, and survival was recorded. Results: A total of 58 patients with CP (36 received pericardiectomy, 22 managed medically), and 43 healthy volunteers were included. CP patients who received surgery had a higher survival rate than those managed medically (P = 0.003), and higher survival was also seen in the subgroup of CP patients with severely impaired right systolic function. Albumin level, left ventricular end-diastolic dimension, and tricuspid regurgitation velocity were associated with survival in CP patients who received surgery. Conclusions: Preoperative right heart function does not affect surgical outcomes. Patients with severely impaired preoperative right systolic function obtain a greater survival advantage with surgery than with medical treatment. PMID:26830985

  16. Heart rate variability biofeedback improves cardiorespiratory resting function during sleep.

    PubMed

    Sakakibara, Masahito; Hayano, Junichiro; Oikawa, Leo O; Katsamanis, Maria; Lehrer, Paul

    2013-12-01

    The present study was designed to examine the effect of heart rate variability (HRV) biofeedback on the cardiorespiratory resting function during sleep in daily life. Forty-five healthy young adults were randomly assigned to one of three groups: HRV biofeedback, Autogenic Training(AT), and no-treatment control. Participants in the HRV biofeedback were instructed to use a handheld HRV biofeedback device before their habitual bedtime, those in the AT were asked to listen to an audiotaped instruction before bedtime,and those in the control were asked to engage in their habitual activity before bedtime. Pulse wave signal during sleep at their own residences was measured continuously with a wrist watch-type transdermal photoelectric sensor for three time points. Baseline data were collected on the first night of measurements, followed by two successive nights for HRV biofeedback, AT, or control. Cardiorespiratory resting function was assessed quantitatively as the amplitude of high frequency(HF) component of pulse rate variability, a surrogate measure of respiratory sinus arrhythmia. HF component increased during sleep in the HRV biofeedback group,although it remained unchanged in the AT and control groups. These results suggest that HRV biofeedback before sleep may improve cardiorespiratory resting function during sleep.

  17. Effect of renal function on prognosis in chronic heart failure.

    PubMed

    Löffler, Adrián Ignacio; Cappola, Thomas P; Fang, James; Hetzel, Scott J; Kadlec, Andrew; Astor, Brad; Sweitzer, Nancy K

    2015-01-01

    Renal dysfunction (RD) is associated with increased mortality in heart failure (HF). The aim of this study was to identify whether worsened or improved renal function during mid-term follow-up is associated with worsened outcomes in patients with chronic HF. A total of 892 participants from a multicenter cohort study of chronic HF were followed over 3.1 ± 1.9 years of enrollment. Worsened and improved renal functions were tested with multivariate models as independent predictors of HF hospitalization and mortality. Although 12% of subjects experienced a ≥25% decrease in estimated glomerular filtration rate (eGFR), 17% experienced a ≥25% increase in eGFR, and there was stability of kidney function observed in the cohort as a whole. The quartile with the worst RD at any point in time had increased risk of HF hospitalization and mortality. Worsened eGFR was associated with HF outcomes in the unadjusted (hazard ratio = 1.71, 95% confidence interval 1.04 to 2.81, p = 0.035), but not the adjusted analysis. Improvement in eGFR was not associated with outcome (p = 0.453). In chronic HF, the severity of RD predicts risk of poor outcome better than changes in renal function during mid-term follow-up. This suggests that in patients with appropriately treated chronic HF, worsening renal function in itself does not yield useful prognostic information and may not reflect poor outcome.

  18. Dynamic heart phantom with functional mitral and aortic valves

    NASA Astrophysics Data System (ADS)

    Vannelli, Claire; Moore, John; McLeod, Jonathan; Ceh, Dennis; Peters, Terry

    2015-03-01

    Cardiac valvular stenosis, prolapse and regurgitation are increasingly common conditions, particularly in an elderly population with limited potential for on-pump cardiac surgery. NeoChord©, MitraClipand numerous stent-based transcatheter aortic valve implantation (TAVI) devices provide an alternative to intrusive cardiac operations; performed while the heart is beating, these procedures require surgeons and cardiologists to learn new image-guidance based techniques. Developing these visual aids and protocols is a challenging task that benefits from sophisticated simulators. Existing models lack features needed to simulate off-pump valvular procedures: functional, dynamic valves, apical and vascular access, and user flexibility for different activation patterns such as variable heart rates and rapid pacing. We present a left ventricle phantom with these characteristics. The phantom can be used to simulate valvular repair and replacement procedures with magnetic tracking, augmented reality, fluoroscopy and ultrasound guidance. This tool serves as a platform to develop image-guidance and image processing techniques required for a range of minimally invasive cardiac interventions. The phantom mimics in vivo mitral and aortic valve motion, permitting realistic ultrasound images of these components to be acquired. It also has a physiological realistic left ventricular ejection fraction of 50%. Given its realistic imaging properties and non-biodegradable composition—silicone for tissue, water for blood—the system promises to reduce the number of animal trials required to develop image guidance applications for valvular repair and replacement. The phantom has been used in validation studies for both TAVI image-guidance techniques1, and image-based mitral valve tracking algorithms2.

  19. Characterization of the phospholemman knockout mouse heart: depressed left ventricular function with increased Na-K-ATPase activity.

    PubMed

    Bell, James R; Kennington, Erika; Fuller, William; Dighe, Kushal; Donoghue, Pamela; Clark, James E; Jia, Li-Guo; Tucker, Amy L; Moorman, J Randall; Marber, Michael S; Eaton, Philip; Dunn, Michael J; Shattock, Michael J

    2008-02-01

    Phospholemman (PLM, FXYD1), abundantly expressed in the heart, is the primary cardiac sarcolemmal substrate for PKA and PKC. Evidence supports the hypothesis that PLM is part of the cardiac Na-K pump complex and provides the link between kinase activity and pump modulation. PLM has also been proposed to modulate Na/Ca exchanger activity and may be involved in cell volume regulation. This study characterized the phenotype of the PLM knockout (KO) mouse heart to further our understanding of PLM function in the heart. PLM KO mice were bred on a congenic C57/BL6 background. In vivo conductance catheter measurements exhibited a mildly depressed cardiac contractile function in PLM KO mice, which was exacerbated when hearts were isolated and Langendorff perfused. There were no significant differences in action potential morphology in paced Langendorff-perfused hearts. Depressed contractile function was associated with a mild cardiac hypertrophy in PLM KO mice. Biochemical analysis of crude ventricular homogenates showed a significant increase in Na-K-ATPase activity in PLM KO hearts compared with wild-type controls. SDS-PAGE and Western blot analysis of ventricular homogenates revealed small, nonsignificant changes in Na- K-ATPase subunit expression, with two-dimensional gel (isoelectric focusing, SDS-PAGE) analysis revealing minimal changes in ventricular protein expression, indicating that deletion of PLM was the primary reason for the observed PLM KO phenotype. These studies demonstrate that PLM plays an important role in the contractile function of the normoxic mouse heart. Data are consistent with the hypothesis that PLM modulates Na-K-ATPase activity, indirectly affecting intracellular Ca and hence contractile function.

  20. Evolutionary diversification in stickleback affects ecosystem functioning.

    PubMed

    Harmon, Luke J; Matthews, Blake; Des Roches, Simone; Chase, Jonathan M; Shurin, Jonathan B; Schluter, Dolph

    2009-04-30

    Explaining the ecological causes of evolutionary diversification is a major focus of biology, but surprisingly little has been said about the effects of evolutionary diversification on ecosystems. The number of species in an ecosystem and their traits are key predictors of many ecosystem-level processes, such as rates of productivity, biomass sequestration and decomposition. Here we demonstrate short-term ecosystem-level effects of adaptive radiation in the threespine stickleback (Gasterosteus aculeatus) over the past 10,000 years. These fish have undergone recent parallel diversification in several lakes in coastal British Columbia, resulting in the formation of two specialized species (benthic and limnetic) from a generalist ancestor. Using a mesocosm experiment, we demonstrate that this diversification has strong effects on ecosystems, affecting prey community structure, total primary production, and the nature of dissolved organic materials that regulate the spectral properties of light transmission in the system. However, these ecosystem effects do not simply increase in their relative strength with increasing specialization and species richness; instead, they reflect the complex and indirect consequences of ecosystem engineering by sticklebacks. It is well known that ecological factors influence adaptive radiation. We demonstrate that adaptive radiation, even over short timescales, can have profound effects on ecosystems.

  1. 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

  2. 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.

  3. Recent heart rate history affects QT interval duration in atrial fibrillation

    PubMed Central

    Riad, Fady S.; Razak, Eathar; Saba, Samir; Shalaby, Alaa; Nemec, Jan

    2017-01-01

    QT interval prolongation is associated with a risk of polymorphic ventricular tachycardia. QT interval shortens with increasing heart rate and correction for this effect is necessary for meaningful QT interval assessment. We aim to improve current methods of correcting the QT interval during atrial fibrillation (AF). Digitized Holter recordings were analyzed from patients with AF. Models of QT interval dependence on RR intervals were tested by sorting the beats into 20 bins based on corrected RR interval and assessing ST-T variability within the bins. Signal-averaging within bins was performed to determine QT/RR dependence. Data from 30 patients (29 men, 69.3±7.3 years) were evaluated. QT behavior in AF is well described by a linear function (slope ~0.19) of steady-state corrected RR interval. Corrected RR is calculated as a combination of an exponential weight function with time-constant of 2 minutes and a smaller “immediate response” component (weight ~ 0.18). This model performs significantly (p<0.0001) better than models based on instantaneous RR interval only including Bazett and Fridericia. It also outperforms models based on shorter time-constants and other previously proposed models. This model may improve detection of repolarization delay in AF. QT response to heart rate changes in AF is similar to previously published QT dynamics during atrial pacing and in sinus rhythm. PMID:28273109

  4. Effects of the organophosphorus pesticide Folisuper 600 (methyl parathion) on the heart function of bullfrog tadpoles, Lithobates catesbeianus (Shaw, 1802).

    PubMed

    Costa, M J; Ribeiro, L R; Salla, R F; Gamero, F U; Alves, L M L M; Silva-Zacarin, E C M

    2015-11-01

    The aim of this work was to evaluate whether the heart function of bullfrog tadpoles (25 Gosner stage) is affected by their acute exposure (48 h) to a sub-lethal concentration (10 µg.L-1) of the active principle of the organophosphorus pesticide Folisuper 600R (methyl parathion - MP). Our results demonstrated that MP causes not only a reduction in tadpoles' cardiac ventricular mass, resulting in a marked reduction in their cardiac twitch force, but also impairs their swimming performance, irrespective of increasing their heart rate. Together, these findings indicate that low and realistic concentration of MP have a negative impact on tadpoles' performance, jeopardizing their survival.

  5. Miniature implantable instrument measures and transmits heart function data

    NASA Technical Reports Server (NTRS)

    Lee, R. D.

    1971-01-01

    Heart diameter is derived from measured transit time of 2.25 MHz ultrasonic pulse between two piezoelectric crystals attached to diametrically opposite heart surfaces. Miniature instrument implanted in chest telemeters information to external receiver-converter. System permits continual dimensional data recording taken from awake animals during long-term experiments.

  6. Aldehyde dehydrogenase 2 activation in heart failure restores mitochondrial function and improves ventricular function and remodelling

    PubMed Central

    Gomes, Katia M.S.; Campos, Juliane C.; Bechara, Luiz R.G.; Queliconi, Bruno; Lima, Vanessa M.; Disatnik, Marie-Helene; Magno, Paulo; Chen, Che-Hong; Brum, Patricia C.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

    2014-01-01

    Aims We previously demonstrated that pharmacological activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects the heart against acute ischaemia/reperfusion injury. Here, we determined the benefits of chronic activation of ALDH2 on the progression of heart failure (HF) using a post-myocardial infarction model. Methods and results We showed that a 6-week treatment of myocardial infarction-induced HF rats with a selective ALDH2 activator (Alda-1), starting 4 weeks after myocardial infarction at a time when ventricular remodelling and cardiac dysfunction were present, improved cardiomyocyte shortening, cardiac function, left ventricular compliance and diastolic function under basal conditions, and after isoproterenol stimulation. Importantly, sustained Alda-1 treatment showed no toxicity and promoted a cardiac anti-remodelling effect by suppressing myocardial hypertrophy and fibrosis. Moreover, accumulation of 4-hydroxynonenal (4-HNE)-protein adducts and protein carbonyls seen in HF was not observed in Alda-1-treated rats, suggesting that increasing the activity of ALDH2 contributes to the reduction of aldehydic load in failing hearts. ALDH2 activation was associated with improved mitochondrial function, including elevated mitochondrial respiratory control ratios and reduced H2O2 release. Importantly, selective ALDH2 activation decreased mitochondrial Ca2+-induced permeability transition and cytochrome c release in failing hearts. Further supporting a mitochondrial mechanism for ALDH2, Alda-1 treatment preserved mitochondrial function upon in vitro aldehydic load. Conclusions Selective activation of mitochondrial ALDH2 is sufficient to improve the HF outcome by reducing the toxic effects of aldehydic overload on mitochondrial bioenergetics and reactive oxygen species generation, suggesting that ALDH2 activators, such as Alda-1, have a potential therapeutic value for treating HF patients. PMID:24817685

  7. Hemodynamics of a functional centrifugal-flow total artificial heart with functional atrial contraction in goats.

    PubMed

    Shiga, Takuya; Shiraishi, Yasuyuki; Sano, Kyosuke; Taira, Yasunori; Tsuboko, Yusuke; Yamada, Akihiro; Miura, Hidekazu; Katahira, Shintaro; Akiyama, Masatoshi; Saiki, Yoshikatsu; Yambe, Tomoyuki

    2016-03-01

    Implantation of a total artificial heart (TAH) is one of the therapeutic options for the treatment of patients with end-stage biventricular heart failure. There is no report on the hemodynamics of the functional centrifugal-flow TAH with functional atrial contraction (fCFTAH). We evaluated the effects of pulsatile flow by atrial contraction in acute animal models. The goats received fCFTAH that we created from two centrifugal-flow ventricular assist devices. Some hemodynamic parameters maintained acceptable levels: heart rate 115.5 ± 26.3 bpm, aortic pressure 83.5 ± 10.1 mmHg, left atrial pressure 18.0 ± 5.9 mmHg, pulmonary pressure 28.5 ± 9.7 mmHg, right atrial pressure 13.6 ± 5.2 mmHg, pump flow 4.0 ± 1.1 L/min (left) 3.9 ± 1.1 L/min (right), and cardiac index 2.13 ± 0.14 L/min/m(2). fCFTAH with atrial contraction was able to maintain the TAH circulation by forming a pulsatile flow in acute animal experiments. Taking the left and right flow rate balance using the low internal pressure loss of the VAD pumps may be easier than by other pumps having considerable internal pressure loss. We showed that the remnant atrial contraction effected the flow rate change of the centrifugal pump, and the atrial contraction waves reflected the heart rate. These results indicate that remnant atria had the possibility to preserve autonomic function in fCFTAH. We may control fCFTAH by reflecting the autonomic function, which is estimated with the flow rate change of the centrifugal pump.

  8. Heart-specific Rpd3 downregulation enhances cardiac function and longevity

    PubMed Central

    Kopp, Zachary A.; Hsieh, Jo-Lin; Li, Andrew; Wang, William; Bhatt, Dhelni T.; Lee, Angela; Kim, Sae Yeon; Fan, David; Shah, Veevek; Siddiqui, Emaad; Ragam, Radhika; Park, Kristen; Ardeshna, Dev; Park, Kunwoo; Wu, Rachel; Parikh, Hardik; Parikh, Ayush; Lin, Yuh-Ru; Park, Yongkyu

    2015-01-01

    Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long-lived flies were tested in the heart-specific manner. Interestingly, the expressions of anti-aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart-specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart-specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly's response to the environment. PMID:26399365

  9. Sexual function of patients with heart failure: facts and numbers

    PubMed Central

    2016-01-01

    Abstract Approximately 60% to 87% of patients with heart failure (HF) report sexual problems, and numbers as low as 31% of HF patients younger than 70 have normal sexual function. When compared with healthy elders, the amount of perceived sexual dysfunction might be similar (around 56%), but patients with HF are reporting more erectile dysfunction (ED) and also perceive that their HF symptoms (20%) or HF medication (10%) is the cause for their problems. The prevalence of ED is highly prevalent in men with cardiac disease and reported in up to 81% of cardiac patients, compared with 50% in the general older population. In total 25–76% of women with HF report sexual problems or concerns. The physical effort related to sexual activity in cardiac patients can be compared to mild to moderate physical activity. The related energy expenditure of sexual activity falls in the range of three to five metabolic units (METs), which can be compared to the energy needed to climb three flights of stairs, general housework, or gardening. Information about sexual activity is often overlooked by health care professionals treating HF patients. Advice and counselling about this subject are needed to decrease worries of patients and partners, avoid skipping medication because of fear for side effects, or prevent inappropriate use of potency enhancing drugs or herbs. PMID:28217306

  10. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction.

    PubMed

    Ngkelo, Anta; Richart, Adèle; Kirk, Jonathan A; Bonnin, Philippe; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Le Gall, Sylvain; Renault, Nisa; Guerin, Coralie; Ranek, Mark J; Kervadec, Anaïs; Danelli, Luca; Gautier, Gregory; Blank, Ulrich; Launay, Pierre; Camerer, Eric; Bruneval, Patrick; Menasche, Philippe; Heymes, Christophe; Luche, Elodie; Casteilla, Louis; Cousin, Béatrice; Rodewald, Hans-Reimer; Kass, David A; Silvestre, Jean-Sébastien

    2016-06-27

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators.

  11. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction

    PubMed Central

    Richart, Adèle; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Guerin, Coralie; Gautier, Gregory; Blank, Ulrich; Heymes, Christophe; Luche, Elodie; Cousin, Béatrice; Rodewald, Hans-Reimer

    2016-01-01

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit–independent MC-deficient (Cpa3Cre/+) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca2+ desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force–Ca2+ interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. PMID:27353089

  12. Suppression of the endoplasmic reticulum calcium pump during zebrafish gastrulation affects left-right asymmetry of the heart and brain.

    PubMed

    Kreiling, Jill A; Balantac, Zaneta L; Crawford, Andrew R; Ren, Yuexin; Toure, Jamal; Zchut, Sigalit; Kochilas, Lazaros; Creton, Robbert

    2008-01-01

    Vertebrate embryos generate striking Ca(2+) patterns, which are unique regulators of dynamic developmental events. In the present study, we used zebrafish embryos as a model system to examine the developmental roles of Ca(2+) during gastrulation. We found that gastrula stage embryos maintain a distinct pattern of cytosolic Ca(2+) along the dorsal-ventral axis, with higher Ca(2+) concentrations in the ventral margin and lower Ca(2+) concentrations in the dorsal margin and dorsal forerunner cells. Suppression of the endoplasmic reticulum Ca(2+) pump with 0.5 microM thapsigargin elevates cytosolic Ca(2+) in all embryonic regions and induces a randomization of laterality in the heart and brain. Affected hearts, visualized in living embryos by a subtractive imaging technique, displayed either a reversal or loss of left-right asymmetry. Brain defects include a left-right reversal of pitx2 expression in the dorsal diencephalon and a left-right reversal of the prominent habenular nucleus in the brain. Embryos are sensitive to inhibition of the endoplasmic reticulum Ca(2+) pump during early and mid gastrulation and lose their sensitivity during late gastrulation and early segmentation. Suppression of the endoplasmic reticulum Ca(2+) pump during gastrulation inhibits expression of no tail (ntl) and left-right dynein related (lrdr) in the dorsal forerunner cells and affects development of Kupffer's vesicle, a ciliated organ that generates a counter-clockwise flow of fluid. Previous studies have shown that Ca(2+) plays a role in Kupffer's vesicle function, influencing ciliary motility and translating the vesicle's counter-clockwise flow into asymmetric patterns of gene expression. The present results suggest that Ca(2+) plays an additional role in the formation of Kupffer's vesicle.

  13. [Ventricular pump function under ectopic excitation of the frog heart].

    PubMed

    Kibler, N A; Belogolova, A S; Vaĭkshnoraĭte, M A; Azarov, Ia E; Shmakov, D N

    2008-02-01

    The ventricular pump function under ectopic excitation of the heart was studied in decapitated and pithed adult frogs Rana temporaria (n = 21) at 18-19 degrees C. The intraventricular pressure was recorded with a catheter via ventricular wall. During pacing of the ventricular base and apex, the systolic pressure decreased (6.1 +/- 4.5 mm Hg and 8.9 +/- 5.0 mm Hg, respectively) as compared to the supraventricular rhythm (8.9 +/- 5.0 mm Hg, p < 0.05). The end-diastolic pressure decreased insignificantly both under basal and apical pacing. The systolic rate of pressure rise during dP/dtmax decreased under ventricular pacing, especially during pacing of the ventricular apex, as compared to the supraventricular rhythm (14.4 +/- 6/9 mm Hg/s and 22.1 +/- 11.2 mm Hg/s, respectively, p < 0.003). The isovolumetric relaxation (dP/dtmin) slowed during apical pacing as compared to the supraventricular rhythm (-25.1 +/- 13.6 and -35.6 +/- 18.3 mm Hg/s, respectively, p < 0.03). Ectopic excitation of the ventricular base and apex resulted in increase of the QRS duration (93 +/- 33 ms and 81 +/- 30 ms, respectively) as compared to the supraventricular rhythm (63 +/- 13 ms, p < 0.05). Thus, pacing of different ventricular areas ventricular myocardium with the ventricular pump function being reduced more obviously during the apical pacing compared to the pacing of ventricular base.

  14. 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

  15. STUDIES IN RESUSCITATION: I. THE GENERAL CONDITIONS AFFECTING RESUSCITATION, AND THE RESUSCITATION OF THE BLOOD AND OF THE HEART

    PubMed Central

    Pike, F. H.; Guthrie, C. C.; Stewart, G. N.

    1908-01-01

    Our results may be briefly summarized: 1. Blood, when defibrinated, soon loses its power to maintain the activity of the higher nervous centers, and its nutritive properties for all tissues quickly diminish. 2. Artificial fluids, as a substitute for blood, are not satisfactory. 3. The proper oxygenation of the blood is an indispensable adjunct in the resuscitation of an animal. 4. The heart usually continues to beat for some minutes after it ceases to affect a mercury manometer, and resuscitation of it within this period by extra-thoracic massage and artificial respiration is sometimes successful. 5. Resuscitation of the heart by direct massage is the most certain method at our command. 6. A proper blood-pressure is an indispensable condition for the continued normal activity of the heart. 7. Anæsthetics, hemorrhage and induced currents applied to the heart render resuscitation more difficult than asphyxia alone. PMID:19867138

  16. Muscular contraction mode differently affects autonomic control during heart rate matched exercise.

    PubMed

    Weippert, Matthias; Behrens, Martin; Gonschorek, Ray; Bruhn, Sven; Behrens, Kristin

    2015-01-01

    The precise contributions of afferent feedback to cardiovascular and respiratory responses to exercise are still unclear. The aim of this crossover study was to assess whether and how autonomic cardiovascular and respiratory control differed in response to dynamic (DYN) and isometric contractions (ISO) at a similar, low heart rate (HR) level. Therefore, 22 healthy males (26.7 ± 3.6 yrs) performed two kinds of voluntary exercises at similar HR: ISO and DYN of the right quadriceps femoris muscle. Although HR was eqivalent (82 ± 8 bpm for DYN and ISO, respectively), rating of exertion, blood pressures, and rate pressure product were higher, whereas breathing frequency, minute ventilation, oxygen uptake and carbon dioxide output were significantly lower during ISO. Tidal volume, end-tidal partial pressures of O2 and CO2, respiratory exchange ratio and capillary blood lactate concentration were comparable between both contraction modes. Heart rate variability (HRV) indicators, SDNN, HF-Power and LF-Power, representing both vagal and sympathetic influences, were significantly higher during ISO. Sample entropy, a non-linear measure of HRV was also significantly affected by contraction mode. It can be concluded that, despite the same net effect on HR, the quality of cardiovascular control during low intensity exercise is significantly different between DYN and ISO. HRV analysis indicated a sympatho-vagal coactivation during ISO. Whether mechanoreceptor feedback alone, a change in central command, or the interaction of both mechanisms is the main contributor of the distinct autonomic responses to the different exercise modes remains to be elucidated.

  17. Post-exercise contractility, diastolic function, and pressure: Operator-independent sensor-based intelligent monitoring for heart failure telemedicine

    PubMed Central

    Bombardini, Tonino; Gemignani, Vincenzo; Bianchini, Elisabetta; Pasanisi, Emilio; Pratali, Lorenza; Pianelli, Mascia; Faita, Francesco; Giannoni, Massimo; Arpesella, Giorgio; Sicari, Rosa; Picano, Eugenio

    2009-01-01

    Background New sensors for intelligent remote monitoring of the heart should be developed. Recently, a cutaneous force-frequency relation recording system has been validated based on heart sound amplitude and timing variations at increasing heart rates. Aim To assess sensor-based post-exercise contractility, diastolic function and pressure in normal and diseased hearts as a model of a wireless telemedicine system. Methods We enrolled 150 patients and 22 controls referred for exercise-stress echocardiography, age 55 ± 18 years. The sensor was attached in the precordial region by an ECG electrode. Stress and recovery contractility were derived by first heart sound amplitude vibration changes; diastolic times were acquired continuously. Systemic pressure changes were quantitatively documented by second heart sound recording. Results Interpretable sensor recordings were obtained in all patients (feasibility = 100%). Post-exercise contractility overshoot (defined as increase > 10% of recovery contractility vs exercise value) was more frequent in patients than controls (27% vs 8%, p < 0.05). At 100 bpm stress heart rate, systolic/diastolic time ratio (normal, < 1) was > 1 in 20 patients and in none of the controls (p < 0.01); at recovery systolic/diastolic ratio was > 1 in only 3 patients (p < 0.01 vs stress). Post-exercise reduced arterial pressure was sensed. Conclusion Post-exercise contractility, diastolic time and pressure changes can be continuously measured by a cutaneous sensor. Heart disease affects not only exercise systolic performance, but also post-exercise recovery, diastolic time intervals and blood pressure changes – in our study, all of these were monitored by a non-invasive wearable sensor. PMID:19442285

  18. Worsening renal function in heart failure: the need for a consensus definition.

    PubMed

    Sheerin, Noella J; Newton, Phillip J; Macdonald, Peter S; Leung, Dominic Y C; Sibbritt, David; Spicer, Stephen Timothy; Johnson, Kay; Krum, Henry; Davidson, Patricia M

    2014-07-01

    Acute decompensated heart failure is a common cause of hospitalisation. This is a period of vulnerability both in altered pathophysiology and also the potential for iatrogenesis due to therapeutic interventions. Renal dysfunction is often associated with heart failure and portends adverse outcomes. Identifying heart failure patients at risk of renal dysfunction is important in preventing progression to chronic kidney disease or worsening renal function, informing adjustment to medication management and potentially preventing adverse events. However, there is no working or consensus definition in international heart failure management guidelines for worsening renal function. In addition, there appears to be no concordance or adaptation of chronic kidney disease guidelines by heart failure guideline development groups for the monitoring of chronic kidney disease in heart failure. Our aim is to encourage the debate for an agreed definition given the prognostic impact of worsening renal function in heart failure. We present the case for the uptake of the Acute Kidney Injury Network criteria for acute kidney injury with some minor alterations. This has the potential to inform study design and meta-analysis thereby building the knowledgebase for guideline development. Definition consensus supports data element, clinical registry and electronic algorithm innovation as instruments for quality improvement and clinical research for better patient outcomes. In addition, we recommend all community managed heart failure patients have their baseline renal function classified and routinely monitored in accordance with established renal guidelines to help identify those at increased risk for worsening renal function or progression to chronic kidney disease.

  19. Heart rate variability as an index of prefrontal neural function in military settings

    NASA Astrophysics Data System (ADS)

    Thayer, Julian F.; Hansen, Anita L.; Sollers, John J., III; Johnsen, Bjorn H.

    2005-05-01

    In the present paper we describe a model of neurovisceral integration in which a set of neural structures involved in cognitive, affective, and autonomic regulation are related to heart rate variability (HRV) and cognitive performance. We will provide pharmacological and neuroimaging data in support of the neural structures linking the central nervous system to HRV. Next, we will review a number of studies from our group using military cadets showing that individual differences in HRV are related to performance on tasks associated with executive function and prefrontal cortical activity. In the first study, individual differences in resting HRV we related to performance on executive and non-executive function tasks. The results showed that greater HRV was associated with better performance on executive function tasks. In the second study we add a stressor (shock avoidance) to the previous paradigm and show that those with greater HRV were more stress tolerant. Specifically, those with greater HRV were not adversely affected by the added stressor. In the last experiment, HRV was manipulated by physical detraining. Again, those that maintained their HRV at the post-test showed better performance on executive function tasks. We propose that these findings have important implications for the development of biomarkers related to performance in modern warfighters.

  20. Loss of the AE3 Cl−/HCO−3 exchanger in mice affects rate-dependent inotropy and stress-related AKT signaling in heart

    PubMed Central

    Prasad, Vikram; Lorenz, John N.; Lasko, Valerie M.; Nieman, Michelle L.; Al Moamen, Nabeel J.; Shull, Gary E.

    2013-01-01

    Cl−/HCO−3 exchangers are expressed abundantly in cardiac muscle, suggesting that HCO−3 extrusion serves an important function in heart. Mice lacking Anion Exchanger Isoform 3 (AE3), a major cardiac Cl−/HCO−3 exchanger, appear healthy, but loss of AE3 causes decompensation in a hypertrophic cardiomyopathy (HCM) model. Using intra-ventricular pressure analysis, in vivo pacing, and molecular studies we identified physiological and biochemical changes caused by loss of AE3 that may contribute to decompensation in HCM. AE3-null mice had normal cardiac contractility under basal conditions and after β-adrenergic stimulation, but pacing of hearts revealed that frequency-dependent inotropy was blunted, suggesting that AE3-mediated HCO−3 extrusion is required for a robust force-frequency response (FFR) during acute biomechanical stress in vivo. Modest changes in expression of proteins that affect Ca2+-handling were observed, but Ca2+-transient analysis of AE3-null myocytes showed normal twitch-amplitude and Ca2+-clearance. Phosphorylation and expression of several proteins implicated in HCM and FFR, including phospholamban (PLN), myosin binding protein C, and troponin I were not altered in hearts of paced AE3-null mice; however, phosphorylation of Akt, which plays a central role in mechanosensory signaling, was significantly higher in paced AE3-null hearts than in wild-type controls and phosphorylation of AMPK, which is affected by Akt and is involved in energy metabolism and some cases of HCM, was reduced. These data show loss of AE3 leads to impaired rate-dependent inotropy, appears to affect mechanical stress-responsive signaling, and reduces activation of AMPK, which may contribute to decompensation in heart failure. PMID:24427143

  1. Static magnetic field influence on rat brain function detected by heart rate monitoring.

    PubMed

    Veliks, Viktors; Ceihnere, Edīte; Svikis, Igors; Aivars, Juris

    2004-04-01

    The aim of the present study was to identify the effects of a static magnetic field (SMF) on rat brain structures that control autonomic functions, specifically heart rate and heart rhythmicity. The experiments were carried out on 44 male Wistar rats under ketamine-xylazine anesthesia. SMF was induced using samarium-cobalt fused magnets (20 x 20 x 10 mm in size) placed bitemporally. Magnetic induction intensity was 100 mT on the surface of the head. Duration of magnetic field application was 15 min. An electrocardiogram was recorded from limb lead II, and both heart rate (average duration of cardiac cycles) and heart rhythmicity were analyzed before and after SMF application. SMF evoked changes in both heart rate and rhythm in 80% of the animals; the predominant effects were bradycardia and disappearance of respiratory sinus arrhythmia. However, the effectiveness of SMF in large measure depends on both functional peculiarities and functional activities of brain autonomic centers.

  2. [Role of myocardial micropump function in the pathogenesis of ischemic heart disease].

    PubMed

    Feketa, V P

    1996-01-01

    Myocardial vibrational activity examined in 40 patients with functional classes II-III coronary heart disease and in 20 apparently healthy individuals, which indirectly reflects the status of its micropump function has been studied by using a spectral analysis of the first heart sound. Inhibition of the micropump function of the myocardium with its higher oxygen demands has been found to substantially contribute to the pathogenesis of myocardial ischemia.

  3. Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

    PubMed

    Ahir, Bhavesh K; Pratten, Margaret K

    2014-01-01

    Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

  4. Still Heart Encodes a Structural HMT, SMYD1b, with Chaperone-Like Function during Fast Muscle Sarcomere Assembly.

    PubMed

    Prill, Kendal; Windsor Reid, Pamela; Wohlgemuth, Serene L; Pilgrim, David B

    2015-01-01

    The vertebrate sarcomere is a complex and highly organized contractile structure whose assembly and function requires the coordination of hundreds of proteins. Proteins require proper folding and incorporation into the sarcomere by assembly factors, and they must also be maintained and replaced due to the constant physical stress of muscle contraction. Zebrafish mutants affecting muscle assembly and maintenance have proven to be an ideal tool for identification and analysis of factors necessary for these processes. The still heart mutant was identified due to motility defects and a nonfunctional heart. The cognate gene for the mutant was shown to be smyd1b and the still heart mutation results in an early nonsense codon. SMYD1 mutants show a lack of heart looping and chamber definition due to a lack of expression of heart morphogenesis factors gata4, gata5 and hand2. On a cellular level, fast muscle fibers in homozygous mutants do not form mature sarcomeres due to the lack of fast muscle myosin incorporation by SMYD1b when sarcomeres are first being assembled (19hpf), supporting SMYD1b as an assembly protein during sarcomere formation.

  5. How Does Maternal Employment Affect Children's Socioemotional Functioning?

    ERIC Educational Resources Information Center

    Lam, Gigi

    2015-01-01

    The maternal employment becomes an irreversible trend across the globe. The effect of maternal employment on children's socioemotional functioning is so pervasive that it warrants special attention to investigate into the issue. A trajectory of analytical framework of how maternal employment affects children's socioemotional functioning originates…

  6. Influence of ethanol extract of Ginkgo biloba leaves on the isolated rat heart work and mitochondria functions.

    PubMed

    Baliutyte, Giedre; Baniene, Rasa; Gendviliene, Vida; Martisiene, Irma; Trumbeckaite, Sonata; Borutaite, Vilmante; Toleikis, Adolfas

    2012-05-01

    In this study, we attempted to elucidate whether the effects of ethanol extract of Ginkgo biloba leaves (GBE) observed previously on isolated rat heart mitochondria may be realized in situ (in case of isolated heart perfused under normal conditions and under ischemia-reperfusion). We found that GBE at low concentrations (0.01, 0.05, and 0.1 μL/mL) does not affect the heart rate and parameters of electrocardiogram (ECG) but produces a small increase in the coronary flow. Higher concentration of GBE (0.2 and 0.3 μL/mL) diminished the heart rate, decreased the coronary flow, and tended to enhance the parameters of ECG. The contractility of isolated rat heart and mitochondrial nicotinamide adenine dinucleotide reduced form fluorescence decreased in a GBE concentration-dependent manner. Mitochondria isolated from hearts pre-perfused with GBE (0.05 μL/mL) for 20 minutes before nonflow global ischemia-reperfusion (45 min/15 min) showed higher respiratory rates with pyruvate + malate in state 2 and state 3, higher respiratory control index, and diminished H₂O₂ generation compared with untreated group. Higher GBE concentration, 0.4 μL/mL, had no effect on H2O2 generation and did not prevent the ischemia-reperfusion-induced decrease of pyruvate + malate oxidation in state 3 but even enhanced it. However, in the case of nonischemic perfusions, this GBE concentration had no significant effect on these parameters of respiratory functions of isolated heart mitochondria.

  7. EFFECT OF PERILLA FRUTESCENS EXTRACTS AND ROSMARINIC ACID ON RAT HEART MITOCHONDRIAL FUNCTIONS.

    PubMed

    Raudone, Lina; Burdulis, Deividas; Raudonis, Raimondas; Janulis, Valdimaras; Jankauskiene, Laima; Viskelis, Pranas; Trumbeckaite, Sonata

    2016-01-01

    Perilla frutescens L. due to its aromatic, antibacterial, anti-inflammatory and antioxidant traits has been traditionally used as medicinal plant in Eastern Asia. Alterations of mitochondria are interconnected with many chronic diseases. Bioactives of herbal extracts can modulate mitochondrial effects and be beneficial in prevention of mitochondrial related chronic diseases. Direct effects of the red-leaf form P. frutescens extract (PFE) and the green-leaf form P. frutescens var. crispa f. viridis extract (PCE) were evaluated investigating activities on the oxidative phosphorylation and antioxidant activity in the rat heart mitochondria in vitro. HPLC-MS analysis was applied for the identification of phenolic compounds. Cell with a Clark-type oxygen electrode was used for mitochondrial respiration measurement. The generation of reactive oxygen species was estimated in isolated rat heart mitochondria and determined fluorimetrically. State 3 respiration rate was not affected by lower concentrations, however, it was inhibited at higher concentrations by 22-70% for PFE and by 45-55% for PCE. PFE containing anthocyanins induced the concentration-dependent stimulation (by 23-76%) of the State 4 respiration rate after addition of cytochrome c due to reducing properties. Significant reduction of H₂O₂ pro- duction was observed with investigated concentrations of rosmarinic acid and both perilla extracts. Our results demonstrate that the effect of PFE and PCE extracts on rat heart mitochondria depend on the qualitative characteristics of complex of biologically active compounds. Selective effects on mitochondrial function could enable the regulation of apoptosis or another mechanisms occurring in cells.

  8. Impact of Obesity on Heart and Lung Transplantation: Does Pre-Transplant Obesity Affect Outcomes?

    PubMed

    Bozso, S J; Nagendran, Je; Gill, R S; Freed, D H; Nagendran, Ja

    2017-03-01

    Increasing prevalence of obesity has led to a rise in the number of prospective obese heart and lung transplant recipients. The optimal management strategy of obese patients with end-stage heart and lung failure remains controversial. This review article discusses and provides a summary of the literature surrounding the impact of obesity on outcomes in heart and lung transplantation. Studies on transplant obesity demonstrate controversy in terms of morbidity and mortality outcomes and obesity pre-transplantation. However, the impact of obesity on outcomes seems to be more consistently demonstrated in lung rather than heart transplantation. The ultimate goal in heart and lung transplantation in the obese patient is to identify those at highest risk of complication that may warrant therapies to mitigate risk by addressing comorbid conditions.

  9. Short-Term Thyroid Hormone Excess Affects the Heart but Does not Affect Adrenal Activity in Rats

    PubMed Central

    Szkudlarek, Ariani Cavazzani; Aldenucci, Bruno; Miyagui, Nelson Itiro; Silva, Ilana Kassouf; Moraes, Rosana Nogueira; Ramos, Helton Estrela; Fogaça, Rosalva Tadeu Hochmuller

    2014-01-01

    Background Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis. Objective Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats. Methods Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5th and 10th days of T3 treatment. Results In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels. Conclusions Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity. PMID:24676225

  10. Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

    PubMed Central

    Khandelwal, Vinoth Kumar Megraj; Balaraman, R.; Pancza, Dezider; Ravingerová, Táňa

    2011-01-01

    Hemidesmus indicus (L.) R. Br. (HI) and Hibiscus rosa-sinensis L. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions. PMID:20953394

  11. Relative contribution of resting haemodynamic profile and lung function to exercise tolerance in male patients with chronic heart failure

    PubMed Central

    Faggiano, P; D'Aloia, A; Gualeni, A; Giordano, A

    2001-01-01

    OBJECTIVE—To clarify the relative contribution of resting haemodynamic profile and pulmonary function to exercise capacity in patients with heart failure.
SETTING—Cardiology department and cardiac rehabilitation unit in a tertiary centre.
DESIGN—161 male patients (mean (SD) age 59 (9) years) with heart failure (New York Heart Association class II-IV, left ventricular ejection fraction 23 (7)%) underwent spirometry, alveolar capillary diffusing capacity (DLCO), and mouth inspiratory and expiratory pressures (MIP, MEP, respectively, in 100 patients). Right heart catheterisation and a symptom limited cardiopulmonary exercise test were performed in 137 patients within 3-4 days.
RESULTS—Mean peak exercise oxygen consumption (V̇O2) was 13 (3.9) ml/kg/min. Among resting haemodynamic variables only cardiac index showed a significant correlation with peak V̇O2. There were no differences in haemodynamic variables between patients with peak V̇O2 ⩽ or > 14 ml/kg/min. There was a moderate correlation (p < 0.05) between several pulmonary function variables and peak V̇O2. Forced vital capacity (3.5 (0.9) v 3.2 (0.8) l, p < 0.05) and DLCO (21.6 (6.9) v 17.7 (5.5) ml/mm Hg/min, p < 0.05) were higher in patients with peak V̇O2 > 14 ml/kg/min than in those with peak V̇O2 ⩽ 14 ml/kg/min. Using a stepwise regression analysis, the respiratory and haemodynamic variables which correlated significantly with peak V̇O2 were DLCO, MEP, and cardiac index, with an overall R value of 0.63.
CONCLUSIONS—The data confirm previous studies showing a poor correlation between resting indices of cardiac function and exercise capacity in heart failure. However, several pulmonary function variables were related to peak exercise V̇O2. In particular, lung diffusing capacity and respiratory muscle function seem to affect exercise tolerance during heart failure.


Keywords: heart failure; exercise; pulmonary function; alveolar-capillary diffusing

  12. [The effectiveness of romifidine on myocardial function in horses with and without heart disease, evaluated with M-mode echocardiography and PW-tissue Doppler imaging].

    PubMed

    Nagel, Deborah; Gehlen, Heidrun

    2013-01-01

    The aim of this study was to evaluate to what extent the myocardial function in horses (measured by PW-tissue Doppler = PW-TDI) is affected during a sedation with romifidine (0.04 mg/kg, i. v.), particularly in case of an accompanying heart disease. Based on an echo- and electrocardiographic examination, a total of 45 horses was subdivided into group 1 (no heart disease), group 2 (heart disease without increased heart dimensions) and group 3 (heart disease with increased heart dimensions). Heart rate (HF), M-mode- (FS%) and TDI-measurements were performed before and after the application of romifidine. The velocities of the radial myocardial movement in the left and right ventricular wall were evaluated using PW-TDI. The TDI parameters included the isovolumic contraction (IVC), the systolic (S) as well as the early (E) and late diastolic maximal velocity (A). After the application of romifidine HF and FS were significantly decreased in all groups. IVC, S and E, determined by PW-TDI were also significantly decreased in both ventricular walls. A significant difference between groups was shown for the isovolumic contraction in the left ventricular wall. This was observed distinctly more in horses with heart disease and increased heart dimensions compared to horses with heart disease but no increased heart dimensions. The results of the study indicate that PW-TDI is a suitable imaging technique to analyse the effects of romifidine on equine myocardial function. The major percentage change after application of romifidine for TDI measurements compared to the M-mode parameters indicate that the parameter myocardial velocity measured with TDI appeared to be the most sensitive parameter to document romifidine--induced changes on the myocardium.

  13. Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure

    PubMed Central

    Park, Bumhee; Roy, Bhaswati; Woo, Mary A.; Palomares, Jose A.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

    2016-01-01

    Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality. PMID:27203600

  14. Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?

    PubMed Central

    Lindenmeyer, M.; Spörri, S.; Stäubli, M.; Studer, A.; Studer, H.

    1984-01-01

    The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3) was investigated. For this purpose we compared the effect of amiodarone with that of another potent inhibitor of the T4----T3 conversion, i.e. the radiographic contrast medium iopanoic acid, on the heart rate of unanaesthetized guinea-pigs. Both amiodarone and, to an even greater extent, iopanoic acid induced an increase in serum 3.5',3' triiodothyronine (reverse T3), indicating effective inhibition of T4----T3 conversion. Both amiodarone and iopanoic acid were accumulated in the liver and in the heart (measured as iodine). While amiodarone induced bradycardia, iopanoic acid did not change the heart rate. Supraphysiological amounts of exogenous T3 reverted the amiodarone induced bradycardia to near normal values. A comparable effect was observed with isoprenaline. The intracellular inhibition of the T4----T3 conversion is not the ultimate mode of the action of the amiodarone effect on heart rate. It is thought that amiodarone interacts with T3 at its receptor or somewhere later along the pathway from the T3-receptor interaction to the final effect of T3 on heart rate. PMID:6733357

  15. Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

    PubMed Central

    Cools, Roshan; Nakamura, Kae; Daw, Nathaniel D

    2011-01-01

    Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin—comprising both affective and activational ones, as well as a number of other functions not overtly related to either—can be seen as consequences of a single root mechanism. PMID:20736991

  16. Longitudinal renal function in pediatric heart transplant recipients: 20-years experience.

    PubMed

    Gupta, Punkaj; Rettiganti, Mallikarjuna; Gossett, Jeffrey M; Gardner, Megan; Bryant, Janet C; Noel, Tommy R; Knecht, Kenneth R

    2015-03-01

    This study was initiated to assess the temporal trends of renal function, and define risk factors associated with worsening renal function in pediatric heart transplant recipients in the immediate post-operative period. We performed a single-center retrospective study in children ≤18 yr receiving OHT (1993-2012). The AKIN's validated, three-tiered AKI staging system was used to categorize the degree of WRF. One hundred sixty-four patients qualified for inclusion. Forty-seven patients (28%) were classified as having WRF after OHT. Nineteen patients (11%) required dialysis after heart transplantation. There was a sustained and steady improvement in renal function in children following heart transplantation in all age groups, irrespective of underlying disease process. The significant factors associated with risk of WRF included body surface area (OR: 1.89 for 0.5 unit increase, 95% CI: 1.29-2.76, p = 0.001) and use of ECMO prior to and/or after heart transplantation (OR: 3.50, 95% CI: 1.51-8.13, p = 0.004). Use of VAD prior to heart transplantation was not associated with WRF (OR: 0.50, 95% CI: 0.17-1.51, p = 0.22). On the basis of these data, we demonstrate that worsening renal function improves early after orthotopic heart transplantation.

  17. Toad heart utilizes exclusively slow skeletal muscle troponin T: an evolutionary adaptation with potential functional benefits.

    PubMed

    Feng, Han-Zhong; Chen, Xuequn; Hossain, M Moazzem; Jin, Jian-Ping

    2012-08-24

    The three isoforms of vertebrate troponin T (TnT) are normally expressed in a muscle type-specific manner. Here we report an exception that the cardiac muscle of toad (Bufo) expresses exclusively slow skeletal muscle TnT (ssTnT) together with cardiac forms of troponin I and myosin as determined using immunoblotting, cDNA cloning, and/or LC-MS/MS. Using RT-PCR and 3'- and 5'-rapid amplification of cDNA ends on toad cardiac mRNA, we cloned full-length cDNAs encoding two alternatively spliced variants of ssTnT. Expression of the cloned cDNAs in Escherichia coli confirmed that the toad cardiac muscle expresses solely ssTnT, predominantly the low molecular weight variant with the exon 5-encoded NH(2)-terminal segment spliced out. Functional studies were performed in ex vivo working toad hearts and compared with the frog (Rana) hearts. The results showed that toad hearts had higher contractile and relaxation velocities and were able to work against a significantly higher afterload than that of frog hearts. Therefore, the unique evolutionary adaptation of utilizing exclusively ssTnT in toad cardiac muscle corresponded to a fitness value from improving systolic function of the heart. The data demonstrated a physiological importance of the functional diversity of TnT isoforms. The structure-function relationship of TnT may be explored for the development of new treatment of heart failure.

  18. Somatic and cognitive-affective depressive symptoms among patients with heart disease: differences by sex and age

    PubMed Central

    Dessotte, Carina Aparecida Marosti; Silva, Fernanda Souza; Furuya, Rejane Kiyomi; Ciol, Marcia Aparecida; Hoffman, Jeanne Marie; Dantas, Rosana Aparecida Spadoti

    2015-01-01

    OBJECTIVE: this study investigated the association of somatic and cognitive-affective symptoms with sex and age, among patients hospitalized with heart disease. METHOD: this study was a secondary analysis of two previous observational studies totaling 531 patients with heart disease, hospitalized from 2005 to 2011 in two public hospitals in Ribeirão Preto, state of São Paulo, Brazil. Somatic and cognitive-affective symptoms were assessed using the subscales of the Beck Depression Inventory - I (BDI-I). RESULTS: of 531 participants, 62.7% were male, with a mean age 57.3 years (SD= 13.0) for males and 56.2 years (SD= 12.1) for females. Analyses of variance showed an effect of sex (p<0.001 for somatic and p=0.005 for cognitive-affective symptoms), but no effect of age. Women presented with higher mean values than men in both BDI-I subscales: 7.1 (4.5) vs. 5.4 (4.3) for somatic, and 8.3 (7.9) vs. 6.7 (7.2) for cognitive-affective symptoms. There were no differences by age for somatic (p=0.84) or cognitive-affective symptoms (p=0.84). CONCLUSION: women hospitalized with heart disease had more somatic and cognitive-affective symptoms than men. We found no association of somatic and cognitive-affective symptoms with age. Future research for these patients could reveal whether these differences according to sex continue throughout the rehabilitation process. PMID:26039290

  19. Hand2 Function in Second Heart Field Progenitors is Essential for Cardiogenesis

    PubMed Central

    Tsuchihashi, Takatoshi; Maeda, Jun; Shin, Chong; Ivey, Kathryn N.; Black, Brian; Olson, Eric N.; Yamagishi, Hiroyuki; Srivastava, Deepak

    2011-01-01

    Cardiogenesis involves the contributions of multiple progenitor pools, including mesoderm-derived cardiac progenitors known as the first and second heart fields. Disruption of genetic pathways regulating individual subsets of cardiac progenitors likely underlies many forms of human cardiac malformations. Hand2 is a member of the basic helix loop helix (bHLH) family of transcription factors and is expressed in numerous cell lineages that contribute to the developing heart. However, the early embryonic lethality of Hand2-null mice has precluded lineage-specific study of its function in myocardial progenitors. Here, we generated and used a floxed allele of Hand2 to ablate its expression in specific cardiac cell populations at defined developmental points. We found that Hand2 expression within the mesoderm-derived second heart field progenitors was required for their survival and deletion in this domain recapitulated the complete Hand2-null phenotype. Loss of Hand2 at later stages of development and in restricted domains of the second heart field revealed a spectrum of cardiac anomalies resembling forms of human congenital heart disease. Molecular analyses of Hand2 mutant cells revealed several genes by which Hand2 may influence expansion of the cardiac progenitors. These findings demonstrate that Hand2 is essential for survival of second heart field progenitors and that the graded loss of Hand2 function in this cardiac progenitor pool can cause a spectrum of congenital heart malformation. PMID:21185281

  20. Pharmacologic strategies to preserve renal function in acute decompensated heart failure.

    PubMed

    Kumar, Sachin; Taylor, David O

    2015-02-01

    Over a million patients get hospitalized with the diagnosis of acute decompensated heart failure which poses an insurmountable financial burden on the health care system. Heart failure alone incurs over 30 billion dollars with half the cost spent towards acute hospitalizations. Majority of the treatment strategies have focused towards decongesting patients which often comes with the cost of worsening renal function. Renal dysfunction in the setting of acute decompensated heart failure portends worse morbidity and mortality. Recently, there has been a change in the focus with shift towards therapies attempting to conserve renal function. In the past decade, we have witnessed several large randomized controlled trials testing the established as well as emerging therapies in this subset of population with mixed results. This review intends to provide a comprehensive overview of the pharmacologic therapies commonly utilized in the management of acute decompensated heart failure and the body of evidence supporting these strategies.

  1. Affective and physiological sexual response patterns: the effects of instructions on sexually functional and dysfunctional men.

    PubMed

    Heiman, J R; Rowland, D L

    1983-01-01

    To more clearly characterize the patterns of cognitive-affective and physiological responses concomitant with male sexual dysfunction, the present study compared 14 sexually dysfunctional and 16 sexually functional men. All individuals listened to two sexually explicit tapes and engaged in a self-generated fantasy, while genital, heart rate and scaled cognitive affective responses were recorded. Two types of instructions, a performance demand set and a non-demand sensate focus set, preceded the erotic tapes in counterbalanced order. As predicted, dysfunctional men showed less genital tumescence to tapes preceded by the demand than the non-demand instructions. Contrary to expectation, functional men showed greater penile tumescence to the tapes preceded by demand instructions. Self-reported sexual arousal did not follow the penile tumescence pattern but instead indicated that the dysfunctional sample was significantly less subjectively aroused to the tapes and fantasy. There were other significant differences between the groups. Dysfunctional men showed greater general psychological distress, as measured by the SCL-90, including elevated somaticism, anxiety and depression scores. During the experimental session, dysfunctional men also evidenced greater awareness of a variety of physiological responses, as well as more negative and fewer positive cognitive-affective states. These data are discussed in terms of the interaction of affective and physiological responses, differences in contextual meanings of instructional sets given the presence of a dysfunction, and theoretical and clinical conceptualizations of male sexual functioning.

  2. Temporal cohesion of the structural, functional and molecular characteristics of the developing zebrafish heart.

    PubMed

    Matrone, Gianfranco; Wilson, Kathryn S; Mullins, John J; Tucker, Carl S; Denvir, Martin A

    2015-06-01

    Heart formation is a complex, dynamic and highly coordinated process of molecular, morphogenetic and functional factors with each interacting and contributing to formation of the mature organ. Cardiac abnormalities in early life can be lethal in mammals but not in the zebrafish embryo which has been widely used to study the developing heart. While early cardiac development in the zebrafish has been well characterized, functional changes during development and how these relate to architectural, cellular and molecular aspects of development have not been well described previously. To address this we have carefully characterised cardiac structure, function, cardiomyocyte proliferation and cardiac-specific gene expression between 48 and 120 hpf in the zebrafish. We show that the zebrafish heart increases in volume and changes shape significantly between 48 and 72 hpf accompanied by a 40% increase in cardiomyocyte number. Between 96 and 120 hpf, while external heart expansion slows, there is rapid formation of a mature and extensive trabecular network within the ventricle chamber. While ejection fraction does not change during the course of development other determinants of contractile function increase significantly particularly between 72 and 96 hpf leading to an increase in cardinal vein blood flow. This study has revealed a number of novel aspects of cardiac developmental dynamics with striking temporal orchestration of structure and function within the first few days of development. These changes are associated with changes in expression of developmental and maturational genes. This study provides important insights into the complex temporal relationship between structure and function of the developing zebrafish heart.

  3. SERCA1a can functionally substitute for SERCA2a in the heart.

    PubMed

    Ji, Y; Loukianov, E; Loukianova, T; Jones, L R; Periasamy, M

    1999-01-01

    We recently generated a transgenic (TG) mouse model in which the fast-twitch skeletal muscle sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA1a) is overexpressed in the heart. Ectopic overexpression of SERCA1a results in remodeling of the cardiac SR containing 80% SERCA1a and 20% endogenous SERCA2a with an approximately 2.5-fold increase in the total amount of SERCA protein (E. Loukianov et al. Circ. Res. 83: 889-897, 1998). We have analyzed the Ca2+ transport properties of membranes from SERCA1a TG hearts in comparison to control hearts. Our data show that the maximal velocity of SR Ca2+ transport was significantly increased ( approximately 1.9-fold) in TG hearts, whereas the apparent affinity of the SERCA pump for Ca2+ was not changed. Addition of phospholamban antibody in the Ca2+ uptake assays increased the apparent affinity for Ca2+ to the same extent in TG and non-TG (NTG) hearts, suggesting that phospholamban regulates the SERCA1a pump in TG hearts. Analysis of SERCA enzymatic properties in TG hearts revealed that the SERCA pump affinity for ATP, the Hill coefficient, the pH dependence of Ca2+ uptake, and the effect of acidic pH on Ca2+ transport were similar to those of NTG hearts. Interestingly, the rate constant of phosphoenzyme decay (turnover rate of SERCA enzyme) was also very similar between TG and NTG hearts. Together these findings suggest that 1) the SERCA1a pump can functionally substitute for SERCA2a and is regulated by endogenous phospholamban in the heart and 2) SERCA1a exhibits several enzymatic properties similar to those of SERCA2a when expressed in a cardiac setting.

  4. Does caregiving stress affect cognitive function in older women?

    PubMed

    Lee, Sunmin; Kawachi, Ichiro; Grodstein, Francine

    2004-01-01

    Increasing numbers of women provide care to their ill spouses; however, no studies have examined possible effects of caregiving stress on cognitive function. We administered 6 tests of cognitive function to 13740 Nurses' Health Study participants aged 70-79 years. We collected information on caregiving and numerous potential confounding variables via biennial mailed questionnaires. After adjustment for potential confounders (age, education, mental health index, vitality index, use of antidepressants, and history of high blood pressure, diabetes, and heart disease), we found modest but significantly increased risks of low cognitive function on three of the cognitive tests among women who provided care to a disabled or ill spouse compared with women who did not provide any care. For example, on the TICS, a test of general cognition, the risk of a low score was 31% higher in women who provided care compared with women who did not (RR = 1.31, 95% CI 1.10, 1.56). We found a moderately increased risk of poor performance on several cognitive tests among women who provided care to their disabled or ill husbands.

  5. Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

    PubMed

    Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret

    2014-04-01

    Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with

  6. How national policy affects the care of patients who suffer a heart attack.

    PubMed

    Green, Meryl

    In October 2008 the Department of Health published the National Infarct Angioplasty Project (NIAP), reviewing its guidance on the treatment of a heart attack. This was framed to update previous 2000 guidance from the National Service Framework for coronary heart disease, and highlighted the need for specialised services and 24-hour care. Recommendations included the need for appropriate assessment/investigation and immediate transfer to a cardiac catheterisation laboratory for primary angioplasty within 120 minutes of calling for professional help. Cardiac services are currently undergoing review, and a significant number of new cardiac catheterisation laboratories are being established throughout the country to accommodate the needs of this client group. This article discusses whether 24-hour care is feasible, cost-effective and realistic for the NHS to manage, as well as analysing policy guidelines in relation to the treatment of heart attack.

  7. Does uninsurance affect the health outcomes of the insured? Evidence from heart attack patients in California.

    PubMed

    Daysal, N Meltem

    2012-07-01

    In this paper, I examine the impact of uninsured patients on the in-hospital mortality rate of insured heart attack patients. I employ panel data models using patient discharge and hospital financial data from California (1999-2006). My results indicate that uninsured patients have an economically significant effect that increases the mortality rate of insured heart attack patients. I show that these results are not driven by alternative explanations, including reverse causality, patient composition effects, sample selection or unobserved trends and that they are robust to a host of specification checks. The primary channel for the observed spillover effects is increased hospital uncompensated care costs. Although data limitations constrain my capacity to check how hospitals change their provision of care to insured heart attack patients in response to reduced revenues, the evidence I have suggests a modest increase in the quantity of cardiac services without a corresponding increase in hospital staff.

  8. Functional and structural regeneration in the axolotl heart (Ambystoma mexicanum) after partial ventricular amputation.

    PubMed

    Cano-Martínez, Agustina; Vargas-González, Alvaro; Guarner-Lans, Verónica; Prado-Zayago, Esteban; León-Oleda, Martha; Nieto-Lima, Betzabé

    2010-01-01

    "In the present study we evaluated the effect of partial ventricular amputation (PVA) in the heart of the adult urodele amphibian (Ambystoma mexicanum) in vivo on spontaneous heart contractile activity recorded in vitro in association to the structural recovery at one, five, 30 and 90 days after injury. One day after PVA, ventricular-tension (VT) (16 ± 3%), atrium-tension (AT) (46 ± 4%) and heart rate (HR) (58+10%) resulted lower in comparison to control hearts. On days five, 30 and 90 after damage, values achieved a 61 ± 5, 93 ± 3, and 98 ± 5% (VT), 60 ± 4, 96 ± 3 and 99 ± 5% (AT) and 74 ± 5, 84 ± 10 and 95 ± 10% (HR) of the control values, respectively. Associated to contractile activity recovery we corroborated a gradual tissue restoration by cardiomyocyte proliferation. Our results represent the first quantitative evidence about the recovery of heart of A. mexicanum restores its functional capacity concomitantly to the structural recovery of the myocardium by proliferation of cardiomyocytes after PVA. These properties make the heart of A. mexicanum a potential model to study the mechanisms underlying heart regeneration in adult vertebrates in vivo.

  9. Impaired dynamics and function of mitochondria caused by mtDNA toxicity leads to heart failure.

    PubMed

    Lauritzen, Knut H; Kleppa, Liv; Aronsen, Jan Magnus; Eide, Lars; Carlsen, Harald; Haugen, Øyvind P; Sjaastad, Ivar; Klungland, Arne; Rasmussen, Lene Juel; Attramadal, Håvard; Storm-Mathisen, Jon; Bergersen, Linda H

    2015-08-01

    Cardiac mitochondrial dysfunction has been implicated in heart failure of diverse etiologies. Generalized mitochondrial disease also leads to cardiomyopathy with various clinical manifestations. Impaired mitochondrial homeostasis may over time, such as in the aging heart, lead to cardiac dysfunction. Mitochondrial DNA (mtDNA), close to the electron transport chain and unprotected by histones, may be a primary pathogenetic site, but this is not known. Here, we test the hypothesis that cumulative damage of cardiomyocyte mtDNA leads to cardiomyopathy and heart failure. Transgenic mice with Tet-on inducible, cardiomyocyte-specific expression of a mutant uracil-DNA glycosylase 1 (mutUNG1) were generated. The mutUNG1 is known to remove thymine in addition to uracil from the mitochondrial genome, generating apyrimidinic sites, which obstruct mtDNA function. Following induction of mutUNG1 in cardiac myocytes by administering doxycycline, the mice developed hypertrophic cardiomyopathy, leading to congestive heart failure and premature death after ∼2 mo. The heart showed reduced mtDNA replication, severely diminished mtDNA transcription, and suppressed mitochondrial respiration with increased Pgc-1α, mitochondrial mass, and antioxidative defense enzymes, and finally failing mitochondrial fission/fusion dynamics and deteriorating myocardial contractility as the mechanism of heart failure. The approach provides a model with induced cardiac-restricted mtDNA damage for investigation of mtDNA-based heart disease.

  10. Nuclear medical determination of left ventricular diastolic function in coronary heart disease

    SciTech Connect

    Brugger, P.; Laesser, W.K.; Kullich, W.; Stoiberer, I.; Klein, G.

    1985-06-01

    In 64 patients with coronary heart disease, the left ventricular diastolic function was determined by means of a new nuclear medical method (nuclear stethoscope). The investigations revealed an abnormal diastolic filling in 85.9% of the cases on the basis of the parameters peak filling rate and time to peak filling rate as manifestation of a disturbed ventricular function.

  11. Heart rate variability and autonomic function tests in HIV positive individuals in India.

    PubMed

    Sakhuja, Ankit; Goyal, Ankur; Jaryal, Ashok Kumar; Wig, Naveet; Vajpayee, Madhu; Kumar, Ajay; Deepak, Kishore Kumar

    2007-06-01

    Supine heart rate variability (HRV) and autonomic tests were carried to determine whether autonomic activity was affected in HIV positive patients. The pressor response following handgrip and cold pressor test was blunted in HIV+ patients, and the degree of dysfunction correlated with CD4 cell counts. The extent of autonomic impairment was mild and subclinical.

  12. Analysis of right ventricular function during bypass of the left side of the heart by afterload alterations in both normal and failing hearts.

    PubMed

    Park, C H; Nishimura, K; Kitano, M; Matsuda, K; Okamoto, Y; Ban, T

    1996-05-01

    This study investigated the mechanism of right ventricular failure during bypass of the left side of the heart by precisely assessing right ventricular function with use of a conductance catheter. Bypass of the left side of the heart was established with a centrifugal pump in 10 mongrel dogs weighing 11 to 19 kg. Right ventricular function during left heart bypass was evaluated by two parameters that were both derived from measurement of relative change in right ventricular volume by the conductance catheter technique. One parameter was the right ventricular end-systolic pressure-volume relationship as a load-independent index, and the other was the peak right ventricular pressure-right ventricular stroke volume relationship as a "force-velocity relationship." These parameters were measured in both normal and failing hearts while afterload was increased by bilateral intrapulmonary balloon inflation. Moreover, changes in these relationships were observed by varying assist ratios of left heart bypass from 0% to 100%. Failing heart models were induced by normothermic aortic clamping for 20 minutes. The right ventricular end-systolic pressure-volume relationship in normal hearts did not change, irrespective of the assist ratio of left heart bypass, whereas that in failing hearts decreased from 4.25 +/- 1.41 mm Hg/ml without bypass of the left side of the heart to 3.53 +/- 1.30 mm Hg/ml after 100% assist of left heart bypass (p < 0.05). In the peak right ventricular pressure-right ventricular stroke volume relationship, right ventricular stroke volume was almost constant in normal hearts when afterload was increased regardless of the assist ratio of left heart bypass. Moreover, right ventricular stroke volume was maintained at a higher level during bypass of the left side of the heart compared with that without left heart bypass. However, that slope of the relationship in failing hearts was inversely linear and became significantly steeper after 100% assist of bypass of

  13. Does visual fatigue from 3D displays affect autonomic regulation and heart rhythm?

    PubMed

    Park, S; Won, M J; Mun, S; Lee, E C; Whang, M

    2014-02-15

    Most investigations into the negative effects of viewing stereoscopic 3D content on human health have addressed 3D visual fatigue and visually induced motion sickness (VIMS). Very few, however, have looked into changes in autonomic balance and heart rhythm, which are homeostatic factors that ought to be taken into consideration when assessing the overall impact of 3D video viewing on human health. In this study, 30 participants were randomly assigned to two groups: one group watching a 2D video, (2D-group) and the other watching a 3D video (3D-group). The subjects in the 3D-group showed significantly increased heart rates (HR), indicating arousal, and an increased VLF/HF (Very Low Frequency/High Frequency) ratio (a measure of autonomic balance), compared to those in the 2D-group, indicating that autonomic balance was not stable in the 3D-group. Additionally, a more disordered heart rhythm pattern and increasing heart rate (as determined by the R-peak to R-peak (RR) interval) was observed among subjects in the 3D-group compared to subjects in the 2D-group, further indicating that 3D viewing induces lasting activation of the sympathetic nervous system and interrupts autonomic balance.

  14. The Use of Heart Rate Variability as a Novel Method to Differentiate between Affective States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The major goal of animal welfare scientists is to determine when animals are experiencing a state of good welfare or poor welfare. The goal of this research was to determine if measures of heart rate variability can be used to differentiate whether animals are experiencing ‘unpleasant’ versus ‘pleas...

  15. Psychosocial problems of donor heart recipients adversely affecting quality of life.

    PubMed

    Bunzel, B; Wollenek, G; Grundböck, A

    1992-10-01

    Heart transplantation has become an accepted therapy for patients suffering from terminal heart disease for whom neither standard forms of medication nor the usual surgery are of any benefit. Although results regarding postoperative quantity and quality of life are encouraging, it must not be overlooked that the patient and his family face, and have to overcome, profound psychosocial problems. The main stressors were identified in interviews with 47 heart transplant patients. The main preoperative problems were: the way of being informed about the diagnosis, the waiting period for transplantation, anguishing doubts about the decision to have a transplant, being a body without heart ('zombie'), guilt and shame regarding the donor, the reactions of others. Postoperatively the patients have to cope with: re-entering social systems, reactions of friends, neighbours and colleagues, rejection episodes, death of a fellow patient, the need to redesign family life. All the problems reported by the patients interviewed are discussed regarding their psychosocial implications, and hints are given on how to minimize them.

  16. Left Atrial Function Predicts Heart Failure Hospitalization in Subjects with Preserved Ejection Fraction and Coronary Heart Disease: Longitudinal Data from the Heart and Soul Study

    PubMed Central

    Welles, Christine C.; Ku, Ivy A.; Kwan, Damon M.; Whooley, Mary A.; Schiller, Nelson B.; Turakhia, Mintu P.

    2012-01-01

    Objectives We sought to determine whether left atrial (LA) dysfunction predicts heart failure (HF) hospitalization in subjects with preserved baseline ejection fraction (EF). Background Among patients with preserved EF, factors leading to HF are not fully understood. Cross-sectional studies have demonstrated LA dysfunction at the time of HF, but longitudinal data on antecedent atrial function are lacking. Methods We performed resting transthoracic echocardiography in 855 subjects with coronary heart disease and EF≥50%. Left atrial functional index (LAFI) was calculated as [(LA emptying fraction × left ventricular outflow tract-velocity time integral)/(indexed LA end systolic volume)], where LA emptying fraction was defined as (LA end systolic volume - LA end diastolic volume)/LA end systolic volume. We used Cox models to evaluate the association between LAFI and HF hospitalization. Results Over a median follow-up of 7.9 years, 106 participants (12.4%) were hospitalized for HF. Rates of HF hospitalization were inversely proportional to quartile of LAFI: Q1: 47 per 1000 person-years; Q2: 18.3; Q3: 9.6; and Q4: 5.3 (p<0.001). Each standard deviation decrease in LAFI was associated with a 2.6-fold increased hazard of adverse cardiovascular outcomes (unadjusted HR: 2.6, 95% CI 2.1–3.3, p<0.001), and the association persisted even after adjustment for clinical risk factors, NT-proBNP, and a wide range of echocardiographic parameters (adjusted HR: 1.5, 95% CI 1.0–2.1, p=0.05). Conclusions LA dysfunction independently predicts HF hospitalization in subjects with coronary heart disease and preserved baseline EF. LAFI may be useful for HF risk stratification, and LA dysfunction may be a potential therapeutic target. PMID:22322084

  17. [Functional reserves of the heart under conditions of alimentary magnesium deficit].

    PubMed

    Spasov, A A; Kharitonova, M V; Iezhitsa, I N; Zheltova, A A; Tiurenkov, I N; Gurova, N A

    2012-01-01

    Aim of the study was to assess functional reserves of myocardium in animals with deficit of magnesium during stress tests. Magnesium deficit was modeled by 10 week long magnesium deficient diet. After 54% lowering of magnesium level in erythrocytes we registered left ventricular pressure, myocardial contraction and relaxation rates, heart rate, systolic and diastolic arterial pressure, intensity of structures functioning. Than we subjected hearts of these animals to volume load, graded stimulation of cardiac adrenoreceptors, maximal isometric load by clamping ascending aorta. In animals with magnesium deficit we noted smaller increases of left ventricular pressure, myocardial contraction and relaxation rates under conditions of all functional tests, and of systolic arterial pressure during loading with volume and adrenaline. Lowering of myocardial reactivity under conditions of volume and adrenaline loading as well as isometric work load could constitute a basis of genesis of heart failure in magnesium deficit.

  18. [Structural and functional changes in the of heart of high-performance (canoeing) athletes].

    PubMed

    Galván, O; Cherebetiu, G; Meléndez, H; Casanova, J M; Huerta, D; Guadalajara, J F

    1999-01-01

    We studied two groups of healthy subjects: Group I was integrated by 13 high-performance sportsmen (10 men and 3 women), devoted to the discipline of the rowing. Group II was integrated by 16 sedentary healthy subjects. All of them were studied with a two-dimensional echocardiogram, in order to study the anatomical and functional characteristics of the heart. Both groups had similar characteristics in regard of total body area, heart rate and blood pressure, the only difference was in age. The ventricular mass and the diastolic volume were greater in athletes in spite of the fact that the dimensions and transverse thicknesses were similar, this imply a longitudinal increase of the heart size. It is possible that this form of ventricular remodeling has functional advantages. On the other hand, it was demonstrated the existence of physiological hypertrophy without disorders in diastolic function.

  19. Classroom Has a Heart: Teachers and Students Affective Alignment in a Persian Heritage Language Classroom

    ERIC Educational Resources Information Center

    Atoofi, Saeid

    2013-01-01

    This research study investigated how the teachers and students at a Persian heritage language class acknowledged and modified their affective behavior based on the affective feedback they received from one another. The notion that interactants can modify their affective output in such fashion is referred in the literature as affective alignment…

  20. Heterogeneity and Function of KATP Channels in Canine Hearts

    PubMed Central

    Zhang, Hai Xia; Silva, Jonathan R.; Lin, Yu-Wen; Verbsky, John W.; Lee, Urvi S.; Kanter, Evelyn M.; Yamada, Kathryn A.; Schuessler, Richard B.; Nichols, Colin G.

    2013-01-01

    Background The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (KATP) channels is challenged by recent reports that SUR1 is predominant in mouse atrial KATP channels. Objective To assess SUR subunit composition of KATP channels and consequence of KATP activation for action potential duration (APD) in dog heart. Methods Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate KATP channel properties. Dynamic current-clamp, by injection of a linear K+ conductance to simulate activation of the native current, was employed to study consequences of KATP activation on APD. Results Metabolic inhibitor (MI)-activated current was not significantly different from pinacidil (SUR2A-specific)-activated current, and both currents were larger than diazoxide (SUR1- specific)-activated current, in both atrium and ventricle. Mean KATP conductance (activated by MI) did not differ significantly between chambers although, within the ventricle, both MI-induced and pinacidil-induced currents tended to decrease from epicardium to endocardium. Dynamic current-clamp results indicate that myocytes with longer baseline APDs are more susceptible to injected “KATP” current, a result reproduced in silico using a canine AP model to simulate Epi and Endo (HRd). Conclusions Even a small fraction of KATP activation significantly shortens APD in a manner that depends on existing heterogeneity in KATP current and APD. PMID:23871704

  1. Lexical and Affective Prosody in Children with High Functioning Autism

    PubMed Central

    Grossman, Ruth B.; Bemis, Rhyannon H.; Skwerer, Daniela Plesa; Tager-Flusberg, Helen

    2012-01-01

    Purpose We investigated perception and production of lexical stress and processing of affective prosody in adolescents with high functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody, but atypical lexical prosody production. Method 16 children with HFA and 15 typically developing (TD) peers participated in three experiments: 1. Perception of affective prosody, 2. Lexical stress perception, 3. Lexical stress production. In Experiment 1, participants labeled sad, happy, and neutral spoken sentences that were low-pass filtered, to eliminate verbal content. In Experiment 2 participants disambiguated word meanings based on lexical stress (HOTdog, vs. hotDOG). In Experiment 3 participants produced these words in a sentence completion task. Productions were analyzed using acoustic measures. Results Accuracy levels showed no group differences. Participants with HFA could determine affect from filtered sentences and disambiguate words based on lexical stress. They produced appropriately differentiated lexical stress patterns but demonstrated atypically long productions indicating reduced ability in natural prosody production. Conclusions Children with HFA were as capable as their TD peers in receptive tasks of lexical stress and affective prosody. Prosody productions were atypically long, despite accurate differentiation of lexical stress patterns. Future research should use larger samples and spontaneous vs. elicited productions. PMID:20530388

  2. 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.

  3. Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

    PubMed

    Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

    2016-12-01

    Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD.

  4. Effect of Ivabradine on Endothelial Function in Diastolic and Right Heart Failure Patients

    PubMed Central

    Orea-Tejeda, Arturo; Balderas-Muñoz, Karla; Castillo-Martínez, Lilia; Infante-Vázquez, Oscar; Martínez Memije, Raúl; Keirns-Davis, Candace; Dorantes-García, Joel; Narváez-David, René; Vázquez-Ortíz, Zuilma

    2013-01-01

    Background. Ivabradine is an If ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility. Photoplethysmography is a simple, low-cost optical technique that can evaluate vascular function and detect changes in blood flow, pulse, and swelling of tissular microvascular space. Objective. To evaluate the effect of ivabradine on endothelial function by photoplethysmography in diastolic and right heart failure patients. Methodology. 15 patients were included (mean age of 78.1 ± 9.2 years) with optimally treated diastolic and right heart failure. They underwent photoplethysmography before and after induced ischemia to evaluate the wave blood flow on the finger, using the maximum amplitude time/total time (MAT/TT) index. Two measurements were made before and after oral Ivabradine (mean 12.5 mg a day during 6 months of followup). Results. In the study group, the MAT/TT index was 29.1 ± 2.2 versus 24.3 ± 3.2 (P = 0.05) in basal recording and 30.4 ± 2.1 versus 23.3 ± 2.9 (P = 0.002), before versus after ischemia and before versus after Ivabradine intervention, respectively. Conclusions. Ivabradine administration improves endothelial function (shear stress) in diastolic and right heart failure patients. PMID:24222884

  5. Effect of ivabradine on endothelial function in diastolic and right heart failure patients.

    PubMed

    Orea-Tejeda, Arturo; Balderas-Muñoz, Karla; Castillo-Martínez, Lilia; Infante-Vázquez, Oscar; Martínez Memije, Raúl; Keirns-Davis, Candace; Dorantes-García, Joel; Narváez-David, René; Vázquez-Ortíz, Zuilma

    2013-01-01

    Background. Ivabradine is an If ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility. Photoplethysmography is a simple, low-cost optical technique that can evaluate vascular function and detect changes in blood flow, pulse, and swelling of tissular microvascular space. Objective. To evaluate the effect of ivabradine on endothelial function by photoplethysmography in diastolic and right heart failure patients. Methodology. 15 patients were included (mean age of 78.1 ± 9.2 years) with optimally treated diastolic and right heart failure. They underwent photoplethysmography before and after induced ischemia to evaluate the wave blood flow on the finger, using the maximum amplitude time/total time (MAT/TT) index. Two measurements were made before and after oral Ivabradine (mean 12.5 mg a day during 6 months of followup). Results. In the study group, the MAT/TT index was 29.1 ± 2.2 versus 24.3 ± 3.2 (P = 0.05) in basal recording and 30.4 ± 2.1 versus 23.3 ± 2.9 (P = 0.002), before versus after ischemia and before versus after Ivabradine intervention, respectively. Conclusions. Ivabradine administration improves endothelial function (shear stress) in diastolic and right heart failure patients.

  6. Monocyte chemo attractant protein-1 in patients with chronic heart failure of different functional class with type 2 diabetes.

    PubMed

    Kravchun, P; Narizhna, A; Ryndina, N

    2014-06-01

    The aim of the study was to assess the dynamics of monocyte chemoattractant protein-1 in patients with chronic heart failure of different functional classes depending on the presence or absence of concomitant type 2 diabetes. 95 patients with chronic heart failure II - III FC were examined due to coronary heart disease who were treated at the cardiological department of the Kharkiv City Clinical Hospital № 27 (mean age 65,13±8,66 years). The first group included 52 patients with CHF with type 2 diabetes, the second - 43 CHF patients without type 2 diabetes. Research was excluded patients with acute coronary syndrome, acute myocardial infarction. 71 patients of patients had II NYHA FC, 24 patients - III FC. Among the patients of first group 40 patients were diagnosed in CHF FC II, 12 - III FC. In II group 31 patients were with CHF class II, 12 patients - with III FC. Concentration of proinflammatory cytokine interleukin-1β and fibrosis factor monocyte chemoattractant protein-1 were determined by ELISA (enzyme-linked immunosorbent assay). In patients with chronic heart failure in presence or absence of type 2 diabetes increase in the profibrotic parameter monocyte chemoattractant protein-1 and proinflammatory cytokine interleukin-1β were increasing in parallel with NYHA FC increasing. Presence of type 2 diabetes negatively affects the work of cytokines and markers of fibrosis, as evidenced by higher levels of interleukin-1β and monocyte chemoattractant protein-1, compared with patients without diabetes in the presence of the same NYHA FC of chronic heart failure.

  7. Changes in extracellular muscle volume affect heart rate and blood pressure responses to static exercise

    NASA Astrophysics Data System (ADS)

    Baum, K.; Essfeld, D.; Stegemann, J.

    To investigate the effect of μg-induced peripheral extracellular fluid reductions on heart rate and blood pressure during isometric exercise, six healthy male subjects performed three calf ergometer test with different extracellular volumes of working muscles. In all tests, body positions during exercise were identical (supine with the knee joint flexed to 900). After a pre-exercise period of 25 min, during which calf volumes were manipulated, subjects had to counteract an external force of 180 N for 5 min. During the pre-exercise period three different protocols were applied. Test A: Subjects rested in the exercise position; test B: Body position was the same as in A but calf volume was increased by venous congestion (cuffs inflated to 80 mm Hg); test C: Calf volumes were decreased by a negative hydrostatic pressure (calves about 40 cm above heart level with the subjects supine). To clamp the changed calf volumes in tests B and C, cuffs were inflated to 300 mm Hg 5 min before the onset of exercise. This occlusion was maintained until termination of exercise. Compared to tests A and B, the reduced volume of test C led to significant increases in heart rate and blood pressure during exercise. Oxygen uptake did not exceed resting levels in B and C until cuffs were deflated, indicating that exclusively calf muscles contributed to the neurogenic peripheral drive. It is concluded that changes in extracellular muscle volume have to be taken into account when comparing heart rate and blood pressure during lg- and μg- exercise.

  8. Enhanced functional preservation of cold-stored rat heart by a nucleoside transport inhibitor.

    PubMed

    Yang, X; Zhu, Q; Claydon, M A; Hicks, G L; Wang, T

    1994-07-15

    This study investigates the hypothesis that inhibition of nucleoside transport during hypothermic storage elevates tissue adenosine (ADO) content and improves the function of the isolated rat heart. The hearts, flushed with a cardioplegic solution containing varying concentrations (0-100 nM) of a nucleoside transport inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI), were immersion-stored at 0 degrees C for 9 hr. Function was assessed after 30 min of working reperfusion. Function of unstored fresh hearts served as controls and poststorage recovery is reported as percentage of control function. Poststorage heart rate in all groups returned to control level after reperfusion. Recovery of other functional parameters in the no-NBTI group was as follows: aortic flow (AF), 56.2 +/- 4.6%; coronary flow (CF), 53.9 +/- 3.2%; cardiac output (CO), 55.5 +/- 4.0%; systolic pressure, 81.6 +/- 2.5%; work, 47.0 +/- 4.2%; and coronary vascular resistance (CVR), 157.1 +/- 7.8% of control. NBTI improved functional recovery in a dose-dependent fashion; the maximal improvement was seen at a dose of 5 nM, in which the recovery was: AF, 78.1 +/- 3.4%; CF, 73.5 +/- 4.4%; CO, 76.7 +/- 3.6%; work, 70.7 +/- 5.0%; and CVR, 127.5 +/- 4.5% of control (P < 0.05 vs. no-NBTI). The ADO A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (0.1 microM) blocked the effects of 5 nM NBTI; the recovery of AF, CF, CO, work, and CVR decreased to 62.8 +/- 8.0%, 58.3 +/- 5.0%, 61.5 +/- 3.9%, 54.4 +/- 4.5%, and 163.8 +/- 12.7% of control, respectively (P < 0.05 vs. 5 nM NBTI). Tissue ADO content in 5 nM NBTI hearts at the end of storage was 0.075 +/- 0.025 mumol/g dry wt, which was significantly elevated from 0.016 +/- 0.004 mumol/g dry wt in no-NBTI hearts. Purine release during initial reperfusion was delayed in 5 nM NBTI hearts, indicating the inhibition of nucleoside transport by NBTI. But NBTI treatment did not improve end-storage or end-reperfusion myocardial ATP. In conclusion, the addition of

  9. Functional significance of preserved affect recognition in schizophrenia

    PubMed Central

    Fiszdon, Joanna M.; Johannesen, Jason K.

    2009-01-01

    Affect recognition (AR) is a core component of social information processing, thus may be critical to understanding social behavior and functioning in broader aspects of daily living. Deficits in AR are well documented in schizophrenia, however, there is also evidence that many individuals with schizophrenia perform AR tasks at near-normal levels. In the current study, we sought to evaluate the functional significance of AR deficits in schizophrenia by comparing subgroups with normal-range and impaired AR performance on proxy and interviewer-rated measures of real-world functioning. Schizophrenia outpatients were classified as normal-range (N=17) and impaired (N=31) based on a logistic cut point in the sample distribution of BLERT scores, referenced to a normative sample of healthy control subjects (N=56). The derived schizophrenia subgroups were then compared on proxy (UCSD, UPSA, SSPA, MMAA) and interviewer-rated (QLS, ILSS) measures of functioning, as well as battery of neurocognitive tests. Initial analyses indicated superior MMAA and QLS performance in the near-normal AR subgroup. Covariate analyses indicated that group differences in neurocognition fully mediated the observed associations between AR and MMAA and attenuated the observed relationships between AR classification and QLS. These results support three main conclusions. First, AR, like many other domains of psychopathology studied in schizophrenia, is preserved in select subgroups. Second, there is a positive relationship between AR performance and functional outcome measures. Third, neurocognition appears to mediate the relationship between AR and measures of functioning. PMID:20202689

  10. A re-appraisal of volume status and renal function impairment in chronic heart failure: combined effects of pre-renal failure and venous congestion on renal function.

    PubMed

    Sinkeler, Steef J; Damman, Kevin; van Veldhuisen, Dirk J; Hillege, Hans; Navis, Gerjan

    2012-03-01

    The association between cardiac failure and renal function impairment has gained wide recognition over the last decade. Both structural damage in the form of systemic atherosclerosis and (patho) physiological hemodynamic changes may explain this association. As regards hemodynamic factors, renal impairment in chronic heart failure is traditionally assumed to be mainly due to a decrease in cardiac output and a subsequent decrease in renal perfusion. This will lead to a decrease in glomerular filtration rate and a compensatory increase in tubular sodium retention. The latter is a physiological renal response aimed at retaining fluids in order to increase cardiac filling pressure and thus renal perfusion. In heart failure, however, larger increases in cardiac filling pressure are needed to restore renal perfusion and thus more volume retention. In this concept, in chronic heart failure, an equilibrium exists where a certain degree of congestion is the price to be paid to maintain adequate renal perfusion and function. Recently, this hypothesis was challenged by new studies, wherein it was found that the association between right-sided cardiac filling pressures and renal function is bimodal, with worse renal function at the highest filling pressures, reflecting a severely congested state. Renal hemodynamic studies suggest that congestion negatively affects renal function in particular in patients in whom renal perfusion is also compromised. Thus, an interplay between cardiac forward failure and backward failure is involved in the renal function impairment in the congestive state, presumably along with other factors. Only few data are available on the impact of intervention in volume status on the cardio-renal interaction. Sparse data in cardiac patients as well as evidence from cohorts with primary renal disease suggest that specific targeting of volume overload may be beneficial for long-term outcome, in spite of a certain further decrease in renal function, at least

  11. Protection of mitochondrial and heart function by amino acids after ischemia and cardioplegia.

    PubMed

    Shug, A L; Madsen, D; Dobbie, R; Paulson, D J

    1994-01-01

    The effects of amino acids in protecting against ischemic/reperfusion injury were tested in two experimental models: the isolated perfused rat heart subjected to 21 min of zero flow ischemia (37 degrees) followed by 40 min of reperfusion and the isolated perfused rabbit heart subjected to 300 min of cardioplegic arrest (29 degrees) followed by 60 min of reperfusion. In both cases, the addition of amino acids to the perfusion medium significantly improved the recovery of cardiac contractile function. The protective effects of amino acids were associated with a preservation of mitochondrial respiratory activity. These findings suggest that amino acids by replenishing mitochondrial matrix levels of critical TCA cycle substrates, such as malate, stimulate mitochondrial respiration and thereby enhance the recovery of heart function.

  12. Impact of Cold Ischemia on Mitochondrial Function in Porcine Hearts and Blood Vessels

    PubMed Central

    Wiedemann, Dominik; Schachner, Thomas; Bonaros, Nikolaos; Dorn, Melissa; Andreas, Martin; Kocher, Alfred; Kuznetsov, Andrey V.

    2013-01-01

    The effects of cold storage using Custodiol® (Histidine-Tryptophan-Ketoglutarate, HTK) or isotonic saline solution on mitochondrial function in hearts (left and rights ventricles) and various blood vessels of pigs were investigated. Hearts, saphenous veins, internal-mammary-arteries and aortas of male landrace pigs were harvested and exposed to cold ischemia in either saline or Custodiol-HTK solution. Mitochondrial function was measured in situ in permeabilized fibers by high-resolution respirometry. Mitochondrial respiratory capacities (maximal respiration rates) were similar in the right and left ventricle in controls and after 14 h of cold storage were significantly better preserved in Custodiol-HTK than in saline solution. Mitochondrial respiration rates in various blood vessels including aorta, arteries and veins were less than 5% of myocardium rates. In contrast to the pig heart, in some blood vessels, like veins, mitochondrial function remained stable even after 24 h of cold ischemia. HTK-Custodiol protection of mitochondrial function after prolonged cold ischemia was observed in the myocardium but not in blood vessels. HTK-Custodiol solution thus offers significant protection of myocardial mitochondria against cold ischemic injury and can be used as efficient preservation solution in organ transplantation but probably has no benefit for blood vessels preservation. Analysis of mitochondrial function can be used as a valuable approach for the assessment of cold ischemic injury in various tissues including pig heart and various blood vessels. PMID:24213604

  13. Colour atlas of first pass functional imaging of the heart

    SciTech Connect

    Schad, N.; Andrews, E.J.; Fleming, J.W.

    1985-01-01

    This book contains 21 chapters. Some of the titles are: Functional imaging; Fist pass radionuclide studies in evaluation of mitral valve replacement in chronic insufficiency using Bjork-Shiley tilting disc valves; First pass radionuclide studies in evaluation of left and right ventricular function in patients with bioprosthetic mitral valve replacement after 9-11 years; and First pass radionuclide studies in the evaluation of long term (up to about 15 years) follow up of aortic valve replacement using Starr-Edwards ball prosthesis.

  14. Heart health peptides from macroalgae and their potential use in functional foods.

    PubMed

    Fitzgerald, Ciaran; Gallagher, Eimear; Tasdemir, Deniz; Hayes, Maria

    2011-07-13

    Macroalgae have for centuries been consumed whole among the East Asian populations of China, Korea, and Japan. Due to the environment in which they grow, macroalgae produce unique and interesting biologically active compounds. Protein can account for up to 47% of the dry weight of macroalgae depending on species and time of cultivation and harvest. Peptides derived from marcoalgae are proven to have hypotensive effects in the human circulatory system. Hypertension is one of the major, yet controllable, risk factors in cardiovascular disease (CVD). CVD is the main cause of death in Europe, accounting for over 4.3 million deaths each year. In the United States it affects one in three individuals. Hypotensive peptides derived from marine and other sources have already been incorporated into functional foods such as beverages and soups. The purpose of this review is to highlight the potential of heart health peptides from macroalgae and to discuss the feasibility of expanding the variety of foods these peptides may be used in.

  15. Abnormal GABAergic function and negative affect in schizophrenia.

    PubMed

    Taylor, Stephan F; Demeter, Elise; Phan, K Luan; Tso, Ivy F; Welsh, Robert C

    2014-03-01

    Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.

  16. Preliminary investigation of cardiopulmonary function in stroke patients with stable heart failure and exertional dyspnea

    PubMed Central

    Liaw, Mei-Yun; Wang, Lin-Yi; Pong, Ya-Ping; Tsai, Yu-Chin; Huang, Yu-Chi; Yang, Tsung-Hsun; Lin, Meng-Chih

    2016-01-01

    Abstract The aim of this study was to investigate the relationships between pulmonary function, respiratory muscle strength, perceived dyspnea, degree of fatigue, and activity of daily living with motor function and neurological status in stroke patients with stable congestive heart failure (CHF). This was a cohort study in a tertiary care medical center. Stroke patients with CHF and exertional dyspnea (New York Heart Association class I–III) were recruited. The baseline characteristics included duration of disease, Brunnstrom stage, spirometry, resting heart rate, resting oxyhemoglobin saturation (SpO2), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), Borg scale, fatigue scale, and Barthel index. A total of 47 stroke patients (24 males, 23 females, mean age 65.9 ± 11.5 years) were included. The average Brunnstrom stages of affected limbs were 3.6 ± 1.3 over the proximal parts and 3.5 ± 1.4 over the distal parts of upper limbs, and 3.9 ± 0.9 over lower limbs. The average forced vital capacity (FVC) was 2.0 ± 0.8 L, with a predicted FVC% of 67.9 ± 18.8%, forced expiratory volume in the first second (FEV1) of 1.6 ± 0.7 L, predicted FEV1% of 70.6 ± 20.1%, FEV1/FVC of 84.2 ± 10.5%, and maximum mid-expiratory flow of 65.4 ± 29.5%. The average MIP and MEP were −52.9 ± 33.3 cmH2O and 60.8 ± 29.0 cmH2O, respectively. The Borg scale was 1.5 ± 0.8. MIP was negatively associated with the average Brunnstrom stage of the proximal (r = −0.318, P < 0.05) and distal (r = −0.391, P < 0.01) parts of the upper extremities and lower extremities (r = −0.288, P < 0.05), FVC (r = −0.471, P < 0.01), predicted FVC% (r = −0.299, P < 0.05), and FEV1 (r = −0.397, P < 0.01). MEP was positively associated with average Brunnstrom stage of the distal area of the upper extremities (r = 0.351, P < 0.05), FVC (r = 0.526, P < 0

  17. Preliminary investigation of cardiopulmonary function in stroke patients with stable heart failure and exertional dyspnea.

    PubMed

    Liaw, Mei-Yun; Wang, Lin-Yi; Pong, Ya-Ping; Tsai, Yu-Chin; Huang, Yu-Chi; Yang, Tsung-Hsun; Lin, Meng-Chih

    2016-10-01

    The aim of this study was to investigate the relationships between pulmonary function, respiratory muscle strength, perceived dyspnea, degree of fatigue, and activity of daily living with motor function and neurological status in stroke patients with stable congestive heart failure (CHF).This was a cohort study in a tertiary care medical center. Stroke patients with CHF and exertional dyspnea (New York Heart Association class I-III) were recruited. The baseline characteristics included duration of disease, Brunnstrom stage, spirometry, resting heart rate, resting oxyhemoglobin saturation (SpO2), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), Borg scale, fatigue scale, and Barthel index.A total of 47 stroke patients (24 males, 23 females, mean age 65.9 ± 11.5 years) were included. The average Brunnstrom stages of affected limbs were 3.6 ± 1.3 over the proximal parts and 3.5 ± 1.4 over the distal parts of upper limbs, and 3.9 ± 0.9 over lower limbs. The average forced vital capacity (FVC) was 2.0 ± 0.8 L, with a predicted FVC% of 67.9 ± 18.8%, forced expiratory volume in the first second (FEV1) of 1.6 ± 0.7 L, predicted FEV1% of 70.6 ± 20.1%, FEV1/FVC of 84.2 ± 10.5%, and maximum mid-expiratory flow of 65.4 ± 29.5%. The average MIP and MEP were -52.9 ± 33.3 cmH2O and 60.8 ± 29.0 cmH2O, respectively. The Borg scale was 1.5 ± 0.8. MIP was negatively associated with the average Brunnstrom stage of the proximal (r = -0.318, P < 0.05) and distal (r = -0.391, P < 0.01) parts of the upper extremities and lower extremities (r = -0.288, P < 0.05), FVC (r = -0.471, P < 0.01), predicted FVC% (r = -0.299, P < 0.05), and FEV1 (r = -0.397, P < 0.01). MEP was positively associated with average Brunnstrom stage of the distal area of the upper extremities (r = 0.351, P < 0.05), FVC (r = 0.526, P < 0.01), FEV1 (r = 0

  18. Combined non-adaptive light and smell stimuli lowered blood pressure, reduced heart rate and reduced negative affect.

    PubMed

    Dong, Shan; Jacob, Tim J C

    2016-03-15

    Bright light therapy has been shown to have a positive impact on seasonal affective disorder (SAD), depression and anxiety. Smell has also has been shown to have effects on mood, stress, anxiety and depression. The objective of this study was to investigate the effect of the combination of light and smell in a non-adaptive cycle. Human subjects were given smell (lemon, lavender or peppermint) and light stimuli in a triangular wave (60scycle) for 15min. Blood pressure and heart rate were monitored before and after each session for 5 consecutive days and a Profile of Mood States (POMS) test was administered before and after the sensory stimulation on days 1, 3 and 5. The light-smell stimulus lowered blood pressure, both systolic and diastolic, and reduced heart rate for all odours compared to control. Of the two sensory stimuli, the odour stimulus contributed most to this effect. The different aromas in the light-smell combinations could be distinguished by their different effects on the mood factors with lemon inducing the greatest mood changes in Dejection-Depression, Anger-Hostility, Tension-Anxiety. In conclusion, combined light and smell stimulation was effective in lowering blood pressure, reducing heart rate and improving mood. The combination was more effective than either smell or light stimuli alone, suggesting that a light-smell combination would be a more robust and efficacious alternative treatment for depression, anxiety and stress.

  19. Metabolic context affects hemodynamic response to bupivacaine in the isolated rat heart.

    PubMed

    Edelman, Lucas B; Ripper, Richard; Kelly, Kemba; Di Gregorio, Guido; Weinberg, Guy L

    2008-03-10

    Previous studies have demonstrated that the local anesthetic bupivacaine selectively inhibits oxidative metabolism of fatty acids in isolated cardiac mitochondria. In the present investigation, we compare the development of bupivacaine cardiotoxicity during fatty acid and carbohydrate metabolism. Hearts from adult male Sprague-Dawley rats were excised and retrograde perfused with a solution containing fatty acid (oleate or octanoate) or carbohydrate substrates for cardiac metabolism. An infusion of bupivacaine was initiated and sustained until asystole, after which full cardiac recovery was allowed. During fatty acid metabolism, substantially lower bupivacaine doses induced both arrhythmia (60.4+/-11.5 microg oleate and 106.8+/-14.8 octanoate versus 153.4+/-21.4 carbohydrate; P<0.05) and asystole (121.0+/-30.1 microg and 171.5+/-20.2 versus 344.7+/-34.6; P<0.001). Dose-response analysis revealed significantly increased sensitivity to bupivacaine toxicity during fatty acid metabolism, indicated by lower V50 doses for both heart rate (70.6+/-5.6 microg oleate and 122.3+/-6.2 octanoate versus 152.6+/-8.6) and rate-pressure product (63.4+/-5.1 microg and 133.7+/-7.9 versus 165.1+/-12.2). Time to recovery following bupivacaine exposure was elevated in the fatty acid group (24.3+/-2.0 s versus 15.8+/-3.1; P<0.04). Fatty acid metabolism was shown to predispose the isolated heart to bupivacaine toxicity, confirming that the local anesthetic exerts specific effects on lipid processes in cardiomyocytes.

  20. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function.

    PubMed

    Li, Wenzhong; Ma, Nan; Ong, Lee-Lee; Nesselmann, Catharina; Klopsch, Christian; Ladilov, Yury; Furlani, Dario; Piechaczek, Christoph; Moebius, Jeannette M; Lützow, Karola; Lendlein, Andreas; Stamm, Christof; Li, Ren-Ke; Steinhoff, Gustav

    2007-08-01

    Engraftment of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for postinfarction left ventricular dysfunction. However, limited cell viability after transplantation into the myocardium has restricted its regenerative capacity. In this study, we genetically modified MSCs with an antiapoptotic Bcl-2 gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a rat left anterior descending ligation model via intracardiac injection. Rat MSCs were manipulated to overexpress the Bcl-2 gene. In vitro, the antiapoptotic and paracrine effects were assessed under hypoxic conditions. In vivo, the Bcl-2 gene-modified MSCs (Bcl-2-MSCs) were injected after myocardial infarction. The surviving cells were tracked after transplantation. Capillary density was quantified after 3 weeks. The left ventricular function was evaluated by pressure-volume loops. The Bcl-2 gene protected MSCs against apoptosis. In vitro, Bcl-2 overexpression reduced MSC apoptosis by 32% and enhanced vascular endothelial growth factor secretion by more than 60% under hypoxic conditions. Transplantation with Bcl-2-MSCs increased 2.2-fold, 1.9-fold, and 1.2-fold of the cellular survival at 4 days, 3 weeks, and 6 weeks, respectively, compared with the vector-MSC group. Capillary density in the infarct border zone was 15% higher in Bcl-2-MSC transplanted animals than in vector-MSC treated animals. Furthermore, Bcl-2-MSC transplanted animals had 17% smaller infarct size than vector-MSC treated animals and exhibited functional recovery remarkably. Our current findings support the premise that transplantation of antiapoptotic gene-modified MSCs may have values for mediating substantial functional recovery after acute myocardial infarction.

  1. Potassium channels in the heart: structure, function and regulation.

    PubMed

    Grandi, Eleonora; Sanguinetti, Michael C; Bartos, Daniel C; Bers, Donald M; Chen-Izu, Ye; Chiamvimonvat, Nipavan; Colecraft, Henry M; Delisle, Brian P; Heijman, Jordi; Navedo, Manuel F; Noskov, Sergei; Proenza, Catherine; Vandenberg, Jamie I; Yarov-Yarovoy, Vladimir

    2017-04-01

    This paper is the outcome of the fourth UC Davis Systems Approach to Understanding Cardiac Excitation-Contraction Coupling and Arrhythmias Symposium, a biannual event that aims to bring together leading experts in subfields of cardiovascular biomedicine to focus on topics of importance to the field. The theme of the 2016 symposium was 'K(+) Channels and Regulation'. Experts in the field contributed their experimental and mathematical modelling perspectives and discussed emerging questions, controversies and challenges on the topic of cardiac K(+) channels. This paper summarizes the topics of formal presentations and informal discussions from the symposium on the structural basis of voltage-gated K(+) channel function, as well as the mechanisms involved in regulation of K(+) channel gating, expression and membrane localization. Given the critical role for K(+) channels in determining the rate of cardiac repolarization, it is hardly surprising that essentially every aspect of K(+) channel function is exquisitely regulated in cardiac myocytes. This regulation is complex and highly interrelated to other aspects of myocardial function. K(+) channel regulatory mechanisms alter, and are altered by, physiological challenges, pathophysiological conditions, and pharmacological agents. An accompanying paper focuses on the integrative role of K(+) channels in cardiac electrophysiology, i.e. how K(+) currents shape the cardiac action potential, and how their dysfunction can lead to arrhythmias, and discusses K(+) channel-based therapeutics. A fundamental understanding of K(+) channel regulatory mechanisms and disease processes is fundamental to reveal new targets for human therapy.

  2. Capturing structure and function in an embryonic heart with biophotonic tools

    PubMed Central

    Karunamuni, Ganga H.; Gu, Shi; Ford, Matthew R.; Peterson, Lindsy M.; Ma, Pei; Wang, Yves T.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Disturbed cardiac function at an early stage of development has been shown to correlate with cellular/molecular, structural as well as functional cardiac anomalies at later stages culminating in the congenital heart defects (CHDs) that present at birth. While our knowledge of cellular and molecular steps in cardiac development is growing rapidly, our understanding of the role of cardiovascular function in the embryo is still in an early phase. One reason for the scanty information in this area is that the tools to study early cardiac function are limited. Recently developed and adapted biophotonic tools may overcome some of the challenges of studying the tiny fragile beating heart. In this chapter, we describe and discuss our experience in developing and implementing biophotonic tools to study the role of function in heart development with emphasis on optical coherence tomography (OCT). OCT can be used for detailed structural and functional studies of the tubular and looping embryo heart under physiological conditions. The same heart can be rapidly and quantitatively phenotyped at early and again at later stages using OCT. When combined with other tools such as optical mapping (OM) and optical pacing (OP), OCT has the potential to reveal in spatial and temporal detail the biophysical changes that can impact mechanotransduction pathways. This information may provide better explanations for the etiology of the CHDs when interwoven with our understanding of morphogenesis and the molecular pathways that have been described to be involved. Future directions for advances in the creation and use of biophotonic tools are discussed. PMID:25309451

  3. High fat fed heart failure animals have enhanced mitochondrial function and acyl-coa dehydrogenase activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously shown that administration of high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARalpha is a nuclear transcription factor that activates expression of genes involved in fatty acid uptake and utilization. We hypoth...

  4. Cardiac function after acute support with direct mechanical ventricular actuation in chronic heart failure.

    PubMed

    McConnell, Patrick I; Anstadt, Mark P; Del Rio, Carlos L; Preston, Thomas J; Ueyama, Yukie; Youngblood, Brad L

    2014-01-01

    Direct mechanical ventricular actuation (DMVA) exerts direct cardiac compression/decompression and does not require blood contact. The safety and effects of DMVA support in chronically dysfunctional beating hearts in vivo have not been established. This study evaluated hemodynamics and load-independent systolic/diastolic cardiac function before/after acute support (2 hours) using DMVA in small hearts with induced chronic failure. Chronic heart failure was created in seven small dogs (15 ± 2 kg) via either serial coronary microembolizations or right-ventricular overdrive pacing. Dogs were instrumented to measure cardiac output, hemodynamic pressures, left ventricular volumes for pressure-volume analysis via preload reduction. Temporary cardiac support using a DMVA device was instituted for 2 hours. Hemodynamic and mechanical assessments, including dobutamine dose-responses, were compared both before and after support. Hemodynamic indices were preserved with support. Both left-ventricular systolic and diastolic function were improved postsupport, as the slopes of the preload-recruitable stroke work (+29 ± 7%, p < 0.05) and the end-diastolic pressure-volume relationship (EDPVR: -28 ± 9%, p < 0.05) improved post-DMVA support. Diastolic/systolic myocardial reserve, as assessed by responsiveness to dobutamine challenges, was preserved after DMVA support. Short-term DMVA support can safely and effectively sustain hemodynamics, whereas triggering favorable effects on cardiac function in the setting of chronic heart failure. In particular, DMVA support preserved load-independent diastolic function and reserve.

  5. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure.

    PubMed

    Yin, Meimei; van der Horst, Iwan C C; van Melle, Joost P; Qian, Cheng; van Gilst, Wiek H; Silljé, Herman H W; de Boer, Rudolf A

    2011-08-01

    Metformin is the first choice drug for the treatment of patients with diabetes, but its use is debated in patients with advanced cardiorenal disease. Epidemiological data suggest that metformin may reduce cardiac events, in patients both with and without heart failure. Experimental evidence suggests that metformin reduces cardiac ischemia-reperfusion injury. It is unknown whether metformin improves cardiac function (remodeling) in a long-term post-MI remodeling model. We therefore studied male, nondiabetic, Sprague-Dawley rats that were subjected to either myocardial infarction (MI) or sham operation. Animals were randomly allocated to treatment with normal water or metformin-containing water (250 mg·kg(-1)·day(-1)). At baseline, 6 wk, and 12 wk, metabolic parameters were analyzed and oral glucose tolerance tests (OGTT) were performed. Echocardiography and hemodynamic parameters were assessed 12 wk after MI. In the MI model, infarct size was significantly smaller after 12-wk metformin treatment (29.6 ± 3.2 vs. 38.0 ± 2.2%, P < 0.05). Moreover, metformin resulted in less left ventricular dilatation (6.0 ± 0.4 vs. 7.6 ± 0.6 mm, P < 0.05) and preservation of left ventricular ejection fraction (65.8 ± 3.7% vs. 48.6 ± 5.6%, P < 0.05) compared with MI control. The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05). Insulin resistance did not occur during cardiac remodeling (as indicated by normal OGTT) and fasting glucose levels and the pattern of the OGTT were not affected by metformin. Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin. Altogether our results indicate that metformin may have potential to attenuate heart failure development after myocardial infarction, in the absence of diabetes and independent of systemic glucose levels.

  6. Electrophysiological Remodeling in Heart Failure

    PubMed Central

    Wang, Yanggan; Hill, Joseph A.

    2010-01-01

    Heart failure affects nearly 6 million Americans, with a half-million new cases emerging each year. Whereas up to 50% of heart failure patients die of arrhythmia, the diverse mechanisms underlying heart failure-associated arrhythmia are poorly understood. As a consequence, effectiveness of antiarrhythmic pharmacotherapy remains elusive. Here, we review recent advances in our understanding of heart failure-associated molecular events impacting the electrical function of the myocardium. We approach this from an anatomical standpoint, summarizing recent insights gleaned from pre-clinical models and discussing their relevance to human heart failure. PMID:20096285

  7. Some factors affecting phosphate transport in a perfused rat heart preparation.

    PubMed Central

    Medina, G; Illingworth, J

    1980-01-01

    Pi uptake by a perfused rat heart preparation did not require the presence of any other permeant anion, but was markedly dependent on the extracellular Na+ concentration and accelerated when tissue oxygenation was inadequate. Pi efflux was also independent of other permeant anions, but apparently varied with the intracellular Na+ concentration. Cardiac Pi efflux was not sensitive to a number of inhibitors that clock Cl- movement in heart and other tissues. Both uptake and efflux apparently proceed via a reversible electroneutral co-transport system linked to the transmembrane Na+ gradient. Pi uptake was independent of cardiac work load, but the efflux rate was sharply accelerated after an increase in aortic pressure development, with a slow return towards basal values during sustained periods of high work output. An inverted biphasic effect on the efflux rate was observed after a reduction in cardiac work load. Mild hypoxia and respiratory and metabolic acidosis each resulted in a transient acceleration of Pi efflux followed by a return towards basal values during prolonged exposure to the stimulus, whereas respiratory and metabolic alkalosis produced a similar but inverted response. The origin of these phasic effects on Pi efflux remains to be identified at present. PMID:7396864

  8. Diastolic function and functional capacity after a single session of continuous positive airway pressure in patients with compensated heart failure

    PubMed Central

    Bussoni, Marjory Fernanda; Guirado, Gabriel Negretti; Matsubara, Luiz Shiguero; Roscani, Meliza Goi; Polegato, Bertha Furlan; Minamoto, Suzana Tanni; Bazan, Silméia Garcia Zanati; Matsubara, Beatriz Bojikian

    2014-01-01

    OBJECTIVE: The effects of acute continuous positive airway pressure therapy on left ventricular diastolic function and functional capacity in patients with compensated systolic heart failure remain unclear. METHODS: This randomized, double-blind, placebo-controlled clinical trial included 43 patients with heart failure and a left ventricular ejection fraction <0.50 who were in functional classes I-III according to the New York Heart Association criteria. Twenty-three patients were assigned to continuous positive airway pressure therapy (10 cmH2O), while 20 patients received placebo with null pressure for 30 minutes. All patients underwent a 6-minute walk test (6MWT) and Doppler echocardiography before and immediately after intervention. Clinicaltrials.gov: NCT01088854. RESULTS: The groups had similar clinical and echocardiographic baseline variables. Variation in the diastolic function index (e′) after intervention was associated with differences in the distance walked in both groups. However, in the continuous positive airway pressure group, this difference was greater (continuous positive airway pressure group: Δ6MWT = 9.44+16.05×Δe′, p = 0.002; sham group: Δ6MWT = 7.49+5.38×Δe′; p = 0.015). There was a statistically significant interaction between e′ index variation and continuous positive airway pressure for the improvement of functional capacity (p = 0.020). CONCLUSIONS: Continuous positive airway pressure does not acurately change the echocardiographic indexes of left ventricle systolic or diastolic function in patients with compensated systolic heart failure. However, 30-minute continuous positive airway pressure therapy appears to have an effect on left ventricular diastolic function by increasing functional capacity. PMID:24838902

  9. Can the hydrophilicity of functional monomers affect chemical interaction?

    PubMed

    Feitosa, V P; Ogliari, F A; Van Meerbeek, B; Watson, T F; Yoshihara, K; Ogliari, A O; Sinhoreti, M A; Correr, A B; Cama, G; Sauro, S

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts.

  10. How does temperature affect the function of tissue macrophages?

    NASA Astrophysics Data System (ADS)

    Lee, Chen-Ting; Repasky, Elizabeth A.

    2011-03-01

    Macrophages create a major danger signal following injury or infection and upon activation release pro-inflammatory cytokines, which in turn help to generate febrile conditions. Thus, like other cells of the body, tissue macrophages are often exposed to naturally occurring elevations in tissue temperature during inflammation and fever. However, whether macrophages sense and respond to temperature changes in a specific manner which modulates their function is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of temperatures on macrophage function, and summarize the possible underlying molecular mechanisms which have been identified. Mild, physiological range hyperthermia has been shown to have both pro- and anti-inflammatory roles in regulating macrophage inflammatory cytokine production and at the meeting presentation, we will show new data demonstrating that hyperthermia can indeed exert both positive and negative signals to macrophages. While some thermal effects are correlated with the induction of heat shock factors/heat shock proteins, overall it is not clear how mild hyperthermia can exert both pro- and anti-inflammatory functions. We also summarize data which shows that hyperthermia can affect other macrophage effector functions, including the anti-tumor cytotoxicity. Overall, these studies may help us to better understand the immunological role of tissue temperature and may provide important information needed to maximize the application of heat in the treatment of various diseases including cancer.

  11. Emotional Processing in High-Functioning Autism--Physiological Reactivity and Affective Report

    ERIC Educational Resources Information Center

    Bolte, Sven; Feineis-Matthews, Sabine; Poustka, Fritz

    2008-01-01

    This study examined physiological response and affective report in 10 adult individuals with autism and 10 typically developing controls. An emotion induction paradigm using stimuli from the International Affective Picture System was applied. Blood pressure, heart and self-ratings of experienced valence (pleasure), arousal and dominance (control)…

  12. Heart rate variability with deep breathing as a clinical test of cardiovagal function.

    PubMed

    Shields, Robert W

    2009-04-01

    Research into heart rate variability (HRV) and respiration over the past 150 years has led to the insight that HRV with deep breathing (HRVdb) is a highly sensitive measure of cardiovagal or parasympathetic cardiac function. This sensitivity makes HRVdb an important part of the battery of cardiovascular autonomic function tests used in clinical autonomic laboratories. HRVdb is a reliable and sensitive clinical test for early detection of cardiovagal dysfunction in a wide range of autonomic disorders.

  13. [Echocardiographic evaluation of the athlete's heart: from morphological adaptations to myocardial function].

    PubMed

    D'Andrea, Antonello; Galderisi, Maurizio; Sciomer, Susanna; Nistri, Stefano; Agricola, Eustachio; Ballo, Piercarlo; Buralli, Simona; D'Errico, Arcangelo; Losi, Maria Angela; Mele, Donato; Mondillo, Sergio

    2009-08-01

    The definition of the athlete's heart includes the mechanisms of cardiac adaptation to training, characterized by the increase of internal chamber dimensions, ventricular wall thickness, and atrial chambers. The morphology of the athlete's heart is intermediate between concentric and eccentric left ventricular hypertrophy (LVH), in relation to the large prevalence of mixed sports activities and training protocols (including both aerobic and anaerobic exercise). Echocardiography is the tool of choice for the assessment of the athlete's heart and also for the differentiation of physiologic and pathologic LVH (hypertrophic cardiomyopathy and LVH due to arterial hypertension). The initial echocardiographic approach includes the quantitative analysis of the left ventricle, in order to calculate left ventricular mass, left ventricular mass index and relative wall thickness for diagnosing concentric or eccentric LVH. Tissue Doppler (pulsed or color modality) and strain rate imaging (Doppler or two-dimensional modality) may give additional information to the standard indices of systolic function. Diastolic function can be evaluated not only by standard Doppler transmitral inflow measurements but also using pulsed tissue Doppler, which may allow to distinguish the athlete's LVH from diastolic impairment of hypertensive patients or hypertrophic cardiomyopathy by the simple determination of myocardial early diastolic velocity. Also the morphological and functional features of the left atrium and of the right ventricle can be assessed in the athlete's heart by combining standard echocardiography with new echocardiographic technologies.

  14. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice

    PubMed Central

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy. PMID:28386378

  15. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice.

    PubMed

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy.

  16. Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure

    NASA Technical Reports Server (NTRS)

    Komamura, K.; Shannon, R. P.; Pasipoularides, A.; Ihara, T.; Lader, A. S.; Patrick, T. A.; Bishop, S. P.; Vatner, S. F.

    1992-01-01

    We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.

  17. Effect of Angiotensin(1-7) on Heart Function in an Experimental Rat Model of Obesity

    PubMed Central

    Blanke, Katja; Schlegel, Franziska; Raasch, Walter; Bader, Michael; Dähnert, Ingo; Dhein, Stefan; Salameh, Aida

    2015-01-01

    Aim: Obesity is a risk factor for the development of cardiovascular diseases. Recently it was shown that overexpression of the Mas-receptor antagonist angiotensin(1-7) could prevent from diet-induced obesity. However, it remained unclear whether diet-induced obesity and angiotensin(1-7) overexpression might also have effects on the cardiovascular system in these rats. Methods:Twenty three male Sprague Dawley rats were fed with standard chow (SD+chow, n = 5) or a cafeteria diet (SD+CD, n = 6) for 5 months. To investigate the effect of angiotensin(1-7) transgenic rats, expressing an angiotensin(1-7)-producing fusion protein in testis were used. These transgenic rats also received a 5 month's feeding period with either chow (TGR+chow, n = 6) or cafeteria diet (TGR+CD, n = 6), respectively. Hemodynamic measurements (pressure-volume loops) were carried out to assess cardiac function and blood pressure. Subsequently, hearts were explanted and investigated according to the Langendorff technique. Furthermore, cardiac remodeling in these animals was investigated histologically. Results:After 5 months cafeteria diet feeding rats showed a significantly increased body weight, which could be prevented in transgenic rats. However, there was no effect on cardiac performance after cafeteria diet in non-transgenic and transgenic rats. Moreover, overexpression of angiotensin(1-7) deteriorated cardiac contractility as indicated by impaired dp/dt. Furthermore, histological analysis revealed that cafeteria diet led to myocardial fibrosis in both, control and transgenic rats and this was not inhibited by an overproduction of angiotensin(1-7). Conclusion:These results indicate that an overexpression of circulating angiotensin(1-7) prevents a cafeteria diet-induced increase in body weight, but does not affect cardiac performance in this experimental rat model of obesity. Furthermore, overexpression of angiotensin(1-7) alone resulted in an impairment of cardiac function. PMID:26733884

  18. Canonical Wnt signaling functions in second heart field to promote right ventricular growth

    PubMed Central

    Ai, Di; Fu, Xueyao; Wang, Jun; Lu, Mei-Fang; Chen, Li; Baldini, Antonio; Klein, William H.; Martin, James F.

    2007-01-01

    The second heart field (SHF), progenitor cells that are initially sequestered outside the heart, migrates into the heart and gives rise to endocardium, myocardium, and smooth muscle. Because of its distinct developmental history, the SHF is likely subjected to different signals from that of the first heart field. Previous experiments revealed that canonical Wnt signaling negatively regulated first heart field specification. We inactivated the obligate canonical Wnt effector β-catenin using a β-catenin conditional null allele and the Mef2c AHF cre driver that directs cre activity specifically in SHF. We also expressed a stabilized form of β-catenin to model continuous Wnt signaling in SHF. Our data indicate that Wnt signaling acts in a positive fashion to promote right ventricular and interventricular myocardial expansion. Cyclin D2 and Tgfβ2 expression was drastically reduced in β-catenin loss-of-function mutants, indicating that Wnt signaling is required for patterning and expansion of SHF derivatives. Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium. PMID:17519332

  19. Coronary artery disease affects cortical circuitry associated with brain-heart integration during volitional exercise.

    PubMed

    Norton, Katelyn N; Badrov, Mark B; Barron, Carly C; Suskin, Neville; Heinecke, Armin; Shoemaker, J Kevin

    2015-08-01

    This study tested the hypothesis that coronary artery disease (CAD) alters the cortical circuitry associated with exercise. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 23 control subjects [control; 8 women; 63 ± 11 yr; mean arterial pressure (MAP): 90 ± 9 mmHg] (mean ± SD) and 17 similarly aged CAD patients (4 women; 59 ± 9 yr; MAP: 87 ± 10 mmHg). Four repeated bouts each of 30%, 40%, and 50% of maximal voluntary contraction (MVC) force (LAB session), and seven repeated bouts of isometric handgrip (IHG) at 40% MVC force (fMRI session), were performed, with each contraction lasting 20 s and separated by 40 s of rest. There was a main effect of group (P = 0.03) on HR responses across all IHG intensities. Compared with control, CAD demonstrated less task-dependent deactivation in the posterior cingulate cortex and medial prefrontal cortex, and reduced activation in the right anterior insula, bilateral precentral cortex, and occipital lobe (P < 0.05). When correlated with HR, CAD demonstrated reduced activation in the bilateral insula and posterior cingulate cortex, and reduced deactivation in the dorsal anterior cingulate cortex, and bilateral precentral cortex (P < 0.05). The increased variability in expected autonomic regions and decrease in total cortical activation in response to the IHG task are associated with a diminished HR response to volitional effort in CAD. Therefore, relative to similarly aged and healthy individuals, CAD impairs the heart rate response and modifies the cortical patterns associated with cardiovascular control during IHG.

  20. Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure.

    PubMed

    van Veldhuisen, Dirk J; Ruilope, Luis M; Maisel, Alan S; Damman, Kevin

    2016-09-01

    Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.

  1. MicroRNAs affect dendritic cell function and phenotype

    PubMed Central

    Smyth, Lesley A; Boardman, Dominic A; Tung, Sim L; Lechler, Robert; Lombardi, Giovanna

    2015-01-01

    MicroRNA (miRNA) are small, non-coding RNA molecules that have been linked with immunity through regulating/modulating gene expression. A role for these molecules in T-cell and B-cell development and function has been well established. An increasing body of literature now highlights the importance of specific miRNA in dendritic cell (DC) development as well as their maturation process, antigen presentation capacity and cytokine release. Given the unique role of DC within the immune system, linking the innate and adaptive immune responses, understanding how specific miRNA affect DC function is of importance for understanding disease. In this review we summarize recent developments in miRNA and DC research, highlighting the requirement of miRNA in DC lineage commitment from bone marrow progenitors and for the development of subsets such as plasmacytoid DC and conventional DC. In addition, we discuss how infections and tumours modulate miRNA expression and consequently DC function. PMID:25244106

  2. Creating frog heart as an organ: in vitro-induced heart functions as a circulatory organ in vivo.

    PubMed

    Kinoshita, Masayoshi; Ariizumi, Takashi; Yuasa, Shinsuke; Miyoshi, Shunichirou; Komazaki, Shinji; Fukuda, Keiichi; Asashima, Makoto

    2010-01-01

    Cardiomyocytes have been induced from various pluripotent cells, such as embryonic stem cells and myeloid stem cells; however, the generation of cardiac tissues beyond two-dimensional cell-sheets has not been reported. Creating higher order, three-dimensional structures that are unique to heart is the long-awaited next step in realizing cardiac regenerative medicine. We have previously shown that cardiomyocytes can be induced in vitro from undifferentiated cells (animal caps) excised from Xenopus embryos. Cardiomyocytes were induced by first dissociating the animal caps and then reaggregating them following treatment with activin. Here, we describe an interesting method for creating a complete ectopic heart in vivo, involving the introduction of in vitro-created tissue during early embryogenesis. Thus, animal cap reaggregates were transplanted into the abdomen of late-neurula-stage embryos, resulting in two-chambered hearts being formed. The dual-heart larvae matured into adult animals with transplanted hearts intact. Involvement of transplanted hearts in systemic circulation was demonstrated. Moreover, the ectopic hearts possessed higher order structures such as atrium and ventricle, and were morphologically, histologically, and electrophysiologically identical to original hearts. This system should facilitate the study of heart organogenesis and may promote a shift from tissue to organ engineering for clinical applications.

  3. Bisphenol A affects androgen receptor function via multiple mechanisms.

    PubMed

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.

  4. How should we measure function in patients with chronic heart and lung disease?

    PubMed

    Guyatt, G H; Thompson, P J; Berman, L B; Sullivan, M J; Townsend, M; Jones, N L; Pugsley, S O

    1985-01-01

    To elucidate the characteristics of measures of function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearman's rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579), and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand, correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease.

  5. Transcriptional analysis of the mammalian heart with special reference to its endocrine function

    PubMed Central

    McGrath, Monica Forero; de Bold, Adolfo J

    2009-01-01

    Background Pharmacological and gene ablation studies have demonstrated the crucial role of the endocrine function of the heart as mediated by the polypeptide hormones ANF and BNP in the maintenance of cardiovascular homeostasis. The importance of these studies lies on the fact that hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative deficiency of ANF and BNP. These hormones are produced by the atrial muscle cells (cardiocytes), which display a dual secretory/muscle phenotype. In contrast, ventricular cardiocytes display mainly a muscle phenotype. Comparatively little information is available regarding the genetic background for this important phenotypic difference with particular reference to the endocrine function of the heart. We postulated that comparison of gene expression profiles between atrial and ventricular muscles would help identify gene transcripts that underlie the phenotypic differences associated with the endocrine function of the heart. Results Comparison of gene expression profiles in the rat heart revealed a total of 1415 differentially expressed genes between the atria and ventricles based on a 1.8 fold cut-off. The identification of numerous chamber specific transcripts, such as ANF for the atria and Irx4 for the ventricles among several others, support the soundness of the GeneChip data and demonstrates that the differences in gene expression profiles observed between the atrial and ventricular tissues were not spurious in nature. Pathway analysis revealed unique expression profiles in the atria for G protein signaling that included Gαo1, Gγ2 and Gγ3, AGS1, RGS2, and RGS6 and the related K+ channels GIRK1 and GIRK4. Transcripts involved in vesicle trafficking, hormone secretion as well as mechanosensors (e.g. the potassium channel TREK-1) were identified in relationship to the synthesis, storage and secretion of hormones. Conclusion The data developed in this investigation

  6. PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis.

    PubMed

    Standage, Stephen W; Bennion, Brock G; Knowles, Taft O; Ledee, Dolena R; Portman, Michael A; McGuire, John K; Liles, W Conrad; Olson, Aaron K

    2017-02-01

    Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα (Ppara(-/-)) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology. Left ventricular shortening fraction, measured 24 h after initiation of sepsis by echocardiography, was higher in WT mice than in Ppara(-/-) mice. Ex vivo working heart studies demonstrated greater developed pressure, contractility, and aortic outflow in WT compared with Ppara(-/-) mice. Furthermore, cardiac fatty acid oxidation was increased in WT but not in Ppara(-/-) mice. Regulatory pathways controlling pyruvate incorporation into the citric acid cycle were inhibited by sepsis in both genotypes, but the regulatory state of enzymes controlling fatty acid oxidation appeared to be permissive in WT mice only. Mitochondrial ultrastructure was not altered in either genotype indicating that severe mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest that PPARα expression supports the hyperdynamic cardiac response early in the course of sepsis and that increased fatty acid oxidation may prevent morbidity and mortality.

  7. Can lifestyle modification affect men’s erectile function?

    PubMed Central

    Hehemann, Marah C.

    2016-01-01

    Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. The pathophysiology and epidemiologic links between ED and risk factors for cardiovascular disease (CVD) are well-established. Lifestyle modifications such as smoking cessation, weight reduction, dietary modification, physical activity, and psychological stress reduction have been increasingly recognized as foundational to the prevention and treatment of ED. The aim of this review is to outline behavioral choices which may increase ones risk of developing ED, to present relevant studies addressing lifestyle factors correlated with ED, and to highlight proposed mechanisms for intervention aimed at improving erectile function in men with ED. These recommendations can provide a framework for counseling patients with ED about lifestyle modification. PMID:27141445

  8. Scorpion venom components that affect ion-channels function

    PubMed Central

    Quintero-Hernández, V.; Jiménez-Vargas, J.M.; Gurrola, G.B.; Valdivia, H.H.F.; Possani, L.D.

    2014-01-01

    SUMMARY The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are now adays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na+-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. PMID:23891887

  9. Functional roles affect diversity-succession relationships for boreal beetles.

    PubMed

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  10. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  11. To what extent does urbanisation affect fragmented grassland functioning?

    PubMed

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  12. Ultraviolet Radiation Affects Thoratec HeartMate II Driveline Mechanical Properties: A Pilot Experiment.

    PubMed

    Evans, Annicka C; Wright, G Andrew; McCandless, Sean P; Stoker, Sandi; Miller, Dylan; Reid, Bruce B; Horne, Benjamin D; Afshar, Kia; Kfoury, Abdallah G

    2015-01-01

    Longevity and quality of life for left ventricular assist device (LVAD) patients are plagued by driveline exit site infections. Ultraviolet (UV) radiation, a current treatment in wound healing clinics, could potentially treat LVAD exit site infections. However, the effect of UV radiation on the tensile properties of HeartMate II (HMII) driveline material is unknown. The sleeve of a single HMII driveline was distributed into six exposure groups (n = 10/group). The six groups were further divided into two treatment cohorts designed to replicate wound treatment schedules of postimplant LVAD patients. Strip biaxial tensile tests were performed on both unexposed and exposed samples to analyze changes in material elasticity (Young's modulus), point of deformation (yield strength), and breaking point. Our data suggest that UV exposure changes the elasticity of the HMII driveline. However, the material endured aberrantly large forces and the properties remained within the safety threshold of device performance. This study warrants further examination of the effect of UV light on driveline material, to determine safety, reliability, and efficacy of UV treatment on exit site infections.

  13. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  14. Assessment of right ventricular systolic function by echocardiography after surgical repair of congenital heart defects.

    PubMed

    Khraiche, Diala; Ben Moussa, Nidhal

    2016-02-01

    Postoperative impairment of right ventricular (RV) systolic function can appear after surgical repair of complex congenital heart defects, such as tetralogy of Fallot; it is caused by chronic volume and/or pressure overload due to pulmonary regurgitation and/or stenosis. RV dysfunction is strongly associated with prognosis in these patients. Cardiac magnetic resonance imaging is the gold standard for quantification of RV volumes and ejection fraction in patients with congenital heart diseases; however, it is costly and is not widely available. Echocardiography is the imaging modality that is most available and most frequently used to assess RV systolic function. However, RV ejection fraction cannot be measured accurately by standard two-dimensional echocardiography because of its pyramidal shape. Surrogate parameters of RV systolic function are mostly used in routine practice. New techniques of two-dimensional strain and three-dimensional quantification of RV volumes and ejection fraction have been developed in recent years. The aim of this article is to show the pertinence of each variable of RV systolic function measured by echocardiography in patients with repaired congenital heart disease and residual chronic RV overload.

  15. Silver nanoparticles administered to chicken affect VEGFA and FGF2 gene expression in breast muscle and heart

    NASA Astrophysics Data System (ADS)

    Hotowy, Anna; Sawosz, Ewa; Pineda, Lane; Sawosz, Filip; Grodzik, Marta; Chwalibog, André

    2012-07-01

    Nanoparticles of colloidal silver (AgNano) can influence gene expression. Concerning trials of AgNano application in poultry nutrition, it is useful to reveal whether they affect the expression of genes crucial for bird development. AgNano were administered to broiler chickens as a water solution in two concentrations (10 and 20 ppm). After dissection of the birds, breast muscles and hearts were collected. Gene expression of FGF2 and VEGFA on the mRNA and protein levels were evaluated using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay methods. The results for gene expression in the breast muscle revealed changes on the mRNA level ( FGF2 was up-regulated, P < 0.05) but not on the protein level. In the heart, 20 ppm of silver nanoparticles in drinking water increased the expression of VEGFA ( P < 0.05), at the same time decreasing FGF2 expression both on the transcriptional and translational levels. Changes in the expression of these genes may lead to histological changes, but this needs to be proven using histological and immunohistochemical examination of tissues. In general, we showed that AgNano application in poultry feeding influences the expression of FGF2 and VEGFA genes on the mRNA and protein levels in growing chicken.

  16. Functional Roles Affect Diversity-Succession Relationships for Boreal Beetles

    PubMed Central

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of “functional” groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience. PMID:23977350

  17. Does Bowel Preparation for Colonoscopy Affect Cognitive Function?

    PubMed Central

    Wadsworth, P.; Blackburne, H.; Dixon, L.; Dobbs, B.; Eglinton, T.; Ing, A.; Mulder, R.; Porter, R.J.; Wakeman, C.; Frizelle, F.A.

    2015-01-01

    Abstract Colonoscopy is a common procedure used in the diagnosis and treatment of a range of bowel disorders. Prior preparation involving potent laxatives is a necessary stage to ensure adequate visualization of the bowel wall. It is known that the sedatives given to most patients during the colonoscopy cause a temporary impairment in cognitive function; however, the potential for bowel preparation to affect cognitive function has not previously been investigated. To assess the effect of bowel preparation for colonoscopy on cognitive function. This was a prospective, nonrandomized controlled study of cognitive function in patients who had bowel preparation for colonoscopy compared with those having gastroscopy and therefore no bowel preparation. Cognitive function was assessed using the Modified Mini Mental State Examination (MMMSE) and selected tests from the Cambridge Neuropsychological Test Automated Battery. Individual test scores and changes between initial and subsequent tests were compared between the groups. Age, gender, and weight were also compared. Forty-three colonoscopy and 25 gastroscopy patients were recruited. The 2 groups were similar for age and gender; however, patients having gastroscopy were heavier. MMMSE scores for colonoscopy and gastroscopy groups, respectively, were 28.6 and 29.5 (P = 0.24) at baseline, 28.7 and 29.8 (P = 0.32) at test 2, 28.1 and 28.5 (P = 0.76) at test 3. Motor screening scores for colonoscopy and gastroscopy groups, respectively, were 349.3 and 354.1 (P = 0.97) at baseline, 307.5 and 199.7 (P = 0.06) at test 2, 212.0 and 183.2 (P = 0.33) at test 3. Spatial working memory scores for colonoscopy and gastroscopy groups, respectively, were 14.4 and 6.7 (P = 0.29) at baseline, 9.7 and 4.3 (P = 0.27) at test 2, 10 and 4.5 (P = 0.33) at test 3. Digit Symbol Substitution Test scores for colonoscopy and gastroscopy groups, respectively, were 36.3 and 37.8 (P = 0.84) at baseline, 36.4 and

  18. Linear and nonlinear analysis of normal and CAD-affected heart rate signals.

    PubMed

    Acharya, U Rajendra; Faust, Oliver; Sree, Vinitha; Swapna, G; Martis, Roshan Joy; Kadri, Nahrizul Adib; Suri, Jasjit S

    2014-01-01

    Coronary artery disease (CAD) is one of the dangerous cardiac disease, often may lead to sudden cardiac death. It is difficult to diagnose CAD by manual inspection of electrocardiogram (ECG) signals. To automate this detection task, in this study, we extracted the heart rate (HR) from the ECG signals and used them as base signal for further analysis. We then analyzed the HR signals of both normal and CAD subjects using (i) time domain, (ii) frequency domain and (iii) nonlinear techniques. The following are the nonlinear methods that were used in this work: Poincare plots, Recurrence Quantification Analysis (RQA) parameters, Shannon entropy, Approximate Entropy (ApEn), Sample Entropy (SampEn), Higher Order Spectra (HOS) methods, Detrended Fluctuation Analysis (DFA), Empirical Mode Decomposition (EMD), Cumulants, and Correlation Dimension. As a result of the analysis, we present unique recurrence, Poincare and HOS plots for normal and CAD subjects. We have also observed significant variations in the range of these features with respect to normal and CAD classes, and have presented the same in this paper. We found that the RQA parameters were higher for CAD subjects indicating more rhythm. Since the activity of CAD subjects is less, similar signal patterns repeat more frequently compared to the normal subjects. The entropy based parameters, ApEn and SampEn, are lower for CAD subjects indicating lower entropy (less activity due to impairment) for CAD. Almost all HOS parameters showed higher values for the CAD group, indicating the presence of higher frequency content in the CAD signals. Thus, our study provides a deep insight into how such nonlinear features could be exploited to effectively and reliably detect the presence of CAD.

  19. Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart.

    PubMed

    Preston, Claudia C; Oberlin, Andrew S; Holmuhamedov, Ekhson L; Gupta, Anu; Sagar, Sandeep; Syed, Rashad H Khazi; Siddiqui, Sabeeh A; Raghavakaimal, Sreekumar; Terzic, Andre; Jahangir, Arshad

    2008-06-01

    Aging is associated with progressive decline in energetic reserves compromising cardiac performance and tolerance to injury. Although deviations in mitochondrial functions have been documented in senescent heart, the molecular bases for the decline in energy metabolism are only partially understood. Here, high-throughput transcription profiles of genes coding for mitochondrial proteins in ventricles from adult (6-months) and aged (24-months) rats were compared using microarrays. Out of 614 genes encoding for mitochondrial proteins, 94 were differentially expressed with 95% downregulated in the aged. The majority of changes affected genes coding for proteins involved in oxidative phosphorylation (39), substrate metabolism (14) and tricarboxylic acid cycle (6). Compared to adult, gene expression changes in aged hearts translated into a reduced mitochondrial functional capacity, with decreased NADH-dehydrogenase and F(0)F(1) ATPase complex activities and capacity for oxygen-utilization and ATP synthesis. Expression of genes coding for transcription co-activator factors involved in the regulation of mitochondrial metabolism and biogenesis were downregulated in aged ventricles without reduction in mitochondrial density. Thus, aging induces a selective decline in activities of oxidative phosphorylation complexes I and V within a broader transcriptional downregulation of mitochondrial genes, providing a substrate for reduced energetic efficiency associated with senescence.

  20. Aging-Induced Alterations in Gene Transcripts and Functional Activity of Mitochondrial Oxidative Phosphorylation Complexes in the Heart

    PubMed Central

    Preston, Claudia C.; Oberlin, Andrew S.; Holmuhamedov, Ekhson L.; Gupta, Anu; Sagar, Sandeep; Khazi Syed, Rashad H.; Siddiqui, Sabeeh; Raghavakaimal, Sreekumar; Terzic, Andre; Jahangir, Arshad

    2008-01-01

    Aging is associated with progressive decline in energetic reserves compromising cardiac performance and tolerance to injury. Although deviations in mitochondrial functions have been documented in senescent heart, the molecular bases for the decline in energy metabolism are only partially understood. Here, high-throughput transcription profiles of genes coding for mitochondrial proteins in ventricles from adult (6-months) and aged (24-months) rats were compared using microarrays. Out of 614 genes encoding for mitochondrial proteins, 94 were differentially expressed with 95% downregulated in the aged. The majority of changes affected genes coding for proteins involved in oxidative phosphorylation (39), substrate metabolism (14) and tricarboxylic acid cycle (6). Compared to adult, gene expression changes in aged hearts translated into a reduced mitochondrial functional capacity, with decreased NADH-dehydrogenase and F0F1-ATPase complex activities and capacity for oxygen-utilization and ATP synthesis. Expression of genes coding for transcription co-activator factors involved in the regulation of mitochondrial metabolism and biogenesis were downregulated in aged ventricles without reduction in mitochondrial density. Thus, aging induces a selective decline in activities of oxidative phosphorylation complexes I and V within a broader transcriptional downregulation of mitochondrial genes, providing a substrate for reduced energetic efficiency associated with senescence. PMID:18400259

  1. High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila.

    PubMed

    Zhu, Jun-Yi; Fu, Yulong; Nettleton, Margaret; Richman, Adam; Han, Zhe

    2017-01-20

    Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins. We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting from specific, patient-derived alleles of candidate disease genes. We describe the first high throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors.

  2. Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs.

    PubMed

    Li, Monica X; Hwang, Peter M

    2015-10-25

    In striated muscle, the protein troponin complex turns contraction on and off in a calcium-dependent manner. The calcium-sensing component of the complex is troponin C, which is expressed from the TNNC1 gene in both cardiac muscle and slow-twitch skeletal muscle (identical transcript in both tissues) and the TNNC2 gene in fast-twitch skeletal muscle. Cardiac troponin C (cTnC) is made up of two globular EF-hand domains connected by a flexible linker. The structural C-domain (cCTnC) contains two high affinity calcium-binding sites that are always occupied by Ca(2+) or Mg(2+) under physiologic conditions, stabilizing an open conformation that remains anchored to the rest of the troponin complex. In contrast, the regulatory N-domain (cNTnC) contains a single low affinity site that is largely unoccupied at resting calcium concentrations. During muscle activation, calcium binding to cNTnC favors an open conformation that binds to the switch region of troponin I, removing adjacent inhibitory regions of troponin I from actin and allowing muscle contraction to proceed. Regulation of the calcium binding affinity of cNTnC is physiologically important, because it directly impacts the calcium sensitivity of muscle contraction. Calcium sensitivity can be modified by drugs that stabilize the open form of cNTnC, post-translational modifications like phosphorylation of troponin I, or downstream thin filament protein interactions that impact the availability of the troponin I switch region. Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy. A detailed understanding of how calcium sensitivity is regulated through the troponin complex is necessary for explaining how mutations perturb its function to promote cardiomyopathy and how post-translational modifications in the thin filament affect heart function and heart failure. Troponin modulating drugs are being developed for the treatment of cardiomyopathies and heart failure.

  3. Structure and Function of Cardiac Troponin C (TNNC1): Implications for Heart Failure, Cardiomyopathies, and Troponin Modulating Drugs

    PubMed Central

    Li, Monica X.; Hwang, Peter M.

    2015-01-01

    In striated muscle, the protein troponin complex turns contraction on and off in a calcium-dependent manner. The calcium-sensing component of the complex is troponin C, which is expressed from the TNNC1 gene in both cardiac muscle and slow-twitch skeletal muscle (identical transcript in both tissues) and the TNNC2 gene in fast-twitch skeletal muscle. Cardiac troponin C (cTnC) is made up of two globular EF-hand domains connected by a flexible linker. The structural C-domain (cCTnC) contains two high affinity calcium-binding sites that are always occupied by Ca2+ or Mg2+ under physiologic conditions, stabilizing an open conformation that remains anchored to the rest of the troponin complex. In contrast, the regulatory N-domain (cNTnC) contains a single low affinity site that is largely unoccupied at resting calcium concentrations. During muscle activation, calcium binding to cNTnC favors an open conformation that binds to the switch region of troponin I, removing adjacent inhibitory regions of troponin I from actin and allowing muscle contraction to proceed. Regulation of the calcium binding affinity of cNTnC is physiologically important, because it directly impacts the calcium sensitivity of muscle contraction. Calcium sensitivity can be modified by drugs that stabilize the open form of cNTnC, post-translational modifications like phosphorylation of troponin I, or downstream thin filament protein interactions that impact the availability of the troponin I switch region. Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy. A detailed understanding of how calcium sensitivity is regulated through the troponin complex is necessary for explaining how mutations perturb its function to promote cardiomyopathy and how post-translational modifications in the thin filament affect heart function and heart failure. Troponin modulating drugs are being developed for the treatment of cardiomyopathies and heart failure. PMID:26232335

  4. Development of frontal electroencephalogram (EEG) and heart rate (ECG) responses to affective musical stimuli during the first 12 months of post-natal life.

    PubMed

    Schmidt, Louis A; Trainor, Laurel J; Santesso, Diane L

    2003-06-01

    We examined the development of infants' regional electrocortical (EEG) and heart rate (ECG) responses to affective musical stimuli during the first 12 months of post-natal life. Separate groups of infants were seen at 3 (n=33), 6 (n=42), 9 (n=52), and 12 (n=40) months of age at which time regional EEG and ECG responses were continuously recorded during a baseline condition and during the presentation of three orchestral pieces that were known to vary in affective valence and intensity (happy, sad, fear). Overall, there were two important findings. First, we found that although the overall amount of EEG 4-8 Hz power increased between 3 and 12 months, the distribution of EEG power changed across age, with the younger infants (3- and 6-month-olds) showing no difference between frontal and parietal regions, but the older infants (9- and 12-month-olds) showing relatively more activation at frontal than at parietal sites. This development likely reflects the maturation of frontal lobe function. Second, we found that the presentation of affective music significantly increased brain activity at 3 months of age, had seemingly little effect at 6 and 9 months, and significantly attenuated brain activity at 12 months. Findings suggest that there is a clear developmental change in the effect of music on brain activity in the first year, with music having a "calming" influence on infants by the end of the first year of life.

  5. Lrrc10 is required for early heart development and function in zebrafish

    PubMed Central

    Kim, Ki-Hyun; Antkiewicz, Dagmara S.; Yan, Long; Eliceiri, Kevin W.; Heideman, Warren; Peterson, Richard E.; Lee, Youngsook

    2007-01-01

    Leucine-rich Repeat Containing protein 10 (LRRC10) has recently been identified as a cardiac-specific factor in mice. However, the function of this factor remains to be elucidated. In this study, we investigated the developmental roles of Lrrc10 using zebrafish as an animal model. Knockdown of Lrrc10 in zebrafish embryos (morphants) using morpholinos caused severe cardiac morphogenic defects including a cardiac looping failure accompanied by a large pericardial edema, and embryonic lethality between day 6 and 7 post fertilization. The Lrrc10 morphants exhibited cardiac functional defects as evidenced by a decrease in ejection fraction and cardiac output. Further investigations into the underlying mechanisms of the cardiac defects revealed that the number of cardiomyocyte was reduced in the morphants. Expression of two cardiac genes was deregulated in the morphants including an increase in atrial natriuretic factor, a hallmark for cardiac hypertrophy and failure, and a decrease in cardiac myosin light chain 2, an essential protein for cardiac contractility in zebrafish. Moreover, a reduced fluorescence intensity from NADH in the morphant heart was observed in live zebrafish embryos as compared to control. Taken together, the present study demonstrates that Lrrc10 is necessary for normal cardiac development and cardiac function in zebrafish embryos, which will enhance our understanding of congenital heart defects and heart disease. PMID:17601532

  6. Electroacupuncture improves cardiac function and remodeling by inhibition of sympathoexcitation in chronic heart failure rats.

    PubMed

    Ma, Luyao; Cui, Baiping; Shao, Yongfeng; Ni, Buqing; Zhang, Weiran; Luo, Yonggang; Zhang, Shijiang

    2014-05-15

    Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.

  7. Hypovitaminosis D in patients with heart failure: effects on functional capacity and patients' survival.

    PubMed

    Saponaro, Federica; Marcocci, Claudio; Zucchi, Riccardo; Prontera, Concetta; Clerico, Aldo; Scalese, Marco; Frascarelli, Sabina; Saba, Alessandro; Passino, Claudio

    2017-03-23

    Chronic heart failure is a major cause of morbidity and mortality, but its prognosis remains poor. Vitamin D hormone has many extra-skeletal functions including a positive impact on the cardiovascular system, and has been proposed for mortality risk evaluation in heart failure patients. The aim of the present study was to evaluate vitamin D status in heart failure patients, measured by high performance liquid chromatography coupled with mass spectrometry and to correlate serum 25 hydroxy-vitamin D (25OHD) levels with functional (peak VO2%) and mortality (Metabolic Exercise Cardiac Kidney Index) heart failure parameters. We enrolled 261 consecutive patients diagnosed with heart failure; all patients underwent a comprehensive clinical and biochemical characterization, and serum 25OHD levels were measured by high performance liquid chromatography coupled with mass spectrometry. Cardiopulmonary test parameters and Metabolic Exercise Cardiac Kidney Index of mortality risk were measured in all patients. Serum 25OHD levels ranged between 2 and 45 ng/ml (mean 17 ± 9 ng/ml); most patients (87%) showed hypovitaminosis D, and 25% showed severe vitamin D deficiency (serum 25OHD < 10 ng/ml). Patients with 25OHD < 10 ng/ml had significantly lower cardiopulmonary test VO2/kg, peak VO2% and significantly higher N-terminalproBrain natriuretic peptide and Metabolic Exercise Cardiac Kidney Index, than patients with 25OHD > 10 ng/ml. Patients with peak VO2% < 50% showed significantly lower 25OHD compared to those with peak VO2% > 50%. There was a significant, positive correlation (r = 0.16, p = 0.008) between 25OHD levels and peak VO2%, and an inverse correlation with Metabolic Exercise Cardiac Kidney Index (r = -0.21, p < 0.001), even when adjusted for age, Body Mass Index, MDRD, N-terminalproBrain natriuretic peptide. In conclusion, our findings show that vitamin D levels are associated with functional and mortality heart failure

  8. Maternal metabolic stress may affect oviduct gatekeeper function.

    PubMed

    Jordaens, Lies; Van Hoeck, Veerle; Maillo, Veronica; Gutierrez-Adan, Alfonso; Marei, Waleed Fawzy A; Vlaeminck, Bruno; Thys, Sofie; Sturmey, Roger G S; Bols, Peter; Leroy, Jo

    2017-03-03

    We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24h-treatments at day 9: 1) CONTROL (0µM NEFA + 0%EtOH), 2) SOLVENT CONTROL (0µM NEFA + 0.45%EtOH), 3) BASAL NEFA (720µM NEFA + 0.45%EtOH in the basal compartment), 4) APICAL NEFA (720µM NEFA + 0.45%EtOH in the apical compartment). FITC-albumin was used for monolayer permeability assessment, and related to Transepithelial Electric Resistance (TER). Fatty acid (FA), glucose, lactate and pyruvate concentrations were measured in spent medium. Intracellular lipid droplets (LD) and FA-uptake were studied using Bodipy 493/503 and immunolabelling of FA-transporters (FAT/CD36, FABP3 and caveolin1). BOEC-mRNA was retrieved for qRT-PCR. Results revealed that APICAL NEFA reduced relative TER-increase (46.85%) during treatment, and increased FITC-albumin flux (27.59%) compared to other treatments. In BASAL NEFA, FAs were transferred to the apical compartment as free FAs: mostly palmitic and oleic acid increased, respectively 56.0 % and 33.5% of initial FA-concentrations. APICAL NEFA allowed no FA-transfer, but induced LD-accumulation and upregulated FA-transporter expression (↑CD36, ↑FABP3, ↑CAV1-protein-expression). Gene expression in APICAL NEFA indicated increased anti-apoptotic (↑BCL2) and anti-oxidative (↑SOD1) capacity, upregulated lipid metabolism (↑CPT1, ↑ACSL1 and ↓ACACA), and FA-uptake (↑CAV1). All treatments had similar carbohydrate metabolism and oviduct function specific gene expression (=OVGP1, ESR1, FOXJ1). Overall, elevated NEFAs affected BOEC-metabolism and barrier function differently depending on NEFA-exposure side. Data substantiate the concept of the oviduct as a gatekeeper that may actively alter early embryonic developmental conditions.

  9. Effect of treppe on isovolumic function in the isolated blood-perfused mouse heart.

    PubMed

    Brooks, W W; Apstein, C S

    1996-08-01

    The effects of treppe on left ventricular function in the isolated mouse heart perfused with physiological buffer or with erythrocyte-rich buffer were compared. Left ventricular systolic and diastolic pressures were measured in the isovolumically contracting (balloon in the left ventricle) mouse hearts. Hearts were isolated from 12 adult Swiss-Webster mice and perfused at constant pressure (approximately 85 mmHg) via the aorta. Perfusate consisted of non-recirculating oxygenated Krebs-Henseleit (KH) solution without or with washed cow red blood cells at a hematocrit of 20% (KH-RBC20). The measured ionized calcium concentration of the perfusates were adjusted to 2.2 mmol/l and the temperature held constant at 37 degrees C. Left ventricular systolic pressure, its derivative and diastolic pressures were recorded via a pressure transducer attached to a small latex balloon which was placed in the left ventricle through a left atrial incision. The balloon volume was adjusted to achieve an end-diastolic pressure of 4-8 mmHg. Left ventricular (LV) developed pressure averaged 111 +/- 4 (mean +/- S.E.M.) with KH alone and 108 +/- 4 mmHg with KH-RBC20 while the coronary flows were 3.1 +/- 0.18 and 0.95 +/- 0.15 ml/min respectively. In both KH solution alone and KH-RBC20, developed pressure remained relatively stable from 3 to 5 Hz while +/- dp/dt increased approximately 10% above values observed at 3 Hz. During KH perfusion with increasing stimulation rates, left ventricular pressure and +/- dP/dt, to a lesser extent, decreased while end-diastolic pressure markedly increased at stimulation rates higher than 5 Hz. However, KH-RBC20 perfusion prevented the marked increase in diastolic pressure with increasing stimulation rates (from 5 to 10 Hz). No significant difference in left ventricular developed pressure or +/dP/dt response to treppe were in evidence between groups. These results demonstrate that diastolic function of the isovolumically contracting mouse heart is sensitive

  10. Dietary supplementation of yucca (Yucca schidigera) affects ovine ovarian functions.

    PubMed

    Vlčková, Radoslava; Sopková, Drahomíra; Andrejčáková, Zuzana; Valocký, Igor; Kádasi, Attila; Harrath, Abdel Halim; Petrilla, Vladimír; Sirotkin, Alexander V

    2017-01-15

    Yucca (Yucca schidigera) is a popular medicinal plant due to its many positive effects on animal and human physiology, including their reproductive systems. To examine the effect of supplemental yucca feeding on sheep reproduction, including ovarian functions and their hormonal regulators, ewes were fed (or not fed, control) yucca powder (1.5 g/head/day, 30 days). Macromorphometric indexes of the oviduct, ovary, and ovarian folliculogenesis were measured. Reproductive hormone levels in the blood were measured using a radioimmunoassay. Granulosa cells were aspirated from the ovary, and their proliferation and apoptosis were detected using immunocytochemistry. To assess secretory activity and its response to gonadotropin, ovarian fragments of treated and control ewes were cultured with and without follicle-stimulating hormone (FSH; 0, 0.1, 1, 10, or 100 IU/mL), and the release of reproductive hormones into the culture medium was evaluated. Finally, to examine the direct action of yucca on the ovary, ovarian fragments from control ewes were cultured with and without yucca extract (1, 10, or 100 μg/mL), and the release of reproductive hormones was measured. Yucca supplementation significantly decreased the size of small antral follicles (2 to <5 mm in diameter), increased accumulation of the apoptosis marker bax, and decreased serum progesterone (P4) and estradiol (E2) levels. It inhibited the release of P4 (but not other hormones), to prevent the stimulatory action of FSH on P4 output and promoted insulin-like growth factor I (IGF-I) release by fragments cultured with FSH. However, yucca supplementation did not affect the size of larger follicles and number of follicles, volume and weight of ovaries, length and weight of oviducts, caspase 3 accumulation, cell proliferation, testosterone (T) or IGF-I serum levels, or T or E2 release by cultured ovarian fragments and their response to FSH. Yucca addition to culture medium inhibited P4 and IGF-I, but not T or E2

  11. 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.

  12. 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

  13. Changes in expression of a functional G sub i protein in cultured rat heart cells

    SciTech Connect

    Allen, I.S.; Gaa, S.T.; Rogers, T.B. )

    1988-07-01

    The muscarinic cholinergic agonist, carbachol, and pertussis toxin were used to examine the functional status of the guanine nucleotide-binding protein that inhibits adenylate cyclase (G{sub i}) in cultured neonatal rat heart myocytes. The isoproterenol stimulation of adenylate cyclase activity in myocyte membranes and adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) accumulation in intact cells (4 days in culture) were insensitive to carbachol. However, in cells cultured for 11 days, carbachol inhibited isoproterenol-stimulated cAMP accumulation by 30%. Angiotensin II (ANG II) was also found to inhibit isoproterenol-stimulated cAMP accumulation in day 11 cells in a dose-dependent manner. Pertussis toxin treatment reversed the inhibitory effects of both ANG II and carbachol, suggesting a role for G{sub i} in the process. Carbachol binding to membranes from day 4 cells was relatively insensitive to guanine nucleotides when compared with binding to membranes from day 11 or adult cells. Furthermore, pertussis toxin-mediated {sup 32}P incorporation into a 39- to 41-kDa substrate in day 11 membranes was increased 3.2-fold over that measured in day 4 membranes. These findings support the view that, although G{sub i} is expressed, it is nonfunctional in 4-day-old cultured neonatal rat heart myocytes and acquisition of functional G{sub i} is dependent on culture conditions. Furthermore, the ANG II receptor can couple to G{sub i} in heart.

  14. Right heart function during simulated altitude in patients with pulmonary arterial hypertension

    PubMed Central

    Seccombe, Leigh M; Chow, Vincent; Zhao, Wei; Lau, Edmund M T; Rogers, Peter G; Ng, Austin C C; Veitch, Elizabeth M; Peters, Matthew J; Kritharides, Leonard

    2017-01-01

    Objective Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. Methods Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. Results The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). Conclusions Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function. PMID:28123765

  15. Cognitive Function in Ambulatory Patients with Systolic Heart Failure: Insights from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

    PubMed Central

    Graham, Susan; Ye, Siqin; Qian, Min; Sanford, Alexandra R.; Di Tullio, Marco R.; Sacco, Ralph L.; Mann, Douglas L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Mohr, J. P.; Labovitz, Arthur J.; Lip, Gregory Y. H.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Thompson, John L. P.; Homma, Shunichi

    2014-01-01

    We sought to determine whether cognitive function in stable outpatients with heart failure (HF) is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE) and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance). The mean (SD) for the MMSE was 28.6 (2.0), with 64 (3.1%) of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001), but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure. PMID:25426862

  16. 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

  17. 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.

  18. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

    SciTech Connect

    Umetani, K.; Fukushima, K.

    2013-03-15

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 {mu}m, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 {mu}m diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 {mu}m was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  19. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

    NASA Astrophysics Data System (ADS)

    Umetani, K.; Fukushima, K.

    2013-03-01

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 μm, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 μm diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 μm was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  20. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography.

    PubMed

    Umetani, K; Fukushima, K

    2013-03-01

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 μm, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 μm diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 μm was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  1. Functional neuroimaging of human vocalizations and affective speech.

    PubMed

    Frühholz, Sascha; Sander, David; Grandjean, Didier

    2014-12-01

    Neuroimaging studies have verified the important integrative role of the basal ganglia during affective vocalizations. They, however, also point to additional regions supporting vocal monitoring, auditory-motor feedback processing, and online adjustments of vocal motor responses. For the case of affective vocalizations, we suggest partly extending the model to fully consider the link between primate-general and human-specific neural components.

  2. 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.

  3. Cardiac resynchronization therapy modulation of exercise left ventricular function and pulmonary O₂ uptake in heart failure.

    PubMed

    Tomczak, Corey R; Paterson, Ian; Haykowsky, Mark J; Lawrance, Richard; Martellotto, Andres; Pantano, Alfredo; Gulamhusein, Sajad; Haennel, Robert G

    2012-06-15

    To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P < 0.05). During moderate-intensity exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P < 0.05), and steady-state stroke volume increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P < 0.05). LV end-diastolic volume did not change from rest to steady-state exercise post-CRT (P > 0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P < 0.05). For peak exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P < 0.05). The increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P < 0.05). These findings demonstrate the chronic CRT-mediated cardiac factors that contribute, in part, to the speeding in Vo(2) kinetics and increase in peak Vo(2) in clinically stable heart failure patients.

  4. Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart

    PubMed Central

    Karlstaedt, Anja; Zhang, Xiaotian; Vitrac, Heidi; Harmancey, Romain; Vasquez, Hernan; Wang, Jing Han; Goodell, Margaret A.; Taegtmeyer, Heinrich

    2016-01-01

    Hematologic malignancies are frequently associated with cardiac pathologies. Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a subset of acute myeloid leukemia patients, causing metabolic and epigenetic derangements. We have now discovered that altered metabolism in leukemic cells has a profound effect on cardiac metabolism. Combining mathematical modeling and in vivo as well as ex vivo studies, we found that increased amounts of the oncometabolite d-2-hydroxyglutarate (D2-HG), produced by IDH2 mutant leukemic cells, cause contractile dysfunction in the heart. This contractile dysfunction is associated with impaired oxidative decarboxylation of α-ketoglutarate, a redirection of Krebs cycle intermediates, and increased ATP citrate lyase (ACL) activity. Increased availability of D2-HG also leads to altered histone methylation and acetylation in the heart. We propose that D2-HG promotes cardiac dysfunction by impairing α-ketoglutarate dehydrogenase and induces histone modifications in an ACL-dependent manner. Collectively, our results highlight the impact of cancer cell metabolism on function and metabolism of the heart. PMID:27582470

  5. Frozen Soil Characteristics That Affect Land Mine Functioning.

    DTIC Science & Technology

    1983-04-01

    ii Introduction .............................................. 1 Backgroun ...Table 3 also presents the results of the mine functioning perform- ance . The M12 mine requires between 1739 and 3287 N to function, as indicated by the

  6. Functional role of voltage gated Ca2+ channels in heart automaticity

    PubMed Central

    Mesirca, Pietro; Torrente, Angelo G.; Mangoni, Matteo E.

    2015-01-01

    Pacemaker activity of automatic cardiac myocytes controls the heartbeat in everyday life. Cardiac automaticity is under the control of several neurotransmitters and hormones and is constantly regulated by the autonomic nervous system to match the physiological needs of the organism. Several classes of ion channels and proteins involved in intracellular Ca2+ dynamics contribute to pacemaker activity. The functional role of voltage-gated calcium channels (VGCCs) in heart automaticity and impulse conduction has been matter of debate for 30 years. However, growing evidence shows that VGCCs are important regulators of the pacemaker mechanisms and play also a major role in atrio-ventricular impulse conduction. Incidentally, studies performed in genetically modified mice lacking L-type Cav1.3 (Cav1.3−/−) or T-type Cav3.1 (Cav3.1−/−) channels show that genetic inactivation of these channels strongly impacts pacemaking. In cardiac pacemaker cells, VGCCs activate at negative voltages at the beginning of the diastolic depolarization and importantly contribute to this phase by supplying inward current. Loss-of-function of these channels also impairs atrio-ventricular conduction. Furthermore, inactivation of Cav1.3 channels promotes also atrial fibrillation and flutter in knockout mice suggesting that these channels can play a role in stabilizing atrial rhythm. Genomic analysis demonstrated that Cav1.3 and Cav3.1 channels are widely expressed in pacemaker tissue of mice, rabbits and humans. Importantly, human diseases of pacemaker activity such as congenital bradycardia and heart block have been attributed to loss-of-function of Cav1.3 and Cav3.1 channels. In this article, we will review the current knowledge on the role of VGCCs in the generation and regulation of heart rate and rhythm. We will discuss also how loss of Ca2+ entry through VGCCs could influence intracellular Ca2+ handling and promote atrial arrhythmias. PMID:25698974

  7. Functional morphology and patterns of blood flow in the heart of Python regius.

    PubMed

    Starck, J Matthias

    2009-06-01

    Brightness-modulated ultrasonography, continuous-wave Doppler, and pulsed-wave Doppler-echocardiography were used to analyze the functional morphology of the undisturbed heart of ball pythons. In particular, the action of the muscular ridge and the atrio-ventricular valves are key features to understand how patterns of blood flow emerge from structures directing blood into the various chambers of the heart. A step-by-step image analysis of echocardiographs shows that during ventricular diastole, the atrio-ventricular valves block the interventricular canals so that blood from the right atrium first fills the cavum venosum, and blood from the left atrium fills the cavum arteriosum. During diastole, blood from the cavum venosum crosses the muscular ridge into the cavum pulmonale. During middle to late systole the muscular ridge closes, thus prohibiting further blood flow into the cavum pulmonale. At the same time, the atrio-ventricular valves open the interventricular canal and allow blood from the cavum arteriosum to flow into the cavum venosum. In the late phase of ventricular systole, all blood from the cavum pulmonale is pressed into the pulmonary trunk; all blood from the cavum venosum is pressed into both aortas. Quantitative measures of blood flow volume showed that resting snakes bypass the pulmonary circulation and shunt about twice the blood volume into the systemic circulation as into the pulmonary circulation. When digesting, the oxygen demand of snakes increased tremendously. This is associated with shunting more blood into the pulmonary circulation. The results of this study allow the presentation of a detailed functional model of the python heart. They are also the basis for a functional hypothesis of how shunting is achieved. Further, it was shown that shunting is an active regulation process in response to changing demands of the organism (here, oxygen demand). Finally, the results of this study support earlier reports about a dual pressure

  8. Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G alpha o* protein.

    PubMed

    Zhu, Ming; Gach, Agnieszka A; Liu, GongXin; Xu, Xiaomei; Lim, Chee Chew; Zhang, Julie X; Mao, Lan; Chuprun, Kurt; Koch, Walter J; Liao, Ronglih; Koren, Gideon; Blaxall, Burns C; Mende, Ulrike

    2008-03-01

    In contrast to the other heterotrimeric GTP-binding proteins (G proteins) Gs and Gi, the functional role of G o is still poorly defined. To investigate the role of G alpha o in the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of G alpha o1* (G alpha o*), the predominant G alpha o isoform in the heart. G alpha o expression was increased 3- to 15-fold in mice from 5 independent lines, all of which had a normal life span and no gross cardiac morphological abnormalities. We demonstrate enhanced contractile function in G alpha o* transgenic mice in vivo, along with increased L-type Ca2+ channel current density, calcium transients, and cell shortening in ventricular G alpha o*-expressing myocytes compared with wild-type controls. These changes were evident at baseline and maintained after isoproterenol stimulation. Expression levels of all major Ca2+ handling proteins were largely unchanged, except for a modest reduction in Na+/Ca2+ exchanger in transgenic ventricles. In contrast, phosphorylation of the ryanodine receptor and phospholamban at known PKA sites was increased 1.6- and 1.9-fold, respectively, in G alpha o* ventricles. Density and affinity of beta-adrenoceptors, cAMP levels, and PKA activity were comparable in G alpha o* and wild-type myocytes, but protein phosphatase 1 activity was reduced upon G alpha o* expression, particularly in the vicinity of the ryanodine receptor. We conclude that G alpha o* exerts a positive effect on Ca2+ cycling and contractile function. Alterations in protein phosphatase 1 activity rather than PKA-mediated phosphorylation might be involved in hyperphosphorylation of key Ca2+ handling proteins in hearts with constitutive G alpha o activation.

  9. Changes in cardiovascular function induced by verapamil in healthy subjects and in patients with ischemic heart disease.

    PubMed

    Vincenzi, M; Morlino, T; Allegri, P; Barbieri, E; Cappelletti, F; De Lio, U; Ometto, R; Maiolino, P

    1981-01-01

    Alterations in cardiovascular function induced by the acute intravenous administration of verapamil (5 or 10 mg) in 52 patients (29 with ischemic heart disease and 23 without heart disease) were evaluated with use of invasive techniques (right and left heart catheterization, left ventricular cineangiography, and coronary arteriography). The most significant changes were represented by a decrease in systemic vascular resistance and systemic arterial pressure, and an increase in heart rate and cardiac output. Contractility indexes were not depressed in either group, and altered ventricular wall motion tended to improve to a slightly smaller degree than in patients treated with nitroglycerin. The use of verapamil in patients with ischemic heart disease appears to be safe, and concern about the negative inotropic influences in humans no longer seems justified.

  10. Pycnogenol® and its fractions influence the function of isolated heart in rats with experimental diabetes mellitus.

    PubMed

    Kralova, Eva; Jankyova, Stanislava; Mucaji, Pavel; Gresakova, Eva; Stankovicova, Tatiana

    2015-02-01

    The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity "in vitro" was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC's fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components.

  11. Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure.

    PubMed

    Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

    2014-12-01

    Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.

  12. DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping and differentiation.

    PubMed

    Choudhry, Priya; Trede, Nikolaus S

    2013-01-01

    DiGeorge syndrome (DGS) is the most common microdeletion syndrome, and is characterized by congenital cardiac, craniofacial and immune system abnormalities. The cardiac defects in DGS patients include conotruncal and ventricular septal defects. Although the etiology of DGS is critically regulated by TBX1 gene, the molecular pathways underpinning TBX1's role in heart development are not fully understood. In this study, we characterized heart defects and downstream signaling in the zebrafish tbx1(-/-) mutant, which has craniofacial and immune defects similar to DGS patients. We show that tbx1(-/-) mutants have defective heart looping, morphology and function. Defective heart looping is accompanied by failure of cardiomyocytes to differentiate normally and failure to change shape from isotropic to anisotropic morphology in the outer curvatures of the heart. This is the first demonstration of tbx1's role in regulating heart looping, cardiomyocyte shape and differentiation, and may explain how Tbx1 regulates conotruncal development in humans. Next we elucidated tbx1's molecular signaling pathway guided by the cardiac phenotype of tbx1(-/-) mutants. We show for the first time that wnt11r (wnt11 related), a member of the non-canonical Wnt pathway, and its downstream effector gene alcama (activated leukocyte cell adhesion molecule a) regulate heart looping and differentiation similarly to tbx1. Expression of both wnt11r and alcama are downregulated in tbx1(-/-) mutants. In addition, both wnt11r (-/-) mutants and alcama morphants have heart looping and differentiation defects similar to tbx1(-/-) mutants. Strikingly, heart looping and differentiation in tbx1(-/-) mutants can be partially rescued by ectopic expression of wnt11r or alcama, supporting a model whereby heart looping and differentiation are regulated by tbx1 in a linear pathway through wnt11r and alcama. This is the first study linking tbx1 and non-canonical Wnt signaling and extends our understanding of DGS and

  13. The Tumorigenicity of Multipotent Adult Germline Stem Cells Transplanted into the Heart Is Affected by Natural Killer Cells and by Cyclosporine A Independent of Its Immunosuppressive Effects

    PubMed Central

    Hübscher, Daniela; Kaiser, Diana; Elsner, Leslie; Monecke, Sebastian; Dressel, Ralf; Guan, Kaomei

    2017-01-01

    Transplantation of stem cells represents an upcoming therapy for many degenerative diseases. For clinical use, transplantation of pluripotent stem cell-derived cells should lead to integration of functional grafts without immune rejection or teratoma formation. Our previous studies showed that the risk of teratoma formation is highly influenced by the immune system of the recipients. In this study, we have observed a higher teratoma formation rate when undifferentiated so-called multipotent adult germline stem cells (maGSCs) were transplanted into the heart of T, B, and natural killer (NK) cell-deficient RAG2−/−γc−/− mice than in RAG2−/− mice, which still have NK cells. Notably, in both strains, the teratoma formation rate was significantly reduced by the immunosuppressive drug cyclosporine A (CsA). Thus, CsA had a profound effect on teratoma formation independent of its immunosuppressive effects. The transplantation into RAG2−/− mice led to an activation of NK cells, which reached the maximum 14 days after transplantation and was not affected by CsA. The in vivo-activated NK cells efficiently killed YAC-1 and also maGSC target cells. This NK cell activation was confirmed in C57BL/6 wild-type mice whether treated with CsA or not. Sham operations in wild-type mice indicated that the inflammatory response to open heart surgery rather than the transplantation of maGSCs activated the NK cell system. An activation of NK cells during the transplantation of stem cell-derived in vitro differentiated grafts might be clinically beneficial by reducing the risk of teratoma formation by residual pluripotent cells. PMID:28220117

  14. Preservation of Myocardial Perfusion and Function by Keeping Hypertrophied Heart Empty and Beating for Valve Surgery: An In Vivo MR Study of Pig Hearts

    PubMed Central

    Xiang, Bo; Deng, Jixian; Lin, Hung-Yu; Freed, Darren H.; Arora, Rakesh C.

    2017-01-01

    Objectives. Normothermic hyperkalemic cardioplegia arrest (NHCA) may not effectively preserve hypertrophied myocardium during open-heart surgery. Normothermic normokalemic beating perfusion (NNBP), keeping hearts empty-beating, was utilized as an alternative to evaluate its cardioprotective role. Materials and Methods. Twelve hypertrophied pig hearts at 58.6 ± 7.2 days after ascending aorta banding underwent NNBP and NHCA, respectively. Near infrared myocardial perfusion imaging with indocyanine green (ICG) was conducted to assess myocardial perfusion. Left ventricular (LV) contractile function was assessed by cine MRI. TUNEL staining and western blotting for caspase-3 cleavage and cardiac troponin I (cTnI) degradation were conducted in LV tissue samples. Results. Ascending aortic diameter was reduced by 52.7% ± 0.4% at approximately fifty-eight days after banding. LV wall thickness was significantly higher in aorta banding than in sham operation. Myocardial blood flow reflected by maximum ICG absorbance value was markedly higher in NNBP than in NHCA. The amount of apoptotic cardiomyocyte was significantly lower in NNBP than in NHCA. NNBP alleviated caspase-3 cleavage and cTnI degradation associated with NHCA. NNBP displayed a substantially increased postoperative ejection fraction relative to NHCA. Conclusions. NNBP was better than NHCA in enhancing myocardial perfusion, inhibiting cardiomyocyte apoptosis, and preserving LV contractile function for hypertrophied hearts.

  15. Effects of Kaempferia parviflora Wall. Ex. Baker and sildenafil citrate on cGMP level, cardiac function, and intracellular Ca2+ regulation in rat hearts.

    PubMed

    Weerateerangkul, Punate; Palee, Siripong; Chinda, Kroekkiat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2012-09-01

    Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes.

  16. 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.

  17. Concomitant gastroparesis negatively affects children with functional gallbladder disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the present study was to determine whether concomitant gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to determine whether concomitant gastroparesis affects clinical outcome in children with BD. We conducted a retrospective chart review of children with BD (ejecti...

  18. The effects of androgen deprivation therapy on cardiac function and heart failure: implications for management of prostate cancer.

    PubMed

    Edelman, Scott; Butler, Javed; Hershatter, Bruce W; Khan, Mohammad K

    2014-12-01

    Conflicting clinical evidence regarding the possible association between androgen deprivation therapy (ADT) with heart failure in men with prostate cancer is reviewed, including 2 population-based registries showing such an association, and 1 showing no association. Studies of the effects of androgens on cardiomyocyte contractility at the molecular level, the effects of testosterone on the cardiovascular system, particularly cardiac function, and the beneficial effects of testosterone therapy for patients with heart failure might help illuminate this controversy. Future studies are needed to evaluate the effect of ADT on end points of heart failure. The authors weigh the possible adverse effects of ADT on cardiac function and heart failure against its known benefits to cancer outcomes, defined according to published, randomized trials, in a discussion of the implications of the preclinical and clinical literature on the management of prostate cancer in men at risk for heart failure. In the absence of conclusive evidence that ADT causes heart failure, the authors discuss clinical situations in which ADT may be delayed, given on a short-term or intermittent basis, or withheld from treatment with the goal of reducing the risks of heart failure without compromising prostate cancer outcomes.

  19. Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate.

    PubMed Central

    Russell, R R; Taegtmeyer, H

    1991-01-01

    To determine the temporal relationship between changes in contractile performance and flux through the citric acid cycle in hearts oxidizing acetoacetate, we perfused isolated working rat hearts with either glucose or acetoacetate (both 5 mM) and freeze-clamped the tissue at defined times. After 60 min of perfusion, hearts utilizing acetoacetate exhibited lower systolic and diastolic pressures and lower cardiac outputs. The oxidation of acetoacetate increased the tissue content of 2-oxoglutarate and glutamate and decreased the content of succinyl-CoA suggesting inhibition of citric acid cycle flux through 2-oxoglutarate dehydrogenase. Whereas hearts perfused with either acetoacetate or glucose were similar with respect to their function for the first 20 min, changes in tissue metabolites were already observed within 5 min of perfusion at near-physiological workloads. The addition of lactate or propionate, but not acetate, to hearts oxidizing acetoacetate improved contractile performance, although inhibition of 2-oxoglutarate dehydrogenase was probably not diminished. If lactate or propionate were added, malate and citrate accumulated indicating utilization of anaplerotic pathways for the citric acid cycle. We conclude that a decreased rate of flux through 2-oxoglutarate dehydrogenase in hearts oxidizing acetoacetate precedes, and may be responsible for, contractile failure and is not the result of decreased cardiac work. Further, anaplerosis play an important role in the maintenance of contractile function in hearts utilizing acetoacetate. Images PMID:1671390

  20. Role of concomitant tricuspid surgery in moderate functional tricuspid regurgitation in patients undergoing left heart valve surgery.

    PubMed

    Mahesh, Balakrishnan; Wells, Francis; Nashef, Samer; Nair, Sukumaran

    2013-01-01

    Functional tricuspid regurgitation (FTR) is frequently present in patients undergoing aortic, and particularly mitral valve, surgery. Untreated FTR may lead to right heart failure. Reoperative cardiac surgery for late FTR is associated with high morbidity and mortality. Therefore, severe FTR has emerged as a Class I indication for concomitant tricuspid valve surgery in patients undergoing left valve surgery. Concomitant tricuspid valve surgery during left heart valve surgery to address moderate and mild FTR is controversial. This review addresses this issue and proposes an algorithm for the treatment of FTR in patients undergoing left heart valve surgery.

  1. Left Atrial Structure and Function in Heart Failure with Preserved Ejection Fraction: A RELAX Substudy

    PubMed Central

    McNulty, Steven E.; Hernandez, Adrian F.; Semigran, Marc J.; Lewis, Gregory D.; Jerosch-Herold, Michael; Kim, Raymond J.; Redfield, Margaret M.; Kwong, Raymond Y.

    2016-01-01

    Given the emerging recognition of left atrial structure and function as an important marker of disease in heart failure with preserved ejection fraction (HF-pEF), we investigated the association between left atrial volume and function with markers of disease severity and cardiac structure in HF-pEF. We studied 100 patients enrolled in the PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial who underwent cardiac magnetic resonance (CMR), cardiopulmonary exercise testing, and blood collection before randomization. Maximal left atrial volume index (LAVi; N = 100), left atrial emptying fraction (LAEF; N = 99; including passive and active components (LAEFP, LAEFA; N = 80, 79, respectively) were quantified by CMR. After adjustment for multiple testing, maximal LAVi was only associated with age (ρ = 0.39), transmitral filling patterns (medial E/e’ ρ = 0.43), and N-terminal pro-BNP (NT-proBNP; ρ = 0.65; all p<0.05). Lower LAEF was associated with older age, higher transmitral E/A ratio and higher NT-proBNP. Peak VO2 and VE/VCO2 slope were not associated with left atrial structure or function. After adjustment for age, sex, transmitral E/A ratio, CMR LV mass, LV ejection fraction, and creatinine clearance, NT-proBNP remained associated with maximal LAVi (β = 0.028, p = 0.0007) and total LAEF (β = -0.033, p = 0.001). Passive and active LAEF were most strongly associated with age and NT-proBNP, but not gas exchange or other markers of ventricular structure or filling properties. Left atrial volume and emptying function are associated most strongly with NT-proBNP and diastolic filling properties, but not significantly with gas exchange, in HFpEF. Further research to explore the relevance of left atrial structure and function in HF-pEF is warranted. PMID:27812147

  2. Female athlete's heart: Systolic and diastolic function related to circulatory dimensions.

    PubMed

    Hedman, K; Tamás, É; Henriksson, J; Bjarnegård, N; Brudin, L; Nylander, E

    2015-06-01

    There are relatively few studies on female athletes examining cardiac size and function and how these measures relate to maximal oxygen uptake (VO2max). When determining sports eligibility, it is important to know what physiological adaptations and characteristics may be expected in female athletes, taking body and cardiac size into account. The purposes of this study were (a) to compare right and left heart dimensions and function in female endurance athletes (ATH) and in non-athletic female controls of similar age (CON); and (b) to explore how these measures related to VO2max. Forty-six ATH and 48 CON underwent a maximal bicycle exercise test and an echocardiographic examination at rest, including standard and color tissue Doppler investigation. All heart dimensions indexed for body size were larger in ATH (all P < 0.01). The diastolic mitral E/A ratio was 27% higher in ATH (P < 0.001) while systolic left and right atrio-ventricular longitudinal displacement was 7% (P = 0.002) and 15% (P < 0.001) larger in ATH, respectively. Half (50.3%) of the variability in VO2max could be explained by left ventricular end-diastolic volume. Our results could be useful in evaluating female endurance athletes with suspected cardiac disease and contribute to understanding differences between female athletes and non-athletes.

  3. Implication of base heart rate in autonomic nervous function, blood pressure and health-related QOL.

    PubMed

    Okano, Yasuko; Hirawa, Nobuhito; Matsushita, Kei; Tamura, Kouichi; Kihara, Minoru; Toya, Yoshiyuki; Tochikubo, Osamu; Umemura, Satoshi

    2005-01-01

    Increased resting heart rate (HR) and increased sympathetic nervous activity are independent risk factors for cardiovascular disease. Recently, base heart rate (HRo: minimum stable HR during sleep) has been reported to relate to cardiac stroke volume and age. However, little is known about the relevance of HRo. The aim of our study was to evaluate how HRo is associated with HR variability (HRV), blood pressure and health-related quality of life (HRQOL) in healthy subjects. A total of 139 volunteers participated in this study that measured 24-hr HR, HRV, and blood pressure. HRo was estimated from the trendgram and the histogram of HR during the nighttime (sleep) period, and calculated as the 1% lowest value of its integral. HRQOL was assessed by Medical Outcome Study Short-Forum 36-Item Health Survey. Sympathetic nervous activity (ratio of low frequency to high frequency component: LF/HF) and parasympathetic nervous activity (high frequency component: HF) were calculated by ECG monitoring. HRo was positively correlated with 24-hr LF/HF and nighttime LF/HF. HRo was negatively correlated with 24-hr HF and nighttime HF. Moreover, HRo was positively correlated with the scores of social functioning and role-physical. Using multivariate analysis, HRo is related to LF/HF, body mass index, and the score of social functioning (HRQOL). HRo may be a useful indicator for assessing sympathetic nervous activity and HRQOL in normotensive healthy subjects.

  4. Potassium currents in the heart: functional roles in repolarization, arrhythmia and therapeutics.

    PubMed

    Chiamvimonvat, Nipavan; Chen-Izu, Ye; Clancy, Colleen E; Deschenes, Isabelle; Dobrev, Dobromir; Heijman, Jordi; Izu, Leighton; Qu, Zhilin; Ripplinger, Crystal M; Vandenberg, Jamie I; Weiss, James N; Koren, Gideon; Banyasz, Tamas; Grandi, Eleonora; Sanguinetti, Michael C; Bers, Donald M; Nerbonne, Jeanne M

    2017-04-01

    This is the second of the two White Papers from the fourth UC Davis Cardiovascular Symposium Systems Approach to Understanding Cardiac Excitation-Contraction Coupling and Arrhythmias (3-4 March 2016), a biennial event that brings together leading experts in different fields of cardiovascular research. The theme of the 2016 symposium was 'K(+) channels and regulation', and the objectives of the conference were severalfold: (1) to identify current knowledge gaps; (2) to understand what may go wrong in the diseased heart and why; (3) to identify possible novel therapeutic targets; and (4) to further the development of systems biology approaches to decipher the molecular mechanisms and treatment of cardiac arrhythmias. The sessions of the Symposium focusing on the functional roles of the cardiac K(+) channel in health and disease, as well as K(+) channels as therapeutic targets, were contributed by Ye Chen-Izu, Gideon Koren, James Weiss, David Paterson, David Christini, Dobromir Dobrev, Jordi Heijman, Thomas O'Hara, Crystal Ripplinger, Zhilin Qu, Jamie Vandenberg, Colleen Clancy, Isabelle Deschenes, Leighton Izu, Tamas Banyasz, Andras Varro, Heike Wulff, Eleonora Grandi, Michael Sanguinetti, Donald Bers, Jeanne Nerbonne and Nipavan Chiamvimonvat as speakers and panel discussants. This article summarizes state-of-the-art knowledge and controversies on the functional roles of cardiac K(+) channels in normal and diseased heart. We endeavour to integrate current knowledge at multiple scales, from the single cell to the whole organ levels, and from both experimental and computational studies.

  5. High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila

    PubMed Central

    Zhu, Jun-yi; Fu, Yulong; Nettleton, Margaret; Richman, Adam; Han, Zhe

    2017-01-01

    Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins. We also demonstrated the use of Drosophila to evaluate cardiac phenotypes resulting from specific, patient-derived alleles of candidate disease genes. We describe the first high throughput in vivo validation system to screen candidate disease genes identified from patients. This approach has the potential to facilitate development of precision medicine approaches for CHD and other diseases associated with genetic factors. DOI: http://dx.doi.org/10.7554/eLife.22617.001 PMID:28084990

  6. 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.

  7. Engineering the heart: evaluation of conductive nanomaterials for improving implant integration and cardiac function.

    PubMed

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; Mengqiu Xing, Malcolm; Wang, Changyong

    2014-01-16

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

  8. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    PubMed Central

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

    2014-01-01

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

  9. Radionuclide noninvasive evaluation of heart failure beyond left ventricular function assessment.

    PubMed

    Flotats, Albert; Carrió, Ignasi

    2009-01-01

    The management of patients with heart failure (HF) is challenging and requires the integration of clinical skills and accurate ancillary tests for the correct diagnosis and estimation of individual prognosis. Although the basic characterization of patients with HF is supported primarily by echocardiographic assessment of the left ventricular function, other noninvasive imaging procedures are being developed, including those involved in the processes of myocardial perfusion, metabolism, cellular injury, intersticial dysregulation, and neurohormonal receptor function. Nuclear techniques for molecular imaging of the myocardium may provide valuable insights into the pathophysiology, severity, management (medical/mechanical/surgical), response to treatment, and prognosis of HF patients. This will permit individualized management decisions and hopefully facilitate better clinical outcomes for patients with HF.

  10. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    NASA Astrophysics Data System (ADS)

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

    2014-01-01

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

  11. Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis.

    PubMed

    Pearson, M J; Mungovan, S F; Smart, N A

    2017-03-01

    Diastolic dysfunction contributes to the development and progression of heart failure. Conventional echocardiography and tissue Doppler imaging are widely utilised in clinical research providing a number of indices of diastolic function valuable in the diagnosis and prognosis of heart failure patients. The aim of this meta-analysis was to quantify the effect of exercise training on diastolic function in patients with heart failure. Exercise training studies that investigate different indices of diastolic function in patients with heart failure have reported that exercise training improves diastolic function in these patients. We sought to add to the current literature by quantifying, where possible, the effect of exercise training on diastolic function. We conducted database searches (PubMed, EBSCO, EMBASE, and Cochrane Trials Register to 31 July 2016) for exercise based rehabilitation trials in heart failure, using the search terms 'exercise training, diastolic function and diastolic dysfunction'. Data from six studies, with a total of 266 heart failure with reduced ejection fraction (HFrEF) participants, 144 in intervention groups and 122 in control groups, indicated a significant reduction in the ratio of early diastolic transmitral velocity (E) to early diastolic tissue velocity (E') (E/E' ratio) with exercise training, exercise vs. control mean difference (MD) of -2.85 (95% CI -3.66 to -2.04, p < 0.00001). Data from five studies in heart failure with preserved ejection fraction (HFpEF) patients, with a total of 204 participants, 115 in intervention groups and 89 in control groups, also demonstrated a significant improvement in E/E' in exercise vs. control MD of -2.38 (95% CI -3.47 to -1.28, p < 0.0001).

  12. Effects of Type 2 Diabetes on Brain Structure and Cognitive Function: African American–Diabetes Heart Study MIND

    PubMed Central

    Whitlow, C.T.; Sink, K.M.; Divers, J.; Smith, S.C.; Xu, J.; Palmer, N.D.; Hugenschmidt, C.E.; Williamson, J.D.; Bowden, D.W.; Freedman, B.I.; Maldjian, J.A.

    2016-01-01

    BACKGROUND AND PURPOSE Rates of type 2 diabetes are higher among African Americans compared with individuals of European ancestry. The purpose of this investigation was to determine the relationship between MR imaging measures of brain structure (volume of GM, WM, WM lesions) and cognitive function in a population of African Americans with type 2 diabetes. These MR imaging measures of brain structure are affected by type 2 diabetes–associated macrovascular and microvascular disease and may be associated with performance on tasks of cognitive function in the understudied African American population. MATERIALS AND METHODS African Americans with type 2 diabetes enrolled in the African American–Diabetes Heart Study MIND study (n = 263) were evaluated across a broad range of cognitive domains and imaged with brain MR imaging. Associations between cognitive parameters and MR imaging measures of whole-brain GM, WM, and WM lesion volumes were assessed by using adjusted multivariate models. RESULTS Lower GM volume was associated with poorer performance on measures of general cognitive function, working memory, and executive function. Higher WM lesion volume was associated with poorer performance on a smaller subset of cognitive domains compared with GM volume but included aspects of working memory and executive function. There were no statistically significant associations with WM volume. CONCLUSIONS Markers of cortical atrophy and WM lesion volume are associated with cognitive function in African Americans with type 2 diabetes. These associations are described in an African American cohort with disease control similar to that of individuals of European ancestry, rather than underserved African Americans with poor access to health care. Interventions to reduce cortical atrophy and WM disease may improve cognitive outcomes in this understudied population. PMID:26206811

  13. Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

    PubMed

    Dan Cao; Yingjie Li; Ling Wei; Yingying Tang

    2016-08-01

    Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

  14. Abnormal calcium homeostasis in heart failure with preserved ejection fraction is related to both reduced contractile function and incomplete relaxation: an electromechanically detailed biophysical modeling study

    PubMed Central

    Adeniran, Ismail; MacIver, David H.; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Heart failure with preserved ejection fraction (HFpEF) accounts for about 50% of heart failure cases. It has features of incomplete relaxation and increased stiffness of the left ventricle. Studies from clinical electrophysiology and animal experiments have found that HFpEF is associated with impaired calcium homeostasis, ion channel remodeling and concentric left ventricle hypertrophy (LVH). However, it is still unclear how the abnormal calcium homeostasis, ion channel and structural remodeling affect the electro-mechanical dynamics of the ventricles. In this study we have developed multiscale models of the human left ventricle from single cells to the 3D organ, which take into consideration HFpEF-induced changes in calcium handling, ion channel remodeling and concentric LVH. Our simulation results suggest that at the cellular level, HFpEF reduces the systolic calcium level resulting in a reduced systolic contractile force, but elevates the diastolic calcium level resulting in an abnormal residual diastolic force. In our simulations, these abnormal electro-mechanical features of the ventricular cells became more pronounced with the increase of the heart rate. However, at the 3D organ level, the ejection fraction of the left ventricle was maintained due to the concentric LVH. The simulation results of this study mirror clinically observed features of HFpEF and provide new insights toward the understanding of the cellular bases of impaired cardiac electromechanical functions in heart failure. PMID:25852567

  15. Association between heart rate variability and fluctuations in resting-state functional connectivity

    PubMed Central

    Chang, Catie; Metzger, Coraline D.; Glover, Gary H.; Duyn, Jeff H.; Heinze, Hans-Jochen; Walter, Martin

    2012-01-01

    Functional connectivity has been observed to fluctuate across the course of a resting state scan, though the origins and functional relevance of this phenomenon remain to be shown. The present study explores the link between endogenous dynamics of functional connectivity and autonomic state in an eyes-closed resting condition. Using a sliding window analysis on resting state fMRI data from 35 young, healthy male subjects, we examined how heart rate variability (HRV) covaries with temporal changes in whole-brain functional connectivity with seed regions previously described to mediate effects of vigilance and arousal (amygdala and dorsal anterior cingulate cortex; dACC). We identified a set of regions, including brainstem, thalamus, putamen, and dorsolateral prefrontal cortex, that became more strongly coupled with the dACC and amygdala seeds during states of elevated HRV. Effects differed between high and low frequency components of HRV, suggesting specific contributions of parasympathetic and sympathetic tone on individual connections. Furthermore, dynamics of functional connectivity could be separated from those primarily related to BOLD signal fluctuations. The present results contribute novel information about the neural basis of transient changes of autonomic nervous system states, and suggest physiological and psychological components of the recently observed non-stationarity in resting state functional connectivity. PMID:23246859

  16. Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

    PubMed

    Yamanushi, Tomoko T; Kabuto, Hideaki; Hirakawa, Eiichiro; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2014-04-01

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

  17. Abdominal obesity and structure and function of the heart in healthy male Koreans

    PubMed Central

    Son, Jung-Woo; Sung, Joong Kyung; Lee, Jun-Won; Youn, Young Jin; Ahn, Min-Soo; Ahn, Sung Gyun; Yoo, Byung-Su; Lee, Seung-Hwan; Yoon, Junghan; Koh, Sang Baek; Kim, Jang-Young

    2016-01-01

    Abstract Although central obesity is a more powerful predictor of cardiovascular disease (CVD) than general obesity, there is limited information on structural and functional changes of the heart in central obesity. Therefore, we evaluated the association between abdominal obesity and geometric and functional changes of the heart in healthy males. A total of 1460 healthy males aged 40 to 70 years without known CVD from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population were included. All individuals underwent conventional 2-dimensional echocardiography and tissue Doppler imaging to measure left atrial (LA) and left ventricle (LV) geometry and function. Increasing tertiles of waist circumference (WC) were associated with stepwise increases in LA volume, LV end-diastolic dimension, LV mass to height2, deceleration time of E wave, and lower E/A ratio (all P trends <0.001). In multivariable logistic regression models, the odds ratios for LA enlargement, LV hypertrophy, LV enlargement, and diastolic dysfunction comparing the upper tertile of WC (>89 cm) to the lowest tertile (<82 cm) were 2.81 (95% confidence interval [CI] 2.24–3.54), 3.65 (95% CI 2.54–5.26), 4.23 (95% CI 2.61–6.87), and 1.75 (95% CI 1.37–2.22), respectively. LV ejection fraction and relative wall thickness were not increased with increasing WC. The association between WC and LA enlargement, LV enlargement, and diastolic dysfunction persisted after stratification by body mass index tertiles. Central obesity may be a stronger predictor than general obesity of geometric and functional changes in the LV and LA. PMID:27684832

  18. Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

    PubMed

    Gilbert, Cameron; Cherney, David Z I; Parker, Andrea B; Mak, Susanna; Floras, John S; Al-Hesayen, Abdul; Parker, John D

    2016-01-15

    Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications.

  19. Estrogen attenuates chronic volume overload induced structural and functional remodeling in male rat hearts.

    PubMed

    Gardner, Jason D; Murray, David B; Voloshenyuk, Tetyana G; Brower, Gregory L; Bradley, Jessica M; Janicki, Joseph S

    2010-02-01

    We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload.

  20. Factors affecting the development of lung function in Tunisian children.

    PubMed

    Trabelsi, Y; Pariès, J; Harrabi, I; Zbidi, A; Tabka, Z; Richalet, J P; Buvry, A

    2008-01-01

    We undertook to evaluate the impacts of morphology at birth, physical activity, anthropometric, socioeconomic and environmental factors on lung function in healthy Tunisian children. Pulmonary function parameters were measured with a Minato portable spirometer in a randomized population of 756 healthy children (388 males and 368 females) aged between 6 and 16. The morphology at birth, the gestational age, the physical activity, the socioeconomic status, the type of habitation, and the environmental factors were all assessed by a standard questionnaire. Using univariate analysis, we found that: (1) morphometric parameters (height, weight, maximal inspiratory, and expiratory perimeter), as well as sex were highly associated with pulmonary function parameters; (2) Height at birth showed strong significant relations with FVC, FEV(1), and FEV(1)/FVC; (3) lung function parameters were influenced by physical training of our children, socioeconomic status, indoor pollution, and passive smoking; and (4) we did not observe any association between the gestational age and the weight at their birth and lung function parameters. Using a general linear model analysis, morphometric parameters, age, sex, type of heating, and maximal inspiratory and expiratory perimeters had significant relation with respiratory parameters. In our population of healthy Tunisian children, the main predictive factors of the pulmonary development were the morphological factors such as height, weight, maximal inspiratory, and expiratory thoracic perimeter, sex and age, and the environmental conditions such as type of heating but not morphology at birth, physical activity, or socioeconomic status.

  1. Outcomes and worsening renal function in patients hospitalized with heart failure with preserved ejection fraction.

    PubMed

    Sharma, Kavita; Hill, Terence; Grams, Morgan; Daya, Natalie R; Hays, Allison G; Fine, Derek; Thiemann, David R; Weiss, Robert G; Tedford, Ryan J; Kass, David A; Schulman, Steven P; Russell, Stuart D

    2015-11-15

    Heart failure with preserved ejection fraction (HFpEF) has been described as a disease of elderly subjects with female predominance and hypertension. Our clinical experience suggests patients with HFpEF from an urban population are far more heterogenous, with greater co-morbidities and significant inhospital morbidity. There are limited data on the hospitalization course and outcomes in acute decompensated HFpEF. Hospitalizations for acute heart failure at our institution from July 2011 to June 2012 were identified by International Classification of Diseases, Ninth Revision, codes and physician review for left ventricular ejection fraction ≥50% and were reviewed for patient characteristics and clinical outcomes. Worsening renal function (WRF) was defined as creatinine increase of ≥0.3 mg/dl by 72 hours after admission. Hospital readmission and mortality data were captured from electronic medical records and the Social Security Death Index. Of 434 heart failure admissions, 206 patients (47%) with HFpEF were identified. WRF developed in 40%, the highest reported in HFpEF to date, and was associated with higher blood pressure and lower volume of diuresis. Compared to previous reports, hospitalized patients with HFpEF were younger (mean age 63.2 ± 13.6 years), predominantly black (74%), and had more frequent and severe co-morbidities: hypertension (89%), diabetes (56%), and chronic kidney disease (55%). There were no significant differences in 1- and 12-month outcomes by gender, race, or WRF. In conclusion, we found hospitalized patients with HFpEF from an urban population develop a high rate of WRF are younger than previous cohorts, often black, and have greater co-morbidities than previously described.

  2. Effect and clinical prediction of worsening renal function in acute decompensated heart failure.

    PubMed

    Breidthardt, Tobias; Socrates, Thenral; Noveanu, Markus; Klima, Theresia; Heinisch, Corinna; Reichlin, Tobias; Potocki, Mihael; Nowak, Albina; Tschung, Christopher; Arenja, Nisha; Bingisser, Roland; Mueller, Christian

    2011-03-01

    We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.

  3. Evaluation of left ventricular function by radionuclide angiography during exercise in normal subjects and in patients with chronic coronary heart disease.

    PubMed

    Iskandrian, A S; Hakki, A H; DePace, N L; Manno, B; Segal, B L

    1983-06-01

    Radionuclide angiography permits evaluation of left ventricular performance during exercise. There are several factors that may affect the results in normal subjects and in patients with chronic coronary heart disease. Important among these are the selection criteria: age, sex, level of exercise, exercise end points, ejection fraction at rest and effects of pharmacologic agents. An abnormal ejection fraction response to exercise is not a specific marker for coronary heart disease but may be encountered in other cardiac diseases. In addition to the diagnostic considerations, important prognostic data can be obtained. Further studies are needed to determine the prognostic implications of anatomic findings versus the functional abnormalities induced by exercise in patients with coronary artery disease.

  4. Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

    PubMed Central

    Marcus, Noah J; Rio, Rodrigo; Schultz, Evan P; Xia, Xiao-Hong; Schultz, Harold D

    2014-01-01

    In congestive heart failure (CHF), carotid body (CB) chemoreceptor activity is enhanced and is associated with oscillatory (Cheyne–Stokes) breathing patterns, increased sympathetic nerve activity (SNA) and increased arrhythmia incidence. We hypothesized that denervation of the CB (CBD) chemoreceptors would reduce SNA, reduce apnoea and arrhythmia incidence and improve ventricular function in pacing-induced CHF rabbits. Resting breathing, renal SNA (RSNA) and arrhythmia incidence were measured in three groups of animals: (1) sham CHF/sham–CBD (sham–sham); (2) CHF/sham–CBD (CHF–sham); and (3) CHF/CBD (CHF–CBD). Chemoreflex sensitivity was measured as the RSNA and minute ventilatory () responses to hypoxia and hypercapnia. Respiratory pattern was measured by plethysmography and quantified by an apnoea–hypopnoea index, respiratory rate variability index and the coefficient of variation of tidal volume. Sympatho-respiratory coupling (SRC) was assessed using power spectral analysis and the magnitude of the peak coherence function between tidal volume and RSNA frequency spectra. Arrhythmia incidence and low frequency/high frequency ratio of heart rate variability were assessed using ECG and blood pressure waveforms, respectively. RSNA and responses to hypoxia were augmented in CHF–sham and abolished in CHF–CBD animals. Resting RSNA was greater in CHF–sham compared to sham–sham animals (43 ± 5% max vs. 23 ± 2% max, P < 0.05), and this increase was not found in CHF–CBD animals (25 ± 1% max, P < 0.05 vs. CHF–sham). Low frequency/high frequency heart rate variability ratio was similarly increased in CHF and reduced by CBD (P < 0.05). Respiratory rate variability index, coefficient of variation of tidal volume and apnoea–hypopnoea index were increased in CHF–sham animals and reduced in CHF–CBD animals (P < 0.05). SRC (peak coherence) was increased in CHF–sham animals (sham–sham 0.49 ± 0.05; CHF–sham 0.79

  5. Drying process strongly affects probiotics viability and functionalities.

    PubMed

    Iaconelli, Cyril; Lemetais, Guillaume; Kechaou, Noura; Chain, Florian; Bermúdez-Humarán, Luis G; Langella, Philippe; Gervais, Patrick; Beney, Laurent

    2015-11-20

    Probiotic formulations are widely used and are proposed to have a variety of beneficial effects, depending on the probiotic strains present in the product. The impact of drying processes on the viability of probiotics is well documented. However, the impact of these processes on probiotics functionality remains unclear. In this work, we investigated variations in seven different bacterial markers after various desiccation processes. Markers were composed of four different viability evaluation (combining two growth abilities and two cytometric measurements) and in three in vitro functionalities: stimulation of IL-10 and IL-12 production by PBMCs (immunomodulation) and bacterial adhesion to hexadecane. We measured the impact of three drying processes (air-drying, freeze-drying and spray-drying), without the use of protective agents, on three types of probiotic bacteria: Bifidobacterium bifidum, Lactobacillus plantarum and Lactobacillus zeae. Our results show that the bacteria respond differently to the three different drying processes, in terms of viability and functionality. Drying methods produce important variations in bacterial immunomodulation and hydrophobicity, which are correlated. We also show that adherence can be stimulated (air-drying) or inhibited (spray-drying) by drying processes. Results of a multivariate analysis show no direct correlation between bacterial survival and functionality, but do show a correlation between probiotic responses to desiccation-rewetting and the process used to dry the bacteria.

  6. Chemical Modifications that Affect Nutritional and Functional Properties of Proteins.

    ERIC Educational Resources Information Center

    Richardson, T.; Kester, J. J.

    1984-01-01

    Discusses chemical alterations of selected amino acids resulting from environmental effects (photooxidations, pH extremes, thermally induced effects). Also dicusses use of intentional chemical derivatizations of various functional groups in amino acid residue side chains and how recombinant DNA techniques might be useful in structure/function…

  7. Functional and hemodynamic cardiac determinants of exercise capacity in patients with systolic heart failure.

    PubMed

    Hummel, Yoran M; Bugatti, Silvia; Damman, Kevin; Willemsen, Suzan; Hartog, Jasper W L; Metra, Marco; Sipkens, Johannes S; van Veldhuisen, Dirk J; Voors, Adriaan A

    2012-11-01

    Decreased exercise capacity is the main symptom in patients with heart failure (HF). We assessed the association among noninvasively determined maximal cardiac output at exercise, systolic and diastolic cardiac functions at rest, and peak oxygen uptake (pVo(2)) exercise capacity in patients with congestive HF. We studied 102 patients 62 ± 11 years of age with New York Heart Association class II to IV stable HF and left ventricular (LV) ejection fraction <45%. All patients underwent echocardiography and a treadmill cardiopulmonary exercise test for evaluation of pVo(2) corrected for fat-free mass. During the cardiopulmonary exercise test, cardiac output was estimated noninvasively and continuously using Nexfin HD. Fat-free mass-corrected pVo(2) was associated in an univariate linear regression analysis with peak exercise cardiac index (CI) (beta 0.511, p <0.001), LV end-diastolic pressure estimates (peak early diastolic filling velocity/early diastolic tissue velocity [E/e'], beta -0.363, p = 0.001), and right ventricular function (tricuspid annular plane systolic excursion, beta 0.393, p <0.001). In multivariate analysis peak exercise CI (beta 0.380, p = 0.001), but not cardiac output or LV ejection fraction at rest, was an independent predictor of pVo(2). Other independent predictors of pVo(2) were E/e' (beta -0.276, p = 0.009) and tricuspid annular plane systolic excursion (beta 0.392, p <0.001), also when adjusted for age and gender. In conclusion, peak CI is an independent predictor of fat-free mass-corrected pVo(2) in patients with systolic HF. Of all echocardiographic parameters at rest, right ventricular function and E/e' were independently and significantly associated with pVo(2), whereas LV ejection fraction at rest was not.

  8. Mechanisms of T-box gene function in the developing heart.

    PubMed

    Greulich, Franziska; Rudat, Carsten; Kispert, Andreas

    2011-07-15

    The multi-chambered mammalian heart arises from a simple tube by polar elongation, myocardial differentiation and morphogenesis. Members of the large family of T-box (Tbx) transcription factors have been identified as crucial players that act in distinct subprogrammes during cardiac regionalization. Tbx1 and Tbx18 ensure elongation of the cardiac tube at the anterior and posterior pole, respectively. Tbx1 acts in the pharyngeal mesoderm to maintain proliferation of mesenchymal precursor cells for formation of a myocardialized and septated outflow tract. Tbx18 is expressed in the sinus venosus region and is required for myocardialization of the caval veins and the sinoatrial node. Tbx5 and Tbx20 function in the early heart tube and independently activate the chamber myocardial gene programme, whereas Tbx2 and Tbx3 locally repress this programme to favour valvuloseptal and conduction system development. Here, we summarize that these T-box factors act in different molecular circuits and control target gene expression using diverse molecular strategies including binding to distinct protein interaction partners.

  9. Engineering of a bio-functionalized hybrid off-the-shelf heart valve.

    PubMed

    Hinderer, Svenja; Seifert, Jan; Votteler, Miriam; Shen, Nian; Rheinlaender, Johannes; Schäffer, Tilman E; Schenke-Layland, Katja

    2014-02-01

    Currently available heart valve replacements are limited in long-term performance or fail due to leaflet thickening, lack of growth or remodeling potential. In order to address these issues, it is necessary to mimic multiple factors of the native valvular extracellular matrix (ECM) such as architecture, mechanical behavior and biochemical signals. Here, we successfully generated an electrospun PEGdma-PLA scaffold adapted to the structure and mechanical properties of native valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells (VECs) were seeded on the scaffold and when cultured under physiological conditions in a bioreactor, the construct performed like a native leaflet. Atomic force microscopy (AFM) was employed to obtain detailed mechanical information from the leaflets, which enabled the first layer-specific measurement of the Young's modulus. Interestingly, spongiosa stiffness was much lower compared to the fibrosa and ventricularis. Moreover, investigations into human fetal heart valve development identified collagen type I and versican as important structural proteins. As a proof of principle, these proteins were introduced to the scaffold, demonstrating the ability to bio-functionalize the hybrid valve based on natures' blueprint.

  10. Platelet function and activation in Cavalier King Charles Spaniels with subclinical chronic valvular heart disease.

    PubMed

    Tong, Linda J; Hosgood, Giselle L; French, Anne T; Irwin, Peter J; Shiel, Robert E

    2016-08-01

    OBJECTIVE To assess platelet closure time (CT), mean platelet component (MPC) concentration, and platelet component distribution width (PCDW) in dogs with subclinical chronic valvular heart disease. ANIMALS 89 Cavalier King Charles Spaniels (CKCSs) and 39 control dogs (not CKCSs). PROCEDURES Platelet count, MPC concentration, PCDW, and Hct were measured by use of a hematology analyzer, and CT was measured by use of a platelet function analyzer. Murmur grade and echocardiographic variables (mitral valve regurgitant jet size relative to left atrial area, left atrial-to-aortic diameter ratio, and left ventricular internal dimensions) were recorded. Associations between explanatory variables (sex, age, murmur grade, echocardiographic variables, platelet count, and Hct) and outcomes (CT, MPC concentration, and PCDW) were examined by use of multivariate regression models. RESULTS A model with 5 variables best explained variation in CT (R(2), 0.74), with > 60% of the variance of CT explained by mitral valve regurgitant jet size. The model of best fit to explain variation in MPC concentration included only platelet count (R(2), 0.24). The model of best fit to explain variation in PCDW included platelet count and sex (R(2), 0.25). CONCLUSIONS AND CLINICAL RELEVANCE In this study, a significant effect of mitral valve regurgitant jet size on CT was consistent with platelet dysfunction. However, platelet activation, as assessed on the basis of the MPC concentration and PCDW, was not a feature of subclinical chronic valvular heart disease in CKCSs.

  11. [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.

  12. 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.

  13. Cell-to-cell communication in the heart: structure-function correlations.

    PubMed

    Délèze, J

    1987-10-15

    The communicating cell junctions that ensure the electrical and diffusional continuity of the intracellular space in the heart fibres can be switched from their normal conducting, or opened state, to an exceptional non-conducting, or closed state. This electrical uncoupling is observed after cell injury in the presence of Ca2+ ions in the extracellular fluid, after metabolic inhibition and in the presence of aliphatic alcohols (C6 to C9). The correlations between electrical uncoupling and gap junction morphology in the heart are briefly reviewed. A decrease of the distance between P-face particles and between the E-face pits has been found in all investigations, but the functional significance of this observation is not understood at present. A quantitatively very similar decrease of the average particle diameter (about -0.7 nm) has been measured in glutaraldehyde-fixed sheep Purkinje fibres and in unfixed, quickly frozen rat auricles that had been electrically uncoupled by three different procedures. About half of this decrease was reversible on short-term electrical recoupling (within 20 min). It is concluded that a measurable decrease of the connexon diameter correlates with electrical uncoupling.

  14. Mitochondrial function in heart and kidney of spontaneously hypertensive rats: influence of captopril treatment.

    PubMed

    Mujkosová, Jana; Ulicná, Olga; Waczulíková, Iveta; Vlkovicová, Jana; Vancová, Ol'ga; Ferko, Miroslav; Polák, Stefan; Ziegelhöffer, Attila

    2010-06-01

    Effect of captopril treatment on capability of heart and kidney mitochondria to produce ATP was investigated in spontaneously hypertensive rats (SHR). Heart mitochondria from SHR responded to hypertension with tendency to compensate the elevated energy demands of cardiac cells by moderate increase in mitochondrial Mg2+-ATPase activity, membrane fluidity (MF) and in majority of functional parameters of the mitochondria (p>0.05). Significant increase exhibited only the oxygen consumption (QO2; p<0.01-0.001) and oxidative phosphorylation rate (OPR; p<0.003) with glutamate+malate (GLUT+MAL) as substrates. Lowering the blood pressure (p<0.02) captopril also eliminated the above compensatory response and impaired the oxidative ATP production by decreasing OPR (p<0.001). Kidney mitochondria of SHR experienced serious disarrangement in parameters of oxidative ATP production: increase in Mg2+-ATPase activity (p<0.05) but, also scattered QO2 values (p<0.03-0.01) leading to decrease in OPR and the ADP:O (p<0.05-0.01) values with both GLUT+MAL and succinate as substrates. Captopril treatment does not alleviated but even worsened the above alterations. Mg2+-ATPase became also decreased and the depression of ADP:O became aggravated (p<0.0001).

  15. Heart Rate Variability Correlates to Functional Aerobic Impairment in Hemodialysis Patients

    PubMed Central

    Carreira, Maria Angela Magalhães de Queiroz; Nogueira, André Barros; Pena, Felipe Montes; Kiuchi, Marcio Galindo; Rodrigues, Ronaldo Campos; Rodrigues, Rodrigo da Rocha; de Matos, Jorge Paulo Strogoff; Lugon, Jocemir Ronaldo

    2015-01-01

    Background Autonomic dysfunction (AD) is highly prevalent in hemodialysis (HD) patients and has been implicated in their increased risk of cardiovascular mortality. Objective To correlate heart rate variability (HRV) during exercise treadmill test (ETT) with the values obtained when measuring functional aerobic impairment (FAI) in HD patients and controls. Methods Cross-sectional study involving HD patients and a control group. Clinical examination, blood sampling, transthoracic echocardiogram, 24-hour Holter, and ETT were performed. A symptom-limited ramp treadmill protocol with active recovery was employed. Heart rate variability was evaluated in time domain at exercise and recovery periods. Results Forty-one HD patients and 41 controls concluded the study. HD patients had higher FAI and lower HRV than controls (p<0.001 for both). A correlation was found between exercise HRV (SDNN) and FAI in both groups. This association was independent of age, sex, smoking, body mass index, diabetes, and clonidine or beta-blocker use, but not of hemoglobin levels. Conclusion No association was found between FAI and HRV on 24-hour Holter or at the recovery period of ETT. Of note, exercise HRV was inversely correlated with FAI in HD patients and controls. PMID:26131705

  16. Development of affective theory of mind across adolescence: disentangling the role of executive functions.

    PubMed

    Vetter, Nora C; Altgassen, Mareike; Phillips, Louise; Mahy, Caitlin E V; Kliegel, Matthias

    2013-01-01

    Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence. Affective theory of mind and three subcomponents of executive functions (inhibition, updating, and shifting) were measured. Affective theory of mind was positively related to age, and all three executive functions. Specifically, inhibition explained the largest amount of variance in age-related differences in affective theory of mind.

  17. Alginate Overproduction Affects Pseudomonas aeruginosa Biofilm Structure and Function

    PubMed Central

    Hentzer, Morten; Teitzel, Gail M.; Balzer, Grant J.; Heydorn, Arne; Molin, Søren; Givskov, Michael; Parsek, Matthew R.

    2001-01-01

    During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development on an abiotic surface. Biofilms formed by an alginate-overproducing strain exhibit a highly structured architecture and are significantly more resistant to the antibiotic tobramycin than a biofilm formed by an isogenic nonmucoid strain. These results suggest that an important consequence of the conversion to mucoidy is an altered biofilm architecture that shows increasing resistance to antimicrobial treatments. PMID:11514525

  18. Nuclear cyclophilins affect spliceosome assembly and function in vitro.

    PubMed

    Adams, B M; Coates, Miranda N; Jackson, S RaElle; Jurica, Melissa S; Davis, Tara L

    2015-07-15

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.

  19. Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

    PubMed Central

    Salzwedel, Andrew P.; Vachet, Clement; Gerig, Guido; Lin, Weili

    2015-01-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala–frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  20. How optimization of potential functions affects protein folding.

    PubMed Central

    Hao, M H; Scheraga, H A

    1996-01-01

    The relationship between the optimization of the potential function and the foldability of theoretical protein models is studied based on investigations of a 27-mer cubic-lattice protein model and a more realistic lattice model for the protein crambin. In both the simple and the more complicated systems, optimization of the energy parameters achieves significant improvements in the statistical-mechanical characteristics of the systems and leads to foldable protein models in simulation experiments. The foldability of the protein models is characterized by their statistical-mechanical properties--e.g., by the density of states and by Monte Carlo folding simulations of the models. With optimized energy parameters, a high level of consistency exists among different interactions in the native structures of the protein models, as revealed by a correlation function between the optimized energy parameters and the native structure of the model proteins. The results of this work are relevant to the design of a general potential function for folding proteins by theoretical simulations. PMID:8643516

  1. Microplastics Affect the Ecological Functioning of an Important Biogenic Habitat.

    PubMed

    Green, Dannielle Senga; Boots, Bas; O'Connor, Nessa E; Thompson, Richard

    2017-01-03

    Biological effects of microplastics on the health of bivalves have been demonstrated elsewhere, but ecological impacts on the biodiversity and ecosystem functioning of bivalve-dominated habitats are unknown. Thus, we exposed intact sediment cores containing European flat oysters (Ostrea edulis) or blue mussels (Mytilus edulis) in seawater to two different densities (2.5 or 25 μg L(-1)) of biodegradable or conventional microplastics in outdoor mesocosms. We hypothesized that filtration rates of the bivalves, inorganic nitrogen cycling, primary productivity of sediment dwelling microphytobenthos, and the structure of invertebrate benthic assemblages would be influenced by microplastics. After 50 days, filtration by M. edulis was significantly less when exposed to 25 μg L(-1) of either type of microplastics, but there were no effects on ecosystem functioning or the associated invertebrate assemblages. Contrastingly, filtration by O. edulis significantly increased when exposed to 2.5 or 25 μg L(-1) of microplastics, and porewater ammonium and biomass of benthic cyanobacteria decreased. Additionally the associated infaunal invertebrate assemblages differed, with significantly less polychaetes and more oligochaetes in treatments exposed to microplastics. These findings highlight the potential of microplastics to impact the functioning and structure of sedimentary habitats and show that such effects may depend on the dominant bivalve present.

  2. Nuclear cyclophilins affect spliceosome assembly and function in vitro

    PubMed Central

    Adams, B.M.; Coates, Miranda N.; Jackson, S. RaElle; Jurica, Melissa S.; Davis, Tara L.

    2015-01-01

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing. PMID:25967372

  3. Aerobic Training Intensity for Improved Endothelial Function in Heart Failure Patients: A Systematic Review and Meta-Analysis

    PubMed Central

    Pearson, M. J.

    2017-01-01

    Objective. Flow-mediated dilation (FMD) is widely utilised to assess endothelial function and aerobic exercise improves FMD in heart failure patients. The aim of this meta-analysis is to quantify the effect of aerobic training intensity on FMD in patients with heart failure. Background. A large number of studies now exist that examine endothelial function in patients with heart failure. We sought to add to the current literature by quantifying the effect of the aerobic training intensity on endothelial function. Methods. We conducted database searches (PubMed, Embase, ProQuest, and Cochrane Trials Register to June 30, 2016) for exercise based rehabilitation trials in heart failure, using search terms exercise training, endothelial function, and flow-mediated dilation (FMD). Results. The 13 included studies provided a total of 458 participants, 264 in intervention groups, and 194 in nonexercising control groups. Both vigorous and moderate intensity aerobic training significantly improved FMD. Conclusion. Overall both vigorous and moderate aerobic exercise training improved FMD in patients with heart failure. PMID:28348916

  4. Visual function affects prosocial behaviors in older adults.

    PubMed

    Teoli, Dac A; Smith, Merideth D; Leys, Monique J; Jain, Priyanka; Odom, J Vernon

    2016-02-01

    Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

  5. Affected functional networks associated with sentence production in classic galactosemia.

    PubMed

    Timmers, Inge; van den Hurk, Job; Hofman, Paul Am; Zimmermann, Luc Ji; Uludağ, Kâmil; Jansma, Bernadette M; Rubio-Gozalbo, M Estela

    2015-08-07

    Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients.

  6. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  7. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-01-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  8. Executive function deficits in congenital heart disease: why is intervention important?

    PubMed

    Calderon, Johanna; Bellinger, David C

    2015-10-01

    It is widely recognised that children with congenital heart disease (CHD) are at high risk for neurodevelopmental impairments including attention deficit hyperactivity disorder and autism spectrum disorder symptoms. Executive function impairments are one of the most prominent neurodevelopmental features associated with CHD. These deficits can have widespread debilitating repercussions in children's neurocognitive, behavioural, and psycho-social development. There is a crucial gap in research regarding the efficacy of preventive or treatment strategies for these important cognitive morbidities. Executive functions are complex neurocognitive skills highly amenable to improvement. Evidence-based interventions have shown promising results in other paediatric populations, strongly suggesting that they might also benefit the growing population of children with CHD. In this review, we summarise the available data on executive function impairments in children and adolescents with CHD. We underline the important co-morbidity of executive dysfunction with other cognitive and psychiatric issues in CHD, which raises awareness of the crucial need to prevent or at least mitigate these deficits. Finally, we summarise future avenues for research in terms of interventions that may help reduce executive function impairments in youth with CHD.

  9. Overlapping and Opposing Functions of G Protein-coupled Receptor Kinase 2 (GRK2) and GRK5 during Heart Development*

    PubMed Central

    Philipp, Melanie; Berger, Ina M.; Just, Steffen; Caron, Marc G.

    2014-01-01

    G protein-coupled receptor kinases 2 (GRK2) and 5 (GRK5) are fundamental regulators of cardiac performance in adults but are less well characterized for their function in the hearts of embryos. GRK2 and -5 belong to different subfamilies and function as competitors in the control of certain receptors and signaling pathways. In this study, we used zebrafish to investigate whether the fish homologs of GRK2 and -5, Grk2/3 and Grk5, also have unique, complementary, or competitive roles during heart development. We found that they differentially regulate the heart rate of early embryos and equally facilitate heart function in older embryos and that both are required to develop proper cardiac morphology. A loss of Grk2/3 results in dilated atria and hypoplastic ventricles, and the hearts of embryos depleted in Grk5 present with a generalized atrophy. This Grk5 morphant phenotype was associated with an overall decrease of early cardiac progenitors as well as a reduction in the area occupied by myocardial progenitor cells. In the case of Grk2/3, the progenitor decrease was confined to a subset of precursor cells with a committed ventricular fate. We attempted to rescue the GRK loss-of-function heart phenotypes by downstream activation of Hedgehog signaling. The Grk2/3 loss-of-function embryos were rescued by this approach, but Grk5 embryos failed to respond. In summary, we found that GRK2 and GRK5 control cardiac function as well as morphogenesis during development although with different morphological outcomes. PMID:25104355

  10. Congestive Heart Failure With Apparently Preserved Left Ventricular Systolic Function: A 10-Year Observational Study.

    PubMed

    El-Menyar, Ayman; Shabana, Adel; Arabi, Abdulrahman; Al-Thani, Hassan; Asaad, Nidal; AlBinALi, Hajar; Singh, Rajvir; Gomaa, Mohammed; Gehani, A

    2015-09-01

    We analyzed the clinical presentation and outcomes (from 2003 to 2013) of heart failure (HF) with apparently normal systolic function (HFPEF). Based on the echocardiographic left ventricular ejection fraction (LVEF), patients were divided into 2 groups, group 1 (<50%) and group 2 (≥50%). Of 2212 patients with HF, 20% were in group 2. Patients in group 2 were more likely to be older, females, Arabs, hypertensive, and obese (P = .001). Patients in group 1 were mostly Asians and had more troponin-T positivity (P = .001). Inhospital cardiac arrest, shock, and deaths were significantly greater in group 1. On multivariate analysis, age, ST-segment elevation myocardial infarction, lack of on-admission β-blockers, and angiotensin-converting enzyme inhibitors use were independent predictors of mortality. HFPEF is associated with less mortality compared to those who presented with reduced LVEF. On admission, use of evidence-based medications could in part predict this difference in the hospital outcome.

  11. Learning discriminative distance functions for valve retrieval and improved decision support in valvular heart disease

    NASA Astrophysics Data System (ADS)

    Voigt, Ingmar; Vitanovski, Dime; Ionasec, Razvan I.; Tsymal, Alexey; Georgescu, Bogdan; Zhou, Shaohua K.; Huber, Martin; Navab, Nassir; Hornegger, Joachim; Comaniciu, Dorin

    2010-03-01

    Disorders of the heart valves constitute a considerable health problem and often require surgical intervention. Recently various approaches were published seeking to overcome the shortcomings of current clinical practice,that still relies on manually performed measurements for performance assessment. Clinical decisions are still based on generic information from clinical guidelines and publications and personal experience of clinicians. We present a framework for retrieval and decision support using learning based discriminative distance functions and visualization of patient similarity with relative neighborhood graphsbased on shape and derived features. We considered two learning based techniques, namely learning from equivalence constraints and the intrinsic Random Forest distance. The generic approach enables for learning arbitrary user-defined concepts of similarity depending on the application. This is demonstrated with the proposed applications, including automated diagnosis and interventional suitability classification, where classification rates of up to 88.9% and 85.9% could be observed on a set of valve models from 288 and 102 patients respectively.

  12. Superior Cardiac Function Via Anaplerotic Pyruvate in the Immature Swine Heart After Cardiopulmonary Bypass and Reperfusion

    SciTech Connect

    Olson, Aaron; Hyyti, Outi M.; Cohen, Gordon A.; Ning, Xue-Han; Sadilek, Martin; Isern, Nancy G.; Portman, Michael A.

    2008-12-01

    Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the citric acid cycle (CAC) via carboxylation are linked to stimulation of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age 10-18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of [2]-13C-pyruvate (to achieve a final concentration of 8 mM) was given for 35 minutes starting either during weaning (Group I), after discontinuation (Group II) or without (Control) CPB. Hemodynamic data was collected. 13C NMR spectroscopy was used to determine the fraction of pyruvate entering the CAC via pyruvate carboxylation (PC) to total CAC entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment.

  13. What physicians need to know about renal function in outpatients with heart failure.

    PubMed

    Waldum-Grevbo, Bård

    2015-01-01

    The majority of outpatients with heart failure (HF) have chronic kidney disease (CKD) as an important comorbidity. Both glomerular filtration rate and abnormal urinary albumin excretion are major predictors of outcome in HF patients. Despite this, patients with renal dysfunction have been systematically excluded from the large randomized HF trials. There is lack of evidence for optimal treatment in these cardiorenal patients and treatment nihilism may account in part for their bad prognosis. Identifying and monitoring the progression of renal disease and making an effort to preserve renal function should be an important task in the management of all patients with HF. In this review, the current understanding of the pathophysiology of renal dysfunction in outpatients with HF will be summarized. Furthermore, important principles of the identification and management of cardiorenal patients will be described in order to make the physician more capable of managing outpatients with HF and renal dysfunction.

  14. Regulation of pumping function of the heart in developing body under changing regimens of motor activity.

    PubMed

    Vafina, E Z; Abzalov, R A; Abzalov, N I; Nikitin, A S; Gulyakov, A A

    2014-06-01

    We analyzed parameters of the pumping function of the heart in rats subjected to enhanced motor activity after a preliminary 70-day hypokinesia under conditions of α- and β-adrenergic receptor stimulation with norepinephrine followed by blockade of β-adrenergic receptor with propranolol (obsidian) and α1-adrenergic receptors with doxazosin. After norepinephrine administration, the HR and cardiac output were higher in rats with enhanced physical activity after preliminary hypokinesia than in rats with low physical activity. After propranolol administration, stroke volume and cardiac output in 100-day-old rats with limited activity were lower, and HR higher was than in rats with enhanced physical activity after preliminary 70-day hypokinesia. After administration of doxazosin, rats with limited motor activity demonstrated more pronounced changes in HR than rats with enhanced physical activity after preliminary 70-day hypokinesia.

  15. Low level methylmercury exposure affects neuropsychological function in adults

    PubMed Central

    Yokoo, Edna M; Valente, Joaquim G; Grattan, Lynn; Schmidt, Sérgio Luís; Platt, Illeane; Silbergeld, Ellen K

    2003-01-01

    -dependent effect. Conclusions This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures. PMID:12844364

  16. Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

    PubMed

    Cartocci, Veronica; Servadio, Michela; Trezza, Viviana; Pallottini, Valentina

    2017-02-01

    Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. © 2016 Wiley Periodicals, Inc.

  17. Does vitamin C deficiency affect cognitive development and function?

    PubMed

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-09-19

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

  18. Enhanced serotonin transporter function during depression in seasonal affective disorder.

    PubMed

    Willeit, Matthäus; Sitte, Harald H; Thierry, Nikolaus; Michalek, Klaus; Praschak-Rieder, Nicole; Zill, Peter; Winkler, Dietmar; Brannath, Werner; Fischer, Michael B; Bondy, Brigitta; Kasper, Siegfried; Singer, Ernst A

    2008-06-01

    Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramine-induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and outward (p=0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (rho=0.421, p=0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

  19. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues.

    PubMed

    Marsano, Anna; Conficconi, Chiara; Lemme, Marta; Occhetta, Paola; Gaudiello, Emanuele; Votta, Emiliano; Cerino, Giulia; Redaelli, Alberto; Rasponi, Marco

    2016-02-07

    In the past few years, microfluidic-based technology has developed microscale models recapitulating key physical and biological cues typical of the native myocardium. However, the application of controlled physiological uniaxial cyclic strains on a defined three-dimension cellular environment is not yet possible. Two-dimension mechanical stimulation was particularly investigated, neglecting the complex three-dimensional cell-cell and cell-matrix interactions. For this purpose, we developed a heart-on-a-chip platform, which recapitulates the physiologic mechanical environment experienced by cells in the native myocardium. The device includes an array of hanging posts to confine cell-laden gels, and a pneumatic actuation system to induce homogeneous uniaxial cyclic strains to the 3D cell constructs during culture. The device was used to generate mature and highly functional micro-engineered cardiac tissues (μECTs), from both neonatal rat and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), strongly suggesting the robustness of our engineered cardiac micro-niche. Our results demonstrated that the cyclic strain was effectively highly uniaxial and uniformly transferred to cells in culture. As compared to control, stimulated μECTs showed superior cardiac differentiation, as well as electrical and mechanical coupling, owing to a remarkable increase in junction complexes. Mechanical stimulation also promoted early spontaneous synchronous beating and better contractile capability in response to electric pacing. Pacing analyses of hiPSC-CM constructs upon controlled administration of isoprenaline showed further promising applications of our platform in drug discovery, delivery and toxicology fields. The proposed heart-on-a-chip device represents a relevant step forward in the field, providing a standard functional three-dimensional cardiac model to possibly predict signs of hypertrophic changes in cardiac phenotype by mechanical and biochemical co-stimulation.

  20. 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.

  1. Hyponatremia, Cognitive Function, and Mobility in an Outpatient Heart Failure Population

    PubMed Central

    Albabtain, Monirah; Brenner, Michael J.; Nicklas, John M.; Hummel, Scott L.; McCormick, Michael P.; Pawlowski, Jeffrey L.; Remington, Tami L.; Gure, Tanya R.; Dorsch, Michael P.; Bleske, Barry E.

    2016-01-01

    Background The association of hyponatremia with cognitive impairment and mobility in heart failure (HF) patients is unknown. The purpose of this study was to determine if hyponatremia is associated with cognitive and mobility impairment as measured by simple, validated, and time-sensitive tests. Material/Methods This was a prospective study in patients with reduced and preserved ejection fraction (HFrEF, HFpEF) seen in outpatient HF clinics. Hyponatremia was defined as sodium level ≤136 mEq/L. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) tool, and mobility was measured with the Timed Up and Go test (TUG-t). Results A total of 121 patients were evaluated; 30% were hyponatremic (134±1.9 mEq/l, range 128–136 mEq/l). Overall, 92% of hyponatremic patients had cognitive impairment (MoCA <26) compared to 76% of the non-hyponatremic patients [relative risk 1.2 (confidence interval: 1.02–1.4, p=0.02)]. In regard to mobility, 72% of hyponatremic patients and 62% of non-hyponatremic patients (p=0.4) had TUG-t times that were considered to be worse than average. A total of 84% (N=76) of HFrEF and 71% (N=22) of HFpEF patients had cognitive impairment (p=0.86). HFrEF patients had significantly lower overall MoCA scores (21.2±3.7 vs. 23.3±3.6, p=0.006) and similar TUG-t times compared to HFpEF patients. Conclusions Most heart failure patients (HFrEF and HFpEF) seen in an ambulatory setting had impairment of cognitive function and mobility, with a higher prevalence among those with hyponatremia. Screening can be done using tests that can be administered in a clinical setting. PMID:27988787

  2. Morphology of the heart associated with its function as conceived by ancient Greeks.

    PubMed

    Mavrodi, Alexandra; Paraskevas, George

    2014-03-01

    According to their writings, ancient Greek physicians had explored the anatomy of the heart. Although pre-Hippocratic medicine, which relied on religion and mysticism, has nothing more to present than implausible theories and speculations, younger physicians thanks to their animal dissections were able to depict the heart with detail. Hippocratic "On the Heart", Aristotle's, Herophilus', Erasistratus' and Galen's writings provide us with the necessary data to take a look at the anatomy of the heart as it was described back then. Despite of some confusing passages in their writings and some erroneous notions, the heart was described with relative accuracy. In the years after antiquity and in the Middle Age the only information about the anatomy of the heart could be derived from the ancient Greek works and only anatomists of the Renaissance managed to displace them. In this paper we present the knowledge of all known ancient Greek physicians about the heart, with emphasis on its anatomy.

  3. Beyond the first year after pediatric heart or heart-lung transplantation: Changes in cognitive function and behaviour.

    PubMed

    Wray, Jo; Radley-Smith, Rosemary

    2005-04-01

    With the increasing use and improved survival rates of heart and lung transplantation as treatments for children with end-stage heart or lung disease, attention is focusing on the longer term psychological implications of these procedures. This paper focuses on the changes in cognitive development and behaviour in a group of 47 children who were seen 12 months and 2 yr after transplantation. There were 24 boys and 23 girls, mean age at transplantation was 8.3 yr (s.d. 5.3 yr), with a range of 0.3-15.1 yr. Assessments were made of developmental level, cognitive ability and problem behaviours, using previously validated measures, and comparisons were made with physically healthy children. For children under three and a half years of age there was a decrease over time in scores on all developmental parameters, with the change reaching significance on the scale assessing eye-hand coordination and on the overall IQ. Whilst all scores were within the normal range, they were at a significantly lower level than those of the healthy children. In contrast, there were no changes over time on any measures of cognitive or academic ability for older children, with correlations between 12 month and 2 yr scores being highly significant. The rate of behaviour problems at home at 12 months was 22%, compared with 34% at 2 yr post-transplant, which was higher than that found in the healthy children. Conversely, there was a drop in the prevalence of behaviour problems at school from 23% at 12 months to 9% at 2 yr. It is concluded that a significant minority of children and adolescents experience psychological difficulties 2 yr after transplant, with particular areas of concern focusing on development in the younger children and the occurrence of behaviour problems at home across the age-range.

  4. Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs Drosophila Heart Structure and Impairs Function

    PubMed Central

    Viswanathan, Meera C.; Blice-Baum, Anna C.; Sang, Tzu-Kang; Cammarato, Anthony

    2016-01-01

    Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps maintain protein homeostasis in all cells and serves specialized functions in distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis and atrophy. However, little is known about VCP's role(s) in the heart. Its functional diversity is determined by differential binding of distinct cofactors/adapters, which is likely disrupted during disease. VCP mutations cause multisystem proteinopathy (MSP), a pleiotropic degenerative disorder that involves inclusion body myopathy. MSP patients display progressive muscle weakness. They also exhibit cardiomyopathy and die from cardiac and respiratory failure, which are consistent with critical myocardial roles for the enzyme. Nonetheless, efficient models to interrogate VCP in cardiac muscle remain underdeveloped and poorly studied. Here, we investigated the significance of VCP and mutant VCP in the Drosophila heart. Cardiac-restricted RNAi-mediated knockdown of TER94, the Drosophila VCP homolog, severely perturbed myofibrillar organization and heart function in adult flies. Furthermore, expression of MSP disease-causing alleles engendered cardiomyopathy in adults and structural defects in embryonic hearts. Drosophila may therefore serve as a valuable model for examining role(s) of VCP in cardiogenesis and for identifying novel heart-specific VCP interactions, which when disrupted via mutation, contribute to or elicit cardiac pathology. PMID:27500162

  5. Discoidin domain receptor 2 germline gene deletion leads to altered heart structure and function in the mouse.

    PubMed

    Cowling, Randy T; Yeo, Seon Ju; Kim, In Jai; Park, Joong Il; Gu, Yusu; Dalton, Nancy D; Peterson, Kirk L; Greenberg, Barry H

    2014-09-01

    Discoidin domain receptor 2 (DDR2) is a fibrillar collagen receptor that is expressed in mesenchymal cells throughout the body. In the heart, DDR2 is selectively expressed on cardiac fibroblasts. We generated a germline DDR2 knockout mouse and used this mouse to examine the role of DDR2 deletion on heart structure and function. Echocardiographic measurements from null mice were consistent with those from a smaller heart, with reduced left ventricular chamber dimensions and little change in wall thickness. Fractional shortening appeared normal. Left ventricular pressure measurements revealed mild inotropic and lusitropic abnormalities that were accentuated by dobutamine infusion. Both body and heart weights from 10-wk-old male mice were ~20% smaller in null mice. The reduced heart size was not simply due to reduced body weight, since cardiomyocyte lengths were atypically shorter in null mice. Although normalized cardiac collagen mass (assayed by hydroxyproline content) was not different in null mice, the collagen area fraction was statistically higher, suggesting a reduced collagen density from altered collagen deposition and cross-linking. Cultured cardiac fibroblasts from null mice deposited collagen at a slower rate than wild-type littermates, possibly due to the expression of lower prolyl 4-hydroxylase α-isoform 1 enzyme levels. We conclude that genetic deletion of the DDR2 collagen receptor alters cardiac fibroblast function. The resulting perturbations in collagen deposition can influence the structure and function of mature cardiomyocytes.

  6. Temporal pattern of left ventricular structural and functional remodeling following reversal of volume overload heart failure

    PubMed Central

    Hutchinson, Kirk R.; Guggilam, Anuradha; Cismowski, Mary J.; Galantowicz, Maarten L.; West, Thomas A.; Stewart, James A.; Zhang, Xiaojin; Lord, Kevin C.

    2011-01-01

    Current surgical management of volume overload-induced heart failure (HF) leads to variable recovery of left ventricular (LV) function despite a return of LV geometry. The mechanisms that prevent restoration of function are unknown but may be related to the timing of intervention and the degree of LV contractile impairment. This study determined whether reduction of aortocaval fistula (ACF)-induced LV volume overload during the compensatory stage of HF results in beneficial LV structural remodeling and restoration of pump function. Rats were subjected to ACF for 4 wk; a subset then received a load-reversal procedure by closing the shunt using a custom-made stent graft approach. Echocardiography or in vivo pressure-volume analysis was used to assess LV morphology and function in sham rats; rats subjected to 4-, 8-, or 15-wk ACF; and rats subjected to 4-wk ACF followed by 4- or 11-wk reversal. Structural and functional changes were correlated to LV collagen content, extracellular matrix (ECM) proteins, and hypertrophic markers. ACF-induced volume overload led to progressive LV chamber dilation and contractile dysfunction. Rats subjected to short-term reversal (4-wk ACF + 4-wk reversal) exhibited improved chamber dimensions (LV diastolic dimension) and LV compliance that were associated with ECM remodeling and normalization of atrial and brain natriuretic peptides. Load-independent parameters indicated LV systolic (preload recruitable stroke work, Ees) and diastolic dysfunction (tau, arterial elastance). These changes were associated with an altered α/β-myosin heavy chain ratio. However, these changes were normalized to sham levels in long-term reversal rats (4-wk ACF + 11-wk reversal). Acute hemodynamic changes following ACF reversal improve LV geometry, but LV dysfunction persists. Gradual restoration of function was related to normalization of eccentric hypertrophy, LV wall stress, and ECM remodeling. These results suggest that mild to moderate LV systolic

  7. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    ERIC Educational Resources Information Center

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  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. Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

    NASA Technical Reports Server (NTRS)

    Zhang, R.; Behbehani, K.; Crandall, C. G.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

    2001-01-01

    To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

  10. Effects of moderate heart failure and functional overload on rat plantaris muscle

    NASA Technical Reports Server (NTRS)

    Spangenburg, Espen E.; Lees, Simon J.; Otis, Jeff S.; Musch, Timothy I.; Talmadge, Robert J.; Williams, Jay H.

    2002-01-01

    It is thought that changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca(2+) uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca(2+) uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca(2+) uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca(2+) handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.

  11. 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.

  12. Patient-prosthesis mismatch in the mitral position affects midterm survival and functional status

    PubMed Central

    Bouchard, Denis; Eynden, Frédéric Vanden; Demers, Philippe; Perrault, Louis P; Carrier, Michel; Cartier, Raymond; Basmadjian, Arsène J; Pellerin, Michel

    2010-01-01

    BACKGROUND: The definition and incidence of patient-prosthesis mismatch (PPM) in the mitral position are unclear. OBJECTIVES: To determine the impact of PPM on late survival and functional status after mitral valve replacement with a mechanical valve. METHODS: Between 1992 and 2005, 714 patients (mean [± SD] age 60±10 years) underwent valve replacement with either St Jude (St Jude Medical Inc, USA) (n=295) or Carbomedics (Sulzer Carbomedics Inc, USA) (n=419) valves. There were 52 concomitant procedures (50 tricuspid annuloplasties, 25 foramen oval closures and 20 radiofrequency mazes). The mean clinical follow-up period was 4.4±3.3 years. The severity of PPM was established with cut-off values for an indexed effective orifice area (EOAi) of lower than 1.2 cm2/m2, lower than 1.3 cm2/m2 and lower than 1.4 cm2/m2. Parametric and nonparametric tests were used to determine predictors of outcome. RESULTS: The prevalence of PPM was 3.7%, 10.1% and 23.5% when considering values of lower than 1.2 cm2/m2, lower than 1.3 cm2/m2 and lower than 1.4 cm2/m2, respectively. When considering functional improvement, patients with an EOAi of 1.4 cm2/m2 or greater had a better outcome than those with an EOAi of lower than 1.4 cm2/m2 (OR 1.98; P=0.03). When building a Cox-proportional hazard model, PPM with an EOAi of less than 1.3 cm2/m2 was an independent predictive factor for midterm survival (HR 2.24, P=0.007). Other factors affecting survival were age (HR 1.039), preoperative New York Heart Association class (HR 1.96) and body surface area (HR 0.31). CONCLUSIONS: In a large cohort of patients undergoing mitral valve replacement with mechanical prostheses, PPM defined as an EOAi of lower than 1.3 cm2/m2 significantly decreased midterm survival. This level of PPM was observed in 10.2% of patients. Patients with an EOAi of 1.4 cm2/m2 or greater had greater improvement of their functional status. PMID:21165362

  13. Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension

    PubMed Central

    Sivak, Joseph A.; Raina, Amresh

    2016-01-01

    Abstract Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects. PMID:27683609

  14. Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension.

    PubMed

    Sivak, Joseph A; Raina, Amresh; Forfia, Paul R

    2016-09-01

    Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects.

  15. Familial Clustering of Executive Functioning in Affected Sibling Pair Families with ADHD

    ERIC Educational Resources Information Center

    Slaats-Willemse, Dorine; Swaab-Barneveld, Hanna; De Sonneville, Leo; Buitelaar, Jan

    2005-01-01

    Objective: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. Method: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the…

  16. 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

    SciTech Connect

    Yan, Lifeng; Zhou, Yong; Yu, Shanhe; Ji, Guixiang; Liu, Wei; Gu, Aihua

    2013-11-15

    Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.

  17. IMPACT OF CALCIUM-CHANNEL BLOCKERS ON RIGHT HEART FUNCTION IN A CONTROLLED MODEL OF CHRONIC PULMONARY HYPERTENSION

    PubMed Central

    Zierer, Andreas; Voeller, Rochus K.; Melby, Spencer J.; Steendijk, Paul; Moon, Marc R.

    2009-01-01

    Purpose Patients with chronic pulmonary hypertension (CPH) who demonstrate a pulmonary vasodilation following calcium channel blocker (CCB) administration are defined as “responders”. In contrast, “non-responders” are patients who do not show such a pulmonary vasodilation with CCB therapy. The purpose of this investigation was to study the effects of CCB therapy on right heart mechanics in experimental CCB responders versus CCB non-responders. Methods In 12 dogs, right atrial (RA) and ventricular (RV) pressure and volume (conductance catheters) were simultaneously recorded after 3 months of progressive pulmonary artery (PA) banding. Diltiazem was given at 10 mg/hr with the PA constricted (simulated CCB non-responder). Responders were then created by releasing the PA band to unload the ventricle. RA and RV contractility and diastolic stiffness (slope of end-systolic and end-diastolic pressure-volume relations) were calculated and RA reservoir and conduit function were quantified as RA inflow with the tricuspid valve closed versus open, respectively. Results With CCB, RA contractility (p<0.03) and cardiac output (p<0.004) were compromised in simulated non-responders while RA stroke work was pharmacologically depressed in the setting of an unchanged afterload. After simulating a responder by controlled PA band release, the RA became less distensible, causing a shift from reservoir to conduit function (p<0.001) towards physiologic baseline conditions and a recovery in the hyperdynamic compensatory response in both chambers (p<0.007) as evidenced in a declined RA and RV contractility with an improved cardiac output as compared to CPH and simulated non-responders. RA and RV diastolic function in both groups was not affected by CCB. Conclusions CCB did not impact RV function in simulated non-responders, but significantly impaired RA contractility and cardiac output. In simulated responders, afterload fell substantially, thereby allowing the RA and RV to recover

  18. 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

  19. Superior cardiac function via anaplerotic pyruvate in the immature swine heart after cardiopulmonary bypass and reperfusion.

    PubMed

    Olson, Aaron K; Hyyti, Outi M; Cohen, Gordon A; Ning, Xue-Han; Sadilek, Martin; Isern, Nancy; Portman, Michael A

    2008-12-01

    Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the tricarboxylic acid (TCA) cycle via carboxylation are linked to the stimulation of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age: 10-18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of [2-(13)C]pyruvate (to achieve an estimated final concentration of 8 mM) was given for 35 min, starting either during weaning (group I) and after its discontinuation (group II) or without (control) CPB. Hemodynamic data were collected. 13C NMR spectroscopy was used to determine the fraction of pyruvate entering the TCA cycle via pyruvate carboxylation (PC) to total TCA cycle entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment. Pyruvate infusion starting during the weaning of mechanical circulatory support improved maximum dP/dt (P<0.05) but waiting to start the infusion until after the discontinuation of CPB did not. Glutamate fractional enrichment was confirmed by liquid chromatography-mass spectroscopy as adequate (>5%) to provide signal to noise in the NMR experiment in all groups. The ratio of pyruvate carboxylase to total pyruvate entry into the TCA cycle did not differ between groups (group I: 20+/-4%, group II: 23+/-7%, and control: 27+/-7%). These data show that robust PC operates in the neonatal pig heart and is maintained during reperfusion under conditions that emulate CPB and reperfusion in human infants.

  20. Establishment of functional primary cultures of heart cells from the clam Ruditapes decussatus.

    PubMed

    Hanana, H; Talarmin, H; Pennec, J P; Droguet, M; Gobin, E; Marcorelle, P; Dorange, G

    2011-05-01

    Heart cells from the clam Ruditapes decussatus were routinely cultured with a high level of reproducibility in sea water based medium. Three cell types attached to the plastic after 2 days and could be maintained in vitro for at least 1 month: epithelial-like cells, round cells and fibroblastic cells. Fibroblastic cells were identified as functional cardiomyocytes due to their spontaneous beating, their ultrastructural characteristics and their reactivity with antibodies against sarcomeric α-actinin, sarcomeric tropomyosin, myosin and troponin T-C. Patch clamp measurements allowed the identification of ionic currents characteristic of cardiomyocytes: a delayed potassium current (I (K slow)) strongly suppressed (95%) by tetraethylammonium (1 mM), a fast inactivating potassium current (I (K fast)) inhibited (50%) by 4 amino-pyridine at 1 mM and, at a lower level (34%) by TEA, a calcium dependent potassium current (I (KCa)) activated by strong depolarization. Three inward voltage activated currents were also characterized in some cardiomyocytes: L-type calcium current (I (Ca)) inhibited by verapamil at 5 × 10(-4) M, T-type Ca(2+) current, rapidly activated and inactivated, and sodium current (I (Na)) observed in only a few cells after strong hyperpolarization. These two currents did not seem to be physiologically essential in the initiation of the beatings of cardiomyocytes. Potassium currents were partially inhibited by tributyltin (TBT) (1 μM) but not by okadaic acid (two marine pollutants). DNA synthesis was also demonstrated in few cultured cells using BrdU (bromo-2'-deoxyuridine). Observed effects of okadaic acid and TBT demonstrated that cultured heart cells from clam Ruditapes decussatus can be used as an experimental model in marine toxicology.

  1. Beneficial effects of beta-blockers on left ventricular function and cellular energy reserve in patients with heart failure.

    PubMed

    Spoladore, Roberto; Fragasso, Gabriele; Perseghin, Gianluca; De Cobelli, Francesco; Esposito, Antonio; Maranta, Francesco; Calori, Giliola; Locatelli, Massimo; Lattuada, Guido; Scifo, Paola; Del Maschio, Alessandro; Margonato, Alberto

    2013-08-01

    Beta-blockers have been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of beta-blockers on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. Ten heart failure patients on full medical therapy were beta-blocked by either carvedilol or bisoprolol. Before and after 3 months of treatment, exercise testing, 2D echocardiography, MRS, New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product and exercise metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. After beta-blockade, NYHA class decreased (from 2.2 ± 0.54 to 1.9 ± 0.52, P = 0.05), whereas EF (from 33 ± 7 to 44 ± 6%, P = 0.0009) and METS (from 6.74 ± 2.12 to 8.03 ± 2.39, P = 0.01) increased. Accordingly, the mean cardiac PCr/ATP ratio increased by 33% (from 1.48 ± 0.22 to 1.81 ± 0.48, P = 0.03). Beta-blockade-induced symptomatic and functional improvement in patients with heart failure is associated to increased PCr/ATP ratio, indicating preservation of myocardial high-energy phosphate levels.

  2. hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function.

    PubMed

    Ye, Junqiang; Beetz, Nadine; O'Keeffe, Sean; Tapia, Juan Carlos; Macpherson, Lindsey; Chen, Weisheng V; Bassel-Duby, Rhonda; Olson, Eric N; Maniatis, Tom

    2015-06-09

    We report that mice lacking the heterogeneous nuclear ribonucleoprotein U (hnRNP U) in the heart develop lethal dilated cardiomyopathy and display numerous defects in cardiac pre-mRNA splicing. Mutant hearts have disorganized cardiomyocytes, impaired contractility, and abnormal excitation-contraction coupling activities. RNA-seq analyses of Hnrnpu mutant hearts revealed extensive defects in alternative splicing of pre-mRNAs encoding proteins known to be critical for normal heart development and function, including Titin and calcium/calmodulin-dependent protein kinase II delta (Camk2d). Loss of hnRNP U expression in cardiomyocytes also leads to aberrant splicing of the pre-mRNA encoding the excitation-contraction coupling component Junctin. We found that the protein product of an alternatively spliced Junctin isoform is N-glycosylated at a specific asparagine site that is required for interactions with specific protein partners. Our findings provide conclusive evidence for the essential role of hnRNP U in heart development and function and in the regulation of alternative splicing.

  3. hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function

    PubMed Central

    Ye, Junqiang; Beetz, Nadine; O’Keeffe, Sean; Tapia, Juan Carlos; Macpherson, Lindsey; Chen, Weisheng V.; Bassel-Duby, Rhonda; Olson, Eric N.; Maniatis, Tom

    2015-01-01

    We report that mice lacking the heterogeneous nuclear ribonucleoprotein U (hnRNP U) in the heart develop lethal dilated cardiomyopathy and display numerous defects in cardiac pre-mRNA splicing. Mutant hearts have disorganized cardiomyocytes, impaired contractility, and abnormal excitation–contraction coupling activities. RNA-seq analyses of Hnrnpu mutant hearts revealed extensive defects in alternative splicing of pre-mRNAs encoding proteins known to be critical for normal heart development and function, including Titin and calcium/calmodulin-dependent protein kinase II delta (Camk2d). Loss of hnRNP U expression in cardiomyocytes also leads to aberrant splicing of the pre-mRNA encoding the excitation–contraction coupling component Junctin. We found that the protein product of an alternatively spliced Junctin isoform is N-glycosylated at a specific asparagine site that is required for interactions with specific protein partners. Our findings provide conclusive evidence for the essential role of hnRNP U in heart development and function and in the regulation of alternative splicing. PMID:26039991

  4. Influence of He-Ne laser radiation of pacemaker on the frog's heart function

    NASA Astrophysics Data System (ADS)

    Porozov, Yury B.; Brill, Gregory E.; Kiritchuk, Vyacheslav F.

    1997-02-01

    In experiments on isolated amphibian hearts changes in photoreactivity of pacemaker cells under the influence of He-Ne laser radiation in different phases of the heart cycle were studied. The specificity of heart photoreaction, peculiarities of relaxation period after laser light action and laser modification of hypodynamic depression development were revealed. Adaptation of pacemaker cells to the He-Ne laser exposure was observed.

  5. Selenium Supplementation Affects Insulin Resistance and Serum hs-CRP in Patients with Type 2 Diabetes and Coronary Heart Disease.

    PubMed

    Farrokhian, A; Bahmani, F; Taghizadeh, M; Mirhashemi, S M; Aarabi, M H; Raygan, F; Aghadavod, E; Asemi, Z

    2016-04-01

    To our knowledge, this study is the first indicating the effects of selenium supplementation on metabolic status of patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This study was conducted to evaluate the effects of selenium supplementation on metabolic profiles, biomarkers of inflammation, and oxidative stress of patients with T2DM and CHD. This randomized, double-blind, placebo-controlled trial was performed among 60 patients with T2DM and CHD aged 40-85 years. Participants were randomly divided into 2 groups. Group A received 200 μg selenium supplements (n=30) and group B received placebo per day (n=30) for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify metabolic profiles. After 8 weeks, compared with the placebo, selenium supplementation resulted in a significant decrease in serum insulin levels (- 2.2±4.6 vs. + 3.6±8.4 μIU/ml, p=0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (- 0.7±1.3 vs. + 0.9±2.4, p=0.004), homeostatic model assessment-beta cell function (HOMA-B) (- 7.5±17.2 vs. + 15.1±34.5, p=0.002) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (+0.01±0.03 vs. - 0.01±0.03, p=0.02). In addition, patients who received selenium supplements had a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (- 1 372.3±2 318.8 vs. - 99.8±1 453.6 ng/ml, p=0.01) and a significant rise in plasma total antioxidant capacity (TAC) concentrations (+ 301.3±400.6 vs. - 127.2±428.0 mmol/l, p<0.001) compared with the placebo. A 200 μg/day selenium supplementation among patients with T2DM and CHD resulted in a significant decrease in insulin, HOMA-IR, HOMA-B, serum hs-CRP, and a significant increase in QUICKI score and TAC concentrations.

  6. Using time-series intervention analysis to model cow heart rate affected by programmed audio and environmental/physiological cues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This research is the first use of the Box-Jenkins time-series models to describe changes in heart rate (HR) of free-ranging crossbred cows (Bos taurus) receiving both programmed audio cues from directional virtual fencing (DVFTM) devices and non-programmed environmental/physiological cues. The DVFT...

  7. Using time-series intervention analysis to model cow heart rate affected by programmed audio and environmental/physiological

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This research is the first use of the Box-Jenkins time-series models to describe changes in heart rate (HR) of free-ranging crossbred cows (Bos taurus) receiving both programmed audio cues from directional virtual fencing (DVFTM) devices and non-programmed environmental/physiological cues. The DVFT...

  8. Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity or cardiac repair

    PubMed Central

    Lorts, Angela; Schwanekamp, Jennifer A.; Elrod, John W.; Sargent, Michelle A.; Molkentin, Jeffery D.

    2009-01-01

    Following a pathologic insult, the adult mammalian heart undergoes hypertrophic growth and remodeling of the extracellular matrix. While a small sub-population of cardiomyocytes can re-enter the cell cycle following cardiac injury, the myocardium is largely thought to be incapable of significant regeneration. Periostin, an extracellular matrix protein, has recently been proposed to induce re-entry of differentiated cardiomyocytes back into the cell cycle and promote meaningful repair following myocardial infarction. Here, we show that while periostin is induced in the heart following injury, it does not stimulate DNA synthesis, mitosis or cytokinesis of cardiomyocytes in vitro or in vivo. Mice lacking the gene encoding periostin and mice with inducible overexpression of full-length periostin were analyzed at baseline and after myocardial infarction. There was no difference in heart size or a change in cardiomyocyte number in either periostin transgenic or gene-targeted mice at baseline. Quantification of proliferating myocytes in the peri-infarct area showed no difference between periostin overexpressing and null mice compared with strain-matched controls. In support of these observations, neither overexpression of periostin in cell culture, via an adenoviral vector, nor stimulation with recombinant protein induced DNA synthesis, mitosis or cytokinesis. Periostin is a regulator of cardiac remodeling and hypertrophy and may be a reasonable pharmacological target to mitigate heart failure, but manipulation of this protein appears to have no obvious effect on myocardial regeneration. PMID:19038863

  9. Formation and function of intracardiac valve cells in the Drosophila heart.

    PubMed

    Lammers, Kay; Abeln, Bettina; Hüsken, Mirko; Lehmacher, Christine; Psathaki, Olympia Ekaterini; Alcorta, Esther; Meyer, Heiko; Paululat, Achim

    2017-03-02

    Drosophila harbors a simple tubular heart that ensures hemolymph circulation within the body. The heart is built by a few different cell types, including cardiomyocytes that define the luminal heart channel and ostia cells that constitute openings in the heart wall allowing hemolymph to enter the heart chamber. Regulation of flow directionality within a tube, such as blood flow in arteries or insect hemolymph within the heart lumen, requires a dedicated gate, valve, or flap-like structure that prevents backflow of fluids. In the Drosophila heart, intracardiac valves provide this directionality of hemolymph streaming, with one valve being present in larvae and three valves in the adult fly. Each valve is built by two specialized cardiomyocytes that exhibit a unique histology. We found that the capacity to open and close the heart lumen relies on a unique myofibrillar setting as well as on the presence of large membranous vesicles. These vesicles are of endocytic origin and probably represent unique organelles of valve cells. Moreover, we characterised the working mode of the cells in real time. Valve cells exhibit a highly flexible shape and during each heartbeat, oscillating shape changes result in closing and opening of the heart channel. Finally, we identified a set of novel valve cell markers useful for future in-depth analyses of cell differentiation in wildtype and mutant animals.

  10. The Relationship of Metabolic Syndrome with Stress, Coronary Heart Disease and Pulmonary Function - An Occupational Cohort-Based Study

    PubMed Central

    Nowobilski, Roman; Dropinski, Jerzy; Kotula-Horowitz, Katarzyna; Laskowicz, Bartosz; Stanisz, Andrzej; Lelakowski, Jacek

    2015-01-01

    Background and Aims Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function. Design and Methods The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters. Results Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24–5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07–29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24–66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03–1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001–1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96–0.99; p = 0.02). MetS subjects had significantly lower values of certain

  11. CHANGES IN HEART RATE VARIABILITY AND LUNG FUNCTION OBSERVED IN NC PATROL TROOPERS EXPOSED TO PM AND AIR TOXICS

    EPA Science Inventory

    Changes in Heart Rate Variability and Lung Function in NC Patrol Troopers exposed to PM and Air Toxics

    Michael Riediker1, Wayne E Cascio1, Robert B Devlin2, Thomas Griggs1&4, Margaret Herbst1, Ronald W Williams3, Steve P McCorquodale4, Philip A Bromberg1
    1) University o...

  12. Decomposition of Heart Rate Variability Spectrum into a Power-Law Function and a Residual Spectrum.

    PubMed

    Kuo, Jane; Kuo, Cheng-Deng

    2016-01-01

    The power spectral density (PSD) of heart rate variability (HRV) contains a power-law relationship that can be obtained by plotting the logarithm of PSD against the logarithm of frequency. The PSD of HRV can be decomposed mathematically into a power-law function and a residual HRV (rHRV) spectrum. Almost all rHRV measures are significantly smaller than their corresponding HRV measures except the normalized high-frequency power (nrHFP). The power-law function can be characterized by the slope and Y-intercept of linear regression. Almost all HRV measures except the normalized low-frequency power have significant correlations with the Y-intercept, while almost all rHRV measures except the total power [residual total power (rTP)] do not. Though some rHRV measures still correlate significantly with the age of the subjects, the rTP, high-frequency power (rHFP), nrHFP, and low-/high-frequency power ratio (rLHR) do not. In conclusion, the clinical significances of rHRV measures might be different from those of traditional HRV measures. The Y-intercept might be a better HRV measure for clinical use because it is independent of almost all rHRV measures. The rTP, rHFP, nrHFP, and rLHR might be more suitable for the study of age-independent autonomic nervous modulation of the subjects.

  13. Microwave influence on the isolated heart function. 1: Effect of modulation

    SciTech Connect

    Pakhomov, A.G.; Dubovick, B.V.; Degtyariov, I.G.; Pronkevich, A.N.

    1995-09-01

    Dependence of the microwave effect on modulation parameters (pulse width, duty ratio, and peak intensity) was studied in an isolated frog auricle preparation. The rate and amplitude of spontaneous auricle twitches were measured during and after a 2 min exposure to 915 or 885 MHz microwaves and were compared to preexposure values. The studied ranges of modulation parameters were: pulse width, 10{sup {minus}6}--10{sup {minus}2} s; duty ratio, 7:100000, and peak specific absorption rate, 100--3,000 W/kg. Combinations of the parameters were chosen by chance, and about 400 various exposure regimes were tested. The experiments established that no regime was effective unless the average microwave power was high enough to induce preparation heating (0.1--0.4 C). The twitch rate instantly increased, and the amplitude decreased, as the temperature rose; similar changes could be induced by equivalent conventional heating. the data provide evidence that the effect of short-term microwave exposure on the isolated heart pacemaker and contractile functions depends on pulse modulation just as much as modulation determines the average absorbed power. These functions demonstrated no specific dependence on exposure parameters such as frequency or power windows.

  14. Microwave influence on the isolated heart function: I. Effect of modulation.

    PubMed

    Pakhomov, A G; Dubovick, B V; Degtyariov, I G; Pronkevich, A N

    1995-01-01

    Dependence of the microwave effect on modulation parameters (pulse width, duty ratio, and peak intensity) was studied in an isolated frog auricle preparation. The rate and amplitude of spontaneous auricle twitches were measured during and after a 2 min exposure to 915 or 885 MHz microwaves and were compared to preexposure values. The studied ranges of modulation parameters were: pulse width, 10(-6)-10(-2) s; duty ratio, 7:100000, and peak specific absorption rate, 100-3000 W/kg. Combinations of the parameters were chosen by chance, and about 400 various exposure regimes were tested. The experiments established that no regime was effective unless the average microwave power was high enough to induce preparation heating (0.1-0.4 degree C). The twitch rate instantly increased, and the amplitude decreased, as the temperature rose; similar changes could be induced by equivalent conventional heating. The data provide evidence that the effect of short-term microwave exposure on the isolated heart pacemaker and contractile functions depends on pulse modulation just as much as modulation determines the average absorbed power. These functions demonstrated no specific dependence on exposure parameters such as frequency or power windows.

  15. Assessing autonomic function by analysis of heart rate recovery from exercise in healthy subjects.

    PubMed

    Pierpont, Gordon L; Voth, Eric J

    2004-07-01

    Although delayed recovery of heart rate (HR) after exercise indicates poor prognosis, the relative role of parasympathetic reactivation versus sympathetic withdrawal in controlling exercise HR recovery remains controversial. Quantifying HR recovery is difficult because the rate of recovery varies with exercise level. This study develops a model of HR recovery applicable to multiple exercise levels simultaneously. Using the Levenberg-Marquardt method for nonlinear models, HR curves for 11 healthy volunteers recovering from 4 different levels of exercise were fit to equations incorporating 1 first-order time constant for parasympathetic reactivation and 1 for sympathetic withdrawal. Results provided time constants for parasympathetic reactivation of 44 +/- 37 seconds and for sympathetic withdrawal of 65 +/- 56 seconds. The model fit the HR recovery curves very closely, explaining 99.7 +/- 0.1% of the variance in the data. In conclusion, this study presents a unique method for quantitatively testing theories on the relative roles of sympathetic withdrawal and parasympathetic reactivation during recovery from exercise. It provides indexes of dynamic sympathetic and parasympathetic functions, with the parasympathetic system having a faster response time. It supports theories of coordinated interaction of parasympathetic reactivation and sympathetic withdrawal during exercise recovery and does not support using simple measures of exercise HR recovery as indexes of vagal function alone.

  16. Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry.

    PubMed

    Tahiliani, A G; McNeill, J H

    1984-06-01

    Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.

  17. [MORPHO-FUNCTIONAL CHANGES OF THYMUS TISSUES IN CHILDREN WITH CONGENITAL HEART DISEASE].

    PubMed

    Loginova, N P; Chetvertnykh, V A; Chemurziyeva, N V

    2016-01-01

    Biopsy specimens of the thymus were studied in children aged under 11 months (n = 77) with congenital heart defects and circulatory hypoxia of varying severity. Histological sections were stained with hematoxylin-eosin and Shubich's method (to demonstrate mast cells). The expression of Ki-67, CD3 and CD34 was assessed by immunohistochemistry. The ultrastructure of thymic tissues was also examined. It was found that the severity of hypoxia determined the morphological changes in the organ associated with a development of large complex of tissue reactions. A disruption of internal structure and a loss of integrity of epithelio-reticular cells and thymocytes were demonstrated in ultrathin sections. Thymocyte proliferation index (Ki-67) and thymocytopoiesis intensity (CD3+) were reduced in all the zones of the thymus. The degree of hypoxia affected the redistribution of CD3+ lymphocytes leading to their accumulation in the medulla. The processes of endogenous regeneration took place which involved the cells of fibroblastic line and progenitor cells (CD34+) together with active formation of new blood vessels. These findings suggest that the morphological changes identified in the tissues of the thymus are a manifestation of tissue adaptation to hypoxia of varying severity under conditions of endogenous regeneration, simultaneously reflecting the processes of substitution cytogenesis.

  18. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

    SciTech Connect

    Benderitter, M.; Assem, M.; Maupoil, V.

    1995-10-01

    During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab.

  19. A meta-analysis of non-invasive brain stimulation and autonomic functioning: Implications for brain-heart pathways to cardiovascular disease.

    PubMed

    Makovac, Elena; Thayer, Julian F; Ottaviani, Cristina

    2017-03-01

    Given the intrinsic connection between the brain and the heart, a recent body of research emerged with the aim to influence cardiovascular system functioning by non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Despite the implications of cardiovascular activity modulation for therapeutic purposes, such effects of NIBS have not yet been quantified. The aim of this study was to meta-analyze studies on NIBS effects on blood pressure (BP), heart rate (HR) and its variability (HRV). PubMed and Scopus databases were searched for English language studies conducted in humans. Twenty-nine studies were eligible for the analyses. Pooled effect sizes (Hedges' g) were compared. Random effect models were used. NIBS was effective in reducing HR (g=0.17) and enhancing HRV (g=0.30). A marginal effect emerged for BP (g=0.21). Significant moderators were the stimulation technique and the site of stimulation. Results show that NIBS affects cardiovascular and autonomic nervous system activity, confirming a potential pathogenic brain-heart pathway to cardiovascular disease.

  20. Calcium-ion movement and contractility in atrial strips of frog heart are not affected by low-frequency-modulated, 1 GHz electromagnetic radiation.

    PubMed

    Schwartz, J L; Mealing, G A

    1993-01-01

    Calcium efflux from electrically stimulated, 45Ca(2+)-preloaded atrial strips of the frog heart was measured from samples of the rinsing perfusate collected at 2-min intervals for 32 min in a continuous perfusion chamber. Contractile force was simultaneously monitored. The specimen chamber was located in a stripline apparatus in which the atrial strips were exposed for 32 min to constant (CW) or amplitude-modulated (AM), 1 GHz electromagnetic (EM) fields at specific absorption rates (SAR) ranging from 3.2 microW/kg to 1.6 W/kg. Amplitude modulation was either at 0.5 Hz, in synchrony with the electrical stimulus applied to the preparation, or at 16 Hz. Neither unmodulated nor 0.5 Hz or 16 Hz modulated 1 GHz waves affected the movement of calcium ions or the contractile force in isolated atrial strips of the frog heart.

  1. Impact of Oral Treatment on Physical Function in Older Patients Hospitalized for Heart Failure: A Randomized Clinical Trial

    PubMed Central

    Ueda, Kazutaka; Kasao, Masashi; Shimamura, Motoaki; Haruta, Hironori; Nitta, Shuya; Kaneko, Mitsunobu; Uemura, Yukari; Morita, Hiroyuki; Komuro, Issei; Shirai, Tetsuro

    2016-01-01

    Background Frailty is a characteristic of older patients with heart failure, who undergo functional decline during hospitalization. At present, continuous intravenous infusion of diuretics is widely used for the treatment of hospitalized patients with heart failure. In this prospective, randomized, open-label controlled trial, we tested whether an early switch from continuous intravenous infusion therapy to oral treatment with diuretics prevents functional decline in patients hospitalized for heart failure. Methods A total of 59 patients hospitalized for heart failure were randomized to either continuous intravenous infusion (n = 30) or oral medication (n = 29) within 48 h of admission. The primary outcome was the Barthel index, a universally utilized scale to assess the functional status of patients in their activities of daily living, assessed at 10 days. Secondary outcomes included the number of daily steps counted using pedometers and average hospital costs. Results Barthel index scores were significantly higher in the oral medication group than in the intravenous group (78.1 ± 20.8 vs. 59.6 ± 34.2, P = 0.029). The number of daily steps was significantly higher in the oral treatment group relative to the intravenous group (P < 0.001), and the average hospital costs were similar between the randomized groups. Multivariate analysis revealed that oral medication was a significant independent predictor of Barthel index score at day 10, and the number of daily steps was significantly associated with the patient’s functional outcome. Conclusions This trial showed that, in patients hospitalized for heart failure, oral medication increased functional independence during hospitalization compared with sustained continuous intravenous infusion, most likely because the release from the infusion line enabled the patients to be more mobile. Notably, these beneficial effects were achieved without increasing hospital costs. PMID:27959941

  2. Ion flux dependent and independent functions of ion channels in the vertebrate heart: lessons learned from zebrafish.

    PubMed

    Keßler, Mirjam; Just, Steffen; Rottbauer, Wolfgang

    2012-01-01

    Ion channels orchestrate directed flux of ions through membranes and are essential for a wide range of physiological processes including depolarization and repolarization of biomechanical activity of cells. Besides their electrophysiological functions in the heart, recent findings have demonstrated that ion channels also feature ion flux independent functions during heart development and morphogenesis. The zebrafish is a well-established animal model to decipher the genetics of cardiovascular development and disease of vertebrates. In large scale forward genetics screens, hundreds of mutant lines have been isolated with defects in cardiovascular structure and function. Detailed phenotyping of these lines and identification of the causative genetic defects revealed new insights into ion flux dependent and independent functions of various cardiac ion channels.

  3. High saturated fat feeding prevents left ventricular dysfunction and enhances mitochondrial function in heart failure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulation of lipids in the heart is associated with contractile dysfunction, and has been proposed to be a causative factor in mitochondrial dysfunction. We have previously shown that administration of a high saturated fat diet in heart failure (HF) increased mitochondrial respiration and ETC com...

  4. Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism.

    PubMed

    Sun, Dan; Yang, Fei

    2017-03-14

    To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks. At the same time, Shame group (Sham) was set up. Changes in cardiac function in mice were detected at 4 weeks after operation. Hearts were taken from mice after 4 weeks, and cell apoptosis in myocardial tissue was detected using TUNEL method; fresh mitochondria were taken and changes in oxygen consumption rate (OCR) and respiratory control rate (RCR) of mitochondria in each group were detected using bio-energy metabolism tester, and change in mitochondrial membrane potential (MMP) of myocardial tissue was detected via JC-1 staining; the expressions and changes in Bcl-2, Bax, Sirt3, PGC-1α and acetylated PGC-1α in myocardial tissue were detected by Western blot. RT-PCR was used to detect mRNA levels in Sirt3 in myocardial tissues. Metformin improved the systolic function of heart failure model rats after myocardial infarction and reduced the apoptosis of myocardial cells after myocardial infarction. Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1α in myocardial tissue of heart failure after myocardial infarction. Metformin decreases the

  5. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    PubMed Central

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  6. Prognostic Value of Estimating Functional Capacity Using the Duke Activity Status Index in Stable Patients with Chronic Heart Failure

    PubMed Central

    Grodin, Justin L.; Hammadah, Muhammad; Fan, Yiying; Hazen, Stanley L.; Wilson Tang, W. H.

    2014-01-01

    Background Over the years several methods have been developed to reliably quantify functional capacity in patients with heart failure. Few studies have investigated the prognostic value of these assessment tools beyond cardio-renal prognostic biomarkers in stable patients with chronic heart failure. Methods and Results We performed Duke Activity Status Index (DASI, a self assessment tool comprised of 12 questions for estimating functional capacity) questionnaire in 1,700 stable, non-acute coronary syndrome patients with history of heart failure who underwent elective diagnostic coronary angiography with 5-year follow-up of all-cause mortality. In a subset of patients (n=800), B-type natriuretic peptide (BNP) was measured. In our study cohort, the median DASI score was 26.2 (IQR 15.5–42.7). Low DASI score provided independent prediction of a 3.3-fold increase in 5-year mortality risk (Quartile 1 versus 4: Hazard ratio [95% confidence interval] 3.33 [2.57–4.36], p<0.0001). After adjusting for traditional risk factors, BNP, and estimated glomerular filtration rate, low DASI score still conferred a 2.6-fold increase in mortality risk (2.57 [1.64–4.15], p<0.0001). Conclusion A simple self-assessment tool of functional capacity provides independent and incremental prognostic value for mortality prediction in stable patients with chronic heart failure beyond cardio-renal biomarkers. PMID:25175697

  7. Health literacy and global cognitive function predict e-mail but not internet use in heart failure patients.

    PubMed

    Schprechman, Jared P; Gathright, Emily C; Goldstein, Carly M; Guerini, Kate A; Dolansky, Mary A; Redle, Joseph; Hughes, Joel W

    2013-01-01

    Background. The internet offers a potential for improving patient knowledge, and e-mail may be used in patient communication with providers. However, barriers to internet and e-mail use, such as low health literacy and cognitive impairment, may prevent patients from using technological resources. Purpose. We investigated whether health literacy, heart failure knowledge, and cognitive function were related to internet and e-mail use in older adults with heart failure (HF). Methods. Older adults (N = 119) with heart failure (69.84 ± 9.09 years) completed measures of health literacy, heart failure knowledge, cognitive functioning, and internet use in a cross-sectional study. Results. Internet and e-mail use were reported in 78.2% and 71.4% of this sample of patients with HF, respectively. Controlling for age and education, logistic regression analyses indicated that higher health literacy predicted e-mail (P < .05) but not internet use. Global cognitive function predicted e-mail (P < .05) but not internet use. Only 45% used the Internet to obtain information on HF and internet use was not associated with greater HF knowledge. Conclusions. The majority of HF patients use the internet and e-mail, but poor health literacy and cognitive impairment may prevent some patients from accessing these resources. Future studies that examine specific internet and email interventions to increase HF knowledge are needed.

  8. Adipose-Derived Cell Construct Stabilizes Heart Function and Increases Microvascular Perfusion in an Established Infarct

    PubMed Central

    Nguyen, Quang T.; Touroo, Jeremy S.; Aird, Allison L.; Chang, Raymond C.; Ng, Chin K.; Hoying, James B.; Williams, Stuart K.

    2013-01-01

    We have previously shown that myocardial infarction (MI) immediately treated with an epicardial construct containing stromal vascular fraction (SVF) from adipose tissue preserved microvascular function and left ventricle contractile mechanisms. In order to evaluate a more clinically relevant condition, we investigated the cardiac recovery potential of an SVF construct implanted onto an established infarct. SVF cells were isolated from rat adipose tissue, plated on Vicryl, and cultured for 14 days. Fischer-344 rats were separated into MI groups: (a) 6-week MI (MI), (b) 6-week MI treated with an SVF construct at 2 weeks (MI SVF), (c) 6-week MI with Vicryl construct at 2 weeks (MI Vicryl), and (d) MI 2wk (time point of intervention). Emax, an indicator of systolic performance and contractile function, was lower in the MI and MI Vicryl versus MI SVF. Positron emission tomography imaging (18F-fluorodeoxyglucose) revealed a decreased percentage of relative infarct volume in the MI SVF versus MI and MI Vicryl. Total vessel count and percentage of perfusion assessed via immunohistochemistry were both increased in the infarct region of MI SVF versus MI and MI Vicryl. Overall cardiac function, percentage of relative infarct, and percentage of perfusion were similar between MI SVF and MI 2wk; however, total vessel count increased after SVF treatment. These data suggest that SVF treatment of an established infarct stabilizes the heart at the time point of intervention by preventing a worsening of cardiac performance and infarcted volume, and is associated with increased microvessel perfusion in the area of established infarct. PMID:24106337

  9. Cognitive Function in Heart Failure is Associated with Nonsomatic Symptoms of Depression but Not Somatic Symptoms

    PubMed Central

    Hawkins, Misty A. W.; Dolansky, Mary A.; Schaefer, Julie T.; Fulcher, Michael J.; Gunstad, John; Redle, Joseph D.; Josephson, Richard; Hughes, Joel W.

    2014-01-01

    Background Patients with heart failure (HF) have high rates of cognitive impairment and depressive symptoms. Depressive symptoms have been associated with greater cognitive impairments in HF; however, it is not known whether particular clusters of depressive symptoms are more detrimental to cognition than others. Objective To identify whether somatic and/or nonsomatic depressive symptom clusters were associated with cognitive function in persons with HF. Methods Participants were 326 HF patients (40.5% female, 26.7% race-ethnicity, aged 68.6±9.7 years). Depressive symptoms were measured using a depression questionnaire commonly used in medical populations: the Patient Health Questionnatire-9 (PHQ-9). Somatic and Nonsomatic subscales scores were created using previous factor analytic results. A neuropsychological battery tested attention, executive function, and memory. Composites were created using averages of age-adjusted scaled scores. Regressions adjusting for demographic and clinical factors were conducted. Results Regressions revealed that PHQ-9 Total was associated with Attention (β=−.14, p=.008) and Executive Function (β=−.17, p=.001). When analyzed separately, the Nonsomatic subscale – but not the Somatic symptoms subscale (ps ≥.092) – was associated with Attention scores (β=−.15, p=.004) and Memory (β=−.11, p=.044). Both Nonsomatic (β=−.18, p<.001) and Somatic symptoms (β=−.11, p=.048) were related to Executive Function. When included together, only the Nonsomatic symptom cluster was associated with Attention (β=−.15, p=.020) and Executive Function (β=−.19, p=.003). Conclusions Greater overall depressive symptom severity was associated with poorer performance on multiple cognitive domains, an effect driven primarily by the nonsomatic symptoms of depression. Clinical Implications These findings suggest that screening explicitly for nonsomatic depressive symptoms may be warranted and that the mechanisms underlying the

  10. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients.

    PubMed

    Biondi, B; Palmieri, E A; Fazio, S; Cosco, C; Nocera, M; Saccà, L; Filetti, S; Lombardi, G; Perticone, F

    2000-12-01

    To determine the clinical impact of endogenous subclinical hyperthyroidism, specific symptoms and signs of thyroid hormone excess and quality of life were assessed in 23 patients (3 males and 20 females; mean age, 43 +/- 9 yr) and 23 age-, sex-, and lifestyle-matched normal subjects by using the Symptoms Rating Scale and the Short Form 36 Health Survey questionnaires. Because the heart is one of the main target organs of the thyroid hormone, cardiac morphology and function were also investigated by means of standard 12-lead electrocardiogram (ECG), 24-h Holter ECG, and complete Doppler echocardiography. Stable endogenous subclinical hyperthyroidism had been diagnosed in all patients at least 6 months before the study (TSH, 0.15 +/- 0.1 mU/L; free T(3), 6.9 +/- 1.1, pmol/L; free T(4), 17.2 +/- 2.3, pmol/L). Fifteen patients were affected by multinodular goiter, and eight patients by autonomously functioning thyroid nodule. The mean Symptoms Rating Scale score (9. 8 +/- 5.5 vs. 4.3 +/- 2.2, P: < 0.001) and both the mental (36.1 +/- 9.5 vs. 50.0 +/- 8.5, P: < 0.001) and physical (42.6 +/- 8.0 vs. 55. 6 +/- 4.1, P: < 0.001) component scores of Short Form 36 Health Survey documented a significant prevalence of specific symptoms and signs of thyroid hormone excess and notable impairment of quality of life in patients. Holter ECG showed a higher prevalence of atrial premature beats in endogenous subclinical hyperthyroid patients than in the controls, but the difference was not statistically significant, although the average heart rate was significantly increased in the patients (P: < 0.001). An increase of left ventricular mass (162 +/- 24 vs. 132 +/- 22 g, P: < 0.001) due to the increase of septal (P: = 0.025) and posterior wall (P: = 0.004) thickness was observed in patients. Systolic function was enhanced in patients as shown by the significant increase of both fractional shortening (P: = 0.005) and mean velocity of heart rate-adjusted circumferential fiber shortening

  11. Pathophysiological relationships between heart failure and depression and anxiety.

    PubMed

    Chapa, Deborah W; Akintade, Bimbola; Son, Heesook; Woltz, Patricia; Hunt, Dennis; Friedmann, Erika; Hartung, Mary Kay; Thomas, Sue Ann

    2014-04-01

    Depression and anxiety are common comorbid conditions in patients with heart failure. Patients with heart failure and depression have increased mortality. The association of anxiety with increased mortality in patients with heart failure is not established. The purpose of this article is to illustrate the similarities of the underlying pathophysiology of heart failure, depression, and anxiety by using the Biopsychosocial Holistic Model of Cardiovascular Health. Depression and anxiety affect biological processes of cardiovascular function in patients with heart failure by altering neurohormonal function via activation of the hypothalamic-pituitary-adrenal axis, autonomic dysregulation, and activation of cytokine cascades and platelets. Patients with heart failure and depression or anxiety may exhibit a continued cycle of heart failure progression, increased depression, and increased anxiety. Understanding the underlying pathophysiological relationships in patients with heart failure who experience comorbid depression and/or anxiety is critical in order to implement appropriate treatments, educate patients and caregivers, and educate other health professionals.

  12. Equestrian expertise affecting physical fitness, body compositions, lactate, heart rate and calorie consumption of elite horse riding players

    PubMed Central

    Sung, Bong-Ju; Jeon, Sang-Yong; Lim, Sung-Ro; Lee, Kyu-Eon; Jee, Hyunseok

    2015-01-01

    Horse riding (HR) is a sport harmonized with rider and horse. HR is renowned as an effective sport for young and old women and men. There is rare study regarding comparison between elite horse riders and amateurs. We aimed to investigate comprehensive ranges of parameters such as change of lactate, heart rate, calorie, VO2max, skeletal muscle mass, body water, body fat, etc between amateurs and professionals to emphasize HR not only as a sport training but also as a therapeutic aspect. We performed 3 experiments for comparing physical fitness, body compositions, lactate value, heart rate and calorie consumption change before and after riding between amateurs and elites. Around 3 yr riding experienced elites are preeminent at balance capability compared to 1 yr riding experienced amateurs. During 18 min horse riding, skeletal muscle mass and body fat were interestingly increased and decreased, respectively. Lactate response was more sensitive in elites rather than amateurs and its recovery was reversely reacted. Exercise intensity estimated from heart rate was significantly higher in elites (P<0.05). The similar pattern of calorie consumption during riding between amateurs and elites was shown. Horse riding possibly induces various physiological (muscle strength, balance, oxidative capability, flexibility, and metabolic control) changes within body and is thus highly recommended as combined exercise for women, children, and aged as therapeutic and leisure sport activity. PMID:26171385

  13. Equestrian expertise affecting physical fitness, body compositions, lactate, heart rate and calorie consumption of elite horse riding players.

    PubMed

    Sung, Bong-Ju; Jeon, Sang-Yong; Lim, Sung-Ro; Lee, Kyu-Eon; Jee, Hyunseok

    2015-06-01

    Horse riding (HR) is a sport harmonized with rider and horse. HR is renowned as an effective sport for young and old women and men. There is rare study regarding comparison between elite horse riders and amateurs. We aimed to investigate comprehensive ranges of parameters such as change of lactate, heart rate, calorie, VO2max, skeletal muscle mass, body water, body fat, etc between amateurs and professionals to emphasize HR not only as a sport training but also as a therapeutic aspect. We performed 3 experiments for comparing physical fitness, body compositions, lactate value, heart rate and calorie consumption change before and after riding between amateurs and elites. Around 3 yr riding experienced elites are preeminent at balance capability compared to 1 yr riding experienced amateurs. During 18 min horse riding, skeletal muscle mass and body fat were interestingly increased and decreased, respectively. Lactate response was more sensitive in elites rather than amateurs and its recovery was reversely reacted. Exercise intensity estimated from heart rate was significantly higher in elites (P<0.05). The similar pattern of calorie consumption during riding between amateurs and elites was shown. Horse riding possibly induces various physiological (muscle strength, balance, oxidative capability, flexibility, and metabolic control) changes within body and is thus highly recommended as combined exercise for women, children, and aged as therapeutic and leisure sport activity.

  14. Predicting the accuracy of facial affect recognition: the interaction of child maltreatment and intellectual functioning.

    PubMed

    Shenk, Chad E; Putnam, Frank W; Noll, Jennie G

    2013-02-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying levels of intellectual functioning. A sample of maltreated (n=50) and nonmaltreated (n=56) adolescent females, 14 to 19 years of age, was recruited to participate in this study. Participants completed demographic and study-related questionnaires and interviews to control for potential psychological and psychiatric confounds such as symptoms of posttraumatic stress disorder, negative affect, and difficulties in emotion regulation. Participants also completed an experimental paradigm that recorded responses to facial affect displays starting in a neutral expression and changing into a full expression of one of six emotions: happiness, sadness, anger, disgust, fear, or surprise. Hierarchical multiple regression assessed the incremental advantage of evaluating the interaction between child maltreatment and intellectual functioning. Results indicated that the interaction term accounted for a significant amount of additional variance in the accurate identification of facial affect after controlling for relevant covariates and main effects. Specifically, maltreated females with lower levels of intellectual functioning were least accurate in identifying facial affect displays, whereas those with higher levels of intellectual functioning performed as well as nonmaltreated females. These results suggest that maltreatment and intellectual functioning interact to predict the recognition of facial affect, with potential long-term consequences for the interpersonal functioning of maltreated females.

  15. Platelet-derived microparticles and platelet function profile in children with congenital heart disease.

    PubMed

    Ismail, Eman Abdel Rahman; Youssef, Omneya Ibrahim

    2013-01-01

    Platelet microparticles (PMPs) and function profile in children with congenital heart disease (CHD) have not been widely explored. We investigated platelet aggregation, flow cytometric platelet surface receptors (P-selectin and glycoprotein (GP) IIb/IIIa) and PMPs in 23 children with cyanotic CHD (CCHD), 30 children with acyanotic CHD (ACHD) and 30 healthy controls correlating these variables to hematological and coagulation parameters including von Willebrand factor antigen (vWF Ag) as a marker of endothelial dysfunction. Hemoglobin, hematocrit (HCT), D-dimer, and vWF Ag were significantly higher in CCHD than ACHD group. Platelet MPs and P-selectin expression were increased in patients than controls, particularly in CCHD and positively correlated to HCT, D-dimer, and vWF Ag while platelet count, aggregation, and GP IIb/IIIa expression were decreased in CCHD compared with ACHD group and negatively correlated to HCT. The overproduction of PMPs and platelet activation with suppressed aggregation may be implicated in the pathogenesis of coagulation/hemostatic abnormalities in children with CCHD.

  16. Noninvasive ventilation improves cardiac function in patients with chronic heart failure

    PubMed Central

    Cheng, Jing; Liu, Yanping; Li, Guishuang; Zhang, Zhongwen; Ma, Lianyue; Yang, Xiaoyan; Yang, Jianmin; Zhang, Kai; Kong, Jing; Dong, Mei; Zhang, Meng; Xu, Xingli; Sui, Wenhai; Wang, Jiali; Shang, Rui; Ji, Xiaoping; Zhang, Yun; Zhang, Cheng; Hao, Panpan

    2016-01-01

    Chronic heart failure (CHF) has been shown to be associated with an increased incidence of sleep-disordered breathing. Whether treatment with noninvasivepositive-pressure ventilation (NPPV), including continuous positive airway pressure, bi-level positive airway pressure and adaptive servo-ventilation, improves clinical outcomes of CHF patients is still debated. 2,832 CHF patients were enrolled in our analysis. NPPV was significantly associated with improvement in left ventricular ejection fraction (39.39% vs. 34.24%; WMD, 5.06; 95% CI, 3.30-6.81; P < 0.00001) and plasma brain natriuretic peptide level (268.23 pg/ml vs. 455.55 pg/ml; WMD, −105.66; 95% CI, [−169.19]-[−42.13]; P = 0.001). However, NPPV did not reduce all-cause mortality (0.26% vs. 0.24%; OR, 1.13; 95% CI, 0.93-1.37; P = 0.22) or re-hospitalization rate (57.86% vs. 59.38%; OR, 0.47; 95% CI, 0.19-1.19; P = 0.02) as compared with conventional therapy. Despite no benefits on hard endpoints, NPPV may improve cardiac function of CHF patients. These data highlight the important role of NPPV in the therapy of CHF. PMID:27391436

  17. Microwave influence on the isolated heart function: II. Combined effect of radiation and some drugs.

    PubMed

    Pakhomov, A G; Dubovick, B V; Degtyariov, I G; Pronkevich, A N

    1995-01-01

    The combined effects of microwave radiation and some drugs were studied in an isolated frog auricle preparation. The experiments established that exposure to pulse-modulated 915 MHz microwaves for up to 40 min had no effect on either the rate or the amplitude of spontaneous auricle twitches, unless the average absorbed power was high enough to produce preparation heating. Treatment of the preparation with saline containing (0.6-3.0) 10(-5) M of propranolol or (0.5-1.5) 10(-7) M of atropine altered neither its pacemaker nor its contractile functions; these drugs also had no effect when they were combined with nonthermal microwave irradiation. Caffeine (1 mM) strongly increased the average heart power, which was calculated as the product of twitch rate and amplitude. The caffeine effect appeared to be significantly augmented (by about 15%, P < 0.02) under exposure to burst-type pulsed microwaves (pulse width, 1.5 msec; pause, 2.5 msec; 8 pulses/burst, 16 bursts/s; average SAR, 8-10 W/kg). By itself, this modulation was not effective; the heating of the preparation and saline during exposure was approximately 0.1 degrees C, which could not account for the detected changes. The experimental results demonstrate that caffeine treatment increases the microwave sensitivity of the frog auricle preparation and reveals primarily subthreshold, nonthermal microwave effect.

  18. Wavelet Based Method for Congestive Heart Failure Recognition by Three Confirmation Functions.

    PubMed

    Daqrouq, K; Dobaie, A

    2016-01-01

    An investigation of the electrocardiogram (ECG) signals and arrhythmia characterization by wavelet energy is proposed. This study employs a wavelet based feature extraction method for congestive heart failure (CHF) obtained from the percentage energy (PE) of terminal wavelet packet transform (WPT) subsignals. In addition, the average framing percentage energy (AFE) technique is proposed, termed WAFE. A new classification method is introduced by three confirmation functions. The confirmation methods are based on three concepts: percentage root mean square difference error (PRD), logarithmic difference signal ratio (LDSR), and correlation coefficient (CC). The proposed method showed to be a potential effective discriminator in recognizing such clinical syndrome. ECG signals taken from MIT-BIH arrhythmia dataset and other databases are utilized to analyze different arrhythmias and normal ECGs. Several known methods were studied for comparison. The best recognition rate selection obtained was for WAFE. The recognition performance was accomplished as 92.60% accurate. The Receiver Operating Characteristic curve as a common tool for evaluating the diagnostic accuracy was illustrated, which indicated that the tests are reliable. The performance of the presented system was investigated in additive white Gaussian noise (AWGN) environment, where the recognition rate was 81.48% for 5 dB.

  19. Wavelet Based Method for Congestive Heart Failure Recognition by Three Confirmation Functions

    PubMed Central

    Daqrouq, K.; Dobaie, A.

    2016-01-01

    An investigation of the electrocardiogram (ECG) signals and arrhythmia characterization by wavelet energy is proposed. This study employs a wavelet based feature extraction method for congestive heart failure (CHF) obtained from the percentage energy (PE) of terminal wavelet packet transform (WPT) subsignals. In addition, the average framing percentage energy (AFE) technique is proposed, termed WAFE. A new classification method is introduced by three confirmation functions. The confirmation methods are based on three concepts: percentage root mean square difference error (PRD), logarithmic difference signal ratio (LDSR), and correlation coefficient (CC). The proposed method showed to be a potential effective discriminator in recognizing such clinical syndrome. ECG signals taken from MIT-BIH arrhythmia dataset and other databases are utilized to analyze different arrhythmias and normal ECGs. Several known methods were studied for comparison. The best recognition rate selection obtained was for WAFE. The recognition performance was accomplished as 92.60% accurate. The Receiver Operating Characteristic curve as a common tool for evaluating the diagnostic accuracy was illustrated, which indicated that the tests are reliable. The performance of the presented system was investigated in additive white Gaussian noise (AWGN) environment, where the recognition rate was 81.48% for 5 dB. PMID:26949412

  20. Physiologically inspired cardiac scaffolds for tailored in vivo function and heart regeneration

    PubMed Central

    Kaiser, Nicholas J; Coulombe, Kareen L K

    2015-01-01

    Tissue engineering is well suited for the treatment of cardiac disease due to the limited regenerative capacity of native cardiac tissue and the loss of function associated with endemic cardiac pathologies, such as myocardial infarction and congenital heart defects. However, the physiological complexity of the myocardium imposes extensive requirements on tissue therapies intended for these applications. In recent years, the field of cardiac tissue engineering has been characterized by great innovation and diversity in the fabrication of engineered tissue scaffolds for cardiac repair and regeneration to address these problems. From early approaches that attempted only to deliver cardiac cells in a hydrogel vessel, significant progress has been made in understanding the role of each major component of cardiac living tissue constructs (namely cells, scaffolds, and signaling mechanisms) as they relate to mechanical, biological, and electrical in vivo performance. This improved insight, accompanied by modern material science techniques, allows for the informed development of complex scaffold materials that are optimally designed for cardiac applications. This review provides a background on cardiac physiology as it relates to critical cardiac scaffold characteristics, the degree to which common cardiac scaffold materials fulfill these criteria, and finally an overview of recent in vivo studies that have employed this type of approach. PMID:25970645

  1. 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.

  2. Microwave influence on the isolated heart function. 2: Combined effect of radiation and some drugs

    SciTech Connect

    Pakhomov, A.G.; Dubovick, B.V.; Degtyariov, I.G.; Pronkevich, A.N.

    1995-09-01

    The combined effects of microwave radiation and some drugs were studied in an isolated frog auricle preparation. The experiments established that exposure to pulse-modulated 915 Mhz microwaves for up to 40 min had no effect on either the rate or the amplitude of spontaneous auricle twitches, unless the average absorbed power was high enough to produce preparation heating. Treatment of the preparation with saline containing (0.6--3.0) 10{sup {minus}5} M of propranolol or (0.5--1.5) 10{sup {minus}7} M of atropine altered neither its pacemaker nor its contractile functions; these drugs also had no effect when they were combined with nonthermal microwave irradiation. Caffeine (1 mM) strongly increased the average heart power, which was calculated as the product of twitch rate ad amplitude. The caffeine effect appeared to be significantly augmented (by about 15%, P<0.02) under exposure to burst-type pulsed microwaves (pulse width, 1.5 msec; pause, 2.5 msec; 8 pulses/burst, 16 bursts/s; average SAR, 8--10 W/kg). By itself, this modulation was not effective; the heating of the preparation and saline during exposure was approximately 0.1 C, which could not account for the detected changes. The experimental results demonstrate that caffeine treatment increases the microwave sensitivity of the frog auricle preparation and reveals primarily subthreshold, nonthermal microwave effect.

  3. Autonomic nervous functions in fetal type Minamata disease patients: assessment of heart rate variability.

    PubMed

    Oka, Tomoko; Matsukura, Makoto; Okamoto, Miwako; Harada, Noriaki; Kitano, Takao; Miike, Teruhisa; Futatsuka, Makoto

    2002-12-01

    In order to assess the cardiovascular autonomic nervous functions in patients with fetal type Minamata disease (FMD), we investigated blood pressure (BP), and conducted time and frequency domain analysis of heart rate variability (HRV). Subjects were 9 patients in Meisuien recognized as FMD, and 13 healthy age matched control subjects. HRV and BP were assessed after subjects rested in a supine position for 10 minutes. Electrocardiographic (ECG) data were collected for 3 minutes during natural breathing. Time domain analysis (the average of R-R intervals [Mean RR], standard deviation of R-R intervals [SD RR], coefficient of variation [CV]), and frequency domain analysis by fast Fourier transformation (FFT) (power of low frequency [LF] and high frequency [HF] component, expressed in normalized units[nu]) were then conducted. In the time domain analysis, the mean RR of the FMD group was significantly lower than that of the control group. Neither SD RR nor CV showed significant differences between the two groups, but both tended to be lower in the FMD group. In the frequency domain analysis, the HF component of the FMD group was significantly lower than that of the control group. Pulse pressure (PP) was significantly lower in the FMD subjects. These findings suggest that parasympathetic nervous dysfunction might exist in FMD patients, who were exposed to high doses of methylmercury (MeHg) during the prenatal period. Decrease of PP might be due to degenerative changes of blood vessels driven by exposure to high doses of MeHg.

  4. Electrophysiological consequences of KATP Gain-of-function in the heart: Conduction abnormalities in Cantu Syndrome

    PubMed Central

    Levin, Mark D.; Zhang, Haixia; Uchida, Keita; Grange, Dorothy K.; Singh, Gautam K.; Nichols, Colin G.

    2015-01-01

    Background Gain-of-function (GOF) mutations in the KATP channel subunits Kir6.1 and SUR2 cause Cantu syndrome (CS), a disease characterized by multiple cardiovascular abnormalities. Objective To better understand the electrophysiological consequences of such GOF mutations in the heart. Methods We generated transgenic mice (Kir6.1-GOF) expressing ATP-insensitive Kir6.1[G343D] subunits under α-myosin heavy chain (α-MHC) promoter control, to target gene expression specifically in cardiomyocytes, and carried out patch-clamp experiments on isolated ventricular myocytes, invasive electrophysiology on anesthetized mice. Results In Kir6.1-GOF ventricular myocytes, KATP channels show decreased ATP sensitivity, but there is no significant change in current density. Ambulatory ECG recordings on Kir6.1-GOF mice reveal AV nodal conduction abnormalities and junctional rhythm. Invasive electrophysiological analyses reveal slowing of conduction and conduction failure through the AV node, but no increase in susceptibility to atrial or ventricular ectopic activity. Surface electrocardiograms recorded from CS patients also demonstrate first degree AV block, and fascicular block. Conclusions The primary electrophysiological consequence of cardiac KATP GOF is on the conduction system, particularly the AV node, resulting in conduction abnormalities in CS patients, who carry KATP GOF mutations. PMID:26142302

  5. Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

    PubMed

    Brooks, W W; Bing, O H; Litwin, S E; Conrad, C H; Morgan, J P

    1994-09-01

    We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30 degrees C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O2/5% CO2) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca2+]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca2+]o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca2+]i and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca2+]i, peak systolic pressure, and +/- dP/dt fell in SHR-F hearts. Peak systolic pressure decreased in the SHR-NF group at rates above 2.4 Hz but did not decline in the WKY group. Peak [Ca2+]i increased in the WKY and SHR-NF groups with increasing heart rates. Peak systolic pressure did not fall significantly in the WKY group at any heart rate. Elevation of diastolic [Ca2+]i and/or calcium transient and pressure alternans were present in 8 of 13 SHR-F hearts at the highest stimulation rate, findings that were absent in both the WKY and SHR-NF hearts. We conclude the following: (1) Under baseline conditions, depressed contractile function of

  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. Illegal Drugs and Heart Disease

    MedlinePlus

    ... vessels and heart valves. Many drugs, such as cocaine, heroin and various forms of amphetamine, affect the ... heart attacks, seizures, and respiratory arrest More about Cocaine - the "perfect heart-attack drug" The powdered form ...

  9. Loss of the eukaryotic initiation factor 2α kinase general control nonderepressible 2 protects mice from pressure overload-induced congestive heart failure without affecting ventricular hypertrophy.

    PubMed

    Lu, Zhongbing; Xu, Xin; Fassett, John; Kwak, Dongmin; Liu, Xiaoyu; Hu, Xinli; Wang, Huan; Guo, Haipeng; Xu, Dachun; Yan, Shuo; McFalls, Edward O; Lu, Fei; Bache, Robert J; Chen, Yingjie

    2014-01-01

    In response to several stresses, including nutrient deprivation, general control nonderepressible 2 kinase (GCN2) attenuates mRNA translation by phosphorylating eukaryotic initiation factor 2α(Ser51). Energy starvation is known to exacerbate congestive heart failure, and eukaryotic initiation factor 2α(Ser51) phosphorylation is increased in the failing heart. However, the effect of GCN2 during the evolution of congestive heart failure has not been tested. In this study, we examined the influence of GCN2 expression in response to a cardiac stress by inducing chronic pressure overload with transverse aortic constriction in wild-type and GCN2 knockout mice. Under basal conditions, GCN2 knockout mice had normal left ventricular structure and function, but after transverse aortic constriction, they demonstrated less contractile dysfunction, less increase in lung weight, less increase in lung inflammation and vascular remodeling, and less myocardial apoptosis and fibrosis compared with wild-type mice, despite an equivalent degree of left ventricular hypertrophy. As expected, GCN2 knockout attenuated transverse aortic constriction-induced cardiac eukaryotic initiation factor 2α(Ser51) phosphorylation and preserved sarcoplasmic reticulum Ca(2+) ATPase expression compared with wild-type mice. Interestingly, the expression of the antiapoptotic protein Bcl-2 was significantly elevated in GCN2 knockout hearts, whereas in isolated neonatal cardiomyocytes, selective knockdown of GCN2 increased Bcl-2 protein expression and enhanced myocyte resistance to an apoptotic stress. Collectively, our data support the notion that GCN2 impairs the ventricular adaptation to chronic pressure overload by reducing Bcl-2 expression and increasing cardiomyocyte susceptibility to apoptotic stimuli. Our findings suggest that strategies to reduce GCN2 activity in cardiac tissue may be a novel approach to attenuate congestive heart failure development.

  10. High Resolution ECG for Evaluation of Heart Function During Exposure to Subacute Hypobaric Hypoxia

    NASA Technical Reports Server (NTRS)

    Zupet, Petra; Finderle, Zarko; Schlegel, Todd T.; Princi, Tanja; Starc, Vito

    2010-01-01

    High altitude climbing presents a wide spectrum of health risks, including exposure to hypobaric hypoxia. Risks are also typically exacerbated by the difficulty in appropriately monitoring for early signs of organ dysfunction in remote areas. We investigated whether high resolution advanced ECG analysis might be helpful as a non-invasive and easy-to-use tool (e.g., instead of Doppler echocardiography) for evaluating early signs of heart overload in hypobaric hypoxia. Nine non-acclimatized healthy trained alpine rescuers (age 43.7 plus or minus 7.3 years) climbed in four days to the altitude of 4,200 m on Mount Ararat. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position on different days but at the same time of day at four different altitudes: 400 m (reference altitude), 1,700 m, 3,200 m and 4,200 m. Changes in conventional and advanced resting ECG parameters, including in beat-to-beat QT and RR variability, waveform complexity, signal-averaged, high-frequency and spatial/spatiotemporal ECG was estimated by calculation of the regression coefficients in independent linear regression models. A p-value of less than 0.05 was adopted as statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with trends k = -96 ms/1000 m with p = 0.000 and k = -9 ms/1000 m with p = 0.001, respectively. Significant changes were found in P-wave amplitude, which nearly doubled from the lowest to the highest altitude (k = 41.6 microvolt/1000 m with p = 0.000), and nearly significant changes in P-wave duration (k = 2.9 ms/1000 m with p = 0.059). Changes were less significant or non-significant in other studied parameters including those of waveform complexity, signal-averaged, high-frequency and spatial/spatiotemporal ECG. High resolution ECG analysis, particularly of the P wave, shows promise as a tool for monitoring early changes in heart function

  11. Correlation of coronary artery stenosis evaluation with left heart structure and function by multi-slice computed tomography.

    PubMed

    Song, L N; Cao, A D; Niu, Y J; Liu, N

    2014-08-07

    The aim of this study was to determine the impact of multi-slice computed tomography (MSCT) evaluation of coronary artery stenosis on left heart structure and systolic function. Coronary artery CT angiography was performed in 200 patients diagnosed with coronary heart disease, and then according to the AHA coronary artery 17-segment fractionation method, the Gensini score (GS) was determined for every narrow segment, and one-stop assessment of the correlation between left heart structure and function was performed. After the grouping of GS quartiles from low to high, there were differences between different patients with regard to LVDD, LADD, LVEDV, LVESV, MM, LVEF, and FS, while no difference in SV and CO. GS showed linear negative correlation with LVEF and FS, and linear positive correlation with LVDD, LADD, LVEDV, LVESV, and MM, while no correlation with SV and CO. That is, GS of coronary artery stenosis was negatively correlated with left ventricular systolic function and positively correlated with myocardial mass. The narrower the coronary artery, the worse the cardiac function and the higher the myocardial hypertrophy. Coronary artery stenosis was one of the important causes of the decrease in left ventricular systolic function and cardiac remodeling.

  12. Attenuated Recovery of Contractile Function in Aging Hearts Following Global Ischemia/Reperfusion: Role of Extracellular HSP27 and TLR4

    PubMed Central

    Ao, Lihua; Zhai, Yufeng; Jin, Chunhua; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong

    2016-01-01

    While cardiac functional recovery is attenuated in the elderly following cardiac surgery with obligatory global myocardial ischemia/reperfusion (I/R), the underlying mechanism remains incompletely understood. We observed previously that human and mouse myocardium releases heat shock protein (HSP) 27 during global I/R. Extracellular HSP27 induces myocardial inflammatory response and plays a role in postischemic cardiac dysfunction in adult mouse hearts. This study was to determine the role of extracellular HSP27 and Toll-like receptor 4 (TLR4) in the attenuated functional recovery in aging mouse hearts following global I/R. Hearts isolated from aging (18–24 months) and adult (4–6 months) mice were subjected to ex vivo global I/R. Augmented release of HSP27 in aging hearts was associated with greater production of cytokines (TNF-α and IL-1β) and worse functional recovery. Anti-HSP27 suppressed the inflammatory response and markedly improved functional recovery in aging hearts. Perfusion of recombinant HSP27 to aging hearts resulted in greater cytokine production and more severe contractile depression in comparison to adult hearts. TLR4 deficiency abolished cytokine production and functional injury in aging hearts exposed to recombinant HSP27. Interestingly, aging hearts had higher TLR4 protein levels and displayed enhanced TLR4-mediated NF-κB activation following HSP27 stimulation or I/R. Extracellular HSP27 and TLR4 jointly enhance the inflammatory response and hamper functional recovery following I/R in aging hearts. The enhanced inflammatory response to global I/R and attenuated postischemic functional recovery in aging hearts are due, at least in part, to augmented myocardial release of HSP27 and elevated myocardial TLR4 levels. PMID:28079228

  13. Vitamin D Insufficiency Is Associated with Lower Physical Function in Patients with Heart Failure and Diabetes

    PubMed Central

    Lopes, M. R.; Ribeiro, Paula A. B.; Souza, Gabriela C.; Clausell, Nadine; Schaan, Beatriz D.

    2014-01-01

    Vitamin D deficiency is frequent among patients with heart failure (HF) and diabetes, disorders associated with exercise intolerance and muscle weakness. This study aims to search for associations between vitamin D sufficiency and physical function indexes in patients with HF and diabetes. A cross-sectional study of 146 HF patients, 39.7% with diabetes, at a Brazilian tertiary outpatient clinic was performed. Patients underwent clinical evaluation, 6-minute walk test (6 MWT), handgrip strength, physical activity level (IPAQ), and biochemical evaluations including serum 25-hydroxyvitamin D. Classification was done according to vitamin D status (≥30 ng/dL, sufficient) and presence/absence of diabetes in vitamin sufficient, no diabetes (DS-C, n = 25), vitamin sufficient, diabetes (DS-DM, n = 18), vitamin deficient, no diabetes (DD-C, n = 63), and vitamin deficient, diabetes (DD-DM, n = 40). Patients age was 55.4 ± 8 yrs; 70.5% had vitamin D deficiency. Clinical characteristics were similar among groups. Total time expended in physical activity was similar among groups (P = 0.26). DS-C covered higher distances in the 6 MWT (392 ± 60 m) versus DD-DM (309 ± 116 m); P = 0.024. Handgrip strength was similar among groups but tended to lower levels in DD-DM (P = 0.074) even after being adjusted to physical activity (P = 0.069). Vitamin D deficiency can influence physical function in HF diabetic patients. PMID:25243195

  14. Functional and structural evaluation of bovine heart cytochrome c oxidase incorporated into bicelles.

    PubMed

    Musatov, Andrey; Siposova, Katarina; Kubovcikova, Martina; Lysakova, Veronika; Varhac, Rastislav

    2016-02-01

    Bilayered long- and short-chain phospholipid assemblies, known as bicelles, have been widely used as model membranes in biological studies. However, to date, there has been no demonstration of structural or functional viability for the fundamental mitochondrial electron transport complexes reconstituted into or interacting with bicelles. In the present work, bicelles were formed from the mixture of long- and short-chain phospholipids, specifically 14:0 and 6:0 phosphatidylcholines (1,2-dimyristoyl-sn-glycero-3-phosphocholine, (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine, (DHPC)). Isolated from bovine heart, cytochrome c oxidase was successfully incorporated into bicelles. Bicelles and cytochrome c oxidase incorporated into bicelles ("proteobicelles") were characterized by absorption spectroscopy, dynamic light scattering, atomic force microscopy, sedimentation velocity and differential scanning calorimetry. It was demonstrated that at total concentration of phospholipids CL = 24 mM and the molar ratio (q) of long-chain DMPC over short-chain DHPC equal to 0.4, the diameter of bicelles formed at neutral pH is in the range of 30-60 nm with the thickness of bicelles of about 4 nm. Adding cytochrome c oxidase to bicelles unified the size of the resulting proteobicelles to about 160 nm. Cytochrome c oxidase in bicelles was fully reducible by artificial donors of electrons, exhibited "normal" reaction with external ligands, and was fully active. Both, sedimentation velocity analysis and temperature-induced denaturation indicated that enzyme in bicelles is monomeric. We concluded that cytochrome c oxidase in bicelles maintains its structural and functional integrity, and that bicelles can be used for more comprehensive investigation of cytochrome c oxidase and most likely other mitochondrial electron transfer complexes.

  15. Lexical and Affective Prosody in Children with High-Functioning Autism

    ERIC Educational Resources Information Center

    Grossman, Ruth B.; Bemis, Rhyannon H.; Skwerer, Daniela Plesa; Tager-Flusberg, Helen

    2010-01-01

    Purpose: To investigate the perception and production of lexical stress and processing of affective prosody in adolescents with high-functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody but atypical lexical prosody production. Method: Sixteen children with HFA and 15 typically developing (TD) peers…

  16. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    SciTech Connect

    Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Moros, Eduardo G.; Zheng, Junying; Hauer-Jensen, Martin; Boerma, Marjan

    2014-01-01

    Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

  17. The importance of lung function, non-malignant diseases associated with asbestos, and symptoms as predictors of ischaemic heart disease in shipyard workers exposed to asbestos.

    PubMed Central

    Sandén, A; Järvholm, B; Larsson, S

    1993-01-01

    The mortality from ischaemic heart disease was studied in a prospective cohort of 1725 shipyard workers exposed to asbestos. The analyses were stratified for age and smoking habits and restricted to men. In agreement with other findings, men with impaired lung function had a significantly higher risk (relative risk (RR) = 3.5) of dying from ischaemic heart disease than men with normal lung function. Men with asbestosis or suspected asbestosis had a significantly higher risk (RR = 3.1) of dying from ischaemic heart disease than men without asbestosis. Thus asbestosis or suspected asbestosis also seemed to be a risk factor for ischaemic heart disease. This finding was independent of respiratory function. There was no increased risk for ischaemic heart disease in men with compared with men without pleural plaques. Men with production of phlegm or sputum and wheezing or whistling had no increased risk for ischaemic heart disease compared with men without these symptoms. In the group with normal lung function men with dyspnoea had a significantly higher risk of dying from ischaemic heart disease than men without dyspnoea. The findings for men with asbestosis or suspected asbestosis indicated a further risk factor besides impaired lung function, in persons exposed to asbestos. Perhaps this risk factor is due to lesions of the pericardium with consequences for heart function. PMID:8398871

  18. Heart Health - Brave Heart

    MedlinePlus

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

  19. Effects of Sildenafil on Ventricular and Vascular Function in Heart Failure With Preserved Ejection Fraction

    PubMed Central

    Borlaug, Barry A.; Lewis, Gregory D.; McNulty, Steven E.; Semigran, Marc J.; LeWinter, Martin; Chen, Horng; Lin, Grace; Deswal, Anita; Margulies, Kenneth B.; Redfield, Margaret M.

    2015-01-01

    Background Early studies showed beneficial effects of phosphodiesterase 5 inhibitors (PDE5i) on cardiovascular function in heart failure (HF) patients, but the RELAX trial observed no improvement in exercise capacity with sildenafil treatment in subjects with HF and preserved ejection fraction (HFpEF). Methods and Results A subgroup of participants in the RELAX trial (n=48) underwent comprehensive noninvasive cardiovascular assessment before and after treatment with sildenafil or placebo in a prospective ancillary study. Left ventricular (LV) contractility was assessed by peak power index (PWR/EDV) and stroke work index (SW/EDV). Systemic arterial load was assessed by arterial elastance (Ea) and right ventricular afterload by pulmonary artery systolic pressure (PASP). Endothelial function was assessed by reactive hyperemia index (RHI) following upper arm cuff occlusion. Compared to placebo (n=25), sildenafil (n=23) decreased Ea (−0.29±0.28mmHg/ml vs +0.02±0.29, p=0.008) and tended to improve RHI (+0.30±0.45 vs −0.17±0.30, p=0.054). In contrast, LV contractility was reduced by 11–16% with sildenafil compared to placebo (ΔPWR/EDV −52±70 vs +0±40 mmHg/s, p=0.006; ΔSW/EDV +0.3±5.8 vs −6.0±5.1 mmHg, p=0.04). Sildenafil had no effect on PASP. Conclusions In subjects with HFpEF, sildenafil displayed opposing effects on ventricular and vascular function. We speculate that beneficial effects of PDE5i in the systemic vasculature and endothelium were insufficient to improve clinical status, or that the deleterious effects on left ventricular function offset any salutary vascular effects, contributing to the absence of benefit observed with sildenafil in subjects with HFpEF in the RELAX trial. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302. PMID:25782985

  20. Viewing nature scenes positively affects recovery of autonomic function following acute-mental stress.

    PubMed

    Brown, Daniel K; Barton, Jo L; Gladwell, Valerie F

    2013-06-04

    A randomized crossover study explored whether viewing different scenes prior to a stressor altered autonomic function during the recovery from the stressor. The two scenes were (a) nature (composed of trees, grass, fields) or (b) built (composed of man-made, urban scenes lacking natural characteristics) environments. Autonomic function was assessed using noninvasive techniques of heart rate variability; in particular, time domain analyses evaluated parasympathetic activity, using root-mean-square of successive differences (RMSSD). During stress, secondary cardiovascular markers (heart rate, systolic and diastolic blood pressure) showed significant increases from baseline which did not differ between the two viewing conditions. Parasympathetic activity, however, was significantly higher in recovery following the stressor in the viewing scenes of nature condition compared to viewing scenes depicting built environments (RMSSD; 50.0 ± 31.3 vs 34.8 ± 14.8 ms). Thus, viewing nature scenes prior to a stressor alters autonomic activity in the recovery period. The secondary aim was to examine autonomic function during viewing of the two scenes. Standard deviation of R-R intervals (SDRR), as change from baseline, during the first 5 min of viewing nature scenes was greater than during built scenes. Overall, this suggests that nature can elicit improvements in the recovery process following a stressor.

  1. Structure and function relationship of Zebrafish embryonic heart from confocal microscopy images

    NASA Astrophysics Data System (ADS)

    Moghaddam, Abbas N.; Forouhar, Arian; Liebling, Michael; Tsai, Huai-Jen; Gharib, Morteza

    2006-03-01

    Confocal microscopy enables us to track myocytes in the embryonic zebrafish heart. The Zeiss LSM 5 Live high speed confocal microscope has been used to take optical sections (at 3 μm intervals and 151 frames per second) through a fluorescently labeled zebrafish heart at two developmental stages (26 and 34 hours post fertilization (hpf)). This data provides unique information allowing us to conjecture on the morphology and biomechanics of the developing vertebrate heart. Nevertheless, the myocytes, whose positions could be determined in a reliable manner, were located sparsely and mostly in one side of the heart tube. This difficulty was overcome using computational methods, that give longitudinal, radial and circumferential displacements of the myocytes as well as their contractile behavior. Applied strain analysis has shown that in the early embryonic heart tube, only the caudal region (near the in-flow) and another point in the middle of the tube can be active; the rest appears to be mostly passive. This statement is based on the delay between major strain and displacement which a material point experiences. Wave-like propagation of all three components of the displacement, especially in the circumferential direction, as well as the almost-periodic changes of the maximum strain support the hypothesis of helical muscle structure embedded in the tube. Changes of geometry in the embryonic heart after several hours are used to verify speculations about the structure based on the earlier images and aforementioned methods.

  2. Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study

    PubMed Central

    Weaver, Anne M.; Wellenius, Gregory A.; Wu, Wen-Chih; Hickson, DeMarc A.; Kamalesh, Masoor; Wang, Yi

    2016-01-01

    Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150–299 m, 1161 lived 300–999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans. PMID:27304962

  3. A flexible home monitoring platform for patients affected by chronic heart failure directly integrated with the remote Hospital Information System

    NASA Astrophysics Data System (ADS)

    Donati, Massimiliano; Bacchillone, Tony; Saponara, Sergio; Fanucci, Luca

    2011-05-01

    Today Chronic Heart Failure (CHF) represents one of leading cause of hospitalization among chronic disease, especially for elderly citizens, with a consequent considerable impact on patient quality of life, resources congestion and healthcare costs for the National Sanitary System. The current healthcare model is mostly in-hospital based and consists of periodic visits, but unfortunately it does not allow to promptly detect exacerbations resulting in a large number of rehospitalization. Recently physicians and administrators identify telemonitoring systems as a strategy able to provide effective and cost efficient healthcare services for CHF patients, ensuring early diagnosis and treatments in case of necessity. This work presents a complete and integrated ICT solution to improve the management of chronic heart failure through the remote monitoring of vital signs at patient home, able to connect in-hospital care of acute syndrome with out-of-hospital follow-up. The proposed platform represents the patient's interface, acting as link between biomedical sensors and the data collection point at the Hospital Information System (HIS) in order to handle in transparent way the reception, analysis and forwarding of the main physiological parameters.

  4. Angiotensin-converting enzyme and matrix metalloproteinase inhibition with developing heart failure: comparative effects on left ventricular function and geometry

    NASA Technical Reports Server (NTRS)

    McElmurray, J. H. 3rd; Mukherjee, R.; New, R. B.; Sampson, A. C.; King, M. K.; Hendrick, J. W.; Goldberg, A.; Peterson, T. J.; Hallak, H.; Zile, M. R.; Spinale, F. G.

    1999-01-01

    The progression of congestive heart failure (CHF) is left ventricular (LV) myocardial remodeling. The matrix metalloproteinases (MMPs) contribute to tissue remodeling and therefore MMP inhibition may serve as a useful therapeutic target in CHF. Angiotensin converting enzyme (ACE) inhibition favorably affects LV myocardial remodeling in CHF. This study examined the effects of specific MMP inhibition, ACE inhibition, and combined treatment on LV systolic and diastolic function in a model of CHF. Pigs were randomly assigned to five groups: 1) rapid atrial pacing (240 beats/min) for 3 weeks (n = 8); 2) ACE inhibition (fosinopril, 2.5 mg/kg b.i.d. orally) and rapid pacing (n = 8); 3) MMP inhibition (PD166793 2 mg/kg/day p.o.) and rapid pacing (n = 8); 4) combined ACE and MMP inhibition (2.5 mg/kg b.i.d. and 2 mg/kg/day, respectively) and rapid pacing (n = 8); and 5) controls (n = 9). LV peak wall stress increased by 2-fold with rapid pacing and was reduced in all treatment groups. LV fractional shortening fell by nearly 2-fold with rapid pacing and increased in all treatment groups. The circumferential fiber shortening-systolic stress relation was reduced with rapid pacing and increased in the ACE inhibition and combination groups. LV myocardial stiffness constant was unchanged in the rapid pacing group, increased nearly 2-fold in the MMP inhibition group, and was normalized in the ACE inhibition and combination treatment groups. Increased MMP activation contributes to the LV dilation and increased wall stress with pacing CHF and a contributory downstream mechanism of ACE inhibition is an effect on MMP activity.

  5. Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

    PubMed Central

    Åsvold, Bjørn O.; Vatten, Lars J.; Bjøro, Trine; Bauer, Douglas C.; Bremner, Alexandra; Cappola, Anne R.; Ceresini, Graziano; den Elzen, Wendy P. J.; Ferrucci, Luigi; Franco, Oscar H.; Franklyn, Jayne A.; Gussekloo, Jacobijn; Iervasi, Giorgio; Imaizumi, Misa; Kearney, Patricia M.; Khaw, Kay-Tee; Maciel, Rui M. B.; Newman, Anne. B.; Peeters, Robin P.; Psaty, Bruce M.; Razvi, Salman; Sgarbi, José A.; Stott, David J.; Trompet, Stella; Vanderpump, Mark P. J.; Völzke, Henry; Walsh, John P.; Westendorp, Rudi G. J.; Rodondi, Nicolas

    2016-01-01

    Importance Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). Objective To assess the association between differences in thyroid function within the reference range and CHD risk. Design, Setting, and Participants Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Exposures Thyroid function as expressed by serum thyrotropin levels at baseline. Mainoutcomes and Measures Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Results Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Conclusions and

  6. Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis.

    PubMed

    Grove, Tyler B; Tso, Ivy F; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Ellingrod, Vicki L; McInnis, Melvin G; Deldin, Patricia J

    2016-09-30

    Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychosis not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms.

  7. Positive Affect in the Midst of Distress: Implications for Role Functioning

    PubMed Central

    Moskowitz, Judith Tedlie; Shmueli-Blumberg, Dikla; Acree, Michael; Folkman, Susan

    2012-01-01

    Stress has been shown to deplete the self-regulation resources hypothesized to facilitate effective role functioning. However, recent research suggests that positive affect may help to replenish these vital self-regulation resources. Based on revised Stress and Coping theory and the Broaden-and-Build theory of positive emotion, three studies provide evidence of the potential adaptive function of positive affect in the performance of roles for participants experiencing stress. Participants were students (Study 1), caregivers of ill children (Study 2), and individuals recently diagnosed with HIV (Study 3). In cross sectional analyses, using role functioning as an indicator of self-regulation performance, we found that positive affect was significantly correlated with better self regulation performance, independent of the effects of negative affect. The effects were not as strong longitudinally, however, and there was little evidence of a reciprocal association between increases in positive affect and improvements in role functioning over time. The results provide some modest support for hypotheses stemming from the Broaden and Build model of positive emotion and revised Stress and Coping theory, both of which argue for unique adaptive functions of positive affect under stressful conditions. PMID:23175617

  8. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    ERIC Educational Resources Information Center

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  9. Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart

    PubMed Central

    Croston, Tara L.; Thapa, Dharendra; Holden, Anthony A.; Tveter, Kevin J.; Lewis, Sara E.; Shepherd, Danielle L.; Nichols, Cody E.; Long, Dustin M.; Olfert, I. Mark; Jagannathan, Rajaganapathi

    2014-01-01

    The mitochondrion has been implicated in the development of diabetic cardiomyopathy. Examination of cardiac mitochondria is complicated by the existence of spatially distinct subpopulations including subsarcolemmal (SSM) and interfibrillar (IFM). Dysfunction to cardiac SSM has been reported in murine models of type 2 diabetes mellitus; however, subpopulation-based mitochondrial analyses have not been explored in type 2 diabetic human heart. The goal of this study was to determine the impact of type 2 diabetes mellitus on cardiac mitochondrial function in the human patient. Mitochondrial subpopulations from atrial appendages of patients with and without type 2 diabetes were examined. Complex I- and fatty acid-mediated mitochondrial respiration rates were decreased in diabetic SSM compared with nondiabetic (P ≤ 0.05 for both), with no change in IFM. Electron transport chain (ETC) complexes I and IV activities were decreased in diabetic SSM compared with nondiabetic (P ≤ 0.05 for both), with a concomitant decline in their levels (P ≤ 0.05 for both). Regression analyses comparing comorbidities determined that diabetes mellitus was the primary factor accounting for mitochondrial dysfunction. Linear spline models examining correlative risk for mitochondrial dysfunction indicated that patients with diabetes display the same degree of state 3 and electron transport chain complex I dysfunction in SSM regardless of the extent of glycated hemoglobin (HbA1c) and hyperglycemia. Overall, the results suggest that independent of other pathologies, mitochondrial dysfunction is present in cardiac SSM of patients with type 2 diabetes and the degree of dysfunction is consistent regardless of the extent of elevated HbA1c or blood glucose levels. PMID:24778174

  10. Right Ventricular Function in Heart Failure with Preserved Ejection Fraction: A Community Based Study

    PubMed Central

    Mohammed, Selma F.; Hussain, Imad; Ezzeddine, Omar F. Abou; Takahama, Hiroyuki; Kwon, Susan H.; Forfia, Paul; Roger, Véronique L.; Redfield, Margaret M.

    2014-01-01

    Background: The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved EF (HFpEF) are not well characterized. Methods and Results: Consecutive, prospectively identified HFpEF (Framingham HF criteria, EF ≥50%) patients (N=562) from Olmsted County, Minnesota underwent echocardiography at HF diagnosis and follow-up for cause specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion (TAPSE) and by semi-quantitative (normal, mild RVD or moderate-severe RVD) 2D assessment. Whether RVD was defined by semi-quantitative assessment or TAPSE ≤ 15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers and chronic diuretic therapy. At echo, patients with RVD had slightly lower LVEF, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure (PASP), and more severe RV enlargement and tricuspid valve regurgitation. Adjusting for age, sex, PASP and comorbidities, the presence of any RVD by semi-quantitative assessment was associated with higher all-cause (hazard ratio (HR) = 1.35 (1.03-1.77; p=0.03)) and cardiovascular (HR=1.85 (1.20-2.80; p=0.006)) mortality and higher first (HR=1.99 (1.35-2.90; p=0.0006) and multiple (HR=1.81 (1.18-2.78; p=0.007) HF hospitalization rates. RVD defined by TAPSE values showed similar but weaker associations with mortality and HF hospitalizations. Conclusions: In the community, RVD is common in HFpEF patients, associated with clinical and echocardiographic evidence of more advanced HF and predictive of poorer outcomes. PMID:25391518

  11. Augmented vagal heart rate modulation in active hypoestrogenic pre-menopausal women with functional hypothalamic amenorrhoea.

    PubMed

    O'Donnell, Emma; Goodman, Jack M; Morris, Beverly L; Floras, John S; Harvey, Paula J

    2015-11-01

    Compared with eumenorrhoeic women, exercise-trained women with functional hypothalamic amenorrhoea (ExFHA) exhibit low heart rates (HRs) and absent reflex renin-angiotensin-system activation and augmentation of their muscle sympathetic nerve response to orthostatic stress. To test the hypothesis that their autonomic HR modulation is altered concurrently, three age-matched (pooled mean, 24 ± 1 years; mean ± S.E.M.) groups of women were studied: active with either FHA (ExFHA; n=11) or eumenorrhoeic cycles (ExOv; n=17) and sedentary with eumenorrhoeic cycles (SedOv; n=17). Blood pressure (BP), HR and HR variability (HRV) in the frequency domain were determined during both supine rest and graded lower body negative pressure (LBNP; -10, -20 and -40 mmHg). Very low (VLF), low (LF) and high (HF) frequency power spectra (ms(2)) were determined and, owing to skewness, log10-transformed. LF/HF ratio and total power (VLF + LF + HF) were calculated. At baseline, HR and systolic BP (SBP) were lower (P<0.05) and HF and total power were higher (P<0.05) in ExFHA than in eumenorrhoeic women. In all groups, LBNP decreased (P<0.05) SBP, HF and total power and increased (P<0.05) HR and LF/HF ratio. However, HF and total power remained higher (P<0.05) and HR, SBP and LF/HF ratio remained lower (P<0.05) in ExFHA than in eumenorrhoeic women, in whom measures did not differ (P>0.05). At each stage, HR correlated inversely (P<0.05) with HF. In conclusion, ExFHA women demonstrate augmented vagal yet unchanged sympathetic HR modulation, both at rest and during orthostatic stress. Although the role of oestrogen deficiency is unclear, these findings are in contrast with studies reporting decreased HRV in hypoestrogenic post-menopausal women.

  12. Functional imaging of murine hearts using accelerated self-gated UTE cine MRI.

    PubMed

    Motaal, Abdallah G; Noorman, Nils; de Graaf, Wolter L; Hoerr, Verena; Florack, Luc M J; Nicolay, Klaas; Strijkers, Gustav J

    2015-01-01

    We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously with the heartbeat, resulting in a randomly undersampled kt-space that facilitates compressed sensing reconstruction. The sequence was tested in 4 healthy rats and 4 rats with chronic myocardial infarction, approximately 2 months after surgery. As a control, a non-accelerated self-gated multi-slice FLASH sequence with an echo time (TE) of 2.76 ms, 4.5 signal averages, a matrix of 192 × 192, and an acquisition time of 2 min 34 s per slice was used to obtain Cine MRI with 15 frames per heartbeat. Non-accelerated UTE MRI was performed with TE = 0.29 ms, a reconstruction matrix of 192 × 192, and an acquisition time of 3 min 47 s per slice for 3.5 averages. Accelerated imaging with 2×, 4× and 5× undersampled kt-space data was performed with 1 min, 30 and 15 s acquisitions, respectively. UTE Cine images up to 5× undersampled kt-space data could be successfully reconstructed using a compressed sensing algorithm. In contrast to the FLASH Cine images, flow artifacts in the UTE images were nearly absent due to the short echo time, simplifying segmentation of the left ventricular (LV) lumen. LV functional parameters derived from the control and the accelerated Cine movies were statistically identical.

  13. Impairment of diastolic function in adult patients affected by osteogenesis imperfecta clinically asymptomatic for cardiac disease: casuality or causality?

    PubMed

    Migliaccio, Silvia; Barbaro, Giuseppe; Fornari, Rachele; Di Lorenzo, Gabriella; Celli, Mauro; Lubrano, Carla; Falcone, Stefania; Fabbrini, Elisa; Greco, Emanuela; Zambrano, Anna; Brama, Marina; Prossomariti, Giancarlo; Marzano, Sara; Marini, Mario; Conti, Francesco; D'Eufemia, Patrizia; Spera, Giovanni

    2009-01-09

    Osteogenesis imperfecta (OI) is a rare inherited connective disorder causing increased bone fragility and low bone mass. OI includes severe bone fragility, impaired dentinogenesis, with less common alterations in the joints, blood vessels, heart valves, skin. Interestingly, description of left ventricular rupture, aortic dissection and heart valves incompetence has been previously described. Death may occur in OI patients for cardiac disease in asyntomatic subjects. Aim of our study has been to evaluate the presence of potential subclinical cardiac disorders and to characterize cardiac functional parameters by echocardiography in adults with OI in absence of cardiac symptoms. Forty patients (21 females and 19 males) affected by type I, III, IV OI and 40 control subjects (20 females and 20 males) were evaluated in the study. Patients and controls underwent clinical examination, screening for endocrine and metabolic disorders, 12-lead electrocardiogram and echocardiogram. In particular, all subjects were evaluated by two-dimensional echocardiography with continuous- and pulse-wave Doppler. Patients and controls belonged to NYHA class I and no significant electrocardiographic alteration was documented in both groups. Thirty-eight patients (95%) showed valvular regurgitation compared to one control subject (2.5%; P<0.001). As regards the diastolic function parameters, in OI patients E wave velocity was reduced by 23% (95% CI: 9% to 29%; P<0.001), E/A ratio was reduced by 17% (95% CI: 15% to 26%; P<0.001) while isovolumetric relaxation time (IRT) was increased by 47% (95% CI: 26% to 53%; P<0.001) and E wave deceleration time (DT) was increased by 18% (95% CI: 13% to 26%; P<0.001) compared to controls. In conclusion, our data indicate that adult patients affected by OI have an altered diastolic function in absence of other metabolic alterations. These diastolic echocardiographic parameters might worsen over time, especially if other cardiovascular risk factors (e

  14. Modeling Syndromic Congenital Heart Defects in Zebrafish.

    PubMed

    Grant, Meagan G; Patterson, Victoria L; Grimes, Daniel T; Burdine, Rebecca D

    2017-01-01

    Cardiac development is a dynamic process regulated by spatial and temporal cues that are integrated to effect molecular, cellular, and tissue-level events that form the adult heart. Disruption of these highly orchestrated events can be devastating for cardiac form and function. Aberrations in heart development result in congenital heart defects (CHDs), which affect 1 in 100 infants in the United States each year. Zebrafish have proven informative as a model organism to understand both heart development and the mechanisms associated with CHDs due to the similarities in heart morphogenesis among vertebrates, as well as their genetic tractability and amenability to live imaging. In this review, we discuss the mechanisms of zebrafish heart development and the utility of zebrafish for understanding syndromic CHDs, those cardiac abnormalities that occur in the context of multisystem disorders. We conclude with avenues of zebrafish research that will potentially inform future therapeutic approaches for the treatment of CHDs.

  15. Heart Failure

    MedlinePlus

    ... version of this page please turn Javascript on. Heart Failure What is Heart Failure? In heart failure, the heart cannot pump enough ... failure often experience tiredness and shortness of breath. Heart Failure is Serious Heart failure is a serious and ...

  16. Low-Dose Irradiation Affects Expression of Inflammatory Markers in the Heart of ApoE -/- Mice

    PubMed Central

    Mathias, Daniel; Mitchel, Ronald E. J.; Barclay, Mirela; Wyatt, Heather; Bugden, Michelle; Priest, Nicholas D.; Scholz, Markus; Hildebrandt, Guido; Kamprad, Manja; Glasow, Annegret

    2015-01-01

    Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025–0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025–2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05–2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and

  17. Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

    PubMed

    Mathias, Daniel; Mitchel, Ronald E J; Barclay, Mirela; Wyatt, Heather; Bugden, Michelle; Priest, Nicholas D; Whitman, Stewart C; Scholz, Markus; Hildebrandt, Guido; Kamprad, Manja; Glasow, Annegret

    2015-01-01

    Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention

  18. [Heart failure and anemia].

    PubMed

    Reda, S; Motloch, L J; Hoppe, U C

    2013-09-01

    Chronic heart failure has an age-dependent prevalence of 2% and is therefore one of the most frequent diseases in western societies. A reduced hemoglobin concentration according to the definition of the World Health Organization is a common comorbidity affecting more than half of all heart failure patients. Elderly patients, patients suffering from renal impairment and women are more likely to develop anemia but a definitive etiology of anemia is only identified in the minority of cases. Anemia is associated with a poor clinical status and a greater risk of hospitalization and is a predictive factor for increased mortality. The incidence of anemia appears to increase with a poorer functional class. Intravenous iron therapy improves the exercise capacity in patients with systolic heart failure and iron deficiency and is currently being recommended for patients with persistent symptoms despite optimal medical and device therapy. However, erythropoietin-stimulating agents as a treatment for anemia in chronic heart failure have failed to improve clinical outcome in a large randomized trial. In patients with heart failure but with maintained ejection fraction, anemia is also associated with a poor prognosis. Specific therapeutic recommendations for these patients are still not available.

  19. The Functional Significance of Affect Recognition, Neurocognition, and Clinical Symptoms in Schizophrenia

    PubMed Central

    Hsiao, Sigmund

    2017-01-01

    Objectives The complex relationship and exact extent of the contribution of plausible indictors to social functional outcome in schizophrenia remain unclear. The present study aimed to explore the functional significance of clinical symptoms, neurocognition, and affect recognition simultaneously in schizophrenia. Methods The clinical symptoms, basic neurocognition, facial emotion recognition, and social functioning of 154 subjects, including 74 with schizophrenia and 80 nonclinical comparisons, were assessed. Results We observed that various subdomains of social functioning were extensively related to general intelligence, basic neurocognition, facial emotion recognition, and clinical symptoms, with different association patterns. Multivariate regression analyses revealed that years of education, age, sustained attention, working memory, and facial emotion recognition were significantly associated with global social functioning in schizophrenia. Conclusion Our findings suggest that affect recognition combined with nonsocial neurocognition demonstrated a crucial role in predicting global social function in schizophrenia. PMID:28099444

  20. [Effect of different concentrations liposomal emoxipine on coronary flow, contractive and pump function of the isolated rat heart after normotermic ischema and further reperfusion].

    PubMed

    Toropova, Ia G; Mukhamadiiarov, R A; Golovkin, A S

    2013-07-01

    In the experiments on the isolated perfused rat heart we studied the effects of liposomes containing different concentrations (0.25 and 0.1 mg/ml) of emoxipine on coronary flow, contractive and pump function of the isolated heart, which was effected by total normothermical ischemia and reperfusion. The parameters of the contractile activity of hearts, coronary flow and pump function of the hearts were assessed. It was detected that the introduction of the liposomal emoxipine during ischemia provides a protective effect against ischemic and reperfusion myocardial damage and smaller concentration of the emoxipin (0.1 mg/ml) in composition with the liposomes promote the best recovery of contractile activity and the pumping function of the ischemic heart in the period of the reperfusion.

  1. The effect of matrix stiffness of injectable hydrogels on the preservation of cardiac function after a heart attack.

    PubMed

    Plotkin, Marian; Vaibavi, Srirangam Ramanujam; Rufaihah, Abdul Jalil; Nithya, Venkateswaran; Wang, Jing; Shachaf, Yonatan; Kofidis, Theo; Seliktar, Dror

    2014-02-01

    This study compares the effect of four injectable hydrogels with different mechanical properties on the post-myocardial infarction left ventricle (LV) remodeling process. The bioactive hydrogels were synthesized from Tetronic-fibrinogen (TF) and PEG-fibrinogen (PF) conjugates; each hydrogel was supplemented with two levels of additional cross-linker to increase the matrix stiffness as measured by the shear storage modulus (G'). Infarcts created by ligating the left anterior descending coronary artery in a rodent model were treated with the hydrogels, and all four treatment groups showed an increase in wall thickness, arterial density, and viable cardiac tissue in the peri-infarct areas of the LV. Echocardiography and hemodynamics data of the PF/TF treated groups showed significant improvement of heart function associated with the attenuated effects of the remodeling process. Multi-factorial regression analysis indicated that the group with the highest modulus exhibited the best rescue of heart function and highest neovascularization. The results of this study demonstrate that multiple properties of an injectable bioactive biomaterial, and notably the matrix stiffness, provide the multifaceted stimulation necessary to preserve cardiac function and prevent adverse remodeling following a heart attack.

  2. Distribution and function of biogenic amines in the heart of Nautilus pompilius L. (Cephalopoda, Tetrabranchiata).

    PubMed

    Springer, Jochen; Ruth, Peter; Beuerlein, Knut; Palus, Sandra; Schipp, Rudolf; Westermann, Bettina

    2005-06-01

    Biogenic amines (serotonin and catecholamines), play an important role in the control of the blood flow not only in vertebrates, but also in invertebrates such as cephalopods. In contrast to the well investigated hearts of the a 'modern', coleoid cephalopods, the innervation of the heart of the archaic Nautilus pompilius L. has not been studied in detail. In this study the distribution and effects of biogenic amines in the Nautilus heart were investigated. Serotonin and catecholamines were visualised by the glyxoylic acid induced fluorescence. High performance liquid chromatotography analysis was performed to discriminate between the catecholamines, which showed a high content of noradrenaline in the 4 auricles, the aorta and the ventricle, whereas the ventricle showed a high dopamine content. Adrenaline was found at a very low concentration in the ventricle. Serotonin and dopamine were also immunohistochemically localised to larger nerves and throughout the heart, respectively. In organ bath experiments, the auricles showed little spontaneous activity. After adding serotonin, they displayed rhythmical contractions, which were accelerated dose-dependently by noradrenaline. In summary, these data suggest an important role for biogenic amines in the control of the heart of Nautilus pompilius L., with serotonin possibly stimulating excitatory nerve fibres, whereas noradrenaline is likely to influence the muscle contraction itself.

  3. The mitochondrial uniporter controls fight or flight heart rate increases.

    PubMed

    Wu, Yuejin; Rasmussen, Tyler P; Koval, Olha M; Joiner, Mei-Ling A; Hall, Duane D; Chen, Biyi; Luczak, Elizabeth D; Wang, Qiongling; Rokita, Adam G; Wehrens, Xander H T; Song, Long-Sheng; Anderson, Mark E

    2015-01-20

    Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

  4. Heart MRI

    MedlinePlus

    Magnetic resonance imaging - cardiac; Magnetic resonance imaging - heart; Nuclear magnetic resonance - cardiac; NMR - cardiac; MRI of the heart; Cardiomyopathy - MRI; Heart failure - MRI; Congenital heart disease - MRI

  5. Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

    PubMed

    Minai, Kosuke; Komukai, Kimiaki; Arase, Satoshi; Nagoshi, Tomohisa; Matsuo, Seiichiro; Ogawa, Kazuo; Kayama, Yosuke; Inada, Keiichi; Tanigawa, Shin-Ichi; Takemoto, Tomoyuki; Sekiyama, Hiroshi; Date, Taro; Ogawa, Takayuki; Taniguchi, Ikuo; Yoshimura, Michihiro

    2013-07-01

    Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

  6. Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

    NASA Technical Reports Server (NTRS)

    Meyerson, F. Z.; Kapelko, V. I.; Gorina, M. S.; Shchegolkov, A. N.; Larinov, N. P.

    1980-01-01

    Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart.

  7. Anatomic and functional imaging of congenital heart disease with digital subtraction angiography

    SciTech Connect

    Buonocore, E.; Pavlicek, W.; Modic, M.T.; Meaney, T.F.; O'Donovan, P.B.; Grossman, L.B.; Moodie, D.S.; Yiannikas, J.

    1983-06-01

    Digital subtraction angiography (DSA) of the heart was performed in 54 patients for the evaluation of congenital heart diagnostic images and accurate physiologic shunt data that compared favorably with catheter angiography and nuclear medicine studies. Retrospective analysis of this series of patients indicated that DSA studies contributed sufficient informantion to shorten significantly or modify cardiac catheterization in 85% (79/93) of the defects that were identified. Interatrial septal defects were particularly well diagnosed, with identification occurring in 10 of 10 cases, wheseas intraventricular septal defects were identified in only 6 of 9 patients. Evaluation of postsurgical patients was accurate in 19 of 20 cases.

  8. Identifying Molecular Regulators of Neuronal Functions Affected in the Movement Disorder Dystonia

    DTIC Science & Technology

    2015-08-01

    AD______________ AWARD NUMBER: W81XWH-14-1-0301 TITLE: Identifying Molecular Regulators of Neuronal Functions Affected in the Movement Disorder...Affected in the Movement Disorder Dystonia 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0301 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT The movement disorder dystonia is characterized by involuntary muscle contractions in the limbs, hands, feet or neck. The aim

  9. Role of affective self-regulatory efficacy in diverse spheres of psychosocial functioning.

    PubMed

    Bandura, Albert; Caprara, Gian Vittorio; Barbaranelli, Claudio; Gerbino, Maria; Pastorelli, Concetta

    2003-01-01

    This prospective study with 464 older adolescents (14 to 19 years at Time 1; 16 to 21 years at Time 2) tested the structural paths of influence through which perceived self-efficacy for affect regulation operates in concert with perceived behavioral efficacy in governing diverse spheres of psychosocial functioning. Self-efficacy to regulate positive and negative affect is accompanied by high efficacy to manage one's academic development, to resist social pressures for antisocial activities, and to engage oneself with empathy in others' emotional experiences. Perceived self-efficacy for affect regulation essentially operated mediationally through the latter behavioral forms of self-efficacy rather than directly on prosocial behavior, delinquent conduct, and depression. Perceived empathic self-efficacy functioned as a generalized contributor to psychosocial functioning. It was accompanied by prosocial behavior and low involvement in delinquency but increased vulnerability to depression in adolescent females.

  10. Aerobic training prior to myocardial infarction increases cardiac GLUT4 and partially preserves heart function in spontaneously hypertensive rats.

    PubMed

    Schaun, Maximiliano Isoppo; Marschner, Rafael Aguiar; Peres, Thiago Rodrigues; Markoski, Melissa Medeiros; Lehnen, Alexandre Machado

    2017-03-01

    We assessed cardiac function (echocardiographic) and glucose transporter 4 (GLUT4) expression (Western blot) in response to 10 weeks of aerobic training (treadmill) prior to acute myocardial infarction (AMI) by ligation of the left coronary artery in spontaneously hypertensive rats. Animals were allocated to sedentary+sham, sedentary+AMI, training+sham, and training+AMI. Aerobic training prior to AMI partially preserves heart function. AMI and/or aerobic training increased GLUT4 expression. However, those animals trained prior to AMI showed a greater increase in GLUT4 in cardiomyocytes.

  11. Evolving hybrid approaches: the preservation of the 'neglected' pulmonary valve function in patients with congenital heart disease.

    PubMed

    Vida, Vladimiro L; Bacha, Emile; Stellin, Giovanni

    2016-07-01

    The involvement of the hemodynamic expertise in the operating room led to the development of new strategies aimed to improve both early and long-term outcome of patients with congenital heart disease. During the last decade, with the aim of preserving the pulmonary valve function, we embarked on a new surgical approach, which combines surgical and interventional techniques, which are performed in the operating room. We believe that the preservation of the pulmonary valve function can be extended to any patients with classic tetralogy of Fallot and other selected patients with congenital pulmonary valve hypoplasia and dysfunction.

  12. Long-term low dose dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in chronic heart failure in rats.

    PubMed

    Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G; Talan, Mark

    2017-03-01

    A short-term exposure to resveratrol at high dosages exerts a remarkable cardioprotective effect. Whether a long-term exposure to resveratrol at low dosages that can be obtained through consumption of a resveratrol-rich diet is beneficial to heart diseases is unknown. We tested the effects of a resveratrol-enriched diet on cardiovascular remodeling of chronic heart failure (CHF) in rats resulting from permanent ligation of left coronary artery. Two weeks after surgery, rats were started on either a resveratrol-enriched (R; 5 mg/kg per day; n = 23) or normal (Control; n = 23) diet for next 10 months. Serial echocardiography in Control showed a significant decline in LV ejection fraction, increases in LV end-systolic and end-diastolic volumes, and expansion in myocardial infarct from pre-treatment values. In R, compared with Control, there were substantial improvements in those parameters. End-point LV pressure-volume loop analysis showed a significantly improved LV systolic function and AV-coupling, an index of energy transfer efficacy between the heart and aortic tree, in R compared with Control (p < 0.05). Aortic pulse wave velocity, a measure of arterial stiffness, was significantly lower in R (389 ± 15 cm/s; p < 0.05) compared with Control (489 ± 38 cm/s). These results demonstrated that long-term dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in CHF.

  13. Metaiodobenzylguanidine (/sup 131/I) scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

    SciTech Connect

    Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.; Chartrand, C.; Wieland, D.M.; Lepanto, L.; Legault, F.; Suissa, S.; Rosenthall, L.; Burgess, J.H.

    1987-12-01

    In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine (/sup 131/I) to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine (/sup 131/I) and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine (/sup 131/I) scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine (/sup 123/I) scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.

  14. Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure.

    PubMed Central

    Baur, L H; Schipperheyn, J J; Baan, J; van der Laarse, A; Buis, B; van der Wall, E E; Manger Cats, V; van Dijk, A D; Blokland, J A; Frölich, M

    1991-01-01

    Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function. PMID:2015121

  15. Lowering body weight in obese mice with diastolic heart failure improves cardiac insulin sensitivity and function: implications for the obesity paradox.

    PubMed

    Sankaralingam, Sowndramalingam; Abo Alrob, Osama; Zhang, Liyan; Jaswal, Jagdip S; Wagg, Cory S; Fukushima, Arata; Padwal, Raj S; Johnstone, David E; Sharma, Arya M; Lopaschuk, Gary D

    2015-05-01

    Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e., the obesity paradox), although obesity and heart failure unfavorably alter cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high-fat (HF) diet (60% kcal from fat) for 4 weeks, following which an abdominal aortic constriction (AAC) was produced. Four weeks post-AAC, mice were switched to a low-fat (LF) diet (12% kcal from fat; HF AAC LF) or maintained on an HF (HF AAC HF) for a further 10 weeks. After 18 weeks, HF AAC LF mice weighed less than HF AAC HF mice. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared with HF AAC HF mice. Insulin-stimulated glucose oxidation was increased in hearts from HF AAC LF mice, compared with HF AAC HF mice. Thus lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.

  16. Observing functional actions affects semantic processing of tools: evidence of a motor-to-semantic priming.

    PubMed

    De Bellis, Francesco; Ferrara, Antonia; Errico, Domenico; Panico, Francesco; Sagliano, Laura; Conson, Massimiliano; Trojano, Luigi

    2016-01-01

    Recent evidence shows that activation of motor information can favor identification of related tools, thus suggesting a strict link between motor and conceptual knowledge in cognitive representation of tools. However, the involvement of motor information in further semantic processing has not been elucidated. In three experiments, we aimed to ascertain whether motor information provided by observation of actions could affect processing of conceptual knowledge about tools. In Experiment 1, healthy participants judged whether pairs of tools evoking different functional handgrips had the same function. In Experiment 2 participants judged whether tools were paired with appropriate recipients. Finally, in Experiment 3 we again required functional judgments as in Experiment 1, but also included in the set of stimuli pairs of objects having different function and similar functional handgrips. In all experiments, pictures displaying either functional grasping (aimed to use tools) or structural grasping (just aimed to move tools independently from their use) were presented before each stimulus pair. The results demonstrated that, in comparison with structural grasping, observing functional grasping facilitates judgments about tools' function when objects did not imply the same functional manipulation (Experiment 1), whereas worsened such judgments when objects shared functional grasp (Experiment 3). Instead, action observation did not affect judgments concerning tool-recipient associations (Experiment 2). Our findings support a task-dependent influence of motor information on high-order conceptual tasks and provide further insights into how motor and conceptual processing about tools can interact.

  17. Layered Functional Network Analysis of Gene Expression in Human Heart Failure

    PubMed Central

    Zhu, Wenliang; Yang, Lei; Du, Zhimin

    2009-01-01

    Background Although dilated cardiomyopathy (DCM) is a leading cause of heart failure (HF), the mechanism underlying DCM is not well understood. Previously, it has been demonstrated that an integrative analysis of gene expression and protein-protein interaction (PPI) networks can provide insights into the molecular mechanisms of various diseases. In this study we develop a systems approach by linking public available gene expression data on ischemic dilated cardiomyopathy (ICM), a main pathological form of DCM, with data from a layered PPI network. We propose that the use of a layered PPI network, as opposed to a traditional PPI network, provides unique insights into the mechanism of DCM. Methods Four Cytoscape plugins including BionetBuilder, NetworkAnalyzer, Cerebral and GenePro were used to establish the layered PPI network, which was based upon validated subcellular protein localization data retrieved from the HRPD and Entrez Gene databases. The DAVID function annotation clustering tool was used for gene ontology (GO) analysis. Results The assembled layered PPI network was divided into four layers: extracellular, plasma membrane, cytoplasm and nucleus. The characteristics of the gene expression pattern of the four layers were compared. In the extracellular and plasma membrane layers, there were more proteins encoded by down-regulated genes than by up-regulated genes, but in the other two layers, the opposite trend was found. GO analysis established that proteins encoded by up-regulated genes, reflecting significantly over-represented biological processes, were mainly located in the nucleus and cytoplasm layers, while proteins encoded by down-regulated genes were mainly located in the extracellular and plasma membrane layers. The PPI network analysis revealed that the Janus family tyrosine kinase-signal transducer and activator of transcription (Jak-STAT) signaling pathway might play an important role in the development of ICM and could be exploited as a

  18. Plant Species and Functional Group Combinations Affect Green Roof Ecosystem Functions

    PubMed Central

    Lundholm, Jeremy; MacIvor, J. Scott; MacDougall, Zachary; Ranalli, Melissa

    2010-01-01

    Background Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. Methodology/Principal Findings We used a replicated modular extensive (shallow growing- medium) green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. Conclusions/Significance Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or facilitation as mechanisms

  19. Effect of dietary polyunsaturated fatty acids on contractile function of hearts isolated from sedentary and trained rats.

    PubMed

    Demaison, L; Blet, J; Sergiel, J P; Gregoire, S; Argaud, D

    2000-01-01

    Moderate physical training induced a decrease in arterial blood pressure in fish oil-fed rats as compared to sunflower seed oil-fed rats. The purpose of this study was to determine if these changes were due to modifications of the left ventricular function of the heart. Forty rats were fed a semi-purified diet containing either 10% sunflower seed oil or 10% fish oil (EPAX 3000TG, Pronova). Each dietary group was assigned to two sub-groups, one being constituted by sedentary animals and the other by trained animals. Training was achieved by daily running for 60 minutes at moderate intensity for three weeks. At the end of the training period, the animals were sacrificed and their hearts were immediately perfused according to the working mode. The phospholipid fatty acid composition and parameters of the left ventricular function were determined. Feeding fish oil markedly reduced the proportion of n-6 polyunsaturated fatty acids (PUFA, 18:2 n-6, 20:4 n-6, 22:4 n-6 and 22:5 n-6) in cardiac phospholipids. The n-6 PUFA were replaced by n-3 PUFA (mainly docosahexaenoic acid). In sedentary animals, the fluid dynamic (aortic and coronary flow, cardiac output) was not modified by the diet. The heart rate was reduced (-10%) in n-3 PUFA-rich hearts. Physical training did not markedly alter the polyunsaturated fatty acid profile of cardiac phospholipids. Conversely, it reduced the heart rate, aortic flow and cardiac output (-11, -21 and -14%, respectively) at a similar extent in the two dietary groups. In a second set of experiments, the training period was repeated in animals fed a commercially available diet (A103, UAR) which simultaneously provided n-6 and n-3 fatty acids. In these dietary conditions, neither the aortic flow nor the heart rate was decreased by physical exercise. These results suggest that both n-6 and n-3 PUFA in the diet are necessary to ensure a good cardiac adaptation to moderate physical training. Furthermore, the fish oil-induced decrease in arterial

  20. Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats

    PubMed Central

    Habibi, Parisa; Alihemmati, Alireza; NourAzar, Alireza; Yousefi, Hadi; Mortazavi, Safieh; Ahmadiasl, Nasser

    2016-01-01

    Objective(s): The beneficial and more potent role of exercise to prevent heart apoptosis in ovariectomized rats has been known. The aim of this study was to examine the effects of swimming training on cardiac expression of Bcl-2, and Mir-133 levels and glycogen changes in the myocyte. Materials and Methods: Forty animals were separated into four groups as control, sham, ovariectomy (OVX) and ovariectomized group with 8 weeks swimming training (OVX.E). Training effects were evaluated by measuring lipid profiles, Bcl-2 and Mir-133 expression levels in the cardiac tissue. Grafts were analyzed by reverse transcription–polymerase chain reaction for Bcl-2 mRNA and Mir-133 and by Western blot for Bcl-2 protein. Results: Ovariectomy down-regulated Bcl-2 and Mir-133 expression levels in the cardiac tissue, and swimming training up-regulated their expression significantly (P<0.05). Conclusion: Our results showed that regular exercise as a physical replacement therapy could prevent and improve the effects of estrogen deficiency in the cardia. PMID:27279981

  1. Modality of fear cues affects acoustic startle potentiation but not heart-rate response in patients with dental phobia

    PubMed Central

    Wannemüller, André; Sartory, Gudrun; Elsesser, Karin; Lohrmann, Thomas; Jöhren, Hans P.

    2015-01-01

    The acoustic startle response (SR) has consistently been shown to be enhanced by fear-arousing cross-modal background stimuli in phobics. Intra-modal fear-potentiation of acoustic SR was rarely investigated and generated inconsistent results. The present study compared the acoustic SR to phobia-related sounds with that to phobia-related pictures in 104 dental phobic patients and 22 controls. Acoustic background stimuli were dental treatment noises and birdsong and visual stimuli were dental treatment and neutral control pictures. Background stimuli were presented for 4 s, randomly followed by the administration of the startle stimulus. In addition to SR, heart-rate (HR) was recorded throughout the trials. Irrespective of their content, background pictures elicited greater SR than noises in both groups with a trend for phobic participants to show startle potentiation to phobia-related pictures but not noises. Unlike controls, phobics showed HR acceleration to both dental pictures and noises. HR acceleration of the phobia group was significantly positively correlated with SR in the noise condition only. The acoustic SR to phobia-related noises is likely to be inhibited by prolonged sensorimotor gating. PMID:25774142

  2. The interaction of Ca2+ with sarcomeric proteins: role in function and dysfunction of the heart.

    PubMed

    ter Keurs, Hendrick E D J

    2012-01-01

    The hallmarks of the normal heartbeat are both rapid onset of contraction and rapid relaxation as well as an inotropic response to both increased end-diastolic volume and increased heart rate. At the microscopic level, Ca(2+) plays a crucial role in normal cardiac contraction. This paper reviews the cycle of Ca(2+) fluxes during the normal heartbeat, which underlie the coupling between excitation and contraction and permit a highly synchronized action of cardiac sarcomeres. Length dependence of the response of the regulatory sarcomeric proteins mediates the Frank-Starling Law of the heart. However, Ca(2+) transport may go astray in heart disease such as in congestive heart failure, and both jeopardize systole and diastole and triggering arrhythmias. The interaction between weak and strong segments in nonuniform cardiac muscle allows partial preservation of force of contraction but may further lead to mechanoelectric feedback or reverse excitation-contraction coupling mediating an early diastolic Ca(2+) transient caused by the rapid force decrease during the relaxation phase. These rapid force changes in nonuniform muscle may cause arrhythmogenic Ca(2+) waves to propagate by the activation of neighboring sarcoplasmic reticulum by diffusing Ca(2+) ions.

  3. ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism

    PubMed Central

    Tian, Zhe; Miyata, Keishi; Kadomatsu, Tsuyoshi; Horiguchi, Haruki; Fukushima, Hiroyuki; Tohyama, Shugo; Ujihara, Yoshihiro; Okumura, Takahiro; Yamaguchi, Satoshi; Zhao, Jiabin; Endo, Motoyoshi; Morinaga, Jun; Sato, Michio; Sugizaki, Taichi; Zhu, Shunshun; Terada, Kazutoyo; Sakaguchi, Hisashi; Komohara, Yoshihiro; Takeya, Motohiro; Takeda, Naoki; Araki, Kimi; Manabe, Ichiro; Fukuda, Keiichi; Otsu, Kinya; Wada, Jun; Murohara, Toyoaki; Mohri, Satoshi; Yamashita, Jun K.; Sano, Motoaki; Oike, Yuichi

    2016-01-01

    A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice. Mice overexpressing ANGPTL2 in heart show cardiac dysfunction caused by both inactivation of AKT and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a signalling and decreased myocardial energy metabolism. Conversely, Angptl2 knockout mice exhibit increased left ventricular contractility and upregulated AKT-SERCA2a signalling and energy metabolism. Finally, ANGPTL2-knockdown in mice subjected to pressure overload ameliorates cardiac dysfunction. Overall, these studies suggest that therapeutic ANGPTL2 suppression could antagonize development of heart failure. PMID:27677409

  4. Arterial wall mechanics as a function of heart rate: role of vascular smooth muscle

    NASA Astrophysics Data System (ADS)

    Salvucci, Fernando Pablo; Schiavone, Jonathan; Craiem, Damian; Barra, Juan Gabriel

    2007-11-01

    Vascular wall viscoelasticity can be evaluated using a first-order lumped model. This model consists of a spring with elastic constant E and a dashpot with viscous constant η. More importantly, this viscoelastic model can be fitted in-vivo measuring arterial pressure and diameter. The aim of this work is to analyze the influence of heart rate over E and η. In two anesthetized sheep, diameter in thoracic aorta and intravascular pressure has been registered. The right atrium was connected to a programmable stimulator through a pair of pace-maker wires to produce changes in stimulation heart rate (HR) from 80 to 160 bpm. Additionally, local activation of vascular smooth muscle was induced with phenylephrine. After converting pressure and diameter signals into stress and strain respectively, E y η were calculated in control state and during muscle activation. The elastic modulus E did not present significant changes with heart rate. The viscous modulus η decreased 49% with a two-fold acceleration in heart rate from 80 to 160 bpm. However, the product η HR remained stable. The viscous modulus η increased 39% with smooth muscle activation. No significant pressure changes were registered during the experiment. The contractile action of vascular smooth muscle could contribute to increasing arterial wall viscosity. The decrease of η when HR increased might be related to smooth muscle relaxation mediated by endothelium activity, which was stimulated by flow increase. We conclude that HR can modulate arterial wall viscoelasticity through endothelium-dependent mechanisms.

  5. Remote heart function monitoring: role of the CardioMEMS HF System.

    PubMed

    Vanoli, Emilio; D'Elia, Emilia; La Rovere, Maria T; Gronda, Edoardo

    2016-07-01

    Heart failure is a pandemic condition that is challenging cardiology today. The primary economical and social burden of this syndrome is hospitalization rate whose costs represent the highest ones within the entire healthcare management. Remote monitoring of physiological data, obtained through self-reporting via telephone calls or, automatically, using external devices is a potential novel approach to implement management of patients with heart failure and reduce hospitalization rates. Relatively large but, sometimes, contradicting information exists about the efficacy of remote monitoring via different noninvasive approaches to reduce the economical and social burden of heart failure management. This leaves still partly unaddressed this critical issue and generates the need for new approaches. In this context, the CardioMEMS device that can chronically monitor pulmonary pressures from a small microchip inserted transvenously in the pulmonary artery seems to represent an innovative tool to challenge hospitalization rates. Consecutive analyses from the CHAMPION study had indeed documented the efficacy of the CardioMEMS in the remote monitoring of the pulmonary circulation status of patients with heart failure and in providing adequate information to optimally manage such patients with the final result of a significant hospitalization rate reduction. The striking information here is that this appears to be true in patients with preserved left ventricular ejection fraction also. Overall, the reports from the CHAMPION study encourage the use of CardioMEMS but larger populations are needed to definitively prove its value.

  6. Total heart volume as a function of clinical and anthropometric parameters in a population of external beam radiation therapy patients

    NASA Astrophysics Data System (ADS)

    Nadège Ilembe Badouna, Audrey; Veres, Cristina; Haddy, Nadia; Bidault, François; Lefkopoulos, Dimitri; Chavaudra, Jean; Bridier, André; de Vathaire, Florent; Diallo, Ibrahima

    2012-01-01

    The aim of this paper was to determine anthropometric parameters leading to the least uncertain estimate of heart size when connecting a computational phantom to an external beam radiation therapy (EBRT) patient. From computed tomography images, we segmented the heart and calculated its total volume (THV) in a population of 270 EBRT patients of both sexes, aged 0.7-83 years. Our data were fitted using logistic growth functions. The patient age, height, weight, body mass index and body surface area (BSA) were used as explanatory variables. For both genders, good fits were obtained with both weight (R2 = 0.89 for males and 0.83 for females) and BSA (R2 = 0.90 for males and 0.84 for females). These results demonstrate that, among anthropometric parameters, weight plays an important role in predicting THV. These findings should be taken into account when assigning a computational phantom to a patient.

  7. Six minute walk test: a simple and useful test to evaluate functional capacity in patients with heart failure.

    PubMed

    Rostagno, Carlo; Gensini, Gian Franco

    2008-09-01

    In heart failure survival is closely related to functional capacity. Peak O2 consumption at cardiopulmonary exercise test (CPET) is considered the gold standard for the evaluation of exercise tolerance. Since >70% of patients with heart failure, usually elderly or with significant comorbidities, are referred to Departments of Internal Medicine where facilities for cardiopulmonary test are rarely available, CPET may be performed in <5% of the patients. Six-minute walk test (6MWT) has been proposed as a simple, inexpensive, reproducible alternative to CPET. The 6MWT reproduces the activity of daily life and this is particularly relevant in elderly patients who usually develop symptoms below their theoretical maximal exercise capacity. Despite some limits 6MWT is attractive for patients referred to Departments of Internal Medicine allowing an objective evaluation of exercise tolerance, a better prognostic evaluation and a guide to evaluate response to medical treatment.

  8. The bHLH Transcription Factor Hand Regulates the Expression of Genes Critical to Heart and Muscle Function in Drosophila melanogaster

    PubMed Central

    Hallier, Benjamin; Hoffmann, Julia; Roeder, Thomas; Tögel, Markus; Meyer, Heiko; Paululat, Achim

    2015-01-01

    Hand proteins belong to the highly conserved family of basic Helix-Loop-Helix transcription factors and are critical to distinct developmental processes, including cardiogenesis and neurogenesis in vertebrates. In Drosophila melanogaster a single orthologous hand gene is expressed with absence of the respective protein causing semilethality during early larval instars. Surviving adult animals suffer from shortened lifespan associated with a disorganized myofibrillar structure being apparent in the dorsal vessel, the wing hearts and in midgut tissue. Based on these data, the major biological significance of Hand seems to be related to muscle development, maintenance or function; however, up to now the physiological basis for Hand functionality remains elusive. Thus, the identification of genes whose expression is, directly or indirectly, regulated by Hand has considerable relevance with respect to understanding its biological functionality in flies and vertebrates. Beneficially, hand mutants are viable and exhibit affected tissues, which renders Drosophila an ideal model to investigate up- or downregulated target genes by a comparative microarray approach focusing on the respective tissues from mutant specimens. Our present work reveals for the first time that Drosophila Hand regulates the expression of numerous genes of diverse physiological relevancy, including distinct factors required for proper muscle development and function such as Zasp52 or Msp-300. These results relate Hand activity to muscle integrity and functionality and may thus be highly beneficial to the evaluation of corresponding hand phenotypes. PMID:26252215

  9. The Cleveland Clinic-Nimbus total artificial heart. Design and in vitro function.

    PubMed

    Massiello, A; Kiraly, R; Butler, K; Himley, S; Chen, J F; McCarthy, P M

    1994-09-01

    We describe the design and in vitro testing of the Cleveland Clinic-Nimbus electrohydraulic permanent total artificial heart as it nears completion of development. The total artificial heart uses an electric motor and hydraulic actuator to drive two diaphragm-type blood pumps. The interventricular space contains the pump control electronics and is vented to an air-filled compliance chamber. Pericardial tissue valves and biolized blood-contacting surfaces potentially eliminate the need for anticoagulation. In vitro studies on a mock circulatory circuit demonstrated preload-sensitive control of pump output over the operating range of the blood pump: 70 to 160 beats/min and 5 to 9.6 L/min at right and left atrial pressures of 1.0 to 7.0 mm Hg and 5.0 to 12.0 mm Hg, respectively. The pump output was found to be insensitive to afterload over a range of 15 to 40 mm Hg mean pulmonary artery pressure and 60 to 130 mm Hg mean systemic pressure. The left master alternate control mode balanced the ventricular outputs during simulated bronchial artery shunting of up to 20% of cardiac output. A 10% to 15% right-pump, stroke-volume limiter balanced ventricular outputs during maximum output of 9.6 L/min. In response to a sustained increase in systemic venous return, the pump increased output by 2 L/min (29%) in 35 seconds. Thus the Cleveland Clinic-Nimbus total artificial heart meets the National Heart, Lung, and Blood Institute hemodynamic performance goals for devices being developed for permanent heart replacement. The biolized blood-contacting surfaces should decrease the risk of thromboembolism associated with circulatory assist devices.

  10. Functional Amyloid Signaling via the Inflammasome, Necrosome, and Signalosome: New Therapeutic Targets in Heart Failure

    PubMed Central

    Parry, Traci L.; Melehani, Jason H.; Ranek, Mark J.; Willis, Monte S.

    2015-01-01

    As the most common cause of death and disability, globally, heart disease remains an incompletely understood enigma. A growing number of cardiac diseases are being characterized by the presence of misfolded proteins underlying their pathophysiology, including cardiac amyloidosis and dilated cardiomyopathy (DCM). At least nine precursor proteins have been implicated in the development of cardiac amyloidosis, most commonly caused by multiple myeloma light chain disease and disease-causing mutant or wildtype transthyretin (TTR). Similarly, aggregates with PSEN1 and COFILIN-2 have been identified in up to one-third of idiopathic DCM cases studied, indicating the potential predominance of misfolded proteins in heart failure. In this review, we present recent evidence linking misfolded proteins mechanistically with heart failure and present multiple lines of new therapeutic approaches that target the prevention of misfolded proteins in cardiac TTR amyloid disease. These include multiple small molecule pharmacological chaperones now in clinical trials designed specifically to support TTR folding by rational design, such as tafamidis, and chaperones previously developed for other purposes, such as doxycycline and tauroursodeoxycholic acid. Last, we present newly discovered non-pathological “functional” amyloid structures, such as the inflammasome and necrosome signaling complexes, which can be activated directly by amyloid. These may represent future targets to successfully attenuate amyloid-induced proteotoxicity in heart failure, as the inflammasome, for example, is being therapeutically inhibited experimentally in autoimmune disease. Together, these studies demonstrate multiple novel points in which new therapies may be used to primarily prevent misfolded proteins or to inhibit their downstream amyloid-mediated effectors, such as the inflammasome, to prevent proteotoxicity in heart failure. PMID:26664897

  11. Association between Genetic Variations Affecting Mean Telomere Length and the Prevalence of Hypertension and Coronary Heart Disease in Koreans

    PubMed Central

    2016-01-01

    In this study, we investigated whether the single nucleotide polymorphisms (SNPs) associated with telomere length (TL) were associated with the incidence of hypertension (HTN)/coronary heart disease (CHD) and cardiovascular risk factors in the Korean population. Data from 5,705 (ages 39–70) participants in the Korean Genome Epidemiology Study (rural Ansung and urban Ansan cohorts) were studied. Twelve SNPs known to be associated with telomere biology were tested for an association with HTN/CHD. As results, no significant associations were found between the selected TL-related SNPs and prevalence of HTN and CHD. Among non-alcohol users, subjects with minor alleles in rs1269304 and rs10936601 (TERC and LRRC34, respectively) exhibited a higher rate of CHD occurrence (odds ratio [OR], 1.862; 95% confidence intervals [CIs], 1.137, 3.049; OR, 1.855; 95% CIs, 1.111, 2.985; respectively). However, alcohol users with minor alleles in rs398652 (PELI2) were significantly associated with higher HTN prevalence (OR, 1.179; 95% CIs, 1.040, 1.336). Of the 3 SNPs related to disease outcomes, rs1296304 was significantly associated with increased levels of diastolic blood pressure (β estimate, 0.470; 95% CIs, 0.013, 0.926). The minor allele in rs398652 was significantly associated with higher levels of body mass index (OR, 0.128; 95% CIs, 0.010, 0.246) and γ-glutamyl transpeptidase (OR, 0.013; 95% CIs, 0.001, 0.024). In conclusion, there were no significant associations between the selected TL-related SNPs and the occurrence of HTN/CHD in Koreans. However, the results suggest the presence of a possible interaction between related SNPs and alcohol behavior associated with HTN/CHD occurrence. PMID:27812514

  12. Plant sterols: factors affecting their efficacy and safety as functional food ingredients

    PubMed Central

    Berger, Alvin; Jones, Peter JH; Abumweis, Suhad S

    2004-01-01

    Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status. PMID:15070410

  13. [UCP2 and UCP3 gene expression, heart function and oxygen cost of myocardial work changes during aging and ischemia-reperfusion].

    PubMed

    Hoshovs'ka, Iu V; Lisovyĭ, O O; Shymans'ka, T V; Sahach, V F

    2009-01-01

    To examine the effects of ischemia/reperfusion on UCPs genes expression, heart function and oxygen cost of myocardial work, hearts of adult (6 mo) and old (24 mo) rats were perfused by Langendorf preparation and subjected to 20 min ischemia followed by 40 min reperfusion. Mitochondrial permeability transition due to ischemic stimuli was evaluated by release of mitochondrial factor (lambda 250 nm) which was previously shown as a marker of MPTP opening. Expression of UCPs was detected by reverse transcriptional polymerase chain reaction. Mitochondrial membrane potential (deltaphi(m)) and oxygen consumption in isolated heart mitochondria of adult and old rats were measured. It was shown that impaired function of aging rat hearts was accompanied with an increased oxygen cost of myocardial work and lower mitochondrial membrane potential compared with adult rats. Reperfusion disturbances of cardiodynamic, contractile activity of myocardium and noneffective oxygen utilization in early period of reperfusion were less intensive in aged hearts than in adult ones. Therefore, the levels of mRNA of UCP2 in aging hearts were higher and mRNA levels of UCP3 were tended to increase. At the same time ischemia/reperfusion increased the expression of UCP2 and UCP3 in adult myocardium: mRNA levels of UCPs were significantly higher that those in control, whereas there was no such effect in aging hearts. It is concluded that uncoupling proteins are implicated in the age-depended heart dysfunction and development of the pathological mechanisms during ischemia-reperfusion.

  14. Self-conscious affects: their adaptive Functions and relationship to depressive mood.

    PubMed

    Uji, Masayo; Kitamura, Toshinori; Nagata, Toshiaki

    2011-01-01

    This study used a structural equation model to examine the influence of resilience on the four self-conscious affects (guilt-proneness, shame-proneness, externalization, and detachment) assessed in the Test of Self-Conscious Affect-3 (TOSCA-3) and their impact on depressive mood. Our subject population consisted of 447 Japanese university students. The first analysis explored which TOSCA-3 affects help an individual adapt to stressful situations. The concept of "resilience" was used as an indicator to evaluate the adaptive functions. We based this on the assumption that an individual with higher resilience is able to use more adaptive affects. In the second analysis, taking the above relationship between resilience and the self-conscious affects into consideration, we examined how those variables as well as a negative life event are related to depressive mood. To assess the resilience level and depressive mood, we adopted the Resilience Scale (RS) and Self-rating Depressive Scale (SDS), respectively. The first analysis showed that the more resilient an individual was, the more prone they were to "detachment" and the less "shame" they experienced. The level of resilience did not have a significant effect on "guilt" or "externalization." In the second analysis we found that "resilience" had a direct inverse effect on depressive mood that was also mediated by "shame" and "detachment." We discuss how the particular self-conscious affects comprising each adaptive function are related to depressive mood.

  15. Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

    PubMed Central

    Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

  16. Connecting teratogen-induced congenital heart defects to neural crest cells and their effect on cardiac function.

    PubMed

    Karunamuni, Ganga H; Ma, Pei; Gu, Shi; Rollins, Andrew M; Jenkins, Michael W; Watanabe, Michiko

    2014-09-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies.

  17. NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets

    PubMed Central

    Bouveret, Romaric; Waardenberg, Ashley J; Schonrock, Nicole; Ramialison, Mirana; Doan, Tram; de Jong, Danielle; Bondue, Antoine; Kaur, Gurpreet; Mohamed, Stephanie; Fonoudi, Hananeh; Chen, Chiann-mun; Wouters, Merridee A; Bhattacharya, Shoumo; Plachta, Nicolas; Dunwoodie, Sally L; Chapman, Gavin; Blanpain, Cédric; Harvey, Richard P

    2015-01-01

    We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off-targets", and retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease. DOI: http://dx.doi.org/10.7554/eLife.06942.001 PMID:26146939

  18. Lamin-B1 contributes to the proper timing of epicardial cell migration and function during embryonic heart development

    PubMed Central

    Tran, Joseph R.; Zheng, Xiaobin; Zheng, Yixian

    2016-01-01

    Lamin proteins form a meshwork beneath the nuclear envelope and contribute to many different cellular processes. Mutations in lamins cause defective organogenesis in mouse models and human diseases that affect adipose tissue, brain, skeletal muscle, and the heart. In vitro cell culture studies have shown that lamins help maintain nuclear shape and facilitate cell migration. However, whether these defects contribute to improper tissue building in vivo requires further clarification. By studying the heart epicardium during embryogenesis, we show that Lb1-null epicardial cells exhibit in vivo and in vitro migratory delay. Transcriptome analyses of these cells suggest that Lb1 influences the expression of cell adhesion genes, which could affect cell migration during epicardium development. These epicardial defects are consistent with incomplete development of both vascular smooth muscle and compact myocardium at later developmental stages in Lb1-null embryos. Further, we found that Lb1-null epicardial cells have a delayed nuclear morphology change in vivo, suggesting that Lb1 facilitates morphological changes associated with migration. These findings suggest that Lb1 contributes to nuclear shape maintenance and migration of epicardial cells and highlights the use of these cells for in vitro and in vivo study of these classic cell biological phenomena. PMID:27798236

  19. Handgrip Strength, Positive Affect, and Perceived Health Are Prospectively Associated with Fewer Functional Limitations among Centenarians

    ERIC Educational Resources Information Center

    Franke, Warren D.; Margrett, Jennifer A.; Heinz, Melinda; Martin, Peter

    2012-01-01

    This study assessed the association between perceived health, fatigue, positive and negative affect, handgrip strength, objectively measured physical activity, body mass index, and self-reported functional limitations, assessed 6 months later, among 11 centenarians (age = 102 plus or minus 1). Activities of daily living, assessed 6 months prior to…

  20. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…