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Sample records for deficiency cardiac functional

  1. Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

    Science.gov (United States)

    Hirooka, K; Yasumura, Y; Ishida, Y; Komamura, K; Hanatani, A; Nakatani, S; Yamagishi, M; Miyatake, K

    2000-09-01

    A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

  2. Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice.

    Science.gov (United States)

    Dobrzyn, Pawel; Dobrzyn, Agnieszka; Miyazaki, Makoto; Ntambi, James M

    2010-08-01

    The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1(-/-) mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin deficiency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA beta-oxidation is also significantly lower in the heart of ob/ob;SCD1(-/-) mice compared with ob/ob controls. Moreover, SCD1 deficiency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by SCD1 deficiency.

  3. Vitamin D deficiency and its relationship with cardiac iron and function in patients with transfusion-dependent thalassemia at Chiang Mai University Hospital.

    Science.gov (United States)

    Dejkhamron, Prapai; Wejaphikul, Karn; Mahatumarat, Tuanjit; Silvilairat, Suchaya; Charoenkwan, Pimlak; Saekho, Suwit; Unachak, Kevalee

    2018-02-01

    Vitamin D deficiency is common in patients with thalassemia. Vitamin D deficiency could be related to cardiac dysfunction. Increased parathyroid hormone (PTH) is also known to be associated with heart failure. To determine the prevalence of Vitamin D deficiency and to explore the impact of Vitamin D deficiency on cardiac iron and function in patients with transfusion-dependent thalassemia. A cross-sectional study in patients with Transfusion-dependent thalassemia was conducted. Patients with liver disease, renal disease, type 1 diabetes, malabsorption, hypercortisolism, malignancy, and contraindication for MRI were excluded. Calcium, phosphate, PTH, vitamin D-25OH were measured. CardiacT2 * and liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) were determined. Results Sixty-one (33M/28F) patients with Transfusion-dependent thalassemia were enrolled. The prevalence of Vitamin D deficiency was 50.8%. Patients with cardiac siderosis had tendency for lower D-25OH than those without siderosis (15.9 (11.7-20.0) vs. 20.2 (15.85-22.3) ng/mL); p = 0.06). Serum calcium, phosphate, PTH, LIC, cardiac T2 * , and LVEF were not different between the groups with or without Vitamin D deficiency. Patients with Vitamin D deficiency had significantly lower hemoglobin levels compared to those without Vitamin D deficiency (7.5 (6.93-8.33) vs. 8.1 (7.30-8.50) g/dL; p = 0.04). The median hemoglobin in the last 12 months was significantly correlated with D-25OH. Cardiac T2 * had significant correlation with PTH. Vitamin D deficiency is prevalent in patients with Transfusion-dependent thalassemia. Vitamin D level is correlated with hemoglobin level. Vitamin D status should be routinely assessed in these patients. Low PTH is correlated with increased cardiac iron. This study did not demonstrate an association between Vitamin D deficiency and cardiac iron or function in patients with Transfusion-dependent thalassemia.

  4. Evaluation of skeletal and cardiac muscle function after chronic administration of thymosin beta-4 in the dystrophin deficient mouse.

    Directory of Open Access Journals (Sweden)

    Christopher F Spurney

    2010-01-01

    Full Text Available Thymosin beta-4 (Tbeta4 is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tbeta4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ and mdx mice, 8-10 weeks old, were treated with 150 microg of Tbeta4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tbeta4 and amount of fibrosis were quantified using immunohistochemistry and Gomori's tri-chrome staining, respectively. Mdx mice treated with Tbeta4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tbeta4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tbeta4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy.

  5. Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

    Science.gov (United States)

    González-Guerra, José Luis; Castilla-Cortazar, Inma; Aguirre, Gabriel A; Muñoz, Úrsula; Martín-Estal, Irene; Ávila-Gallego, Elena; Granado, Miriam; Puche, Juan E; García-Villalón, Ángel Luis

    2017-01-01

    Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

  6. Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

    Directory of Open Access Journals (Sweden)

    José Luis González-Guerra

    Full Text Available Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R. In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides; carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

  7. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

    Science.gov (United States)

    Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

    2016-01-01

    Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

  8. Improvement of cardiac contractile function by peptide-based inhibition of NF-κB in the utrophin/dystrophin-deficient murine model of muscular dystrophy

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    Guttridge Denis C

    2011-05-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain, targeted at blunting Nuclear Factor κB (NF-κB signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted β-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as β-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice. Results At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to β-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice. Conclusions We conclude

  9. Insulin-Like Growth Factor I (IGF-1) Deficiency Ameliorates Sex Difference in Cardiac Contractile Function and Intracellular Ca2+ Homeostasis

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    Ceylan-Isik, Asli F.; Li, Qun; Ren, Jun

    2011-01-01

    Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR90), fura-fluorescence intensity (FFI) and intracellular Ca2+ clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ± dL/dt, longer TPS, TR90 and intracellular Ca2+ clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na+-Ca2+ exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca2+ regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca2+ regulation. PMID:21763763

  10. Insulin-like growth factor I (IGF-1) deficiency ameliorates sex difference in cardiac contractile function and intracellular Ca(2+) homeostasis.

    Science.gov (United States)

    Ceylan-Isik, Asli F; Li, Qun; Ren, Jun

    2011-10-10

    Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (±dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR(90)), fura-fluorescence intensity (FFI) and intracellular Ca(2+) clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ±dL/dt, longer TPS, TR(90) and intracellular Ca(2+) clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na(+)-Ca(2+) exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca(2+) regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca(2+) regulation. Copyright © 2011 Elsevier Ireland

  11. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T

    2015-01-01

    to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ2 protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby...

  12. Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis

    NARCIS (Netherlands)

    Frank, Deborah U.; Carter, Kandis L.; Thomas, Kirk R.; Burr, R. Michael; Bakker, Martijn L.; Coetzee, William A.; Tristani-Firouzi, Martin; Bamshad, Michael J.; Christoffels, Vincent M.; Moon, Anne M.

    2012-01-01

    TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development,

  13. Cardiac remodeling after myocardial infarction is impaired in IGF-1 deficient mice

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    Palmen, M.; Daemen, M. J.; Bronsaer, R.; Dassen, W. R.; Zandbergen, H. R.; Kockx, M.; Smits, J. F.; van der Zee, R.; Doevendans, P. A.

    2001-01-01

    To obtain more insight in the role of IGF-1 in cardiac remodeling and function after experimental myocardial infarction. We hypothesized that cardiac remodeling is altered in IGF-1 deficient mice, which may affect cardiac function. A myocardial infarction was induced by surgical coronary artery

  14. Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

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    Walker LeeAnn

    2002-01-01

    Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

  15. Left ventricular dysfunction with reduced functional cardiac reserve in diabetic and non-diabetic LDL-receptor deficient apolipoprotein B100-only mice

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    Bosch Fatima

    2011-06-01

    Full Text Available Abstract Background Lack of suitable mouse models has hindered the studying of diabetic macrovascular complications. We examined the effects of type 2 diabetes on coronary artery disease and cardiac function in hypercholesterolemic low-density lipoprotein receptor-deficient apolipoprotein B100-only mice (LDLR-/-ApoB100/100. Methods and results 18-month-old LDLR-/-ApoB100/100 (n = 12, diabetic LDLR-/-ApoB100/100 mice overexpressing insulin-like growth factor-II (IGF-II in pancreatic beta cells (IGF-II/LDLR-/-ApoB100/100, n = 14 and age-matched C57Bl/6 mice (n = 15 were studied after three months of high-fat Western diet. Compared to LDLR-/-ApoB100/100 mice, diabetic IGF-II/LDLR-/-ApoB100/100 mice demonstrated more calcified atherosclerotic lesions in aorta. However, compensatory vascular enlargement was similar in both diabetic and non-diabetic mice with equal atherosclerosis (cross-sectional lesion area ~60% and consequently the lumen area was preserved. In coronary arteries, both hypercholesterolemic models showed significant stenosis (~80% despite positive remodeling. Echocardiography revealed severe left ventricular systolic dysfunction and anteroapical akinesia in both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice. Myocardial scarring was not detected, cardiac reserve after dobutamine challenge was preserved and ultrasructural changes revealed ischemic yet viable myocardium, which together with coronary artery stenosis and slightly impaired myocardial perfusion suggest myocardial hibernation resulting from chronic hypoperfusion. Conclusions LDLR-/-ApoB100/100 mice develop significant coronary atherosclerosis, severe left ventricular dysfunction with preserved but diminished cardiac reserve and signs of chronic myocardial hibernation. However, the cardiac outcome is not worsened by type 2 diabetes, despite more advanced aortic atherosclerosis in diabetic animals.

  16. Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload

    NARCIS (Netherlands)

    Wang, Jiong-Wei; Fontes, Magda S. C.; Wang, Xiaoyuan; Chong, Suet Yen; Kessler, Elise L.; Zhang, Ya-Nan; de Haan, Judith J.; Arslan, Fatih; de Jager, Saskia C. A.; Timmers, Leo; van Veen, Toon A. B.; Lam, Carolyn S. P.; de Kleijn, Dominique P. V.

    2017-01-01

    An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure

  17. Cardiac function studies

    International Nuclear Information System (INIS)

    Horn, H.J.

    1986-01-01

    A total of 27 patients were subjected tointramyocardial sequential scintiscanning (first pass) using 99m-Tc human serum albumin. A refined method is described that is suitable to analyse clinically relevant parameters like blood volume, cardiac output, ejection fraction, stroke volume, enddiastolic and endsystolic volumes as well as pulmonal transition time and uses a complete camaracomputer system adapted to the requirements of a routine procedure. Unless there is special hardware available, the method does not yet appear mature enough to be put into general practice. Its importance recently appeared in a new light due to the advent of particularly shortlived isotopes. For the time being, however, ECG-triggered equilibrium studies are to be preferred for cardiac function tests. (TRV) [de

  18. Iron deficiency and cognitive functions

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    Jáuregui-Lobera I

    2014-11-01

    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  19. Cardiac manifestations of GH deficiency after treatment for acromegaly: a comparison to patients with biochemical remission and controls

    NARCIS (Netherlands)

    van der Klaauw, Agatha A.; Bax, Jeroen J.; Bleeker, Gabe B.; Holman, Eduard R.; Delgado, V.; Smit, Johannes W. A.; Romijn, Johannes A.; Pereira, Alberto M.

    2008-01-01

    Both GH excess and GH deficiency (GHD) lead to specific cardiac pathology. The aim of this study was to evaluate cardiac morphology and function in patients with GHD after treatment for acromegaly. Cross-sectional study. Cardiac parameters were studied by conventional two-dimensional

  20. Cardiac function in acute hypothyroidism

    International Nuclear Information System (INIS)

    Donaghue, K.; Hales, I.; Allwright, S.; Cooper, R.; Edwards, A.; Grant, S.; Morrow, A.; Wilmshurst, E.; Royal North Shore Hospital, Sydney

    1985-01-01

    It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total tyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidisms, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P<0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effussion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function. (orig.)

  1. Skeletal, cardiac, and respiratory muscle function and histopathology in the P448Lneo- mouse model of FKRP-deficient muscular dystrophy.

    Science.gov (United States)

    Yu, Qing; Morales, Melissa; Li, Ning; Fritz, Alexander G; Ruobing, Ren; Blaeser, Anthony; Francois, Ershia; Lu, Qi-Long; Nagaraju, Kanneboyina; Spurney, Christopher F

    2018-04-06

    Fukutin-related protein (FKRP) mutations are the most common cause of dystroglycanopathies known to cause both limb girdle and congenital muscular dystrophy. The P448Lneo- mouse model has a knock-in mutation in the FKRP gene and develops skeletal, respiratory, and cardiac muscle disease. We studied the natural history of the P448Lneo- mouse model over 9 months and the effects of twice weekly treadmill running. Forelimb and hindlimb grip strength (Columbus Instruments) and overall activity (Omnitech Electronics) assessed skeletal muscle function. Echocardiography was performed using VisualSonics Vevo 770 (FujiFilm VisualSonics). Plethysmography was performed using whole body system (ADInstruments). Histological evaluations included quantification of inflammation, fibrosis, central nucleation, and fiber size variation. P448Lneo- mice had significantly increased normalized tissue weights compared to controls at 9 months of age for the heart, gastrocnemius, soleus, tibialis anterior, quadriceps, and triceps. There were no significant differences seen in forelimb or hindlimb grip strength or activity monitoring in P448Lneo- mice with or without exercise compared to controls. Skeletal muscles demonstrated increased inflammation, fibrosis, central nucleation, and variation in fiber size compared to controls (p muscular dystrophies.

  2. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin induced cardiac injury in mice

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    Yousif Nasser

    2011-10-01

    Full Text Available Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin induced cardiac toxicity. Toll-like receptors (TLRs are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p., left ventricular pressure volume loops were measured in HeN compotent (TLR4+/+ and HeJ mutant (TLR4-/- treated with trastuzumab and control mice. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α, Western immunoblotting assay for ICAM-1, and used troponin I for cardiac injury marker. Results Trastuzumab injection resulted in an impairment of left ventricular function in TLR-4 competent (HeN, in contrast TLR4-/- trastuzumab mice showed improved left ventricular function EF%, CO; p -/-; p -/-, marked reduction of myocardial troponin-I levels in TLR4-deficient mice. Data are presented as means ± SE; n = 8 in each group p Conclusions Treatment with trastuzumab induces an inflammatory response that contributes to myocardial tissue TLR4 mediates chemokine expression (TNF-α, MCP-1and ICAM-1, so in experimental animals TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in trastuzumab induced cardiomyopathy.

  3. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    International Nuclear Information System (INIS)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj; Schönberger, Tanja; Noegel, Angelika A.; Gawaz, Meinrad; Lang, Florian

    2014-01-01

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca 2+ signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7 −/− ) and wild-type mice (anxa7 +/+ ) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7 −/− mice than in anxa7 +/+ mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions

  4. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj [Department of Physiology, University of Tübingen, Tübingen (Germany); Schönberger, Tanja [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Noegel, Angelika A. [Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln (Germany); Gawaz, Meinrad [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tübingen, Tübingen (Germany)

    2014-02-28

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{sup +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

  5. Cardiac function and cognition in older community-dwelling cardiac patients

    NARCIS (Netherlands)

    Eggermont, Laura H.P.; Aly, Mohamed F.A.; Vuijk, Pieter J.; de Boer, Karin; Kamp, Otto; van Rossum, Albert C.; Scherder, Erik J.A.

    2017-01-01

    Background: Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older

  6. Mathematical Models of Cardiac Pacemaking Function

    Science.gov (United States)

    Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

    2013-10-01

    Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  7. Mathematical Models of Cardiac Pacemaking Function

    Directory of Open Access Journals (Sweden)

    Pan eLi

    2013-10-01

    Full Text Available Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  8. Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout

    Science.gov (United States)

    Balbo, Bruno E.; Amaral, Andressa G.; Fonseca, Jonathan M.; de Castro, Isac; Salemi, Vera M.; Souza, Leandro E.; dos Santos, Fernando; Irigoyen, Maria C.; Qian, Feng; Chammas, Roger; Onuchic, Luiz F.

    2016-01-01

    Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations, in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1cond/cond:Nestincre (CYG+) cystic mice exposed to increased blood pressure, at 5–6 and 20–24 weeks of age, and Pkd1+/− (HTG+) noncystic mice at 5–6 and 10–13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1cond/cond and Pkd1+/+ controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1cond/cond:Nestincre;Lgals3−/− (CYG−) and Pkd1+/−;Lgals3−/− (HTG−) mice displayed improved cardiac deformability and systolic parameters compared to single-mutants, not differing from their controls. CYG− and HTG− showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1V/V; VVG+) showed that Pkd1V/V;Lgals3−/− (VVG−) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG− and VVG− animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkd1-deficient models and suppression of galectin-3 expression rescues this phenotype. PMID:27475230

  9. Functional cardiac imaging: positron emission tomography

    International Nuclear Information System (INIS)

    Mullani, N.A.; Gould, K.L.

    1984-01-01

    Dynamic cardiovascular imaging plays a vital role in the diagnosis and treatment of cardiac disease by providing information about the function of the heart. During the past 30 years, cardiovascular imaging has evolved from the simple chest x-ray and fluoroscopy to such sophisticated techniques as invasive cardiac angiography and cinearteriography and, more recently, to noninvasive cardiac CT scanning, nuclear magnetic resonance, and positron emission tomography, which reflect more complex physiologic functions. As research tools, CT, NMR, and PET provide quantitative information on global as well as regional ventricular function, coronary artery stenosis, myocardial perfusion, glucose and fatty acid metabolism, or oxygen utilization, with little discomfort or risk to the patient. As imaging modalities become more sophisticated and more oriented toward clinical application, the prospect of routinely obtaining such functional information about the heart is becoming realistic. However, these advances are double-edged in that the interpretation of functional data is more complex than that of the anatomic imaging familiar to most physicians. They will require an enhanced understanding of the physiologic and biochemical processes, as well as of the instrumentation and techniques for analyzing the data. Of the new imaging modalities that provide functional information about the heart, PET is the most useful because it quantitates the regional distribution of radionuclides in vivo. Clinical applications, interpretation of data, and the impact of PET on our understanding of cardiac pathophysiology are discussed. 5 figures

  10. Congenital leptin deficiency and thyroid function

    Directory of Open Access Journals (Sweden)

    Paz-Filho Gilberto

    2009-11-01

    Full Text Available Abstract Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four leptin-deficient humans (2 males aged 5 and 27, and 2 females aged 35 and 40, before and during leptin replacement with recombinant human methionyl leptin (r-metHuLeptin. The child was evaluated for four years, and the adults, for eight years. In addition, the adults were submitted to a brief withdrawal of leptin during six weeks in the sixth year. Our results show that, regardless of leptin replacement, our leptin-deficient patients have normal thyroid function. In spite of having an important role in regulating the hypothalamic-pituitary-thyroidal axis, leptin is not required for normal thyroid function. Trial Registration ClinicalTrials.gov Identifiers: NCT00659828 and NCT00657605

  11. Cardiac Morphology and Function, and Blood Gas Transport in Aquaporin-1 Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Samer eAl-Samir

    2016-05-01

    Full Text Available We have studied cardiac and respiratory functions of aquaporin- 1-deficient mice by the Pressure-Volume-loop technique and by blood gas analysis. In addition, the morphological properties of the animals’ hearts were analysed. In anesthesia under maximal dobutamine stimulation, the mice exhibit a moderately elevated heart rate of < 600 min-1 and an O2 consumption of ~0.6 ml/min/g, which is about twice the basal rate. In this state, which is similar to the resting state of the conscious animal, all cardiac functions including stroke volume and cardiac output exhibited resting values and were identical between deficient and wildtype animals. Likewise, pulmonary and peripheral exchange of O2 and CO2 were normal. In contrast, several morphological parameters of the heart tissue of deficient mice were altered: 1 left ventricular wall thickness was reduced by 12%, 2 left ventricular mass, normalized to tibia length, was reduced by 10-20%, 3 cardiac muscle fiber cross sectional area was decreased by 17%, and 4 capillary density was diminished by 10%. As the P-V-loop technique yielded normal end-diastolic and end-systolic left ventricular volumes, the deficient hearts are characterized by thin ventricular walls in combination with normal intraventricular volumes. The aquaporin-1-deficient heart thus seems to be at a disadvantage compared to the wildtype heart by a reduced left-ventricular wall thickness and an increased diffusion distance between blood capillaries and muscle mitochondria. While under the present quasi-resting conditions these morphological alterations have no consequences for cardiac function, we expect that the deficient hearts will show a reduced maximal cardiac output.

  12. Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Nielsen, Olav W; Lund, Allan M

    2013-01-01

    Several episodes of sudden death among young Faroese individuals have been associated with primary carnitine deficiency (PCD). Patients suffering from PCD have low carnitine levels and can present with metabolic and/or cardiac complications. Pivalic acid exposure decreases carnitine levels...

  13. Normal macrophage function in copper deficient mice

    International Nuclear Information System (INIS)

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-01-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

  14. Relationship between cobalamin deficiency and delirium in elderly patients undergoing cardiac surgery

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    Sevuk U

    2015-08-01

    Full Text Available Utkan Sevuk,1 Erkan Baysal,2 Nurettin Ay,3 Yakup Altas,2 Rojhat Altindag,2 Baris Yaylak,2 Vahhac Alp,3 Ertan Demirtas4 1Department of Cardiovascular Surgery, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 2Department of Cardiology, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 3Department of General Surgery, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 4Department of Cardiovascular Surgery, Liv Hospital, Ankara, Turkey Background: Delirium is common after cardiac surgery and is independently associated with increased morbidity, mortality, prolonged hospital stays, and higher costs. Cobalamin (vitamin B12 deficiency is a common cause of neuropsychiatric symptoms and affects up to 40% of elderly people. The relationship between cobalamin deficiency and the occurrence of delirium after cardiac surgery has not been examined in previous studies. We examined the relationship between cobalamin deficiency and delirium in elderly patients undergoing coronary artery bypass grafting (CABG surgery.Material and methods: A total of 100 patients with cobalamin deficiency undergoing CABG were enrolled in this retrospective study. Control group comprised 100 patients without cobalamin deficiency undergoing CABG. Patients aged 65 years or over were included. Diagnosis of delirium was made using Intensive Care Delirium Screening Checklist. Delirium severity was measured using the Delirium Rating Scale-revised-98.Results: Patients with cobalamin deficiency had a significantly higher incidence of delirium (42% vs 26%; P=0.017 and higher delirium severity scores (16.5±2.9 vs 15.03±2.48; P=0.034 than patients without cobalamin deficiency. Cobalamin levels were significantly lower in patients with delirium than patients without delirium (P=0.004. Delirium severity score showed a moderate correlation with cobalamin levels (Ρ=-0.27; P=0.024. Logistic regression analysis demonstrated that

  15. Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses

    International Nuclear Information System (INIS)

    Nan, Changlong; Li, Yuejin; Jean-Charles, Pierre-Yves; Chen, Guozhen; Kreymerman, Alexander; Prentice, Howard; Weissbach, Herbert; Huang, Xupei

    2010-01-01

    Research highlights: → Deficiency of MsrA in the heart renders myocardial cells more sensitive to oxidative stress. → Mitochondrial damage happens in the heart lacking MsrA. → More protein oxidation in myocardial cells lacking MsrA. → MsrA protects the heart against oxidative stress. -- Abstract: Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA -/- ) mouse model, we have investigated the role of MsrA in the heart. Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA -/- mice if the hearts are not stressed. However, the cellular contractility, when stressed using a higher stimulation frequency (2 Hz), is significantly reduced in MsrA -/- cardiac myocytes. MsrA -/- cardiac myocytes also show a significant decrease in contractility after oxidative stress using H 2 O 2 . Corresponding changes in Ca 2+ transients are observed in MsrA -/- cardiomyocytes treated with 2 Hz stimulation or with H 2 O 2 . Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA -/- mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA -/- mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.

  16. Cardiac Subtype-Specific Modeling of Kv1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Maike Marczenke

    2017-07-01

    Full Text Available The ultrarapid delayed rectifier K+ current (IKur, mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF. Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout. This model as well as isogenic wild-type control hiPSCs could selectively be differentiated into ventricular or atrial cardiomyocytes at high efficiency, based on the specific manipulation of retinoic acid signaling. Investigation of electrophysiological properties in Kv1.5-deficient cardiomyocytes compared to isogenic controls revealed a strictly atrial-specific disease phentoype, characterized by cardiac subtype-specific field and action potential prolongation and loss of 4-aminopyridine sensitivity. Atrial Kv1.5-deficient cardiomyocytes did not show signs of arrhythmia under adrenergic stress conditions or upon inhibiting additional types of K+ current. Exposure of bulk cultures to carbachol lowered beating frequencies and promoted chaotic spontaneous beating in a stochastic manner. Low-frequency, electrical stimulation in single cells caused atrial and mutant-specific early afterdepolarizations, linking the loss of KCNA5 function to a putative trigger mechanism in familial AF. These results clarify for the first time the role of Kv1.5 in atrial hiPSC-cardiomyocytes and demonstrate the feasibility of cardiac subtype-specific disease modeling using engineered hiPSCs.

  17. GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice.

    Science.gov (United States)

    Lenhart, Kaitlin C; O'Neill, Thomas J; Cheng, Zhaokang; Dee, Rachel; Demonbreun, Alexis R; Li, Jianbin; Xiao, Xiao; McNally, Elizabeth M; Mack, Christopher P; Taylor, Joan M

    2015-01-01

    The plasma membranes of striated muscle cells are particularly susceptible to rupture as they endure significant mechanical stress and strain during muscle contraction, and studies have shown that defects in membrane repair can contribute to the progression of muscular dystrophy. The synaptotagmin-related protein, dysferlin, has been implicated in mediating rapid membrane repair through its ability to direct intracellular vesicles to sites of membrane injury. However, further work is required to identify the precise molecular mechanisms that govern dysferlin targeting and membrane repair. We previously showed that the bin-amphiphysin-Rvs (BAR)-pleckstrin homology (PH) domain containing Rho-GAP GTPase regulator associated with focal adhesion kinase-1 (GRAF1) was dynamically recruited to the tips of fusing myoblasts wherein it promoted membrane merging by facilitating ferlin-dependent capturing of intracellular vesicles. Because acute membrane repair responses involve similar vesicle trafficking complexes/events and because our prior studies in GRAF1-deficient tadpoles revealed a putative role for GRAF1 in maintaining muscle membrane integrity, we postulated that GRAF1 might also play an important role in facilitating dysferlin-dependent plasma membrane repair. We used an in vitro laser-injury model to test whether GRAF1 was necessary for efficient muscle membrane repair. We also generated dystrophin/GRAF1 doubledeficient mice by breeding mdx mice with GRAF1 hypomorphic mice. Evans blue dye uptake and extensive morphometric analyses were used to assess sarcolemmal integrity and related pathologies in cardiac and skeletal muscles isolated from these mice. Herein, we show that GRAF1 is dynamically recruited to damaged skeletal and cardiac muscle plasma membranes and that GRAF1-depleted muscle cells have reduced membrane healing abilities. Moreover, we show that dystrophin depletion exacerbated muscle damage in GRAF1-deficient mice and that mice with dystrophin/GRAF1

  18. Cardiac function and cognition in older community-dwelling cardiac patients.

    Science.gov (United States)

    Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

    2017-11-01

    Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

  19. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Peter Moritz Becher

    2017-01-01

    Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

  20. Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Hao Wang

    Full Text Available Hepatoma-derived growth factor (HDGF related protein 2 (HRP2 and lens epithelium-derived growth factor (LEDGF/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E 13.5. Histological examination revealed ventricular septal defect (VSD associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s, RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality

  1. Novel axolotl cardiac function analysis method using magnetic resonance imaging

    NARCIS (Netherlands)

    Sanches, Pedro Gomes; Op 't Veld, Roel C.; de Graaf, Wolter; Strijkers, Gustav J.; Grüll, Holger

    2017-01-01

    The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a non-invasive technique to image heart function

  2. Novel axolotl cardiac function analysis method using magnetic resonance imaging

    NARCIS (Netherlands)

    Sanches, P.G.; Op ‘t Veld, R.C.; de Graaf, W.; Strijkers, G.J.; Grüll, H.

    2017-01-01

    The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a noninvasive technique to image heart function of

  3. Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Xiong-Zhi Li

    2017-12-01

    Full Text Available Background: Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. Methods: The ApoE-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67, senescence (p16INK4a, oxidant (NADPH oxidase 4, NOX4 and antioxidant (superoxide dismutase, SOD were observed by immunofluorescence staining. Results: Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE-/- mice. However, the decreased left ventricular ejection fraction (LVEF and fractional shortening (FS in ApoE–/– mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53-apoptosis pathway and oxidant-antioxidants in the hearts of ApoE-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16INK4a in the hearts of ApoE-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. Conclusion: AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress.

  4. Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets

    Science.gov (United States)

    Gerber, Karen; Harvey, John W.; D'Agorne, Sara; Wood, Jonathan; Giger, Urs

    2009-01-01

    Two male castrated Whippet littermates were presented at 1 year of age for pallor, tachycardia, systolic heart murmur, dark yellow to orange feces, intermittent lethargy, pigmenturia, and muscle shivering or cramping after exercise. Persistent macrocytic hypochromic anemia with marked reticulocytosis and metarubricytosis was found when CBC results were compared with reference values for Whippets. Increased serum creatine kinase activity and hyperkalemia also were sometimes present over the 4-year period of evaluation. Progressively increasing serum concentrations of N-terminal prohormone brain natriuretic peptide suggested cardiac disease. Erythrocytes from the whippets were less osmotically fragile but more alkaline fragile than those from control dogs. Erythrocyte phosphofructokinase (PFK) activities and 2,3-diphosphoglycerate concentrations were decreased. Restriction enzyme-based DNA test screening and DNA sequencing revealed the same mutation in the muscle-PFK gene of the Whippets as seen in English Springer Spaniel dogs with PFK deficiency. This is the first report of PFK deficiency in Whippet dogs. In addition to causing hemolysis and exertional myopathy, heart disease may be a prominent clinical component of PFK deficiency in this breed and has not been previously recognized in PFK-deficient English Springer Spaniels. PMID:19228357

  5. Iodine deficiency, thyroid function and hearing deficit: a review

    NARCIS (Netherlands)

    Boonstra, A.; MacKenzie, I.

    2013-01-01

    Iodine deficiency affects an estimated 241 million school-aged children in the world. Little is known about iodine deficiency in relation to auditory function, except for the fact that deaf-mutism is one of the features of cretinism. In the present review, we documented the scientific knowledge on

  6. Deficiency in Cardiac Dystrophin Affects the Abundance of the α-/β-Dystroglycan Complex

    Directory of Open Access Journals (Sweden)

    James Lohan

    2005-01-01

    Full Text Available Although Duchenne muscular dystrophy is primarily categorised as a skeletal muscle disease, deficiency in the membrane cytoskeletal protein dystrophin also affects the heart. The central transsarcolemmal linker between the actin membrane cytoskeleton and the extracellular matrix is represented by the dystrophin-associated dystroglycans. Chemical cross-linking analysis revealed no significant differences in the dimeric status of the α-/β-dystroglycan subcomplex in the dystrophic mdx heart as compared to normal cardiac tissue. In analogy to skeletal muscle fibres, heart muscle also exhibited a greatly reduced abundance of both dystroglycans in dystrophin-deficient cells. Immunoblotting demonstrated that the degree of reduction in α-dystroglycan is more pronounced in matured mdx skeletal muscle as contrasted to the mdx heart. The fact that the deficiency in dystrophin triggers a similar pathobiochemical response in both types of muscle suggests that the cardiomyopathic complications observed in x-linked muscular dystrophy might be initiated by the loss of the dystrophin-associated surface glycoprotein complex.

  7. Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Keith Dadson

    Full Text Available Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM remodeling in response to pressure overload (PO. Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO and wild-type (WT mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson's trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects.

  8. Evaluation of cardiac function in active and hibernating grizzly bears.

    Science.gov (United States)

    Nelson, O Lynne; McEwen, Margaret-Mary; Robbins, Charles T; Felicetti, Laura; Christensen, William F

    2003-10-15

    To evaluate cardiac function parameters in a group of active and hibernating grizzly bears. Prospective study. 6 subadult grizzly bears. Indirect blood pressure, a 12-lead ECG, and a routine echocardiogram were obtained in each bear during the summer active phase and during hibernation. All measurements of myocardial contractility were significantly lower in all bears during hibernation, compared with the active period. Mean rate of circumferential left ventricular shortening, percentage fractional shortening, and percentage left ventricular ejection fraction were significantly lower in bears during hibernation, compared with the active period. Certain indices of diastolic function appeared to indicate enhanced ventricular compliance during the hibernation period. Mean mitral inflow ratio and isovolumic relaxation time were greater during hibernation. Heart rate was significantly lower for hibernating bears, and mean cardiac index was lower but not significantly different from cardiac index during the active phase. Contrary to results obtained in hibernating rodent species, cardiac index was not significantly correlated with heart rate. Cardiac function parameters in hibernating bears are opposite to the chronic bradycardic effects detected in nonhibernating species, likely because of intrinsic cardiac muscle adaptations during hibernation. Understanding mechanisms and responses of the myocardium during hibernation could yield insight into mechanisms of cardiac function regulation in various disease states in nonhibernating species.

  9. The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.

    Science.gov (United States)

    Arioglu, E; Guner, S; Ozakca, I; Altan, V M; Ozcelikay, A T

    2010-02-01

    Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.

  10. Cardiac telomere length in heart development, function, and disease.

    Science.gov (United States)

    Booth, S A; Charchar, F J

    2017-07-01

    Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

  11. Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

    Science.gov (United States)

    Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

    2018-02-27

    Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

  12. Vitamin B12 Deficiency in Relation to Functional Disabilities

    Directory of Open Access Journals (Sweden)

    Heather E. Rasmussen

    2013-11-01

    Full Text Available This study was designed to assess whether symptoms, functional measures, and reported disabilities were associated with vitamin B12 (B12 deficiency when defined in three ways. Participants, aged 60 or more years of age, in 1999–2002 National Health and Nutrition Examination Surveys (NHANES were categorized in relation to three previously used definitions of B12 deficiency: (1 serum B12 20 μmol/L; and (3 serum B12 0.21 μmol/L. Functional measures of peripheral neuropathy, balance, cognitive function, gait speed, along with self-reported disability (including activities of daily living were examined with standardized instruments by trained NHANES interviewers and technicians. Individuals identified as B12 deficient by definition 2 were more likely to manifest peripheral neuropathy OR (odds (95% confidence intervals, p value: 9.70 (2.24, 42.07, 0.004 and report greater total disability, 19.61 (6.22, 61.86 0.0001 after adjustments for age, sex, race, serum creatinine, and ferritin concentrations, smoking, diabetes, and peripheral artery disease. Smaller, but significantly increased, odds of peripheral neuropathy and total disability were also observed when definition 3 was applied. Functional measures and reported disabilities were associated with B12 deficiency definitions that include B12 biomarkers (homocysteine or methylmalonic acid. Further study of these definitions is needed to alert clinicians of possible subclinical B12 deficiency because functional decline amongst older adults may be correctable if the individual is B12 replete.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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....

  14. Functional modulation of cardiac form through regionally confined cell shape changes.

    Directory of Open Access Journals (Sweden)

    Heidi J Auman

    2007-03-01

    Full Text Available Developing organs acquire a specific three-dimensional form that ensures their normal function. Cardiac function, for example, depends upon properly shaped chambers that emerge from a primitive heart tube. The cellular mechanisms that control chamber shape are not yet understood. Here, we demonstrate that chamber morphology develops via changes in cell morphology, and we determine key regulatory influences on this process. Focusing on the development of the ventricular chamber in zebrafish, we show that cardiomyocyte cell shape changes underlie the formation of characteristic chamber curvatures. In particular, cardiomyocyte elongation occurs within a confined area that forms the ventricular outer curvature. Because cardiac contractility and blood flow begin before chambers emerge, cardiac function has the potential to influence chamber curvature formation. Employing zebrafish mutants with functional deficiencies, we find that blood flow and contractility independently regulate cell shape changes in the emerging ventricle. Reduction of circulation limits the extent of cardiomyocyte elongation; in contrast, disruption of sarcomere formation releases limitations on cardiomyocyte dimensions. Thus, the acquisition of normal cardiomyocyte morphology requires a balance between extrinsic and intrinsic physical forces. Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis.

  15. The effects of malnutrition on cardiac function in African children.

    Science.gov (United States)

    Silverman, Jonathan A; Chimalizeni, Yamikani; Hawes, Stephen E; Wolf, Elizabeth R; Batra, Maneesh; Khofi, Harriet; Molyneux, Elizabeth M

    2016-02-01

    Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. Prospective cross-sectional study. Public referral hospital in Blantyre, Malawi. We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Cardiac dimensions and function in female handball players.

    Science.gov (United States)

    Malmgren, A; Dencker, M; Stagmo, M; Gudmundsson, P

    2015-04-01

    Long-term intensive endurance training leads to increased left ventricular mass and increased left ventricular end-diastolic and left atrial end-systolic diameters. Different types of sports tend to give rise to distinct morphological forms of the athlete's heart. However, the sport-specific aspects have not been fully investigated in female athletes. The purpose of the present study was to investigate differences in left and right cardiac dimensions, cardiac volumes, and systolic and diastolic function in elite female handball players compared to sedentary controls. A cross-sectional study of 33 elite female handball players was compared to 33 matched sedentary controls. Mean age was 21.5±2 years. The subjects underwent echocardiography examinations, both 2-dimensional (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were also evaluated. All cardiac dimensions and volumes were adjusted for body surface area (BSA). Left atrium and left ventricle volumes were significantly (Phandball players compared with sedentary controls. Even right atrium area as well as right ventricular end-diastolic and end-systolic area were significantly (Phandball players. Significant differences were observed in three out of five systolic parameters. Most diastolic function parameters did not differ between the two groups. The findings from the present study suggest that similar cardiac remodeling takes place in elite female handball players as it does in athletes pursuing endurance or team game sports.

  17. Mammalian enabled (Mena) is a critical regulator of cardiac function.

    Science.gov (United States)

    Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

    2011-05-01

    Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

  18. EANM/ESC guidelines for radionuclide imaging of cardiac function

    DEFF Research Database (Denmark)

    Hesse, B.; Lindhardt, T.B.; Acampa, W.

    2008-01-01

    radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes...

  19. [Structure and functional organization of integrated cardiac intensive care].

    Science.gov (United States)

    Scherillo, Marino; Miceli, Domenico; Tubaro, Marco; Guiducci, Umberto

    2007-05-01

    The early invasive strategy for the treatment of acute coronary syndromes and the increasing number of older and sicker patients requiring prolonged and more complex intensive care have induced many changes in the function of the intensive care units. These changes include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the intensive care units. This document indicates the structure of the units and specific recommendations for the number of beds, monitoring system, respirators, pacemaker/defibrillators and additional equipment.

  20. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    inflammatory response; rather, autoimmune response would keep affecting decreased heart function in. RHD patients who ... untreated children. Nearly 30 - 45 % of the affected children could ..... Technology Department of Anhui Province (PR.

  1. Evaluation of left ventricular function by cardiac CT

    International Nuclear Information System (INIS)

    Naito, Hiroaki; Kozuka, Takahiro

    1982-01-01

    Left ventricular function was evaluated by CT, which was compared with the data of left ventriculography for various cardiac diseases. The end diastolic volume of the left ventricle can be readily computed from CT, with a satisfactory correlation with that of left ventriculography (r = 0.95). The left ventricular ejection fraction, calculated from the areal ratio of the left ventricular lumen in end-diastolic imaging to that in end-sytolic imaging, also roughly reflects left ventricular contractile function, but shows correlation with left ventriculography by only r = 0.79. Although the cardiac output is not sensitive for functional evaluation, it can be directly calculated by means of dynamic scanning and shows a satisfactory correlation with the ear piece pigment dilution (r = 0.85). Evaluation of left ventricular function by CT shows a high precision in comparison with left ventriculography, but still lacks temporal resolving power. (Chiba, N.)

  2. Comparative impact of AAV and enzyme replacement therapy on respiratory and cardiac function in adult Pompe mice

    Directory of Open Access Journals (Sweden)

    Darin J Falk

    Full Text Available Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA. Cardiac dysfunction and respiratory muscle weakness are primary features of this disorder. To attenuate the progressive and rapid accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa−/− mice were administered a single systemic injection of rAAV2/9-DES-hGAA (AAV9-DES or bimonthly injections of recombinant human GAA (enzyme replacement therapy (ERT. Assessment of cardiac function and morphology was measured 1 and 3 months after initiation of treatment while whole-body plethysmography and diaphragmatic contractile function was evaluated at 3 months post-treatment in all groups. Gaa−/− animals receiving either AAV9-DES or ERT demonstrated a significant improvement in cardiac function and diaphragmatic contractile function as compared to control animals. AAV9-DES treatment resulted in a significant reduction in cardiac dimension (end diastolic left ventricular mass/gram wet weight; EDMc at 3 months postinjection. Neither AAV nor ERT therapy altered minute ventilation during quiet breathing (eupnea. However, breathing frequency and expiratory time were significantly improved in AAV9-DES animals. These results indicate systemic delivery of either strategy improves cardiac function but AAV9-DES alone improves respiratory parameters at 3 months post-treatment in a murine model of Pompe disease.

  3. Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

    Science.gov (United States)

    Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

    2014-11-01

    Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

  4. Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Christian Stevns; Hasbak, Philip

    2016-01-01

    Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM......). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

  5. Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

    DEFF Research Database (Denmark)

    Paul, David S; Grevengoed, Trisha J; Pascual, Florencia

    2014-01-01

    In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1(H-/-)), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy...... and B-type natriuretic peptide. mTOR activation of the related Acsl3 gene, usually associated with pathologic hypertrophy, was also attenuated in the Acsl1(H-/-) hearts, indicating that alternative pathways of fatty acid activation did not compensate for the loss of Acsl1. Compared to controls, Acsl1(H......-/-) hearts exhibited an 8-fold higher uptake of 2-deoxy[1-(14)C]glucose and a 35% lower uptake of the fatty acid analog 2-bromo[1-(14)C]palmitate. These data indicate that Acsl1-deficiency causes diastolic dysfunction and that mTOR activation is linked to the development of cardiac hypertrophy in Acsl1(H...

  6. Iron deficiency anemia and cognitive function in infancy.

    Science.gov (United States)

    Carter, R Colin; Jacobson, Joseph L; Burden, Matthew J; Armony-Sivan, Rinat; Dodge, Neil C; Angelilli, Mary Lu; Lozoff, Betsy; Jacobson, Sandra W

    2010-08-01

    This study examined effects of iron deficiency anemia (IDA) on specific domains of infant cognitive function and the role of IDA-related socioemotional deficits in mediating and/or moderating these effects. Infants were recruited during routine 9-month visits to an inner-city clinic. IDA was defined as hemoglobin level or =2 abnormal iron deficiency indicators (mean corpuscular volume, red cell distribution width, zinc protoporphyrin, transferrin saturation, and ferritin). At 9 and 12 months, the Fagan Test of Infant Intelligence (FTII); A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale were administered. Analyses were adjusted for potential confounders, including age and sociodemographic variables. Twenty-eight infants met criteria for IDA, 28 had nonanemic iron deficiency (NA ID) and 21 had iron sufficiency (IS). There was a linear effect for object permanence at 9 months: infants with IDA were least likely to exhibit object permanence, IS most likely, and NA ID intermediate. Infants with IDA and those with hemoglobin level object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months. These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function.

  7. Exercise improves cardiac autonomic function in obesity and diabetes.

    Science.gov (United States)

    Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

    2013-05-01

    Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Proangiogenic scaffolds as functional templates for cardiac tissue engineering

    OpenAIRE

    Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

    2010-01-01

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-s...

  9. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

  10. Novel axolotl cardiac function analysis method using magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Pedro Gomes Sanches

    Full Text Available The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a non-invasive technique to image heart function of axolotls. Three axolotls were imaged with magnetic resonance imaging using a retrospectively gated Fast Low Angle Shot cine sequence. Within one scanning session the axolotl heart was imaged three times in all planes, consecutively. Heart rate, ejection fraction, stroke volume and cardiac output were calculated using three techniques: (1 combined long-axis, (2 short-axis series, and (3 ultrasound (control for heart rate only. All values are presented as mean ± standard deviation. Heart rate (beats per minute among different animals was 32.2±6.0 (long axis, 30.4±5.5 (short axis and 32.7±4.9 (ultrasound and statistically similar regardless of the imaging method (p > 0.05. Ejection fraction (% was 59.6±10.8 (long axis and 48.1±11.3 (short axis and it differed significantly (p = 0.019. Stroke volume (μl/beat was 133.7±33.7 (long axis and 93.2±31.2 (short axis, also differed significantly (p = 0.015. Calculations were consistent among the animals and over three repeated measurements. The heart rate varied depending on depth of anaesthesia. We described a new method for defining and imaging the anatomical planes of the axolotl heart and propose one of our techniques (long axis analysis may prove useful in defining cardiac function in regenerating axolotl hearts.

  11. Pim-1 Kinase Phosphorylates Cardiac Troponin I and Regulates Cardiac Myofilament Function

    Directory of Open Access Journals (Sweden)

    Ni Zhu

    2018-03-01

    Full Text Available Background/Aims: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI, a key component in regulating myofilament function in the heart. Methods: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes. Biochemical, site directed mutagenesis, and mass spectrometric analyses were utilized to identify the phosphorylation sites of Pim1 in cTnI. Myofilament functional assay using skinned cardiac fiber was used to assess the effect of Pim1-mediated phosphorylation on cardiac myofilament activity. Lastly, the functional significance of Pim1-mediated cTnI in heart disease was determined in diabetic mice. Results: We found that Pim-1 specifically interacts with cTnI in cardiomyocytes and this interaction leads to Pim1-mediated cTnI phosphorylation, predominantly at Ser23/24 and Ser150. Furthermore, our functional assay demonstrated that Pim-1 induces a robust phosphorylation of cTnI within the troponin complex, thus leading to a decreased Ca2+ sensitivity. Insulin-like growth factor 1 (IGF-1, a peptide growth factor that has been shown to stimulate myocardial contractility, markedly induces cTnI phosphorylation at Ser23/24 and Ser150 through increasing Pim-1 expression in cardiomyocytes. In a high-fat diabetic mice model, the expression of Pim1 in the heart is significantly decreased, which is accompanied by a decreased phosphorylation of cTnI at Ser23/24 and Ser150, further implicating the pathological significance of the Pim1/cTnI axis in the development of diabetic cardiomyopathy. Conclusion: Our results demonstrate that Pim-1 is a

  12. Identification and functional characterization of cardiac pacemaker cells in zebrafish.

    Directory of Open Access Journals (Sweden)

    Federico Tessadori

    Full Text Available In the mammalian heart a conduction system of nodes and conducting cells generates and transduces the electrical signals evoking myocardial contractions. Specialized pacemaker cells initiating and controlling cardiac contraction rhythmicity are localized in an anatomically identifiable structure of myocardial origin, the sinus node. We previously showed that in mammalian embryos sinus node cells originate from cardiac progenitors expressing the transcription factors T-box transcription factor 3 (Tbx3 and Islet-1 (Isl1. Although cardiac development and function are strikingly conserved amongst animal classes, in lower vertebrates neither structural nor molecular distinguishable components of a conduction system have been identified, questioning its evolutionary origin. Here we show that zebrafish embryos lacking the LIM/homeodomain-containing transcription factor Isl1 display heart rate defects related to pacemaker dysfunction. Moreover, 3D reconstructions of gene expression patterns in the embryonic and adult zebrafish heart led us to uncover a previously unidentified, Isl1-positive and Tbx2b-positive region in the myocardium at the junction of the sinus venosus and atrium. Through their long interconnecting cellular protrusions the identified Isl1-positive cells form a ring-shaped structure. In vivo labeling of the Isl1-positive cells by transgenic technology allowed their isolation and electrophysiological characterization, revealing their unique pacemaker activity. In conclusion we demonstrate that Isl1-expressing cells, organized as a ring-shaped structure around the venous pole, hold the pacemaker function in the adult zebrafish heart. We have thereby identified an evolutionary conserved, structural and molecular distinguishable component of the cardiac conduction system in a lower vertebrate.

  13. 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Lifeng [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Zhou, Yong [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Yu, Shanhe [Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025 (China); Ji, Guixiang [Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042 (China); Wang, Lei [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Liu, Wei [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Gu, Aihua, E-mail: aihuagu@njmu.edu.cn [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China)

    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.

  14. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    International Nuclear Information System (INIS)

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J.

    1990-01-01

    Sites of uptake, storage, and metabolism of [ 18 F]fluorodopamine and excretion of [ 18 F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [ 18 F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [ 18 F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function

  15. Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

    Science.gov (United States)

    Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

    2010-08-24

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

  16. Functional capacity and mental state of patients undergoing cardiac surgery

    Directory of Open Access Journals (Sweden)

    Bruna Corrêa

    Full Text Available Abstract Introduction: Cardiovascular diseases are a serious public health problem in Brazil. Myocardial revascularization surgery (MRS as well as cardiac valve replacement and repair are procedures indicated to treat them. Thus, extracorporeal circulation (ECC is still widely used in these surgeries, in which patients with long ECC times may have greater neurological deficits. Neurological damage resulting from MRS can have devastating consequences such as loss of independence and worsening of quality of life. Objective: To assess the effect of cardiac surgery on a patient’s mental state and functional capacity in both the pre- and postoperative periods. Methods: We conducted a cross-sectional study with convenience sampling of subjects undergoing MRS and valve replacement. Participants were administered the Mini-Mental State Exam (MMSE and the Duke Activity Status Index (DASI in the pre- and postoperative periods, as well as before their hospital discharge. Results: This study assessed nine patients (eight males aged 62.4 ± 6.3 years with a BMI of 29.5 ± 2.3 kg/m2. There was a significant decrease in DASI scores and VO2 from preoperative to postoperative status (p = 0.003 and p = 0.003, respectively. Conclusion: This study revealed a loss of cognitive and exercise capacity after cardiac surgery. A larger sample however is needed to consolidate these findings.

  17. Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Helena U Westergren

    Full Text Available Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

  18. Deficiency of Smad7 enhances cardiac remodeling induced by angiotensin II infusion in a mouse model of hypertension.

    Directory of Open Access Journals (Sweden)

    Li Hua Wei

    Full Text Available Smad7 has been shown to negatively regulate fibrosis and inflammation, but its role in angiotensin II (Ang II-induced hypertensive cardiac remodeling remains unknown. Therefore, the present study investigated the role of Smad7 in hypertensive cardiopathy induced by angiotensin II infusion. Hypertensive cardiac disease was induced in Smad7 gene knockout (KO and wild-type (WT mice by subcutaneous infusion of Ang II (1.46 mg/kg/day for 28 days. Although equal levels of high blood pressure were developed in both Smad7 KO and WT mice, Smad7 KO mice developed more severe cardiac injury as demonstrated by impairing cardiac function including a significant increase in left ventricular (LV mass (P<0.01,reduction of LV ejection fraction(P<0.001 and fractional shortening(P<0.001. Real-time PCR, Western blot and immunohistochemistry detected that deletion of Smad7 significantly enhanced Ang II-induced cardiac fibrosis and inflammation, including upregulation of collagen I, α-SMA, interleukin-1β, TNF-α, and infiltration of CD3(+ T cells and F4/80(+ macrophages. Further studies revealed that enhanced activation of the Sp1-TGFβ/Smad3-NF-κB pathways and downregulation of miR-29 were mechanisms though which deletion of Smad7 promoted Ang II-mediated cardiac remodeling. In conclusions, Smad7 plays a protective role in AngII-mediated cardiac remodeling via mechanisms involving the Sp1-TGF-β/Smad3-NF.κB-miR-29 regulatory network.

  19. Effect of prolonged space flight on cardiac function and dimensions

    Science.gov (United States)

    Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

    1974-01-01

    Echocardiographic studies were performed preflight 5 days before launch and on recovery day and 1, 2, 4, 11, 31 and 68 days postflight. From these echocardiograms measurements were made. From these primary measurements, left ventricular end-diastolic volume, end-systolic volume, stroke volume, and mass were derived using the accepted assumptions. Findings in the Scientist Pilot and Pilot resemble those seen in trained distance runners. Wall thickness measurements were normal in all three crewmembers preflight. Postflight basal studies were unchanged in the Commander on recovery day through 68 days postflight in both the Scientist Pilot and Pilot, however, the left ventricular end-diastolic volume, stroke volume, and mass were decreased slightly. Left ventricular function curves were constructed for the Commander and Pilot by plotting stroke volume versus end-diastolic volume. In both astronauts, preflight and postflight data fell on the same straight line demonstrating that no deterioration in cardiac function had occurred. These data indicate that the cardiovascular system adapts well to prolonged weightlessness and suggest that alterations in cardiac dimensions and function are unlikely to limit man's future in space.

  20. Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death.

    Directory of Open Access Journals (Sweden)

    Ludger Hauck

    Full Text Available The maintenance of normal heart function requires proper control of protein turnover. The ubiquitin-proteasome system is a principal regulator of protein degradation. Mdm2 is the main E3 ubiquitin ligase for p53 in mitotic cells thereby regulating cellular growth, DNA repair, oxidative stress and apoptosis. However, which of these Mdm2-related activities are preserved in differentiated cardiomyocytes has yet to be determined. We sought to elucidate the role of Mdm2 in the control of normal heart function. We observed markedly reduced Mdm2 mRNA levels accompanied by highly elevated p53 protein expression in the hearts of wild type mice subjected to myocardial infarction or trans-aortic banding. Accordingly, we generated conditional cardiac-specific Mdm2 gene knockout (Mdm2f/f;mcm mice. In adulthood, Mdm2f/f;mcm mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction with early mortality post-tamoxifen. A decreased polyubiquitination of myocardial p53 was observed, leading to its stabilization and activation, in the absence of acute stress. In addition, transcriptomic analysis of Mdm2-deficient hearts revealed that there is an induction of E2f1 and c-Myc mRNA levels with reduced expression of the Pgc-1a/Ppara/Esrrb/g axis and Pink1. This was associated with a significant degree of cardiomyocyte apoptosis, and an inhibition of redox homeostasis and mitochondrial bioenergetics. All these processes are early, Mdm2-associated events and contribute to the development of pathological hypertrophy. Our genetic and biochemical data support a role for Mdm2 in cardiac growth control through the regulation of p53, the Pgc-1 family of transcriptional coactivators and the pivotal antioxidant Pink1.

  1. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    Science.gov (United States)

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. The effect of childhood obesity on cardiac functions.

    Science.gov (United States)

    Üner, Abdurrahman; Doğan, Murat; Epcacan, Zerrin; Epçaçan, Serdar

    2014-03-01

    Obesity is a metabolic disorder defined as excessive accumulation of body fat, which is made up of genetic, environmental, and hormonal factors and has various social, psychological, and medical complications. Childhood obesity is a major indicator of adult obesity. The aim of this study is to evaluate the cardiac functions via electrocardiography (ECG), echocardiography (ECHO), and treadmill test in childhood obesity. A patient group consisting of 30 obese children and a control group consisting of 30 non-obese children were included in the study. The age range was between 8 and 17 years. Anthropometric measurements, physical examination, ECG, ECHO, and treadmill test were done in all patients. P-wave dispersion (PD) was found to be statistically significantly high in obese patients. In ECHO analysis, we found that end-diastolic diameter, end-systolic diameter, left ventricle posterior wall thickness, and interventricular septum were significantly greater in obese children. In treadmill test, exercise capacity was found to be significantly lower and the hemodynamic response to exercise was found to be defective in obese children. Various cardiac structural and functional changes occur in childhood obesity and this condition includes important cardiovascular risks. PD, left ventricle end-systolic and end-diastolic diameter, left ventricle posterior wall thickness, interventricular septum thickness, exercise capacity, and hemodynamic and ECG measurements during exercise testing are useful tests to determine cardiac dysfunctions and potential arrhythmias even in early stages of childhood obesity. Early recognition and taking precautions for obesity during childhood is very important to intercept complications that will occur in adulthood.

  5. Cardiac structure and function and dependency in the oldest old.

    Science.gov (United States)

    Leibowitz, David; Jacobs, Jeremy M; Stessman-Lande, Irit; Cohen, Aharon; Gilon, Dan; Ein-Mor, Eliana; Stessman, Jochanan

    2011-08-01

    To examine the association between cardiac function and activities of daily living (ADLs) in an age-homogenous, community-dwelling population born in 1920 and 1921. Cross-sectional analysis of a prospective cohort study. Community-dwelling elderly population. Participants were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920 and 1921. Four hundred eighty-nine of the participants (228 male, 261 female) from the most recent set of data collection in 2005 and 2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. A home-based comprehensive assessment was performed to assess health and functional status, including performance of ADLs. Dependence was defined as needing assistance with one or more basic ADLs. Standard echocardiographic assessment of cardiac structure and function, including ejection fraction (EF) and diastolic function as assessed using early diastolic mitral annular tissue velocity measurements obtained using tissue Doppler, was performed. Of the participants with limitation in at least one ADL, significantly more had low EF (dependence in ADL had higher left ventricular mass index (LVMI) (129.3 vs 119.7 g/m²) and left atrial volume index (LAVI) (41.3 vs 36.7 mL/m²). There were no differences between the groups in percentage of participants with impaired diastolic function or average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (11.5 vs 11.8; P=.64). In this age-homogenous cohort of the oldest old, high LVMI and LAVI and indices of systolic but not diastolic function as assessed according to Doppler were associated with limitations in ADLs. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

  6. Baroreflex deficiency induces additional impairment of vagal tone, diastolic function and calcium handling proteins after myocardial infarction

    Science.gov (United States)

    Mostarda, Cristiano; Rodrigues, Bruno; Medeiros, Alessandra; Moreira, Edson D; Moraes-Silva, Ivana C; Brum, Patricia C; Angelis, Katia De; Irigoyen, Maria-Cláudia

    2014-01-01

    Baroreflex dysfunction has been considered an important mortality predictor after myocardial infarction (MI). However, the impact of baroreflex deficiency prior to MI on tonic autonomic control and cardiac function, and on the profile of proteins associated with intracellular calcium handling has not yet been studied. The aim of the present study was to analyze how the impairment of baroreflex induced by sinoaortic denervation (SAD) prior to MI in rats affects the tonic autonomic control, ventricular function and cardiomyocyte calcium handling proteins. After 15 days of following or SAD surgery, rats underwent MI. Echocardiographic, hemodynamic, autonomic and molecular evaluations were performed 90 days after MI. Baroreflex impairment led to additional damage on: left ventricular remodeling, diastolic function, vagal tonus and intrinsic heart rate after MI. The loss of vagal component of the arterial baroreflex and vagal tonus were correlated with changes in the cardiac proteins involved in intracellular calcium homeostasis. Furthermore, additional increase in sodium calcium exchanger expression levels was associated with impaired diastolic function in experimental animals. Our findings strongly suggest that previous arterial baroreflex deficiency may induce additional impairment of vagal tonus, which was associated with calcium handling proteins abnormalities, probably triggering ventricular diastolic dysfunction after MI in rats. PMID:24936224

  7. A structure-function analysis in patients with prekallikrein deficiency.

    Science.gov (United States)

    Girolami, Antonio; Ferrari, Silvia; Cosi, Elisabetta; Lombardi, Anna Maria

    2017-11-22

    To investigate the structure-function relation in prekallikrein (PK) deficiency. PK is one of the proteins of the contact phase of blood coagulation which at the present time is the object of a revival of interest. All patients with PK deficiency who had been investigated by molecular biology techniques are the object of the present investigation. Details of patients were obtained from personal files and a time-unlimited PubMed search. Only cases with a molecular-biology-based diagnosis were included. Twelve families were included. The total number of missense mutation was 10, together with 3 stop codons and 2 insertions. These mutations involved mainly exons 11 and 14. There were eight proved homozygotes and three compound heterozygotes. In one instance, homozygosity was probable but not proved. In nine cases, the defect was Type I, whereas it was Type II in the remaining three. No bleeding manifestations were present in 11 of the 12 probands. One proband had epistaxis, but she had hypertension. Altogether, four patients had hypertension and one of them had also two myocardial infarctions. Despite the paucity of cases, it was established that the majority of mutations involved the catalytic domain. It is auspicable that future reports of patients with this disorder should include molecular studies. This would certainly contribute to the understanding of the contact phase of blood coagulation.

  8. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    Science.gov (United States)

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

  9. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  10. Functional significance of cardiac reinnervation in heart transplant recipients.

    Science.gov (United States)

    Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C

    1999-09-01

    There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation

  11. Cardiac function adaptations in hibernating grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    Nelson, O Lynne; Robbins, Charles T

    2010-03-01

    Research on the cardiovascular physiology of hibernating mammals may provide insight into evolutionary adaptations; however, anesthesia used to handle wild animals may affect the cardiovascular parameters of interest. To overcome these potential biases, we investigated the functional cardiac phenotype of the hibernating grizzly bear (Ursus arctos horribilis) during the active, transitional and hibernating phases over a 4 year period in conscious rather than anesthetized bears. The bears were captive born and serially studied from the age of 5 months to 4 years. Heart rate was significantly different from active (82.6 +/- 7.7 beats/min) to hibernating states (17.8 +/- 2.8 beats/min). There was no difference from the active to the hibernating state in diastolic and stroke volume parameters or in left atrial area. Left ventricular volume:mass was significantly increased during hibernation indicating decreased ventricular mass. Ejection fraction of the left ventricle was not different between active and hibernating states. In contrast, total left atrial emptying fraction was significantly reduced during hibernation (17.8 +/- 2.8%) as compared to the active state (40.8 +/- 1.9%). Reduced atrial chamber function was also supported by reduced atrial contraction blood flow velocities and atrial contraction ejection fraction during hibernation; 7.1 +/- 2.8% as compared to 20.7 +/- 3% during the active state. Changes in the diastolic cardiac filling cycle, especially atrial chamber contribution to ventricular filling, appear to be the most prominent macroscopic functional change during hibernation. Thus, we propose that these changes in atrial chamber function constitute a major adaptation during hibernation which allows the myocardium to conserve energy, avoid chamber dilation and remain healthy during a period of extremely low heart rates. These findings will aid in rational approaches to identifying underlying molecular mechanisms.

  12. Oxidative Stress in Cardiac Mitochondria Caused by Copper Deficiency May Be Insufficient to Damage Mitochondrial Proteins

    Science.gov (United States)

    Copper (Cu) deficiency may promote the generation of reactive oxygen species (ROS) by the mitochondrial electron transport chain through inhibition of cytochrome c oxidase (CCO) and increased reduction of respiratory complexes upstream from CCO. In the present study, respiration, H2O2 production and...

  13. Cardiac structure and functions in patients with asymptomatic primary hyperparathyroidism.

    Science.gov (United States)

    Aktas Yılmaz, B; Akyel, A; Kan, E; Ercin, U; Tavil, Y; Bilgihan, A; Cakır, N; Arslan, M; Balos Toruner, F

    2013-11-01

    The data about cardiovascular (CV) changes in patients with asymptomatic primary hyperparathyroidism (PHPT) are scarce. The aim of this study is to compare cardiac structure and functions in patients with asymptomatic PHPT and controls by using tissue Doppler echocardiography. Thirty-eight patients with asymptomatic PHPT and 31 sex- and age-matched controls with similar cardiac risk factors were evaluated. There was no significant difference in ejection fraction (EF) between the patients and the controls [64±5.95 vs 62±3.25% (p=0.094)]. Left ventricular mass index (LVMI) was significantly higher in patients than controls [105.96 (66.45-167.24) vs 93.79 (64.25- 139.25) g/m2, p=0.014]. There was a significant correlation between LVMI and serum calcium (Ca) (r=0.240, p<0.005). Myocardial performance index (MPI) was significantly higher in patients than controls [0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.001]. There was positive correlation between theMPI and serumCa levels (r=0.505, p<0.001), parathyroid hormone (PTH) levels (r=0.464, p<0.001) and LVMI (r=0.270, p<0.005). When the normotensive patients and controls were evaluated, the difference between the groups remained statistically significant considering LVMI and MPI [109 (66.45-167.24) g/m2 vs 94.17 (64.25-75.10) g/m2, p=0.03; and 0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.01, respectively]. There were significant correlations between MPI and Ca (r=0.566, p<0.001), and PTH (r=0.472, p<0.001). Our study results showed that cardiacmorphology and diastolic functions are altered in the patients with asymptomatic PHPT. High serum PTH and Ca levels may have an impact on these CV changes. Whether these subtle CV changes would affect cardiac systolic functions and mortality in patients with asymptomatic PHPT should be investigated in further prospective studies.

  14. Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function

    Science.gov (United States)

    Beaumont, Eric; Salavatian, Siamak; Southerland, E Marie; Vinet, Alain; Jacquemet, Vincent; Armour, J Andrew; Ardell, Jeffrey L

    2013-01-01

    The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias. PMID:23818689

  15. Sex differences in cardiac function after prolonged strenuous exercise.

    Science.gov (United States)

    Cote, Anita T; Phillips, Aaron A; Foulds, Heather J; Charlesworth, Sarah A; Bredin, Shannon S D; Burr, Jamie F; Koehle, Michael S; Warburton, Darren E R

    2015-05-01

    To evaluate sex differences in left ventricular (LV) function after an ultramarathon, and the association of vascular and training indices with the magnitude of exercise-induced cardiac fatigue. Descriptive field study. Fat Dog 100 Ultramarathon Trail Race, Canada. Thirty-four (13 women) recreational runners (aged 28-56 years). A 100-km or 160-km mountain marathon. Baseline baroreceptor sensitivity, heart rate variability, and arterial compliance; Pre-exercise and postexercise echocardiographic evaluations of LV dimensions, volumes, Doppler flow velocities, tissue velocities, strain, and strain rate. Finishers represented 17 men (44.8 ± 6.6 years) and 8 women (45.9 ± 10.2 years; P = 0.758). After ultraendurance exercise, significant reductions (P training status/experience. These findings suggest that vascular health is an important contributor to the degree of cardiovascular strain incurred as the result of an acute bout of prolonged strenuous exercise.

  16. Cardiac diastolic function after recovery from pre-eclampsia.

    Science.gov (United States)

    Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

    Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

  17. Functional consequences of iron deficiency in Chinese female workers

    NARCIS (Netherlands)

    Li, R.

    1993-01-01

    Women of the reproductive age in China play a very important role in the labour force. Information on anaemia prevalence in this group is hardly available, notwithstanding the fact that iron deficiency anaemia is considered to be a major public health problem in China. Iron deficiency may

  18. Chronic zinc deficiency alters chick gut microbiota composition and function

    Science.gov (United States)

    Zinc (Zn) deficiency is a prevalent micronutrient insufficiency. Although the gut is a vital organ for Zn utilization, and Zn deficiency is associated with impaired intestinal permeability and a global decrease in gastrointestinal health, alterations in the gut microbial ecology of the host under co...

  19. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    Directory of Open Access Journals (Sweden)

    Fabricio Furtado Vieira

    Full Text Available Abstract Background: Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX in the cardiac muscle. Objectives: To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. Methods: We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt and relaxation (-df/dt, contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP, and contraction force induced by caffeine. Results: In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05, increased +df/dt and -df/dt (p < 0.001, low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001, reduction of the maximum force in caffeine-induced contraction (p < 0.003, and decreased total contraction time (p < 0.001. The maximal contraction force did not differ significantly between groups (p = 0.973. Conclusion: We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  20. Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

    Science.gov (United States)

    Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

    2009-01-01

    The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.

  1. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats.

    Science.gov (United States)

    Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; Silva, Priscyla Oliveira da; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

    2016-12-01

    Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  2. Relationship between cardiac function and resting cerebral blood flow

    DEFF Research Database (Denmark)

    Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja

    2014-01-01

    ) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P...... = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed...

  3. Interoception across modalities: on the relationship between cardiac awareness and the sensitivity for gastric functions.

    Directory of Open Access Journals (Sweden)

    Beate M Herbert

    Full Text Available The individual sensitivity for ones internal bodily signals ("interoceptive awareness" has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals ("cardiac awareness" which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality.

  4. Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization after Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Leela K Lella

    Full Text Available The significance of right ventricular ejection fraction (RVEF, independent of left ventricular ejection fraction (LVEF, following isolated coronary artery bypass grafting (CABG and valve procedures remains unknown. The aim of this study is to examine the significance of abnormal RVEF by cardiac magnetic resonance (CMR, independent of LVEF in predicting outcomes of patients undergoing isolated CABG and valve surgery.From 2007 to 2009, 109 consecutive patients (mean age, 66 years; 38% female were referred for pre-operative CMR. Abnormal RVEF and LVEF were considered 30 days outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months.Forty-eight patients had reduced RVEF (mean 25% and 61 patients had normal RVEF (mean 50% (p<0.001. Fifty-four patients had reduced LVEF (mean 30% and 55 patients had normal LVEF (mean 59% (p<0.001. Patients with reduced RVEF had a higher incidence of long-term cardiac re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05. Abnormal RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5-7.9], p<0.03. Reduced LVEF did not influence long-term cardiac re-hospitalization.Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures.

  5. Spironolactone in chronic hemodialysis patients improves cardiac function

    International Nuclear Information System (INIS)

    Taheri, Shahram; Mortazavi, Mojhgan; Shahidi Shahrzad; Seirafian, Shiva; Pourmoghadas, Ali; Garakyaraghi, Mohammad; Eshaghian, Afrooz; Ghassami, Maryam

    2009-01-01

    We performed this study to assess whether low dose spironolactone could be administered in hemodialysis (HD) patients with moderate to severe heart failure to improve cardiovascular function and reduce hospitalization without inducing hyperkalemia. We enrolled 16 chronic HD patients with moderate to severe heart failure and left ventricle ejection fraction :5 45%. In a double blinded randomized placebo controlled study, one group of 8 patients received 25 mg of spironolactone after each dialysis session within six months, and the rest received a placebo. Echocardiography was performed on all the patients to assess ejection fraction and left ventricular mass during 12 hours after completion of hemodialysis at the beginning and the end of study. Serum potassium was measured predialysis every 4 weeks. The mean ejection fraction increased significantly more in spironolactone group during the study period than in the placebo group (6.2 + - 1.64 vs. 0.83 + - 4.9, P0.046). The mean left ventricular mass decreased in the spironolactone group, but increased significantly in the placebo group during the period (-8.4 + - 4.72 vs. 3 + -7.97. 95%, P= 0.021). The incidence of hyperkalemia was not significantly increased in the study or controlled groups. In conclusion, we found in this study that administration of spironolactone in chronic HD patients with moderate to severe heart failure substantially improved their cardiac function and decreases left ventricular mass without development of significant hyperkalemia. (author)

  6. Sodium Channel (Dys)Function and Cardiac Arrhythmias

    NARCIS (Netherlands)

    Remme, Carol Ann; Bezzina, Connie R.

    2010-01-01

    P>Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation

  7. Evaluation of the cardiac efficiency by means of functional radiocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Scheibe, J; Stoll, W [Friedrich-Schiller-Universitaet, Jena (German Democratic Republic). Bereich Medizin

    1982-01-01

    A new method of evaluating the cardiac efficiency by means of radiocardiography performed on exertion with /sup 113m/InCl is reported. Analysis of stroke volume, end diastolic volume and of the quotient of cardiac output to end diastolic volume on exertion enables an adequate evaluation of the actual myocardial efficiency.

  8. Electron transfer flavoprotein deficiency: Functional and molecular aspects

    DEFF Research Database (Denmark)

    Schiff, M; Froissart, R; Olsen, Rikke Katrine Jentoft

    2006-01-01

    Multiple acyl-CoA dehydrogenase deficiency (MADD) is a recessively inherited metabolic disorder that can be due to a deficiency of electron transfer flavoprotein (ETF) or its dehydrogenase (ETF-ubiquinone oxidoreductase). ETF is a mitochondrial matrix protein consisting of alpha- (30kDa) and beta......- (28kDa) subunits encoded by the ETFA and ETFB genes, respectively. In the present study, we have analysed tissue samples from 16 unrelated patients with ETF deficiency, and we report the results of ETF activity, Western blot analysis and mutation analysis. The ETF assay provides a reliable diagnostic...... tool to confirm ETF deficiency in patients suspected to suffer from MADD. Activity ranged from less than 1 to 16% of controls with the most severely affected patients disclosing the lowest activity values. The majority of patients had mutations in the ETFA gene while only two of them harboured...

  9. ABC of the cardiac magnetic resonance. Part 1: anatomy and function

    International Nuclear Information System (INIS)

    Loureiro, Ricardo; Rached, Heron; Castro, Claudio C.; Cerri, Giovanni G.; Favaro, Daniele; Baptista, Luciana; Andrade, Joalbo; Rochitte, Carlos E.; Parga Filho, Jose; Avila, Luiz F.; Piva, Rosa M.V.

    2003-01-01

    The objective of this work is to demonstrate the fundamental concepts, the basic sequences and the clinical and potential applications of cardiac magnetic resonance as a diagnostic technique in updated radiology and cardiology practices. In this first part, we present the basic planning of the cardiac image acquisition, the nomenclature and standardized myocardial segmentation, image synchronization principles for electrocardiogram and the heart functional and anatomical evaluation by cardiac magnetic resonance. (author)

  10. Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

    Science.gov (United States)

    Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

    2014-11-01

    Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  11. The effects of levosimendan in cardiac surgery patients with poor left ventricular function

    NARCIS (Netherlands)

    de Hert, Stefan G.; Lorsomradee, Suraphong; Cromheecke, Stefanie; van der Linden, Philippe J.

    2007-01-01

    BACKGROUND: Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely

  12. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

    Science.gov (United States)

    O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

    2014-01-01

    Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

  13. Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

    Science.gov (United States)

    Grimes, Kelly M; Voorhees, Andrew; Chiao, Ying Ann; Han, Hai-Chao; Lindsey, Merry L; Buffenstein, Rochelle

    2014-03-01

    The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope. Echocardiography showed that young (2-4 yr old) healthy NMRs have low fractional shortening (28 ± 2%), ejection fraction (43 ± 2%), and cardiac output (6.5 ± 0.4 ml/min), indicating low basal cardiac function. Histology revealed large NMR cardiomyocyte cross-sectional area (216 ± 10 μm(2)) and cardiac collagen deposition of 2.2 ± 0.4%. Neither of these histomorphometric traits was considered pathological, since biaxial tensile testing showed no increase in passive ventricular stiffness. NMR cardiomyocyte fibers showed a low degree of rotation, contributing to the observed low NMR cardiac contractility. Interestingly, when the exercise mimetic dobutamine (3 μg/g ip) was administered, NMRs showed pronounced increases in fractional shortening, ejection fraction, cardiac output, and stroke volume, indicating an increased cardiac reserve. The relatively low basal cardiac function and enhanced cardiac reserve of NMRs are likely to be ecophysiological adaptations to life in an energetically taxing environment.

  14. New developments in paediatric cardiac functional ultrasound imaging.

    Science.gov (United States)

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

    2014-07-01

    Ultrasound imaging can be used to estimate the morphology as well as the motion and deformation of tissues. If the interrogated tissue is actively deforming, this deformation is directly related to its function and quantification of this deformation is normally referred as 'strain imaging'. Tissue can also be deformed by applying an internal or external force and the resulting, induced deformation is a function of the mechanical tissue characteristics. In combination with the load applied, these strain maps can be used to estimate or reconstruct the mechanical properties of tissue. This technique was named 'elastography' by Ophir et al. in 1991. Elastography can be used for atherosclerotic plaque characterisation, while the contractility of the heart or skeletal muscles can be assessed with strain imaging. Rather than using the conventional video format (DICOM) image information, radio frequency (RF)-based ultrasound methods enable estimation of the deformation at higher resolution and with higher precision than commercial methods using Doppler (tissue Doppler imaging) or video image data (2D speckle tracking methods). However, the improvement in accuracy is mainly achieved when measuring strain along the ultrasound beam direction, so it has to be considered a 1D technique. Recently, this method has been extended to multiple directions and precision further improved by using spatial compounding of data acquired at multiple beam steered angles. Using similar techniques, the blood velocity and flow can be determined. RF-based techniques are also beneficial for automated segmentation of the ventricular cavities. In this paper, new developments in different techniques of quantifying cardiac function by strain imaging, automated segmentation, and methods of performing blood flow imaging are reviewed and their application in paediatric cardiology is discussed.

  15. Multi-Functions of Carbonated Calcium Deficient Hydroxyapatite (CDHA)

    Science.gov (United States)

    Zhou, Huan

    Natural bone is a complex composite mainly constituted of inorganic minerals and organic collagen molecules. Calcium phosphate (CaP) based materials have been proposed as the predominant bone substitute for bone tissue engineering applications due to their chemical similarity to bone mineral. Amorphous carbonated calcium deficient hydroxyapatite (CDHA) is an important compound among CaP materials because of the amorphous crystallite structure. The presence of extra ions in its lattice structure not only influences cell attachment and proliferation of osteoblasts, but also helps in bone metabolism. Biomimetic coating approach is the most widely used approach to produce CDHA coatings to implant. It is a process using simulated body fluid (SBF) to deposit bone-like CDHA coating to various material surfaces. The CDHA formation mechanism, SBF compositions and reacting conditions of biomimetic coating have already been sufficiently studied and compared in the past 20 years. It is an attempt in this thesis to explore new applications of SBF in biomedical research, focusing on different biomaterial applications: 1) based on the low temperature reaction condition of SBF, bisphosphonate incorporated CDHA coatings were deposited onto Ti6Al4V surface for the treatment of osteoporosis; 2) amorphous calcium phosphate nanospheres with extra elements in the lattice structure were prepared by a novel microwave assisted approach, providing a new potential of CaP materials production; 3) CDHA particles formed in SBF can be used as great fillers with biopolymers for preparing biocomposites for biomedical applications; 4) based on the high activity of CDHA amorphous structure and the stabilization ability of ethanol, yttrium and europium doped calcium phosphates were prepared using CDHA as a sacrificing template. In the end, future work based on these observations in the thesis is addressed, including areas of drug delivery, biocomposite fabrication and preparation of functionalized

  16. Changes of cardiac function in hyperthyroidism and hypothyroidism

    International Nuclear Information System (INIS)

    Morishita, Takeshi; Kawamura, Yasuaki; Yamazaki, Junichi; Okuzumi, Ichio; Muto, Toshinori; Wakakura, Manabu; Okamoto, Kiyoshi; Irie, Minoru; Inoue, Kazuko.

    1988-01-01

    Changes of cardiac parameters in patients with 21 hyperthyroidisms and 11 primary hypothyroidisms were studied administered by methimazole or 1-thyroxine using radionuclide method. In hyperthyroidisms, cardiac parameter (CI, EF, PEP/LVET, PEP) normalized 4 - 6 week delayed compared with hormonal level (T 3 , T 4 ) recovery period. On the other hand, in hypothyroidism PEP/LVET delayed about 2 weeks compared with hormonal level, however, other cardiac parameters were maintained within normal level, relatively. Correlation between T 3 and LVET was significant statistically (r = -0.59, p 3 and PEP was significant (r = -0.60, p < 0.01) in hypothyroidisms, respectively. (author)

  17. Evaluation of cardiac functions in patients with thalassemia major

    International Nuclear Information System (INIS)

    Kucuk, N.O.; Aras, G.; Sipahi, T.; Ibis, E.; Akar, N.; Soylu, A.; Erbay, G.

    1999-01-01

    It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV). Twenty-one patients at ages 9-16 (mean 12.1±3.2) who have been diagnosed with thalassemia for 4-15 years mean 12.7±4.8) were included in the study. They had blood transfusion 78-318 times (mean 162.1±71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p<0.05). We conclude that ischemia or fixed defects may be seen in stress MPS as results of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up. (author)

  18. Evaluation of cardiac functions in patients with thalassemia major

    Energy Technology Data Exchange (ETDEWEB)

    Kucuk, N.O.; Aras, G.; Sipahi, T.; Ibis, E.; Akar, N.; Soylu, A.; Erbay, G. [Ankara Univ. (Turkey). Medical School

    1999-06-01

    It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV). Twenty-one patients at ages 9-16 (mean 12.1{+-}3.2) who have been diagnosed with thalassemia for 4-15 years mean 12.7{+-}4.8) were included in the study. They had blood transfusion 78-318 times (mean 162.1{+-}71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p<0.05). We conclude that ischemia or fixed defects may be seen in stress MPS as results of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up. (author)

  19. Cardiac Function in 7-8-Year-Old Offspring of Women with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Maarten Rijpert

    2011-01-01

    Full Text Available Offspring of type 1 diabetic mothers (ODMs are at risk of short-term and long-term complications, such as neonatal macrosomia (birth weight >90th percentile, hypertrophic cardiomyopathy, and cardiovascular morbidity in later life. However, no studies have been performed regarding cardiac outcome. In this study, we investigated cardiac dimensions and function in 30 ODMs at 7-8 years of age in relation to neonatal macrosomia and maternal glycemic control during pregnancy and compared these with those in a control group of 30 children of nondiabetic women. We found that cardiac dimensions and systolic and diastolic function parameters in ODMs were comparable with those in controls. Neonatal macrosomia and poorer maternal glycemic control during pregnancy were not related to worse cardiac outcome in ODM. We conclude that cardiac function at 7-8 years of age in offspring of women with type 1 diabetes is reassuring and comparable with that in controls.

  20. Assessment of Cardiac Function in Fetuses of Gestational Diabetic Mothers During the Second Trimester.

    Science.gov (United States)

    Atiq, Mehnaz; Ikram, Anum; Hussain, Batool M; Saleem, Bakhtawar

    2017-06-01

    Fetuses of diabetic mothers may have structural or functional cardiac abnormalities which increase morbidity and mortality. Isolated functional abnormalities have been identified in the third trimester. The aim of the present study was to assess fetal cardiac function (systolic, diastolic, and global myocardial performance) in the second trimester in mothers with gestational diabetes, and also to relate cardiac function with glycemic control. Mothers with gestational diabetes mellitus referred for fetal cardiac evaluation in the second trimester (between 19 and 24 weeks) from March 2015 to February 2016 were enrolled as case subjects in this study. Non-diabetic mothers who had a fetal echocardiogram done between 19 and 24 weeks for other indications were enrolled as controls. Functional cardiac variables showed a statistically significant difference in isovolumetric relaxation and contraction times and the myocardial performance index and mitral E/A ratios in the gestational diabetic group (p = 0.003). Mitral annular plane systolic excursion was significantly less in the diabetic group (p = 0.01). The only functional cardiac variable found abnormal in mothers with poor glycemic control was the prolonged isovolumetric relaxation time. Functional cardiac abnormalities can be detected in the second trimester in fetuses of gestational diabetic mothers and timely intervention can improve postnatal outcomes.

  1. Assessment of cardiac neuronal function with iodine-123 MIBG scintigraphy in children with idiopathic dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Ch.; Sebahoun, St.; Hallaj, I.; Barritault, L.; Acar, Ph.; Sidi, D.; Kachaner, J.; Agostini, D.; Bouvard, G.

    2000-01-01

    The I-123 MIBG cardiac scintigraphy can assess norepinephrine uptake. It has been showed that cardiac adrenergic neuronal function was impaired in adults with dilated cardiomyopathy. The aim of this prospective study was to assess cardiac neuronal function in children with idiopathic dilated cardiomyopathy (DCM) and to compare cardiac uptake of I-123 MIBG with left ventricular ejection fraction (LVEF). We studied 26 consecutive patients with idiopathic DCM, aged 44 ± 50 months, and 12 controls, aged 49 ±65 months. A planar scintigraphy was performed in all children 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. A static anterior view was acquired for 10 minutes. Cardiac uptake of I-123 MIBG was expressed as the heart to mediastinum count ratio (HMR). Equilibrium radionuclide angiography was performed following a standard protocol. Cardiac uptake of I-123 MIBG was significantly decreased in patients with idiopathic DCM when compared with cardiac uptake in controls (172±34% vs 277±14%, P<0.0001. There was a good correlation between RCM and LVEF in patients with idiopathic DCM (y = 2.5 x +113.3, r = 0.80, P < 0.0001). In conclusion, cardiac neuronal function was impaired in children with idiopathic DCM and related to impairment of left ventricular function. (author)

  2. Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

    International Nuclear Information System (INIS)

    Fiechter, Michael; Gaemperli, Oliver; Kaufmann, Philipp A; Fuchs, Tobias A; Gebhard, Catherine; Stehli, Julia; Klaeser, Bernd; Stähli, Barbara E; Manka, Robert; Manes, Costantina; Tanner, Felix C

    2013-01-01

    The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20–29, 30–49, 50–69, and ≥70 years) and cardiac measurements were compared using Pearson’s rank correlation over the four different groups. With advanced age a slight but significant decrease in ESV (r=−0.41 for both ventricles, P<0.001) and EDV (r=−0.39 for left ventricle, r=−0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies

  3. Inhalation of Simulated Smog Atmospheres Affects Cardiac Function in Mice

    Science.gov (United States)

    The health effects of individual criteria air pollutants have been well investigated. However, little is known about the health effects of air pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the cardiac eff...

  4. Chronic Cardiac-Targeted RNA Interference for the Treatment of Heart Failure Restores Cardiac Function and Reduces Pathological Hypertrophy

    Science.gov (United States)

    Suckau, Lennart; Fechner, Henry; Chemaly, Elie; Krohn, Stefanie; Hadri, Lahouaria; Kockskämper, Jens; Westermann, Dirk; Bisping, Egbert; Ly, Hung; Wang, Xiaomin; Kawase, Yoshiaki; Chen, Jiqiu; Liang, Lifan; Sipo, Isaac; Vetter, Roland; Weger, Stefan; Kurreck, Jens; Erdmann, Volker; Tschope, Carsten; Pieske, Burkert; Lebeche, Djamel; Schultheiss, Heinz-Peter; Hajjar, Roger J.; Poller, Wolfgang Ch.

    2009-01-01

    Background RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. We report on targeted RNAi for the treatment of heart failure (HF), an important disorder in humans resulting from multiple etiologies. Successful treatment of HF is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban (PLB), a key regulator of cardiac Ca2+ homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy employs regulatory RNAs to achieve its effect. Methods and Results We describe structural requirements to obtain high RNAi activity from adenoviral (AdV) and adeno-associated virus (AAV9) vectors and show that an AdV short hairpin RNA vector (AdV-shRNA) silenced PLB in cardiomyocytes (NRCMs) and improved hemodynamics in HF rats 1 month after aortic root injection. For simplified long-term therapy we developed a dimeric cardiotropic AAV vector (rAAV9-shPLB) delivering RNAi activity to the heart via intravenous injection. Cardiac PLB protein was reduced to 25% and SERCA2a suppression in the HF groups was rescued. In contrast to traditional vectors rAAV9 shows high affinity for myocardium, but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (LVEDP, dp/dtmin, Tau) and systolic (fractional shortening) functional parameters to normal range. The massive cardiac dilation was normalized and the cardiac hypertrophy, cardiomyocyte diameter and cardiac fibrosis significantly reduced. Importantly, there was no evidence of microRNA deregulation or hepatotoxicity during these RNAi therapies. Conclusion Our data show, for the first time, high efficacy of an RNAi therapeutic strategy in a cardiac disease. PMID:19237664

  5. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

    DEFF Research Database (Denmark)

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva

    2011-01-01

    better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

  6. Functional Significance of Iron Deficiency. Annual Nutrition Workshop Series, Volume III.

    Science.gov (United States)

    Enwonwu, Cyril O., Ed.

    Iron deficiency anemia impairs cognitive performance, physical capacity, and thermoregulation. Recent evidence suggests that these functional impairments are also evident in subclinical nonanemic iron deficiency. Very little is known about the relevance of the latter to the health of blacks, who have been shown to have the highest prevalence of…

  7. Marginal Iodide Deficiency and Thyroid Function: Dose-response analysis for quantitative pharmacokinetic modeling

    Science.gov (United States)

    Severe iodine deficiency is known to cause adverse health outcomes and remains a benchmark for understanding the effects of hypothyroidism. However, the implications of marginal iodine deficiency on function of the thyroid axis remain less well known. The current study examined t...

  8. Children with congenital deficiencies or acquired amputations of the lower limbs : functional aspects

    NARCIS (Netherlands)

    Boonstra, AM; Rijnders, LJM; Groothoff, J W; Eisma, W H

    The aim of the study was to evaluate the use of prostheses, some secondary complications and functional aspects among children who had a congenital leg deficiency or an acquired leg amputation. Rehabilitation physicians were asked to refer children, aged 1-18 years, with a leg deficiency or

  9. Immune function during GH treatment in GH-deficient adults

    DEFF Research Database (Denmark)

    Sneppen, S B; Mersebach, H; Ullum, H

    2002-01-01

    investigated were unaltered. CONCLUSIONS: GH deficiency was associated with changes in lymphocyte subsets and impaired unstimulated and stimulated natural killer cell activity, but these remained abnormal during 18 months of GH replacement therapy. Extra-pituitary GH gene expression in, e.g. lymphoid tissues...

  10. Iodine deficiency and functional performance of schoolchildren in Benin

    NARCIS (Netherlands)

    Briel-van Ingen, van den T.

    2001-01-01

    The notion that iodine deficiency may lead not only to goiter and cretinism, but to a much wider range of disorders, from stillbirth and abortions, to hearing problems and mental and physical underdevelopment began to be accepted beyond the research community since the early 1980's. In 1990 it was

  11. Fermitins, the orthologs of mammalian Kindlins, regulate the development of a functional cardiac syncytium in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    James H Catterson

    Full Text Available The vertebrate Kindlins are an evolutionarily conserved family of proteins critical for integrin signalling and cell adhesion. Kindlin-2 (KIND2 is associated with intercalated discs in mice, suggesting a role in cardiac syncytium development; however, deficiency of Kind2 leads to embryonic lethality. Morpholino knock-down of Kind2 in zebrafish has a pleiotropic effect on development that includes the heart. It therefore remains unclear whether cardiomyocyte Kind2 expression is required for cardiomyocyte junction formation and the development of normal cardiac function. To address this question, the expression of Fermitin 1 and Fermitin 2 (Fit1, Fit2, the two Drosophila orthologs of Kind2, was silenced in Drosophila cardiomyocytes. Heart development was assessed in adult flies by immunological methods and videomicroscopy. Silencing both Fit1 and Fit2 led to a severe cardiomyopathy characterised by the failure of cardiomyocytes to develop as a functional syncytium and loss of synchrony between cardiomyocytes. A null allele of Fit1 was generated but this had no impact on the heart. Similarly, the silencing of Fit2 failed to affect heart function. In contrast, the silencing of Fit2 in the cardiomyocytes of Fit1 null flies disrupted syncytium development, leading to severe cardiomyopathy. The data definitively demonstrate a role for Fermitins in the development of a functional cardiac syncytium in Drosophila. The findings also show that the Fermitins can functionally compensate for each other in order to control syncytium development. These findings support the concept that abnormalities in cardiomyocyte KIND2 expression or function may contribute to cardiomyopathies in humans.

  12. Myocardin-related transcription factors are required for cardiac development and function

    Science.gov (United States)

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2016-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

  13. Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

    Science.gov (United States)

    Barton, Gregory P; Vildberg, Lauren; Goss, Kara; Aggarwal, Niti; Eldridge, Marlowe; McMillan, Alan B

    2018-05-01

    Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model. Following an overnight fast, healthy pigs (45-50 kg) were anesthetized and mechanically ventilated. 18 F-fluorodeoxyglucose ( 18 F-FDG) solution was administered intravenously at a constant rate of 0.01 mL/s for 60 minutes. A cardiac PET/MR stress test was performed using normoxic gas (F I O 2  = .209) and hypoxic gas (F I O 2  = .12). Simultaneous cardiac imaging was performed on an integrated 3T PET/MR scanner. Hypoxic stress induced a significant increase in heart rate, cardiac output, left ventricular (LV) ejection fraction (EF), and peak torsion. There was a significant decline in arterial SpO 2 , LV end-diastolic and end-systolic volumes in hypoxia. Increased LV systolic function was coupled with an increase in myocardial FDG uptake (Ki) during hypoxic stress. PET/MR with continuous FDG infusion captures dynamic changes in both cardiac metabolism and contractile function. This technique warrants evaluation in human cardiac disease for assessment of subtle functional and metabolic abnormalities.

  14. Functional Relevance of Coronary Artery Disease by Cardiac Magnetic Resonance and Cardiac Computed Tomography: Myocardial Perfusion and Fractional Flow Reserve

    Directory of Open Access Journals (Sweden)

    Gianluca Pontone

    2015-01-01

    Full Text Available Coronary artery disease (CAD is one of the leading causes of morbidity and mortality and it is responsible for an increasing resource burden. The identification of patients at high risk for adverse events is crucial to select those who will receive the greatest benefit from revascularization. To this aim, several non-invasive functional imaging modalities are usually used as gatekeeper to invasive coronary angiography, but the diagnostic yield of elective invasive coronary angiography remains unfortunately low. Stress myocardial perfusion imaging by cardiac magnetic resonance (stress-CMR has emerged as an accurate technique for diagnosis and prognostic stratification of the patients with known or suspected CAD thanks to high spatial and temporal resolution, absence of ionizing radiation, and the multiparametric value including the assessment of cardiac anatomy, function, and viability. On the other side, cardiac computed tomography (CCT has emerged as unique technique providing coronary arteries anatomy and more recently, due to the introduction of stress-CCT and noninvasive fractional flow reserve (FFR-CT, functional relevance of CAD in a single shot scan. The current review evaluates the technical aspects and clinical experience of stress-CMR and CCT in the evaluation of functional relevance of CAD discussing the strength and weakness of each approach.

  15. Nebivolol: impact on cardiac and endothelial function and clinical utility

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2012-03-01

    Full Text Available Jorge Eduardo Toblli1, Federico DiGennaro1, Jorge Fernando Giani2, Fernando Pablo Dominici21Hospital Aleman, 2Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, Facultad de Farmacia y Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with

  16. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

  17. Effect of Cardiac Rehabilitation on Heart Rate and Functional Capacity in Patients After Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Mandana Parvand

    2016-09-01

    Discussion: Cardiac rehabilitation can increase the performance of blood circulation and uptake of oxygen in body. Due to these changes, there was a significant increase in the functional capacity and an insignificant reduction in the heart rate.

  18. Functions of PDE3 Isoforms in Cardiac Muscle

    Science.gov (United States)

    Movsesian, Matthew; Ahmad, Faiyaz

    2018-01-01

    Isoforms in the PDE3 family of cyclic nucleotide phosphodiesterases have important roles in cyclic nucleotide-mediated signalling in cardiac myocytes. These enzymes are targeted by inhibitors used to increase contractility in patients with heart failure, with a combination of beneficial and adverse effects on clinical outcomes. This review covers relevant aspects of the molecular biology of the isoforms that have been identified in cardiac myocytes; the roles of these enzymes in modulating cAMP-mediated signalling and the processes mediated thereby; and the potential for targeting these enzymes to improve the profile of clinical responses. PMID:29415428

  19. Comparative Toxicity of Different Crude Oils on the Cardiac Function of Marine Medaka (Oryzias melastigma Embryo

    Directory of Open Access Journals (Sweden)

    Zhendong Zhang

    2014-12-01

    Full Text Available The acute toxic effect of different crude oils (heavy crude oil and bonny light crude oil on embryos of marine medaka Oryzias melastigma was measured and evaluated by exposure to the water-accommodated fraction (WAF in the present study. The cardiac function of medaka embryos was used as target organ of ecotoxicological effect induced by oil exposure. Results showed that the developing marine medaka heart was a sensitive target organ to crude oil exposure the heavy crude oil WAF was more toxic to cardiac function of medaka embryos than bonny light cured oil one. Cardiac function of medaka embryos was clearly affected by exposure to heavy crude oil WAF after 24 hours exposure and showed a dose-dependent slowing of heart rate. Furthermore, swelled and enlarged heart morphology, lowered blood circulation and accumulation of blood cells around the heart area were found. However, the toxic effect of bonny light crude oil on cardiac function of medaka embryos was comparatively low. Statistical results showed that the cardiac function was only affected by highest bonny light crude oil WAF (9.8 mg/L exposure treatment. These findings indicated that cardiac function of marine medaka embryo was a good toxicity model for oil pollution and could be used to compare and evaluate the toxicity of different crude oils. The heart rate was an appropriate endpoint in the acute toxicity test.

  20. A portable cadmium telluride multidetector probe for cardiac function monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B. E-mail: eclan@alsace.u-strasbg.fr; Prat, V

    1999-06-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5x5x2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients.

  1. A portable cadmium telluride multidetector probe for cardiac function monitoring

    International Nuclear Information System (INIS)

    Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B.; Prat, V.

    1999-01-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5x5x2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients

  2. IGF-I replacement therapy in children with congenital IGF-I deficiency (Laron syndrome) maintains heart dimension and function.

    Science.gov (United States)

    Scheinowitz, Mickey; Feinberg, Micha S; Laron, Zvi

    2009-06-01

    Untreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy. Two to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients, mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg, and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/-33.1cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group. Left ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean. IGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.

  3. Cardiac structure and function predicts functional decline in the oldest old.

    Science.gov (United States)

    Leibowitz, David; Jacobs, Jeremy M; Lande-Stessman, Irit; Gilon, Dan; Stessman, Jochanan

    2018-02-01

    Background This study examined the association between cardiac structure and function and the deterioration in activities of daily living (ADLs) in an age-homogenous, community-dwelling population of patients born in 1920-1921 over a five-year follow-up period. Design Longitudinal cohort study. Methods Patients were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920-1921. Patients underwent home echocardiography and were followed up for five years. Dependence was defined as needing assistance with one or more basic ADL. Standard echocardiographic assessment of cardiac structure and function, including systolic and diastolic function, was performed. Reassessment of ADLs was performed at the five-year follow-up. Results A total of 459 patients were included in the study. Of these, 362 (79%) showed a deterioration in at least one ADL at follow-up. Patients with functional deterioration had a significantly higher left ventricular mass index and left atrial volume with a lower ejection fraction. There was no significant difference between the diastolic parameters the groups in examined. When the data were examined categorically, a significantly larger percentage of patients with functional decline had an abnormal left ventricular ejection fraction and left ventricular hypertrophy. The association between left ventricular mass index and functional decline remained significant in all multivariate models. Conclusions In this cohort of the oldest old, an elevated left ventricular mass index, higher left atrial volumes and systolic, but not diastolic dysfunction, were predictive of functional disability.

  4. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Science.gov (United States)

    Onofriescu, Mihai; Siriopol, Dimitrie; Voroneanu, Luminita; Hogas, Simona; Nistor, Ionut; Apetrii, Mugurel; Florea, Laura; Veisa, Gabriel; Mititiuc, Irina; Kanbay, Mehmet; Sascau, Radu; Covic, Adrian

    2015-01-01

    .29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

  5. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Mihai Onofriescu

    .67, 95%CI = 2.29-5.89 for RFO >17.4% and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4% Cox regression analysis.The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

  6. Multiple nutritional deficiencies in cerebral palsy compounding physical and functional impairments

    Directory of Open Access Journals (Sweden)

    P G Hariprasad

    2017-01-01

    Full Text Available Introduction: Cerebral palsy (CP refers to a spectrum of disorders causing physical and intellectual morbidity. Macro and micro nutrient deficiencies often contribute to the subnormal physical and mental capabilities of them. Objectives: To assess the growth, nutritional status, physical and functional ability and quality of life in cerebral palsy children and to determine any relation with their gross motor and functional capabilities. Method: The study was conducted at a Tertiary Care Centre, with the participants in the age group 1-16 years. A pretested evaluation tool was prepared which included Anthropometric measurements, tests for hemoglobin and Vitamin D estimation, evidence of micronutrient deficiencies, Dietary patterns, Epidemiological factors, Functional assessment using GMFM (Gross Motor Function Measure and FIM (Functional Independent Measurement scales and Quality of life (QOL assessment. The data was statistically analyzed. Results: Out of the 41 children, 30 had quadriplegia, 3 had hemiplegia and 8 had spastic diplegia. 34 (82.9% were severely underweight, 35 (85.4% had severe stunting and 38 (92.7% had severe wasting. Micronutrient deficiencies were noted like vitamin B complex deficiency in 37 (90.2%, vitamin A deficiency in 31 (75.6%, low vitamin D levels in 27 (65.9% and insufficient levels in 9 (22%, severe anemia in 5 (12.2% and moderate anemia in 26 (63.4%.The gross motor and functional scores were suboptimum in the majority of patients and the care givers had significant impairment in the quality of life. Conclusion: Majority of children with cerebral palsy had multiple nutritional deficiencies, gross motor and functional disabilities. QOL of the children and their care givers were suboptimum. A comprehensive package that address dietary intake, correction of micronutrient deficiencies especially anemia and vitamin D deficiency, physical and emotional support is recommended for the wellbeing of the affected children.

  7. Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin-resistant rats

    Science.gov (United States)

    Apaijai, Nattayaporn; Pintana, Hiranya; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2013-01-01

    Background and Purpose Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance. Experimental Approach Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined. Key Results Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV. Conclusions and Implications Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats. PMID:23488656

  8. Multimodality Cardiac Imaging for the Assessment of Left Atrial Function and the Association With Atrial Arrhythmias

    DEFF Research Database (Denmark)

    Olsen, Flemming Javier; Bertelsen, Litten; de Knegt, Martina Chantal

    2016-01-01

    Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the c......Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function...... atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered...... an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing...

  9. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice

    Directory of Open Access Journals (Sweden)

    Zuheng Liu

    2017-09-01

    Full Text Available Physical exercise is commonly regarded as protective against cardiovascular disease (CVD. Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI. Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.

  10. Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, C.; Acar, P.; Sidi, D.

    2006-01-01

    I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 ± 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 ± 49% vs 162 ± 26%, p < 0.0001 and LVEF = 43 ± 17% vs 26 ± 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

  11. The cardiac copper chaperone proteins Sco1 and CCS are up-regulated, but Cox 1 and Cox4 are down-regulated, by copper deficiency.

    Science.gov (United States)

    Getz, Jean; Lin, Dingbo; Medeiros, Denis M

    2011-10-01

    Copper is ferried in a cell complexed to chaperone proteins, and in the heart much copper is required for cytochrome c oxidase (Cox). It is not completely understood how copper status affects the levels of these proteins. Here we determined if dietary copper deficiency could up- or down-regulate select copper chaperone proteins and Cox subunits 1 and 4 in cardiac tissue of rats. Sixteen weanling male Long-Evans rats were randomized into treatment groups, one group receiving a copper-deficient diet (CCS, Sco1, Ctr1, Cox17, Cox1, and Cox4 by SDS-PAGE and Western blotting. No changes were observed in the concentrations of CTR1 and Cox17 between copper-adequate and copper-deficient rats. CCS and Sco1 were up-regulated and Cox1 and Cox4 were both down-regulated as a result of copper deficiency. These data suggest that select chaperone proteins and may be up-regulated, and Cox1 and 4 down-regulated, by a dietary copper deficiency, whereas others appear not to be affected by copper status.

  12. Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis.

    Science.gov (United States)

    Herrera, José A; Ward, Christopher S; Wehrens, Xander H T; Neul, Jeffrey L

    2016-11-15

    Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.

  13. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    Science.gov (United States)

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  14. Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice.

    Science.gov (United States)

    Takeda, K; Kamanaka, M; Tanaka, T; Kishimoto, T; Akira, S

    1996-10-15

    IL-13 shares many biologic responses with IL-4. In contrast to well-characterized IL-4 signaling pathways, which utilize STAT6 and 4PS/IRS2, IL-13 signaling pathways are poorly understood. Recent studies performed with STAT6-deficient mice have demonstrated that STAT6 plays an essential role in IL-4 signaling. In this study, the functions of peritoneal macrophages of STAT6-deficient mice in response to IL-13 were analyzed. In STAT6-deficient mice, neither morphologic changes nor augmentation of MHC class II expression in response to IL-13 was observed. In addition, IL-13 did not decrease the nitric oxide production by activated macrophages. Taken together, these results suggest that the macrophage functions in response to IL-13 were impaired in STAT6-deficient mice, indicating that IL-13 and IL-4 share the signaling pathway via STAT6.

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

    Science.gov (United States)

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

    2016-06-01

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

  16. The profound effects of microcystin on cardiac antioxidant enzymes, mitochondrial function and cardiac toxicity in rat

    International Nuclear Information System (INIS)

    Qiu Tong; Xie Ping; Liu Ying; Li Guangyu; Xiong Qian; Hao Le; Li Huiying

    2009-01-01

    Deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, while some recent studies suggest that cardiogenic complication is also involved. So far, information on cardiotoxic effects of MC has been rare and the underlying mechanism is still puzzling. The present study examined toxic effects of microcystins on heart muscle of rats intravenously injected with extracted MC at two doses, 0.16LD 50 (14 μg MC-LReq kg -1 body weight) and 1LD 50 (87 μg MC-LReq kg -1 body weight). In the dead rats, both TTC staining and maximum elevations of troponin I levels confirmed myocardial infarction after MC exposure, besides a serious interstitial hemorrhage in liver. In the 1LD 50 dose group, the coincident falls in heart rate and blood pressure were related to mitochondria dysfunction in heart, while increases in creatine kinase and troponin I levels indicated cardiac cell injury. The corresponding pathological alterations were mainly characterized as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. MC administration at a dose of 1LD 50 not only enhanced activities and up-regulated mRNA transcription levels of antioxidant enzymes, but also increased GSH content. At both doses, level of lipid peroxides increased obviously, suggesting serious oxidative stress in mitochondria. Simultaneously, complex I and III were significantly inhibited, indicating blocks in electron flow along the mitochondrial respiratory chain in heart. In conclusion, the findings of this study implicate a role for MC-induced cardiotoxicity as a potential factor that should be considered when evaluating the mechanisms of death associated with microcystin intoxication in Brazil

  17. Cardiac autonomic function in patients with diabetes improves with practice of comprehensive yogic breathing program

    Directory of Open Access Journals (Sweden)

    Viveka P Jyotsna

    2013-01-01

    Full Text Available Background: The aim of this study was to observe the effect comprehensive yogic breathing (Sudarshan Kriya Yoga [SKY] and Pranayam had on cardiac autonomic functions in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 64 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program. Standard therapy included dietary advice, brisk walking for 45 min daily, and administration of oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to the participants through a course of 12 h spread over 3 days. It was an interactive session in which SKY, a rhythmic cyclical breathing, preceded by Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic function tests were done before and after 6 months of intervention. Results: In the intervention group, after practicing the breathing techniques for 6 months, the improvement in sympathetic functions was statistically significant (P 0.04. The change in sympathetic functions in the standard therapy group was not significant (P 0.75.Parasympathetic functions did not show any significant change in either group. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P 0.06. In the standard therapy group, no change in cardiac autonomic functions was noted (P 0.99. Conclusion: Cardiac autonomic functions improved in patients with diabetes on standard treatment who followed the comprehensive yogic breathing program compared to patients who were on standard therapy alone.

  18. Regulatory effects of phospholamban on cardiac sarcoplasmic reticulum function

    International Nuclear Information System (INIS)

    Kim, Hae Won.

    1989-01-01

    In this thesis, the author reports the effect of phospholamban on: (a) Ca 2+ release by cardiac SR and (b) the Ca 2+ -ATPase activity in a purified reconstituted system. Phosphorylation of phospholamban by Ca 2+ · calmodulin-dependent protein kinase had no appreciable effect on the initial rates of Ca 2+ release from cardiac SR vesicles loaded under passive conditions and on the apparent 45 Ca 2+ - 40 Ca 2+ exchange from cardiac SR vesicles loaded under active conditions. us, it appears that Ca 2+ · calmodulin-dependent phosphorylation of phospholamban is not involved in the regulation of Ca 2+ release and 45 Ca 2+-40 Ca 2+ exchange. To determine the molecular mechanism by which phospholamban regulates the Ca 2+ pump, a reconstituted system was developed, using a freeze-thaw sonication procedure. The Ca 2+ -ATPase was purified by a method which yields an active enzyme preparation essentially free of phospholamban. The best rates of Ca 2+ uptake were obtained when cholate and phosphatidylcholine (PC) were used at a ratio of cholate/PC/Ca 2 + -ATPase of 2/80/1. The maximal rates of Ca 2+ Uptake were 700 nmol/min/mg reconstituted vesicles compared to 800 nmol/min/mg SR vesicles. The EC 50 values for Ca 2+ were 0.05 μM for both Ca 2+ uptake and Ca 2+ -ATPase activity in the reconstituted vesicles compared to 0.63 μM Ca 2+ in native SR vesicles. To determine the effect of phospholamban on the Ca + -ATPase activity in the reconstituted vesicles, purified phospholamban was added to the cholate/Ca 2+ -ATPase mixture prior to combining it with liposomes

  19. Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

    Science.gov (United States)

    Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

    2012-12-01

    IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Endothelial Function as a Possible Significant Determinant of Cardiac Function during Exercise in Patients with Structural Heart Disease

    Directory of Open Access Journals (Sweden)

    Bonpei Takase

    2009-01-01

    Full Text Available This study was investigated the role that endothelial function and systemic vascular resistance (SVR play in determining cardiac function reserve during exercise by a new ambulatory radionuclide monitoring system (VEST in patients with heart disease. The study population consisted of 32 patients. The patients had cardiopulmonary stress testing using the treadmill Ramp protocol and the VEST. The anaerobic threshold (AT was autodetermined using the V-slope method. The SVR was calculated by determining the mean blood pressure/cardiac output. Flow-mediated vasodilation (FMD was measured in the brachial artery to evaluate endotheilial function. FMD and the percent change f'rom rest to AT in SVR correlated with those from rest to AT in ejection fraction and peak ejection ratio by VEST, respectively. Our findings suggest that FMD in the brachial artery and the SVR determined by VEST in patients with heart disease can possibly reflect cardiac function reserve during aerobic exercise.

  1. Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency.

    Directory of Open Access Journals (Sweden)

    Jonghan Kim

    Full Text Available Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI. Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT and dopamine receptor D(1 (D1R levels were reduced and dopamine receptor D(2 (D2R levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.

  2. Vitamin D deficiency is associated with functional decline and falls in frail elderly women despite supplementation.

    Science.gov (United States)

    Kotlarczyk, M P; Perera, S; Ferchak, M A; Nace, D A; Resnick, N M; Greenspan, S L

    2017-04-01

    We examined the impact of daily supplementation on vitamin D deficiency, function, and falls in female long-term care residents. Initial vitamin D deficiency was associated with greater functional decline and increased fall risk despite guideline-recommended supplementation, highlighting the importance of preventing vitamin D deficiency in frail elderly. Institute of Medicine (IOM) guidelines recommend 800 IU vitamin D daily for older adults and maintaining serum 25-hydroxyvitamin D [25(OH) D] above 20 ng/ml for optimal skeletal health. The adequacy of IOM guidelines for sustaining function and reducing falls in frail elderly is unknown. Female long-term care residents aged ≥65 enrolled in an osteoporosis clinical trial were included in this analysis (n = 137). Participants were classified based on baseline 25(OH) D levels as deficient (30 ng/ml, n = 71). Deficient women were provided initial vitamin D repletion (50,000 IU D 3 weekly for 8 weeks). All were supplemented with 800 IU vitamin D 3 daily for 24 months. Annual functional assessments included Activities of Daily Living (ADLs), Instrumental ADL (IADL), physical performance test (PPT), gait speed, cognition (SPMSQ), and mental health (PHQ-9). We used linear mixed models for analysis of functional measures and logistic regression for falls. Daily supplementation maintained 25(OH) D levels above 20 ng/ml in 95% of participants. All groups demonstrated functional decline. Women initially deficient had a greater decline in physical function at 12 (IADL -2.0 ± 0.4, PPT -3.1 ± 0.7, both p elderly. Further study of optimal 25(OH) D levels for maintaining function and preventing falls is needed.

  3. Stable xenon CT measurement of cerebral blood flow in cardiac transplantation candidates: Correlation with cognitive function

    International Nuclear Information System (INIS)

    Bello, J.A.; Fink, M.E.; Hilal, S.K.; Rose, E.A.; Reemtsma, K.

    1987-01-01

    Thirteen consecutive unselected patients with NYHA class 4 cardiac failure referred for cardiac transplantation underwent neurologic examination and cerebral blood flow measurement (rCBF) using the stable xenon enhanced CT method on a GE9800 system. Eleven men and two women were studied (mean age = 43.8 +- 6.1). On neurological examination, six of the patients demonstrated normal mental function; the remaining seven patients demonstrated memory, language, or learning impairment. There was no difference in mean cardiac output between the groups (4.9 L/min +- 1.68 vs. 4.2L/min +- 1.57). rCBF was significantly reduced in the impaired group. Cognitive impairment in patients with cardiac failure can be correlated with cerebral ischemia. Stable xenon CT measurement of rCBF in transplant candidates may help identify patients requiring more rapid transplantation to prevent permanent cerebral injury

  4. A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

    Science.gov (United States)

    Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

  5. Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

    Directory of Open Access Journals (Sweden)

    Dong Ho Shin

    Full Text Available Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD. However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis.This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU to measure residual renal function. First, abdominal aortic calcification score (AACS and brachial-ankle pulse wave velocity (baPWV were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment.The median KRU was 0.9 (0.3-2.5 mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05 and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01 were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002 and baPWV (ß = -0.19, P = 0.05 after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05. Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08.Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

  6. Color Functionality Used in Visual Display for Occupational and Environmental Safety and Managing Color Vision Deficiency.

    Science.gov (United States)

    Ochiai, Nobuhisa; Kondo, Hiroyuki

    2017-01-01

    The effects of color perception are utilized in visual displays for the purpose of safety in the workplace and in daily life. These effects, generally known as color functionality, are divided into four classifications: visibility, legibility, conspicuity and discriminability. This article focuses on the relationship between the color functionality of color schemes used in visual displays for occupational and environmental safety and color vision deficiency (particularly congenital red-green color deficiency), a critical issue in ophthalmology, and examines the effects of color functionality on the perception of the color red in individuals with protan defects. Due to abrupt system reforms, current Japanese clinical ophthalmology finds itself in a situation where it is insufficiently prepared to handle congenital red-green color deficiencies. Indeed, occupational problems caused by color vision deficiencies have been almost completely neglected, and are an occupational safety and health concern that will need to be solved in the future. This report will present the guidelines for the color vision testing established by the British Health and Safety Executive (HSE), a pioneering example of a model meant to solve these problems. Issues relating to the creation of guidelines adapted to Japanese clinical ophthalmology will also be examined, and we will discuss ways to utilize color functionality used in visual displays for occupational and environmental safety to help manage color vision deficiency.

  7. PET measures of pre- and post-synaptic cardiac beta adrenergic function

    Energy Technology Data Exchange (ETDEWEB)

    Link, Jeanne M.; Stratton, John R.; Levy, Wayne; Poole, Jeanne E.; Shoner, Steven C.; Stuetzle, Werner; Caldwell, James H. E-mail: jcald@u.washington.edu

    2003-11-01

    Positron Emission Tomography was used to measure global and regional cardiac {beta}-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [{sup 11}C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [{sup 11}C]-CGP12177 was used to measure cell surface {beta}-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.

  8. Functional Reflective Polarizer for Augmented Reality and Color Vision Deficiency

    Science.gov (United States)

    2016-03-03

    augment reality system is relatively high as compared to a polarizing beam splitter or a conventional reflective polarizer. Such a functional reflective...brightness of the display [7]. A key component for polarization management is polarizing beam splitter (PBS). Even though the PBS has exceptional...polarizer that can be incorporated into a compact augmented reality system. The design principle of the functional reflective polarizer is explained and

  9. Gravity Reception and Cardiac Function in the Spider

    Science.gov (United States)

    Finck, A.

    1985-01-01

    The following features of the arachnid gravity system were studied. (1) the absolute threshold to hyper-gz is quite low indicating fine proprioreceptive properties of the lyriform organ, the Gz/vibration detector; (2) the neurogenic heart of the spider is a good dependent variable for assessing its behavior to Gz and other stimuli which produce mechanical effects on the exoskeleton; (3) Not only is the cardiac response useful but it is now understood to be an integral part of the system which compensates for the consequences of gravity in the spider (an hydraulic leg extension); and (4) a theoretical model was proposed in which a mechanical amplifier, the leg lever, converts a weak force (at the tarsus) to a strong force (at the patella), capable of compressing the exoskeleton and consequently the lyriform receptor.

  10. Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment.

    Science.gov (United States)

    Lyra-Leite, Davi M; Andres, Allen M; Petersen, Andrew P; Ariyasinghe, Nethika R; Cho, Nathan; Lee, Jezell A; Gottlieb, Roberta A; McCain, Megan L

    2017-10-01

    Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. NEW & NOTEWORTHY A new methodology has been developed to measure O 2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix

  11. Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction.

    Science.gov (United States)

    Sharp, Thomas E; Schena, Giana J; Hobby, Alexander R; Starosta, Timothy; Berretta, Remus M; Wallner, Markus; Borghetti, Giulia; Gross, Polina; Yu, Daohai; Johnson, Jaslyn; Feldsott, Eric; Trappanese, Danielle M; Toib, Amir; Rabinowitz, Joseph E; George, Jon C; Kubo, Hajime; Mohsin, Sadia; Houser, Steven R

    2017-11-10

    Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×10 7 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU + cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve

  12. Effects of a single terlipressin administration on cardiac function and perfusion in cirrhosis

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Mortensen, Christian

    2010-01-01

    BACKGROUND: The vasoconstrictor terlipressin is widely used in the treatment of the hepatorenal syndrome and variceal bleeding. However, terlipressin may compromise cardiac function and induce ischemia. AIM: Therefore, we aimed to assess the effects of terlipressin on cardiac function and perfusion...... with nonrefractory ascites, both at baseline and after terlipressin treatment. The decrease in the left ventricular wall thickening and wall motion correlated with the Child--Pugh score, r=-0.59, P=0.005 and r=-0.48, P=0.03. CONCLUSION: In advanced cirrhosis, the increase in afterload and EDV after terlipressin...

  13. Evaluating the cardiac function of duchenne muscular dystrophy with Doppler Tei index

    International Nuclear Information System (INIS)

    Yao Fengjuan; Zheng Ju; Lu Kun; Liu Donghong; Wu Miaoling; Lin Hong; Zhang Cheng; Yu Hongkui

    2007-01-01

    Objective: To evaluate the cardiac function of early Duchenne muscular dystrophy (DMD) by left ventricular ejection fraction (LVEF) and pulse Doppler Tei index. Methods: Twenty-eight DMD patients and fifteen normal people were studied. LVEF, E/A and Tei index were measured and calculated by M-mode and Pulse wave Doppler respectively. Results: Compared with control group, Tei index and IRT were significantly high, and there were not significant difference in LVEF(%) and E/A. Conclusion: Tei index was valuable in assessing cardiac function of early DMD. (authors)

  14. Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

    Science.gov (United States)

    Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

    2017-10-01

    Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Association Between Severe Vitamin D Deficiency, Lung Function and Asthma Control.

    Science.gov (United States)

    Beyhan-Sagmen, Seda; Baykan, Ozgur; Balcan, Baran; Ceyhan, Berrin

    2017-04-01

    To examine the relationship between severe vitamin D deficiency, asthma control, and pulmonary function in Turkish adults with asthma. One hundred six asthmatic patients underwent pulmonary function tests skin prick test, peripheral blood eosinophil counts, IgE, body mass index and vitamin D levels were determined. Patients were divided into 2 subgroups according to vitamin D levels (vitamin D level<10ng/ml and vitamin D level≥10 ng/ml). Asthma control tests were performed. The mean age of subgroup i (vitamin D level<10) was 37±10 and the mean age of subgroup ii (vitamin D level≥10ng/ml) was 34±8. Sixty-six percent of patients had severe vitamin D deficiency (vitamin D level<10 ng/ml). There was a significant trend towards lower absolute FEV 1 (L) values in patients with lower vitamin D levels (P=.001). Asthma control test scores were significantly low in the severe deficiency group than the other group (P=.02). There were a greater number of patients with uncontrolled asthma (asthma control test scores<20) in the severe vitamin D deficiency group (P=.040). Patients with severe vitamin D deficiency had a higher usage of inhaled corticosteroids than the group without severe vitamin D deficiency (P=.015). There was a significant trend towards lower absolute FEV 1 (L) (P=.005, r=.272) values in patients with lower vitamin D levels. Vitamin D levels were inversely related with body mass index (P=.046). The incidence of severe vitamin D deficiency was high in adult Turkish asthmatics. In addition, lower vitamin D levels were associated with poor asthma control and decreased pulmonary function. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Investigations of new cardiac functional imaging using Fourier analysis of gated blood-pool study

    International Nuclear Information System (INIS)

    Maeda, H.; Takeda, K.; Nakagawa, T.; Yamaguchi, N.; Taguchi, M.; Konishi, T.; Hamada, M.

    1982-01-01

    A new cardiac functional imaging, using temporal Fourier analysis of 28-frame gated cardiac blood-pool studies, was developed. A time-activity curve of each pixel was approximated by its Fourier series. Approximation by the sum for terms to the 3rd frequency of its Fourier series was considered to be most reasonable because of having the least aberration due to statistical fluctuation and close agreement between the global left ventricular curve and the regional fitted curves in normal subjects. To evaluate the ventricular systolic and diastolic performances, 9 parameters were analyzed from thus fitted curves on a pixel-by-pixel basis and displayed on a colour CRT in 64x64 matrix form. In patients with hypertrophic obstructive cardiomyopathy and other cardiac lesions, detailed information on the regional ventricular systolic and diastolic performances was clearly visualized by this method, which was difficult to obtain from the usual functional images of phase and amplitude at the fundamental frequency alone

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

    Science.gov (United States)

    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

  18. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    Energy Technology Data Exchange (ETDEWEB)

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert [Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne (Germany); Volz, Cornelia; Jägle, Herbert [Department of Ophthalmology, University Hospital Regensburg, Regensburg (Germany); Liebisch, Gerhard [Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg (Germany); Utermöhlen, Olaf [Institute for Medical Microbiology, Immunology and Hygiene and Center for Molecular Medicine Cologne, University of Cologne, Cologne (Germany); Langmann, Thomas, E-mail: thomas.langmann@uk-koeln.de [Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne (Germany)

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  19. Deficiency Mutations of Alpha-1 Antitrypsin. Effects on Folding, Function, and Polymerization.

    Science.gov (United States)

    Haq, Imran; Irving, James A; Saleh, Aarash D; Dron, Louis; Regan-Mochrie, Gemma L; Motamedi-Shad, Neda; Hurst, John R; Gooptu, Bibek; Lomas, David A

    2016-01-01

    Misfolding, polymerization, and defective secretion of functional alpha-1 antitrypsin underlies the predisposition to severe liver and lung disease in alpha-1 antitrypsin deficiency. We have identified a novel (Ala336Pro, Baghdad) deficiency variant and characterized it relative to the wild-type (M) and Glu342Lys (Z) alleles. The index case is a homozygous individual of consanguineous parentage, with levels of circulating alpha-1 antitrypsin in the moderate deficiency range, but is a biochemical phenotype that could not be classified by standard methods. The majority of the protein was present as functionally inactive polymer, and the remaining monomer was 37% active relative to the wild-type protein. These factors combined indicate an 85 to 95% functional deficiency, similar to that seen with ZZ homozygotes. Biochemical, biophysical, and computational studies further defined the molecular basis of this deficiency. These studies demonstrated that native Ala336Pro alpha-1 antitrypsin could populate the polymerogenic intermediate-and therefore polymerize-more readily than either wild-type alpha-1 antitrypsin or the Z variant. In contrast, folding was far less impaired in Ala336Pro alpha-1 antitrypsin than in the Z variant. The data are consistent with a disparate contribution by the "breach" region and "shutter" region of strand 5A to folding and polymerization mechanisms. Moreover, the findings demonstrate that, in these variants, folding efficiency does not correlate directly with the tendency to polymerize in vitro or in vivo. They therefore differentiate generalized misfolding from polymerization tendencies in missense variants of alpha-1 antitrypsin. Clinically, they further support the need to quantify loss-of-function in alpha-1 antitrypsin deficiency to individualize patient care.

  20. The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

    Science.gov (United States)

    Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

    2018-03-21

    It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

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

    Science.gov (United States)

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

    2013-11-01

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

  2. A portable cadmium telluride multidetector probe for cardiac function monitoring

    CERN Document Server

    Arntz, Y; Dumitresco, B; Eclancher, B; Prat, V

    1999-01-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5x5x2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) wh...

  3. Analysis of cardiac diastolic function: application in coronary artery disease

    International Nuclear Information System (INIS)

    Miller, T.R.; Goldman, K.J.; Sampathkumaran, K.S.; Biello, D.R.; Ludbrook, P.A.; Sobel, B.E.

    1983-01-01

    Separation of systolic and diastolic parameters in gated cardiac blood-pool imaging (RVG) was achieved with the retention of two harmonics in the Fourier-series representation of the time-activity curve. Regional and global analysis of left-ventricular peak filling rate (PFR) and time to peak filling (TPF) was performed in 18 control subjects, 20 patients with coronary artery disease (CAD) but with normal RVG (normal regional wall motion and ejection fraction, and 16 CAD patients with abnormal RVG. In regional analysis of CAD patients, the standard deviation of the TPF histogram identified 13/20 (65%) of normal RVG patients and 12/16 (75%) of abnormal RVG patients as abnormal. In global analysis of CAD patients, PFR values identified 10/20 (50%) of normal RVG patients and 11/16 (69%) of abnormal RVG patients as abnormal. Thus, left-ventricular systolic and diastolic parameters can be separately measured with retention of higher-order harmonics in the Fourier transform, and regional inhomogeneity of diastolic filling can be detected in CAD patients with normal resting ejection fraction and wall motion

  4. Vitamin D deficiency plays an important role in cardiac disease and affects patient outcome: Still a myth or a fact that needs exploration?

    Directory of Open Access Journals (Sweden)

    Zaher Fanari

    2015-10-01

    Full Text Available There is increasing evidence that a low vitamin D status may be an important and hitherto neglected factor of cardiovascular disease. This review is an overview of the current body of literature, and presents evidence of the mechanisms through which vitamin D deficiency affects the cardiovascular system in general and the heart in particular. Available data indicate that the majority of congestive heart failure patients have 25-hydroxyvitamin D deficiency. Furthermore, the low serum 25-hydroxyvitamin D level has a higher impact on hypertension, coronary artery disease an on the occurrence of relevant cardiac events. A serum 25-hydroxyvitamin D level below 75 nmol/l (30 ng/l is generally regarded as vitamin D insufficiency in both adults and children, while a level below 50 nmol/l (20 ng/l is considered deficiency. Levels below 50 nmol/l (20 ng/l are linked independently to cardiovascular morbidity and mortality.

  5. [Ubiquinone: metabolism and functions. Ubiquinone deficiency and its implication in mitochondrial encephalopathies. Treatment with ubiquinone].

    Science.gov (United States)

    Artuch, R; Colomé, C; Vilaseca, M A; Pineda, M; Campistol, J

    Review of ubiquinone-10 metabolism and functions in humans, focusing its implication in the pathogenesis and physiopathology of mitochondrial encephalomyopathies. Ubiquinone-10 is an endogenously synthesized lipid with a wide distribution in tissues. Tyrosine and acetil-CoA are involved in ubiquinone biosynthesis. This molecule has several biological functions in cells: it is a movil electron carrier in the mitochondrial respiratory chain and also acts as antioxidant. Owing to its implication in these functions, ubiquinone deficiency may cause important deletereous effects in tissues. Several authors reported ubiquinone deficient status in some physiological and pathological conditions. Mitochondrial encephalomyopathies may be related to a primary or secondary ubiquinone deficient status, or even to an altered function of ubiquinone in the respiratory chain. Moreover, some relevant aspects about ubiquinone therapy in mitochondrial disorders are reported. According to recent reports about ubiquinone implication in several diseases, its determination in different biological samples seems very useful to elucidate the physiopathological mechanisms involved and even the to start a therapy in cases with ubiquinone deficiency.

  6. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1.

    NARCIS (Netherlands)

    Williams, K.J.; Telfer, B.A.; Xenaki, D.; Sheridan, M.R.; Desbaillets, I.; Peters, H.J.; Honess, D.; Harris, A.L.; Dachs, G.U.; Kogel, A.J. van der; Stratford, I.J.

    2005-01-01

    BACKGROUND AND PURPOSE: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. PATIENTS AND METHODS: Tumours comprising mouse hepatoma cells lacking HIF-1beta (and thereby HIF-1 function) were grown

  7. Functional Capacity Evaluation in Upper Limb Reduction Deficiency and Amputation : Development and Pilot Testing

    NARCIS (Netherlands)

    Postema, S G; Bongers, R M; Reneman, M F; van der Sluis, C K

    Purpose To develop and pilot test a functional capacity evaluation (FCE) for individuals with upper limb absence (ULA) due to reduction deficiency or amputation, and to examine the relationship between FCE results and presence of musculoskeletal complaints (MSC). Method Five tests (overhead lifting,

  8. The effect of melatonin on vascular function in NO-deficient hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Paulis, L.; Pecháňová, O.; Zicha, Josef; Gardlik, R.; Celec, P.; Kuneš, Jaroslav

    2008-01-01

    Roč. 26, Suppl.1 (2008), S382-S382 ISSN 0263-6352. [Scientific Meeting International Society of Hypertension /22./ , Scientific Meeting European Society of Hypertension /18./. 14.06.2008-19.06.2008, Berlin] Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * melatonin * NO-deficient hypertension * vascular function Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  9. Structural and functional cardiac adaptations to 6 months of football training in untrained hypertensive men

    DEFF Research Database (Denmark)

    Andersen, L. J.; Randers, M. B.; Hansen, P. R.

    2014-01-01

    We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men. Thirty-one untrained males with mild-to-moderate hypertension were randomized 2:1 to a football training group (n = 20) and a control group receiving traditional...... training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension. Furthermore, it may improve longitudinal systolic function of both ventricles. The results suggest that football training has favorable effects on cardiac function in hypertensive men....... function improved with respect to tricuspid annular plane systolic excursion (21.8 ± 3.2 to 24.5 ± 3.7 mm). Arterial blood pressure decreased in both groups, but significantly more in the football training group. No significant changes were observed in the control group. In conclusion, short-term football...

  10. Survivors of cardiac arrest with good neurological outcome show considerable impairments of memory functioning.

    Science.gov (United States)

    Sulzgruber, Patrick; Kliegel, Andreas; Wandaller, Cosima; Uray, Thomas; Losert, Heidrun; Laggner, Anton N; Sterz, Fritz; Kliegel, Matthias

    2015-03-01

    Deficits in cognitive function are a well-known dysfunction in survivors of cardiac arrest. However, data concerning memory function in this neurological vulnerable patient collective remain scarce and inconclusive. Therefore, we aimed to assess multiple aspects of retrospective and prospective memory performance in patients after cardiac arrest. We prospectively enrolled 33 survivors of cardiac arrest, with cerebral performance categories (CPC) 1 and 2 and a control-group (n=33) matched in sex, age and educational-level. To assess retrospective and prospective memory performance we administrated 4 weeks after cardiac arrest the "Rey Adult Learning Test" (RAVLT), the "Digit-Span-Backwards Test", the "Logic-Memory Test" and the "Red-Pencil Test". Results indicate an impairment in immediate and delayed free recall, but not in recognition. However, the overall impairment in immediate recall was qualified by analyzing RAVLT performance, showing that patients were only impaired in trials 4 and 5 of the learning sequence. Moreover, working and prospective memory as well as prose recall were worse in cardiac arrest survivors. Cranial computed tomography was available in 61% of all patients (n=20) but there was no specific neurological damage detectable that could be linked to this cognitive impairment. Episodic long-term memory functioning appears to be particularly impaired after cardiac arrest. In contrast, short-term memory storage, even tested via free-call, seems not to be affected. Based on cranial computed tomography we suggest that global brain ischemia rather than focal brain lesions appear to underlie these effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Exercise and Type 2 Diabetes Mellitus : Changes in Tissue-specific Fat Distribution and Cardiac Function

    NARCIS (Netherlands)

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

    2013-01-01

    Purpose: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Materials and Methods: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics

  12. The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children

    NARCIS (Netherlands)

    Chockalingam, Priya; Clur, Sally-Ann B.; Breur, Johannes M. P. J.; Kriebel, Thomas; Paul, Thomas; Rammeloo, Lukas A.; Wilde, Arthur A. M.; Blom, Nico A.

    2012-01-01

    BACKGROUND Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. OBJECTIVE To analyze the diagnostic and therapeutic aspects of these disorders in children. METHODS Patients aged <= 16 years with genetically

  13. Tei index in determination of fetal cardiac function in pregnant women with gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Guo-Dong Li

    2016-09-01

    Full Text Available Objective: To explore the application value of Tei index in determination of fetal cardiac function in pregnant women with gestational diabetes mellitus (GDM. Methods: A total of 60 gestational diabetes mellitus pregnant women with single birth were included in the study and served as GDM group, while 60 healthy pregnant women with single birth were served as the control group. The fetal echocardiography was performed. The cardiac structure, function, and other related indicators were detected and compared. Results: IVSs, LVWT, RVWT, LVEF, LVFS, and RVFS in GDM group were significantly greater than those in the control group (P<0.05. E/A MV and E/A TV in GDM group were significantly lower than those in the control group (P<0.05. The left and right ventricular Tei index in GDM group was significantly higher than that in the control group (P<0.05. Conclusions: The fetal cardiac structure and function in GDM pregnant women can cause damage to a different degree. Tei index is an important indicator to evaluate the fetal cardiac function in GDM pregnant women, and can be applied in the early diagnosis and treatment; therefore, it deserved to be widely recommended in the clinic.

  14. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    Science.gov (United States)

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  15. Zebrafish Lacking Circadian Gene per2 Exhibit Visual Function Deficiency

    Directory of Open Access Journals (Sweden)

    Deng-feng Huang

    2018-03-01

    Full Text Available The retina has an intrinsic circadian clock, but the importance of this clock for vision is unknown. Zebrafish offer many advantages for studying vertebrate vision and circadian rhythm. Here, we explored the role of zebrafish per2, a light-regulated gene, in visual behavior and the underlying mechanisms. We observed that per2 mutant zebrafish larvae showed decreased contrast sensitivity and visual acuity using optokinetic response (OKR assays. Using a visual motor response (VMR assay, we observed normal OFF responses but abnormal ON responses in mutant zebrafish larvae. Immunofluorescence showed that mutants had a normal morphology of cone photoreceptor cells and retinal organization. However, electron microscopy showed that per2 mutants displayed abnormal and decreased photoreceptor ribbon synapses with arciform density, which resulted in retinal ON pathway defect. We also examined the expression of three cone opsins by quantitative real-time PCR (qRT-PCR, and the expression of long-wave-sensitive opsin (opn1lw and short-wave-sensitive opsin (opn1sw was reduced in mutant zebrafish larvae. qRT-PCR analyses also showed a down-regulation of the clock genes cry1ba and bmal1b in the adult eye of per2 mutant zebrafish. This study identified a mechanism by which a clock gene affects visual function and defined important roles of per2 in retinal information processing.

  16. Action Potential Shortening and Impairment of Cardiac Function by Ablation of Slc26a6.

    Science.gov (United States)

    Sirish, Padmini; Ledford, Hannah A; Timofeyev, Valeriy; Thai, Phung N; Ren, Lu; Kim, Hyo Jeong; Park, Seojin; Lee, Jeong Han; Dai, Gu; Moshref, Maryam; Sihn, Choong-Ryoul; Chen, Wei Chun; Timofeyeva, Maria Valeryevna; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Chiamvimonvat, Nipavan; Chen-Izu, Ye; Yamoah, Ebenezer N; Zhang, Xiao-Dong

    2017-10-01

    Intracellular pH (pH i ) is critical to cardiac excitation and contraction; uncompensated changes in pH i impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH i regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl - /HCO 3 - exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH i , but also cardiac excitability. To test the mechanistic role of Slc26a6 in the heart, we took advantage of Slc26a6 knockout ( Slc26a6 -/ - ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of Slc26a6 results in action potential shortening. There are reduced Ca 2+ transient and sarcoplasmic reticulum Ca 2+ load, together with decreased sarcomere shortening in Slc26a6 -/ - cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH i is elevated in Slc26a6 -/ - cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl - /HCO 3 - exchange activities of Slc26a6. Moreover, Slc26a6 -/ - mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl - /HCO 3 - transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH i , excitability, and contractility. pH i is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in Slc26a6 -/ - mice. © 2017 American Heart Association, Inc.

  17. Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy.

    Science.gov (United States)

    Miyata, Makiko; Yoshihisa, Akiomi; Suzuki, Satoshi; Yamada, Shinya; Kamioka, Masashi; Kamiyama, Yoshiyuki; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

    2012-09-01

    Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  18. Ultrasonographic assessment of maternal cardiac function and peripheral circulation during normal gestation in dogs.

    Science.gov (United States)

    Blanco, Paula G; Tórtora, Mariana; Rodríguez, Raúl; Arias, Daniel O; Gobello, Cristina

    2011-10-01

    The aim of this study was to describe changes in cardiac morphology, systolic function and some peripheral hemodynamic parameters during normal pregnancy in dogs. Twenty healthy bitches, 10 pregnant (PG) and 10 non-pregnant controls (CG), were evaluated every 10 days using echocardiography from day 0 of the estrus cycle to parturition or to day 65 for the PG and CG groups, respectively. Systolic blood pressure (SBP) and uterine artery resistance index (RI) were also assessed. Throughout the study, the shortening fraction and cardiac output increased up to 30% vs. 5% (Pdogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Marija Bozhinovska

    2016-06-01

    Full Text Available The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes.

  20. Use of the cardiopulmonary flow index to evaluate cardiac function in thoroughbred horses

    International Nuclear Information System (INIS)

    Guthrie, A.J.; Killeen, V.M.; Grosskopf, J.F.W.

    1991-01-01

    The ratio of the cardiopulmonary blood volume to stroke volume is called the cardiopulmonary flow index (CPFI). The CPFI can be determined indirectly from the simultaneous recording of a radiocardiogram and an electrocardiogram. The CPFI and cardiac output were measured simultaneously in horses that were diagnosed as having cardiac disease. The results obtained from these subjects were compared with those from control animals and significant differences were found between the mean CPFI of the control horses and those with macroscopically visible myocardial fibrosis on post mortem examination. No significant differences were found between the means of the cardiac output measured in either of the groups of horses. The effect of pharmacological acceleration of the heart rate on the CPFI was also studied. Significant differences were found between the mean CPFI and the slopes of the regression lines of CPFI on heart rate of the control and principal groups of horses. These differences were greatest at heart rates near to the resting heart rates of the individuals. The CPFI was found to be a more sensitive measure of cardiac function than cardiac output, in the horses. 16 refs., 2 figs., 2 tabs

  1. Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

    Science.gov (United States)

    Liu, Zhenzhen; Du, Lupei; Li, Minyong

    2012-01-01

    The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

  2. Assessment of cardiac morphology and ventricular function in healthy Chinese individuals using MRI

    International Nuclear Information System (INIS)

    Lu Minjie; Zhao Shihua; Jiang Shiliang

    2011-01-01

    Objective: To investigate reproducibility of cardiac MRI for assessment of cardiac morphology and ventricular function in selected normal Chinese Han population. Methods: Two hundred and sixty-nine normal volunteers underwent cardiac MRI using a 1.5 T MR system. HASTE and steady state free precession imaging were performed with long and short axis images and cine mode through the ventricle with wireless vector cardiac gating. The images were reviewed by two independent observers. The dimensions of cardiac chambers and ventricular function including ejection fraction (EF), end diastolic volume (EDV) , end systolic volume (ESV) and myocardial mass were evaluated. The data between male and female were compared by using two-tailed unpaired t test. Results: Total imaging time was (15±3) min. The anteroposterior diameter of the left atrium was (2.87±0.77) cm, the right atrial diameter perpendicular to the atrial septum was (3.61±0.57) cm, the end diastolic diameter of the left ventricle was (4.97± 0.52) cm, the end diastolic diameter of the right ventricle was (2.65±0.48) cm. On the left ventricle, EF was (60.62±7.08)%, EDV was (115.37±26.71) ml, ESV was (46.02±15.72) ml and LV mass was (82.97±24.03) g. On the right ventricle, EF was (47.73±6.50)%, EDV was (128.27±32.16) ml, ESV was (67.7±21.07) ml and RV mass was (48.24±13.42) g. There were no statistically significant differences in LVESV (P=0.144), LVEDV index (P=0.714), LVESV index (P=0.113), LVCI (P=0.199), RVEF (P=0.296) and RV mass (P=0.093), and statistically significant differences in other cardiac parameters between male and female. Conclusion: Cardiac MRI can provide useful information about cardiac function and morphology with a high level of reproducibility in normal Chinese Han population. (authors)

  3. Myocardin-related transcription factors are required for cardiac development and function

    OpenAIRE

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2015-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the d...

  4. TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

    International Nuclear Information System (INIS)

    Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min

    2013-01-01

    The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function

  5. Effects of plasma viscosity modulation on cardiac function during moderate hemodilution

    Directory of Open Access Journals (Sweden)

    Chatpun Surapong

    2010-01-01

    Full Text Available Background : Previous studies have found that increasing plasma viscosity as whole blood viscosity decrease has beneficial effects in microvascular hemodynamics. As the heart couples with systemic vascular network, changes in plasma and blood viscosity during hemodilution determine vascular pressure drop and flow rate, which influence cardiac function. This study aimed to investigate how changes in plasma viscosity affect on cardiac function during acute isovolemic hemodilution. Materials and Methods: Plasma viscosity was modulated by hemodilution of 40% of blood volume with three different plasma expanders (PEs. Dextran 2000 kDa (Dx2M, 6.3 cP and dextran 70 kDa (Dx70, 3.0 cP were used as high and moderate viscogenic PEs, respectively. Polyethylene glycol conjugated with human serum albumin (PEG-HSA, 2.2 cP was used as low viscogenic PE. The cardiac function was assessed using a miniaturized pressure-volume conductance catheter. Results: After hemodilution, pressure dropped to 84%, 79%, and 78% of baseline for Dx2M, Dx70 and PEG-HSA, respectively. Cardiac output markedly increased for Dx2M and PEG-HSA. Dx2M significantly produced higher stroke work relative to baseline and compared to Dx70. Conclusion: Acute hemodilution with PEG-HSA without increasing plasma viscosity provided beneficial effects on cardiac function compared to Dx70, and similar to those measured with Dx2M. Potentially negative effects of increasing peripheral vascular resistance due to the increase in plasma viscosity were prevented.

  6. Absolute and Functional Iron Deficiency Anemia among Different Tumors in Cancer Patients in South Part of Iran, 2014

    Science.gov (United States)

    Hashemi, Seyed Mehdi; Mashhadi, Mohammad Ali; Mohammadi, Mehdi; Ebrahimi, Maryam; Allahyari, Abolghasem

    2017-01-01

    Background: Anemia is a common problem in cancer patients. This study aimed to investigate the frequency rate of absolute and functional iron deficiency anemia among different tumors and its distribution in different stages of cancer in solid tumors. Materials and Methods: This study was performed on 597 patients with cancer referred to Ali-Ebne-Abitaleb Hospital in Zahedan. Laboratory tests included serum iron, transferrin saturation, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and complete blood count (CBC). The malignancy type and stages were recorded. Data were analysed using SPSS statistics software (Ver.19). Results: Four hundred and fifty-seven patients (76.5 %) diagnosed with solid tumors and 140 (23.5%) suffered from hematologic malignancies. Among patients with solid tumors, functional iron deficiency had the highest rate (300 patients had anemia and 243 (53.2%) of whom were functionally iron deficient), but in hematologic malignancies most of patients had not iron deficiency (66 patients had not iron deficiency against 12 patients had absolute iron deficiency and 62 patients had functional iron deficiency anemia) (P-value=0.021). No significant differences were observed among the various stages of cancers in terms of degrees of iron deficiency (P>0.05). Conclusion: The results of the study showed that solid tumors had a higher rate of absolute and functional iron deficiency anemia, compared to hematologic malignancies. But there was no difference between the different stages of the disease. PMID:28989585

  7. Functional substitution by TAT-utrophin in dystrophin-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kevin J Sonnemann

    2009-05-01

    Full Text Available The loss of dystrophin compromises muscle cell membrane stability and causes Duchenne muscular dystrophy and/or various forms of cardiomyopathy. Increased expression of the dystrophin homolog utrophin by gene delivery or pharmacologic up-regulation has been demonstrated to restore membrane integrity and improve the phenotype in the dystrophin-deficient mdx mouse. However, the lack of a viable therapy in humans predicates the need to explore alternative methods to combat dystrophin deficiency. We investigated whether systemic administration of recombinant full-length utrophin (Utr or DeltaR4-21 "micro" utrophin (muUtr protein modified with the cell-penetrating TAT protein transduction domain could attenuate the phenotype of mdx mice.Recombinant TAT-Utr and TAT-muUtr proteins were expressed using the baculovirus system and purified using FLAG-affinity chromatography. Age-matched mdx mice received six twice-weekly intraperitoneal injections of either recombinant protein or PBS. Three days after the final injection, mice were analyzed for several phenotypic parameters of dystrophin deficiency. Injected TAT-muUtr transduced all tissues examined, integrated with members of the dystrophin complex, reduced serum levels of creatine kinase (11,290+/-920 U versus 5,950+/-1,120 U; PBS versus TAT, the prevalence of muscle degeneration/regeneration (54%+/-5% versus 37%+/-4% of centrally nucleated fibers; PBS versus TAT, the susceptibility to eccentric contraction-induced force drop (72%+/-5% versus 40%+/-8% drop; PBS versus TAT, and increased specific force production (9.7+/-1.1 N/cm(2 versus 12.8+/-0.9 N/cm(2; PBS versus TAT.These results are, to our knowledge, the first to establish the efficacy and feasibility of TAT-utrophin-based constructs as a novel direct protein-replacement therapy for the treatment of skeletal and cardiac muscle diseases caused by loss of dystrophin.

  8. Cardiac function associated with home ventilator care in Duchenne muscular dystrophy.

    Science.gov (United States)

    Lee, Sangheun; Lee, Heeyoung; Eun, Lucy Youngmin; Gang, Seung Woong

    2018-02-01

    Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy because mechanically assisted lung ventilation and assisted coughing have helped resolve respiratory complications. To clarify cardiopulmonary function, we compared cardiac function between the home ventilator-assisted and non-ventilator-assisted groups. We retrospectively reviewed patients with Duchenne muscular dystrophy from January 2010 to March 2016 at Gangnam Severance Hospital. Demographic characteristics, pulmonary function, and echocardiography data were investigated. Fifty-four patients with Duchenne muscular dystrophy were divided into 2 groups: home ventilator-assisted and non-ventilator-assisted. The patients in the home ventilator group were older (16.25±1.85 years) than those in the nonventilator group (14.73±1.36 years) ( P =0.001). Height, weight, and body surface area did not differ significantly between groups. The home ventilator group had a lower seated functional vital capacity (1,038±620.41 mL) than the nonventilator group (1,455±603.12 mL). Mean left ventricular ejection fraction and fractional shortening were greater in the home ventilator group, but the data did not show any statistical difference. The early ventricular filling velocity/late ventricular filling velocity ratio (1.7±0.44) was lower in the home ventilator group than in the nonventilator group (2.02±0.62). The mitral valve annular systolic velocity was higher in the home ventilator group (estimated β, 1.06; standard error, 0.48). Patients with Duchenne muscular dystrophy on a ventilator may have better systolic and diastolic cardiac functions. Noninvasive ventilator assistance can help preserve cardiac function. Therefore, early utilization of noninvasive ventilation or oxygen may positively influence cardiac function in patients with Duchenne muscular dystrophy.

  9. Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells.

    Science.gov (United States)

    Kemp, Kevin; Dey, Rimi; Cook, Amelia; Scolding, Neil; Wilkins, Alastair

    2017-08-01

    Friedreich's ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich's ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich's ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich's ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich's ataxia.

  10. [Cardiac Synchronization Function Estimation Based on ASM Level Set Segmentation Method].

    Science.gov (United States)

    Zhang, Yaonan; Gao, Yuan; Tang, Liang; He, Ying; Zhang, Huie

    At present, there is no accurate and quantitative methods for the determination of cardiac mechanical synchronism, and quantitative determination of the synchronization function of the four cardiac cavities with medical images has a great clinical value. This paper uses the whole heart ultrasound image sequence, and segments the left & right atriums and left & right ventricles of each frame. After the segmentation, the number of pixels in each cavity and in each frame is recorded, and the areas of the four cavities of the image sequence are therefore obtained. The area change curves of the four cavities are further extracted, and the synchronous information of the four cavities is obtained. Because of the low SNR of Ultrasound images, the boundary lines of cardiac cavities are vague, so the extraction of cardiac contours is still a challenging problem. Therefore, the ASM model information is added to the traditional level set method to force the curve evolution process. According to the experimental results, the improved method improves the accuracy of the segmentation. Furthermore, based on the ventricular segmentation, the right and left ventricular systolic functions are evaluated, mainly according to the area changes. The synchronization of the four cavities of the heart is estimated based on the area changes and the volume changes.

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

    Science.gov (United States)

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

    2015-01-01

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

  12. The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery.

    Science.gov (United States)

    Brims, Fraser J H; Davies, Michael G; Elia, Andy; Griffiths, Mark J D

    2015-01-01

    Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients. We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT). In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); pdrain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028). Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation.

  13. The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery

    Science.gov (United States)

    Brims, Fraser J H; Davies, Michael G; Elia, Andy; Griffiths, Mark J D

    2015-01-01

    Background Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients. Methods We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT). Results In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); pdrain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028). Conclusions Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation. PMID:26339492

  14. Awareness of cardiac function in anxious, phobic and hypochondriacal patients.

    Science.gov (United States)

    Tyrer, P; Lee, I; Alexander, J

    1980-02-01

    Awareness of pulse rate was tested in 60 psychiatric out-patients with anxiety, phobic or hypochondriacal neuroses by asking them to record how fast their hearts were beating during exposure to short film sequences. Correlations between subjective and objective heart rate (ECG) were significantly higher in anxious and hypochondriacal patients than in phobic ones. The results suggest that somatic symptoms in hypochondriacal and anxiety neurosis reflect increased awareness of bodily function.

  15. Clinical research on correlation between BNP and left cardiac function in patients with heart failure

    International Nuclear Information System (INIS)

    Yin Xin; Xu Dandan; Wu Chunxu

    2005-01-01

    To investigate the correlation between brain natriuretic peptide (BNP) and the cardiac function in patients with heart failure(HF), the plasma level of BNP was determined by IRMA and the left cardiac function parameters were measured on echocardiogram in patients with different grade of HF. The results showed that the plasma level of BNP elevated with the worsening of heart failure (NYHA classification). The plasma levels of BNP were negatively correlated with left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVDd). The plasma level of BNP increases significantly along with the severity of HF classified by NYHA, and might be a biochemical parameter for evaluating the left ventricular function. (authors)

  16. Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature.

    Science.gov (United States)

    Maagaard, Marie; Heiberg, Johan

    2016-09-01

    Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3-168 patients, mean age-ranges of 5-33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22-34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O 2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac

  17. LRRC10 is required to maintain cardiac function in response to pressure overload.

    Science.gov (United States)

    Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

    2016-01-15

    We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. Copyright © 2016 the American Physiological Society.

  18. Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.

    Science.gov (United States)

    Miyanishi, Hiroshi; Okubo, Kataaki; Nobata, Shigenori; Takei, Yoshio

    2013-01-01

    Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.

  19. An Echocardiographic Study of Left Ventricular Size and Cardiac Function in Adolescent Females with Anorexia Nervosa.

    Science.gov (United States)

    Escudero, Carolina A; Potts, James E; Lam, Pei-Yoong; De Souza, Astrid M; Mugford, Gerald J; Sandor, George G S

    2016-01-01

    This retrospective case-control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls. Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and >10th percentile (AN > 10th). Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN > 10th. Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  20. Tansig activation function (of MLP network) for cardiac abnormality detection

    Science.gov (United States)

    Adnan, Ja'afar; Daud, Nik Ghazali Nik; Ishak, Mohd Taufiq; Rizman, Zairi Ismael; Rahman, Muhammad Izzuddin Abd

    2018-02-01

    Heart abnormality often occurs regardless of gender, age and races. This problem sometimes does not show any symptoms and it can cause a sudden death to the patient. In general, heart abnormality is the irregular electrical activity of the heart. This paper attempts to develop a program that can detect heart abnormality activity through implementation of Multilayer Perceptron (MLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP network by using several training algorithms with Tansig activation function.

  1. Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber scaffolds.

    Science.gov (United States)

    Hussain, Ali; Collins, George; Yip, Derek; Cho, Cheul H

    2013-02-01

    The in vitro generation of a three-dimensional (3-D) myocardial tissue-like construct employing cells, biomaterials, and biomolecules is a promising strategy in cardiac tissue regeneration, drug testing, and tissue engineering applications. Despite significant progress in this field, current cardiac tissue models are not yet able to stably maintain functional characteristics of cardiomyocytes for long-term culture and therapeutic purposes. The objective of this study was to fabricate bioactive 3-D chitosan nanofiber scaffolds using an electrospinning technique and exploring its potential for long-term cardiac function in the 3-D co-culture model. Chitosan is a natural polysaccharide biomaterial that is biocompatible, biodegradable, non-toxic, and cost effective. Electrospun chitosan was utilized to provide structural scaffolding characterized by scale and architectural resemblance to the extracellular matrix (ECM) in vivo. The chitosan fibers were coated with fibronectin via adsorption in order to enhance cellular adhesion to the fibers and migration into the interfibrous milieu. Ventricular cardiomyocytes were harvested from neonatal rats and studied in various culture conditions (i.e., mono- and co-cultures) for their viability and function. Cellular morphology and functionality were examined using immunofluorescent staining for alpha-sarcomeric actin (SM-actin) and gap junction protein, Connexin-43 (Cx43). Scanning electron microscopy (SEM) and light microscopy were used to investigate cellular morphology, spatial organization, and contractions. Calcium indicator was used to monitor calcium ion flux of beating cardiomyocytes. The results demonstrate that the chitosan nanofibers retained their cylindrical morphology in long-term cell cultures and exhibited good cellular attachment and spreading in the presence of adhesion molecule, fibronectin. Cardiomyocyte mono-cultures resulted in loss of cardiomyocyte polarity and islands of non-coherent contractions. However

  2. Use of cardiac magnetic resonance imaging to evaluate cardiac structure, function and fibrosis in children with infantile Pompe disease on enzyme replacement therapy.

    Science.gov (United States)

    Barker, Piers C A; Pasquali, Sara K; Darty, Stephen; Ing, Richard J; Li, Jennifer S; Kim, Raymond J; DeArmey, Stephanie; Kishnani, Priya S; Campbell, Michael J

    2010-12-01

    Pompe disease (acid α-glucosidase deficiency) is one of several lysosomal storage diseases amenable to treatment with enzyme replacement therapy (ERT). While echocardiography (echo) has been the standard method to evaluate the cardiac response to ERT, cardiac magnetic resonance imaging (CMR) has the advantage of a better tissue definition and characterization of myocardial fibrosis. However, CMR for Pompe disease is not frequently performed due to a high risk of sedation. We report the first use of CMR in a feasible protocol to quantify left ventricular (LV) mass, function, and the presence of myocardial fibrosis in the Pompe population. Children with Pompe disease on ERT were assessed with transthoracic echo and CMR over a 3 year period at a single institution. Echocardiography was performed using standard techniques without sedation. CMR was performed using retrospectively gated and real-time imaging, with and without sedation. LV mass indexed to body surface area (LVMI) and ejection fraction (EF) were measured by both echo and CMR, and evaluated for change over time. Myocardial fibrosis was assessed by CMR with delayed enhancement imaging 5-10 min after gadolinium contrast using single shot inversion recovery sequences with inversion time set to null the signal from normal myocardium. Seventeen CMR scans were successfully performed in 10 subjects with Pompe disease (median age at first CMR is 9 months, range 1-38 months, 80% male), with sedation only performed in 4 studies. There was a median interval of 5 months (range 0-34 months) from the start of ERT to first CMR (baseline). At baseline, the median indexed LVMI by CMR (140.0 g/m(2), range 43.8-334.0) tended to be lower than that assessed by echo (median 204.0 g/m(2), range 52.0-385.0), but did not reach statistical significance. At baseline, CMR EF was similar to that assessed by echo (55% vs. 55%). Overall, there was no significant decrease in CMR measured LVMI over time (CMR median LVMI at baseline 94 g

  3. [Limits of cardiac functional adaptation in "top level" resistance athletes].

    Science.gov (United States)

    Carù, B; Righetti, G; Bossi, M; Gerosa, C; Gazzotti, G; Maranetto, D

    2001-02-01

    Sports activity, particularly when performed at high level, provokes cardiovascular adjustments depending on the type of sport and on the level of the load. We evaluated 15 athletes from the Italian national team during a non-agonistic period of cross country skiing, with non-invasive tests including exercise test, color Doppler echocardiography, Holter monitoring, physical examination and standard rest electrocardiogram. Physical examination, rest electrocardiogram, exercise testing and echocardiography were all within the range of the expected values for this type of subjects. Holter monitoring recorded during the periods of agonistic activity revealed significant hypokinetic arrhythmias such as severe bradycardia, pauses, I and II degree atrioventricular blocks, and complete atrioventricular block in 2 cases; these features were not observed on Holter monitoring recorded during the non-agonistic period. The perfect health status of subjects and their racing results may bring about physiological functional adjustments, but these observations suggest the need for a follow-up to evaluate possible pathologic outcomes.

  4. Blood conservation techniques and platelet function in cardiac surgery.

    Science.gov (United States)

    Boldt, J; Zickmann, B; Czeke, A; Herold, C; Dapper, F; Hempelmann, G

    1991-09-01

    Postoperative alterations in platelet function induced by cardiopulmonary bypass (CPB) are of importance. The effect on platelet aggregation of three different techniques for reducing blood consumption was studied in 30 patients undergoing elective aortocoronary bypass grafting from the beginning of anesthesia until the 1st postoperative day. The patients were randomly divided into three groups, in which 1) a cell separator was used during and after CPB; 2) a hemofiltration device was used; and 3) high-dose aprotinin was used in order to reduce the need of homologous blood. A fourth group undergoing neurosurgery procedures served as a control. Platelet aggregation induced by adenosine diphosphate (concentration 0.25, 0.50, 1.0, and 2.0 microM), collagen (4 microliters/ml), and epinephrine (25 microM) was determined by the turbidimetric method. Platelet aggregation was not significantly changed in the control group, indicating that the operation itself did not impair platelet function. At the end of the operation (after retransfusion of the salvaged pump blood), the maximum aggregation and maximum gradient of aggregation induced by all three inductors were most reduced (significantly) in the cell-separator patients. On the 1st postoperative day, platelet aggregation in the hemofiltration patients and the patients treated with aprotinin had normalized. Aggregation of patients pretreated with high-dose aprotinin was not different from that of the hemofiltration patients throughout the investigation. Blood loss was significantly highest in the cell-separator group (770 +/- 400 ml on the 1st postoperative day) but was not different between the hemofiltration (390 +/- 230 ml) and the aprotinin-treated patients (260 +/- 160 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Preserved cardiac function despite marked impairment of cAMP generation.

    Directory of Open Access Journals (Sweden)

    Mei Hua Gao

    Full Text Available So many clinical trials of positive inotropes have failed, that it is now axiomatic that agents that increase cAMP are deleterious to the failing heart. An alternative strategy is to alter myocardial Ca(2+ handling or myofilament response to Ca(2+ using agents that do not affect cAMP. Although left ventricular (LV function is tightly linked to adenylyl cyclase (AC activity, the beneficial effects of AC may be independent of cAMP and instead stem from effects on Ca(2+ handling. Here we ask whether an AC mutant molecule that reduces LV cAMP production would have favorable effects on LV function through its effects on Ca(2+ handling alone.We generated transgenic mice with cardiac-directed expression of an AC6 mutant (AC6mut. Cardiac myocytes showed impaired cAMP production in response to isoproterenol (74% reduction; p<0.001, but LV size and function were normal. Isolated hearts showed preserved LV function in response to isoproterenol stimulation. AC6mut expression was associated with increased sarcoplasmic reticulum Ca(2+ uptake and the EC50 for SERCA2a activation was reduced. Cardiac myocytes isolated from AC6mut mice showed increased amplitude of Ca(2+ transients in response to isoproterenol (p = 0.0001. AC6mut expression also was associated with increased expression of LV S100A1 (p = 0.03 and reduced expression of phospholamban protein (p = 0.01.LV AC mutant expression is associated with normal cardiac function despite impaired cAMP generation. The mechanism appears to be through effects on Ca(2+ handling - effects that occur despite diminished cAMP.

  6. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

  7. Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Hermans Mieke CE

    2012-07-01

    Full Text Available Abstract Background Myotonic dystrophy type 1 (MD1 is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1. Methods Eighty MD1 patients underwent physical examination, electrocardiography (ECG, echocardiography and cardiovascular magnetic resonance (CMR. Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length. Results Functional and structural abnormalities were detected in 35 patients (44%. Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%. In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04, male gender (p Conclusions CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.

  8. Pulse wave velocity and cardiac autonomic function in type 2 diabetes mellitus.

    Science.gov (United States)

    Chorepsima, Stamatina; Eleftheriadou, Ioanna; Tentolouris, Anastasios; Moyssakis, Ioannis; Protogerou, Athanasios; Kokkinos, Alexandros; Sfikakis, Petros P; Tentolouris, Nikolaos

    2017-05-19

    Increased carotid-femoral pulse wave velocity (PWV) has been associated with incident cardiovascular disease, independently of traditional risk factors. Cardiac autonomic dysfunction is a common complication of diabetes and has been associated with reduced aortic distensibility. However, the association of cardiac autonomic dysfunction with PWV is not known. In this study we examined the association between cardiac autonomic function and PWV in subjects with type 2 diabetes mellitus. A total of 290 patients with type 2 diabetes were examined. PWV was measured at the carotid-femoral segment with applanation tonometry. Central mean arterial blood pressure (MBP) was determined by the same apparatus. Participants were classified as having normal (n = 193) or abnormal (n = 97) PWV values using age-corrected values. Cardiac autonomic nervous system activity was determined by measurement of parameters of heart rate variability (HRV). Subjects with abnormal PWV were older, had higher arterial blood pressure and higher heart rate than those with normal PWV. Most of the values of HRV were significantly lower in subjects with abnormal than in those with normal PWV. Multivariate analysis, after controlling for various confounding factors, demonstrated that abnormal PWV was associated independently only with peripheral MBP [odds ratio (OR) 1.049, 95% confidence intervals (CI) 1.015-1.085, P = 0.005], central MBP (OR 1.052, 95% CI 1.016-1.088, P = 0.004), log total power (OR 0.490, 95% CI 0.258-0.932, P = 0.030) and log high frequency power (OR 0.546, 95% CI 0.301-0.991, P = 0.047). In subjects with type 2 diabetes, arterial blood pressure and impaired cardiac autonomic function is associated independently with abnormal PWV.

  9. New structural and functional defects in polyphosphate deficient bacteria: A cellular and proteomic study

    Directory of Open Access Journals (Sweden)

    Chávez Francisco P

    2010-01-01

    Full Text Available Abstract Background Inorganic polyphosphate (polyP, a polymer of tens or hundreds of phosphate residues linked by ATP-like bonds, is found in all organisms and performs a wide variety of functions. PolyP is synthesized in bacterial cells by the actions of polyphosphate kinases (PPK1 and PPK2 and degraded by exopolyphosphatase (PPX. Bacterial cells with polyP deficiencies due to knocking out the ppk1 gene are affected in many structural and important cellular functions such as motility, quorum sensing, biofilm formation and virulence among others. The cause of this pleiotropy is not entirely understood. Results The overexpression of exopolyphosphatase in bacteria mimicked some pleitropic defects found in ppk1 mutants. By using this approach we found new structural and functional defects in the polyP-accumulating bacteria Pseudomonas sp. B4, which are most likely due to differences in the polyP-removal strategy. Colony morphology phenotype, lipopolysaccharide (LPS structure changes and cellular division malfunction were observed. Finally, we used comparative proteomics in order to elucidate the cellular adjustments that occurred during polyP deficiency in this bacterium and found some clues that helped to understand the structural and functional defects observed. Conclusions The results obtained suggest that during polyP deficiency energy metabolism and particularly nucleoside triphosphate (NTP formation were affected and that bacterial cells overcame this problem by increasing the flux of energy-generating metabolic pathways such as tricarboxilic acid (TCA cycle, β-oxidation and oxidative phosphorylation and by reducing energy-consuming ones such as active transporters and amino acid biosynthesis. Furthermore, our results suggest that a general stress response also took place in the cell during polyP deficiency.

  10. Evaluation of cardiac motion and function by cine magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kondo, Takeshi; Kurokawa, Hiroshi; Anno, Hirofumi

    1992-01-01

    Cardiac cine magnetic resonance imaging (MRI) was studied to evaluate the cardiac motion and function, and a water-stream phantom study was performed to clarify whether it was possible to quantitatively assess the valvular regurgitation flow by the size of the flow void. In normal subjects, the left ventricular (LV) epicardial apex swung up to the base only a few millimeters, and the mitral annulus ring moved about 14 mm as mean value toward the apex during systole. Those motions of mitral annulus ring may contribute to the left atrial filling. The LV longitudinal shortening and torsions were shown by the tagging method. This tagging method was the best method for estimating cardiac motions. Cardiac cine MRI using software including a modified Simpson's method program and a wall motion analysis program was useful for routine LV volumetry and wall motion analysis because it was a simple and reliable method. Our water-stream phantom studies demonstrated that it might be difficult to perform quantitative evaluation of valvular regurgitation flow by using only the size of the flow void without acquiring information relating to the orifice area. (author)

  11. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus

    NARCIS (Netherlands)

    van der Meer, Rutger W.; Rijzewijk, Luuk J.; de Jong, Hugo W. A. M.; Lamb, Hildo J.; Lubberink, Mark; Romijn, Johannes A.; Bax, Jeroen J.; de Roos, Albert; Kamp, Otto; Paulus, Walter J.; Heine, Robert J.; Lammertsma, Adriaan A.; Smit, Johannes W. A.; Diamant, Michaela

    2009-01-01

    Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy

  12. A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice.

    Science.gov (United States)

    Carbone, Salvatore; Mauro, Adolfo G; Mezzaroma, Eleonora; Kraskauskas, Donatas; Marchetti, Carlo; Buzzetti, Raffaella; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano

    2015-11-01

    Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. Published by Elsevier Ireland Ltd.

  13. Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Margaret E McCormick

    Full Text Available A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.

  14. Cardiodynamicsgram: a novel tool for monitoring cardiac function in exercise training.

    Science.gov (United States)

    Wen, Xu; Guo, Bokai; Gong, Yinglan; Xia, Ling; Yu, Jie

    2018-04-27

    This study evaluated the feasibility of cardiodynamicsgram (CDG) for monitoring the cardiac functions of athletes and exercisers. CDG could provide an effective, simple, and economical tool for exercise training. Seventeen middle-distance race athletes aged 14-28 years old were recruited. CDG tests and blood test including creatine kinase (CK), CK-MB isoenzyme, and high-sensitivity troponin I (hsTnI) were performed before a high-intensity prolonged training, as well as 2 and 14 h after training, respectively. The CDG test result was unsatisfactory when the CK test result was used as standard. However, the accuracy of CDG test was about 80% when CK-MB and hsTnI were used as standards. Thus, CDG offers a noninvasive, simple, and economical approach for monitoring the cardiac function of athletes and exercisers during exercise training. Nonetheless, the applicability of CDG needs further investigation.

  15. Hypothalamus-pituitary-thyroid axis activity and function of cardiac muscle in energy deficit

    Directory of Open Access Journals (Sweden)

    Katarzyna Lachowicz

    2017-12-01

    Full Text Available Frequently repeated statement that energy restriction is a factor that improves cardiovascular system function seems to be not fully truth. Low energy intake modifies the hypothalamus-pituitary-thyroid axis activity and thyroid hormone peripheral metabolism. Thyroid hormones, as modulators of the expression and activity of many cardiomyocyte proteins, control heart function. Decreased thyroid hormone levels and their disturbanced conversion and action result in alternation of cardiac remodeling, disorder of calcium homeostasis and diminish myocardial contractility. This review provides a summary of the current state of knowledge about the mechanisms of energy restriction effects on thyroidal axis activity, thyroid hormone peripheral metabolism and action in target tissues, especially in cardiac myocytes. We also showed the existence of energy restriction-thyroid-heart pathway.

  16. Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

    Science.gov (United States)

    Tanaka, Kayo; Tanaka, Hiroaki; Maki, Shintaro; Kubo, Michiko; Nii, Masafumi; Magawa, Shoichi; Hatano, Fumi; Tsuji, Makoto; Osato, Kazuhiro; Kamimoto, Yuki; Umekawa, Takashi; Ikeda, Tomoaki

    2018-02-20

    The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

  17. Exposure to occupational air pollution and cardiac function in workers of the Esfahan Steel Industry, Iran.

    Science.gov (United States)

    Golshahi, Jafar; Sadeghi, Masoumeh; Saqira, Mohammad; Zavar, Reihaneh; Sadeghifar, Mostafa; Roohafza, Hamidreza

    2016-06-01

    Air pollution is recognized as an important risk factor for cardiovascular disease. We investigated association of exposure to occupational air pollution and cardiac function in the workers of the steel industry. Fifty male workers of the agglomeration and coke-making parts of the Esfahan Steel Company were randomly selected (n = 50). Workers in the administrative parts were studied as controls (n = 50). Those with known history of hypertension, dyslipidemia, or diabetes, and active smokers were not included. Data of age, body mass index, employment duration, blood pressure, fasting blood sugar, and lipid profile were gathered. Echocardiography was performed to evaluate cardiac function. Left ventricular ejection fraction was lower in workers of the agglomeration/coke-making parts than in controls (mean difference = 5 to 5.5 %, P steel industry is associated with left heart systolic dysfunction. Possible right heart insults due to air pollution exposure warrant further investigations.

  18. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    Directory of Open Access Journals (Sweden)

    A. O. Shevchenko

    2015-01-01

    Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

  19. Renal and cardiac function during alpha1-beta-blockade in congestive heart failure

    DEFF Research Database (Denmark)

    Heitmann, M; Davidsen, U; Stokholm, K H

    2002-01-01

    The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control...... of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function....

  20. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    International Nuclear Information System (INIS)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats

  1. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Directory of Open Access Journals (Sweden)

    Camilla Figueiredo Grans

    2014-07-01

    Full Text Available Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week. At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32% and trained infarcted (+46% in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%, myocardial performance index (-39% and systolic blood pressure (+6% improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%, as well as in the low frequency band of systolic blood pressure (-46% in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  2. Image processing of x-ray left ventricular cineangiocardiograms and displays of cardiac functions

    International Nuclear Information System (INIS)

    Eiho, Shigeru; Yamada, Shigeru; Kuwahara, Michiyoshi

    1980-01-01

    Cineangiocardiography has been often used as one of the highly helpful techniques to examine the cardiac function. This paper deals with the method of tracing automatically the boundaries of the left ventricle on cineangiocardiograms, the method to evaluate and display various cardiac functions, the method to reconstruct the left ventricular cavity from biplane cineangiocardiograms and the method to display a 3-dimensional shape of the left ventricle reconstructed. Our algorithm of boundary tracing is based on a heuristic search for a local maximum of the changing rate in the gray level of cineangiocardiogram. The boundaries of endocardial margins of the left ventricle on 80 to 120 consecutive frames are automatically traced by our method. By using the detected boundaries of the left ventricle, a lot of quantitative information may be established on the cardiac function. The volume change, the wall motions and the %-shortening are displayed graphically. The motion of the boundary of the left ventricle is displayed on a CRT as a moving picture. The left ventricular cavity is reconstructed from the detected boundaries of the left ventricle on biplane cineangiocardiograms. A reconstructed image can be shown as superimposed lines or halftone planes to produce a 3-dimensional perspective. The %-shortening which shows the contractility of the regional myocardium is displayed on a silhouette of the left ventricle. We can easily recognize the abnormal area of contraction and the level and spread of abnormality from this displayed image. With the use of the system described in this paper, we can grasp the movement of the left ventricle exactly and evaluate the cardiac function quantitatively. (author)

  3. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Energy Technology Data Exchange (ETDEWEB)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

    2014-07-15

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  4. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Science.gov (United States)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Background Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats. PMID:25014059

  5. Cardiovascular measurement and cardiac function analysis with electron beam computed tomography in health Chinese people (50 cases report)

    International Nuclear Information System (INIS)

    Lu Bin; Dai Ruping; Zhang Shaoxiong; Bai Hua; Jing Baolian; Cao Cheng; He Sha; Ren Li

    1998-01-01

    Purpose: To quantitatively measure cardiovascular diameters and function parameters by using electron beam computed tomography, EBCT. Methods: Men 50 health Chinese people accepted EBCT common transverse and short-axis enhanced movie scan (27 men, 23 women, average age 47.7 years.). The transverse scan was used to measure the diameters of the ascending aorta, descending aorta, pulmonary artery and left atrium. The movie study was used to measure the left ventricular myocardium thickness and analysis global, sectional and segmental function of the right and left ventricles. Results: The cardiovascular diameters and cardiac functional parameters were calculated. The diameters and most functional parameters (end syspoble volume, syspole volume, ejection fraction, cardiac-output, cardiac index) of normal Chinese men were greater than those of women (P>0.05). However, the EDV and MyM(myocardium mass) of both ventricles were significant (p<0.01). Conclusion: EBCT is a minimally invasive method for cardiovascular measurement and cardiac function evaluation

  6. Combining computer modelling and cardiac imaging to understand right ventricular pump function.

    Science.gov (United States)

    Walmsley, John; van Everdingen, Wouter; Cramer, Maarten J; Prinzen, Frits W; Delhaas, Tammo; Lumens, Joost

    2017-10-01

    Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  7. Usefulness of true FISP cine MR imaging in patients with poor cardiac function

    Energy Technology Data Exchange (ETDEWEB)

    Sakuma, Toshiharu; Yamada, Naoaki; Motooka, Makoto; Enomoto, Naoyuki; Maeshima, Isamu; Matsuda, Kazuhide; Urayama, Shinichi; Ikeo, Miki [National Cardiovascular Center, Suita, Osaka (Japan)

    2002-01-01

    This study was done to assess the value of True FISP cine in patients with poor cardiac function. True FISP cine and FLASH cine imaging were performed on a 1.5 T machine. Both short axis and horizontal long axis imaging sections were used. The imaging sections used a Matrix (120 x 128), FOV (24 x 32 cm), and had a slice thickness of 8 mm. The imaging time for True FISP cine was 8 heart beats and 17 heart beats for FLASH cine. The contrast-to-noise ratio between the blood and myocardium (CNR) was measured at enddiastole and endsystole. The subjects in the study were 10 healty volunteers (average age 26.5{+-}3.2 years) and 12 patients with hypofunction (average age 53.9{+-}13.2 years). In the volunteers, the CNR of the short axis imaging was similar in both True FISP (24.6{+-}3.7) and FLASH (23.4{+-}5.9). In the patients with poor cardiac function however, the CNR of True FISP was larger than FLASH in both the short and long axis. In the short axis (22.7{+-}6.1 vs. 17.9{+-}5.3, P<0.01) and in the long axis (17.4{+-}4.3 vs. 9.3{+-}4.0, P<0.01). We conclude that True FISP cine has a higher contrast in a shorter imaging time than FLASH cine. True FISP cine is especially useful in patients with poor cardiac function. (author)

  8. The specific case: cardiac amyloidosis as differential diagnosis in case of restricted cardiac pump function; Der besondere Fall. Amyloidose des Herzens als Differenzialdiagnose bei eingeschraenkter kardialer Pumpfunktion

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, L. [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Zellweger, M.; Niemann, T.

    2014-03-15

    The NMR imaging data in combination with clinical characterization and echocardiography are consistent with the diagnosis of a cardiac amyloidosis. The article describes disease pattern and diagnosis based on contrast agent accumulation and diastolic functional disturbances. CT was performed to exclude pulmonary embolism.

  9. Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model.

    Science.gov (United States)

    Tveita, Torkjel; Sieck, Gary C

    2012-08-01

    Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15 °C. Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15 °C (60 min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30 min at 37 °C and during cooling. In normothermic controls continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15 °C were found: Compared to saline treated animals throughout cooling from 33 to 15 °CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24 °C. Likewise, during cooling between 33 and 28 °C also LVdP/dt(max) was significantly higher in the milrinone group. Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15 °C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15 °C. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study

    NARCIS (Netherlands)

    Janssens, Karin A. M.; Riese, Harriette; Van Roon, Arie M.; Hunfeld, Joke A. M.; Groot, Paul F. C.; Oldehinkel, Albertine J.; Rosmalen, Judith G. M.

    2016-01-01

    Objective Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac

  11. Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study

    Directory of Open Access Journals (Sweden)

    Kotb Abbass Metwalley

    2013-01-01

    Full Text Available Background: Growth hormone deficiency (GHD in adults is associated with a cluster of cardiovascular risk factors that may contribute to an increased mortality for cardiovascular disease. In children, relatively few studies have investigated the effect of GHD and replacement therapy on cardiac performance and metabolic abnormalities that may place them at a higher risk of cardiovascular disease (CVD at an early age. Aim: This study was aimed to assess the left ventricular function, lipid profile, and degree of insulin resistance in Egyptian children with GHD before and after 1 year of GH replacement therapy. Settings and Design: Prospective case-control study, single-center study. Materials and Methods: Thirty children with short stature due to GHD were studied in comparison to 20 healthy age- and sex-matched children. All subjects were subjected to history, clinical examination, auxological assessment, and echocardiography to assess the left ventricular function. Blood samples were collected for measuring IGF-1, lipid profile (Total, LDL, HDL cholesterol, triglyceride, and atherogenic index (AI, fasting blood sugar, and fasting insulin levels. In addition, basal and stimulated GH levels were measured in children with suspected GHD. Statistical Analysis Used: Student′s t-test was used for parametric data, and the Mann-Whitney U-test was used for non-parametric data. Results: Total, LDL cholesterol, triglyceride, AI, and insulin were significantly higher in children with GHD than in healthy controls at baseline. After 12 months of GH replacement therapy, total, LDL cholesterol, triglyceride, AI and insulin were significantly decreased, while homeostatic model assessment for insulin resistance index (HOMA-IR was significantly increased compared to both pre-treatment and control values. At baseline, the left ventricular mass (LVM and left ventricular mass index (LVMi were significantly lower in GHD children than in controls. After 12 months of GH

  12. Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

    Directory of Open Access Journals (Sweden)

    Antônio Carlos Cicogna

    1999-04-01

    Full Text Available OBJECTIVE: To assess the effect of food restriction (FR on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR. METHODS: Isolated papillary muscle preparations of the left ventricle (LV of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1 reduction in the body weight and LV weight of SHR and WKY rats; 2 increase in the time to peak shortening and the time to peak developed tension (DT in the hypertrophied myocardium of the SHR; 3 diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

  13. Pulmonary function and health-related quality of life 1-year follow up after cardiac surgery.

    Science.gov (United States)

    Westerdahl, Elisabeth; Jonsson, Marcus; Emtner, Margareta

    2016-07-08

    Pulmonary function is severely reduced in the early period after cardiac surgery, and impairments have been described up to 4-6 months after surgery. Evaluation of pulmonary function in a longer perspective is lacking. In this prospective study pulmonary function and health-related quality of life were investigated 1 year after cardiac surgery. Pulmonary function measurements, health-related quality of life (SF-36), dyspnoea, subjective breathing and coughing ability and pain were evaluated before and 1 year after surgery in 150 patients undergoing coronary artery bypass grafting, valve surgery or combined surgery. One year after surgery the forced vital capacity and forced expiratory volume in 1 s were significantly decreased (by 4-5 %) compared to preoperative values (p < 0.05). Saturation of peripheral oxygen was unchanged 1 year postoperatively compared to baseline. A significantly improved health-related quality of life was found 1 year after surgery, with improvements in all eight aspects of SF-36 (p < 0.001). Sternotomy-related pain was low 1 year postoperatively at rest (median 0 [min-max; 0-7]), while taking a deep breath (0 [0-4]) and while coughing (0 [0-8]). A more pronounced decrease in pulmonary function was associated with dyspnoea limitations and impaired subjective breathing and coughing ability. One year after cardiac surgery static and dynamic lung function measurements were slightly decreased, while health-related quality of life was improved in comparison to preoperative values. Measured levels of pain were low and saturation of peripheral oxygen was same as preoperatively.

  14. Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males.

    Science.gov (United States)

    Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

    1997-12-01

    Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

  15. Relationship between myocardial T2* values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Carlo, E-mail: c.liguori@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Pitocco, Francesca, E-mail: f.pitocco@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Di Giampietro, Ilenia, E-mail: i.digiampietro@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Vivo, Aldo Eros de, E-mail: devivoeros@gmail.com [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Schena, Emiliano, E-mail: e.schena@unicampus.it [Unit of Measurements and Biomedical Instrumentation, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Cianciulli, Paolo, E-mail: CIANCIULLI.PAOLO@aslrmc.it [Thalassemia Unit, Ospedale Sant Eugenio, Piazzale dell’Umanesimo 10, 00143 Rome (Italy); Zobel, Bruno Beomonte, E-mail: b.zobel@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy)

    2013-09-15

    Purpose: Myocardial T2* cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2* value in myocardium and left–right ventricular volumetric and functional parameters and to evaluate the existing associations between left–right ventricles volumetric and functional parameter, myocardial T2* values and blood ferritin levels. Materials and methods: A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. Results: A significant correlation was observed between EFLV and T2* (p = 0.0001), EFRV and T2* (p = 0.0279). An inverse correlation was present between DVLV and T2* (p = 0.0468), SVLV and T2* (p = 0.0003), SVRV and T2* (p = 0.0001). There was no significant correlation between cardiac T2* and LV–RV mass indices. A significant correlation was observed between T2* and serum ferritin levels (p < 0.001) and between EFLV and serum ferritin (p < 0.05). Conclusion: Myocardial iron load assessed by T2* cardiac magnetic resonance is associated with deterioration in left–right ventricular function; this is more evident when T2* values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients.

  16. Relationship between myocardial T2* values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels

    International Nuclear Information System (INIS)

    Liguori, Carlo; Pitocco, Francesca; Di Giampietro, Ilenia; Vivo, Aldo Eros de; Schena, Emiliano; Cianciulli, Paolo; Zobel, Bruno Beomonte

    2013-01-01

    Purpose: Myocardial T2* cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2* value in myocardium and left–right ventricular volumetric and functional parameters and to evaluate the existing associations between left–right ventricles volumetric and functional parameter, myocardial T2* values and blood ferritin levels. Materials and methods: A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. Results: A significant correlation was observed between EFLV and T2* (p = 0.0001), EFRV and T2* (p = 0.0279). An inverse correlation was present between DVLV and T2* (p = 0.0468), SVLV and T2* (p = 0.0003), SVRV and T2* (p = 0.0001). There was no significant correlation between cardiac T2* and LV–RV mass indices. A significant correlation was observed between T2* and serum ferritin levels (p < 0.001) and between EFLV and serum ferritin (p < 0.05). Conclusion: Myocardial iron load assessed by T2* cardiac magnetic resonance is associated with deterioration in left–right ventricular function; this is more evident when T2* values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients

  17. Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

    Science.gov (United States)

    Schlegel, Todd; Starc, Vito; Leban, Manja; Sinigoj, Petra; Vrhovec, Milos

    2011-01-01

    In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

  18. Intravital imaging of cardiac function at the single-cell level.

    Science.gov (United States)

    Aguirre, Aaron D; Vinegoni, Claudio; Sebas, Matt; Weissleder, Ralph

    2014-08-05

    Knowledge of cardiomyocyte biology is limited by the lack of methods to interrogate single-cell physiology in vivo. Here we show that contracting myocytes can indeed be imaged with optical microscopy at high temporal and spatial resolution in the beating murine heart, allowing visualization of individual sarcomeres and measurement of the single cardiomyocyte contractile cycle. Collectively, this has been enabled by efficient tissue stabilization, a prospective real-time cardiac gating approach, an image processing algorithm for motion-artifact-free imaging throughout the cardiac cycle, and a fluorescent membrane staining protocol. Quantification of cardiomyocyte contractile function in vivo opens many possibilities for investigating myocardial disease and therapeutic intervention at the cellular level.

  19. Effects of cigarette smoking on cardiac autonomic function during dynamic exercise.

    Science.gov (United States)

    Mendonca, Goncalo V; Pereira, Fernando D; Fernhall, Bo

    2011-06-01

    The purpose of this study was to investigate the acute effect of cigarette smoking on cardiac autonomic function in young adult smokers during dynamic exercise. Fourteen healthy young smokers (21.4 ± 3.4 years) performed peak and submaximal exercise protocols under control and smoking conditions. Resting and submaximal beat-to-beat R-R series were recorded and spectrally decomposed using the fast Fourier transformation. Smoking resulted in a significant decrease in work time, VO(2peak) and peak O(2) pulse (P exercise after smoking (P smoking, both at rest and during exercise (P smoking (P smoking, but only at rest (P smoking is accompanied by acute changes in heart rate spectral components both at rest and during exercise. Therefore, the cardiac autonomic control is altered by smoking not only at rest, but also during exercise, resulting in reduced vagal modulation and increased sympathetic dominance.

  20. Functional Near-Infrared Fluorescence Imaging for Cardiac Surgery and Targeted Gene Therapy

    Directory of Open Access Journals (Sweden)

    Akira Nakayama

    2002-10-01

    Full Text Available Cardiac revascularization is presently performed without realtime visual assessment of myocardial blood flow or perfusion. Moreover, gene therapy of the heart cannot, at present, be directed to specific territories at risk for myocardial infarction. We have developed a surgical imaging system that exploits the low autofluorescence, deep tissue penetration, low tissue scatter, and invisibility of near-infrared (NIR fluorescent light. By completely isolating visible and NIR light paths, one is able to visualize, simultaneously, the anatomy and/or function of the heart, or any desired tissue. In rat model systems, we demonstrate that the heptamethine indocyanine-type NIR fluorophores IR-786 and the carboxylic acid form of IRDye78 can be injected intravenously in the living animal to provide real-time visual assessment of myocardial blood flow or perfusion intraoperatively. This imaging system may prove useful for the refinement of revascularization techniques, and for the administration of cardiac gene therapy.

  1. Hyperpolarized metabolic MR in the study of cardiac function and disease

    DEFF Research Database (Denmark)

    Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

    2014-01-01

    Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

  2. Efficacy of cardiac resynchronization with defibrillator insertion in patients undergone coronary artery bypass graft: A cohort study of cardiac function

    Directory of Open Access Journals (Sweden)

    Reza Karbasi Afshar

    2015-01-01

    Full Text Available Introduction: Cardiac resynchronization therapy (CRT is a proven therapeutic method in selected patients with heart failure and systolic dysfunction which increases left ventricular function and patient survival. We designed a study that included patients undergoing coronary artery bypass graft (CABG, with and without CRT-defibrillator (CRT-D inserting and then measured its effects on these two groups. Patients and Methods: Between 2010 and 2013, we conducted a prospective cohort study on 100 coronary artery disease patients where candidate for CABG. Then based on the receiving CRT-D, the patients were categorized in two groups; Group 1 ( n = 48, with CRT-D insertion before CABG and Group 2 ( n = 52 without receiving CRT-D. Thereafter both of these groups were followed-up at 1-3 months after CABG for mortality, hospitalization, atrial fibrillation (AF, echocardiographic assessment, and New York Heart Association (NYHA class level. Results: The mean age of participants in Group 1 (48 male and in Group 2 (52 male was 58 ± 13 and 57 ± 12 respectively. Difference between Groups 1 and 2 in cases of mean left ventricular ejection fraction (LVEF changes and NYHA class level was significant ( P > 0.05. Hospitalization ( P = 0.008, mortality rate ( P = 0.007, and AF were significantly different between these two groups. Conclusions: The results showed that the increase in LVEF and patient′s improvement according to NYHA-class was significant in the first group, and readmission, mortality rate and AF was increased significantly in the second group.

  3. Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function.

    Science.gov (United States)

    Wengrowski, Anastasia M; Wang, Xin; Tapa, Srinivas; Posnack, Nikki Gillum; Mendelowitz, David; Kay, Matthew W

    2015-02-01

    Release of norepinephrine (NE) from sympathetic neurons enhances heart rate (HR) and developed force through activation of β-adrenergic receptors, and this sympathoexcitation is a key risk for the generation of cardiac arrhythmias. Studies of β-adrenergic modulation of cardiac function typically involve the administration of exogenous β-adrenergic receptor agonists to directly elicit global β-adrenergic receptor activation by bypassing the involvement of sympathetic nerve terminals. In this work, we use a novel method to activate sympathetic fibres within the myocardium of Langendorff-perfused hearts while measuring changes in electrical and mechanical function. The light-activated optogenetic protein channelrhodopsin-2 (ChR2) was expressed in murine catecholaminergic sympathetic neurons. Sympathetic fibres were then photoactivated to examine changes in contractile force, HR, and cardiac electrical activity. Incidence of arrhythmia was measured with and without exposure to photoactivation of sympathetic fibres, and hearts were optically mapped to detect changes in action potential durations and conduction velocities. Results demonstrate facilitation of both developed force and HR after photostimulated release of NE, with increases in contractile force and HR of 34.5 ± 5.5 and 25.0 ± 9.3%, respectively. Photostimulation of sympathetic fibres also made hearts more susceptible to arrhythmia, with greater incidence and severity. In addition, optically mapped action potentials displayed a small but significant shortening of the plateau phase (-5.5 ± 1.0 ms) after photostimulation. This study characterizes a powerful and clinically relevant new model for studies of cardiac arrhythmias generated by increasing the activity of sympathetic nerve terminals and the resulting activation of myocyte β-adrenergic receptors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  4. Evaluation of cardiac morphology and function in mitral stenosis using CT

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Masaki [Chiba Univ. (Japan). School of Medicine

    1992-11-01

    The purpose of this study was to evaluate cardiac morphology and function in patients with mitral stenosis (MS). The subjects consisted of 96 patients (23 males and 73 females) with MS who underwent plain and contrast-enhanced CT. Follow-up examinations were performed at least twice in 42 patients, including 18 who were examined before and after surgery. The volume of each cardiac chamber was calculated by Simpson's rule and was divided by body surface area (BSA). The average left atrial (LA) volume was 171[+-]80 cm[sup 3]/m[sup 2] BSA in the 96 MS patients, and 46[+-]10 cm[sup 3]/m[sup 2] BSA in normal control subjects. Atrial fibrillation (Af) was present in 61 patients (64%), and left atrial thrombi were detected in 15 (25%) of them. LA volume increased by 16% in 24 patients without surgery during a mean follow-up period of 4.1 years. The LA tended to enlarge more in the patients with a smaller mitral valve area, a larger LA volume at the first examination, or Af. In 18 patients, after open surgery or percutaneous transvenous mitral commissurotomy, pulmonary CT values decreased significantly as a result of the improvement of pulmonary congestion. LA and RA volume decreased significantly and LV volume increased after surgery. It was concluded that CT was useful for evaluating cardiac function and morphological changes, not only by detecting mitral valve calcification and LA thrombi but also by measuring cardiac volume and pulmonary CT values. (author).

  5. Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

    Science.gov (United States)

    Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

    2013-01-01

    Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

  6. Influence of functional knee bracing on the isokinetic and functional tests of anterior cruciate ligament deficient patients.

    Directory of Open Access Journals (Sweden)

    Niyousha Mortaza

    Full Text Available Use of functional knee braces has been suggested to provide protection and to improve kinetic performance of the knee in Anterior cruciate ligament(ACL-injured patients. However, many athletes might refrain from wearing the braces because of the fear of performance hindrance in the playing field. The aim of this study was to examine the effect of three functional knee brace/sleeves upon the isokinetic and functional performance of ACL-deficient and healthy subjects. Six anterior cruciate ligament deficient (29.0 ± 5.3 yrs., 175.2 ± 5.4 cm, and 73.0 ± 10.0 kg and six healthy male subjects (27.2 ± 3.7 yrs., 176.4 ± 6.4 cm, and 70.3 ± 6.9 kg were selected. The effect of a custom-made functional knee brace, and two neoprene knee sleeves, one with four metal supports and one without support were examined via the use of isokinetic and functional tests in four sets (non-braced,wearing functional knee brace,and wearing the sleeves. Cross-over hop and single leg vertical jump test were performed and jump height, and hop distance were recorded. Peak torque to body weight ratio and average power in two isokinetic velocities(60°.s(-1,180°.s(-1 were recorded and the brace/sleeves effect was calculated as the changes in peak torque measured in the brace/sleeves conditions, expressed as a percentage of peak torque measured in non-braced condition. Frequency content of the isokinetic torque-time curves was also analyzed. Wilcoxon signed rank test was used to compare the measured values in four test conditions within each control and ACL-deficient group,and Mann-Whitney U test was used for the comparison between the two groups. No significant differences in peak torque, average power, torque-time curve frequency content, vertical-jump and hop measurements were found within the experimental and the non-braced conditions (p>0.05. Although the examined functional knee brace/sleeves had no significant effect on the knee muscle performance, there have been

  7. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1

    International Nuclear Information System (INIS)

    Williams, Kaye J.; Telfer, Brian A.; Xenaki, Dia; Sheridan, Mary R.; Desbaillets, Isabelle; Peters, Hans J.W.; Honess, Davina; Harris, Adrian L.; Dachs, Gabi U.; Kogel, Albert van der; Stratford, Ian J.

    2005-01-01

    Background and purpose: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. Patients and methods: Tumours comprising mouse hepatoma cells lacking HIF-1β (and thereby HIF-1 function) were grown in nude mice and radiation-induced growth delay compared with that seen for wild-type tumours and tumours derived from HIF-1β negative cells where HIF-1 function had been restored. Results: The xenografts that lack HIF-1 activity take longer to establish their growth and are more radioresponsive than both parental xenografts and those with restored HIF-1 function. Pre-treatment of the HIF-1 deficient xenografts with the hypoxic radiosensitizer misonidazole, had little effect on radioresponse. In contrast this treatment radiosensitized the parental xenografts. In spite of this, no difference in oxygenation status was found between the tumour types as measured by Eppendorf O 2 -electrodes and by binding of the hypoxic cell marker NITP. Admixing wild type and HIF-1 deficient cells in the same tumour at ratios of 1 in 10 and 1 in 100 restores the growth of the mixed tumours to that of a 100% HIF-1 proficient cell population. However, when comparing the effects of radiation on the mixed tumours, radioresponsiveness is maintained in those tumours containing the high proportion of HIF-1 deficient cells. Conclusions: The differences in radioresponse do not correlate with tumour oxygenation, suggesting that the hypoxic cells within the HIF-1 deficient tumours do not contribute to the outcome of radiotherapy. Thus, hypoxia impacts on tumour radioresponsiveness not simply because of the physio-chemical mechanism of oxygen with radiation-induced radicals causing damage 'fixation', but also because hypoxia/HIF-1 promotes expression of genes that allow tumour cells to survive under these adverse conditions. Further, the results from the cell mixing experiments uncouple the growth

  8. Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

    Science.gov (United States)

    Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

    1998-01-01

    To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.

  9. Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies.

    LENUS (Irish Health Repository)

    Killeen, Ronan P

    2012-02-01

    OBJECTIVE: To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE). METHODS: Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global\\/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis. RESULTS: All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +\\/- 7 mm vs. 22 +\\/- 4 mm, P < 0.02) and thickness (3.0 +\\/- 1 mm vs. 2.2 +\\/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with\\/without MV prolapse were detected in MV tent area (-1.0 +\\/- 0.6 mm vs. 1.3 +\\/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +\\/- 0.3 mm vs. 0.8 +\\/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +\\/- 19.1 degrees vs. 22.9 +\\/- 14 degrees , P < 0.018) and less for valvular MR (0.6 +\\/- 35.5 degrees vs. 22.9 +\\/- 14 degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%. CONCLUSION: Cardiac MDCT allows the differentiation between functional and valvular causes of MR.

  10. Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Iwasaki, Tsutomu; Suzuki, Tadashi [Gunma Univ., Maebashi (Japan). School of Medicine; Hoshizaki, Hiroshi; Oshima, Shigeru; Taniguchi, Koichi; Nagai, Ryozo

    2000-07-01

    This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59{+-}13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 {mu}g/kg/min before treatment. Patients were divided into good responders (LVEF increase {>=}15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with {beta}-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28{+-}6 to 17{+-}12 (p<0.05), H/M ratio increased from 1.79{+-}0.26 to 2.07{+-}0.32 (p<0.05), LVEF increased from 29{+-}8% to 48{+-}10% (p<0.01), and LVDd decreased from 65{+-}4 mm to 58{+-}5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

  11. Right and left ventricular cardiac function in a developed world population with human immunodeficiency virus studied with radionuclide ventriculography

    DEFF Research Database (Denmark)

    Lebech, Anne-Mette; Gerstoft, Jan; Hesse, Birger

    2004-01-01

    . No correlations were found between reduced cardiac function and levels of the 3 peptides measured. CONCLUSIONS: No major dysfunction of the left ventricle is present in a developed world HIV population. However, a small but significant part of this population has modestly reduced right-sided systolic function.......-associated morbidity and mortality rates. Accordingly, the prevalence of HIV-associated cardiac dysfunction may also have changed. The aim of the study was to establish the prevalence of right- and left-sided cardiac dysfunction in a Danish HIV population, most of whom were undergoing HAART, with radionuclide...... ventricular ejection fraction and 6 (7%) had a reduced right ventricle ejection fraction (0.35-0.42) compared with reference values from the age- and sex-matched reference population. Patients with HIV and reduced cardiac function did not differ in the duration of HIV, CD4 count, CD4 nadir, or HIV RNA load...

  12. Long-lasting functional disabilities in patients who recover from coma after cardiac operations.

    Science.gov (United States)

    Rodriguez, Rosendo A; Nair, Shona; Bussière, Miguel; Nathan, Howard J

    2013-03-01

    Uncertainty regarding the long-term functional outcome of patients who awaken from coma after cardiac operations is difficult for families and physicians and may delay rehabilitation. We studied the long-term functional status of these patients to determine if duration of coma predicted outcome. We followed 71 patients who underwent cardiac operations; recovered their ability to respond to verbal commands after coma associated with postoperative stroke, encephalopathy, and/or seizures; and were discharged from the hospital. The Glasgow Outcome Scale Extended (GOSE) was used to assess functional disability 2 to 4 years after discharge. Outcomes were classified as favorable (GOSE scores 7 and 8) and unfavorable (GOSE scores 1-6). Of 71 patients identified, 39 were interviewed, 15 died, 1 refused to be interviewed, and 16 were lost to follow-up. Of the 54 patients with completed GOSE evaluations, only 15 (28%) had favorable outcomes. Among patients with unfavorable outcomes, 15 (28%) died, 14 (26%) survived with moderate disabilities, and 10 (18%) had severe disabilities. Factors associated with unfavorable outcomes were increases in duration of coma (p = 0.007), time in intensive care (p = 0.006), length of hospitalization (p = 0.004), and postoperative serum creatine kinase levels (p = 0.006). Only duration of coma was an independent predictor of unfavorable outcome (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.008-1.537; p = 0.042). Patients with durations of coma greater than 4 days were more likely to have unfavorable outcomes (OR, 5.1; 95% CI, 1.3-21.3; p = 0.02). Two thirds of comatose patients who survived to discharge after cardiac operations had unfavorable long-term functional outcomes. A longer duration of unconsciousness is a predictor of unfavorable outcome. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function.

    Science.gov (United States)

    Bjursell, Magnus K; Blom, Henk J; Cayuela, Jordi Asin; Engvall, Martin L; Lesko, Nicole; Balasubramaniam, Shanti; Brandberg, Göran; Halldin, Maria; Falkenberg, Maria; Jakobs, Cornelis; Smith, Desiree; Struys, Eduard; von Döbeln, Ulrika; Gustafsson, Claes M; Lundeberg, Joakim; Wedell, Anna

    2011-10-07

    Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  14. Cardiac MRI in pulmonary artery hypertension: correlations between morphological and functional parameters and invasive measurements

    Energy Technology Data Exchange (ETDEWEB)

    Alunni, Jean-Philippe; Otal, Philippe; Rousseau, Herve; Chabbert, Valerie [CHU Rangueil, Department of Radiology, Toulouse (France); Degano, Bruno; Tetu, Laurent; Didier, Alain [CHU Larrey, Department of Pneumology, Toulouse (France); Arnaud, Catherine [CHU Rangueil, Department of Methods in Clinical Research, Toulouse (France); Blot-Souletie, Nathalie [CHU Rangueil, Department of Cardiology, Toulouse (France)

    2010-05-15

    To compare cardiac MRI with right heart catheterisation in patients with pulmonary hypertension (PH) and to evaluate its ability to assess PH severity. Forty patients were included. MRI included cine and phase-contrast sequences, study of ventricular function, cardiac cavity areas and ratios, position of the interventricular septum (IVS) in systole and diastole, and flow measurements. We defined four groups according to the severity of PH and three groups according to IVS position: A, normal position; B, abnormal in diastole; C, abnormal in diastole and systole. IVS position was correlated with pulmonary artery pressures and PVR (pulmonary vascular resistance). Median pulmonary artery pressures and resistance were significantly higher in patients with an abnormal septal position compared with those with a normal position. Correlations were good between the right ventricular ejection fraction and PVR, right ventricular end-systolic volume and PAP, percentage of right ventricular area change and PVR, and diastolic and systolic ventricular area ratio and PVR. These parameters were significantly associated with PH severity. Cardiac MRI can help to assess the severity of PH. (orig.)

  15. Cardiac magnetic resonance imaging in evaluation of anatomical structure and function of the ventricles

    International Nuclear Information System (INIS)

    Suzuki, Jun-ichi; Usui, Masahiro; Takenaka, Katsu

    1990-01-01

    Cardiac magnetic resonance imaging (MRI) is being widely employed for evaluation of cardiovascular anatomies and functions. However, the indications for cardiac MRI to obtain information which cannot be obtained using other conventional methods have not yet been determined. To demonstrate the usefulness of MRI in delineating the apex of the left ventricle and free wall of the right ventricle, end-diastolic short axis MRI images were obtained in 20 patients with apical hypertrophy and in 9 normal volunteers. To compare the accuracy of estimations of left ventricular volumes obtained using the modified Simpson's method of MRI with that using the MRI area length method, 19 patients, in whom left ventriculography had been performed, were studied. The apex of the left ventricle was evaluated circumferentially and distribution of hypertrophied muscles was defined. Sixty-five percent of the length of the right ventricular free wall was clearly delineated. Correlation coefficients of the ejection fraction between MRI and angiography were 0.85 with the modified Simpson's method of MRI, and 0.62 with the area length method of MRI. Three themes were chosen to demonstrate good clinical indications for cardiac MRI. (author)

  16. Cardiac function and myocardial perfusion immediately following maximal treadmill exercise inside the MRI room

    Directory of Open Access Journals (Sweden)

    Ballinger Michelle R

    2008-01-01

    Full Text Available Abstract Treadmill exercise stress testing is an essential tool in the prevention, detection, and treatment of a broad spectrum of cardiovascular disease. After maximal exercise, cardiac images at peak stress are typically acquired using nuclear scintigraphy or echocardiography, both of which have inherent limitations. Although CMR offers superior image quality, the lack of MRI-compatible exercise and monitoring equipment has prevented the realization of treadmill exercise CMR. It is critical to commence imaging as quickly as possible after exercise to capture exercise-induced cardiac wall motion abnormalities. We modified a commercial treadmill such that it could be safely positioned inside the MRI room to minimize the distance between the treadmill and the scan table. We optimized the treadmill exercise CMR protocol in 20 healthy volunteers and successfully imaged cardiac function and myocardial perfusion at peak stress, followed by viability imaging at rest. Imaging commenced an average of 30 seconds after maximal exercise. Real-time cine of seven slices with no breath-hold and no ECG-gating was completed within 45 seconds of exercise, immediately followed by stress perfusion imaging of three short-axis slices which showed an average time to peak enhancement within 57 seconds of exercise. We observed a 3.1-fold increase in cardiac output and a myocardial perfusion reserve index of 1.9, which agree with reported values for healthy subjects at peak stress. This study successfully demonstrates in-room treadmill exercise CMR in healthy volunteers, but confirmation of feasibility in patients with heart disease is still needed.

  17. Thyroid function in girls with menstrual disturbances in iodine-deficiency region

    Directory of Open Access Journals (Sweden)

    O Konstantinova

    2010-06-01

    Full Text Available The estimate the functional state of the female adolescent thyroid with menstrual cycle disorder, living in the iodine deficiency regions, 130 female adolescents with irregular menstrual cycle were examined. Hypothyroidism incidence (in them was 16.9%. In addition we considered TSH range 2.5–4.0 mU/l (highly normal TSH level the extent of which was 12.3%. High extent of antibody carriage to the thyroid (31.3% in girls with irregular menses, having high blood TSH level. There were no statistical differences between the structure of menstrual dysfunction and menstrual duration depending on thyroid function (p = 0.2383, respectively, as well as the average values of estradiol levels depending on TSH level (p = 0.3213. Thus, the influence of highly normal TSH on menstrual function development in female adolescents.

  18. Usefulness of true FISP cine MR imaging in patients with poor cardiac function

    International Nuclear Information System (INIS)

    Sakuma, Toshiharu; Yamada, Naoaki; Motooka, Makoto; Enomoto, Naoyuki; Maeshima, Isamu; Matsuda, Kazuhide; Urayama, Shinichi; Ikeo, Miki

    2002-01-01

    This study was done to assess the value of True FISP cine in patients with poor cardiac function. True FISP cine and FLASH cine imaging were performed on a 1.5 T machine. Both short axis and horizontal long axis imaging sections were used. The imaging sections used a Matrix (120 x 128), FOV (24 x 32 cm), and had a slice thickness of 8 mm. The imaging time for True FISP cine was 8 heart beats and 17 heart beats for FLASH cine. The contrast-to-noise ratio between the blood and myocardium (CNR) was measured at enddiastole and endsystole. The subjects in the study were 10 healty volunteers (average age 26.5±3.2 years) and 12 patients with hypofunction (average age 53.9±13.2 years). In the volunteers, the CNR of the short axis imaging was similar in both True FISP (24.6±3.7) and FLASH (23.4±5.9). In the patients with poor cardiac function however, the CNR of True FISP was larger than FLASH in both the short and long axis. In the short axis (22.7±6.1 vs. 17.9±5.3, P<0.01) and in the long axis (17.4±4.3 vs. 9.3±4.0, P<0.01). We conclude that True FISP cine has a higher contrast in a shorter imaging time than FLASH cine. True FISP cine is especially useful in patients with poor cardiac function. (author)

  19. Effect of urokinase thrombolysis on the cardiac function, coagulation, and fibrinolytic system in patients with AMI

    Directory of Open Access Journals (Sweden)

    Zhi-Bin Kuang

    2017-06-01

    Full Text Available Objective: To observe the effect of urokinase thrombolysis on the cardiac function, coagulation, and fibrinolytic system in patients with acute myocardial infarction (AMI. Methods: A total of 39 patients with AMI who were admitted in our hospital from March, 2016 to November, 2016 were included in the study and served as the observation group. The peripheral venous blood before and after thrombolysis was collected. The plasma NTproBNP level, related coagulation factors, and fibrinolysis indicators were detected. The cardiac function before treatment was evaluated. A total of 30 healthy individuals who came for physical examinations were served as the control group for contrastive analysis. Results: The plasma NT-proBNP, Fg, and D-D levels before thrombolysis in the observation group were significantly higher than those in the control group, while PT, APTT, and TT in the observation group were significantly shortened. The plasma NT-proBNP and D-D levels 2-48 h after thrombolysis in the observation group were significantly elevated first and reduced later and reached the peak 4 h after treatment, while PT, APTT, and TT were significantly extended first and shortened later. The plasma Fg level was significantly reduced first and elevated later and reached the minimum 4 h after treatment. During the treatment process, in the observation group, 2 had mucocutaneous hemorrhage, 3 had nasal hemorrhage, and 1 had gingival bleeding, but no gastrointestinal bleeding or cerebral hemorrhage occurred. Conclusions: The thrombolytic therapy can effectively reduce the coagulation activity in patients with AMI, strengthen the fibrinolysis activity, and improve the cardiac function.

  20. Adaptive responses of cardiac function to fetal postural change as gestational age increases

    Science.gov (United States)

    Kim, Woo Jin; Choi, Hye Jin; Yang, Sun Young; Koo, Boo Hae; Ahn, Ki Hoon; Hong, Soon Cheol; Oh, Min-Jeong; Kim, Hai-Joong

    2016-01-01

    Objective The cardiovascular system maintains homeostasis through a series of adaptive responses to physiological requirements. However, little is known about the adaptation of fetal cardiac function to gravity, according to gestational age. In the present study, we aimed to evaluate the adaptive responses of cardiac function to postural changes, using Tei index measurements. Methods Fetal echocardiography and Doppler examination were performed on 114 women with vertex singleton pregnancies at 19 to 40 weeks' gestation. Participants were placed in an upright seated position, and the Tei index for fetal left ventricular cardiac function was measured. The women were then moved into a supine position and the Tei index was re-measured. Results The mean Tei index when measured in an upright seated position was significantly lower than that measured in a supine positioning for all fetuses (0.528±0.103 vs. 0.555±0.106, P=0.014, respectively). This difference was also noted in fetuses with a gestational age of 28–40 weeks (0.539±0.107 vs. 0.574±0.102, P=0.011, respectively). However, there was no difference in the Tei index between an upright seated and a supine position among fetuses with a gestational age of Postural changes from an upright seated to a supine position result in an increased Tei index after a gestational age of 28 weeks. This appears to reflect maturation in the adaptive responses of the fetal cardiovascular system to postural changes. PMID:27896244

  1. Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

    Science.gov (United States)

    Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

    2017-05-26

    BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

  2. The incidence and functional consequences of RT-associated cardiac perfusion defects

    International Nuclear Information System (INIS)

    Marks, Lawrence B.; Yu Xiaoli; Prosnitz, Robert G.; Zhou Sumin; Hardenbergh, Patricia H.; Blazing, Michael; Hollis, Donna; Lind, Pehr; Tisch, Andrea; Wong, Terence Z.; Borges-Neto, Salvador

    2005-01-01

    Purpose: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. Methods: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. Results: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. Conclusions: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects

  3. Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory.

    Science.gov (United States)

    Lukowski, Angela F; Koss, Marlene; Burden, Matthew J; Jonides, John; Nelson, Charles A; Kaciroti, Niko; Jimenez, Elias; Lozoff, Betsy

    2010-04-01

    Iron deficiency in infancy negatively impacts a variety of neurodevelopmental processes at the time of nutrient insufficiency, with persistent central nervous system alterations and deficits in behavioral functioning, despite iron therapy. In rodent models, early iron deficiency impairs the hippocampus and the dopamine system. We examined the possibility that young adults who had experienced chronic, severe, iron deficiency as infants would exhibit deficits on neurocognitive tests with documented frontostriatal (Trail Making Test, Intra-/Extra-dimensional Shift, Stockings of Cambridge, Spatial Working Memory, Rapid Visual Information Processing) and hippocampal specificity (Pattern Recognition Memory, Spatial Recognition Memory). Participants with chronic, severe iron deficiency in infancy performed less well on frontostriatal-mediated executive functions, including inhibitory control, set-shifting, and planning. Participants also exhibited impairment on a hippocampus-based recognition memory task. We suggest that these deficits may result from the long-term effects of early iron deficiency on the dopamine system, the hippocampus, and their interaction.

  4. Effects of ioxaglic acid on cardiac functions during coronary arteriography in canines

    Energy Technology Data Exchange (ETDEWEB)

    Traegaardh, B. (Malmoe Allmaenna Sjukhus, Malmoe, Sweden); Lynch, P.R. (Temple Univ., Philadelphia, PA (USA). School of Medicine)

    1983-01-01

    The new monoacid dimer ioxaglic acid (P286), the non-ionic metrizamide (Amipaque) and diatrizoate (Renografin 76) were compared regarding their effects on left ventricular pressure, the first derivative of left ventricular pressure, aortic pressures and on ECG changes during left and right coronary angiography in dogs. Ioxaglate was found to affect most of these parameters less than diatrizoate probably due to its lower osmolality. Ioxaglate should be regarded suitable for coronary angiography. However, ioxaglate was found to have greater effects on the cardiac function than the equiosmolar metrizamide. This is probably due to the chemotoxicity of the anion or possibly to the sodium content of the ioxaglic acid solution.

  5. Soccer training improves cardiac function in men with type 2 diabetes

    DEFF Research Database (Denmark)

    Schmidt, Jakob Friis; Rostgaard Andersen, Thomas; Horton, Joshua

    2013-01-01

    training can counteract the early signs of diabetic heart disease. PURPOSE: To evaluate the effects of soccer training on cardiac function, exercise capacity and blood pressure in middle-aged men with T2DM. METHODS: Twenty-one men aged 49.8±1.7 yrs with T2DM and no history of cardiovascular disease......INTRODUCTION: Patients with type 2 diabetes (T2DM) have an increased risk of cardiovascular disease which is worsened by physical inactivity. Subclinical myocardial dysfunction is associated with increased risk of heart failure and impaired prognosis in T2DM; however, it is not clear if exercise...

  6. Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.

    Directory of Open Access Journals (Sweden)

    Jianqin Ye

    Full Text Available BACKGROUND: Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI. However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear. METHODOLOGY/PRINCIPAL FINDING: Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+CD45(- cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1 in Sca-1(+CD45(- cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+CD45(- cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that cloned Sca-1(+CD45(- cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+ precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

  7. Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Fang-Fang Shen

    2014-01-01

    Full Text Available The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM. Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg−1·day−1 (TXL-H, n=9 or 0.15 g·kg−1·day−1 (TXL-L, n=10 of tongxinluo, or normal saline at the same volume (DCM-C, n=10 intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n=9. After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD increased in the TXL-H group compared with the DCM-C group (all P<0.01. Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r=-0.683, P<0.05, MVD and LVEF (r=0.895, P<0.05, and MVD and CVF (r=-0.798, P<0.05. It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.

  8. Prospective randomized controlled intervention trial: Comprehensive Yogic Breathing Improves Cardiac autonomic functions and Quality of life in Diabetes

    Directory of Open Access Journals (Sweden)

    V P Jyotsna

    2012-01-01

    Full Text Available Aims and Objectives: To assess the effect of Comprehensive Yogic Breathing Program on glycemic control, quality of life, and cardiac autonomic functions in diabetes. Material and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 120 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes (n = 56 and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program (n = 64. Standard therapy included advice on diet, walk, and oral antidiabetic drugs. Comprehensive yogic breathing program was an interactive session in which Sudarshan kriya yoga, a rhythmic cyclical breathing, preceded by Pranayam was taught under guidance of a certified teacher. Change in fasting, post prandial blood sugars, glycated hemoglobin, and quality of life were assessed. Cardiac autonomic function tests were done before and six months after intervention. Results: There was significant improvement in psychological (P = 0.006 and social domains (P = 0.04 and total quality of life (P = 0.02 in the group practicing comprehensive yogic breathing program as compared to the group following standard therapy alone. In the group following breathing program, the improvement in sympathetic cardiac autonomic functions was statistically significant (P = 0.01, while the change in the standard group was not significant (P = 0.17. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P = 0.07. In the standard therapy group, no change in cardiac autonomic functions was noted (P = 0.76. The parameters of glycemic control were comparable in both groups. Conclusion: There was significant improvement in quality of life and cardiac autonomic functions in the diabetes patients practicing comprehensive yogic breathing

  9. Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices (Postprint)

    Science.gov (United States)

    2015-11-10

    Albumin to saturate the non-specific binding sites on the paper substrate prior to troponin exposure. For testing the biosensor, troponin of various...AFRL-RX-WP-JA-2016-0191 PEPTIDE FUNCTIONALIZED GOLD NANORODS FOR THE SENSITIVE DETECTION OF A CARDIAC BIOMARKER USING PLASMONIC PAPER ...SENSITIVE DETECTION OF A CARDIAC BIOMARKER USING PLASMONIC PAPER DEVICES (POSTPRINT) 5a. CONTRACT NUMBER FA8650-15-D-5405-0001 5b. GRANT NUMBER 5c

  10. Impaired exercise performance and skeletal muscle mitochondrial function in rats with secondary carnitine deficiency

    Directory of Open Access Journals (Sweden)

    Jamal BOUITBIR

    2016-08-01

    Full Text Available Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP, a carnitine analogue inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats.Methods: Male Sprague Dawley rats were treated daily with water (control rats; n=12 or with 20 mg/100 g body weight THP (n=12 via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion.Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (-24% and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected.Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle.

  11. Growth hormone deficiency in the transition period: body composition and gonad function.

    Science.gov (United States)

    Balercia, G; Giovannini, L; Paggi, F; Spaziani, M; Tahani, N; Boscaro, M; Lenzi, A; Radicioni, A

    2011-10-01

    Recombinant GH therapy is normally administered to GH-deficient children in order to achieve a satisfactory height - the main target during childhood and adolescence. However, the role of GH does not end once final height has been reached, but continues during the so-called transition period. In this phase of life, the body undergoes several changes, both physical and psychological, that culminate in adulthood. During this period, GH has a part in numerous metabolic functions. These include the lipid profile, where it increases HDL and reduces LDL, with the global effect of cardiovascular protection. It also has important effects on body composition (improved muscle strength and lean body mass and reduced body fat), the achievement of proper peak bone density, and gonad maturation. Retesting during the transition period, involving measurement of IGF-I plus a provocative test (insulin tolerance test or GHRH + arginine test), is thus necessary to establish any persistent GH deficiency requiring additional replacement therapy. The close cooperation of the medical professionals involved in the patient's transition from a pediatric to an adult endocrinologist is essential. The aim of this review is to point out the main aspects of GH treatment on body composition, metabolic and gonad functions in the transition period.

  12. Impact of type 2 diabetes and duration of type 2 diabetes on cardiac structure and function

    DEFF Research Database (Denmark)

    Jørgensen, Peter G; Jensen, Magnus T; Mogelvang, Rasmus

    2016-01-01

    BACKGROUND: Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have affected myocardial structure and function. We aimed to describe the effect of T2D and T2D duration on cardiac structure and function in a large outpatient population. METHODS: We performed...... comprehensive echocardiography on a representative sample of 1004 persons including a representative sample of 770 patients with T2D without known heart disease and 234 age- and sex-matched controls. RESULTS: T2D was associated with increased left ventricular (LV) wall thicknesses and decreased LV internal...... dysfunction persisted after multivariable adjustment (P=0.013). CONCLUSIONS: In patients with T2D, LV structural and functional alterations persist and are accentuated with increasing diabetes duration despite reductions in overall risk of cardiovascular disease in this patient population....

  13. Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats.

    Directory of Open Access Journals (Sweden)

    Peter Nordbeck

    Full Text Available BACKGROUND: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. METHODS: Female Wistar rats (n = 6 per group were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. RESULTS: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05 and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05 after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw, such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05, or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05. Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass, but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. CONCLUSION: Cardio-thoracic surgical procedures in experimental myocardial infarction

  14. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

    Science.gov (United States)

    Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

    2016-04-01

    In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

  15. Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

    Science.gov (United States)

    See Hoe, Louise E.; Schilling, Jan M.; Tarbit, Emiri; Kiessling, Can J.; Busija, Anna R.; Niesman, Ingrid R.; Du Toit, Eugene; Ashton, Kevin J.; Roth, David M.; Headrick, John P.; Patel, Hemal H.

    2014-01-01

    Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02–1.0 mM MβCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. MβCD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10–30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with ≥20 μM MβCD, whereas SLP was more robust and only inhibited with ≥200 μM MβCD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression. PMID:25063791

  16. Empagliflozin Prevents Worsening of Cardiac Function in an Experimental Model of Pressure Overload-Induced Heart Failure

    Directory of Open Access Journals (Sweden)

    Nikole J. Byrne, BSc

    2017-08-01

    Full Text Available This study sought to determine whether the sodium/glucose cotransporter 2 (SGLT2 inhibitor empagliflozin improved heart failure (HF outcomes in nondiabetic mice. The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients trial demonstrated that empagliflozin markedly prevented HF and cardiovascular death in subjects with diabetes. However, despite ongoing clinical trials in HF patients without type 2 diabetes, there are no objective and translational data to support an effect of SGLT2 inhibitors on cardiac structure and function, particularly in the absence of diabetes and in the setting of established HF. Male C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Following surgery, mice that progressed to HF received either vehicle or empagliflozin for 2 weeks. Cardiac function was then assessed in vivo using echocardiography and ex vivo using isolated working hearts. Although vehicle-treated HF mice experienced a progressive worsening of cardiac function over the 2-week treatment period, this decline was blunted in empagliflozin-treated HF mice. Treatment allocation to empagliflozin resulted in an improvement in cardiac systolic function, with no significant changes in cardiac remodeling or diastolic dysfunction. Moreover, isolated hearts from HF mice treated with empagliflozin displayed significantly improved ex vivo cardiac function compared to those in vehicle-treated controls. Empagliflozin treatment of nondiabetic mice with established HF blunts the decline in cardiac function both in vivo and ex vivo, independent of diabetes. These data provide important basic and translational clues to support the evaluation of SGLT2 inhibitors as a treatment strategy in a broad range of patients with established HF.

  17. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

    Science.gov (United States)

    Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

    2015-11-15

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

  18. Functional characterization of malaria parasites deficient in the K+ channel Kch2

    DEFF Research Database (Denmark)

    Ellekvist, Peter; Mlambo, Godfree; Kumar, Nirbhay

    2017-01-01

    parasite P. berghei, the functional significance of K+ channel homologue PbKch2 was studied using targeted gene knock-out. The knockout parasites were characterized in a mouse model in terms of growth-kinetics and infectivity in the mosquito vector. Furthermore, using a tracer-uptake technique with 86Rb...... of forming oocysts in female Anopheles stephensi mosquitoes. 86Rb+ uptake in Kch2-deficient blood-stage P. berghei parasites (Kch2-null) did not differ from that of wild-type (WT) parasites. About two-thirds of the 86Rb+ uptake in WT and in Kch2-null parasites could be inhibited by K+ channel blockers...... and could be inferred to the presence of functional Kch1 in Kch2 knockout parasites. Kch2 is therefore not required for transport of K+ in P. berghei and is not essential to mosquito-stage sporogonic development of the parasite....

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

    Science.gov (United States)

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

    2015-07-06

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

  20. Evaluation of right cardiac function with sup(81m)Kr

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Kotsuka, Takahiro [National Cardiovascular Center, Suita, Osaka (Japan)

    1982-10-01

    Right cardiac function was evaluated by a first-pass method of repeated rapid injections of sup(81m)Kr, and by a multigated scanning of continuous injections using a scinticamera and a computer system. Right ventricular ejection fraction (RVEF) was rather low in the ascending course of time-activity curve and rather high in the descending course by the use of rapid injection. The RVEF estimated by the rapid injection method was relatively high in ischemic heart disease; but the figure was a little changed in tricuspid insufficiency, especially in the case with high reflux, showing no effect of rapid injection. There was a good correlation between the result of rapid injection and that of the sup(99m)Tc-first-pass method. Clinically, a little increase in RVEF due to exercise was observed in a group of right coronary artery obstruction, and in all the cases of tricuspid insufficiency changes in RVEF due to exercise was in good accordance with the result of classification of severity of the disease. Accuracy in RVEF estimated by the rapid injection method was correlated with that of multi-gated scanning. In continuous observation of right cardiac function by the continuous injection method, decreased RVEF following exercise was noted in cases of inferior wall infarction with atrial fibrillation, compared with the RVEF in cases of anterior wall infarction with normal right coronary arteries.

  1. Morphological and Functional Evaluation of Quadricuspid Aortic Valves Using Cardiac Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Song, Inyoung; Park, Jung Ah; Choi, Bo Hwa; Ko, Sung Min [Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030 (Korea, Republic of); Shin, Je Kyoun; Chee, Hyun Keun; Kim, Jun Seok [Department of Thoracic Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030 (Korea, Republic of)

    2016-11-01

    The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with severity of aortic regurgitation (AR) by TTE and the regurgitant fraction (RF) by CMR. All of the patients had AR; 9 had pure AR, 1 had combined aortic stenosis and regurgitation, and 1 had combined subaortic stenosis and regurgitation. Two patients had a subaortic fibrotic membrane and 1 of them showed a subaortic stenosis. One QAV was misdiagnosed as tricuspid aortic valve on TTE. In accordance with the Hurwitz and Robert's classification, consensus was reached on the QAV classification between the CCT and TTE findings in 7 of 10 patients. The patients were classified as type A (n = 1), type B (n = 3), type C (n = 1), type D (n = 4), and type F (n = 2) on CCT. A very high correlation existed between ROA by CCT and RF by CMR (r = 0.99) but a good correlation existed between ROA by CCT and regurgitant severity by TTE (r = 0.62). Cardiac computed tomography provides comprehensive anatomical and functional information about the QAV.

  2. Morphological and functional evaluation of quadricuspid aortic valves using cardiac computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Song, In Young; Park, Jung Ah; Choi, Bo Hwa; Ko, Sung Min; Shin, Je Kyoun; Chee, Hyun Keun; KIm, Jun Seok [Konkuk University Medical Center, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2016-07-15

    The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with severity of aortic regurgitation (AR) by TTE and the regurgitant fraction (RF) by CMR. All of the patients had AR; 9 had pure AR, 1 had combined aortic stenosis and regurgitation, and 1 had combined subaortic stenosis and regurgitation. Two patients had a subaortic fibrotic membrane and 1 of them showed a subaortic stenosis. One QAV was misdiagnosed as tricuspid aortic valve on TTE. In accordance with the Hurwitz and Robert's classification, consensus was reached on the QAV classification between the CCT and TTE findings in 7 of 10 patients. The patients were classified as type A (n = 1), type B (n = 3), type C (n = 1), type D (n = 4), and type F (n = 2) on CCT. A very high correlation existed between ROA by CCT and RF by CMR (r = 0.99) but a good correlation existed between ROA by CCT and regurgitant severity by TTE (r = 0.62). Cardiac computed tomography provides comprehensive anatomical and functional information about the QAV.

  3. The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease

    Directory of Open Access Journals (Sweden)

    W. H. Davin Townley-Tilson

    2015-01-01

    Full Text Available Ischemic heart disease is the leading cause of death worldwide. Oxygen-sensing proteins are critical components of the physiological response to hypoxia and reperfusion injury, but the role of oxygen and oxygen-mediated effects is complex in that they can be cardioprotective or deleterious to the cardiac tissue. Over 200 oxygen-sensing proteins mediate the effects of oxygen tension and use oxygen as a substrate for posttranslational modification of other proteins. Hydroxylases are an essential component of these oxygen-sensing proteins. While a major role of hydroxylases is regulating the transcription factor HIF, we investigate the increasing scope of hydroxylase substrates. This review discusses the importance of oxygen-mediated effects in the heart as well as how the field of oxygen-sensing proteins is expanding, providing a more complete picture into how these enzymes play a multifaceted role in cardiac function and disease. We also review how oxygen-sensing proteins and hydroxylase function could prove to be invaluable in drug design and therapeutic targets for heart disease.

  4. Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Steen, V.D.; Uretsky, B.F.; Owens, G.R.; Rodnan, G.P.

    1984-01-01

    To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thallium defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury

  5. Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

    Science.gov (United States)

    Newman, M F; Grocott, H P; Mathew, J P; White, W D; Landolfo, K; Reves, J G; Laskowitz, D T; Mark, D B; Blumenthal, J A

    2001-12-01

    The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

  6. Study on the relationship between plasma BNP levels and left cardiac function in patients with heart failure

    International Nuclear Information System (INIS)

    Yin Xin; Xu Dandan; Wu Chunxu

    2005-01-01

    Objective: To investigate the relationship between plasma brain natriuretic peptide (BNP) levels and cardiac function in patients with heart failure. Methods: Plasma levels of BNP (with IRMA) and left cardiac function parameters (examined with echocardiogram) were obtained in 80 patients with heart failure at admission and repeatedly examined in 43 of them later after 2w treatment a swell as in 30 controls. Results: The plasma BNP levels increased along with the deterioration of cardiac function, with significant differences among the patients with different cardiac function grades (P<0.01). After 2w treatment, the plasma BNP levels were significantly lower than those before (P<0.01). The plasma levels of BNP were negatively correlated with left ventricular ejection fraction (LVEF) and left ventricle fraction shortening, but positively correlated with left ventricular end-systolic diameter (LVSd) and left ventricular end-diastolic diameter (LVDd). Conclusion: Plasma levels of BNP were closely related to the severity of heart failure and could serve as a biochemical marker for assessing the left cardiac function. (authors)

  7. The natural history of cardiac and pulmonary function decline in patients with duchenne muscular dystrophy.

    Science.gov (United States)

    Roberto, Rolando; Fritz, Anto; Hagar, Yolanda; Boice, Braden; Skalsky, Andrew; Hwang, Hosun; Beckett, Laurel; McDonald, Craig; Gupta, Munish

    2011-07-01

    Retrospective review of scoliosis progression, pulmonary and cardiac function in a series of patients with Duchenne Muscular Dystrophy (DMD). To determine whether operative treatment of scoliosis decreases the rate of pulmonary function loss in patients with DMD. It is generally accepted that surgical intervention should be undertaken in DMD scoliosis once curve sizes reach 35° to allow intervention before critical respiratory decline has occurred. There are conflicting reports, however, regarding the effect of scoliosis stabilization on the rate of pulmonary function decline when compared to nonoperative cohorts. We reviewed spinal radiographs, echocardiograms, and spirometry, hospital, and operative records of all patients seen at our tertiary referral center from July 1, 1992 to June 1, 2007. Data were recorded to Microsoft Excel (Microsoft, Redmond, WA) and analyzed with SAS (SAS Institute, Cary, NC) and R statistical processing software (www.r-project.org). The percent predicted forced vital capacity (PPFVC) decreased 5% per year before operation. The mean PPFVC was 54% (SD = 21%) before operation with a mean postoperative PPFVC of 43% (SD = 14%). Surgical treatment was associated with a 12% decline in PPFVC independent of other treatment variables. PPFVC after operation declined at a rate of 1% per year and while this rate was lower, it was not significantly different than the rate of decline present before operation (P = 0.18). Cardiac function as measured by left ventricular fractional shortening declined at a rate of 1% per year with most individuals exhibiting a left ventricular fractional shortening rate of more than 30 before operation. Operative treatment of scoliosis in DMD using the Luque Galveston method was associated with a reduction of forced vital capacity related to operation. The rate of pulmonary function decline after operation was not significantly reduced when compared with the rate of preoperative forced vital capacity decline.

  8. New aspects of HERG K⁺ channel function depending upon cardiac spatial heterogeneity.

    Directory of Open Access Journals (Sweden)

    Pen Zhang

    Full Text Available HERG K(+ channel, the genetic counterpart of rapid delayed rectifier K(+ current in cardiac cells, is responsible for many cases of inherited and drug-induced long QT syndromes. HERG has unusual biophysical properties distinct from those of other K(+ channels. While the conventional pulse protocols in patch-clamp studies have helped us elucidate these properties, their limitations in assessing HERG function have also been progressively noticed. We employed AP-clamp techniques using physiological action potential waveforms recorded from various regions of canine heart to study HERG function in HEK293 cells and identified several novel aspects of HERG function. We showed that under AP-clamp IHERG increased gradually with membrane repolarization, peaked at potentials around 20-30 mV more negative than revealed by pulse protocols and at action potential duration (APD to 60%-70% full repolarization, and fell rapidly at the terminal phase of repolarization. We found that the rising phase of IHERG was conferred by removal of inactivation and the decaying phase resulted from a fall in driving force, which were all determined by the rate of membrane repolarization. We identified regional heterogeneity and transmural gradient of IHERG when quantified with the area covered by IHERG trace. In addition, we observed regional and transmural differences of IHERG in response to dofetilide blockade. Finally, we characterized the influence of HERG function by selective inhibition of other ion currents. Based on our results, we conclude that the distinct biophysical properties of HERG reported by AP-clamp confer its unique function in cardiac repolarization thereby in antiarrhythmia and arrhythmogenesis.

  9. Heme oxygenase-1 induction improves cardiac function following myocardial ischemia by reducing oxidative stress.

    Directory of Open Access Journals (Sweden)

    Yossi Issan

    Full Text Available Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1, a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation.In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP and tin protoporphyrin (SnPP prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured.HO-1 induction lowered release of lactate dehydrogenase (LDH and creatine phospho kinase (CK, decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05. CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01, reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively. CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05. The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05. CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05 in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects.HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by the increased levels of pAKT with

  10. [Sodium hydrosulfide improves cardiac functions and structures in rats with chronic heart failure].

    Science.gov (United States)

    Li, Xiao-hui; Zhang, Chao-ying; Zhang, Ting

    2011-11-22

    To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling. A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared. At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed an amelioration of myocardial damage, an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-I collagen). Compared with the sham operation and shunt + NaHS groups, the shunt group displayed increased right ventricular hydroxyproline (mg×g(-1)·pro: 1.32 ± 0.25 vs 0.89 ± 0.18 and 0.83 ± 0.19, all P < 0

  11. Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function.

    Science.gov (United States)

    Armstrong, Patrick A; Wood, Scott J; Shimizu, Naoki; Kuster, Kael; Perachio, Adrian; Makishima, Tomoko

    2015-06-01

    Genetically engineered mice are valuable models for elucidation of auditory and vestibular pathology. Our goal was to establish a comprehensive vestibular function testing system in mice using: (1) horizontal angular vestibulo-ocular reflex (hVOR) to evaluate semicircular canal function and (2) otolith-ocular reflex (OOR) to evaluate otolith organ function and to validate the system by characterizing mice with vestibular dysfunction. We used pseudo off-vertical axis rotation to induce an otolith-only stimulus using a custom-made centrifuge. For the OOR, horizontal slow-phase eye velocity and vertical eye position were evaluated as a function of acceleration. Using this system, we characterized hVOR and OOR in the caspase-3 (Casp3) mutant mice. Casp3 (-/-) mice had severely impaired hVOR gain, while Casp3 (+/-) mice had an intermediate response compared to WT mice. Evaluation of OOR revealed that at low-to-mid frequencies and stimulus intensity, Casp3 mutants and WT mice had similar responses. At higher frequencies and stimulus intensity, the Casp3 mutants displayed mildly reduced otolith organ-related responses. These findings suggest that the Casp3 gene is important for the proper function of the semicircular canals but less important for the otolith organ function.

  12. Preserved otolith organ function in caspase-3 deficient mice with impaired horizontal semicircular canal function

    Science.gov (United States)

    Armstrong, Patrick A; Wood, Scott J; Shimizu, Naoki; Kuster, Kael; Perachio, Adrian; Makishima, Tomoko

    2015-01-01

    Genetically engineered mice are valuable models for elucidation of auditory and vestibular pathology. Our goal was to establish a comprehensive vestibular function testing system in mice using: 1) horizontal angular vestibular-ocular reflex (hVOR) to evaluate semicircular canal function, and 2) otolith-ocular reflex (OOR) to evaluate otolith organ function, and to validate the system by characterizing mice with vestibular dysfunction. We used pseudo-off vertical axis rotation (pOVAR) to induce an otolith-only stimulus using a custom-made centrifuge. For the OOR, horizontal slow phase eye velocity (HEV) and vertical eye position (VEP) was evaluated as a function of acceleration. Using this system, we characterized hVOR and OOR in the caspase-3 (Casp3) mutant mice. Casp3 −/− mice had severely impaired hVOR gain, while Casp3 +/− mice had an intermediate response compared to WT mice. Evaluation of OOR revealed that at low to mid frequencies and stimulus intensity, Casp3 mutants and WT mice had similar responses. At higher frequencies and stimulus intensity, the Casp3 mutants displayed mildly reduced otolith organ related responses. These findings suggest that the Casp3 gene is important for the proper function of the semicircular canals but less important for the otolith organ function. PMID:25827332

  13. Asymptomatic Changes in Cardiac Function Can Occur in DCIS Patients Following Treatment with HER-2/neu Pulsed Dendritic Cell Vaccines

    Science.gov (United States)

    Bahl, Susan; Roses, Robert; Sharma, Anupama; Koldovsky, Ursula; Xu, Shuwen; Weinstein, Susan; Nisenbaum, Harvey; Fox, Kevin; Pasha, Theresa; Zhang, Paul; Araujo, Louis; Carver, Joseph; Czerniecki, Brian J

    2009-01-01

    Background Targeting HER-2/neu with Trastuzumab has been associated with development of cardiac toxicity. Methods Twenty-seven patients with ductal carcinoma in situ (DCIS) of the breast completed an IRB approved clinical trial of a HER-2/neu targeted dendritic cell based vaccine. Four weekly vaccinations were administered prior to surgical resection. All subjects underwent pre- and post-vaccine cardiac monitoring by MUGA/ECHO scanning allowing for a comparison of cardiac function. Results In 3 of 27 vaccinated patients (11%) transient asymptomatic decrements in ejection fraction of greater than 15% were noted after vaccination. Notably, evidence of circulating anti-HER-2/neu antibody was found prior to vaccination in all three patients, but cardiac toxicity was not noted until induction of cellular mediated immune responses. Conclusions This is the first description of HER-2/neu targeted vaccination associated with an incidence of cardiac changes, and the induction of cellular immune responses combined with antibody may contribute to changes in cardiac function. PMID:19800453

  14. Functional IRF3 deficiency in a patient with herpes simplex encephalitis.

    Science.gov (United States)

    Andersen, Line Lykke; Mørk, Nanna; Reinert, Line S; Kofod-Olsen, Emil; Narita, Ryo; Jørgensen, Sofie E; Skipper, Kristian A; Höning, Klara; Gad, Hans Henrik; Østergaard, Lars; Ørntoft, Torben F; Hornung, Veit; Paludan, Søren R; Mikkelsen, Jacob Giehm; Fujita, Takashi; Christiansen, Mette; Hartmann, Rune; Mogensen, Trine H

    2015-08-24

    Herpes simplex encephalitis (HSE) in children has previously been linked to defects in type I interferon (IFN) production downstream of Toll-like receptor 3. Here, we describe a novel genetic etiology of HSE by identifying a heterozygous loss-of-function mutation in the IFN regulatory factor 3 (IRF3) gene, leading to autosomal dominant (AD) IRF3 deficiency by haploinsufficiency, in an adolescent female patient with HSE. IRF3 is activated by most pattern recognition receptors recognizing viral infections and plays an essential role in induction of type I IFN. The identified IRF3 R285Q amino acid substitution results in impaired IFN responses to HSV-1 infection and particularly impairs signaling through the TLR3-TRIF pathway. In addition, the R285Q mutant of IRF3 fails to become phosphorylated at S386 and undergo dimerization, and thus has impaired ability to activate transcription. Finally, transduction with WT IRF3 rescues the ability of patient fibroblasts to express IFN in response to HSV-1 infection. The identification of IRF3 deficiency in HSE provides the first description of a defect in an IFN-regulating transcription factor conferring increased susceptibility to a viral infection in the CNS in humans. © 2015 Andersen et al.

  15. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

    Science.gov (United States)

    Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

    2007-01-01

    Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

  16. Cardiac Function in Patients with Early Cirrhosis during Maximal Beta-Adrenergic Drive

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Dahl, Emilie Kristine

    2014-01-01

    BACKGROUND AND AIM: Cardiac dysfunction in patients with early cirrhosis is debated. We investigated potential cardiac dysfunction by assessing left ventricular systolic performance during a dobutamine stress test in patients with early cirrhosis. PATIENTS AND METHODS: Nineteen patients with Chil...

  17. TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

    Energy Technology Data Exchange (ETDEWEB)

    Kurhanewicz, Nicole [Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 (United States); McIntosh-Kastrinsky, Rachel [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 (United States); Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hazari, Mehdi, E-mail: hazari.mehdi@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2017-06-01

    Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

  18. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    Directory of Open Access Journals (Sweden)

    Hong Jin

    Full Text Available The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  19. TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

    International Nuclear Information System (INIS)

    Kurhanewicz, Nicole; McIntosh-Kastrinsky, Rachel; Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen; Hazari, Mehdi

    2017-01-01

    Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

  20. Motion estimation for cardiac functional analysis using two x-ray computed tomography scans.

    Science.gov (United States)

    Fung, George S K; Ciuffo, Luisa; Ashikaga, Hiroshi; Taguchi, Katsuyuki

    2017-09-01

    This work concerns computed tomography (CT)-based cardiac functional analysis (CFA) with a reduced radiation dose. As CT-CFA requires images over the entire heartbeat, the scans are often performed at 10-20% of the tube current settings that are typically used for coronary CT angiography. A large image noise then degrades the accuracy of motion estimation. Moreover, even if the scan was performed during the sinus rhythm, the cardiac motion observed in CT images may not be cyclic with patients with atrial fibrillation. In this study, we propose to use two CT scan data, one for CT angiography at a quiescent phase at a standard dose and the other for CFA over the entire heart beat at a lower dose. We have made the following four modifications to an image-based cardiac motion estimation method we have previously developed for a full-dose retrospectively gated coronary CT angiography: (a) a full-dose prospectively gated coronary CT angiography image acquired at the least motion phase was used as the reference image; (b) a three-dimensional median filter was applied to lower-dose retrospectively gated cardiac images acquired at 20 phases over one heartbeat in order to reduce image noise; (c) the strength of the temporal regularization term was made adaptive; and (d) a one-dimensional temporal filter was applied to the estimated motion vector field in order to decrease jaggy motion patterns. We describe the conventional method iME1 and the proposed method iME2 in this article. Five observers assessed the accuracy of the estimated motion vector field of iME2 and iME1 using a 4-point scale. The observers repeated the assessment with data presented in a new random order 1 week after the first assessment session. The study confirmed that the proposed iME2 was robust against the mismatch of noise levels, contrast enhancement levels, and shapes of the chambers. There was a statistically significant difference between iME2 and iME1 (accuracy score, 2.08 ± 0.81 versus 2.77

  1. Forward lunge as a functional performance test in ACL deficient subjects: test-retest reliability

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Henriksen, Marius; Dyhre-Poulsen, Poul

    2009-01-01

    The forward lunge movement may be used as a functional performance test of anterior cruciate ligament (ACL) deficient and reconstructed subjects. The purposes were 1) to determine the test-retest reliability of a forward lunge in healthy subjects and 2) to determine the required numbers...... of repetitions necessary to yield satisfactory reliability. Nineteen healthy subjects performed four trials of a forward lunge on two different days. The movement time, impulses of the ground reaction forces (IFz, IFy), knee joint kinematics and dynamics during the forward lunge were calculated. The relative...... reliability was determined by calculation of Intraclass Correlation Coefficients (ICC). The IFz, IFy and the positive work of the knee extensors showed excellent reliability (ICC >0.75). All other variables demonstrated acceptable reliability (0.4>ICCreliability increased when more than...

  2. Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

    2013-10-09

    Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Functional property of the cardiac valve prosthesis evaluated in vivo by cine-radiography

    Energy Technology Data Exchange (ETDEWEB)

    Murakoshi, Sadaaki

    1986-07-01

    Functional property of the convexo-concave Bjoerk-Shiley cardiac valve prosthesis implanted in the mitral position of 21 patients was investigated by integrated cine-radiography repeated for a long term after operation. The maximum opening angle of the tilting disc was 58 +- 2 deg, and was not affected by atrial fibrillation nor by tachycardia up to 160 bpm. There was no change in the maximum opening angle of the disc observed during follow-up period. Good correlation between shortning of the disc opening time and increase in pulse rate suggests excellent adaptation of this prosthesis for tachycardia induced by exercise or electric pacing. However, atrial fibrillation causes time delay in disc closure immediately after prolonged R-R interval. Disc rotation alleviating disc wear was observed in all the patients whether it moves slow or quick. Dysfunction of the disc opening can be readily determined not only by measuring the maximum disc opening angle, but also by observing the characteristic movement indicated in this study. It is concluded from these results that clinical apprication for the convexo-concave Bjoerk-Shiley valve prosthesis is appropriate and cine-radiography is an useful non-invasive examination of cardiac valve prosthesis for long follow-up period.

  4. Functional property of the cardiac valve prosthesis evaluated in vivo by cine-radiography

    International Nuclear Information System (INIS)

    Murakoshi, Sadaaki

    1986-01-01

    Functional property of the convexo-concave Bjoerk-Shiley cardiac valve prosthesis implanted in the mitral position of 21 patients was investigated by integrated cine-radiography repeated for a long term after operation. The maximum opening angle of the tilting disc was 58 ± 2 deg, and was not affected by atrial fibrillation nor by tachycardia up to 160 bpm. There was no change in the maximum opening angle of the disc observed during follow-up period. Good correlation between shortning of the disc opening time and increase in pulse rate suggests excellent adaptation of this prosthesis for tachycardia induced by exercise or electric pacing. However, atrial fibrillation causes time delay in disc closure immediately after prolonged R-R interval. Disc rotation alleviating disc wear was observed in all the patients whether it moves slow or quick. Dysfunction of the disc opening can be readily determined not only by measuring the maximum disc opening angle, but also by observing the characteristic movement indicated in this study. It is concluded from these results that clinical apprication for the convexo-concave Bjoerk-Shiley valve prosthesis is appropriate and cine-radiography is an useful non-invasive examination of cardiac valve prosthesis for long follow-up period. (author)

  5. Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

    Directory of Open Access Journals (Sweden)

    Chao He

    2018-01-01

    Full Text Available Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF- 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO- 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp. before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg, after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

  6. Model-based imaging of cardiac electrical function in human atria

    Science.gov (United States)

    Modre, Robert; Tilg, Bernhard; Fischer, Gerald; Hanser, Friedrich; Messnarz, Bernd; Schocke, Michael F. H.; Kremser, Christian; Hintringer, Florian; Roithinger, Franz

    2003-05-01

    Noninvasive imaging of electrical function in the human atria is attained by the combination of data from electrocardiographic (ECG) mapping and magnetic resonance imaging (MRI). An anatomical computer model of the individual patient is the basis for our computer-aided diagnosis of cardiac arrhythmias. Three patients suffering from Wolff-Parkinson-White syndrome, from paroxymal atrial fibrillation, and from atrial flutter underwent an electrophysiological study. After successful treatment of the cardiac arrhythmia with invasive catheter technique, pacing protocols with stimuli at several anatomical sites (coronary sinus, left and right pulmonary vein, posterior site of the right atrium, right atrial appendage) were performed. Reconstructed activation time (AT) maps were validated with catheter-based electroanatomical data, with invasively determined pacing sites, and with pacing at anatomical markers. The individual complex anatomical model of the atria of each patient in combination with a high-quality mesh optimization enables accurate AT imaging, resulting in a localization error for the estimated pacing sites within 1 cm. Our findings may have implications for imaging of atrial activity in patients with focal arrhythmias.

  7. Assessment of left ventricular function by thallium-201 quantitative gated cardiac SPECT

    International Nuclear Information System (INIS)

    Baba, Akira; Hano, Takuzo; Ohmori, Hisashi; Ibata, Masayo; Kawabe, Tetsuya; Kubo, Takashi; Kimura, Keizo; Nishio, Ichiro

    2002-01-01

    Present study was designed to evaluate the accuracy of the measurement of left ventricular volume by quantitative gated SPECT (QGS) software using 201 Tl and the effect of cutoff frequency of Butterworth prereconstruction filter on the calculation of volume. The RH-2 type cardiac phantom and 20 patients with ischemic heart disease were studied. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated by the QGS software using the various frequency of Butterworth filter. These parameters were evaluated by Simpson's method using left ventriculography (LVG). The volume of the phantom calculated by QGS was under-estimated by 14%. In the clinical study, EDV and ESV measured by QGS were smaller than those obtained from LVG by 10%. When the cutoff frequency of Butterworth filter was 0.43 cycles/cm, the values measured by QGS were best correlated with those by LVG (EDV: r=0.80, p 201 Tl quantitative gated cardiac SPECT can estimate myocardial ischemia and left ventricular function simultaneously. (author)

  8. Assessment of left ventricular function by thallium-201 quantitative gated cardiac SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Akira; Hano, Takuzo; Ohmori, Hisashi; Ibata, Masayo; Kawabe, Tetsuya; Kubo, Takashi; Kimura, Keizo; Nishio, Ichiro [Wakayama Medical Coll. (Japan)

    2002-02-01

    Present study was designed to evaluate the accuracy of the measurement of left ventricular volume by quantitative gated SPECT (QGS) software using {sup 201}Tl and the effect of cutoff frequency of Butterworth prereconstruction filter on the calculation of volume. The RH-2 type cardiac phantom and 20 patients with ischemic heart disease were studied. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated by the QGS software using the various frequency of Butterworth filter. These parameters were evaluated by Simpson's method using left ventriculography (LVG). The volume of the phantom calculated by QGS was under-estimated by 14%. In the clinical study, EDV and ESV measured by QGS were smaller than those obtained from LVG by 10%. When the cutoff frequency of Butterworth filter was 0.43 cycles/cm, the values measured by QGS were best correlated with those by LVG (EDV: r=0.80, p<0.001; ESV: r=0.86, p<0.001; EF: r=0.80, p<0.001). These data suggest that {sup 201}Tl quantitative gated cardiac SPECT can estimate myocardial ischemia and left ventricular function simultaneously. (author)

  9. Left ventricular volume analysis as a basic tool to describe cardiac function.

    Science.gov (United States)

    Kerkhof, Peter L M; Kuznetsova, Tatiana; Ali, Rania; Handly, Neal

    2018-03-01

    The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.

  10. Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

    Science.gov (United States)

    Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

    2017-07-01

    If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  11. Nuclear cardiac

    International Nuclear Information System (INIS)

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques

  12. Deficiencia de zinc y sus implicaciones funcionales Zinc deficiency and its functional implications

    Directory of Open Access Journals (Sweden)

    JORGE L ROSADO

    1998-03-01

    closely associated to protein synthesis, among other functions. It is therefore related to functional and health impairments, specially in children. A marginal deficiency of zinc in Mexican children is relevant because of its potential effects. Studies suggest that marginal zinc deficiency is associated to diets based on plant foods wich are rich in zinc absorption inhibitors. Such diets are habitually consumed in rural areas and in poors areas of the cities. Marginal zinc deficiency was found to cause an increase in infectious diseases, specially diarrhea, and an impairment of the cognitive functions.

  13. Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development.

    Science.gov (United States)

    Etheridge, S Leah; Ray, Saugata; Li, Shuangding; Hamblet, Natasha S; Lijam, Nardos; Tsang, Michael; Greer, Joy; Kardos, Natalie; Wang, Jianbo; Sussman, Daniel J; Chen, Ping; Wynshaw-Boris, Anthony

    2008-11-01

    Dishevelled (Dvl) proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3(-/-) mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3(-/-) and LtapLp/+ mutants, Dvl3(+/-);LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant.

  14. Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development.

    Directory of Open Access Journals (Sweden)

    S Leah Etheridge

    2008-11-01

    Full Text Available Dishevelled (Dvl proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3(-/- mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+. Although neurulation appeared normal in both Dvl3(-/- and LtapLp/+ mutants, Dvl3(+/-;LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant.

  15. Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.

    Science.gov (United States)

    Cardinal, R; Nadeau, R; Laurent, C; Boudreau, G; Armour, J A

    1996-09-01

    To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.

  16. Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO.

    Science.gov (United States)

    Yin, Haifang; Moulton, Hong M; Betts, Corinne; Merritt, Thomas; Seow, Yiqi; Ashraf, Shirin; Wang, Qingsong; Boutilier, Jordan; Wood, Matthew Ja

    2010-10-01

    Splice modulation using antisense oligonucleotides (AOs) has been shown to yield targeted exon exclusion to restore the open reading frame and generate truncated but partially functional dystrophin protein. This has been successfully demonstrated in dystrophin-deficient mdx mice and in Duchenne muscular dystrophy (DMD) patients. However, DMD is a systemic disease; successful therapeutic exploitation of this approach will therefore depend on effective systemic delivery of AOs to all affected tissues. We have previously shown the potential of a muscle-specific/arginine-rich chimeric peptide-phosphorodiamidate morpholino (PMO) conjugate, but its long-term activity, optimized dosing regimen, capacity for functional correction and safety profile remain to be established. Here, we report the results of this chimeric peptide-PMO conjugate in the mdx mouse using low doses (3 and 6 mg/kg) administered via a 6 biweekly systemic intravenous injection protocol. We show 100% dystrophin-positive fibers and near complete correction of the dystrophin transcript defect in all peripheral muscle groups, with restoration of 50% dystrophin protein over 12 weeks, leading to correction of the DMD pathological phenotype and restoration of muscle function in the absence of detectable toxicity or immune response. Chimeric muscle-specific/cell-penetrating peptides therefore represent highly promising agents for systemic delivery of splice-correcting PMO oligomers for DMD therapy.

  17. Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.

    Science.gov (United States)

    Kero, Jukka; Ahmed, Kashan; Wettschureck, Nina; Tunaru, Sorin; Wintermantel, Tim; Greiner, Erich; Schütz, Günther; Offermanns, Stefan

    2007-09-01

    The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein-coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase-dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the alpha subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Galphaq/Galpha11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.

  18. The impact of therapeutic hypothermia on neurological function and quality of life after cardiac arrest

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Kjaergaard, Jesper; Horsted, Tina I

    2008-01-01

    AIMS: To assess the impact of therapeutic hypothermia on cognitive function and quality of life in comatose survivors of out of Hospital Cardiac arrest (OHCA). METHODS: We prospectively studied comatose survivors of OHCA consecutively admitted in a 4-year period. Therapeutic hypothermia......=0.01. No significant differences were found in long-term survival (57% vs. 56% alive at 30 months), MMSE, or SF-36. Therapeutic hypothermia (hazard ratio: 0.15, p=0.007) and bystander CPR (hazard ratio 0.19, p=0.002) were significantly related to survival in the intervention period. CONCLUSION: CPC...... at discharge from hospital was significantly improved following implementation of therapeutic hypothermia in comatose patients resuscitated from OCHA with VF/VT. However, significant improvement in survival, cognitive status or quality of life could not be detected at long-term follow-up....

  19. Trial of quantitative analysis of cardiac function by 3D reconstruction of multislice cine MR images

    International Nuclear Information System (INIS)

    Yamamoto, Hideki; Sei, Tetsurou; Nakagawa, Tomio; Hiraki, Yoshio.

    1994-01-01

    Non-invasive techniques for measuring the dynamic behavior of the left ventricle (LV) can be invaluable tool in the diagnosis of the heart disease. In this paper we present methods for quantitative analysis of cardiac function using a compact magnetic resonance image processing system. A 256 x 256 magnetic resonance transaxial image of the left ventricle in a normal case is obtained. After gray level thresholding and region segmentation, the boundary of the left ventricular chamber is extracted. Then, the boundaries of the left ventricular chamber are displayed three-dimensionally by using the Z-buffer algorithm. Thus, LV volume and ejection fraction are calculated. Here, the value of LV ejection fraction is 60%. These results agree reasonably well with the corresponding data obtained by the echocardiography. (author)

  20. Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals

    DEFF Research Database (Denmark)

    Young, Lari C; Roediger, Mollie P; Grandits, Greg

    2014-01-01

    Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and D-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectionally and longitudinally. RESULTS: Cross-sectional analysis revealed significant inverse associations between IL-6, hs......CRP and d-dimer with SDNN and rMSSD (p Cross-sectionally, higher levels of inflammatory and coagulation biomarkers were......AIM: To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV. MATERIALS & METHODS: This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral...

  1. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  2. Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence.

    Science.gov (United States)

    de Zambotti, Massimiliano; Willoughby, Adrian R; Baker, Fiona C; Sugarbaker, David S; Colrain, Ian M

    2015-06-01

    Chronic alcoholism is associated with the development of cardiac and peripheral autonomic nervous system (ANS) pathology. The aim of the present study was to evaluate the extent to which recovery in ANS function could be demonstrated over the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on three occasions: within a month of detoxification, at approximately 2 months post-detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also studied on three occasions with inter-study intervals matching those of the alcoholics. Six alcoholics relapsed, 48.7 ± 27.9 days following the initial PSG session. ANS function was assessed in the first part of stable non-rapid eye movement sleep. Frequency-domain power spectral analysis of heart rate variability (HRV) produced variables including: heart rate (HR), total power (TP; an index representing total HR variability), High Frequency power (HFa; an index reflecting cardiac vagal modulation), HF proportion of total power (HFprop sympathovagal balance), and HF peak frequency (HFpf; an index reflecting respiration rate). Overall, high total and high frequency variability and low sympathovagal balance and myocardial contractility are considered as desired conditions to promote cardiovascular health. At initial assessment, alcoholics had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with higher TP at the initial visit showed a greater improvement in TP from the initial to the 4 month follow-up session (r = 0.75, p < 0.05). Alcoholics showed substantial recovery in HR and vagal modulation of HRV with 4 months of abstinence, with evidence that the extent of recovery in HRV may be partially determined by the extent of alcohol dependence-related insult to the cardiac ANS system. These data support other studies

  3. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    International Nuclear Information System (INIS)

    Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.

    2007-01-01

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion

  4. American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function.

    Science.gov (United States)

    Folsom, Aaron R; Shah, Amil M; Lutsey, Pamela L; Roetker, Nicholas S; Alonso, Alvaro; Avery, Christy L; Miedema, Michael D; Konety, Suma; Chang, Patricia P; Solomon, Scott D

    2015-09-01

    Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Cardiac biopotentials influence on central nervous system functioning: first steps in hypothesis verification

    Directory of Open Access Journals (Sweden)

    Kondal'skaya Yu.O.

    2012-12-01

    Full Text Available The research goal is to verify the hypothesis on influence of cardiac biopotentials on central nervous system. Materials: 20 healthy individuals aged 18-26 years old have been participated in the investigations. Two groups composed of 10 patients each have been formed. Double increase in heart biopotentials by means of artificial impulse insertion between natural cardiac contractions has been modeled. Artificial impulses have been similar to unaffected ones, produced in a normal heart work. Additional impulses have been generated using external pacemaker and have been linked up with electrodes on the chest. They have been synchronized with the heart rhythm and located in-between R waves. The duration of those impulses has been fully matched to ventricular complex. Their amplitude has been adjusted individually depending on the height of R wave. Nervous system mobility has been used as the indicator reflecting the central nervous system functioning. Degree of mobility has been defined on the basis of tapping test results. The test has been repeated at specific intervals. Groups have been exposed to two adverse testing modes. Additional impulses have been conducted to the patients of group I within an hour over a period of the first and the third 15-minute intervals and to the patients of group II over a period of the second and the fourth 15-minute intervals. In the middle and in the end of each time interval tapping test has been carried out. After preliminary analysis two other modes of stimulation have been tested. The stimulation has been performed within the 40-minute course: over a period of the first 20-minute interval and vice versa. Results: Detailed evaluation has revealed that short-time increase of nervous processes has been checked in combination with decrease in their stability. Conclusion: The data obtained have shown that there is possible influence on central nervous system functioning. The article ends with prospects of further

  6. Evaluation of cardiac function using multi-shot echo planar imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Tadashi; Tanitame, Nobuko; Hata, Ryoichiro; Hirai, Nobuhiko; Ikeda, Midori; Ono, Chiaki; Fukuoka, Haruhito; Ito, Katsuhide [Hiroshima Univ. (Japan). School of Medicine

    1998-01-01

    In this study, we performed multi-shot echo planar imaging (8 shot, TR/TE/FL=55 ms/18 ms/60 degrees) and k-space segmented fast gradient echo sequence (8 views per segment, TR/TE/FL=9.9 ms/1.8 ms/30 degrees) to assess cardiac function in healthy volunteers. Transaxial sections of the entire heart were obtained with both sequences in ECG triggered, breath hold, and with a 256 x 128 matrix. Resulting temporal resolution was 55 ms for echo planar imaging, and 71 ms for k-space segmented fast gradient echo sequence, respectively. Ventricular volume and ejection fraction of both ventricles and left ventricular mass obtained with multi-shot echo planar imaging were assessed in comparison with k-space segmented fast gradient echo sequence. Measurements of left ventricular volume, ejection fraction and mass obtained with multi-shot echo planar imaging demonstrated close correlation with those obtained with k-space segmented fast gradient echo sequence. Right ventricular volumes obtained with echo planar imaging were significantly higher than those obtained with k-space segmented fast gradient echo sequence. This tendency is considered to be due to differing contrast between right ventricular myocardium and fat tissue observed with echo planar imaging relative to that observed with fast gradient echo sequence, because fat suppression is always performed in echo planar images. Multi-shot echo planar imaging can be a reliable tool for measurement of cardiac functional parameters, although wall motion analysis of the left ventricle requires higher temporal resolution and a short axial section. (K.H.)

  7. Cardiac Function After Multimodal Breast Cancer Therapy Assessed With Functional Magnetic Resonance Imaging and Echocardiography Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Heggemann, Felix, E-mail: felix.heggemann@umm.de [First Medical Department, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); German Center for Cardiovascular Research, Mannheim (Germany); Grotz, Hanna; Welzel, Grit [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Dösch, Christina [First Medical Department, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); German Center for Cardiovascular Research, Mannheim (Germany); Hansmann, Jan [Institute of Diagnostic Radiology and Nuclear Medicine, University Medical Center Mannheim University of Heidelberg, Mannheim (Germany); Kraus-Tiefenbacher, Uta [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Attenberger, Ulrike; Schönberg, Stephan Oswald [German Center for Cardiovascular Research, Mannheim (Germany); Institute of Diagnostic Radiology and Nuclear Medicine, University Medical Center Mannheim University of Heidelberg, Mannheim (Germany); Borggrefe, Martin [First Medical Department, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); German Center for Cardiovascular Research, Mannheim (Germany); Wenz, Frederik [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Papavassiliu, Theano [First Medical Department, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); German Center for Cardiovascular Research, Mannheim (Germany); Lohr, Frank [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany)

    2015-11-15

    Purpose: Breast intensity modulated radiation therapy (IMRT) reduces high-dose heart volumes but increases low-dose volumes. We prospectively assessed heart changes after 3D conformal RT (3DCRT) and IMRT for left-sided breast cancer. Heart dose was analyzed individually, 3DCRT patients were moderately exposed, and IMRT was performed only in patients with unacceptably high heart doses upon 3DCRT planning. Methods and Materials: In 49 patients (38 patients received 3DCRT; 11 patients received IMRT; and 20 patients received neoadjuvant or adjuvant chemotherapy) magnetic resonance imaging (MRI) and echocardiography were performed before and at 6, 12, and 24 months after treatment. Results: Mean heart dose for IMRT was 12.9 ± 3.9 Gy versus 4.5 ± 2.4 Gy for 3DCRT. Heart volumes receiving >40 Gy were 2.6% (3DCRT) versus 1.3% (IMRT); doses were >50 Gy only with 3DCRT. Temporary ejection fraction (EF) decrease was observed on MRI after 6 months (63%-59%, P=.005) resolving at 24 months. Only 3 patients had pronounced largely transient changes of EF and left ventricular enddiastolic diameter (LVEDD). Mitral (M) and tricuspid (T) annular plane systolic excursion (MAPSE and TAPSE) were reduced over the whole cohort (still within normal range). After 24 months left ventricular remodeling index decreased in patients receiving chemotherapy (0.80 vs 0.70, P=.028). Neither wall motion abnormalities nor late enhancements were found. On echocardiography, in addition to EF findings that were similar to those on MRI, global strain was unchanged over the whole cohort at 24 months after a transient decrease at 6 and 12 months. Longitudinal strain decreased in the whole cohort after 24 months in some segments, whereas it increased in others. Conclusions: Until 24 months after risk-adapted modern multimodal adjuvant therapy, only subclinical cardiac changes were observed in both 3DCRT patients with inclusion of small to moderate amounts of heart volume in RT tangents and

  8. Different Modes of Monitoring and Correction of Cardiac Function During Operations Under Extracorporeal Circulation

    Directory of Open Access Journals (Sweden)

    L. A. Krichevsky

    2007-01-01

    Full Text Available Objective: to comparatively evaluate the efficiency of intensive care measures chosen on the basis of traditional monitoring of central hemodynamics (CH or on that of the data of transesophageal echocardiography (TE echoCG.Materials and methods: 50 patients were examined at coronary bypass surgery under extracorporeal circulation. Under a prospective comparative analysis were two algorithms of treatment policy: maintenance of cardiac index, by using the maximum volemic load, or that of left ventricular systolic function under guidance of transesophageal echocardiography.Results: Significantly (p<0.05 larger doses of dopamine and/or dobutamine were required to maintain adequate left ventricular systolic function. However, this treatment policy showed much better (p<0.05 circulatory parameters in the postperfusion period. At the same time the duration of postoperative inotropic therapy in these patients proved to be significantly (p<0.05 less.Conclusion. The treatment policy based on the maintenance of left ventricular systolic function under guidance of TE echoCG leads to the shortest circulatory stabilization during myocardial revascularization. The application of a volemic load and the expectant use of inotropic drugs result in a longer restoration of operated heart function

  9. Persistence of normal cardiac function and myocardial perfusion in irradiated long-term survivors of Hodgkin's disease

    International Nuclear Information System (INIS)

    Constine, L.S.; Schwartz, R.G.; Savage, D.E.; King, V.; Muhs, A.; Rubin, P.

    1996-01-01

    Purpose: The risk of myocardial infarction and cardiac dysfunction following mantle irradiation (RT) for Hodgkin's disease is controversial. The relative risk of fatal myocardial infarction is 2.8 in our Hodgkin's patients, similar to other reports. Sensitive evaluations of cardiac function and myocardial perfusion might be expected to reveal pre-clinical abnormalities of potential significance. We hypothesized the presence of pre-clinical cardiac toxicity and progressive deterioration of left ventricular performance and myocardial ischemia over time in long-term survivors of Hodgkin's disease. The data reported herein extend our previous study in patient number (n=50) and follow-up duration (mean 16.5 years). Materials and Methods: Equilibrium radionuclide angiocardiography (ERNA) was used to quantify left ventricular (LV) systolic and diastolic function with LV ejection fraction (LVEF) and peak filling rate (PFR), respectively. Quantitative myocardial perfusion scintigraphy (MPS) and ECG stress testing with exercise or dipyridamole were used to assess myocardial perfusion and electrical function. Patients at least 1.0 year after RT were eligible if ≤ 50 years old at RT and without known Hodgkin's or cardiac disease. Fifty patients, ages 10-46 years (mean 26.0) at RT, were tested 1.1 to 29.1 years (mean 9.1) after RT. Seventeen patients were tested 2 - 3 times separated by 0.5 - 6.5 years (mean 3.3). The mean central cardiac RT dose was 35.1 Gy (range 18.5 - 47.5) in daily 1.5-2.0 Gy fractions. Twelve patients were additionally irradiated to the left ventricle (LVRT), usually through partial transmission left lung shields (range 14.3-21.3 Gy). Results: No patient had symptomatic cardiac disease at the time of evaluation. The mean LVEF (first test, n = 50) was 60 ± 6% (range 42-73%) [normal ≥ 50%], and PFR (first test, n=44) was 3.43 ± 0.83 end diastolic volume per second (range 1.5-5.2 EDV/sec) [normal ≥ 2.54 EDV/sec] with 2 and 7 patients below normal

  10. Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency.

    Directory of Open Access Journals (Sweden)

    Ileana Pacheco-Colón

    Full Text Available Ornithine transcarbamylase deficiency (OTCD is an X-chromosome linked urea cycle disorder (UCD that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks--default mode and set-maintenance--between OTCD patients and healthy controls.Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA and region-of-interest (ROI analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.Group comparisons revealed reduced functional connectivity in the default mode network (DMN of OTCD patients, particularly between the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC node and bilateral inferior parietal lobule (IPL, as well as between the ACC/mPFC node and the posterior cingulate cortex (PCC node. Patients also showed reduced connectivity in the set-maintenance network, especially between right anterior insula/frontal operculum (aI/fO node and bilateral superior frontal gyrus (SFG, as well as between the right aI/fO and ACC and between the ACC and right SFG.Internodal functional connectivity in the DMN and set-maintenance network is reduced in patients with partial OTCD compared to controls, most likely due to hyperammonemia-related white matter damage. Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain.

  11. The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice

    Directory of Open Access Journals (Sweden)

    Güínever Eustáquio do Império

    2015-08-01

    Full Text Available Background/Aims: Thyroid hormone (TH signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs; THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function. Methods: The experiments were performed using adult male mice expressing TRβΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRβΔ337T mice, showing the fundamental role of THRβ in cardiac hypertrophy. Results: We identified a group of independently regulated THRβ genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRβΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRβ. The TRβΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRβ-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRβΔ337T mice. Conclusion: THRβ has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.

  12. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  13. Impact of exercise rehabilitation on cardiac neuronal function in heart failure. An iodine-123 metaiodobenzylguanidine scintigraphy study

    Energy Technology Data Exchange (ETDEWEB)

    Agostini, D.; Bouvard, G. [Service de Medecine Nucleaire, CHU Cote de Nacre, Caen (France); Lecluse, E.; Grollier, G.; Potier, J.C. [Service de Cardiologie, CHU Cote de Nacre, Caen (France); Belin, A. [Service de Readaptation Cardiaque, CHU Cote de Nacre, Caen (France); Babatasi, G. [Service de Chirurgie Cardio-Thoracique, CHU Cote de Nacre, Caen (France); Amar, M.H. [Centre Francois Baclesse, Caen (France). Service de Recherche Clinique

    1998-03-01

    Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiobodenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable chronic heart failure of NYHA class II-III and an initial resting radionuclide left ventricular ejection fraction (LVEF) <50% were enrolled in the study. Patients underwent progressive, supervised endurance training (treadmill test, Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a cardiac rehabilitation referral centre in order to measure exercise parameters. Planar {sup 123}I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801{+-}428 vs 1229{+-}245 kpm.min{sup -1}, P=0.001), exercise duration (504{+-}190 vs 649{+-}125 s, P=0.02), and myocardial MIBG uptake (135%{+-}19% vs 156%{+-}25%, P=0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%{+-}9% vs 21%{+-}10%, p=NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. (orig.)

  14. NRC Information No. 91-29: Deficiencies identified during electrical distribution system functional inspections

    International Nuclear Information System (INIS)

    Rossi, C.E.

    1992-01-01

    During multidisciplinary inspections, the US Nuclear Regulatory Commission (NRC) has identified many deficiencies related to the electrical distribution system. To address these deficiencies, the NRC has developed an inspection to specifically evaluate the electrical distribution system. During the last year, the NRC completed eight EDSFIs, performing at least one in each of the several common deficiencies in the licensees' programs and in the electrical distribution systems as designed and configured at each plant. These deficiencies included inadequate ac voltages at the 480 Vac and 120 Vac distribution levels, inadequate procedures to test circuit breakers, and inadequate determinations and evaluations of setpoints

  15. Plasminogen deficiency causes reduced corticospinal axonal plasticity and functional recovery after stroke in mice.

    Directory of Open Access Journals (Sweden)

    Zhongwu Liu

    Full Text Available Tissue plasminogen activator (tPA has been implicated in neurite outgrowth and neurological recovery post stroke. tPA converts the zymogen plasminogen (Plg into plasmin. In this study, using plasminogen knockout (Plg-/- mice and their Plg-native littermates (Plg+/+, we investigated the role of Plg in axonal remodeling and neurological recovery after stroke. Plg+/+ and Plg-/- mice (n = 10/group were subjected to permanent intraluminal monofilament middle cerebral artery occlusion (MCAo. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA was injected into the left motor cortex to anterogradely label the corticospinal tract (CST. Animals were euthanized 4 weeks after stroke. Neurite outgrowth was also measured in primary cultured cortical neurons harvested from Plg+/+ and Plg-/- embryos. In Plg+/+ mice, the motor functional deficiency after stroke progressively recovered with time. In contrast, recovery in Plg-/- mice was significantly impaired compared to Plg+/+ mice (p0.82, p<0.01. Plg-/- neurons exhibited significantly reduced neurite outgrowth. Our data suggest that plasminogen-dependent proteolysis has a beneficial effect during neurological recovery after stroke, at least in part, by promoting axonal remodeling in the denervated spinal cord.

  16. In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors.

    Directory of Open Access Journals (Sweden)

    Matteo Vecellio

    Full Text Available Adult human cardiac mesenchymal-like stromal cells (CStC represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS in the presence of 5 µM all-trans Retinoic Acid (ATRA, 5 µM Phenyl Butyrate (PB, and 200 µM diethylenetriamine/nitric oxide (DETA/NO, to create a novel epigenetically active cocktail (EpiC. Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and α-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors.

  17. Evaluation of the diagnostic accuracy of ultra-miniaturized pocket ultrasound device on cardiac function in critically ill patients

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    Li WANG

    2016-09-01

    Full Text Available Objective  To compare the diagnostic accuracy of a new ultra-miniaturized pocket ultrasound device (PUD (VscanTM, GE Healthcare, Wauwatosa, WI and conventional high-quality echocardiography system (Vivid qTM, GE Healthcare for a cardiac focused ultrasonography in critical patients. Methods  The patients admitted to our hospital and receiving transthoracic echocardiography (TTE using a PUD and a conventional echocardiography system were included in this study during the 10 months from December 2013 to October 2014. Each examination was performed independently by an intensive care unit (ICU physician and an experienced ultrasound doctor, unaware of the results found by the alternative device. The following parameters were assessed: global cardiac systolic function, identification of ventricular size, whether or not accompanying enlargement or hypertrophy, assessment for the morphology of cardiac valves and its function, pericardial effusion and estimation of the inferior vena cava (IVC diameter. The time-consuming of each device were recorded. Results  One hundred and twenty-eight patients were included in the study. Their left ventricular wall motion abnormalities, global left ventricular systolic dysfunction, pericardial effusion, IVC dilation were assessed by PUD and the assessment results were highly consistent with those by Vivid q (κ>0.84. The consistency was slightly lower in evaluating the left and right ventricular size. For evaluating the cardiac valves function, the agreement of two devices were relatively low (κ=0.69-0.84. Compared with Vivid q, PUD took less time (4.7±1.4min vs 6.3±2.6min; P<0.05. Conclusion  PUD can provide fast, reliable cardiac examination, thus being an effective method for ICU physicians to assess the cardiac f unction in critical patients. DOI: 10.11855/j.issn.0577-7402.2016.08.10

  18. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study

    NARCIS (Netherlands)

    Janssens, Karin A. M.; Riese, Harriëtte; van Roon, Arie M.; Hunfeld, Joke A. M.; Groot, Paul F. C.; Oldehinkel, Albertine J.; Rosmalen, Judith G. M.

    2016-01-01

    Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac autonomic nervous

  19. Association of Weight and Body Composition on Cardiac Structure and Function in the ARIC Study (Atherosclerosis Risk in Communities).

    Science.gov (United States)

    Bello, Natalie A; Cheng, Susan; Claggett, Brian; Shah, Amil M; Ndumele, Chiadi E; Roca, Gabriela Querejeta; Santos, Angela B S; Gupta, Deepak; Vardeny, Orly; Aguilar, David; Folsom, Aaron R; Butler, Kenneth R; Kitzman, Dalane W; Coresh, Josef; Solomon, Scott D

    2016-08-01

    Obesity increases cardiovascular risk. However, the extent to which various measures of body composition are associated with abnormalities in cardiac structure and function, independent of comorbidities commonly affecting obese individuals, is not clear. This study sought to examine the relationship between body mass index, waist circumference, and percent body fat with conventional and advanced measures of cardiac structure and function. We studied 4343 participants of the ARIC study (Atherosclerosis Risk in Communities) who were aged 69 to 82 years, free of coronary heart disease and heart failure, and underwent comprehensive echocardiography. Increasing body mass index, waist circumference, and body fat were associated with greater left ventricular (LV) mass and left atrial volume indexed to height(2.7) in both men and women (Pheart disease or heart failure, obesity was associated with subclinical abnormalities in cardiac structure in both men and women and with adverse LV remodeling and impaired LV systolic function in women. These data highlight the association of obesity and subclinical abnormalities of cardiac structure and function, particularly in women. © 2016 American Heart Association, Inc.

  20. Atorvastatin improves cardiac function and remodeling in chronic non-ischemic heart failure: A clinical and pre-clinical study

    Directory of Open Access Journals (Sweden)

    Ibrahim Elmadbouh

    2015-12-01

    Conclusions: Atorvastatin with standard CHF therapy improved cardiac function and remodeling. Cardio-protective “pleiotropic” actions of atorvastatin are anti-inflammatory, anti-fibrotic and anti-oxidative. Thus, atorvastatin has a potential therapeutic value in the management of CHF patients.

  1. Manual hyperinflation partly prevents reductions of functional residual capacity in cardiac surgical patients--a randomized controlled trial

    NARCIS (Netherlands)

    Paulus, Frederique; Veelo, Denise P.; de Nijs, Selma B.; Beenen, Ludo F. M.; Bresser, Paul; de Mol, Bas A. J. M.; Binnekade, Jan M.; Schultz, Marcus J.

    2011-01-01

    Cardiac surgery is associated with post-operative reductions of functional residual capacity (FRC). Manual hyperinflation (MH) aims to prevent airway plugging, and as such could prevent the reduction of FRC after surgery. The main purpose of this study was to determine the effect of MH on

  2. Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

    Science.gov (United States)

    Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

    2007-09-01

    In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

  3. Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

    Science.gov (United States)

    Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

    2006-03-01

    Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

  4. Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT

    International Nuclear Information System (INIS)

    Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia

    2015-01-01

    Introduction: Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III–IV) after CRT using 11 C-hydroxyephedrine (HED) PET/CT. Methods: Ten IHF patients (mean age = 68; range = 55–81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. Results: At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with “impaired innervation” (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). Conclusion: As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. Advances in Knowledge: These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation

  5. Right-sided cardiac function in healthy volunteers measured by first-pass radionuclide ventriculography and gated blood-pool SPECT: comparison with cine MRI

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Lebech, Anne-Mette; Hesse, Birger

    2005-01-01

    for evaluation of right-sided cardiac function. The aim of our study was to compare the agreement between these methods when measuring right-sided cardiac function. METHODS: Twenty-four healthy volunteers were included. Mean age was 44 years (range: 25-60) and 29% were females. All participants had FP, GBPS...

  6. Competing Risk of Cardiac Status and Renal Function During Hospitalization for Acute Decompensated Heart Failure.

    Science.gov (United States)

    Salah, Khibar; Kok, Wouter E; Eurlings, Luc W; Bettencourt, Paulo; Pimenta, Joana M; Metra, Marco; Verdiani, Valerio; Tijssen, Jan G; Pinto, Yigal M

    2015-10-01

    The aim of this study was to analyze the dynamic changes in renal function in combination with dynamic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). Treatment of ADHF improves cardiac parameters, as reflected by lower levels of NT-proBNP. However this often comes at the cost of worsening renal parameters (e.g., serum creatinine, estimated glomerular filtration rate [eGFR], or serum urea). Both the cardiac and renal markers are validated indicators of prognosis, but it is not yet clear whether the benefits of lowering NT-proBNP are outweighed by the concomitant worsening of renal parameters. This study was an individual patient data analysis assembled from 6 prospective cohorts consisting of 1,232 patients hospitalized for ADHF. Endpoints were all-cause mortality and the composite of all-cause mortality and/or readmission for a cardiovascular reason within 180 days after discharge. A significant reduction in NT-proBNP was not associated with worsening of renal function (WRF) or severe WRF (sWRF). A reduction of NT-proBNP of more than 30% during hospitalization determined prognosis (all-cause mortality hazard ratio [HR]: 1.81; 95% confidence Interval [CI]: 1.32 to 2.50; composite endpoint: HR: 1.36, 95% CI: 1.13 to 1.64), regardless of changes in renal function and other clinical variables. When we defined prognosis, NT-proBNP changes during hospitalization for treatment of ADHF prevailed over parameters for worsening renal function. Severe WRF is a measure of prognosis, but is of lesser value than, and independent of the prognostic changes induced by adequate NT-proBNP reduction. This suggests that in ADHF patients it may be warranted to strive for an optimal decrease in NT-proBNP, even if this induces WRF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. Utility of QGS for 201Tl electrocardiogram-gated SPECT in cardiac function evaluations

    International Nuclear Information System (INIS)

    Shimazaki, Hiroshi; Oono, Ryuichi

    2001-01-01

    QGS (quantitative gated SPECT) was applied to 201 Tl SPECT, whose images are inferior to those of Tc SPECT, and its utility was evaluated. More specifically, the cardiac function index was calculated by QGS, and local wall motion was evaluated visually. Accuracy was assessed by comparison with left ventriculography. The subjects were 29 patients (21 males, 8 females; 6 with myocardial infarction, 18 with stenocardia, 2 with pericardial disease, 3 with other heart diseases) who had undergone myocardial scintigraphy and left ventriculography between February and May, 2000. 201 Tl (74 or 111 MBq) was administered to all patients. The resting image was obtained 10 minutes later, and the delayed image during loading was obtained 4 hours later. The conditions for acquiring the images were as follows. Two detectors were arranged at a 90-degree angle in the form of an L. The 180 degrees from 45 degrees right anterior oblique (RAO) to 45 degrees left posterior oblique (LPO) were divided into 30 sections at 6-degree intervals, and the image in each section was acquired for 60 seconds. The matrix was 64 x 64. As a cardiac function index, the left ventricular ejection function (LVEF) obtained by electrocardiogram-gated SPECT (QGS-EF) at the rest (14 cases) and the QGS-EF on the delayed images (15 cases) were compared with the LVEF determined by left ventriculography (LVG-EF). There was an excellent positive correlation between the data obtained by two methods, with a correlation coefficient of r=0.93 (y=1.04x-0.04). Most of the difference between the values fell within two standard deviations, and the error was in the clinically allowable range. There was no significant difference between the correlation coefficient at rest and during loading or between the cases that showed an obvious defect on the image and those that did not. The local wall motion of the left ventricle was visually evaluated in five stages in two directions (RAO, 30 degrees, and LAO, 60 degrees). The motion

  8. Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

    NARCIS (Netherlands)

    Oosterveer, Maaike H.; Koolman, Anniek H.; de Boer, Pieter T.; Bos, Trijnie; Bleeker, Aycha; Bloks, Vincent W.; Kuipers, Folkert; Sauer, Pieter J. J.; van Dijk, Gertjan

    2011-01-01

    Background: Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat

  9. The human serum metabolome of vitamin B-12 deficiency and repletion, and associations with neurological function

    Science.gov (United States)

    We characterize the human serum metabolome in sub-clinical vitamin B-12 (B-12) deficiency and repletion. A pre-post treatment study provided one injection of 10 mg B-12 to 27 community-dwelling elderly Chileans with B-12 deficiency evaluated with serum B-12, plasma homocysteine, methylmalonic acid a...

  10. Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

    Science.gov (United States)

    Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

    2012-01-01

    The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

  11. Thyroid function and deiodinase activities in rats with marginal iodine deficiency

    NARCIS (Netherlands)

    K.P.L.T.M.K. Janssen (Karin); D. van der Heide (Daan); T.J. Visser (Theo); E. Kaptein (Ellen); A.C. Beynen (Anton)

    1994-01-01

    textabstractThe hypothesis tested was whether marginal iodine deficiency for a period of 6 wk affects iodothyronine deiodinase activities in liver and brain of rats. Male rats were fed purified diets either deficient or sufficient in iodine; the diets were fed on a restricted basis (60% of ad

  12. Thyroid function and body weight in girls with irregular menstrual cycle living in mild iodine deficiency region

    OpenAIRE

    L Sh Vagapova; O D Konstantinova; Ya I Koz; L M Shukshina; E O Skrynnik

    2011-01-01

    To establish the relation of body weight indexes and functional state of thyroid in female adolescents with menstrual cycle disorder, living in the iodine-deficiency region, the investigation was conducted in 130 female adolescents with irregular menses. Obesity incidence and overweight in them was 18.5%, body weight deficiency was 43.8%.37.7% of the girls had normal body weight. Statistically significant differences were not defined according to TSH, fT4 and fT3 in patients with different bo...

  13. Self-reported physical activity and lung function two months after cardiac surgery--a prospective cohort study.

    Science.gov (United States)

    Jonsson, Marcus; Urell, Charlotte; Emtner, Margareta; Westerdahl, Elisabeth

    2014-03-28

    Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health's national survey. Formal lung function testing was performed preoperatively and two months postoperatively. The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results.

  14. The Unilateral Below Elbow Test: a function test for children with unilateral congenital below elbow deficiency.

    Science.gov (United States)

    Bagley, Anita M; Molitor, Fred; Wagner, Lisa V; Tomhave, Wendy; James, Michelle A

    2006-07-01

    The Unilateral Below Elbow Test (UBET) was developed to evaluate function in bimanual activities for both the prosthesis wearer and non-wearer. Nine tasks were chosen for each of four age-specific categories defined by development stages of hand function (2-4y, 5-7y, 8-10y, and 11-21y). Two scales, Completion of Task and Method of Use, were designed to rate performance. To measure reliability, four occupational therapists scored samples of videotaped UBET performances. For Completion of Task, an interval scale, agreement in scoring was measured with interclass correlation coefficients (ICC; n=9; five females, four males). For Method of Use, a nominal scale, chance-adjusted association was calculated with Cohen's kappa coefficients (interobserver n=198; 111 females, 87 males; intraobserver n=93; 56 females, 37 males). For Completion of Task, the average ICC was 0.87 for the prosthesis-on condition, and 0.85 for the prosthesis-off condition. ICCs exceeded 0.80 for eight out of nine tasks for the two older age groups, but for only five out of nine tasks in the younger age groups. Higher inter- and intraobserver kappa coefficients for Method of Use resulted when scoring children with their prostheses on versus off. The oldest age group had lower kappa values than the other three groups. The UBET is recommended for the functional evaluation of Completion of Task in children with unilateral congenital below elbow deficiency with and without their prostheses. Method of Use scoring can evaluate individuals for directed therapy interventions or prosthetic training.

  15. On the Averaging of Cardiac Diffusion Tensor MRI Data: The Effect of Distance Function Selection

    Science.gov (United States)

    Giannakidis, Archontis; Melkus, Gerd; Yang, Guang; Gullberg, Grant T.

    2016-01-01

    Diffusion tensor magnetic resonance imaging (DT-MRI) allows a unique insight into the microstructure of highly-directional tissues. The selection of the most proper distance function for the space of diffusion tensors is crucial in enhancing the clinical application of this imaging modality. Both linear and nonlinear metrics have been proposed in the literature over the years. The debate on the most appropriate DT-MRI distance function is still ongoing. In this paper, we presented a framework to compare the Euclidean, affine-invariant Riemannian and log-Euclidean metrics using actual high-resolution DT-MRI rat heart data. We employed temporal averaging at the diffusion tensor level of three consecutive and identically-acquired DT-MRI datasets from each of five rat hearts as a means to rectify the background noise-induced loss of myocyte directional regularity. This procedure is applied here for the first time in the context of tensor distance function selection. When compared with previous studies that used a different concrete application to juxtapose the various DT-MRI distance functions, this work is unique in that it combined the following: (i) Metrics were judged by quantitative –rather than qualitative– criteria, (ii) the comparison tools were non-biased, (iii) a longitudinal comparison operation was used on a same-voxel basis. The statistical analyses of the comparison showed that the three DT-MRI distance functions tend to provide equivalent results. Hence, we came to the conclusion that the tensor manifold for cardiac DT-MRI studies is a curved space of almost zero curvature. The signal to noise ratio dependence of the operations was investigated through simulations. Finally, the “swelling effect” occurrence following Euclidean averaging was found to be too unimportant to be worth consideration. PMID:27754986

  16. On the averaging of cardiac diffusion tensor MRI data: the effect of distance function selection

    Science.gov (United States)

    Giannakidis, Archontis; Melkus, Gerd; Yang, Guang; Gullberg, Grant T.

    2016-11-01

    Diffusion tensor magnetic resonance imaging (DT-MRI) allows a unique insight into the microstructure of highly-directional tissues. The selection of the most proper distance function for the space of diffusion tensors is crucial in enhancing the clinical application of this imaging modality. Both linear and nonlinear metrics have been proposed in the literature over the years. The debate on the most appropriate DT-MRI distance function is still ongoing. In this paper, we presented a framework to compare the Euclidean, affine-invariant Riemannian and log-Euclidean metrics using actual high-resolution DT-MRI rat heart data. We employed temporal averaging at the diffusion tensor level of three consecutive and identically-acquired DT-MRI datasets from each of five rat hearts as a means to rectify the background noise-induced loss of myocyte directional regularity. This procedure is applied here for the first time in the context of tensor distance function selection. When compared with previous studies that used a different concrete application to juxtapose the various DT-MRI distance functions, this work is unique in that it combined the following: (i) metrics were judged by quantitative—rather than qualitative—criteria, (ii) the comparison tools were non-biased, (iii) a longitudinal comparison operation was used on a same-voxel basis. The statistical analyses of the comparison showed that the three DT-MRI distance functions tend to provide equivalent results. Hence, we came to the conclusion that the tensor manifold for cardiac DT-MRI studies is a curved space of almost zero curvature. The signal to noise ratio dependence of the operations was investigated through simulations. Finally, the ‘swelling effect’ occurrence following Euclidean averaging was found to be too unimportant to be worth consideration.

  17. Estrogen Therapy, Independent of Timing, Improves Cardiac Structure and Function in Oophorectomized mRen2.Lewis Rats

    Science.gov (United States)

    Jessup, Jewell A.; Wang, Hao; MacNamara, Lindsay M.; Presley, Tennille D.; Kim-Shapiro, Daniel B.; Zhang, Lili; Chen, Alex F.; Groban, Leanne

    2013-01-01

    Objective mRen2.Lewis Rats exhibit exacerbated increases in blood pressure, left ventricular (LV) remodeling, and diastolic impairment following the loss of estrogens. In this same model, depletion of estrogens has marked effects on the cardiac biopterin profile concomitant with suppressed nitric oxide (NO) release. With respect to the establishment of overt systolic hypertension after oophorectomy (OVX), we assessed the effects of timing chronic 17 β-estradiol (E2) therapy on myocardial function, structure, and the cardiac NO system. Methods Oophrectomy (OVX; n=24) or sham-operation (Sham; n=13) was performed in 4-week-old, female mRen2.Lewis rats. Following randomization, OVX rats received E2 immediately (OVX + early E2; n=7), E2 at 11 weeks of age (OVX + late E2 N=8), or no E2 at all (OVX N=9). Results Early E2 was associated with lower body weight, less hypertension-related cardiac remodeling, and decreased LV filling pressure compared to OVX rats without E2 supplementation. Late E2 similarly attenuated the adverse effects of ovarian hormone loss on tissue-Doppler derived LV filling pressures and perivascular fibrosis, and significantly improved myocardial relaxation, or mitral annular velocity (e′). Early and late exposure to E2 decreased dihydrobiopterin, but only late E2 yielded significant increases in cardiac nitrite concentrations. Conclusions Although there were some similarities between early and late E2 treatment on preservation of diastolic function and cardiac structure after OVX, the lusitropic potential of E2 was most consistent with late supplementation. The cardioprotective effects of late E2 were independent of blood pressure and may have occurred through regulation of cardiac biopterins and NO production. PMID:23481117

  18. The Incidence of Functional Disorders and Clinical Symptoms that May be Associated with Lactase Deficiency in Infants of Lviv

    Directory of Open Access Journals (Sweden)

    R.V. Tkach

    2016-08-01

    Full Text Available Today, the violations of the digestive system in children of the first years of life remain the actual problem of practical pediatrics and are the common cause for parents to visit a doctor. The importance in the genesis of functional disorders of the digestive system in children of this age may belongs to lactase deficiency. 327 children from Lviv were included in the questionnaire survey. The aim of the study was to evaluate the incidence of clinical symptoms that may be associated with lactase deficiency in infants. Among the clinical symptoms in young children, according to the survey, regurgitation and colic, stool disorders dominated. The diagnosis of lactase deficiency was established in 3.4 % (11 of children, 2.8 % (9 children received enzyme of lactase.

  19. The physiology of functional hypothalamic amenorrhea associated with energy deficiency in exercising women and in women with anorexia nervosa.

    Science.gov (United States)

    Allaway, Heather C M; Southmayd, Emily A; De Souza, Mary Jane

    2016-02-01

    An energy deficiency is the result of inadequate energy intake relative to high energy expenditure. Often observed with the development of an energy deficiency is a high drive for thinness, dietary restraint, and weight and shape concerns in association with eating behaviors. At a basic physiologic level, a chronic energy deficiency promotes compensatory mechanisms to conserve fuel for vital physiologic function. Alterations have been documented in resting energy expenditure (REE) and metabolic hormones. Observed metabolic alterations include nutritionally acquired growth hormone resistance and reduced insulin-like growth factor-1 (IGF-1) concentrations; hypercortisolemia; increased ghrelin, peptide YY, and adiponectin; and decreased leptin, triiodothyronine, and kisspeptin. The cumulative effect of the energetic and metabolic alterations is a suppression of the hypothalamic-pituitary-ovarian axis. Gonadotropin releasing hormone secretion is decreased with consequent suppression of luteinizing hormone and follicle stimulating hormone release. Alterations in hypothalamic-pituitary secretion alters the production of estrogen and progesterone resulting in subclinical or clinical menstrual dysfunction.

  20. Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity.

    Science.gov (United States)

    Kwon, Yong-Soo; Cho, Young-Nan; Kim, Moon-Ju; Jin, Hye-Mi; Jung, Hyun-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Kim, Tae-Jong; Kee, Hae Jin; Kim, Nacksung; Kee, Seung-Jung; Park, Yong-Wook

    2015-05-01

    Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in Epileptic Children.

    Science.gov (United States)

    Doksöz, Önder; Çeleğen, Kübra; Güzel, Orkide; Yılmaz, Ünsal; Uysal, Utku; İşgüder, Rana; Çeleğen, Mehmet; Meşe, Timur

    2015-09-01

    Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy. Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients. The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Burnout versus work engagement in their effects on 24-hour ambulatory monitored cardiac autonomic function

    NARCIS (Netherlands)

    L.J.P. van Doornen (Lorenz); J.H. Houtveen (Jan); S. Langelaan (Saar); A.B. Bakker (Arnold); W. van Rhenen (Willem); W.B. Schaufeli (Wilmar)

    2009-01-01

    textabstractBurnout has been associated with increased risk of cardiovascular disease. This relationship may be mediated by a stress-related disruption in cardiac autonomic activity. The aim of the present study was to assess cardiac autonomic activity (sympathetic and parasympathetic) during a

  3. Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure

    NARCIS (Netherlands)

    D. Westermann (Dirk); A. Riad (Alexander); O. Lettau (Olga); A.J.M. Roks (Anton); K. Sawatis (Konstantinos); P.M. Becher (Peter Moritz); F. Escher (Felicitas); A.H.J. Danser (Jan); H.P. Schultheiss (Heinz-Peter); C. Tschöpe (Carsten)

    2008-01-01

    textabstractPharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac

  4. Cardiac autonomic function and hot flashes among perimenopausal and postmenopausal women.

    Science.gov (United States)

    Gibson, Carolyn J; Mendes, Wendy Berry; Schembri, Michael; Grady, Deborah; Huang, Alison J

    2017-07-01

    Abnormalities in autonomic function are posited to play a pathophysiologic role in menopausal hot flashes. We examined relationships between resting cardiac autonomic activity and hot flashes in perimenopausal and postmenopausal women. Autonomic function was assessed at baseline and 12 weeks among perimenopausal and postmenopausal women (n = 121, mean age 53 years) in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, was measured with impedance cardiography. Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, was measured with electrocardiography. Participants self-reported hot flash frequency and severity in 7-day symptom diaries. Analysis of covariance models were used to relate autonomic function and hot flash frequency and severity at baseline, and to relate changes in autonomic function to changes in hot flash frequency and severity over 12 weeks, adjusting for age, body mass index, and intervention assignment. PEP was not associated with hot flash frequency or severity at baseline or over 12 weeks (P > 0.05 for all). In contrast, there was a trend toward greater frequency of moderate-to-severe hot flashes with higher RSA at baseline (β = 0.43, P = 0.06), and a positive association between change in RSA and change in frequency of moderate-to-severe hot flashes over 12 weeks (β = 0.63, P = 0.04). Among perimenopausal and postmenopausal women with hot flashes, variations in hot flash frequency and severity were not explained by variations in resting sympathetic activation. Greater parasympathetic activation was associated with more frequent moderate-to-severe hot flashes, which may reflect increased sensitivity to perceiving hot flashes.

  5. Evaluation of Exercise Performance, Cardiac Function, and Quality of Life in Children After Liver Transplantation.

    Science.gov (United States)

    Vandekerckhove, Kristof; Coomans, Ilse; De Bruyne, Elke; De Groote, Katya; Panzer, Joseph; De Wolf, Daniel; Boone, Jan; De Bruyne, Ruth

    2016-07-01

    In children, after having liver transplantation (LT), it is important to assess the quality of life (QOL). Physical fitness is an important determinant of QOL, and because cardiac function can influence exercise performance, it is the purpose of the present study to assess these factors. Children in stable follow-up for more than 6 months post-LT were invited to participate in a case control study. Patients underwent cardiopulmonary exercise testing and echocardiography to assess systolic and diastolic function, and left ventricular wall dimensions. Health-related QOL was evaluated using child- and adolescent-reported PedsQL questionnaire. Twenty-eight of 31 included patients performed a maximal exercise test (15 boys, 11.6 ± 2.9 years, weight, 40.9 ± 13.1 kg; length, 148.6 ± 17.3 cm; body mass index, 17.6 ± 2.3). Liver transplantation patients had lower maximal oxygen consumption (VO2max/kg) (37.5 ± 9.3 mL/kg per minute vs 44.1 ± 8.8 mL/kg per minute), shorter exercise duration (9.3 ± 2.8 minutes vs 13.3 ± 3 minutes) and lower load (71 ± 14 vs 85 ± 20%). They reached the ventilatory anaerobic threshold earlier (81.4 ± 9.5 vs 88.3 ± 11.9%). Echocardiography demonstrated increased interventricular septal wall thickness (interventricular septum in diastole Z value, +0.45 ± 0.49, P exercise testing. Health-related QOL showed lower overall, emotional, psychosocial, and school functioning scores. Children on antihypertensive medication had impaired physical functioning compared with other LT patients. Lower physical fitness level, more deconditioning and lower health-related QOL in children after LT emphasize the importance of exercise stimulation and fitness programs. Patients on antihypertensive medication seem to be the most vulnerable group suffering from decreased physical fitness.

  6. Evaluation of Cardiac Mitochondrial Function by a Nuclear Imaging Technique using Technetium-99m-MIBI Uptake Kinetics

    International Nuclear Information System (INIS)

    Matsuo, Shinro; Nakajima, Kenichi; Kinuya, Seigo

    2013-01-01

    Mitochondria play an important role in energy production for the cell. The proper function of a myocardial cell largely depends on the functional capacity of the mitochondria. Therefore it is necessary to establish a novel and reliable method for a non-invasive assessment of mitochondrial function and metabolism in humans. Although originally designed for evaluating myocardial perfusion, 99m Tc-MIBI can be also used to evaluate cardiac mitochondrial function. In a clinical study on ischemic heart disease, reverse redistribution of 99m Tc-MIBI was evident after direct percutaneous transluminal coronary angioplasty. The presence of increased washout of 99m Tc-MIBI was associated with the infarct-related artery and preserved left ventricular function. In non-ischemic cardiomyopathy, an increased washout rate of 99m Tc-MIBI, which correlated inversely with left ventricular ejection fraction, was observed in patients with congestive heart failure. Increased 99m Tc-MIBI washout was also observed in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and in doxorubicin-induced cardiomyopathy. Noninvasive assessment of cardiac mitochondrial function could be greatly beneficial in monitoring possible cardiotoxic drug use and in the evaluation of cardiac damage in clinical medicine

  7. Exercise capacity in diabetes mellitus is predicted by activity status and cardiac size rather than cardiac function: a case control study.

    Science.gov (United States)

    Roberts, Timothy J; Burns, Andrew T; MacIsaac, Richard J; MacIsaac, Andrew I; Prior, David L; La Gerche, André

    2018-03-23

    The reasons for reduced exercise capacity in diabetes mellitus (DM) remains incompletely understood, although diastolic dysfunction and diabetic cardiomyopathy are often favored explanations. However, there is a paucity of literature detailing cardiac function and reserve during incremental exercise to evaluate its significance and contribution. We sought to determine associations between comprehensive measures of cardiac function during exercise and maximal oxygen consumption ([Formula: see text]peak), with the hypothesis that the reduction in exercise capacity and cardiac function would be associated with co-morbidities and sedentary behavior rather than diabetes itself. This case-control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and 10 healthy controls age/sex-matched to each diabetes subtype] performing cardiopulmonary exercise testing and bicycle ergometer echocardiography studies. Measures of biventricular function were assessed during incremental exercise to maximal intensity. T2DM subjects were middle-aged (52 ± 11 years) with a mean T2DM diagnosis of 12 ± 7 years and modest glycemic control (HbA 1c 57 ± 12 mmol/mol). T1DM participants were younger (35 ± 8 years), with a 19 ± 10 year history of T1DM and suboptimal glycemic control (HbA 1c 65 ± 16 mmol/mol). Participants with T2DM were heavier than their controls (body mass index 29.3 ± 3.4 kg/m 2 vs. 24.7 ± 2.9, P = 0.001), performed less exercise (10 ± 12 vs. 28 ± 30 MET hours/week, P = 0.031) and had lower exercise capacity ([Formula: see text]peak = 26 ± 6 vs. 38 ± 8 ml/min/kg, P accounting for age, sex and body surface area in a multivariate analysis, significant positive predictors of [Formula: see text]peak were cardiac size (LV end-diastolic volume, LVEDV) and estimated MET-hours, while T2DM was a negative predictor. These combined factors accounted for 80% of the variance in [Formula: see text

  8. Cardiac systolic function in cirrhotic patients’ candidate of liver trans-plantation compared with control group

    Directory of Open Access Journals (Sweden)

    Roya Sattarzadeh-Badkoubeh

    2017-02-01

    systolic dysfunction in cirrhotic patients. These effects were due to chamber enlargement and we cannot use the most of cardiac indices for evaluation systolic function in cirrhotic patients. So, we suggest that systolic time interval and Tei index are useful indices in evaluation of systolic function in cirrhotic patients.

  9. Homologous recombination mediates functional recovery of dysferlin deficiency following AAV5 gene transfer.

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    William E Grose

    Full Text Available The dysferlinopathies comprise a group of untreatable muscle disorders including limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment syndrome, and rigid spine syndrome. As with other forms of muscular dystrophy, adeno-associated virus (AAV gene transfer is a particularly auspicious treatment strategy, however the size of the DYSF cDNA (6.5 kb negates packaging into traditional AAV serotypes known to express well in muscle (i.e. rAAV1, 2, 6, 8, 9. Potential advantages of a full cDNA versus a mini-gene include: maintaining structural-functional protein domains, evading protein misfolding, and avoiding novel epitopes that could be immunogenic. AAV5 has demonstrated unique plasticity with regards to packaging capacity and recombination of virions containing homologous regions of cDNA inserts has been implicated in the generation of full-length transcripts. Herein we show for the first time in vivo that homologous recombination following AAV5.DYSF gene transfer leads to the production of full length transcript and protein. Moreover, gene transfer of full-length dysferlin protein in dysferlin deficient mice resulted in expression levels sufficient to correct functional deficits in the diaphragm and importantly in skeletal muscle membrane repair. Intravascular regional gene transfer through the femoral artery produced high levels of transduction and enabled targeting of specific muscle groups affected by the dysferlinopathies setting the stage for potential translation to clinical trials. We provide proof of principle that AAV5 mediated delivery of dysferlin is a highly promising strategy for treatment of dysferlinopathies and has far-reaching implications for the therapeutic delivery of other large genes.

  10. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation.

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    Esra Cagavi

    Full Text Available As heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP expression that is directed by the mef2c gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8±0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of

  11. Comparison of yoga and walking-exercise on cardiac time intervals as a measure of cardiac function in elderly with increased pulse pressure.

    Science.gov (United States)

    Patil, Satish Gurunathrao; Patil, Shankargouda S; Aithala, Manjunatha R; Das, Kusal Kanti

    Arterial aging along with increased blood pressure(BP) has become the major cardiovascular(CV) risk in elderly. The aim of the study was to compare the effects of yoga program and walking-exercise on cardiac function in elderly with increased pulse pressure (PP). An open label, parallel-group randomized controlled study design was adopted. Elderly individuals aged ≥60 years with PP≥60mmHg were recruited for the study. Yoga (study) group (n=30) was assigned for yoga training and walking (exercise) group (n=30) for walking with loosening practices for one hour in the morning for 6days in a week for 3 months. The outcome measures were cardiac time intervals derived from pulse wave analysis and ECG: resting heart rate (RHR), diastolic time(DT), ventricular ejection time(LVET), upstroke time(UT), ejection duration index (ED%), pre-ejection period (PEP), rate pressure product (RPP) and percentage of mean arterial pressure (%MAP). The mean within-yoga group change in RHR(bpm) was 4.41 (p=0.031), PD(ms): -50.29 (p=0.042), DT(ms): -49.04 (p=0.017), ED%: 2.107 (p=0.001), ES(mmHg/ms): 14.62 (p=0.118), ET(ms): -0.66 (p=0.903), UT(ms): -2.54 (p=0.676), PEP(ms): -1.25 (p=0.11) and %MAP: 2.08 (p=0.04). The mean within-control group change in HR (bpm) was 0.35 (p=0.887), PD (ms): 11.15(p=0.717), DT (ms): 11.3 (p=0.706), ED%: -0.101 (p=0.936), ES (mmHg/ms): 0.75 (p=0.926), ET(ms): 2.2 (p=0.721), UT(ms):4.7(p=455), PEP (ms): 2.1(p=0.11), %MAP: 0.65 (p=0.451). A significant difference between-group was found in RHR (p=0.036), PD (p=0.02), ED% (p=0.049), LVET (p=0.048), DT (p=0.02) and RPP (p=0.001). Yoga practice for 3 months showed a significant improvement in diastolic function with a minimal change in systolic function. Yoga is more effective than walking in improving cardiac function in elderly with high PP. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  12. Impact of exercise rehabilitation on cardiac neuronal function in heart failure. An iodine-123 metaiodobenzylguanidine scintigraphy study

    International Nuclear Information System (INIS)

    Agostini, D.; Bouvard, G.; Lecluse, E.; Grollier, G.; Potier, J.C.; Belin, A.; Babatasi, G.; Amar, M.H.

    1998-01-01

    Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiobodenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable chronic heart failure of NYHA class II-III and an initial resting radionuclide left ventricular ejection fraction (LVEF) 123 I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801±428 vs 1229±245 kpm.min -1 , P=0.001), exercise duration (504±190 vs 649±125 s, P=0.02), and myocardial MIBG uptake (135%±19% vs 156%±25%, P=0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%±9% vs 21%±10%, p=NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. (orig.)

  13. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

    Science.gov (United States)

    Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

    2016-01-01

    Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

  14. Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis.

    Science.gov (United States)

    Feng, Han-Zhong; Biesiadecki, Brandon J; Yu, Zhi-Bin; Hossain, M Moazzem; Jin, J-P

    2008-07-15

    The N-terminal variable region of cardiac troponin T (TnT) is a regulatory structure that can be selectively removed during myocardial ischaemia reperfusion by mu-calpain proteolysis. Here we investigated the pathophysiological significance of this post-translational modification that removes amino acids 1-71 of cardiac TnT. Working heart preparations were employed to study rat acute myocardial infarction and transgenic mouse hearts over-expressing the N-terminal truncated cardiac TnT (cTnT-ND). Ex vivo myocardial infarction by ligation of the left anterior descending coronary artery induced heart failure and produced cTnT-ND not only in the infarct but also in remote zones, including the right ventricular free wall, indicating a whole organ response in the absence of systemic neurohumoral mechanisms. Left ventricular pressure overload in mouse working hearts produced increased cTnT-ND in both ventricles, suggesting a role of haemodynamic stress in triggering an acute whole organ proteolytic regulation. Transgenic mouse hearts in which the endogenous intact cardiac TnT was partially replaced by cTnT-ND showed lowered contractile velocity. When afterload increased from 55 mmHg to 90 mmHg, stroke volume decreased in the wild type but not in the transgenic mouse hearts. Correspondingly, the left ventricular rapid-ejection time of the transgenic mouse hearts was significantly longer than that of wild type hearts, especially at high afterload. The restricted deletion of the N-terminal variable region of cardiac troponin T demonstrates a novel mechanism by which the thin filament regulation adapts to sustain cardiac function under stress conditions.

  15. Impaired cerebrovascular function in coronary artery disease patients and recovery following cardiac rehabilitation.

    Directory of Open Access Journals (Sweden)

    Udunna C Anazodo

    2016-01-01

    Full Text Available Coronary artery disease (CAD poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF and cerebrovascular reactivity (CVR to hypercapnia in 34 coronary artery disease (CAD patients and 21 age-matched controls. Gray matter volume images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate, insular, pre- and post-central gyri, middle temporal and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the anterior cingulate, insula, postcentral and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in gray matter volume were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-month exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral anterior cingulate, as well as recovery of CBF in the dorsal aspect of the right anterior cingulate, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the anterior cingulate is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control.

  16. Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle function

    Science.gov (United States)

    Gallagher, Thomas L.; Arribere, Joshua A.; Geurts, Paul A.; Exner, Cameron R. T.; McDonald, Kent L.; Dill, Kariena K.; Marr, Henry L.; Adkar, Shaunak S.; Garnett, Aaron T.; Amacher, Sharon L.; Conboy, John G.

    2012-01-01

    Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos was strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle function. PMID:21925157

  17. Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions.

    Science.gov (United States)

    Gallagher, Thomas L; Arribere, Joshua A; Geurts, Paul A; Exner, Cameron R T; McDonald, Kent L; Dill, Kariena K; Marr, Henry L; Adkar, Shaunak S; Garnett, Aaron T; Amacher, Sharon L; Conboy, John G

    2011-11-15

    Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos were strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle functions. Published by Elsevier Inc.

  18. A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia.

    Science.gov (United States)

    Fu, Liang-Wu; Longhurst, John C

    2010-12-01

    Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and α,β-methylene ATP (α,β-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T(2)-T(5)) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25-4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 Aδ, 37 C fibers). Epicardial application of ATP (1-4 μmol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 μmol), ADP (2 μmol), a P2Y agonist, and α,β-meATP (0.5 μmol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 μmol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2-4 μmol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory

  19. The effect of traditional Persian music on the cardiac functioning of young Iranian women.

    Science.gov (United States)

    Abedi, Behzad; Abbasi, Ataollah; Goshvarpour, Atefeh; Khosroshai, Hamid Tayebi; Javanshir, Elnaz

    In the past few decades, several studies have reported the physiological effects of listening to music. The physiological effects of different music types on different people are not similar. Therefore, in the present study, we have sought to examine the effects of traditional Persian music on the cardiac function in young women. Twenty-two healthy females participated in this study. ECG signals were recorded in two conditions: rest and music. For each of the 21 ECG signals (15 morphological and six wavelet based feature) features were extracted. SVM classifier was used for the classification of ECG signals during and before the music. The results showed that the mean of heart rate, the mean amplitude of R-wave, T-wave, and P-wave decreased in response to music. Time-frequency analysis revealed that the mean of the absolute values of the detail coefficients at higher scales increased during rest. The overall accuracy of 91.6% was achieved using polynomial kernel and RBF kernel. Using linear kernel, the best result (with the accuracy rate of 100%) was attained. Copyright © 2016. Published by Elsevier B.V.

  20. The effects of detomidine, romifidine or acepromazine on echocardiographic measurements and cardiac function in normal horses.

    Science.gov (United States)

    Buhl, Rikke; Ersbøll, Annette K; Larsen, Nanna H; Eriksen, Lis; Koch, Jørgen

    2007-01-01

    To evaluate by echo- and electrocardiography the cardiac effects of sedation with detomidine hydrochloride, romifidine hydrochloride or acepromazine maleate in horses. An experimental study using a cross-over design without randomization. Eight clinically normal Standardbred trotters. Echocardiographic examinations (two-dimensional, guided M-mode and colour Doppler) were recorded on five different days. Heart rate (HR) and standard limb lead electrocardiograms were also obtained. Subsequently, horses were sedated with detomidine (0.01 mg kg(-1)), romifidine (0.04 mg kg(-1)) or acepromazine (0.1 mg kg(-1)) administered intravenously and all examinations repeated. Heart rate before treatment with the three drugs did not differ significantly (p = 0.98). Both detomidine and romifidine induced a significant decrease (p detomidine, there was a significant increase in LVIDd (left ventricular internal diameter in diastole; p = 0.034) and LVIDs (left ventricular internal diameter in systole; p detomidine and to a lesser extent romifidine at the doses given in this study has a significant effect on heart function, echocardiographic measurements of heart dimensions and the occurrence of valvular regurgitation. Although the clinical significance of these results may be minimal, the potential effects of sedative drugs should be taken into account when echocardiographic variables are interpreted in clinical cases.

  1. Exercise capacity in the Bidirectional Glenn physiology: Coupling cardiac index, ventricular function and oxygen extraction ratio.

    Science.gov (United States)

    Vallecilla, Carolina; Khiabani, Reza H; Trusty, Phillip; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P

    2015-07-16

    In Bi-directional Glenn (BDG) physiology, the superior systemic circulation and pulmonary circulation are in series. Consequently, only blood from the superior vena cava is oxygenated in the lungs. Oxygenated blood then travels to the ventricle where it is mixed with blood returning from the lower body. Therefore, incremental changes in oxygen extraction ratio (OER) could compromise exercise tolerance. In this study, the effect of exercise on the hemodynamic and ventricular performance of BDG physiology was investigated using clinical patient data as inputs for a lumped parameter model coupled with oxygenation equations. Changes in cardiac index, Qp/Qs, systemic pressure, oxygen extraction ratio and ventricular/vascular coupling ratio were calculated for three different exercise levels. The patient cohort (n=29) was sub-grouped by age and pulmonary vascular resistance (PVR) at rest. It was observed that the changes in exercise tolerance are significant in both comparisons, but most significant when sub-grouped by PVR at rest. Results showed that patients over 2 years old with high PVR are above or close to the upper tolerable limit of OER (0.32) at baseline. Patients with high PVR at rest had very poor exercise tolerance while patients with low PVR at rest could tolerate low exercise conditions. In general, ventricular function of SV patients is too poor to increase CI and fulfill exercise requirements. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different exercise levels according to patient specific data. Published by Elsevier Ltd.

  2. Affect during incremental exercise: The role of inhibitory cognition, autonomic cardiac function, and cerebral oxygenation.

    Directory of Open Access Journals (Sweden)

    Weslley Quirino Alves da Silva

    Full Text Available Pleasure is a key factor for physical activity behavior in sedentary individuals. Inhibitory cognitive control may play an important role in pleasure perception while exercising, especially at high intensities. In addition, separate work suggests that autonomic regulation and cerebral hemodynamics influence the affective and cognitive responses during exercise.We investigated the effects of exercise intensity on affect, inhibitory control, cardiac autonomic function, and prefrontal cortex (PFC oxygenation.Thirty-seven sedentary young adults performed two experimental conditions (exercise and control in separate sessions in a repeated-measures design. In the exercise condition, participants performed a maximum graded exercise test on a cycle ergometer as we continuously measured oxygen consumption, heart rate variability (HRV, and PFC oxygenation. At each of 8 intensity levels we also measured inhibitory control (Stroop test, associative and dissociative thoughts (ADT, and affective/pleasure ratings. In the control condition, participants sat motionless on a cycle ergometer without active pedaling, and we collected the same measures at the same points in time as the exercise condition. We evaluated the main effects and interactions of exercise condition and intensity level for each measure using two-way repeated measures ANOVAs. Additionally, we evaluated the relationship between affect and inhibitory control, ADT, HRV, and PFC oxygenation using Pearson's correlation coefficients.For exercise intensities below and at the ventilatory threshold (VT, participants reported feeling neutral, with preservation of inhibitory control, while intensities above the VT were associated with displeasure (p<0.001, decreased inhibitory control and HRV (p<0.001, and increased PFC oxygenation (p<0.001. At the highest exercise intensity, pleasure was correlated with the low-frequency index of HRV (r = -0.34; p<0.05 and the low-frequency/high-frequency HRV ratio (r

  3. De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

    Science.gov (United States)

    Gebert, Dorothea; Auer, Matthias K; Stieg, Mareike R; Freitag, Martin T; Lahne, Madlén; Fuss, Johannes; Schilbach, Katharina; Schopohl, Jochen; Stalla, Günter K; Kopczak, Anna

    2018-02-01

    Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline

  4. Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33°C versus 36°C

    DEFF Research Database (Denmark)

    Lilja, Gisela; Nielsen, Niklas; Friberg, Hans

    2015-01-01

    assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest...... was more affected among cardiac arrest patients, but results for memory and executive functioning were similar. CONCLUSIONS: Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest...... performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed...

  5. Improving adherence to alpha-1 antitrypsin deficiency screening guidelines using the pulmonary function laboratory

    Directory of Open Access Journals (Sweden)

    Luna Diaz LV

    2017-07-01

    Full Text Available Landy V Luna Diaz,1 Isabella Iupe,1 Bruno Zavala,1 Kira C Balestrini,1 Andrea Guerrero,1 Gregory Holt,1,2 Rafael Calderon-Candelario,1,2 Mehdi Mirsaeidi,1,2 Michael Campos1,21Miami Veterans Administration Medical Center, Miami, FL, 2Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Miami School of Medicine, Miami, FL, USAAlpha-1 antitrypsin deficiency (AATD is the only well-recognized genetic disorder associated with an increased risk of emphysema and COPD.1 Identifying AATD allows genetic counseling and the chance to offer specific augmentation therapy to slow emphysema progression. Despite specific recommendations from the World Health Organization, American Thoracic Society and European Respiratory Society to screen all patients with COPD and other at-risk conditions,2–4 testing rates are low (<15%.5We conducted a project to improve AATD screening at the Miami VA Medical Center using the pulmonary function test (PFT laboratory. We instructed the PFT personnel to perform reflex testing on all patients with pre-bronchodilator airflow obstruction (forced expiratory volume in 1 second/forced vital capacity <70% and then evaluated if the screening was appropriate according to guidelines. Trained PFT personnel explained AATD disease to patients and provided them with an informational brochure. After obtaining verbal consent, AATD screening was performed using dried blood spot kits provided by the Alpha-1 Foundation as part of the Florida Screening Program (noncommercial.6 The PFT lab director was the responsible physician of record, in charge of discussing positive results to patients and documenting results in the electronic medical record. The Miami Veterans Affairs Medical Center Institutional Review Board approved the protocol as a quality improvement project.

  6. Development of a rabbit's urethral sphincter deficiency animal model for anatomical-functional evaluation

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    M. Skaff

    2012-02-01

    Full Text Available OBJECTIVE: The aim of the study was to develop a new durable animal model (using rabbits for anatomical-functional evaluation of urethral sphincter deficiency. MATERIALS AND METHODS: A total of 40 New Zealand male rabbits, weighting 2.500 kg to 3.100 kg, were evaluated to develop an incontinent animal model. Thirty-two animals underwent urethrolysis and 8 animals received sham operation. Before and at 2, 4, 8 and 12 weeks after urethrolysis or sham operation, it was performed cystometry and leak point pressure (LPP evaluation with different bladder distension volumes (10, 20, 30 mL. In each time point, 10 animals (8 from the study group and 2 from the sham group were sacrificed to harvest the bladder and urethra. The samples were evaluated by H&E and Masson's Trichrome to determine urethral morphology and collagen/smooth muscle density. RESULTS: Twelve weeks after urethrolysis, it was observed a significant decrease in LPP regardless the bladder volume (from 33.7 ± 6.6 to 12.8 ± 2.2 cmH2O. The histological analysis evidenced a decrease of 22% in smooth muscle density with a proportional increase in the collagen, vessels and elastin density (p < 0.01. CONCLUSIONS: Transabdominal urethrolysis develops urethral sphincter insufficiency in rabbits, with significant decrease in LPP associated with decrease of smooth muscle fibers and increase of collagen density. This animal model can be used to test autologous cell therapy for stress urinary incontinence treatment.

  7. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.

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    Kazuaki Nakajima

    Full Text Available Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6 or 1x10(6 cells were transplanted with GH (10 mg/ml to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS, only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6 CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05, only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05. Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01 and angiogenesis was significantly enhanced (p<0.05 in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05. Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH

  8. Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function.

    Science.gov (United States)

    Hurwitz, Barry E; Coryell, Virginia T; Parker, Meela; Martin, Pedro; Laperriere, Arthur; Klimas, Nancy G; Sfakianakis, George N; Bilsker, Martin S

    2009-10-19

    The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue syndrome) cohort were present and linked to illness severity and sedentary lifestyle. Follow-up analyses assessed whether differences in cardiac output levels between CFS and control groups were corrected by controlling for cardiac contractility and TBV (total blood volume). The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) and non-sedentary (n=32). Controls were matched to CFS participants using age, gender, ethnicity and body mass. Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups. Dual tag blood volume assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood cell volume) than control groups. Of the CFS subjects with a TBV deficit (i.e. > or = 8% below ideal levels), the mean+/-S.D. percentage deficit in TBV, PV and RBCV were -15.4+/-4.0, -13.2+/-5.0 and -19.1+/-6.3% respectively. Lower cardiac volume levels in CFS were substantially corrected by controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility levels. Analyses indicated that the TBV deficit explained 91-94% of the group differences in cardiac volume indices. Group differences in cardiac structure were offsetting and, hence, no differences emerged for left ventricular mass index. Therefore the findings indicate that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition. Further study is needed to address

  9. Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature

    International Nuclear Information System (INIS)

    Seemann, Ingar; Gabriels, Karen; Visser, Nils L.; Hoving, Saske; Poele, Johannes A. te; Pol, Jeffrey F.; Gijbels, Marion J.; Janssen, Ben J.; Leeuwen, Fijs W. van; Daemen, Mat J.; Heeneman, Sylvia; Stewart, Fiona A.

    2012-01-01

    Background: Radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiotoxicity, but the underlying mechanisms are unclear. Methods: Single doses of 2, 8, or 16 Gy were delivered to the hearts of mice and damage was evaluated at 20, 40, and 60 weeks, relative to age matched controls. Single photon emission computed tomography (SPECT/CT) and ultrasound were used to measure cardiac geometry and function, which was related to histo-morphology and microvascular damage. Results: Gated SPECT/CT and ultrasound demonstrated decreases in end diastolic and systolic volumes, while the ejection fraction was increased at 20 and 40 weeks after 2, 8, and 16 Gy. Cardiac blood volume was decreased at 20 and 60 weeks after irradiation. Histological examination revealed inflammatory changes at 20 and 40 weeks after 8 and 16 Gy. Microvascular density in the left ventricle was decreased at 40 and 60 weeks after 8 and 16 Gy, with functional damage to remaining microvasculature manifest as decreased alkaline phosphatase (2, 8, and 16 Gy), increased von Willebrand Factor and albumin leakage from vessels (8 and 16 Gy), and amyloidosis (16 Gy). 16 Gy lead to sudden death between 30 and 40 weeks in 38% of mice. Conclusions: Irradiation with 2 and 8 Gy induced modest changes in murine cardiac function within 20 weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death.

  10. Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study

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    Anne M. Weaver

    2016-06-01

    Full Text Available 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.

  11. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    Science.gov (United States)

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  12. In Vivo Functional Selection Identifies Cardiotrophin-1 as a Cardiac Engraftment Factor for Mesenchymal Stromal Cells.

    Science.gov (United States)

    Bortolotti, Francesca; Ruozi, Giulia; Falcione, Antonella; Doimo, Sara; Dal Ferro, Matteo; Lesizza, Pierluigi; Zentilin, Lorena; Banks, Lawrence; Zacchigna, Serena; Giacca, Mauro

    2017-10-17

    Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here, we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell engraftment into the heart both in normal conditions and after myocardial infarction. An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral vectors. Pools from this library were then used for the batch transduction of bone marrow-derived mesenchymal stromal cells ex vivo, followed by intramyocardial cell administration in normal and infarcted mice. Three weeks after injection, vector genomes were recovered from the few persisting cells and identified by sequencing DNA barcodes uniquely labeling each of the tested cytokines. The most effective molecule identified by this competitive engraftment screening was cardiotrophin-1, a member of the interleukin-6 family. Intracardiac injection of mesenchymal stromal cells transiently preconditioned with cardiotrophin-1 preserved cardiac function and reduced infarct size, parallel to the persistence of the transplanted cells in the healing hearts for at least 2 months after injection. Engraftment of cardiotrophin-1-treated mesenchymal stromal cells was consequent to signal transducer and activator of transcription 3-mediated activation of the focal adhesion kinase and its associated focal adhesion complex and the consequent acquisition of adhesive properties by the cells. These results support the feasibility of selecting molecules in vivo for their functional properties with adeno-associated viral vector libraries and identify cardiotrophin-1 as a powerful cytokine promoting cell engraftment and thus improving cell therapy of the infarcted myocardium. © 2017 American Heart Association, Inc.

  13. EFFECTS OF LONG-TERM PHYSICAL ACTIVITY ON CARDIAC STRUCTURE AND FUNCTION: A TWIN STUDY

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    Urho M.Kujala

    2009-12-01

    Full Text Available Previous studies have shown that athletic training or other physical activity causes structural and functional adaptations in the heart, but less is known how long-term physical activity affects heart when genetic liability and childhood environment are taken into account. The aim of this study was to investigate the effects of long-term physical activity vs. inactivity on cardiac structure and function in twin pairs discordant for physical activity for 32 years. Twelve same-sex twin pairs (five monozygotic and seven dizygotic, 50-67 years were studied as a part of the TWINACTIVE study. Discordance in physical activity was initially determined in 1975 and it remained significant throughout the follow-up. At the end of the follow-up in 2007, resting echocardiographic and electrocardiographic measurements were performed. During the follow-up period, the active co-twins were on average 8.2 (SD 4.0 MET hours/day more active than their inactive co-twins (p < 0.001. At the end of the follow-up, resting heart rate was lower in the active than inactive co-twins [59 (SD 5 vs. 68 (SD 10 bpm, p=0.03]. The heart rate-corrected QT interval was similar between the co-twins. Also, there was a tendency for left ventricular mass per body weight to be greater and T wave amplitude in lead II to be higher in the active co-twins (18% and 15%, respectively, p=0.08 for both. Similar trends were found for both monozygotic and dizygotic twin pairs. In conclusion, the main adaptation to long- term physical activity is lowered resting heart rate, even after partially or fully controlling for genetic liability and childhood environment

  14. Evaluation of cardiac autonomic function in overweight males: A cross-sectional study

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    Debasish Das

    2017-01-01

    Full Text Available Background and Aim: Cardiovascular autonomic function tests (CAFTs are non-invasive tests that can assess both sympathetic and parasympathetic autonomic functions. Autonomic dysfunction may be considered as a risk factor for obesity and vice versa. For measurement of obesity, body mass index (BMI is a simple, valid and inexpensive method. Hence, this study was designed to evaluate the effect of obesity based on BMI criteria on autonomic nervous system based on CAFT in young adult males. Methods: A cross-sectional study was carried out on 43 young adult males in the age group of 18–25 years with an age-matched control (n = 43 group. After initial screening, anthropometric measurements were recorded. CAFTs were performed and recorded by the Cardiac Autonomic Neuropathy Analysis System (CANWin. Unpaired t- test was done to compare the parameters of study and control groups in Microsoft Excel® 2010. Results: Parasympathetic test parameters of study and control groups when expressed in mean ± standard deviation were not found statistically significant (P > 0.05. The fall in systolic blood pressure (BP in orthostatic test of study group (12.19 ± 4.8 mmHg was significantly (P = 0.0001 higher than that of control group (7.33 ± 5.16 mmHg. Increase in diastolic BP in isometric handgrip exercise test of study group (11.84 ± 5.39 mmHg was significantly less (P = 0.004 than that of control group (16.39 ± 8.71 mmHg. Conclusion: Overweight young males have altered sympathetic activity but parasympathetic activity did not show any significant difference when compared to normal weight males.

  15. Cardiac MRI assessment of right ventricular function: impact of right bundle branch block on the evaluation of cardiac performance parameters

    Energy Technology Data Exchange (ETDEWEB)

    Marterer, Robert; Tschauner, Sebastian; Sorantin, Erich [Medical University of Graz, Division of Pediatric Radiology, Department of Radiology, Graz (Austria); Zeng, Hongchun [First Affiliated Hospital of Xinjiang Medical University, Department of Ultrasonography, Urumqi (China); Koestenberger, Martin [Medical University of Graz, Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Graz (Austria)

    2015-12-15

    Right ventricular (RV) function represents a prognostic marker in patients with corrected congenital heart disease. In up to 80 % of these patients, right branch bundle block (RBBB) exists and leads to asynchronous ventricular contraction. The aim of this retrospective study was to evaluate the change of RV performance parameters considering delayed RV end-systolic contraction. RV volumes of 33 patients were assessed twice: 1) not taking account of RBBB (group I), and 2) considering RBBB (group II). According to the RV ejection fraction (EF) for both groups, RV function was classified in different categories (>50 % = normal, 40-50 % = mildly-, 30-40 % = moderately-, <30 % = severely-reduced). The mean time difference between maximal systolic contraction of the septum and RV free wall was 90.7 ms ± 42.6. Consequently, RV end-systolic volume was significantly decreased in group II (p < 0.001). Accordingly, RV stroke volume and RV EF were significantly higher in group II (p < 0.001). There was also a significant change in the assessment of RV function (p < 0.02). RBBB induced delayed RV contraction can be detected at CMR. Ignoring the RV physiology in RBBB patients leads to a statistically significant underscoring of RV performance parameters. (orig.)

  16. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

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    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  17. Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

    Science.gov (United States)

    Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

    2014-05-01

    Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P model. In cardiac light-chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

  18. Thyroid function and body weight in girls with irregular menstrual cycle living in mild iodine deficiency region

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    L Sh Vagapova

    2011-09-01

    Full Text Available To establish the relation of body weight indexes and functional state of thyroid in female adolescents with menstrual cycle disorder, living in the iodine-deficiency region, the investigation was conducted in 130 female adolescents with irregular menses. Obesity incidence and overweight in them was 18.5%, body weight deficiency was 43.8%.37.7% of the girls had normal body weight. Statistically significant differences were not defined according to TSH, fT4 and fT3 in patients with different body weight indexes. So, the results of investigation can help to come to the conclusion about the absence of true correlation between body weight and functional thyroid state in female adolescents with irregular menses.

  19. Evaluation of Right Ventricular Function with Radionuclide Cardiac Angiography - Right Ventricular Ejection Fraction in Chronic Obstructive Lung Disease

    International Nuclear Information System (INIS)

    Sohn, In; Shin, Sung Hae; Chung, June Key; Lee, Myung Chul; Cho, Bo Youn; Lee, Young Woo; Han, Yong Cheol; Koh, Chang Soon

    1982-01-01

    To evaluate the usefulness of radionuclide cardiac angiography in the assessment of the right ventricular function, we measured right ventricular ejection fraction (RVEF) using single pass method. In 12 normal persons, RVEF averaged 52.7±5.9% (mean±S.D.). In 25 patients with chronic obstructive lung disease, RVEF was 37.2±10.6% and significantly lower than that of normal person (p<0.01). All 10 patients with right ventricular failure had abnormal RVEF, which was significantly lower than that of 14 persons without right ventricular failure (27.6±5.7%, 43.9±8.5%, respectively, p<0.01). It concluded that RVEF measured by single pass radionuclide cardiac angiography was a useful, noninvasive method to assess right ventricular function.

  20. Metallothionein Abrogates GTP Cyclohydrolase I inhibition-Induced Cardiac Contractile and Morphological Defect: Role of Mitochondrial Biogenesis

    OpenAIRE

    Ceylan-Isik, Asli F.; Guo, Kelly K.; Carlson, Edward C.; Privratsky, Jamie R.; Liao, Song-Jie; Cai, Lu; Chen, Alex F.; Ren, Jun

    2009-01-01

    One key mechanism for endothelial dysfunction is eNOS uncoupling, whereby eNOS generates O2•− rather than NO, due to deficient eNOS cofactor tetrahydrobiopterin (BH4). This study was designed to examine the effect of BH4 deficiency on cardiac morphology and function as well as the impact of metallothionein (MT) on BH4 deficiency-induced abnormalities, if any. FVB and cardiac-specific MT transgenic mice were exposed to 2,4-diamino-6-hydroxy-pyrimidine (DAHP, 10 mmol/l, 3 wks), an inhibitor of ...

  1. Evaluation of the effect of different types and location of pacemaker on cardiac function using radionuclide techniques

    International Nuclear Information System (INIS)

    Shi Rongfang; Liu Xiujie; Guo Xiuzhen

    1993-01-01

    Left ventricular function was measured in 24 patients using radionuclide ventriculography before and after planting different types of pacemakers. The results showed that the heart rate, peak filling rate (PFR) and relative cardiac output (RCO) were significantly increased after planting the pacemaker. However, the effects of AAI and VVI on the synchronism of LV were different. AAI can significantly improve the synchronism and compliance of LV

  2. Myocardial function during transesophageal cardiac pacing in patients with coronary heart diseases when selected for surgical management: nuclear stethoscopic findings

    International Nuclear Information System (INIS)

    Fitilev, S.B.; Mironova, M.A.; Gordeev, V.F.; Satrapinskij, V.Yu.; Badalyan, E.A.; Akademiya Meditsinskikh Nauk SSSR, Moscow

    1991-01-01

    Studies of myocardial function during transesophageal cardiac pacing (TECP) were carried out in 70 patients with coronary heart diseases (CHD). All the patients were examined for central and intracardiac hemodynamics during TECP using nuclear stetoscope Bios (USA). The obtained data of central hemodynamics and myocardium contractibility make it possible to judge not only of pathological hemodynamics changes, as a CHD diagnostic factor, but of factors limiting reserve of cardiovascular system as well, depending on morphological heart changes

  3. Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.

    Science.gov (United States)

    Mao, Chenggang; Hou, Xu; Wang, Benzhen; Chi, Jingwei; Jiang, Yanjie; Zhang, Caining; Li, Zipu

    2017-01-28

    Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model. A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy. Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity. Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.

  4. Cardiac function and perfusion dynamics measured on a beat-by-beat basis in the live mouse using ultra-fast 4D optoacoustic imaging

    Science.gov (United States)

    Ford, Steven J.; Deán-Ben, Xosé L.; Razansky, Daniel

    2015-03-01

    The fast heart rate (~7 Hz) of the mouse makes cardiac imaging and functional analysis difficult when studying mouse models of cardiovascular disease, and cannot be done truly in real-time and 3D using established imaging modalities. Optoacoustic imaging, on the other hand, provides ultra-fast imaging at up to 50 volumetric frames per second, allowing for acquisition of several frames per mouse cardiac cycle. In this study, we combined a recently-developed 3D optoacoustic imaging array with novel analytical techniques to assess cardiac function and perfusion dynamics of the mouse heart at high, 4D spatiotemporal resolution. In brief, the heart of an anesthetized mouse was imaged over a series of multiple volumetric frames. In another experiment, an intravenous bolus of indocyanine green (ICG) was injected and its distribution was subsequently imaged in the heart. Unique temporal features of the cardiac cycle and ICG distribution profiles were used to segment the heart from background and to assess cardiac function. The 3D nature of the experimental data allowed for determination of cardiac volumes at ~7-8 frames per mouse cardiac cycle, providing important cardiac function parameters (e.g., stroke volume, ejection fraction) on a beat-by-beat basis, which has been previously unachieved by any other cardiac imaging modality. Furthermore, ICG distribution dynamics allowed for the determination of pulmonary transit time and thus additional quantitative measures of cardiovascular function. This work demonstrates the potential for optoacoustic cardiac imaging and is expected to have a major contribution toward future preclinical studies of animal models of cardiovascular health and disease.

  5. Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

    Science.gov (United States)

    Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

    2018-05-09

    Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac

  6. Effects of valsartan combined with atorvastatin on cardiac function, myocardial enzymes and thyroxine levels in patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Xiao-Gang Wang1

    2017-04-01

    Full Text Available Objective: To observe the effects of valsartan combined with atorvastatin on cardiac function, myocardial enzymes and thyroxine levels in patients with chronic heart failure (CHF. Methods: 90 cases of CHF cases were divided into observation group and control group according to the order of single and double number, 45 cases each. In the control group, atorvastatin was given on the basis of conventional therapy, and the observation group was given valsartan on the basis of the control group. After 6 months, the differences of cardiac function indexes (LVEF, LVEDD, LVESD, E/A, myocardial enzymes (LDH, AST, CK, CKMB and thyroxine (TT3, TT4, FT3, FT4, TSH in the two groups were observed. Results: After treatment, LVEF and E/A in both groups increased significantly (P0.05, the observation group TT3 and FT3 were respectively (1.37±0.33 mol/L and (2.61±0.69 pmol/L , higher than the control group, the difference was statistically significant (P<0.05. Conclusion: valsartan combined with atorvastatin in the treatment of CHF, can improve cardiac function and myocardial protection effect, and can effectively promote the recovery of thyroid hormone levels, better than the single use of atorvastatin.

  7. Storage Pool Deficiencies

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  8. Use of {sup 123}I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, Christophe [Service de Medecine Nucleaire, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743, Paris Cedex 15 (France); Acar, Philippe; Sidi, Daniel [Service de Cardiologie Pediatrique, Hopital Necker-Enfants Malades, Paris (France)

    2003-12-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using {sup 123}I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39{+-}57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent {sup 123}I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of {sup 123}I-MIBG. Cardiac neuronal uptake of {sup 123}I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%{+-}49% vs 162%{+-}26%, P<0.0001, and LVEF=43%{+-}17% vs 26%{+-}11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  9. Use of 123I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Christophe; Acar, Philippe; Sidi, Daniel

    2003-01-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using 123 I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent 123 I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of 123 I-MIBG. Cardiac neuronal uptake of 123 I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  10. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study.

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    Karin A M Janssens

    Full Text Available Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS. However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac autonomic nervous system (ANS levels during a standardized stressful situation, and whether these associations are symptom-specific.We examined 715 adolescents (16.1 years, 51.3% girls from the Dutch cohort study Tracking Adolescents' Individual Lives Sample during the Groningen Social Stress Test (GSST. FSS were assessed by the Youth Self-Report, and clustered into a cluster of overtiredness, dizziness and musculoskeletal pain and a cluster of headache and gastrointestinal symptoms. Perceived stress levels (i.e. unpleasantness and arousal were assessed by the Self-Assessment Manikin, and cardiac ANS activity by assessing heart rate variability (HRV-HF and pre-ejection period (PEP. Perceived stress and cardiac ANS levels before, during, and after the GSST were studied as well as cardiac ANS reactivity. Linear regression analyses were used to examine the associations.Perceived arousal levels during (beta = 0.09, p = 0.04 and after (beta = 0.07, p = 0.047 the GSST, and perceived unpleasantness levels before (beta = 0.07, p = 0.048 and during (beta = 0.12, p = 0.001 the GSST were related to FSS during the past couple of months. The association between perceived stress and FSS was stronger for the FSS cluster of overtiredness, dizziness and musculoskeletal pain than for the cluster of headache and gastrointestinal symptoms. Neither ANS activity levels before, during, and after the GSST, nor maximal HF-HRV and PEP reactivity were related to FSS.This study suggests that perceived stress levels during social stress are related to FSS, whereas cardiac ANS activity and reactivity are not related to FSS.

  11. Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats

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    Maranhão RC

    2017-05-01

    Full Text Available Raul C Maranhão,1,2 Maria C Guido,1 Aline D de Lima,1 Elaine R Tavares,1 Alyne F Marques,1 Marcelo D Tavares de Melo,3 Jose C Nicolau,3 Vera MC Salemi,3 Roberto Kalil-Filho3 1Laboratory of Metabolism and Lipids, 2Faculty of Pharmaceutical Sciences, 3Heart Failure Unit, Clinical Cardiology Division, Heart Institute (InCor, Medical School Hospital, University of São Paulo, São Paulo, Brazil Purpose: Acute myocardial infarction (MI is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE used as carriers of the anti-inflammatory drug methotrexate (MTX produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment.Materials and methods: Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery or with LDE without drug (MI-controls. A sham-surgery group (n=12 was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy.Results: LDE-MTX treatment achieved a 40% improvement in left ventricular (LV systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine

  12. Effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats.

    Science.gov (United States)

    Di Petta, Antonio; Simas, Rafael; Ferreira, Clebson L; Capelozzi, Vera L; Salemi, Vera M C; Moreira, Luiz F P; Sannomiya, Paulina

    2015-10-01

    Chronic obstructive pulmonary disease is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate the effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats. Wistar rats were divided into control non-diabetic instilled with saline (CS) or elastase (CE), diabetic instilled with saline (DS) or elastase (DE), DE treated with insulin (DEI) groups and echocardiographic measurements, morphometric analyses of the heart and lungs, and survival analysis conducted 50 days after instillation. Diabetes mellitus was induced [alloxan, 42 mg/kg, intravenously (iv)] 10 days before the induction of emphysema (elastase, 0.25 IU/100 g). Rats were treated with NPH insulin (4 IU before elastase plus 2 IU/day, 50 days). Both CE and DE exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in right ventricular (RV) wall thickness (P = 0.0022), cavity area (P = 0.0001) and cardiomyocyte thickness (P = 0.0001). Diabetic saline group demonstrated a reduction in left ventricular (LV) wall, interventricular (IV) septum, cardiomyocyte thickness and an increase in cavity area, associated with a reduction in LV fractional shortening (P emphysema, even in the presence of insulin. Diabetes per se induced left ventricular dysfunction, which was less evident in the presence of RV hypertrophy. Survival rate was substantially reduced as a consequence, at least in part, of the coexistence of RV hypertrophy and diabetic cardiomyopathy. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

  13. A functional study of the esophagus in patients with non-cardiac chest pain and dysphagia.

    Science.gov (United States)

    Gullo, Roberto; Inviati, Angela; Almasio, Piero Luigi; Di Paola, Valentina; Di Giovanni, Silvia; Scerrino, Gregorio; Gulotta, Gaspare; Bonventre, Sebastiano

    2015-03-01

    Nutcracker esophagus and non-specific motility disorders are the main causes of non-cardiac chest pain (NCCP), with gastroesophageal reflux in 60% of cases. Achalasia and diffuse esophageal spasm are the most frequent anomalies described in patients with dysphagia. The goal of this study was to evaluate the occurrence of esophageal body and lower esophageal sphincter motor abnormalities in patients with dysphagia, NCCP, or both. This study is a retrospective analysis of 716 patients with NCCP and/or dysphagia tested between January 1994 and December 2010. 1023 functional studies were performed, 707 of which were esophageal manometries, 225 esophageal pH-meters, and 44 bilimetries. We divided the patients into three groups: group 1 was composed of patients affected with dysphagia, group 2 with NCCP and group 3 with NCCP and dysphagia. Manometric anomalies were detected in 84.4% of cases (p<0.001). The most frequent esophageal motility alteration was achalasia (36%). The lower esophageal sphincter was normal in 45.9% of patients (p<0.001). In all 3 groups, 80.9%, 98.8%, and 93.8, respectively, of patients showed normal upper esophageal sphincter (p=0.005). Our data differs from those of other studies because they were collected from and analyzed by a single tertiary level referral center by a single examiner. This could have eliminated the variability found in different hands and different experiences. The high percentage of symptomatic patients with non-pathologic esophageal motility pattern suggests an unclear origin of the disease, with possible neuromuscular involvement. As a result, these patients may need more-detailed diagnostic studies.

  14. Influence of hydrotherapy on clinical and cardiac autonomic function in migraine patients.

    Science.gov (United States)

    Sujan, M U; Rao, M Raghavendra; Kisan, Ravikiran; Abhishekh, Hulegar A; Nalini, Atchayaram; Raju, Trichur R; Sathyaprabha, T N

    2016-01-01

    Migraine is associated with autonomic symptoms. The growing body of literature suggests that the dysfunctional autonomic nervous system might play a pivotal role in the pathogenesis of migraine. Thermal therapies have been hypothesized to modulate these changes and alleviate pain. However, data regarding the efficacy of hydrotherapy in migraine remain scant. We evaluated the effect of add on hydrotherapy procedure (a hot arm and foot bath with ice massage to head) in migraine patients. Forty chronic migraine patients fulfilling the International Classification of Headache Disorders II criteria were recruited from the neurology outpatient clinic. Patients were randomized to receive either hydrotherapy plus conventional pharmacological care (n = 20) or conventional medication only (n = 20). Hydrotherapy group received treatment with hot arm and foot bath (103°F to 110°F) and ice massage to head daily for 20 min for 45 days. Patients were assessed using headache impact test (HIT), visual analog scale for pain and cardiac autonomic function by heart rate variability (HRV) before and after intervention period. There was a significant decrease in HIT score, frequency, and intensity of headaches following treatment in both the groups. However, it was more evident in add on hydrotherapy group compared to pharmacological treatment alone group. There was also significant improvement in the HRV parameters. In particular, there was a significant decrease in heart rate (P = 0.017), increase in high frequency (HF) (P = 0.014) and decrease in low frequency/HF ratio (P = 0.004) in add on hydrotherapy group. Our study shows that add on hydrotherapy enhanced the vagal tone in addition to reducing the frequency and intensity of headaches in migraine patients.

  15. Influence of hydrotherapy on clinical and cardiac autonomic function in migraine patients

    Directory of Open Access Journals (Sweden)

    M U Sujan

    2016-01-01

    Full Text Available Background: Migraine is associated with autonomic symptoms. The growing body of literature suggests that the dysfunctional autonomic nervous system might play a pivotal role in the pathogenesis of migraine. Thermal therapies have been hypothesized to modulate these changes and alleviate pain. However, data regarding the efficacy of hydrotherapy in migraine remain scant. We evaluated the effect of add on hydrotherapy procedure (a hot arm and foot bath with ice massage to head in migraine patients. Methods: Forty chronic migraine patients fulfilling the International Classification of Headache Disorders II criteria were recruited from the neurology outpatient clinic. Patients were randomized to receive either hydrotherapy plus conventional pharmacological care (n = 20 or conventional medication only (n = 20. Hydrotherapy group received treatment with hot arm and foot bath (103°F to 110°F and ice massage to head daily for 20 min for 45 days. Patients were assessed using headache impact test (HIT, visual analog scale for pain and cardiac autonomic function by heart rate variability (HRV before and after intervention period. Results: There was a significant decrease in HIT score, frequency, and intensity of headaches following treatment in both the groups. However, it was more evident in add on hydrotherapy group compared to pharmacological treatment alone group. There was also significant improvement in the HRV parameters. In particular, there was a significant decrease in heart rate (P = 0.017, increase in high frequency (HF (P = 0.014 and decrease in low frequency/HF ratio (P = 0.004 in add on hydrotherapy group. Conclusion: Our study shows that add on hydrotherapy enhanced the vagal tone in addition to reducing the frequency and intensity of headaches in migraine patients.

  16. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

  17. Oral vitamin C supplementation reduces erythropoietin requirement in hemodialysis patients with functional iron deficiency.

    Science.gov (United States)

    Sultana, Tanjim; DeVita, Maria V; Michelis, Michael F

    2016-09-01

    Functional iron deficiency (FID) is a major cause of persistent anemia in dialysis patients and also contributes to a suboptimal response to erythropoietin (Epo) administration. Vitamin C acts as an enzyme cofactor and enhances mobilization of the ferrous form of iron to transferrin thus increasing its bioavailability. High-dose intravenous vitamin C has been shown to decrease the Epo requirement and improve hemoglobin levels in previous studies. This study assessed the effect of low-dose oral vitamin C on possible reduction in Epo dose requirements in stable hemodialysis patients with FID. This prospective study included 22 stable hemodialysis patients with FID defined as transferrin saturation (T sat) 100 mcg/L with Epo requirement of ≥4000 U/HD session. Patients received oral vitamin C 250 mg daily for 3 months. Hemoglobin, iron and T sat levels were recorded monthly. No one received iron supplementation during the study period. There was a significant reduction in median Epo dose requirement in the 15 patients who completed the study, from 203.1 U/kg/week (95 % CI 188.4-270.6) to 172.8 U/kg/week (95 % CI 160.2-214.8), (P = 0.01). In the seven responders, there was 33 % reduction in Epo dose from their baseline. Despite adjustment of Epo dose, the mean hemoglobin level was significantly increased from 10.1 ± 0.6 to 10.7 ± 0.6 mg/dL (P = 0.03). No adverse effects of oral vitamin C were observed. Daily low-dose oral vitamin C supplementation reduced Epo dose requirements in hemodialysis patients with FID. Limitations of this study include a small sample size and the lack of measurements of vitamin C and oxalate levels. Despite concerns regarding oral vitamin C absorption in dialysis patients, this study indicates vitamin C was well tolerated by all participants without reported adverse effect.

  18. Association of Vitamin D Deficiency and Thyroid Function in Postmenopausal Women

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    Mitra Niafar

    2016-12-01

    Full Text Available Pupose: Although there are reports of vitamin D (VitD insufficiency in immune-mediated hypothyroidism, an association between VitD and thyroid-stimulating hormone (TSH levels has yet to be shown. We aim to examine VitD and TSH levels among postmenopausal women, as both conditions are more prevalent in elderly women. Methods: The clinic records of postmenopausal women during their routine maintenance visits were reviewed. All patients were examined for the symptoms related to thyroid function and osteoporosis. Participants were divided into three subgroups according to their TSH levels (below 4.0 mIU/L. Patient characteristics and VitD levels were compared between these subgroups. Multivariate linear regression model was constructed using serum VitD and serum TSH as the dependent variables to identify factors independently associated with these laboratory values. Results: Two-hundred and nighty nine postmenopausal women were included. Average age was 62.2±7.5 years old. VitD was insufficient (10-30 ng/mL in 12.0% and deficient (<10 ng/mL in 60.9% of the participants. In 11.3%, TSH was low and in 7.6% of women, TSH was high, while the remaining 80.1%, had normal TSH levels. Subjects with low TSH had significantly higher VitD concentrations (34.2±29.1 ng/mL compared to the other two groups (P-value: 0.039. In multivariate regression analysis, TSH was not a contributing factor, as age was the only significant predictor of VitD levels. Meanwhile, no predictor (including age and VitD was identified for TSH levels in linear regression analysis. Conclusion: Age was the only independent predictor of serum VitD in this study population. Though suppressed TSH was associated with higher VitD levels, the association was not linear between TSH and VitD in postmenopausal women.

  19. Evaluation of Esophageal Functions by Manometry in Iron Deficiency Anemia Patients.

    Science.gov (United States)

    Kubilay, Pinar; Doganay, Beyza; Bektas, Mehmet

    2017-06-01

    The aim of this study was to investigate whether any esophageal motor dysfunction exists in patients with iron deficiency anemia (IDA). The study included 39 patients (34 women, mean age: 44.17 ± 14.21 years) who met WHO diagnostic criteria for IDA. An additional 30 functional dyspepsia patients were also included as a control group. Esophageal motility testing was performed; esophagus contraction amplitude, peak velocity, contraction time, lower esophageal sphincter (LES) resting pressure, LES relaxation, and LES relaxation duration were assessed. A majority (76.4%) of patients had at least one IDA symptom, such as reflux, chest pain, or dysphagia. Manometric findings in IDA patients vs. controls were as follows: mean LES resting pressure (mm Hg): 25.41 ± 11.67 vs. 19.96 ± 6.58 (P = 0.025); mean esophageal contraction amplitude (mm Hg): 61.61 ± 24.21 vs. 63.23 ± 18.86 (P = 0.764); mean LES relaxation duration (s, x ± SD): 5.33 ± 1.61 vs. 8.75 ± 1.86 (P = 0.000); mean LES relaxation (%): 93.30 ± 9.88 vs. 95.53 ± 5.81 (P = 0.278); mean peak velocity (cm/s): 12.67 ± 37.95 vs. 3.50 ± 1.63 (P = 0.191). Esophageal dysmotility was found in 11 (28.2%) IDA patients. Non-specific esophageal motor disorder was found in three patients, hypomotility of the esophagus was found in three patients, achalasia was found in two patients, hypertensive LES was found in two patients, and hypotensive LES was found in one patient. LES resting pressure was higher and LES relaxation duration was shorter in patients with IDA. Esophageal dysmotility was present in 28.2% of the patients with IDA A little more than half of patients had dysphagia symptoms. IDA may contribute to esophageal motility dysfunction and esophageal symptoms.

  20. Alteration of proteins and pigments influence the function of photosystem I under iron deficiency from Chlamydomonas reinhardtii.

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    Venkateswarlu Yadavalli

    Full Text Available BACKGROUND: Iron is an essential micronutrient for all organisms because it is a component of enzyme cofactors that catalyze redox reactions in fundamental metabolic processes. Even though iron is abundant on earth, it is often present in the insoluble ferric [Fe (III] state, leaving many surface environments Fe-limited. The haploid green alga Chlamydomonas reinhardtii is used as a model organism for studying eukaryotic photosynthesis. This study explores structural and functional changes in PSI-LHCI supercomplexes under Fe deficiency as the eukaryotic photosynthetic apparatus adapts to Fe deficiency. RESULTS: 77K emission spectra and sucrose density gradient data show that PSI and LHCI subunits are affected under iron deficiency conditions. The visible circular dichroism (CD spectra associated with strongly-coupled chlorophyll dimers increases in intensity. The change in CD signals of pigments originates from the modification of interactions between pigment molecules. Evidence from sucrose gradients and non-denaturing (green gels indicates that PSI-LHCI levels were reduced after cells were grown for 72 h in Fe-deficient medium. Ultrafast fluorescence spectroscopy suggests that red-shifted pigments in the PSI-LHCI antenna were lost during Fe stress. Further, denaturing gel electrophoresis and immunoblot analysis reveals that levels of the PSI subunits PsaC and PsaD decreased, while PsaE was completely absent after Fe stress. The light harvesting complexes were also susce