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Sample records for subclinical cardiac dysfunction

  1. Late gadolinium enhancement and subclinical cardiac dysfunction on cardiac MRI in asymptomatic HIV-positive men

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    A Loy

    2012-11-01

    Full Text Available Background: HIV is associated with an increased risk of cardiovascular disease (CVD and related clinical events. While traditional risk factors play an important role in the pathology of cardiovascular disease, HIV infection and its sequelae of immune activation and inflammation may have significant effects on the myocardium before becoming clinically evident. Cardiac MRI (CMR can be used to detect the pattern of these subclinical changes. This will lead to a better understanding of risk factors contributing to cardiovascular disease prior to it becoming clinically significant in HIV-positive patients. Methods: Prospective cohort study of 127 asymptomatic HIV-positive men on ART compared to 35 matched controls. Baseline demographics, HIV parameters, 12-lead ECG, routine biochemistry, and traditional cardiovascular risk factors were recorded. Images were acquired on a 3T Achieva Philips MRI scanner with 5 channel phase array cardiac coil and weight-based IV gadolinium was given at 0.15 mmol/kg dose with post-contrast inversion recovery imaging after 10 minutes. Results: 6/127 (4.7% of asymptomatic HIV-positive men had late gadolinium enhancement (LGE on MRI verses 1/35 (2.9% in the control group. In 3/6 (50% of cases this was in a classical infarction pattern with subendocardial involvement. 3/6 (50% were consistent with prior myocarditis. There was no significant difference in mean LVEF (66.93% vs 65.18%, LVMI (60.05g/m2 vs 55.94g/m2 or posterolateral wall thickness (8.28 mm and 8.16 mm between cases and controls respectively. There was significantly more diastolic dysfunction, E:A ratio < 1, found in the HIV-positive group, 18% vs 7% of controls (p = 0.037. Framingham risk did not predict either of these outcomes. Conclusions: There is an increased incidence of LGE detected on CMR in this asymptomatic HIV-positive cohort. Two distinct pathological processes were identifed as causing these changes, myocardial infarction and myocarditis

  2. Subclinical Thyroid Dysfunction and Fracture Risk

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    Blum, Manuel R; Bauer, Douglas C; Collet, Tinh-Hai

    2015-01-01

    IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE...... and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION: Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan....... Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH

  3. Young Women With Abdominal Obesity Have Subclinical Myocardial Dysfunction.

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    Share, Bianca L; La Gerche, André; Naughton, Geraldine A; Obert, Philippe; Kemp, Justin G

    2015-09-01

    Abdominal obesity is an independent risk factor for cardiovascular disease. The effect of abdominal obesity on myocardial function in young obese women remains unknown. Therefore, we aimed to investigate cardiac morphology and function, myocardial deformation, and mechanical indices, in young women with and without abdominal obesity. Cross-sectional analyses of 39 women with abdominal obesity (waist circumference ≥ 80 cm) and 33 nonobese control subjects (waist circumference factors including anthropometric, hypertension, biochemistry, and fitness were also assessed. Standard echocardiography results for cardiac morphology and function were similar between groups, with the exception of larger left atrial dimensions in women with abdominal obesity (P ≤ 0.05). Compared with control subjects, women with abdominal obesity also demonstrated reduced systolic and diastolic mitral annular plane velocities, increased left atrial pressure surrogates (E/diastolic mitral annular plane velocity), and prolonged timing measures of diastolic function including isovolumic relaxation time and transmitral deceleration time (P ≤ 0.05). In addition, longitudinal strain and diastolic strain rate were reduced in women with abdominal obesity (P ≤ 0.05) but circumferential deformation and myocardial mechanics (twist indices and rotation) were preserved. Markers of abdominal obesity retained an independent direct correlation with parameters of cardiac dysfunction, explaining 12%-39% of the overall variability. A young, otherwise healthy group of women with abdominal obesity displayed subclinical cardiac dysfunction indicated using selected tissue Doppler imaging and speckle tracking echocardiography measures. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Subclinical Thyroid Dysfunction and Depressive Symptoms among Elderly

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    Blum, Manuel R; Wijsman, Liselotte W; Virgini, Vanessa S

    2016-01-01

    on the association of persistent subclinical thyroid dysfunction and depression, subclinical hypothyroidism was not associated with increased depressive symptoms among older adults at high cardiovascular risk. Persistent subclinical hyperthyroidism might be associated with increased depressive symptoms, which...... adults aged 70-82 years with pre-existing cardiovascular disease or known cardiovascular risk factors, TSH and free T4 levels were measured at baseline and repeated after 6 months to define persistent thyroid function status. Main outcome measures were depressive symptoms, assessed with the Geriatric...... Depression Scale 15 (GDS) at baseline and after 3 years. All analyses were adjusted for age, gender and education. RESULTS: Among 606 participants (41% women, mean age 75 years) without anti-depressant medication, GDS scores at baseline did not differ for participants with subclinical hypothyroidism (n = 47...

  5. Cardiac dysfunction in cancer survivors unmasked during exercise.

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    Kearney, Maria C; Gallop-Evans, Eve; Cockcroft, John R; Stöhr, Eric J; Lee, Eveline; Backx, Karianne; Haykowsky, Mark; Yousef, Zaheer; Shave, Rob

    2017-03-01

    The cardiac dysfunction associated with anthracycline-based chemotherapy cancer treatment can exist subclinically for decades before overt presentation. Stress echocardiography, the measurement of left ventricular (LV) deformation and arterial haemodynamic evaluation, has separately been used to identify subclinical cardiovascular (CV) dysfunction in several patient groups including those with hypertension and diabetes. The purpose of the present cross-sectional study was to determine whether the combination of these techniques could be used to improve the characterisation of subclinical CV dysfunction in long-term cancer survivors previously treated with anthracyclines. Thirteen long-term cancer survivors (36 ± 10 years) with prior anthracycline exposure (11 ± 8 years posttreatment) and 13 age-matched controls were recruited. Left ventricular structure, function and deformation were assessed using echocardiography. Augmentation index was used to quantify arterial haemodynamic load and was measured using applanation tonometry. Measurements were taken at rest and during two stages of low-intensity incremental cycling. At rest, both groups had comparable global LV systolic, diastolic and arterial function (all P > 0·05); however, longitudinal deformation was significantly lower in cancer survivors (-18 ± 2 vs. -20 ± 2, P exercise, this difference between groups persisted and further differences were uncovered with significantly lower apical circumferential deformation in the cancer survivors (-24 ± 5 vs. -29 ± 5, -29 ± 5 vs. 35 ± 8 for first and second stage of exercise respectively, both P exercise provides a more comprehensive characterisation of subclinical LV dysfunction. Larger studies are required to determine the clinical relevance of these preliminary findings. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  6. Myocardial Dysfunction and Shock after Cardiac Arrest

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    Jentzer, Jacob C.; Chonde, Meshe D.; Dezfulian, Cameron

    2015-01-01

    Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies. PMID:26421284

  7. Cardiac changes with subclinical hypothyroidism in obese women.

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    Kılıçaslan, Barış; Tigen, Mustafa Kürşat; Tekin, Ahmet Selami; Ciftçi, Hilmi

    2013-09-01

    Obesity has been linked to a spectrum of minor cardiovascular changes. The aim of this study was to determine the effect of obesity on cardiac functions and its relations with subclinical hypothyroidism in healthy women. Eighty-eight consecutive "healthy" females (mean age: 31.2±6.6 years) were included in the study. Thyroid function tests and echocardiography studies were performed in all patients. Height, weight, and waist and hip circumference were also measured. A body mass index (BMI) above 30 kg/m2 was considered obese. Left ventricular mass (LVM) was higher in obese subjects (pobese subjects with higher E/e' (p=0.001) and larger left atrial volume (LAV) (pobese subjects (p=0.033). Thyroid-stimulating hormone (TSH) levels were significantly higher in obese subjects (p=0.011) and were positively correlated with BMI, waist circumference, LAV, and LVM. The prevalence of abnormal systolic and diastolic functions showed stepwise increases with higher TSH levels in obese subjects. Multiple regression analysis was used to evaluate the association of E/e' with anthromorphometric and biochemical parameters, and waist circumference was found to be the strongest independent variable correlated with the E/e' ratio. Cardiac structural and functional deteriorations may be related with subclinical hypothyroidism in obese subjects.

  8. Diabetic cardiac autonomic dysfunction. Parasympathetic versus sympathetic

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    Uehara, Akihiko; Kurata, Chinori; Sugi, Toshihiko; Mikami, Tadashi; Shouda, Sakae [Hamamatsu Univ. School of Medicine, Shizuoka (Japan)

    1999-04-01

    Diabetic cardiac autonomic dysfunction often causes lethal arrhythmia and sudden cardiac death. {sup 123}I-Metaiodobenzylguanidine (MIBG) can evaluate cardiac sympathetic dysfunction, and analysis of heart rate variability (HRV) can reflect cardiac parasympathetic activity. We examined whether cardiac parasympathetic dysfunction assessed by HRV may correlate with sympathetic dysfunction assessed by MIBG in diabetic patients. In 24-hour electrocardiography, we analyzed 4 HRV parameters: high-frequency power (HF), HF in the early morning (EMHF), rMSSD and pNN50. MIBG planar images and SPECT were obtained 15 minutes (early) and 150 minutes (late) after injection and the heart washout rate was calculated. The defect score in 9 left ventricular regions was scored on a 4 point scale (0=normal - 3=severe defect). In 20 selected diabetic patients without congestive heart failure, coronary artery disease and renal failure, parasympathetic HRV parameters had a negative correlation with the sum of defect scores (DS) in the late images (R=-0.47 to -0.59, p<0.05) and some parameters had a negative correlation with the washout rate (R=-0.50 to -0.55, p<0.05). In a total of 64 diabetic patients also, these parameters had a negative correlation with late DS (R=-0.28 to -0.35, p<0.05) and early DS (R=-0.27 to -0.32, p<0.05). The progress of diabetic cardiac parasympathetic dysfunction may parallel the sympathetic one. (author)

  9. Endothelial dysfunction after non-cardiac surgery

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    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...

  10. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events

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    Selmer, Christian; Olesen, Jonas Bjerring; Hansen, Morten Lock

    2014-01-01

    cardiovascular events (MACEs), and cause-specific events in subjects with overt and subclinical thyroid dysfunction. DESIGN: This was a retrospective cohort study. SETTING AND PARTICIPANTS: Participants in the study were subjects who underwent thyroid blood tests, without prior thyroid disease, consulting...

  11. Frequency of subclinical thyroid dysfunction and risk factors for cardiovascular disease among women at a workplace

    Directory of Open Access Journals (Sweden)

    Rodrigo Diaz-Olmos

    Full Text Available CONTEXT AND OBJECTIVE: Subclinical thyroid dysfunction is very common in clinical practice and there is some evidence that it may be associated with cardiovascular disease. The aim here was to evaluate the frequencies of subclinical thyroid disease and risk factors for cardiovascular disease among women at a workplace, and to evaluate the association between subclinical thyroid disease and cardiovascular risk factors among them. DESIGN AND SETTING: Cross-sectional study on 314 women aged 40 years or over who were working at Universidade de São Paulo (USP. METHODS: All the women answered a questionnaire on sociodemographic characteristics and risk factors for cardiovascular disease and the Rose angina questionnaire. Anthropometric variables were measured and blood samples were analyzed for blood glucose, total cholesterol and fractions, high-sensitivity C-reactive protein, thyroid-stimulating hormone (TSH, free thyroxine (free-T4 and anti-thyroperoxidase antibodies (anti-TPO. RESULTS: The frequencies of subclinical hypothyroidism and hyperthyroidism were, respectively, 7.3% and 5.1%. Women with subclinical thyroid disease presented higher levels of anti-TPO than did women with normal thyroid function (P = 0.01. There were no differences in sociodemographic factors and cardiovascular risk factors according to thyroid function status, except for greater sedentarism among the women with subclinical hypothyroidism. Restricting the comparison to women with subclinical hypothyroidism (TSH > 10 mIU/l did not change the results. CONCLUSION: In this sample of women, there was no association between poor profile of cardiovascular risk factors and presence of subclinical thyroid disease that would justify screening at the workplace.

  12. Evaluation of early cardiac dysfunction in patients with systemic lupus erythematosus with or without anticardiolipin antibodies.

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    Barutcu, A; Aksu, F; Ozcelik, F; Barutcu, C A E; Umit, G E; Pamuk, O N; Altun, A

    2015-09-01

    The aim of this study was to use transthoracic Doppler echocardiographic (TTE) imaging methods to identify cardiac dysfunction, an indicator of subclinical atherosclerosis in asymptomatic systemic lupus erythematosus (SLE) patients in terms of cardiac effects. This study involved 80 patients: a study group (n = 50) and control group (n = 30). They were categorized into four subgroups: anticardiolipin antibodies (aCL) (+) (n = 14) and aCL (-) (n = 36); systemic lupus erythematosus disease activity index (SLEDAI) ≥ 6 (n = 15) and SLEDAI 5 years group compared with the disease period <5 years group (p < 0.01, p < 0.05, respectively). Carrying out regular scans with TTE image of SLE patients is important in order to identify early cardiac involvement during monitoring and treatment. Identifying early cardiac involvement in SLE may lead to a reduction in mortality and morbidity rates. © The Author(s) 2015.

  13. Heterogeneity of peripheral blood monocytes, endothelial dysfunction and subclinical atherosclerosis in patients with systemic lupus erythematosus.

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    Mikołajczyk, T P; Osmenda, G; Batko, B; Wilk, G; Krezelok, M; Skiba, D; Sliwa, T; Pryjma, J R; Guzik, T J

    2016-01-01

    Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular morbidity and mortality. SLE patients have increased prevalence of subclinical atherosclerosis, although the mechanisms of this observation remain unclear. Considering the emerging role of monocytes in atherosclerosis, we aimed to investigate the relationship between subclinical atherosclerosis, endothelial dysfunction and the phenotype of peripheral blood monocytes in SLE patients. We characterized the phenotype of monocyte subsets defined by the expression of CD14 and CD16 in 42 patients with SLE and 42 non-SLE controls. Using ultrasonography, intima-media thickness (IMT) of carotid arteries and brachial artery flow-mediated dilation (FMD) as well as nitroglycerin-induced dilation (NMD) were assessed. Patients with SLE had significantly, but only modestly, increased IMT when compared with non-SLE controls (median (25th/75th percentile) 0.65 (0.60/0.71) mm vs 0.60 (0.56/0.68) mm; p subclinical atherosclerosis in SLE, although the mechanism appears to be independent of endothelial dysfunction. © The Author(s) 2015.

  14. The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction.

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    Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

    2015-01-01

    To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that

  15. Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis

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    Haissman, Judith M; Haugaard, Anna Karen; Knudsen, Andreas

    2016-01-01

    with viral replication, immune activation, coagulation, platelet function, and subclinical atherosclerosis. METHODS: Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction) and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma from two previously established cross....... CONCLUSIONS: Evidence of endothelial dysfunction was found in HIV infection and in untreated compared with treated HIV infection. In untreated HIV infection, the main driver of endothelial dysfunction was viral replication. Importantly, in treated HIV infection, ADMA was not associated with subclinical...... atherosclerosis. Thus, our data question the potential of ADMA as a useful biomarker of early atherosclerosis in treated HIV infection....

  16. Severe Obesity in Adolescents and Young Adults Is Associated With Subclinical Cardiac and Vascular Changes.

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    Shah, Amy S; Dolan, Lawrence M; Khoury, Philip R; Gao, Zhiqan; Kimball, Thomas R; Urbina, Elaine M

    2015-07-01

    Severe obesity is the fastest growing subgroup of obesity in youth. We sought to explore the association between severe obesity and subclinical measures of cardiac and vascular structure and function in adolescents and young adults. This was a cross-sectional comparison of 265 adolescents and young adults with severe obesity (defined as body mass index [BMI] ≥120% of the 95th percentile) to 182 adolescents and young adults with obesity (defined as BMI ≥100-119th of the 95th percentile) at tertiary medical center. Noninvasive measures of cardiac and vascular structure and function were assessed. Participants were a mean age of 17.9 years, 62% were non-Caucasian, and 68% were female. Systolic blood pressure, fasting insulin, C-reactive protein, IL-6, and frequency of type 2 diabetes were higher in participants with severe obesity (all P severe obesity as measured by higher left ventricular mass index, worse diastolic function, higher carotid intima media thickness, and pulse wave velocity and lower brachial distensibility (all P severe obesity (compared with obesity) was independently associated with each of the above outcomes after adjustment for age, race, sex, blood pressure, lipids, and inflammatory markers (P severe obesity have a more adverse cardiovascular risk profile and worse cardiac and vascular structure and function. More importantly, severe obesity is independently associated with these subclinical cardiac and vascular changes.

  17. Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice.

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    Wilbur Y W Lew

    Full Text Available BACKGROUND: Circulating subclinical lipopolysaccharide (LPS occurs in health and disease. Ingesting high fatty meals increases LPS that cause metabolic endotoxemia. Subclinical LPS in periodontal disease may impair endothelial function. The heart may be targeted as cardiac cells express TLR4, the LPS receptor. It was hypothesized that recurrent exposure to subclinical LPS increases mortality and causes cardiac fibrosis. METHODS: C57Bl/6 mice were injected with intraperitoneal saline (control, low dose LPS (0.1 or 1 mg/kg, or moderate dose LPS (10 or 20 mg/kg, once a week for 3 months. Left ventricular (LV function (echocardiography, hemodynamics (tail cuff pressure and electrocardiograms (telemetry were measured. Cardiac fibrosis was assessed by picrosirius red staining and LV expression of fibrosis related genes (QRT-PCR. Adult cardiac fibroblasts were isolated and exposed to LPS. RESULTS: LPS injections transiently increased heart rate and blood pressure (<6 hours and mildly decreased LV function with full recovery by 24 hours. Mice tolerated weekly LPS for 2-3 months with no change in activity, appearance, appetite, weight, blood pressure, LV function, oximetry, or blood chemistries. Mortality increased after 60-90 days with moderate, but not low dose LPS. Arrhythmias occurred a few hours before death. LV collagen fraction area increased dose-dependently from 3.0±0.5% (SEM in the saline control group, to 5.6±0.5% with low dose LPS and 9.7±0.9% with moderate dose LPS (P<0.05 moderate vs low dose LPS, and each LPS dose vs control. LPS increased LV expression of collagen Iα1, collagen IIIα1, MMP2, MMP9, TIMP1, periostin and IL-6 (P<0.05 moderate vs low dose LPS and vs control. LPS increased α-SMA immunostaining of myofibroblasts. LPS dose-dependently increased IL-6 in isolated adult cardiac fibroblasts. CONCLUSIONS: Recurrent exposure to subclinical LPS increases mortality and induces cardiac fibrosis.

  18. Ca(2+) mishandling and cardiac dysfunction in obesity and insulin resistance: role of oxidative stress.

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    Carvajal, Karla; Balderas-Villalobos, Jaime; Bello-Sanchez, Ma Dolores; Phillips-Farfán, Bryan; Molina-Muñoz, Tzindilu; Aldana-Quintero, Hugo; Gómez-Viquez, Norma L

    2014-11-01

    Obesity and insulin resistance (IR) are strongly connected to the development of subclinical cardiac dysfunction and eventually can lead to heart failure, which is the main cause of morbidity and death in patients having these metabolic diseases. It has been considered that excessive fat tissue may play a critical role in producing systemic IR and enhancing reactive oxygen species (ROS) generation. This oxidative stress (OS) may elicit or exacerbate IR. On the other hand, evidence suggests that some of the cellular mechanisms involved in the pathophysiology of obesity and IR-related cardiomyopathy are excessive myocardial ROS production and abnormal Ca(2+) homeostasis. In addition, emerging evidence suggests that augmented ROS production may contribute to Ca(2+) mishandling by affecting the redox state of key proteins implicated in this process. In this review, we focus on the role of Ca(2+) mishandling in the development of cardiac dysfunction in obesity and IR and address the evidence suggesting that OS might also contribute to cardiac dysfunction by affecting Ca(2+) handling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Risk factors for cardiac dysfunction in children on treatment for ...

    African Journals Online (AJOL)

    Objective: To determine the point prevalence of abnormal cardiac function and to assess the risk factors for cardiac dysfunction in paediatric oncology patients on treatment at Kenyatta National Hospital. Design: Descriptive cross-sectional study with a nested case control. Setting: Kenyatta National Hospital between ...

  20. The association between subclinical thyroid dysfunction and dementia: The Health, Aging and Body Composition (Health ABC) Study.

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    Aubert, Carole E; Bauer, Douglas C; da Costa, Bruno R; Feller, Martin; Rieben, Carole; Simonsick, Eleanor M; Yaffe, Kristine; Rodondi, Nicolas

    2017-11-01

    Data on the association between subclinical thyroid dysfunction and dementia are limited and conflicting. We aimed to determine whether subclinical thyroid dysfunction was associated with dementia and cognitive decline. Population-based prospective cohort study. Adults aged 70-79 years with measured thyroid function, but no dementia at baseline, and Modified Mini-Mental State (3MS) at baseline and follow-up. Primary outcome was incident-adjudicated dementia, based on 3MS, hospital records and dementia drugs. Secondary outcome was change in 3MS. Models were adjusted for age, sex, race, education and baseline 3MS, and then further for cardiovascular risk factors. Among 2558 adults, 85% were euthyroid (TSH 0.45-4.49mIU/L), 2% had subclinical hyperthyroidism with mildly decreased TSH (TSH 0.10-0.44 mIU/L), 1% subclinical hyperthyroidism with suppressed TSH (TSH < 0.10 mIU/L with normal free thyroxine [FT4]) and 12% subclinical hypothyroidism (TSH 4.50-19.99 mIU/L with normal FT4). Over 9 years, 22% developed dementia. Compared to euthyroidism, risk of dementia was higher in participants with subclinical hyperthyroidism with suppressed TSH (HR 2.38, 95% CI = 1.13;5.04), while we found no significant association in those with mildly decreased TSH (HR 0.79, 95% CI = 0.45;1.38) or with subclinical hypothyroidism (HR 0.91, 95% CI = 0.70;1.19). Participants with subclinical hyperthyroidism with suppressed TSH had a larger decline in 3MS (-3.89, 95% CI = -7.62; -0.15). Among older adults, subclinical hyperthyroidism with a TSH < 0.10 mIU/L was associated with a higher risk of dementia and a larger cognitive decline, while subclinical hyperthyroidism with mildly decreased TSH or subclinical hypothyroidism were not. © 2017 John Wiley & Sons Ltd.

  1. Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure.

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    Swoboda, Peter P; McDiarmid, Adam K; Erhayiem, Bara; Ripley, David P; Dobson, Laura E; Garg, Pankaj; Musa, Tarique A; Witte, Klaus K; Kearney, Mark T; Barth, Julian H; Ajjan, Ramzi; Greenwood, John P; Plein, Sven

    2017-07-17

    Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease. In a case-controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin-angiotensin-aldosterone therapy, 50 ACR-ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1-year treatment with renin-angiotensin-aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P=0.0002) and in ACR+ve than ACR-ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P=0.004). ACR+ve patients also had lower E' measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P=0.04) and elevated high-sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L (P=0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin-angiotensin-aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P=0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P=0.01) but no changes in diastolic function or high-sensitivity cardiac troponin T levels. Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high-sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin-angiotensin-aldosterone blockade. Increased risk in these patients may be mediated by subclinical

  2. Subclinical LV dysfunction and 10-year outcomes in type 2 diabetes mellitus.

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    Holland, David J; Marwick, Thomas H; Haluska, Brian A; Leano, Rodel; Hordern, Matthew D; Hare, James L; Fang, Zhi You; Prins, Johannes B; Stanton, Tony

    2015-07-01

    New imaging techniques have permitted the detection of subclinical LV dysfunction (LVD) in up to half of patients with type 2 diabetes mellitus (DM) with a normal EF. However, the connection between early LVD and prognosis is unclear. This study aimed to define the long-term outcome of LVD associated with type 2 DM. In this prospective cohort study, 230 asymptomatic patients with type 2 DM underwent measurement of global longitudinal 2D strain (GLS) for detection of LVD and were followed for up to 10 years. All subjects had normal EF (≥50%) and no evidence of coronary artery disease at recruitment. Outcome data were obtained through centralised state-wide death and hospital admission registries. The primary endpoint was all-cause mortality and hospitalisation. On study entry, almost half (45%) of the cohort had evidence of LVD as detected by GLS. Over a median follow-up of 7.4±2.6 years (range 0.6-9.7 years), 68 patients (30%) met the primary endpoint (LVD: 37%; normal LV function: 24%). GLS was independently associated with the primary endpoint (HR=1.10; p=0.04), as was systolic blood pressure (HR=1.02; p<0.001) and levels of glycosylated haemoglobin (HR=1.28; p=0.011). Patients with LVD had significantly worse outcome than those without (χ(2)=4.73; p=0.030). Subclinical LVD is common in asymptomatic patients with type 2 DM, is readily detectable by GLS imaging and is independently associated with adverse outcome. Australian and New Zealand Clinical Trials Registry (ACTRN12612001178831). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Cardiac dysfunction in a porcine model of pediatric malnutrition

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    Fabiansen, Christian; Lykke, Mikkel; Nielsen, Anne-Louise Hother

    2015-01-01

    BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet...... groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (pMalnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide...

  4. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis

    Directory of Open Access Journals (Sweden)

    Ying Li

    2013-12-01

    Full Text Available Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction, which is one of the leading causes of mortality in these patients. Acute sepsis decreases cardiac contractility and impairs myocardial compliance. Chronic inflammation such as that occurring in Duchenne muscular dystropshy and myocarditis may cause adverse cardiac remodeling including myocyte hypertrophy and death, fibrosis, and altered myocyte function. However, the underlying cellular and molecular mechanisms for inflammatory cardiomyopathy are still controversial probably due to multiple factors involved. Potential mechanisms include the change in circulating blood volume; a direct inhibition of myocyte contractility by cytokines (tumor necrosis factor (TNF-a, interleukin (IL-1b; abnormal nitric oxide and reactive oxygen species (ROS signaling; mitochondrial dysfunction; abnormal excitation-contraction coupling; and reduced calcium sensitivity at the myofibrillar level and blunted b-adrenergic signaling. This review will summarize recent advances in diagnostic technology, mechanisms, and potential therapeutic strategies for inflammation-induced cardiac dysfunction.

  5. Association between endothelial dysfunction, epicardial fat and subclinical atherosclerosis during menopause.

    Science.gov (United States)

    Cabrera-Rego, Julio Oscar; Navarro-Despaigne, Daisy; Staroushik-Morel, Liudmila; Díaz-Reyes, Karel; Lima-Martínez, Marcos M; Iacobellis, Gianluca

    Menopausal transition is critical for the development of early, subclinical vascular damage. Multiple factors, such as atherosclerosis, increased epicardial fat, and endothelial dysfunction can play a role. Hence, the objective of this study was the comparison of epicardial adipose tissue and carotid intima media thickness in order to establish the best predictor of carotid stiffness in middle-aged women with endothelial dysfunction. A total of 43 healthy women aged 40-59 years old with endothelial dysfunction previously demonstrated by flow mediated dilation were recruited to have anthropometric, biochemical, hormonal and ultrasound determinations of carotid intima media thickness and epicardial fat thickness. Carotid arterial stiffness parameters (local pulse wave velocity [4.7±0.7 vs 4.8±0.5 vs 5.6±0.5m/s, respectively, p<0.001], pressure strain elastic modulus [55.2±13.4 vs 59.2±11.8 vs 81.9±15.6kPa, respectively, p<0.001], arterial stiffness index β [4.4±1.4 vs 5.0±1.1 vs 6.4±1.3, respectively, p<0.001]) and epicardial fat thickness (2.98±1.4 vs 3.28±1.9 vs 4.70±1.0mm, respectively, p=0.007) showed a significant and proportional increase in the group of late post-menopausal women when compared to early post-menopausal and pre-menopausal groups, respectively. Among body fat markers, epicardial fat was the strongest predictor of local pulse wave velocity, independent of age. In menopausal women with endothelial dysfunction, menopausal transition is associated with increased carotid arterial stiffness and epicardial fat thickness, independent of age. Ultrasound measured epicardial fat was a better independent predictor of arterial stiffness than carotid intima media thickness in these women. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Leptin as a mediator between obesity and cardiac dysfunction

    Directory of Open Access Journals (Sweden)

    Joanna Karbowska

    2012-05-01

    Full Text Available  Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and in­volved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue.These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

  7. Cardiac Autonomic Dysfunction in Children and Adolescents with ...

    African Journals Online (AJOL)

    Introduction: Autonomic neuropathy is less well documented in children with type 1 diabetes mellitus and has received less attention than other diabetic complications. Sudden death and cardio-respiratory arrest in patients with type 1 and type 2 diabetes mellitus have been attributed to cardiac autonomic dysfunction.

  8. Minocycline attenuates cardiac dysfunction in tumor-burdened mice.

    Science.gov (United States)

    Devine, Raymond D; Eichenseer, Clayton M; Wold, Loren E

    2016-11-01

    Cardiovascular dysfunction as a result of tumor burden is becoming a recognized complication; however, the mechanisms remain unknown. A murine model of cancer cachexia has shown marked increases of matrix metalloproteinases (MMPs), known mediators of cardiac remodeling, in the left ventricle. The extent to which MMPs are involved in remodeling remains obscured. To this end a common antibiotic, minocycline, with MMP inhibitory properties was used to elucidate MMP involvement in tumor induced cardiovascular dysfunction. Tumor-bearing mice showed decreased cardiac function with reduced posterior wall thickness (PWTs) during systole, increased MMP and collagen expression consistent with fibrotic remodeling. Administration of minocycline preserved cardiac function in tumor bearing mice and decreased collagen RNA expression in the left ventricle. MMP protein levels were unaffected by minocycline administration, with the exception of MMP-9, indicating minocycline inhibition mechanisms are directly affecting MMP activity. Cancer induced cardiovascular dysfunction is an increasing concern; novel therapeutics are needed to prevent cardiac complications. Minocycline is a well-known antibiotic and recently has been shown to possess MMP inhibitory properties. Our findings presented here show that minocycline could represent a novel use for a long established drug in the prevention and treatment of cancer induced cardiovascular dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Short-Term Subclinical Zinc Deficiency in Weaned Piglets Affects Cardiac Redox Metabolism and Zinc Concentration.

    Science.gov (United States)

    Brugger, Daniel; Windisch, Wilhelm M

    2017-04-01

    Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism. Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets. Methods: Forty-eight weaned German Large White × Landrace × Piétrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d. Measurements included cardiac parameters of antioxidative capacity, stress-associated gene expression, and tissue zinc status. Analyses comprised (linear, broken-line) regression models and Pearson correlation coefficients. Results: Glutathione and α-tocopherol concentrations as well as catalase, glutathione reductase, B-cell lymphoma 2-associated X protein, and caspase 9 gene expression plateaued in response to reduction in dietary zinc from 88.0 to 57.6, 36.0, 36.5, 41.3, 55.3, and 33.8 mg/kg, respectively ( P SZD decreased cardiac antioxidative capacity of weaned piglets while simultaneously increasing stress-associated gene expression and zinc concentration. This is the first report to our knowledge on the effects of SZD on redox metabolism. © 2017 American Society for Nutrition.

  10. Cardiovascular risk with subclinical hyperthyroidism and hypothyroidism: pathophysiology and management.

    Science.gov (United States)

    Duggal, Jasleen; Singh, Sarabjeet; Barsano, Charles P; Arora, Rohit

    2007-01-01

    Previous studies have suggested that subclinical thyroid dysfunction, as manifested by abnormalities in thyroid-stimulating hormone (TSH) levels, are associated with detrimental effects on the cardiovascular system. Subclinical hypothyroidism is characterized by abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated risk of atherosclerosis, and ischemic heart disease. Similarly, patients with subclinical hyperthyroidism have nearly 3 times the likelihood of atrial fibrillation over a 10-year follow-up interval, raising the question of whether patients with subclinical hyperthyroidism should be treated to prevent atrial fibrillation. A single measurement of low serum TSH in individuals aged 60 years or older has been reported to be associated with increased mortality from all causes and in particular from circulatory and cardiovascular disease in a 10-year follow-up study. Subclinical thyroid dysfunction is currently the subject of numerous studies and remains controversial, particularly as it relates to cardiovascular morbidity and mortality and clinical applications.

  11. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Quan He

    2014-01-01

    Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

  12. Procalcitonin and midregional proatrial natriuretic peptide as biomarkers of subclinical cerebrovascular damage: the northern manhattan study

    OpenAIRE

    Katan, Mira; Moon, Yeseon; von Eckardstein, Arnold; Spanaus, Kathartina; DeRosa, Janet; Gutierrez, Jose; DeCarli, Charles; Wright, Clinton; Sacco, Ralph; Elkind, Mitchell

    2017-01-01

    BACKGROUND AND PURPOSE: Chronic infections and cardiac dysfunction are risk factors for stroke. We hypothesized that blood biomarkers of infection (procalcitonin) and cardiac dysfunction (midregional proatrial natriuretic peptide [MR-proANP]), previously associated with small vessel stroke and cardioembolic stroke are also associated with subclinical cerebrovascular damage, including silent brain infarcts and white matter hyperintensity volume. METHODS: The NOMAS (Northern Manhattan Study)...

  13. Primary proteasome inhibition results in cardiac dysfunction

    Science.gov (United States)

    Herrmann, Joerg; Wohlert, Christine; Saguner, Ardan M.; Flores, Ana; Nesbitt, Lisa L.; Chade, Alejandro; Lerman, Lilach O.; Lerman, Amir

    2013-01-01

    Aims The proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart. Methods and results Female domestic pigs were randomized to a normal diet without (N) or with twice-weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, N + PSI, n = 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 ± 16.4 g vs. 183.1 ± 24.2 g, P < 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 ± 0.6 vs. 1.8 ± 0.1, P < 0.05). The EF tended to be lower (46 ± 12% and 53 ± 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 ± 1.1 vs. 4.7 ± 1.1 L/min, P < 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI. Conclusion The current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic–restrictive cardiomyopathy phenotype. PMID:23616520

  14. Protective role of antioxidants in diabetes-induced cardiac dysfunction.

    Science.gov (United States)

    Vassort, Guy; Turan, Belma

    2010-06-01

    Cardiac dysfunction occurs during type 1 and type 2 diabetes and results from multiple parameters including glucotoxicity, lipotoxicity, fibrosis and mitochondrial uncoupling. Oxidative stress arises from an imbalance between the production of ROS and the biological system's ability to readily detoxify the reactive intermediates. It is involved in the etiology of diabetes-induced downregulation of heart function. Several studies have reported beneficial effects of a therapy with antioxidant agents, including trace elements and other antioxidants, against the cardiovascular system consequences of diabetes. Antioxidants act through one of three mechanisms to prevent oxidant-induced cell damages. They can reduce the generation of ROS, scavenge ROS, or interfere with ROS-induced alterations. Modulating mitochondrial activity is an important possibility to control ROS production. Hence, the use of PPARalpha agonist to reduce fatty acid oxidation and of trace elements such as zinc and selenium as antioxidants, and physical exercise to induce mitochondrial adaptation, contribute to the prevention of diabetes-induced cardiac dysfunction. The paradigm that inhibiting the overproduction of superoxides and peroxides would prevent cardiac dysfunction in diabetes has been difficult to verify using conventional antioxidants like vitamin E. That led to use of catalytic antioxidants such as SOD/CAT mimetics. Moreover, increases in ROS trigger a cascade of pathological events, including activation of MMPs, PPARs and protein O-GlcNAcation. Multiple tools have been developed to counteract these alterations. Hence, well-tuned, balanced and responsive antioxidant defense systems are vital for proper prevention against diabetic damage. This review aims to summarize our present knowledge on various strategies to control oxidative stress and antagonize cardiac dysfunction during diabetes.

  15. Adenosine prevents isoprenaline-induced cardiac contractile and electrophysiological dysfunction.

    Science.gov (United States)

    Shao, Yangzhen; Redfors, Björn; Mattson-Hultén, Lillemor; Scharing Täng, Margareta; Daryoni, Elma; Said, Mohammed; Omerovic, Elmir

    2013-10-15

    Excessive levels of catecholamines are believed to contribute to cardiac dysfunction in a variety of disease states, including myocardial infarction and heart failure, and are particularly implicated in stress-induced cardiomyopathy, an increasingly recognized cardiomyopathy associated with significant morbidity and mortality. We have previously shown that a high dose of isoprenaline induces reversible regional dysfunction of the left ventricle in mice. We now hypothesize that adenosine can prevent cardiac dysfunction in this mouse model of stress-induced cardiomyopathy. Hundred male C57BL/6 mice were injected with 400mg/kg isoprenaline and then randomized to either 400mg/kg adenosine or saline. Cardiac function was evaluated by echocardiography at baseline and 2, 24, 48, 72, 96 and 120 min post isoprenaline. Myocardial fibrosis was quantified after 10 days. Intracellular lipid accumulation was quantified after 2 and 24h. Electrophysiological parameters and degree of lipid accumulation were evaluated in cultured HL1 cardiomyocytes. Two hours post isoprenaline treatment, echocardiographic parameters of global and posterior wall regional function were significantly better in adenosine-treated mice (P<0.05). This difference persisted at 24h, but saline-treated mice gradually recovered over the next 96 h. Intracellular lipid accumulation was also significantly lower in adenosine mice. We found no sign of fibrosis in the adenosine mice, whereas the extent of fibrosis in isoprenaline mice was 1.3% (P<0.05). Furthermore, adenosine-treated HL1 cells showed preserved electrophysiological function and displayed less severe intracellular lipid accumulation in response to isoprenaline. In conclusion, adenosine attenuates isoprenaline-induced cardiac dysfunction in mice and cells. © 2013 Elsevier B.V. All rights reserved.

  16. Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition.

    Directory of Open Access Journals (Sweden)

    Christian Fabiansen

    Full Text Available Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition.To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model.Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12 or a reference diet (AGE-REF, n = 12 for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8. Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5-7 (p ≤ 0.001. There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2-19.7; p = 0.03. However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0-15.9; p < 0.001 in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p < 0.001, whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p < 0.001 and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025.Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition.

  17. Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction.

    Science.gov (United States)

    Freitas, Felipe; Estato, Vanessa; Carvalho, Vinícius Frias; Torres, Rafael Carvalho; Lessa, Marcos Adriano; Tibiriçá, Eduardo

    2013-10-01

    The pathophysiology underlying hyperthyroidism-induced left ventricle (LV) dysfunction and hypertrophy directly involves the heart and indirectly involves the neuroendocrine systems. The effects of hyperthyroidism on the microcirculation are still controversial in experimental models. We investigated the effects of hyperthyroidism on the cardiac function and microcirculation of an experimental rat model. Male Wistar rats (170-250 g) were divided into two groups: the euthyroid group (n = 10), which was treated with 0.9% saline solution, and the hyperthyroid group (n = 10), which was treated with l-thyroxine (600 μg/kg/day, i.p.) during 14 days. An echocardiographic study was performed to evaluate the alterations in cardiac function, structure and geometry. The structural capillary density and the expression of angiotensin II AT1 receptor in the LV were analyzed using histochemistry and immunohistochemistry, respectively. Hyperthyroidism was found to induce profound cardiovascular alterations, such as systolic hypertension, tachycardia, LV dysfunction, cardiac hypertrophy, and myocardial fibrosis. This study demonstrates the existence of structural capillary rarefaction and the down-regulation of the cardiac angiotensin II AT1 receptor in the myocardium of hyperthyroid rats in comparison with euthyroid rats. Microvascular rarefaction may be involved in the pathophysiology of hyperthyroidism-induced cardiovascular alterations. © 2013 John Wiley & Sons Ltd.

  18. Early cardiac changes induced by a hypercaloric Western-type diet in "subclinical" obesity.

    Science.gov (United States)

    Gonçalves, Nádia; Silva, Ana Filipa; Rodrigues, Patrícia Gonçalves; Correia, Eugénia; Moura, Cláudia; Eloy, Catarina; Roncon-Albuquerque, Roberto; Falcão-Pires, Inês; Leite-Moreira, Adelino F

    2016-03-15

    "Obesity cardiomyopathy" effects have been widely described; however, the specific contribution of metabolic changes and altered adipokine secretion are still uncharacterized. Moreover, a diagnosis based on body mass index might not be the most accurate to identify increased adiposity and its outcomes. In this study, we aimed to determine the impact of a Western-type diet [hypercaloric diet (HCD)] ingestion on biventricular structure and function, as well as the metabolic and endocrine changes that occur before the establishment of overt obesity. Wistar rats were fed for 6 wk with a regular diet or HCD. At the end of the protocol, metabolic tests, cardiac structure, and functional evaluation were performed, and blood and tissue samples collected to perform histological, molecular biology, and functional studies. The animals that ingested the HCD presented increased adiposity and larger adipocyte cross-sectional area, but similar body weight compared with the regular diet group. At the cardiac level, HCD induced biventricular cardiomyocyte hypertrophy, fibrosis, increased stiffness, and impaired relaxation. Galectin-3 plasma expression was likewise elevated in the same animals. The nutritional modulation also altered the secretory pattern of the adipose tissue, originating a proinflammatory systemic environment. In this study, we observed that before "clinical" overweight or frank obesity is established, the ingestion of a HCD-induced cardiac remodeling manifests by increased biventricular stiffness and diastolic dysfunction. The mechanism triggering the cardiac alterations appears to be the proinflammatory environment promoted by the adipose tissue dysfunction. Furthermore, galectin-3, a profibrotic molecule, might be a potential biomarker for the myocardial alterations promoted by the HCD before overweight or obesity. Copyright © 2016 the American Physiological Society.

  19. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure.

    Science.gov (United States)

    Wang, Han-Jun; Wang, Wei; Cornish, Kurtis G; Rozanski, George J; Zucker, Irving H

    2014-10-01

    The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympathoexcitation in chronic heart failure (CHF). Increased sympathoexcitation is positively related to mortality in patients with CHF. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here, we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. To delete the transient receptor potential vanilloid 1 receptor-expressing CSAR afferents selectively, epicardial application of resiniferatoxin (50 μg/mL), an ultrapotent analog of capsaicin, was performed during myocardium infarction surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of resiniferatoxin largely prevented the elevated left ventricle end-diastolic pressure, lung edema, and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart, and increased cardiac contractile reserve in response to β-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that resiniferatoxin attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and transforming growth factor-β receptor I in CHF rats. Pressure-volume loop analysis showed that resiniferatoxin reduced the end-diastolic pressure volume relationships in CHF rats, indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF. © 2014 American Heart Association, Inc.

  20. Distribution of response time, cortical, and cardiac correlates during emotional interference in persons with subclinical psychotic symptoms

    Directory of Open Access Journals (Sweden)

    Lisa Kathinka Barbara Holper

    2016-09-01

    Full Text Available A psychosis phenotype can be observed below the threshold of clinical detection. The study aimed to investigate whether subclinical psychotic symptoms are associated with deficits in controlling emotional interference, and whether cortical brain and cardiac correlates of these deficits can be detected using functional near-infrared spectroscopy (fNIRS. A data set derived from a community sample was obtained from the Zurich Program for Sustainable Development of Mental Health Services. 174 subjects (mean age 29.67 ± 6.41, 91 females were assigned to four groups ranging from low to high levels of subclinical psychotic symptoms (derived from the Symptom Checklist-90-R. Emotional interference was assessed using the emotional Stroop task comprising neutral, positive, and negative conditions. Statistical distributional methods based on delta plots (behavioral response time data and quantile analysis (fNIRS data were applied to evaluate the emotional interference effects.Results showed that both interference effects and disorder-specific (i.e., group-specific effects could be detected, based on behavioral response times, cortical hemodynamic signals (brain correlates, and heart rate variability (cardiac correlates. Subjects with high compared to low subclinical psychotic symptoms revealed significantly reduced amplitudes in dorsolateral prefrontal cortices (interference effect, p < 0.001 and middle temporal gyrus (disorder-specific group effect, p < 0.001, supported by behavioral and heart rate results. The present findings indicate that distributional analyses methods can support the detection of emotional interference effects in the emotional Stroop. The results suggested that subjects with high subclinical psychosis exhibit enhanced emotional interference effects. Based on these observations, subclinical psychosis may therefore prove to represent a valid extension of the clinical psychosis phenotype.

  1. Distribution of Response Time, Cortical, and Cardiac Correlates during Emotional Interference in Persons with Subclinical Psychotic Symptoms.

    Science.gov (United States)

    Holper, Lisa K B; Aleksandrowicz, Alekandra; Müller, Mario; Ajdacic-Gross, Vladeta; Haker, Helene; Fallgatter, Andreas J; Hagenmuller, Florence; Kawohl, Wolfram; Rössler, Wulf

    2016-01-01

    A psychosis phenotype can be observed below the threshold of clinical detection. The study aimed to investigate whether subclinical psychotic symptoms are associated with deficits in controlling emotional interference, and whether cortical brain and cardiac correlates of these deficits can be detected using functional near-infrared spectroscopy (fNIRS). A data set derived from a community sample was obtained from the Zurich Program for Sustainable Development of Mental Health Services. 174 subjects (mean age 29.67 ± 6.41, 91 females) were assigned to four groups ranging from low to high levels of subclinical psychotic symptoms (derived from the Symptom Checklist-90-R). Emotional interference was assessed using the emotional Stroop task comprising neutral, positive, and negative conditions. Statistical distributional methods based on delta plots [behavioral response time (RT) data] and quantile analysis (fNIRS data) were applied to evaluate the emotional interference effects. Results showed that both interference effects and disorder-specific (i.e., group-specific) effects could be detected, based on behavioral RTs, cortical hemodynamic signals (brain correlates), and heart rate variability (cardiac correlates). Subjects with high compared to low subclinical psychotic symptoms revealed significantly reduced amplitudes in dorsolateral prefrontal cortices (interference effect, p < 0.001) and middle temporal gyrus (disorder-specific group effect, p < 0.001), supported by behavioral and heart rate results. The present findings indicate that distributional analyses methods can support the detection of emotional interference effects in the emotional Stroop. The results suggested that subjects with high subclinical psychosis exhibit enhanced emotional interference effects. Based on these observations, subclinical psychosis may therefore prove to represent a valid extension of the clinical psychosis phenotype.

  2. Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Speerschneider, Tobias; Winther, Sine V

    2014-01-01

    Background: The aim of this study was to probe cardiac complications, including heart-rate control, in a mouse model of type-2 diabetes. Heart-rate development in diabetic patients is not straight forward: In general, patients with diabetes have faster heart rates compared to non-diabetic...... and electrophysiological characteristics were investigated in diabetic db/db and control db/+mice.ResultsWe found improved contractile function and impaired filling dynamics of the heart in db/db mice, relative to db/+controls. Electrophysiologically, we observed comparable heart rates in the two mouse groups, but SAN...... individuals, yet diabetic patients are frequently found among patients treated for slow heart rates. Hence, we hypothesized that sinoatrial node (SAN) dysfunction could contribute to our understanding the mechanism behind this conundrum and the consequences thereof.MethodsCardiac hemodynamic...

  3. Lipotoxicity in obesity and diabetes-related cardiac dysfunction.

    Science.gov (United States)

    Zlobine, Igor; Gopal, Keshav; Ussher, John R

    2016-10-01

    Patients with type 2 diabetes (T2D) are at increased risk for cardiovascular diseases including diabetic cardiomyopathy, which is ventricular dysfunction independent of underlying coronary artery disease and/or hypertension. With numerous advancements in our ability to detect ventricular dysfunction, as well as the molecular mechanisms contributing to ventricular dysfunction in diabetic patients, it is now appreciated that diabetic cardiomyopathy is becoming more prevalent in our population. In spite of these advancements, we do not have any specific therapies currently approved for treating this condition. As obesity increases the risk for both T2D and cardiovascular disease, it has been postulated that obesity-mediated alterations in myocardial lipid metabolism are critical to the pathophysiology of diabetic cardiomyopathy. Indeed, animal studies have provided strong evidence that alterations in either myocardial fatty acid uptake or fatty acid β-oxidation lead to the accumulation of various lipid intermediates including triacylglycerol, diacylglycerol, ceramide, long-chain acyl CoA, acylcarnitine, and many others that are tightly linked to the progression of ventricular dysfunction. We review herein why lipid intermediates accumulate in the heart during obesity and/or T2D, with a focus on which of these various lipid intermediates may be responsible for cardiac lipotoxicity, and whether findings in animal models are relevant to humans. An improved understanding of how these lipid intermediates accumulate in the heart and how they produce cardiac toxicity may lead to the discovery of novel targets to pursue for the treatment of human diabetic cardiomyopathy. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Respiratory physiotherapy in the pulmonary dysfunction after cardiac surgery.

    Science.gov (United States)

    Renault, Julia Alencar; Costa-Val, Ricardo; Rossetti, Márcia Braz

    2008-01-01

    The aim of this work is to make a critical review about the different techniques of respiratory physiotherapy used following cardiac surgery and this effectiveness in reverting pulmonary dysfunction. It has been used as reference publications in English and Portuguese using as key words thoracic surgery, respiratory exercises, physical therapy modalities, postoperative complications and myocardial revascularization, contained in the following databases BIREME, SciELO Brazil, LILACS, PUBMED, from 1997 to 2007. A secondary search of the reference list of identified articles also was made. It has been selected eleven randomized trials (997 patients). For the articles included incentive spirometry was used in three; deep breathing exercises in six; deep breathing exercises added to positive expiratory pressure in four and positive airway pressure added to inspiratory resistance in two. Three trials used intermittent positive pressure breathing. Continuous positive airway pressure and bi-level positive airway pressure has been used in three and two trials. The protocols used in the studies were varied and the co interventions were present in a big part of these. The different analyzed varieties and the time of postoperatory follow up make a comparative analysis difficult. Pulmonary dysfunction is evident in the postoperatory period of cardiac surgery. The use of noninvasive ventilation has been associated with good results in the first postoperatory days. Despite the known importance of postoperatory respiratory physiotherapy, until now, there is no literary consensus about the superiority of one technique over the others.

  5. Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis.

    Science.gov (United States)

    Zheng, Zhibo; Ma, He; Zhang, Xia; Tu, Fei; Wang, Xiaohui; Ha, Tuanzhu; Fan, Min; Liu, Li; Xu, Jingjing; Yu, Kaijiang; Wang, Ruitao; Kalbfleisch, John; Kao, Race; Williams, David; Li, Chuanfu

    2017-05-01

    Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism. This study investigated whether modulation of glycolysis by inhibition of hexokinase will be beneficial to septic cardiomyopathy. Male C57B6/J mice were treated with a hexokinase inhibitor (2-deoxy-d-glucose [2-DG], 0.25-2 g/kg, n = 6-8) before cecal ligation and puncture (CLP) induced sepsis. Untreated septic mice served as control. Sham surgically operated mice treated with or without the 2-DG inhibitor served as sham controls. Cardiac function was assessed 6 hours after CLP sepsis by echocardiography. Serum was harvested for measurement of inflammatory cytokines and lactate. Sepsis-induced cardiac dysfunction was significantly attenuated by administration of 2-DG. Ejection fraction and fractional shortening in 2-DG-treated septic mice were significantly (P sepsis-increased serum levels of tumor necrosis factor α and interleukin 1β as well as lactate, and enhanced the expression of Sirt1 and Sirt3 in the myocardium, which play an important role in mitochondrial function and metabolism. In addition, 2-DG administration suppresses sepsis-increased expression of apoptotic inducers Bak and Bax as well as JNK phosphorylation in the myocardium. Glycolytic metabolism plays an important role in mediating sepsis-induced septic cardiomyopathy. The mechanisms may involve regulation of inflammatory response and apoptotic signaling.

  6. Clinical Predictive Value of Cystatin C in Pediatric Sickle Cell Disease: A Marker of Disease Severity and Subclinical Cardiovascular Dysfunction.

    Science.gov (United States)

    Tantawy, Azza Abdel Gawad; Adly, Amira Abdel Moneam; Ismail, Eman Abdel Rahman; Abdelazeem, Mai

    2017-11-01

    Patients with sickle cell disease (SCD) are at high risk of renal dysfunction and cardiovascular morbidity. The association between cystatin C and renal function is well known, however, cystatin C has recently emerged as a strong predictor of cardiovascular events and adverse outcomes in patients with and without kidney disease, mostly related to both inflammation and atherosclerosis. To determine cystatin C levels in 53 children and adolescents with SCD compared to 40 age- and sex-matched healthy controls and assess its relation to markers of hemolysis, iron overload, sickle vasculopathy, and carotid intima-media thickness (CIMT). Patients with SCD in steady state were studied, focusing on hydroxyurea therapy, hematological profile, serum ferritin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin-creatinine ratio (UACR), and serum cystatin C. Echocardiography and CIMT were assessed using high-resolution ultrasound. Heart disease was defined by systolic left ventricle dysfunction (shortening fraction C levels than those without ( P C levels than untreated patients ( P = .039). High-sensitivity C-reactive protein, UACR, ejection fraction, and CIMT were independently related to cystatin C in multiple regression analysis. The cutoff values of cystatin C for detection of renal or cardiovascular complications were determined. Cystatin C may be considered a biological marker for vascular dysfunction and subclinical atherosclerosis in SCD.

  7. The evaluation of diastolic dysfunction with tissue Doppler echocardiography in women with subclinical hypothyroidism and the effect of L-thyroxine treatment on diastolic dysfunction: a pilot study.

    Science.gov (United States)

    Erkan, Gulbanu; Erkan, Aycan Fahri; Cemri, Mustafa; Karaahmetoglu, Selma; Cesur, Mustafa; Cengel, Atiye

    2011-01-01

    Background. Subclinical hypothyroidism (SH) predominantly affects women. The necessity of treatment in SH is controversial. Objective. We aimed to investigate the response of diastolic dysfunction to thyroid hormone replacement therapy (THRT) in women. Methods and Results. Twenty-two female subjects with SH and 20 euthyroid female controls were enrolled. Baseline and follow-up biochemical, hormonal, and echocardiographic evaluations were performed. Repeat echocardiograms were performed three months after the achievement of a euthyroid status with THRT. Mean baseline myocardial performance index (MPI) was 0.27 ± 0.08 in the SH group, and 0.22 ± 0.06 in the control group (P = 0.03). MPI did not change significantly after THRT. Pulsed-wave Doppler findings were not different among the groups. However, tissue Doppler-derived mitral annular E' velocities were significantly lower in the SH group. A moderate but significant improvement was observed in E' velocities after THRT (13.2 ± 3.87 versus 14.53 ± 2.75, P = 0.04). We also observed left ventricular concentric remodeling in SH patients which was reversible with THRT. Conclusions. Tissue Doppler echocardiography may be a useful tool for monitoring the response of diastolic dysfunction to thyroid hormone replacement therapy in patients with SH. Our findings suggest that THRT may reverse diastolic dysfunction in women with SH.

  8. The Evaluation of Diastolic Dysfunction with Tissue Doppler Echocardiography in Women with Subclinical Hypothyroidism and the Effect of L-Thyroxine Treatment on Diastolic Dysfunction: A Pilot Study

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    Gulbanu Erkan

    2011-01-01

    Full Text Available Background. Subclinical hypothyroidism (SH predominantly affects women. The necessity of treatment in SH is controversial. Objective. We aimed to investigate the response of diastolic dysfunction to thyroid hormone replacement therapy (THRT in women. Methods and Results. Twenty-two female subjects with SH and 20 euthyroid female controls were enrolled. Baseline and follow-up biochemical, hormonal, and echocardiographic evaluations were performed. Repeat echocardiograms were performed three months after the achievement of a euthyroid status with THRT. Mean baseline myocardial performance index (MPI was 0.27±0.08 in the SH group, and 0.22±0.06 in the control group (P=0.03. MPI did not change significantly after THRT. Pulsed-wave Doppler findings were not different among the groups. However, tissue Doppler-derived mitral annular E’ velocities were significantly lower in the SH group. A moderate but significant improvement was observed in E’ velocities after THRT (13.2±3.87 versus 14.53±2.75, P=0.04. We also observed left ventricular concentric remodeling in SH patients which was reversible with THRT. Conclusions. Tissue Doppler echocardiography may be a useful tool for monitoring the response of diastolic dysfunction to thyroid hormone replacement therapy in patients with SH. Our findings suggest that THRT may reverse diastolic dysfunction in women with SH.

  9. Cardio-oncology: a multidisciplinary approach for detection, prevention and management of cardiac dysfunction in cancer patients.

    Science.gov (United States)

    Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

    2017-08-01

    Cardiac dysfunction that develops during or after completion of cancer therapy is a growing health concern that should be addressed in a multidisciplinary setting. Cardio-oncology is a new discipline that focuses on screening, monitoring and treating cardiovascular disease during and after cancer treatment. A baseline cardiovascular risk assessment is essential. For high-risk patients, a tailored and detailed plan for cardiovascular management throughout treatment and beyond should also be established. Anthracycline and/or trastuzumab-containing chemotherapy and chest-directed radiation therapy are well known cardiotoxic cancer therapies. Monitoring for the development of subclinical cardiotoxicity is crucial for the prevention of clinical heart failure. Detecting a decreased left ventricular ejection fraction after cancer therapy might be a late finding; therefore, earlier markers of cardiac injury are being actively explored. Abnormal myocardial strain and increased serum cardiac biomarkers (e.g. troponins and natriuretic peptides) are possible candidates for this purpose. An important method for preventing heart failure is the avoidance or minimization of the use of cardiotoxic therapies. Decisions must balance the anti-tumor efficacy of the treatment with its potential cardiotoxicity. If patients develop cardiac dysfunction or heart failure, they should be treated in accordance with established guidelines for heart failure. Cancer survivors who have been exposed to cardiotoxic cancer therapies are at high risk of developing heart failure. The management of cardiovascular risk factors and periodic screening with cardiac imaging and biomarkers should be considered in high-risk survivors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Paediatric cancer survivors demonstrate a high rate of subclinical renal dysfunction.

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    Mudi, Abdullahi; Levy, Cecil Steven; Geel, Jennifer Ann; Poole, Janet Elizabeth

    2016-11-01

    Clinical manifestations of renal dysfunction in childhood cancer survivors include hypertension, proteinuria, tubulopathy (and its biochemical consequences) and renal insufficiency. This study aimed to determine the factors associated with renal dysfunction in paediatric cancer survivors at a single centre in Johannesburg. A descriptive cross-sectional study was performed on 130 cancer survivors between 2 and 18 years of age. Physical examination and screening urine dipstick were performed on all patients. Blood results of samples routinely drawn were analysed. After a median follow-up period of 2 years, the various manifestations of renal dysfunction included decreased estimated glomerular filtration rate (eGFR), hypomagnesaemia, hypophosphataemia, proteinuria, haematuria and hypertension. In total, 34 survivors (26.15%) had at least one manifestation of renal dysfunction after completing treatment. The most prevalent manifestation of renal dysfunction was decreased eGFR (17.7%) followed by hypomagnesaemia (6.2%) and hypophosphataemia (4.6%). Patients with pre-existing renal dysfunction were three times more likely to have renal dysfunction post-treatment (P = 0.020). Ifosfamide (P = 0.010) and nephrectomy (P = 0.003) had independent significant impact on reduction in eGFR. High cumulative ifosfamide doses were identified as a possible cause for hypophosphataemia (P = 0.021). While not clinically evident in the early follow-up period, the high rate of renal dysfunction is concerning. We suggest that patients with pre-existing renal dysfunction should be assessed by a nephrologist prior to initiation of cancer therapy, and nephro-protective measures should be employed stringently in all children with cancer. Patients with decreased eGFR should be followed up closely in a multidisciplinary late effects clinic. © 2016 Wiley Periodicals, Inc.

  11. Postoperative Pulmonary Dysfunction and Mechanical Ventilation in Cardiac Surgery

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    Rafael Badenes

    2015-01-01

    Full Text Available Postoperative pulmonary dysfunction (PPD is a frequent and significant complication after cardiac surgery. It contributes to morbidity and mortality and increases hospitalization stay and its associated costs. Its pathogenesis is not clear but it seems to be related to the development of a systemic inflammatory response with a subsequent pulmonary inflammation. Many factors have been described to contribute to this inflammatory response, including surgical procedure with sternotomy incision, effects of general anesthesia, topical cooling, and extracorporeal circulation (ECC and mechanical ventilation (VM. Protective ventilation strategies can reduce the incidence of atelectasis (which still remains one of the principal causes of PDD and pulmonary infections in surgical patients. In this way, the open lung approach (OLA, a protective ventilation strategy, has demonstrated attenuating the inflammatory response and improving gas exchange parameters and postoperative pulmonary functions with a better residual functional capacity (FRC when compared with a conventional ventilatory strategy. Additionally, maintaining low frequency ventilation during ECC was shown to decrease the incidence of PDD after cardiac surgery, preserving lung function.

  12. Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

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    Linz Dominik

    2012-09-01

    Full Text Available Abstract Background The additive effects of obesity and metabolic syndrome on left ventricular (LV maladaptive remodeling and function in hypertension are not characterized. Methods We compared an obese spontaneously hypertensive rat model (SHR-ob with lean spontaneously hypertensive rats (SHR-lean and normotensive controls (Ctr. LV-function was investigated by cardiac magnetic resonance imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was quantified and protein levels of phospholamban (PLB, Serca2a and glucose transporters (GLUT1 and GLUT4 were determined by immunohistochemistry. Results Systolic blood pressure was similar in SHR-lean and SHR-ob (252 ± 7 vs. 242 ± 7 mmHg, p = 0.398 but was higher when compared to Ctr (155 ± 2 mmHg, p  Conclusion In addition to hypertension alone, metabolic syndrome and obesity adds to the myocardial phenotype by aggravating diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may be a useful model to develop new interventional and pharmacological treatment strategies for hypertensive heart disease and metabolic disorders.

  13. [Therapeutic aspects in coronary cardiac patients who suffer from sexual dysfunction in a cardiac rehabilitation program].

    Science.gov (United States)

    Klein, Rivka; Bar-On, Elcahnan; Klein, Jacob; Benbenishty, Rami

    2006-05-01

    Sexual dysfunction is one of the severe consequences of acute coronary events. Rehabilitation programs should address this aspect of functioning that has important implications for the patient's quality of life. In order to improve patients' sexual functioning and improve their quality of life we developed a comprehensive model of sexual therapy designed specifically for cardiac patients undergoing rehabilitation program. This model integrates educational, supportive and cognitive-behavioral therapy with appropriate medication (such as viagra). The model is implemented in co-therapy by two sexologists, a social worker and a physician. An empirical study has shown the positive outcomes of this model. This article describes the model and reports case vignettes that exemplify its effects on cardiac patients in rehabilitation and their spouses.

  14. Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

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    Henrique Silveira Costa

    2015-04-01

    Full Text Available INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5 years, and 38 healthy individuals, aged 44.0 (9.2 years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48% than in the control group (23.7% during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease.

  15. Is subclinical gambling really subclinical?

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    Weinstock, Jeremiah; April, Laura M; Kallmi, Selmi

    2017-10-01

    Gambling disorder and substance use disorders (SUD) overlap in terms of etiology and diagnostic constructs (e.g., preoccupation, loss of control), yet diagnostic thresholds for the disorders are different. Currently, endorsing 2-3 gambling disorder criteria does not warrant a diagnosis while endorsing 2-3 SUD criteria does. The aim of this study was to examine whether subclinical gamblers (i.e., endorsing 2-3 gambling disorder criteria) experience psychosocial dysfunction equivalent to individuals who are diagnosed with mild severity SUD (i.e., 2-3 SUD criteria) and whether this level of dysfunction is significantly different from individuals with no psychopathology. Data are from the first wave of Quinte Longitudinal Study, a large epidemiological sample (N=4121). Psychometrically supported measures assessed for psychosocial functioning and the presence of Axis-I psychiatric disorders. Cross-sectional analysis examined 7 domains of psychosocial functioning using ANCOVA, which allowed for the inclusion of covariates, to test for difference between subclinical gamblers and individuals with no psychopathology and individuals with mild severity SUD. Equivalency testing compared subclinical gamblers in relation to mild severity SUD. Subclinical gamblers reported significantly poorer psychosocial functioning in relation to individuals endorsing no current psychopathology. Subclinical gamblers were also equivalent to and not significantly different from individuals with mild severity SUD. Subclinical gamblers experience similar psychosocial impairment to those individuals who endorse mild severity SUD, and this significantly differed from healthy individuals. The threshold for diagnosis of gambling disorder therefore warrants re-examination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Risk factors for transient dysfunction of gas exchange after cardiac surgery

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    Cristiane Delgado Alves Rodrigues

    2015-02-01

    Full Text Available Objective: A retrospective cohort study was preformed aiming to verify the presence of transient dysfunction of gas exchange in the postoperative period of cardiac surgery and determine if this disorder is linked to cardiorespiratory events. Methods: We included 942 consecutive patients undergoing cardiac surgery and cardiac procedures who were referred to the Intensive Care Unit between June 2007 and November 2011. Results: Fifteen patients had acute respiratory distress syndrome (2%, 199 (27.75% had mild transient dysfunction of gas exchange, 402 (56.1% had moderate transient dysfunction of gas exchange, and 39 (5.4% had severe transient dysfunction of gas exchange. Hypertension and cardiogenic shock were associated with the emergence of moderate transient dysfunction of gas exchange postoperatively (P=0.02 and P=0.019, respectively and were risk factors for this dysfunction (P=0.0023 and P=0.0017, respectively. Diabetes mellitus was also a risk factor for transient dysfunction of gas exchange (P=0.03. Pneumonia was present in 8.9% of cases and correlated with the presence of moderate transient dysfunction of gas exchange (P=0.001. Severe transient dysfunction of gas exchange was associated with patients who had renal replacement therapy (P=0.0005, hemotherapy (P=0.0001, enteral nutrition (P=0.0012, or cardiac arrhythmia (P=0.0451. Conclusion: Preoperative hypertension and cardiogenic shock were associated with the occurrence of postoperative transient dysfunction of gas exchange. The preoperative risk factors included hypertension, cardiogenic shock, and diabetes. Postoperatively, pneumonia, ventilator-associated pneumonia, renal replacement therapy, hemotherapy, and cardiac arrhythmia were associated with the appearance of some degree of transient dysfunction of gas exchange, which was a risk factor for reintubation, pneumonia, ventilator-associated pneumonia, and renal replacement therapy in the postoperative period of cardiac surgery and

  17. Overweight and Cardiac Rhythm Disturbances as Burdening Factors of Forming of Subclinical Systemic Inflammatory Response, Imbalance of Carbohydrate and Lipid Metabolism at Bronchial Asthma in Children

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    N.N. Kaladze

    2012-02-01

    Full Text Available Insulin resistance, metabolic syndrome (in whole, imbalance in «oxidants — antioxidants» system and systemic subclinical inflammation including imbalance of cytokine homoeostasis belong to the main pathogenetic points of contact of bronchial asthma, cardiac rhythm disturbances and overweight. Bronchial asthma, overweight and cardiac rhythm disturbances are the factors of mutual burden of each disease course. It requires the differentiated treatment of mentioned polypathy.

  18. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia

    NARCIS (Netherlands)

    van Harten, A. E.; Scheeren, T. W. L.; Absalom, A. R.

    Postoperative cognitive dysfunction is receiving increasing attention, particularly as it mainly affects the (growing) elderly population. Until recently, cognitive deficits after cardiac surgery were thought to be caused by physiological disturbances associated with the cardiopulmonary bypass

  19. Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction

    Science.gov (United States)

    Sy, Jay C.; Seshadri, Gokulakrishnan; Yang, Stephen C.; Brown, Milton; Oh, Teresa; Dikalov, Sergey; Murthy, Niren; Davis, Michael E.

    2008-11-01

    Cardiac dysfunction following acute myocardial infarction is a major cause of death in the world and there is a compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK), improves cardiac function following myocardial infarction. Drug-delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium. PCADK is unique among currently used polymers in drug delivery in that its hydrolysis generates neutral degradation products. We show here that PCADK causes minimal tissue inflammatory response, thus enabling PCADK for the treatment of inflammatory diseases, such as cardiac dysfunction. PCADK holds great promise for treating myocardial infarction and other inflammatory diseases given its neutral, biocompatible degradation products and its ability to deliver a wide range of therapeutics.

  20. Detection of subclinical atherosclerosis and diastolic dysfunction in patients with schizophrenia

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    Ünsal C

    2013-10-01

    Full Text Available Cüneyt Ünsal,1 Mustafa Oran,2 Hande Oktay Tureli,3 Seref Alpsoy,4 Sema Yesilyurt,5 Mehtap Arslan,6 Birol Topcu,7 Osman Karakaya,8 Erhan Kurt6 1Department of Psychiatry, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 2Department of Internal Medicine, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 3Department of Cardiology, Bakirkoy Dr Sadi Konuk Education and Research Hospital, Istanbul, Turkey; 4Department of Cardiology, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 5Department of Psychiatry, Bağcilar Training and Research Hospital, Istanbul, Turkey; 6Department of Psychiatry, Bakirkoy Training and Research Hospital for Psychiatry Neurology and Neurosurgery, Istanbul, Turkey; 7Department of Biostatistics, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 8Department of Social Service, Yalova University, Faculty of Economics and Administrative Sciences, Yalova, Turkey Background: Patients with schizophrenia have a higher risk for cardiovascular diseases, which is associated with early mortality compared with the nonschizophrenic population. Early diagnosis of cardiovascular diseases in asymptomatic periods in patients with schizophrenia would enhance their quality of life and reduce mortality. Echocardiography, carotid ultrasonography, and ankle brachial index (ABI measurement are known to be beneficial methods of detecting subclinical cardiovascular diseases and of risk stratification. The present study investigated carotid intima media thickness (CIMT and ABI and echocardiographic parameters measured via conventional and tissue Doppler echocardiography in patients with schizophrenia in comparison with a control group. Methods: The present case-control study included 116 patients with schizophrenia and 88 healthy patients. Participants with any current comorbid psychiatric disorder, current or lifetime neurological and medical problems, current coronary artery disease, diabetes

  1. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.

    Science.gov (United States)

    Wang, Wei; Zhang, Fuyang; Xia, Yunlong; Zhao, Shihao; Yan, Wenjun; Wang, Helin; Lee, Yan; Li, Congye; Zhang, Ling; Lian, Kun; Gao, Erhe; Cheng, Hexiang; Tao, Ling

    2016-11-01

    Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF. Copyright © 2016 the American Physiological Society.

  2. Overt and Subclinical Baroreflex Dysfunction After Bilateral Carotid Body Tumor Resection: Pathophysiology, Diagnosis, and Implications for Management.

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    Ghali, Michael G Z; Srinivasan, Visish M; Hanna, Ehab; DeMonte, Franco

    2017-05-01

    Carotid body paragangliomas are rare, usually benign, tumors arising from glomus cells of the carotid body. Bilateral involvement is present in ∼5% of sporadic cases and up to one third of familial cases. In most patients undergoing bilateral resection of carotid body tumors, a condition known as baroreflex failure syndrome (BFS) develops after resection of the second tumor characterized by headache, anxiety, emotional lability, orthostatic lightheadedness, hypertension, and tachycardia. This condition is believed to result from damage to the carotid baroreceptor apparatus. Patients without overt cardiovascular abnormalities may have subclinical baroreceptor dysfunction evident only on specific testing, measuring heart rate and sympathetic nerve responses to baroloading (e.g., phenylephrine) and barounloading (e.g., Valsalva maneuver). Given the high incidence of BFS in patients undergoing bilateral resection of carotid body tumors, it is suggested that operation is limited to unilateral resection of the dominant/symptomatic lesion and nonsurgical intervention (i.e., embolization, radiotherapy) on the contralateral side. Alternatively, refinement of surgical technique to prevent injury to elements of the baroreceptor apparatus may prevent this complication of bilateral tumor resection. We present a case of a 16-year-old girl with bilateral jugular vagale and carotid body tumors who developed hypertension after surgical resection of her left jugular vagale tumor and worsening of hypertension concurrent with progression, requiring intensity-modulated radiation therapy and a resection for significant progression of her left jugular vagale tumor. Additional case studies and series of bilateral carotid body tumors and BFS were identified through a comprehensive literature search in the PubMed database. Our case shows the generalizability of BFS to patients with tumors involving the vagal baroafferent fibers. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Self-reported sleep duration and napping, cardiac risk factors and markers of subclinical vascular disease: cross-sectional study in older men.

    Science.gov (United States)

    Zonoozi, Shahrzad; Ramsay, Sheena E; Papacosta, Olia; Lennon, Lucy; Ellins, Elizabeth A; Halcox, Julian P J; Whincup, Peter H; Goya Wannamethee, S

    2017-07-02

    Daytime sleep has been associated with increased risk of cardiovascular disease and heart failure (HF), but the mechanisms remain unclear. We have investigated the association between daytime and night-time sleep patterns and cardiovascular risk markers in older adults including cardiac markers and subclinical markers of atherosclerosis (arterial stiffness and carotid intima-media thickness (CIMT)). Cross-sectional study of 1722 surviving men aged 71-92 examined in 2010-2012 across 24 British towns from a prospective study initiated in 1978-1980. Participants completed a questionnaire and were invited for a physical examination. Men with a history of heart attack or HF (n=251) were excluded from the analysis. Self-reported daytime sleep duration was associated with higher fasting glucose and insulin levels (p=0.02 and p=0.01, respectively) even after adjustment for age, body mass index, physical activity and social class. Compared with those with no daytime sleep, men with daytime sleep >1 hour, defined as excessive daytime sleepiness (EDS), had a higher risk of raised N-terminal pro-brain natriuretic peptide of ≥400 pg/mL, the diagnostic threshold for HF (OR (95% CI)=1.88 (1.15 to 3.1)), higher mean troponin, reduced lung function (forced expiratory volume in 1 s) and elevated von Willebrand factor, a marker of endothelial dysfunction. However, EDS was unrelated to CIMT and arterial stiffness. By contrast, night-time sleep was only associated with HbA1c (short or long sleep) and arterial stiffness (short sleep). Daytime sleep duration of >1 hour may be an early indicator of HF. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. 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

  5. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    LENUS (Irish Health Repository)

    Phelan, Dermot

    2012-11-01

    In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g\\/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  6. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    Directory of Open Access Journals (Sweden)

    Dermot Phelan

    Full Text Available In asymptomatic subjects B-type natriuretic peptide (BNP is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS and peripheral serum from patients with low (n = 14 and high BNP (n = 27. Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001. CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008, CITP (r = 0.35, p = 0.03 and PIIINP (r = 0.35, p = 0.001, and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002, IL-6 (r = 0.35, p = 0.04, and IL-8 (r = 0.54, p<0.001. The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007, TNF-α (3.2±0.5 versus 3.7±1.1, p = 003, IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02 and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04, and greater left ventricular mass index (97±20 versus 118±26 g/m(2, p = 0.03 and left atrial volume index (18±2 versus 21±4, p = 0.008. Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  7. Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

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    Luiz Fernando Junqueira Junior

    2012-04-01

    Full Text Available INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

  8. Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease.

    Science.gov (United States)

    Junqueira, Luiz Fernando

    2012-01-01

    Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

  9. Cardiac desmosomal (dys)function and myocyte viability

    NARCIS (Netherlands)

    Remme, Carol Ann; Bezzina, Connie R.

    2010-01-01

    Cardiac desmosomes form intercellular junctions at the boundaries of intercalated discs between neighboring cardiomyocytes and are essential for proper cell-to-cell coupling between cardiomyocytes and for normal mechanical and electrical function of myocardial tissue. Genetic mutations in desmosomal

  10. Assessment of Subclinical Left Ventricular Dysfunction in Patients with Chronic Mitral Regurgitation Using Torsional Parameters Described by Tissue Doppler Imaging

    Directory of Open Access Journals (Sweden)

    Zahra Ojaghi-Haghighi

    2015-10-01

    Full Text Available Background: Left ventricular (LV twist is due to oppositely directed apical and basal rotation and has been proposed as a sensitive marker of LV function. We sought to assess the impact of chronic pure mitral regurgitation (MR on the torsional mechanics of the left human ventricle using tissue Doppler imaging.Methods: Nineteen severe MR patients with a normal LV ejection fraction and 16 non-MR controls underwent conventional echocardiography and apical and basal short-axis color Doppler myocardial imaging (CDMI. LV rotation at the apical and basal short-axis levels was calculated from the averaged tangential velocities of the septal and lateral regions, corrected for the LV radius over time. LV twist was defined as the difference in LV rotation between the two levels, and the LV twist and twisting/untwisting rate profiles were analyzed throughout the cardiac cycle.Results: LV twist and LV torsion were significantly lower in the MR group than in the non-MR group (10.38˚ ± 4.04˚ vs.13.95˚ ± 4.27˚; p value = 0.020; and 1.29 ± 0.54 ˚/cm vs. 1.76 ± 0.56 ˚/cm; p value = 0.021, respectively, both suggesting incipient LV dysfunction in the MR group. Similarly, the untwisting rate was lower in the MR group (-79.74 ± 35.97 ˚/s vs.-110.96 ± 34.65 ˚/s; p value = 0.020, but there was statistically no significant difference in the LV twist rate.Conclusion: The evaluation of LV torsional parameters in MR patients with a normal LV ejection fraction suggests the potential role of these sensitive variables in assessing the early signs of ventricular dysfunction in asymptomatic patients

  11. Preoperative therapy with amiodarone and the incidence of acute organ dysfunction after cardiac surgery.

    Science.gov (United States)

    Rady, M Y; Ryan, T; Starr, N J

    1997-09-01

    We examined the influence of preoperative therapy with amiodarone on the incidence of acute organ dysfunction after cardiac surgery in a matched case-control study. There were 220 case-control pairs matched by day of surgery, source of admission, demographic characteristics, placement of intraaortic balloon pump before surgery, repeat operations, emergency surgery, thoracic aorta surgery and other surgical procedures. History of congestive heart failure was more prevalent in the amiodarone group than in the control group before surgery (60% vs 38%, P amiodarone group. However, the difference was not significant after adjustment for congestive heart failure (Cochran-Mantel-Haenszel test P = 0.15, P = 0.25, P = 0.16, respectively). Amiodarone did not increase the incidence of acute organ dysfunction or death after cardiac surgery. The requirement for inotropes and vasopressors and the incidence of nosocomial infections were related to the severity of the underlying cardiac disease. The practice of discontinuing amiodarone treatment before surgery to reduce the incidence of postoperative organ dysfunction should be critically reevaluated. Amiodarone is often used for the treatment of life-threatening rhythm disorder. Amiodarone has been blamed for causing organ injury after cardiac surgery. In a study of 220 patients, amiodarone did not increase the risk of organ injury or death after cardiac surgery when compared with control patients. There was no evidence to support the practice of stopping amiodarone before cardiac surgery to avoid serious complications.

  12. Transient cardiac dysfunction but elevated cardiac and kidney biomarkers 24 h following an ultra-distance running event in Mexican Tarahumara

    DEFF Research Database (Denmark)

    Christensen, Dirk L.; Espino, Diana; Infante-Ramirez, Rocio

    2017-01-01

    parameters), cardiac output (39%, p copeptin-ultra sensitive, and high-sensitivity cardiac...... troponin T remained significantly elevated at 24 h post-race, and the two latter were inversely associated with LVEF (p copeptin-ultra sensitive. Conclusions: The athletes participating in this study had acute transient cardiac dysfunction...

  13. Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

    Science.gov (United States)

    Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

    2009-01-01

    Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

  14. Right ventricular dysfunction after cardiac surgery - diagnostic options

    DEFF Research Database (Denmark)

    Grønlykke, Lars; Ravn, Hanne Berg; Gustafsson, Finn

    2017-01-01

    Right ventricular (RV) failure after cardiac surgery is associated with an ominous prognosis. The etiology of RV failure is multifaceted and the ability to recognize RV failure early is paramount in order to initiate timely treatment. The present review focuses on different diagnostic modalities...

  15. Inflammatory mediators in diet-induced cardiac dysfunction

    NARCIS (Netherlands)

    Louwe, Maria Cornelia (Mieke)

    2013-01-01

    The studies in this thesis are performed to provide additional and improved insight into the effects and interplay of dietary lipids and metabolic inflammation on cardiac performance in the presence or absence of atherosclerosis and myocardial infarctions (MI). We show that high-fat diet feeding has

  16. Cardiac hypertrophy and dysfunction induced by overexpression of miR-214 in vivo.

    Science.gov (United States)

    Yang, Tao; Gu, Haihua; Chen, Xiaofan; Fu, Shaozhi; Wang, Cheng; Xu, Hongfei; Feng, Qiang; Ni, Yiming

    2014-12-01

    An increasing number of studies have demonstrated the critical role of microRNAs in the pathogenesis of cardiac hypertrophy and dysfunction. This study evaluated whether miR-214 plays a pivotal role in the development of cardiac hypertrophy and heart failure. In human tissues, miR-214 overexpression was determined to promote cardiac hypertrophy. We predicted miR-214 direct target by bioinformatics database and verifed it using luciferase dual reporting system. We silenced miR-214 using a specific antagomir in a pressure-overload mouse model of heart failure. Analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-214 indicated that their hearts were 21% heavier than wild-type hearts and expressed several biochemical and functional markers consistent with dilated cardiomyopathy. These findings include enlarged left ventricular internal diameters, wall thinning, reduced ejection fraction, fractional shortening, and an increased fetal gene expression. The enhancer of zeste homolog 2 (EZH2) was confirmed as a direct target of miR-214 in cardiomyocytes. In vivo silencing of miR-214 using a specific antagomir rescued cardiac EZH2 expression and prevented cardiac hypertrophy and dysfunction. Taken together, these results suggest that miR-214 may induce pathologic cardiac hypertrophy in part by reducing EZH2 messenger RNA levels. MiR-214 may therefore be a potential therapeutic target for treating certain cardiac disease states. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery.

    Science.gov (United States)

    Mehta, Rajendra H; Leimberger, Jeffrey D; van Diepen, Sean; Meza, James; Wang, Alice; Jankowich, Rachael; Harrison, Robert W; Hay, Douglas; Fremes, Stephen; Duncan, Andra; Soltesz, Edward G; Luber, John; Park, Soon; Argenziano, Michael; Murphy, Edward; Marcel, Randy; Kalavrouziotis, Dimitri; Nagpal, Dave; Bozinovski, John; Toller, Wolfgang; Heringlake, Matthias; Goodman, Shaun G; Levy, Jerrold H; Harrington, Robert A; Anstrom, Kevin J; Alexander, John H

    2017-05-25

    Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a

  18. High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker.

    Science.gov (United States)

    Choi, He Yun; Park, Ji Hye; Jang, Woong Bi; Ji, Seung Taek; Jung, Seok Yun; Kim, Da Yeon; Kang, Songhwa; Kim, Yeon Ju; Yun, Jisoo; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang-Mo

    2016-07-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.

  19. Cardiac magnetic resonance markers of progressive RV dilation and dysfunction after tetralogy of Fallot repair

    NARCIS (Netherlands)

    Wald, Rachel M.; Valente, Anne Marie; Gauvreau, Kimberlee; Babu-Narayan, Sonya V.; Assenza, Gabriele Egidy; Schreier, Jenna; Gatzoulis, Michael A.; Kilner, Philip J.; Koyak, Zeliha; Mulder, Barbara; Powell, Andrew J.; Geva, Tal

    2015-01-01

    Patients with repaired tetralogy of Fallot (TOF) are followed serially by cardiac magnetic resonance (CMR) for surveillance of RV dilation and dysfunction. We sought to define the prevalence of progressive RV disease and the optimal time interval between CMR evaluations. Candidates were selected

  20. Exercise training prior to myocardial infarction attenuates cardiac deterioration and cardiomyocyte dysfunction in rats.

    Science.gov (United States)

    Bozi, Luiz Henrique Marchesi; Maldonado, Izabel Regina dos Santos Costa; Baldo, Marcelo Perim; Silva, Márcia Ferreira da; Moreira, José Bianco Nascimento; Novaes, Rômulo Dias; Ramos, Regiane Maria Soares; Mill, José Geraldo; Brum, Patricia Chakur; Felix, Leonardo Bonato; Gomes, Thales Nicolau Prímola; Natali, Antônio José

    2013-04-01

    The present study was performed to investigate 1) whether aerobic exercise training prior to myocardial infarction would prevent cardiac dysfunction and structural deterioration and 2) whether the potential cardiac benefits of aerobic exercise training would be associated with preserved morphological and contractile properties of cardiomyocytes in post-infarct remodeled myocardium. Male Wistar rats underwent an aerobic exercise training protocol for eight weeks. The rats were then assigned to sham surgery (SHAM), sedentary lifestyle and myocardial infarction or exercise training and myocardial infarction groups and were evaluated 15 days after the surgery. Left ventricular tissue was analyzed histologically, and the contractile function of isolated myocytes was measured. Student's t-test was used to analyze infarct size and ventricular wall thickness, and the other parameters were analyzed by the Kruskal-Wallis test followed by Dunn's test or a one-way analysis of variance followed by Tukey's test (pmyocardial infarction extension, a thicker infarcted wall and less collagen accumulation as compared to myocardial infarctions in sedentary animals. Myocardial infarction-induced left ventricular dilation and cardiac dysfunction, as evaluated by +dP/dt and -dP/dt, were both prevented by previous aerobic exercise training. Moreover, aerobic exercise training preserved cardiac myocyte shortening, improved the maximum shortening and relengthening velocities in infarcted hearts and enhanced responsiveness to calcium. Previous aerobic exercise training attenuated the cardiac dysfunction and structural deterioration promoted by myocardial infarction, and such benefits were associated with preserved cardiomyocyte morphological and contractile properties.

  1. Longitudinal Association Between Endothelial Dysfunction, Inflammation, and Clotting Biomarkers With Subclinical Atherosclerosis in Type 1 Diabetes: An Evaluation of the DCCT/EDIC Cohort.

    Science.gov (United States)

    Hunt, Kelly J; Baker, Nathaniel L; Cleary, Patricia A; Klein, Richard; Virella, Gabriel; Lopes-Virella, Maria F

    2015-07-01

    There is considerable interest in identifying biomarkers that predict high risk for the development of macrovascular complications in patients with diabetes. Therefore, the longitudinal association between subclinical atherosclerosis as measured by internal carotid artery intima-media thickness (IMT) and acute-phase reactants, cytokines/adipokines, thrombosis, and adhesion molecules was examined. Biomarkers were measured at four time points over 20 years in 886 DCCT/EDIC participants with type 1 diabetes. Four composite scores were created by combining z scores generated from within the data set of individual biomarkers: acute-phase reactants (fibrinogen, C-reactive protein), thrombosis (fibrinogen, active and total plasminogen activator inhibitor [PAI]-1), cytokines/adipokines (tumor necrosis factor receptor-1 and -2, active and total PAI-1, IL-6), and endothelial dysfunction (soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble E-selectin). Internal carotid IMT was measured at EDIC years 1, 6, and 12, with elevated IMT defined at each time point as being in the upper quintile of its distribution. Logistic regression models indicate that while individual biomarkers were not predictive of or associated with subclinical atherosclerosis, composite scores of acute-phase reactants (odds ratio [OR] 2.78 [95% CI 1.42, 5.42]), thrombolytic factors (OR 2.83 [95% CI 1.45, 5.52]), and cytokines/adipokines (OR 2.83 [95% CI 1.48, 5.41]) measured at our final time point EDIC years 8-11 were associated with higher levels of atherosclerosis at EDIC year 12, but findings were not consistent at early time points. The endothelial dysfunction score was not appreciably predictive of or associated with subclinical atherosclerosis at any of the time points measured. The pathophysiologic relationship between higher biomarker levels and progression of subclinical atherosclerosis remains unclear. © 2015 by the American Diabetes Association

  2. Cardiac Potassium Channel Dysfunction in Sudden Infant Death Syndrome

    OpenAIRE

    Rhodes, Troy E.; Abraham, Robert A.; Welch, Richard C.; Vanoye, Carlos G.; Crotti, Lia; Arnestad, Marianne; Insolia, Roberto; Pedrazzini, Matteo; Ferrandi, Chiara; Vege, Ashild; Rognum, Torleiv; Roden, Dan M.; Schwartz, Peter J.; George, Alfred L.

    2007-01-01

    Life-threatening arrhythmias have been suspected as one cause of the sudden infant death syndrome (SIDS), and this hypothesis is supported by the observation that mutations in arrhythmia susceptibility genes occur in 5–10% of cases. However, the functional consequences of cardiac potassium channel gene mutations associated with SIDS and how these alleles might mechanistically predispose to sudden death are unknown. To address these questions, we studied four missense KCNH2 (encoding HERG) var...

  3. Exercise ameliorates high fat diet induced cardiac dysfunction by increasing interleukin 10.

    Science.gov (United States)

    Kesherwani, Varun; Chavali, Vishalakshi; Hackfort, Bryan T; Tyagi, Suresh C; Mishra, Paras K

    2015-01-01

    Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming 1 h/day for 5 days/week for 8 weeks). The four treatment groups: normal diet (ND), HFD, HFD + exercise (HFD + Ex) and ND + Ex were analyzed for mean body weight, blood glucose level, TNF-α, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction by echocardiography. Mean body weights were increased in HFD but comparatively less in HFD + Ex. The level of TNF-α was elevated and IL-10 was downregulated in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was attenuated by exercise in the HFD + Ex group. The percentage ejection fraction and fractional shortening were decreased in HFD but comparatively increased in HFD + Ex. There was no difference between ND and ND + Ex for the above parameters except an increase in IL-10 level following exercise. Based on these results, we conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing obesity, inducing IL-10, and reducing TNF-α in mice.

  4. Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction by Increasing Interleukin 10

    Directory of Open Access Journals (Sweden)

    Varun eKesherwani

    2015-04-01

    Full Text Available Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α and attenuation of anti-inflammatory cytokine such as interleukin10 (IL-10 contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, eight week old, female C57BL/6J mice were fed with HFD and exercised (swimming 1hr/day for 5 days/week for eight weeks. The four treatment groups: normal diet (ND, HFD, HFD + exercise (HFD + Ex and ND + Ex were analyzed for mean body weight, blood glucose level, TNF-α, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction by echocardiography. Mean body weights were increased in HFD but comparatively less in HFD + Ex. The level of TNF-α was elevated and IL-10 was downregulated in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was attenuated by exercise in the HFD + Ex group. The percentage ejection fraction and fractional shortening were decreased in HFD but comparatively increased in HFD + Ex. There was no difference between ND and ND + Ex for the above parameters except an increase in IL-10 level following exercise. Based on these results, we conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing obesity, inducing IL-10, and reducing TNF-α in mice.

  5. Prevalence of myocardial fibrosis patterns in patients with systolic dysfunction: prognostic significance for the prediction of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.

    Science.gov (United States)

    Almehmadi, Fahad; Joncas, Sebastien Xavier; Nevis, Immaculate; Zahrani, Mohammad; Bokhari, Mahmoud; Stirrat, John; Fine, Nowell M; Yee, Raymond; White, James A

    2014-07-01

    Late gadolinium enhancement-cardiac magnetic resonance is increasingly performed in patients with systolic dysfunction. Numerous patterns of fibrosis are commonly reported among this population. However, the relative prevalence and prognostic significance of these findings remains uncertain. Three hundred eighteen consecutive patients referred for late gadolinium enhancement-cardiac magnetic resonance and a left ventricular ejection fraction 35% (40% versus 6%; P=0.005). Patients with systolic dysfunction frequently demonstrate multiple patterns of myocardial fibrosis. Of these, a midwall striae pattern of fibrosis is the strongest independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy. © 2014 American Heart Association, Inc.

  6. Genistein alleviates pressure overload-induced cardiac dysfunction and interstitial fibrosis in mice.

    Science.gov (United States)

    Qin, Wei; Du, Ning; Zhang, Longyin; Wu, Xianxian; Hu, Yingying; Li, Xiaoguang; Shen, Nannan; Li, Yang; Yang, Baofeng; Xu, Chaoqian; Fang, Zhiwei; Lu, Yanjie; Zhang, Yong; Du, Zhimin

    2015-12-01

    Pressure overload-induced cardiac interstitial fibrosis is viewed as a major cause of heart failure in patients with hypertension or aorta atherosclerosis. The purpose of this study was to investigate the effects and the underlying mechanisms of genistein, a natural phytoestrogen found in soy bean extract, on pressure overload-induced cardiac fibrosis. Genisten was administered to mice with pressure overload induced by transverse aortic constriction. Eight weeks later, its effects on cardiac dysfunction, hypertrophy and fibrosis were determined. Its effects on proliferation, collagen production and myofibroblast transformation of cardiac fibroblasts (CFs) and the signalling pathways were also assessed in vitro. Pressure overload-induced cardiac dysfunction, hypertrophy and fibrosis were markedly attenuated by genistein. In cultured CFs, genistein inhibited TGFβ1-induced proliferation, collagen production and myofibroblast transformation. Genistein suppressed TGFβ-activated kinase 1 (TAK1) expression and produced anti-fibrotic effects by blocking the TAK1/MKK4/JNK pathway. Further analysis indicated that it up-regulated oestrogen-dependent expression of metastasis-associated gene 3 (MTA3), which was found to be a negative regulator of TAK1. Silencing MTA3 by siRNA, or inhibiting the activity of the MTA3-NuRD complex with trichostatin A, abolished genistein's anti-fibrotic effects. Genistein improved cardiac function and inhibited cardiac fibrosis in response to pressure overload. The underlying mechanism may involve regulation of the MTA3/TAK1/MKK4/JNK signalling pathway. Genistein may have potential as a novel agent for prevention and therapy of cardiac disorders associated with fibrosis. © 2014 The British Pharmacological Society.

  7. Cardiac autonomic dysfunction in obese normotensive children and adolescents

    Directory of Open Access Journals (Sweden)

    Isabelle Magalhães G. Freitas

    2014-06-01

    Full Text Available OBJECTIVE:To test the hypothesis that obese normotensive children and adolescents present impaired cardiac autonomic control compared to non-obese normotensive ones.METHODS:For this cross-sectional study, 66 children and adolescents were divided into the following groups: Obese (n=31, 12±3 years old and Non-Obese (n=35, 13±3 years old. Obesity was defined as body mass index greater than the 95thpercentile for age and gender. Blood pressure was measured by oscillometric method after 15 minutes of rest in supine position. The heart rate was continuously registered during ten minutes in the supine position with spontaneous breathing. The cardiac autonomic control was assessed by heart rate variability, which was calculated from the five-minute minor variance of the signal. The derivations were the index that indicates the proportion of the number of times in which normal adjacent R-R intervals present differences >50 miliseconds (pNN50, for the time domain, and, for the spectral analysis, low (LF and high frequency (HF bands, besides the low and high frequencies ratio (LF/HF. The results were expressed as mean±standard deviation and compared by Student's t-test or Mann-Whitney's U-test.RESULTS: Systolic blood pressure (116±14 versus 114±13mmHg, p=0.693 and diastolic blood pressure (59±8 versus 60±11mmHg, p=0.458 were similar between the Obese and Non-Obese groups. The pNN50 index (29±21 versus 43±23, p=0.015 and HF band (54±20 versus 64±14 normalized units - n.u., p=0.023 were lower in the Obese Group. The LF band (46±20 versus 36±14 n.u., p=0.023 and LF/HF ratio (1.3±1.6 versus 0.7±0.4, p=0.044 were higher in Obese Group.CONCLUSIONS: Obese normotensive children and adolescents present impairment of cardiac autonomic control.

  8. Mitochondrial polymerase gamma dysfunction and aging cause cardiac nuclear DNA methylation changes.

    Science.gov (United States)

    Koczor, Christopher A; Ludlow, Ivan; Fields, Earl; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Lewis, William

    2016-04-01

    Cardiomyopathy (CM) is an intrinsic weakening of myocardium with contractile dysfunction and congestive heart failure (CHF). CHF has been postulated to result from decreased mitochondrial energy production and oxidative stress. Effects of decreased mitochondrial oxygen consumption also can accelerate with aging. We previously showed DNA methylation changes in human hearts with CM. This was associated with mitochondrial DNA depletion, being another molecular marker of CM. We examined the relationship between mitochondrial dysfunction and cardiac epigenetic DNA methylation changes in both young and old mice. We used genetically engineered C57Bl/6 mice transgenic for a cardiac-specific mutant of the mitochondrial polymerase-γ (termed Y955C). Y955C mice undergo left ventricular hypertrophy (LVH) at a young age (∼ 94 days old), and LVH decompensated to CHF at old age (∼ 255 days old). Results found 95 genes differentially expressed as a result of Y955C expression, while 4,452 genes were differentially expressed as a result of aging hearts. Moreover, cardiac DNA methylation patterns differed between Y955C (4,506 peaks with 68.5% hypomethylation) and aged hearts (73,286 peaks with 80.2% hypomethylated). Correlatively, of the 95 Y955C-dependent differentially expressed genes, 30 genes (31.6%) also displayed differential DNA methylation; in the 4,452 age-dependent differentially expressed genes, 342 genes (7.7%) displayed associated DNA methylation changes. Both Y955C and aging demonstrated significant enrichment of CACGTG-associated E-box motifs in differentially methylated regions. Cardiac mitochondrial polymerase dysfunction alters nuclear DNA methylation. Furthermore, aging causes a robust change in cardiac DNA methylation that is partially associated with mitochondrial polymerase dysfunction. Copyright © 2016 the American Physiological Society.

  9. Cardiac Potassium Channel Dysfunction in Sudden Infant Death Syndrome

    Science.gov (United States)

    Rhodes, Troy E.; Abraham, Robert A.; Welch, Richard C.; Vanoye, Carlos G.; Crotti, Lia; Arnestad, Marianne; Insolia, Roberto; Pedrazzini, Matteo; Ferrandi, Chiara; Vege, Ashild; Rognum, Torleiv; Roden, Dan M.; Schwartz, Peter J.; George, Alfred L.

    2008-01-01

    Life-threatening arrhythmias have been suspected as one cause of the sudden infant death syndrome (SIDS), and this hypothesis is supported by the observation that mutations in arrhythmia susceptibility genes occur in 5–10% of cases. However, the functional consequences of cardiac potassium channel gene mutations associated with SIDS and how these alleles might mechanistically predispose to sudden death are unknown. To address these questions, we studied four missense KCNH2 (encoding HERG) variants, one compound KCNH2 genotype, and a missense KCNQ1 mutation all previously identified in Norwegian SIDS cases. Three of the six variants exhibited functional impairments while three were biophysically similar to wild-type channels (KCNH2 variants V279M, R885C, S1040G). When coexpressed with WT-HERG, R273Q and K897T/R954C generated currents resembling the rapid component of the cardiac delayed rectifier current (IKr) but with significantly diminished amplitude. Action potential modeling demonstrated that this level of functional impairment was sufficient to evoke increased action potential duration and pause-dependent early afterdepolarizations. By contrast, KCNQ1-I274V causes a gain-of-function in IKs characterized by increased current density, faster activation, and slower deactivation leading to accumulation of instantaneous current upon repeated stimulation. Action potential simulations using a Markov model of heterozygous I274V-IKs incorporated into the Luo-Rudy (LRd) ventricular cell model demonstrated marked rate-dependent shortening of action potential duration predicting a short QT phenotype. Our results indicate that certain potassium channel mutations associated with SIDS confer overt functional defects consistent with either LQTS or SQTS, and further emphasize the role of congenital arrhythmia susceptibility in this syndrome. PMID:18222468

  10. Subclinical left ventricular systolic dysfunction in patients with metabolic syndrome: A case-control study using two-dimensional speckle tracking echocardiography.

    Science.gov (United States)

    Moaref, Alireza; Faraji, Majid; Tahamtan, Maryam

    2016-11-01

    The dramatic increase in the prevalence of metabolic syndrome is associated with more increased cardiovascular morbidity and mortality in this group. Some recent studies suggested that metabolic syndrome is associated with increased risk of subclinical left ventricular (LV) systolic dysfunction. In the present cross-sectional case-control study, the utility of two-dimensional speckle tracking echocardiography (STE) was examined to detect early LV systolic dysfunction in this population. A total of 75 clinically asymptomatic subjects with left ventricular ejection fraction (LVEF) ≥ 55%, 39 without metabolic syndrome and 36 with metabolic syndrome, matched for gender and age, were enrolled in this case-control study. Metabolic syndrome was diagnosed using the National Cholesterol Education Program/Adult Treatment Panel III criteria. LV systolic function was assessed by STE-derived global and segmental longitudinal strain (εLL). Global εLL was significantly lower in patients with metabolic syndrome compared with normal population (-18.41 ± 2.20% vs. -21.2 ± 2.1%, P metabolic syndrome in comparison to control group except for basal anteroseptal (-19.95 ± 2.90% vs. -21.15 ± 3.30%, P = 0.106), basal anterolateral (-17.5 ± 5.0% vs. -18.3 ± 4.1%, P = 0.437), and basal inferolateral segments (-18.1 ± 6.3% vs. -18.9 ± 4.1%, P = 0.526). STE-derived longitudinal LV strain (εLL), a marker of subclinical cardiovascular disease, is impaired in asymptomatic individuals with metabolic syndrome and normal LVEF.

  11. Cardio-oncology Related to Heart Failure: Pediatric Considerations for Cardiac Dysfunction.

    Science.gov (United States)

    Rose-Felker, Kirsten; Border, William L; Hong, Borah J; Chow, Eric J

    2017-04-01

    Although tremendous advances in pediatric cancer treatment have improved the survival of many children, these patients remain at increased risk of early morbidity and mortality with cardiovascular disease as a leading cause of death. Heightened awareness in providers with increased surveillance and improvement in cardiovascular imaging modalities have led to earlier detection of cardiac dysfunction, but the outcomes remain poor once this has dysfunction developed. A great deal of work remains to be done to refine screening and identify high-risk patients more precisely, and to develop more evidence-based strategies for effective primary and secondary cardioprotection and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Discriminating between cardiac and pulmonary dysfunction in the general population with dyspnea by plasma pro-B-type natriuretic peptide

    DEFF Research Database (Denmark)

    Mogelvang, R; Goetze, JP; Schnohr, P

    2007-01-01

    OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac...... with dyspnea, left ventricular hypertrophy and/or systolic dysfunction was associated with a 2.6-fold increase in plasma proBNP concentration (p ...% to 17%). CONCLUSIONS: In the general population with dyspnea, plasma proBNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction, but are unaffected by pulmonary dysfunction....

  13. Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

    Science.gov (United States)

    Maslow, Andrew D; Chaudrey, Alyas; Bert, Arthur; Schwartz, Carl; Singh, Arun

    2008-02-01

    The administration of aprotinin to patients with pre-existing renal dysfunction who are undergoing cardiac surgery is controversial. Therefore, the authors present their experience with the use of aprotinin for patients with preoperative renal dysfunction who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB). Retrospective analysis. University hospital. Consecutive cardiac surgical patients with preoperative serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery requiring CPB. None. One hundred twenty-three patients either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as decided by the attending anesthesiologist and surgeon. Data were collected from the Society of Thoracic Surgeons database and from automated intraoperative anesthesia records. Renal function was assessed from measured serum creatinine (SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal dysfunction was defined as a worsening of perioperative renal function by > or =25% and/or the need for hemodialysis (HD). Data were recorded as mean and standard deviation or percentage of population depending on whether the data were continuous or not. Data were compared by using an analysis of variance, chi-square analysis, Student paired and unpaired t tests, Fisher exact test, Wilcoxon rank sum test, and Mann-Whitney U test. A p value or =3 months after surgery was significantly lower in the aprotinin group compared with the EACA group (1.8 v 2.2 mg/dL, p < 0.05). Acute perioperative renal dysfunction was associated with worse patient outcome and longer CPB and AoXCl times. Demographic and surgical variables indicated that the sicker patients undergoing more complex surgeries were more likely to be treated with aprotinin. Although aprotinin patients had a higher renal risk score, the administration of aprotinin did not negatively impact renal outcome.

  14. Electrophysiological basis of metabolic-syndrome-induced cardiac dysfunction.

    Science.gov (United States)

    Okatan, Esma N; Durak, Aysegul Toy; Turan, Belma

    2016-10-01

    Myocardial contractility is controlled by intracellular Ca2+ cycling with the contribution of sarcoplasmic reticulum (SR). In this study, we aimed to investigate the role of altered SR function in defective regulation of intracellular Ca2+ levels in rats with metabolic syndrome (MetS) induced by a 16-week high-sucrose drinking-water diet. Electric-field stimulated transient intracellular Ca2+ changes in MetS cardiomyocytes exhibited significantly reduced amplitude (∼30%) and prolonged time courses (2-fold), as well as depressed SR Ca2+ loading (∼55%) with increased basal Ca2+ level. Consistent with these data, altered ryanodine receptor (RyR2) function and SERCA2a activity were found in MetS cardiomyocytes through Ca2+ spark measurements and caffeine application assay in a state in which sodium calcium exchanger was inhibited. Furthermore, tetracaine application assay results and hyperphosphorylated level of RyR2 also support the "leaky RyR2" hypothesis. Moreover, altered phosphorylation levels of phospholamban (PLN) support the depressed SERCA2a-activity thesis and these alterations in the phosphorylation of Ca2+-handling proteins are correlated with altered protein kinase and phosphatase activity in MetS cardiomyocytes. In conclusion, MetS-rat heart exhibits altered Ca2+ signaling largely due to altered SR function via changes in RyR2 and SERCA2a activity. These results point to RyR2 and SERCA2a as potential pharmacological targets for restoring intracellular Ca2+ homeostasis and, thereby, combatting dysfunction in MetS-rat heart.

  15. Preservation of CGRP in myocardium attenuates development of cardiac dysfunction in diabetic rats.

    Science.gov (United States)

    Sun, Tao; Guo, Zheng; Liu, Chao-Jie; Li, Mu-Rong; Li, Tu-Ping; Wang, Xin; Yuan, Da-Jiang

    2016-10-01

    Calcitonin gene-related peptide (CGRP) plays an important role in cardiovascular regulation, which was found reduced in serum of diabetic patients. To test the hypothesis that lack of CGRP in myocardium is associated with diabetic cardiac dysfunction, which may be improved by preservation of CGRP in diabetic rats. Diabetes was induced in male Sprague-Dawley rats by streptozotocin (50mg/kg). Two groups of the diabetic rats, one fed with standard laboratory chew and another with the laboratory food plus hot pepper (containing 0.0174% of capsaicin), to stimulate production and release of CGRP. Cardiac functions were evaluated by measurements of intraventricular pressures after 8weeks of development of diabetes. Transient receptor potential vanilloid type 1 (TRPV1), CGRP, β1-adreneregic receptor and norepinephrine were analyzed. Significantly lower levels of TRPV1 and CGRP were detected in the thoracic dorsal root ganglia (DRG) and myocardium of the diabetic animals, along with significant decline in left ventricular systolic pressure (by 24%) and heart rate (by 25%) and increase of the end-diastolic pressure (by 83%) with obvious reduction of CGRP in the DRG, by 41%, the myocardium (by 30%) and the serum (by 20%). The cardiac performance, the TRPV1 and the CGRP in the diabetic animals fed with hot pepper were well preserved. No any significant change in β1-adreneregic receptor and norepinephrine was detected. The findings may suggest a novel mechanism underlying diabetic cardiac dysfunctions via impairing TRPV1-CGRP pathway in myocardium. Preservation of the TRPV1-CGRP mechanism may prevent the development of cardiac dysfunction in diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Exercise training prior to myocardial infarction attenuates cardiac deterioration and cardiomyocyte dysfunction in rats

    Directory of Open Access Journals (Sweden)

    Luiz Henrique Marchesi Bozi

    2013-04-01

    Full Text Available OBJECTIVES: The present study was performed to investigate 1 whether aerobic exercise training prior to myocardial infarction would prevent cardiac dysfunction and structural deterioration and 2 whether the potential cardiac benefits of aerobic exercise training would be associated with preserved morphological and contractile properties of cardiomyocytes in post-infarct remodeled myocardium. METHODS: Male Wistar rats underwent an aerobic exercise training protocol for eight weeks. The rats were then assigned to sham surgery (SHAM, sedentary lifestyle and myocardial infarction or exercise training and myocardial infarction groups and were evaluated 15 days after the surgery. Left ventricular tissue was analyzed histologically, and the contractile function of isolated myocytes was measured. Student's t-test was used to analyze infarct size and ventricular wall thickness, and the other parameters were analyzed by the Kruskal-Wallis test followed by Dunn's test or a one-way analysis of variance followed by Tukey's test (p<0.05. RESULTS: Myocardial infarctions in exercise-trained animals resulted in a smaller myocardial infarction extension, a thicker infarcted wall and less collagen accumulation as compared to myocardial infarctions in sedentary animals. Myocardial infarction-induced left ventricular dilation and cardiac dysfunction, as evaluated by +dP/dt and -dP/dt, were both prevented by previous aerobic exercise training. Moreover, aerobic exercise training preserved cardiac myocyte shortening, improved the maximum shortening and relengthening velocities in infarcted hearts and enhanced responsiveness to calcium. CONCLUSION: Previous aerobic exercise training attenuated the cardiac dysfunction and structural deterioration promoted by myocardial infarction, and such benefits were associated with preserved cardiomyocyte morphological and contractile properties.

  17. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  18. Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by reducing inflammation, oxidative stress, apoptosis and enhancing autophagy

    National Research Council Canada - National Science Library

    Zhao, Yanli; Zhang, Lina; Qiao, Yu; Zhou, Xiaoling; Wu, Guodong; Wang, Lujing; Peng, Yahui; Dong, Xingli; Huang, Hui; Si, Lining; Zhang, Xueying; Zhang, Lei; Li, Jihong; Wang, Wei; Zhou, Lingyun; Gao, Xu

    2013-01-01

    Heme oxygenase-1 (HO-1) has been implicated in cardiac dysfunction, oxidative stress, inflammation, apoptosis and autophagy associated with heart failure, and atherosclerosis, in addition to its recognized role in metabolic...

  19. Melatonin alleviates postinfarction cardiac remodeling and dysfunction by inhibiting Mst1.

    Science.gov (United States)

    Hu, Jianqiang; Zhang, Lei; Yang, Yang; Guo, Yanjie; Fan, Yanhong; Zhang, Mingming; Man, Wanrong; Gao, Erhe; Hu, Wei; Reiter, Russel J; Wang, Haichang; Sun, Dongdong

    2017-01-01

    Melatonin reportedly protects against several cardiovascular diseases including ischemia/reperfusion (I/R), atherosclerosis, and hypertension. The present study investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy, apoptosis, and mitochondrial injury in the context of myocardial infarction (MI). We demonstrated that melatonin significantly alleviated cardiac dysfunction after MI. Four weeks after MI, echocardiography and Masson staining indicated that melatonin notably mitigated adverse left ventricle remodeling. The mechanism may be associated with increased autophagy, reduced apoptosis, and alleviated mitochondrial dysfunction. Furthermore, melatonin significantly inhibited Mst1 phosphorylation while promoting Sirt1 expression after MI, which indicates that Mst1/Sirt1 signaling may serve as the downstream target of melatonin. We thus constructed a MI model using Mst1 transgenic (Mst1 Tg) and Mst1 knockout (Mst1(-/-) ) mice. The absence of Mst1 abolished the favorable effects of melatonin on cardiac injury after MI. Consistently, melatonin administration did not further increase autophagy, decrease apoptosis, or alleviate mitochondrial integrity and biogenesis in Mst1 knockout mice subjected to MI injury. These results suggest that melatonin alleviates postinfarction cardiac remodeling and dysfunction by upregulating autophagy, decreasing apoptosis, and modulating mitochondrial integrity and biogenesis. The attributed mechanism involved, at least in part, Mst1/Sirt1 signaling. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Rosiglitazone suppresses cyclosporin-induced chronic transplant dysfunction and prolongs survival of rat cardiac allografts.

    Science.gov (United States)

    Chen, Yan; Liu, Yan; Yuan, Zhengwei; Tian, Lina; Dallman, Margaret J; Thompson, Paul W; Tam, Paul K H; Lamb, Jonathan R

    2007-06-27

    The lack of effective treatment for chronic transplant dysfunction restricts the long-term survival of solid organ allografts. Peroxisome proliferator-activated receptor ligands can suppress vascular inflammation. The aim of this study was to analyze the effects of rosiglitazone on chronic transplant dysfunction in a rat cardiac transplant model. Inbred male Fisher 344 (F344, RT1lvl) and Lewis (LEW, RT1(1)) rats were subjected to heterotopic abdominal heart transplantation according to standard procedures. Cyclosporine A was administered intraperitoneally to cover acute rejection, and rosiglitazone was administered orally by gavage daily from 3 days before the operation to the end of experiments. Rosiglitazone significantly prolonged the survival of cardiac allografts in rats (F344 to LEW) that had received a 10-day course of cyclosporin A compared to treatment with immunosuppressant alone. Analysis of allografts at 120 days posttransplantation showed that rosiglitazone reduced the inflammatory cell infiltrate in both the vessels and graft parenchyma as were neointimal formation, vascular occlusion, and fibrosis. Expression of transforming growth factor-beta and related proteins was less abundant after cyclosporin A/rosiglitazone treatment. The findings reported here demonstrate that rosiglitazone given under the cover of short-term treatment with cyclosporin A prolongs cardiac allograft survival and reduces the severity of chronic transplant dysfunction. This may be mediated in part through the downregulation of transforming growth factor-beta and related proteins. The combined effects of rosiglitazone and immunosuppressive drugs are potentially beneficial to patients receiving organ transplants.

  1. Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: the link with cardiac arrhythmogenesis

    Directory of Open Access Journals (Sweden)

    Gary Tse

    2016-08-01

    Full Text Available Background: Cardiac arrhythmias represent a significant problem globally, leading to cerebrovascular accidents, myocardial infarction, and sudden cardiac death. There is increasing evidence to suggest that increased oxidative stress from reactive oxygen species (ROS, which is elevated in conditions such as diabetes and hypertension, can lead to arrhythmogenesis. Method: A literature review was undertaken to screen for articles that investigated the effects of ROS on cardiac ion channel function, remodelling and arrhythmogenesis. Results: Prolonged endoplasmic reticulum stress is observed in heart failure, leading to increased production of ROS. Mitochondrial ROS, which is elevated in diabetes and hypertension, can stimulate its own production in a positive feedback loop, termed ROS-induced ROS release. Together with activation, mitochondrial inner membrane anion channels, it leads to mitochondrial depolarization. Abnormal function of these organelles can then activate downstream signalling pathways, ultimately culminating in altered function or expression of cardiac ion channels responsible for generating the cardiac action potential (AP. Vascular and cardiac endothelial cells become dysfunctional, leading to altered paracrine signalling to influence the electrophysiology of adjacent cardiomyocytes. All of these changes can in turn produce abnormalities in AP repolarization or conduction, thereby increasing likelihood of triggered activity and reentry. Conclusion: ROS plays a significant role in producing arrhythmic substrate. Therapeutic strategies targeting upstream events include production of a strong reducing environment or the use of pharmacological agents that target organelle-specific proteins and ion channels. These may relieve oxidative stress and in turn prevent arrhythmic complications in patients with diabetes, hypertension and heart failure.

  2. Pathophysiology of Sepsis-Related Cardiac Dysfunction: Driven by Inflammation, Energy Mismanagement, or Both?

    Science.gov (United States)

    Lymperopoulos, Anastasios; Kennel, Peter Johannes; Pollak, Nina; Schulze, P. Christian; Goldberg, Ira J.

    2015-01-01

    Sepsis is a systemic inflammatory response that follows bacterial infection. Cardiac dysfunction is an important consequence of sepsis that affects mortality and has been attributed to either elevated inflammation or suppression of both fatty acid and glucose oxidation and eventual ATP depletion. Moreover, cardiac adrenergic signaling is compromised in septic patients and this aggravates further heart function. While anti-inflammatory therapies are important for the treatment of the disease, administration of anti-inflammatory drugs did not improve survival in septic patients. This review article summarizes findings on inflammatory and other mechanisms that are triggered in sepsis and affect cardiac function and mortality. Particularly, it focuses on the effects of the disease in metabolic pathways, as well as in adrenergic signaling and the potential interplay of the latter with inflammation. It is suggested that therapeutic approaches should include combination of anti-inflammatory treatments, stimulation of energy production, and restoration of adrenergic signaling in the heart. PMID:25475180

  3. Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training.

    Science.gov (United States)

    Giampá, Sara Quaglia de Campos; Mônico-Neto, Marcos; de Mello, Marco Tulio; Souza, Helton de Sá; Tufik, Sergio; Lee, Kil Sun; Koike, Marcia Kiyomi; Dos Santos, Alexandra Alberta; Antonio, Ednei Luiz; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Antunes, Hanna Karen Moreira

    2016-01-01

    Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

  4. Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine Treatment

    Directory of Open Access Journals (Sweden)

    Sriranjini Sitaram Jaideep

    2014-01-01

    Full Text Available Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory (mean age 39.26 ± 9.88 years; male 43, female 7 were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I or Ayurveda treatment (Group II for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS. Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F=8.16, P=0.007, F=9.73, P=0.004, F=13.51, and P=0.001, resp.. The BRS too increased following the treatment period (F=10.129, P=0.004. Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted.

  5. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    Marilisa Molinaro

    2015-01-01

    Full Text Available Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV dysfunction, and heart failure (HF. The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure.

  6. A Pre-clinical Animal Model of Trypanosoma brucei Infection Demonstrating Cardiac Dysfunction.

    Directory of Open Access Journals (Sweden)

    Charlotte S McCarroll

    2015-05-01

    Full Text Available African trypanosomiasis (AT, caused by Trypanosoma brucei species, results in both neurological and cardiac dysfunction and can be fatal if untreated. Research on the pathogenesis and treatment of the disease has centred to date on the characteristic neurological symptoms, whereas cardiac dysfunction (e.g. ventricular arrhythmias in AT remains largely unstudied. Animal models of AT demonstrating cardiac dysfunction similar to that described in field cases of AT are critically required to transform our understanding of AT-induced cardiac pathophysiology and identify future treatment strategies. We have previously shown that T. brucei can interact with heart muscle cells (cardiomyocytes to induce ventricular arrhythmias in ex vivo adult rat hearts. However, it is unknown whether the arrhythmias observed ex vivo are also present during in vivo infection in experimental animal models. Here we show for the first time the characterisation of ventricular arrhythmias in vivo in two animal models of AT infection using electrocardiographic (ECG monitoring. The first model utilised a commonly used monomorphic laboratory strain, Trypanosoma brucei brucei Lister 427, whilst the second model used a pleomorphic laboratory strain, T. b. brucei TREU 927, which demonstrates a similar chronic infection profile to clinical cases. The frequency of ventricular arrhythmias and heart rate (HR was significantly increased at the endpoint of infection in the TREU 927 infection model, but not in the Lister 427 infection model. At the end of infection, hearts from both models were isolated and Langendorff perfused ex vivo with increasing concentrations of the β-adrenergic agonist isoproterenol (ISO. Interestingly, the increased frequency of arrhythmias observed in vivo in the TREU 927 infection model was lost upon isolation of the heart ex vivo, but re-emerged with the addition of ISO. Our results demonstrate that TREU 927 infection modifies the substrate of the myocardium

  7. The effect of preoperative renal dysfunction with or without dialysis on early postoperative outcome following cardiac surgery.

    LENUS (Irish Health Repository)

    Al-Sarraf, Nael

    2011-01-01

    Although previous studies have shown increased mortality in renal dysfunction patients undergoing cardiac surgery, there is lack of data on the pattern of postoperative complications that occur in such patients and their distribution among dialysis and non-dialysis dependent renal dysfunction.

  8. The activity of circulating dipeptidyl peptidase-4 is associated with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Ravassa, Susana; Barba, Joaquín; Coma-Canella, Isabel; Huerta, Ana; López, Begoña; González, Arantxa; Díez, Javier

    2013-10-07

    Patients with type 2 diabetes mellitus (T2DM) present subclinical left ventricular systolic and/or diastolic dysfunction (LVD). Dipeptidyl peptidase-4 (DPP4) inactivates peptides that possess cardioprotective actions. Our aim was to analyze whether the activity of circulating DPP4 is associated with echocardiographically defined LVD in asymptomatic patients with T2DM. In this cross-sectional study, we examined 83 T2DM patients with no coronary or valve heart disease and 59 age and gender-matched non-diabetic subjects. Plasma DPP4 activity (DPP4a) was measured by enzymatic assay and serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by enzyme-linked immunosorbent assay. LV function was assessed by two-dimensional echocardiographic imaging, targeted M-mode recordings and Doppler ultrasound measurements. Differences in means were assessed by t-tests and one-way ANOVA. Associations were assessed by adjusted multiple linear regression and logistic regression analyses. DPP4a was increased in T2DM patients as compared with non-diabetic subjects (5855 ± 1632 vs 5208 ± 957 pmol/min/mL, p regression analysis confirmed the independent associations of DPP4a with LVD in T2DM patients (p multiple logistic regression analysis showed that an increase of 100 pmol/min/min plasma DPP4a was independently associated with an increased frequency of LVD with an adjusted odds ratio of 1.10 (95% CI, 1.04 to 1.15, p = 0.001). An excessive activity of circulating DPP4 is independently associated with subclinical LVD in T2DM patients. Albeit descriptive, these findings suggest that DPP4 may be involved in the mechanisms of LVD in T2DM.

  9. Endocan, TGF-beta, and ADMA as Risk Factors for Endothelial Dysfunction and Possible Vascular Disease in Patients with Subclinical Hypothyroidism.

    Science.gov (United States)

    Arpaci, Dilek; Karakece, Engin; Tocoglu, Aysel Gurkan; Ergenc, Hasan; Gurol, Gonul; Ciftci, Ihsan Hakki; Tamer, Ali

    2016-12-01

    Although the relationship between atherosclerosis and overt hypothyroidism has been confirmed, it remains controversial in cases of subclinical hypothyroidism. Higher TSH and similar T4 suggest differences in set-points or differences due to diagnostic limitations regarding subclinical hypothyroidism. Endothelial dysfunction (ED) is a marker rather than a precursor of cardiovascular disease. Asymmetric dimethylarginine (ADMA) and endocan are known as novel markers of ED in various diseases. Transforming growth factor-beta (TGF-β) has a protective role against autoimmune diseases such as thyroiditis. This study aimed to determine the relationships between serum ADMA, endocan, TGF-β, and the high-sensitivity C-reactive protein (hs-CRP) levels, a proven indicator of ED, in patients with SH. Thirty-five patients with SH and 21 age- and sex-matched euthyroid subjects were included in the study. The levels of TSH, FT4, lipid parameters, endocan, ADMA, TGF-β, and hs-CRP were measured. No significant differences in age or sex were found between the patient and control groups (p=0.294 and 0.881, respectively). Mean TSH level was higher in the patient group (p=0.005), whereas mean fT4 level was similar in two groups (p=0.455). The average hs-CRP, endocan, TGF-β l level in the patient group was higher than control group (p=0.001; P=0.012; P=0.025; Phypothyroidism is associated with increased levels of serum endocan, ADMA, and TGF-β, which are new markers for ED. In particular, ADMA was correlated with both endocan and hs-CRP levels. These findings are suggestive for increased risk of ED and subsequent development of atherosclerosis in patients with SH. © 2016 by the Association of Clinical Scientists, Inc.

  10. 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

  11. High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

    OpenAIRE

    Choi, He Yun; Park, Ji Hye; Jang, Woong Bi; Ji, Seung Taek; Jung, Seok Yun; Kim, Da Yeon; Kang, Songhwa; Kim, Yeon Ju; Yun, Jisoo; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang-Mo

    2016-01-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor...

  12. Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction.

    Science.gov (United States)

    Wang, Ning-Ping; Wang, Zhang-Feng; Tootle, Stephanie; Philip, Tiji; Zhao, Zhi-Qing

    2012-12-01

    Curcumin, the natural yellow pigment extracted from the rhizomes of the plant curcuma longa, has been demonstrated to exhibit a variety of potent beneficial effects, acting as an antioxidant, anti-inflammatory and anti-fibrotic. In this study we tested the hypothesis that curcumin attenuates maladaptive cardiac repair and improves cardiac function after ischaemia and reperfusion by reducing degradation of extracellular matrix (ECM) and inhibiting synthesis of collagens via TGFβ/Smad-mediated signalling pathway. Sprague-Dawley rats were subjected to 45 min of ischaemia followed by 7, 21 and 42 days of reperfusion respectively. Curcumin was fed orally at a dose of 150 mg·kg(-1) ·day(-1) only during reperfusion. Curcumin reduced the level of malondialdehyde, inhibited activity of MMPs, preserved ECM from degradation and attenuated collagen deposition, as it reduced the extent of collagen-rich scar and increased mass of viable myocardium. In addition to reducing collagen synthesis and fibrosis in the ischaemic/reperfused myocardium, curcumin significantly down-regulated the expression of TGFβ1 and phospho-Smad2/3, and up-regulated Smad7 and also increased the population of α-smooth muscle actin expressing myofibroblasts within the infarcted myocardium relative to the control. Echocardiography showed it significantly improved left ventricular end-diastolic volume, stroke volume and ejection fraction. The wall thickness of the infarcted middle anterior septum in the curcumin group was also greater than that in the control group. Dietary curcumin is effective at inhibiting maladaptive cardiac repair and preserving cardiac function after ischaemia and reperfusion. Curcumin has potential as a treatment for patients who have had a heart attack. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  13. MicroRNA-208a Silencing Attenuates Doxorubicin Induced Myocyte Apoptosis and Cardiac Dysfunction

    Directory of Open Access Journals (Sweden)

    Hasahya Tony

    2015-01-01

    Full Text Available Aims. GATA4 depletion is a distinct mechanism by which doxorubicin leads to cardiomyocyte apoptosis, and preservation of GATA4 mitigates doxorubicin induced myocyte apoptosis and cardiac dysfunction. We investigated a novel approach of attenuating doxorubicin induced cardiac toxicity by silencing miR-208a, a heart specific microRNA known to target GATA4. Methods and Results. Eight-week-old female Balb/C mice were randomly assigned to sham, antagomir, and control groups. Antagomir group were pretreated with miR-208a antagomir 4 days before doxorubicin administration. At day 0, control and antagomir groups received 20 mg/kg of doxorubicin, while sham mice received phosphate buffered solution. Echocardiography was done at day 7, after which animals were sacrificed and hearts harvested and assessed for apoptosis and expression of miR-208a, GATA4, and BCL-2. Doxorubicin significantly upregulated miR-208a, downregulated GATA4, and increased myocyte apoptosis, with resulting decrease in cardiac function. In contrast, therapeutic silencing of miR-208a salvaged GATA4 and BCL-2 and decreased apoptosis, with improvement in cardiac function. Conclusion. Doxorubicin upregulates miR-208a and promotes cardiomyocyte apoptosis, while therapeutic silencing of miR-208a attenuates doxorubicin induced myocyte apoptosis with subsequent improvement in cardiac function. These novel results highlight the therapeutic potential of targeting miR-208a to prevent doxorubicin cardiotoxicity.

  14. Antiandrogenic therapy with finasteride attenuates cardiac hypertrophy and left ventricular dysfunction.

    Science.gov (United States)

    Zwadlo, Carolin; Schmidtmann, Elisa; Szaroszyk, Malgorzata; Kattih, Badder; Froese, Natali; Hinz, Hebke; Schmitto, Jan Dieter; Widder, Julian; Batkai, Sandor; Bähre, Heike; Kaever, Volkhard; Thum, Thomas; Bauersachs, Johann; Heineke, Joerg

    2015-03-24

    In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether antiandrogenic therapy with finasteride, which inhibits the generation of dihydrotestosterone by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure. We found a strongly induced expression of all 3 isoforms of the 5-α-reductase (Srd5a1 to Srd5a3) in human and mouse hearts with pathological hypertrophy, which was associated with increased myocardial accumulation of dihydrotestosterone. Starting 1 week after the induction of pressure overload by transaortic constriction, mice were treated with finasteride for 2 weeks. Cardiac function, hypertrophy, dilation, and fibrosis were markedly improved in response to finasteride treatment in not only male, but also in female mice. In addition, finasteride also very effectively improved cardiac function and mortality after long-term pressure overload and prevented disease progression in cardiomyopathic mice with myocardial Gαq overexpression. Mechanistically, finasteride, by decreasing dihydrotestosterone, potently inhibited hypertrophy and Akt-dependent prohypertrophic signaling in isolated cardiac myocytes, whereas the introduction of constitutively active Akt blunted these effects of finasteride. Finasteride, which is currently used in patients to treat prostate disease, potently reverses pathological cardiac hypertrophy and dysfunction in mice and might be a therapeutic option for heart failure. © 2015 American Heart Association, Inc.

  15. Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction.

    Science.gov (United States)

    Chung, Ha-Yeun; Kollmey, Anna S; Schrepper, Andrea; Kohl, Matthias; Bläss, Markus F; Stehr, Sebastian N; Lupp, Amelie; Gräler, Markus H; Claus, Ralf A

    2017-04-15

    Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients' mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and transient generation of the lipid mediator ceramide-is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1 +/+ as well as SMPD1 -/- animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1 -/- littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine.

  16. Treatment with Fenofibrate plus a low dose of Benznidazole attenuates cardiac dysfunction in experimental Chagas disease

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    Ágata C. Cevey

    2017-12-01

    Full Text Available Trypanosoma cruzi induces serious cardiac alterations during the chronic infection. Intense inflammatory response observed from the beginning of infection, is critical for the control of parasite proliferation and evolution of Chagas disease. Peroxisome proliferator-activated receptors (PPAR-α, are known to modulate inflammation.In this study we investigated whether a PPAR-α agonist, Fenofibrate, improves cardiac function and inflammatory parameters in a murine model of T. cruzi infection. BALB/c mice were sequentially infected with two T. cruzi strains of different genetic background. Benznidazole, commonly used as trypanocidal drug, cleared parasites but did not preclude cardiac pathology, resembling what is found in human chronic chagasic cardiomyopathy. Fenofibrate treatment restored to normal values the ejection and shortening fractions, left ventricular end-diastolic, left ventricular end-systolic diameter, and isovolumic relaxation time. Moreover, it reduced cardiac inflammation and fibrosis, decreased the expression of pro-inflammatory (IL-6, TNF-α and NOS2 and heart remodeling mediators (MMP-9 and CTGF, and reduced serum creatine kinase activity. The fact that Fenofibrate partially inhibited NOS2 expression and NO release in the presence of a PPAR-α non-competitive inhibitor, suggested it also acted through PPAR-α-independent pathways. Since IκBα cytosolic degradation was inhibited by Fenofibrate, it can be concluded that the NFκB pathway has a role in its effects. Thus, we demonstrate that Fenofibrate acts through PPAR-α-dependent and -independent pathways.Our study shows that combined treatment with Fenofibrate plus Benznidazole is able both to reverse the cardiac dysfunction associated with the ongoing inflammatory response and fibrosis and to attain parasite clearance in an experimental model of Chagas disease. Keywords: Trypanosoma cruzi, Heart dysfunction, PPAR-α, Fenofibrate treatment, Inflammatory

  17. Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction

    Science.gov (United States)

    Chung, Ha-Yeun; Kollmey, Anna S.; Schrepper, Andrea; Kohl, Matthias; Bläss, Markus F.; Stehr, Sebastian N.; Lupp, Amelie; Gräler, Markus H.; Claus, Ralf A.

    2017-01-01

    Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients’ mortality. Acid sphingomyelinase (SMPD1)—the principal regulator for rapid and transient generation of the lipid mediator ceramide—is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1+/+ as well as SMPD1−/− animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1−/− littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine. PMID:28420138

  18. Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure.

    Science.gov (United States)

    Koyani, Chintan N; Kolesnik, Ewald; Wölkart, Gerald; Shrestha, Niroj; Scheruebel, Susanne; Trummer, Christopher; Zorn-Pauly, Klaus; Hammer, Astrid; Lang, Petra; Reicher, Helga; Maechler, Heinrich; Groschner, Klaus; Mayer, Bernd; Rainer, Peter P; Sourij, Harald; Sattler, Wolfgang; Malle, Ernst; Pelzmann, Brigitte; von Lewinski, Dirk

    2017-12-01

    Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca2+/calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca2+-ATPase 2a axis and Na+-Ca2+ exchanger function in Ca2+ extrusion. This resulted in reduced sarcoplasmic reticulum Ca2+ content, diastolic Ca2+ overload, systolic dysfunction and impaired contractile force. Furthermore, saxagliptin reduced protein kinase C-mediated delayed rectifier K+ current that prolonged action potential duration and consequently QTc interval. Importantly, saxagliptin aggravated pre-existing cardiac dysfunction induced by ischemia/reperfusion injury. In conclusion, our novel results provide mechanisms for the off-target deleterious effects of saxagliptin on cardiac function and support the outcome of SAVOR-TIMI 53 trial that linked saxagliptin with the risk of heart failure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Left atrial dysfunction in type 2 diabetes mellitus: insights from cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Graca, Bruno; Donato, Paulo; Caseiro-Alves, Filipe [University of Coimbra, Faculty of Medicine, Coimbra (Portugal); Coimbra' s Hospital Centre and University, Medical Imaging Department, Coimbra (Portugal); Joao Ferreira, Maria [University of Coimbra, Faculty of Medicine, Coimbra (Portugal); Coimbra' s Hospital Centre and University, Cardiology Department, Coimbra (Portugal); Gomes, Leonor [University of Coimbra, Faculty of Medicine, Coimbra (Portugal); Coimbra' s Hospital Centre and University, Endocrinology Department, Coimbra (Portugal); Castelo-Branco, Miguel [University of Coimbra, Faculty of Medicine, Coimbra (Portugal)

    2014-11-15

    The left atrium (LA) modulates left ventricular filling through reservoir, conduit and booster pump functions. Only limited data exist on LA involvement in type 2 diabetes mellitus (DM2). This study sought to assess LA function in asymptomatic DM2 with cardiac MRI. We hypothesized that cardiac MRI can detect LA dysfunction in asymptomatic DM2. Forty-five patients with asymptomatic DM2 and 24 normoglycaemic controls were studied. MRI cine imaging was performed to measure LA maximal and minimal volumes. A flow-sensitive phase-contrast gradient-echo sequence was used for flow measurements perpendicular to the orifice of the mitral valve, to quantify active LA stroke volume. LA total, passive and active emptying volumes and fractions were calculated. LA reservoir function, namely LA total ejection fraction, was significantly greater in controls compared to patients with DM2 (62.2 ± 5.2 vs 57.0 ± 7.6 %, P = 0.004). LA passive ejection fraction was also greater in the controls (26.2 ± 9.5 vs 16.1 ± 11.0 %, P < 0.001). Regarding parameters of LA booster pump function, LA active ejection fraction was not significantly different between groups. DM2 was demonstrated to be an independent determinant of LA function. Cardiac MRI enables the detection of LA dysfunction in asymptomatic DM2, characterized by a reduction in LA reservoir and conduit functions. (orig.)

  20. PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis.

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    Takuya Taniguchi

    Full Text Available Mutations in the PTRF/Cavin-1 gene cause congenital generalized lipodystrophy type 4 (CGL4 associated with myopathy. Additionally, long-QT syndrome and fatal cardiac arrhythmia are observed in patients with CGL4 who have homozygous PTRF/Cavin-1 mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and caveolin-3 (Cav3 protein expression in skeletal muscle, and Cav3 deficiency in the heart causes cardiac hypertrophy with loss of caveolae. However, it remains unknown how loss of PTRF/Cavin-1 affects cardiac morphology and function. Here, we present a characterization of the hearts of PTRF/Cavin-1-null (PTRF-/- mice. Electron microscopy revealed the reduction of caveolae in cardiomyocytes of PTRF-/- mice. PTRF-/- mice at 16 weeks of age developed a progressive cardiomyopathic phenotype with wall thickening of left ventricles and reduced fractional shortening evaluated by echocardiography. Electrocardiography revealed that PTRF-/- mice at 24 weeks of age had low voltages and wide QRS complexes in limb leads. Histological analysis showed cardiomyocyte hypertrophy accompanied by progressive interstitial/perivascular fibrosis. Hypertrophy-related fetal gene expression was also induced in PTRF-/- hearts. Western blotting analysis and quantitative RT-PCR revealed that Cav3 expression was suppressed in PTRF-/- hearts compared with that in wild-type (WT ones. ERK1/2 was activated in PTRF-/- hearts compared with that in WT ones. These results suggest that loss of PTRF/Cavin-1 protein expression is sufficient to induce a molecular program leading to cardiomyocyte hypertrophy and cardiomyopathy, which is partly attributable to Cav3 reduction in the heart.

  1. Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

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    Hui Wang

    2016-01-01

    Full Text Available Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS. However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.

  2. Cardiac dysfunction in cirrhosis - does adrenal function play a role? A hypothesis

    DEFF Research Database (Denmark)

    Theocharidou, Eleni; Krag, Aleksander; Bendtsen, Flemming

    2013-01-01

    conditions, such as sepsis, bleeding and surgery. CCM reverses after liver transplantation and potentially has a role in the pathogenesis of hepatorenal syndrome. In adrenal insufficiency (AI), cardiac dysfunction is a feature with low ejection fraction, decreased left ventricular chamber size......Cirrhotic cardiomyopathy (CCM), a condition of unknown pathogenesis, is characterized by suboptimal ventricular contractile response to stress, diastolic dysfunction and QT interval prolongation. It is most often found in patients with advanced cirrhosis. It is clinically relevant during stressful...... and electrocardiographic abnormalities, including QT interval prolongation. With optimal diagnostic tests, AI is present in approximately 10% of patients with cirrhosis, particularly in those with advanced disease. Down-regulation and decreased number of beta-adrenergic receptors, and high catecholamine levels are common...

  3. Cardiac dysfunction in cirrhosis - does adrenal function play a role? A hypothesis

    DEFF Research Database (Denmark)

    Theocharidou, Eleni; Krag, Aleksander; Bendtsen, Flemming

    2012-01-01

    conditions, such as sepsis, bleeding and surgery. CCM reverses after liver transplantation and potentially has a role in the pathogenesis of hepatorenal syndrome. In adrenal insufficiency (AI), cardiac dysfunction is a feature with low ejection fraction, decreased left ventricular chamber size......Cirrhotic cardiomyopathy (CCM), a condition of unknown pathogenesis, is characterized by suboptimal ventricular contractile response to stress, diastolic dysfunction and QT interval prolongation. It is most often found in patients with advanced cirrhosis. It is clinically relevant during stressful...... and electrocardiographic abnormalities, including QT interval prolongation. With optimal diagnostic tests, AI is present in approximately 10% of patients with cirrhosis, particularly in those with advanced disease. Down-regulation and decreased number of beta-adrenergic receptors, and high catecholamine levels are common...

  4. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

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    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  5. Cardiac Autonomic Dysfunction in Type 2 Diabetes – Effect of Hyperglycemia and Disease Duration

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    Mika P. Tarvainen

    2014-08-01

    Full Text Available Heart rate variability (HRV is reduced in diabetes mellitus (DM patients, suggesting dysfunction of cardiac autonomic regulation and an increased risk for cardiac events. The aim of this paper was to examine the associations of blood glucose level (BGL, glycated hemoglobin (HbA1c and duration of diabetes with cardiac autonomic regulation assessed by HRV analysis. Resting electrocardiogram (ECG, recorded over 20 minutes in supine position, and clinical measurements of 189 healthy controls and 93 type 2 DM (T2DM patients were analyzed. HRV was assessed using several time-domain, frequency-domain and nonlinear methods. HRV parameters showed a clear difference between healthy controls and T2DM patients. Hyperglycemia was associated with increase in mean heart rate and decrease in HRV, indicated by negative correlations of BGL and HbA1c with mean RR interval and most of the HRV parameters. Duration of diabetes was strongly associated with decrease in HRV, the most significant decrease in HRV was found within the first 5-10 years of the disease. In conclusion, elevated blood glucose levels have an unfavorable effect on cardiac autonomic function and this effect is pronounced in long-term T2DM patients. The most significant decrease in HRV related to diabetes and thus presence of autonomic neuropathy was observed within the first 5-10 years of disease progression.

  6. Advanced Heart Failure Therapies for Cancer Therapeutics-Related Cardiac Dysfunction.

    Science.gov (United States)

    Bianco, Christopher M; Al-Kindi, Sadeer G; Oliveira, Guilherme H

    2017-04-01

    End-stage heart failure in cancer survivors may result from cardiotoxic chemotherapy and/or chest radiation and require advanced therapies, including left ventricular assist devices (LVADs) and transplantation. Traditionally, such therapies have been underutilized in cancer survivors owing to lack of experience and perceived risk of cancer recurrence. Recent data from large registries, however, have shown excellent outcomes of LVADs and transplantation in cancer survivors, albeit subject to careful selection and special considerations. This article summarizes all aspects of advanced heart failure therapies in patients with cancer therapy-related cardiac dysfunction and underscores the need for careful selection of these candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Response and outcomes of cardiac resynchronization therapy in patients with renal dysfunction.

    Science.gov (United States)

    Moreira, Rita Ilhão; Cunha, Pedro Silva; Rio, Pedro; da Silva, Manuel Nogueira; Branco, Luísa Moura; Galrinho, Ana; Feliciano, Joana; Soares, Rui; Ferreira, Rui Cruz; Oliveira, Mário Martins

    2018-02-19

    Renal dysfunction is often associated with chronic heart failure, leading to increased morbi-mortality. However, data regarding these patients after cardiac resynchronization therapy (CRT) is sparse. We sought to evaluate response and long-term mortality in patients with heart failure and renal dysfunction and assess renal improvement after CRT. We analyzed 178 consecutive patients who underwent successful CRT device implantation (age 64 ± 11 years; 69% male; 92% in New York Heart Association (NYHA) functional class ≥ III; 34% with ischemic cardiomyopathy). Echocardiographic response was defined as ≥ 15% reduction in left ventricular end-systolic diameter and clinical response as a sustained improvement of at least one NYHA functional class. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m 2 . Renal dysfunction was present in 34.7%. Renal dysfunction was not an independent predictor of echocardiographic response (OR 1.109, 95% CI 0.713-1.725, p 0.646) nor clinical response (OR 1.003; 95% CI 0.997-1.010; p 0.324). During follow-up (mean 55.2 ± 32 months), patients with eGFR < 60mL/min/1.73 m 2 had higher overall mortality (HR 4.902, 95% CI 1.118-21.482, p 0.035). However, clinical response in patients with renal dysfunction was independently associated with better long-term survival (HR 0.236, 95% CI 0.073-0.767, p 0.016). Renal function was significantly improved in patients who respond to CRT (ΔeGFR + 5.5 mL/min/1.73 m 2 at baseline vs. follow-up, p 0.049), while this was not evident in nonresponders. Improvements in eGFR of at least 10 mL/min/1.73 m 2 were associated with improved survival in renal dysfunction patients (log-rank p 0.036). Renal dysfunction was associated with higher long-term mortality in CRT patients, though, it did not influence echocardiographic nor functional response. Despite worse overall prognosis, renal dysfunction patients who are responders showed long-term survival benefit

  8. Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling.

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    Patrick Meybohm

    Full Text Available BACKGROUND: Mild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia. METHODOLOGY/PRINCIPAL FINDINGS: Thirty pigs (28-34 kg were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21, coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group n = 7 for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01, reduced infarct size (34+/-7 versus 57+/-12%; p<0.05 and improved left ventricular function compared to normothermia (p<0.05. Hypothermia was associated with a reduction in: (i immune cell infiltration, (ii apoptosis, (iii IL-1beta and IL-6 mRNA up-regulation, and (iv IL-1beta protein expression (p<0.05. Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached. CONCLUSIONS/SIGNIFICANCE: Hypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis

  9. A History of Alcohol Dependence Increases the Incidence and Severity of Postoperative Cognitive Dysfunction in Cardiac Surgical Patients

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    Paul S. Pagel

    2009-10-01

    Full Text Available Postoperative cognitive dysfunction (POCD commonly occurs after cardiac surgery. We tested the hypothesis that a history of alcohol dependence is associated with an increased incidence and severity of POCD in male patients undergoing cardiac surgery using cardiopulmonary bypass. Recent verbal and nonverbal memory and executive functions were assessed before and one week after surgery in patients with or without a history of alcohol dependence. Cognitive function was significantly reduced after cardiac surgery in patients with versus without a history of alcohol dependence. The results suggest that a history of alcohol dependence increases the incidence and severity of POCD after cardiac surgery.

  10. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid

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    Li Chun-jun

    2012-06-01

    Full Text Available Abstract Background Alpha-lipoic acid (ALA, a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS, extracellular matrix (ECM remodeling and interrelated signaling pathways in a diabetic rat model. Methods Diabetes was induced in rats by I.V. injection of streptozotocin (STZ at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2 levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA and transforming growth factor–β (TGF-β. Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK, p38 MAPK and ERK were also assayed by Western blot. Results DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated

  11. Burden of Systolic and Diastolic Left Ventricular Dysfunction among Hispanics in the United States: Insights from the Echocardiographic Study of Latinos (ECHO-SOL)

    Science.gov (United States)

    Mehta, Hardik; Armstrong, Anderson; Swett, Katrina; Shah, Sanjiv J.; Allison, Matthew A.; Hurwitz, Barry; Bangdiwala, Shrikant; Dadhania, Rupal; Kitzman, Dalane W.; Arguelles, William; Lima, Joao; Youngblood, Marston; Schneiderman, Neil; Daviglus, Martha L.; Spevack, Daniel; Talavera, Greg A.; Raisinghani, Ajit; Kaplan, Robert; Rodriguez, Carlos J.

    2016-01-01

    Background Population-based estimates of cardiac dysfunction and clinical heart failure (HF) remain undefined among Hispanics/Latino adults. Methods and Results Participants of Hispanic/Latino origin across the US, aged 45–74 years were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL) and underwent a comprehensive echocardiography exam to define left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction (LVDD). Clinical HF was defined according to self-report; and those with cardiac dysfunction but without clinical HF were characterized as having subclinical or unrecognized cardiac dysfunction. Of 1,818 ECHO-SOL participants (mean age 56.4 years; 42.6% male) , 49.7% had LVSD and/or LVDD. LVSD prevalence was 3.6%, while LVDD was detected in 50.3%. Participants with LVSD were more likely to be males and current smokers (all p<0.05). Female sex, hypertension, diabetes, higher body-mass index and renal dysfunction were more common among those with LVDD (all p<0.05). In age-sex adjusted models, individuals of Central American and Cuban backgrounds were almost two-fold more likely to have LVDD compared to those of Mexican backgrounds. Prevalence of clinical HF with LVSD (HF with reduced EF) was 7.3%; prevalence of clinical HF with LVDD (HF with preserved EF) was 3.6%. 96.1% of the cardiac dysfunction seen was subclinical or unrecognized. Compared to those with clinical cardiac dysfunction, prevalent coronary heart disease was the only factor independently associated with subclinical or unrecognized cardiac dysfunction (odds ratio: 0.1; 95% confidence interval: 0.1–0.4). Conclusions Among Hispanics/Latinos, most cardiac dysfunction is subclinical or unrecognized, with a high prevalence of diastolic dysfunction. This identifies a high-risk population for the development of clinical HF. PMID:27048764

  12. Burden of Systolic and Diastolic Left Ventricular Dysfunction Among Hispanics in the United States: Insights From the Echocardiographic Study of Latinos.

    Science.gov (United States)

    Mehta, Hardik; Armstrong, Anderson; Swett, Katrina; Shah, Sanjiv J; Allison, Matthew A; Hurwitz, Barry; Bangdiwala, Shrikant; Dadhania, Rupal; Kitzman, Dalane W; Arguelles, William; Lima, Joao; Youngblood, Marston; Schneiderman, Neil; Daviglus, Martha L; Spevack, Daniel; Talavera, Greg A; Raisinghani, Ajit; Kaplan, Robert; Rodriguez, Carlos J

    2016-04-01

    Population-based estimates of cardiac dysfunction and clinical heart failure (HF) remain undefined among Hispanics/Latino adults. Participants of Hispanic/Latino origin across the United States aged 45 to 74 years were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL) and underwent a comprehensive echocardiography examination to define left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction (LVDD). Clinical HF was defined according to self-report, and those with cardiac dysfunction but without clinical HF were characterized as having subclinical or unrecognized cardiac dysfunction. Of 1818 ECHO-SOL participants (mean age 56.4 years; 42.6% male), 49.7% had LVSD or LVDD or both. LVSD prevalence was 3.6%, whereas LVDD was detected in 50.3%. Participants with LVSD were more likely to be males and current smokers (all P<0.05). Female sex, hypertension, diabetes mellitus, higher body mass index, and renal dysfunction were more common among those with LVDD (all P<0.05). In age-sex adjusted models, individuals of Central American and Cuban backgrounds were almost 2-fold more likely to have LVDD compared with those of Mexican backgrounds. Prevalence of clinical HF with LVSD (HF with reduced EF) was 7.3%; prevalence of clinical HF with LVDD (HF with preserved EF) was 3.6%. 96.1% of the cardiac dysfunction seen was subclinical or unrecognized. Compared with those with clinical cardiac dysfunction, prevalent coronary heart disease was the only factor independently associated with subclinical or unrecognized cardiac dysfunction (odds ratio: 0.1; 95% confidence interval: 0.1-0.4). Among Hispanics/Latinos, most cardiac dysfunction is subclinical or unrecognized, with a high prevalence of diastolic dysfunction. This identifies a high-risk population for the development of clinical HF. © 2016 American Heart Association, Inc.

  13. Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction.

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    Huang, Chien-Hua; Wang, Chih-Hung; Tsai, Min-Shan; Hsu, Nai-Tan; Chiang, Chih-Yen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

    2016-01-01

    Hemodynamic instability occurs following cardiac arrest and is associated with high mortality during the post-cardiac period. Urocortin is a novel peptide and a member of the corticotrophin-releasing factor family. Urocortin has the potential to improve acute cardiac dysfunction, as well as to reduce the myocardial damage sustained after ischemia reperfusion injury. The effects of urocortin in post-cardiac arrest myocardial dysfunction remain unclear. We developed a preclinical cardiac arrest model and investigated the effects of urocortin. After cardiac arrest induced by 6.5 min asphyxia, male Wistar rats were resuscitated and randomized to either the urocortin treatment group or the control group. Urocortin (10 μg/kg) was administrated intravenously upon onset of resuscitation in the experimental group. The rate of return of spontaneous circulation (ROSC) was similar between the urocortin group (76%) and the control group (72%) after resuscitation. The left ventricular systolic (dP/dt40) and diastolic (maximal negative dP/dt) functions, and cardiac output, were ameliorated within 4 h after ROSC in the urocortin-treated group compared to the control group (Pcardiac arrest myocardial dysfunction.

  14. Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats.

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    Pacagnelli, Francis Lopes; Sabela, Ana Karênina Dias de Almeida; Mariano, Thaoan Bruno; Ozaki, Guilherme Akio Tamura; Castoldi, Robson Chacon; Carmo, Edna Maria do; Carvalho, Robson Francisco; Tomasi, Loreta Casquel; Okoshi, Katashi; Vanderlei, Luiz Carlos Marques

    2016-07-01

    Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Male Wistar rats were divided into 2 groups: control (C; n = 8) and monocrotaline-induced pulmonary arterial hypertension (M; n = 8). Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test), and the groups were compared with non-paired Student t test or Mann Whitney test (p cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction.

  15. Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction.

    Science.gov (United States)

    Beer, Lynn A; Kossenkov, Andrew V; Liu, Qin; Luning Prak, Eline; Domchek, Susan; Speicher, David W; Ky, Bonnie

    2016-10-28

    There is a critical need to develop robust, mechanistic strategies to identify patients at increased risk of cancer therapeutics-related cardiac dysfunction (CTRCD). We aimed to discover new biomarkers associated with doxorubicin- and trastuzumab-induced CTRCD using high-throughput proteomic profiling. Plasma, echocardiograms, and clinical outcomes were collected at standardized intervals in breast cancer patients undergoing doxorubicin and trastuzumab cancer therapy. Thirty-one longitudinal plasma samples from 3 cases with CTRCD and 4 age- and cancer-matched controls without CTRCD were processed and analyzed using label-free liquid chromatography-mass spectrometry. From these analyses, 862 proteins were identified from case/control pairs 1 and 2 and 1360 proteins from case/control pair 3. Proteins with a >1.5-fold change in cases compared with controls with a Ptrastuzumab, high baseline immunoglobulin E levels were associated with a significantly lower risk of CTRCD (P=0.018). In patients receiving doxorubicin and trastuzumab, high baseline immunoglobulin E levels are associated with a lower risk of CTRCD. These novel findings suggest a new paradigm in cardio-oncology, implicating the immune system as a potential mediator of doxorubicin- and trastuzumab-induced cardiac dysfunction. © 2016 American Heart Association, Inc.

  16. Matrix Metalloproteinase-9 Production following Cardiopulmonary Bypass Was Not Associated with Pulmonary Dysfunction after Cardiac Surgery

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    Tso-Chou Lin

    2015-01-01

    Full Text Available Background. Cardiopulmonary bypass (CPB causes release of matrix metalloproteinase- (MMP- 9, contributing to pulmonary infiltration and dysfunction. The aims were to investigate MMP-9 production and associated perioperative variables and oxygenation following CPB. Methods. Thirty patients undergoing elective cardiac surgery were included. Arterial blood was sampled at 6 sequential points (before anesthesia induction, before CPB and at 2, 4, 6, and 24 h after beginning CPB for plasma MMP-9 concentrations by ELISA. The perioperative laboratory data and variables, including bypass time, PaO2/FiO2, and extubation time, were also recorded. Results. The plasma MMP-9 concentrations significantly elevated at 2–6 h after beginning CPB (P<0.001 and returned to the preanesthesia level at 24 h (P=0.23, with predominant neutrophil counts after surgery (P<0.001. The plasma MMP-9 levels at 4 and 6 h were not correlated with prolonged CPB time and displayed no association with postoperative PaO2/FiO2, regardless of reduced ratio from preoperative 342.9±81.2 to postoperative 207.3±121.3 mmHg (P<0.001. Conclusion. Elective cardiac surgery with CPB induced short-term elevation of plasma MMP-9 concentrations within 24 hours, however, without significant correlation with CPB time and postoperative pulmonary dysfunction, despite predominantly increased neutrophils and reduced oxygenation.

  17. Coronary artery calcium scoring is a better predictor of cardiac risk in subclinical hypothyroidism patients with low-risk Framingham score

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    Rajesh Verma

    2016-01-01

    Full Text Available Context: Overt hypothyroidism accelerates the cardiovascular disease. Subclinical hypothyroidism (SCH, being considered as a preclinical state, impacts on cardiovascular status is not clear. Aims: This study was aimed at assessing cardiac risk stratification by Framingham risk scoring (FRS and coronary coronary artery calcium score (CACS by noncontrast cardiac computed tomography in SCH. Study Design: Observational study. Subjects and Methods: We enrolled thirty treatment-naive SCH patients (aged 30–60 years with no serious concurrent medical conditions, thirty euthyroid (age, sex, and body mass index-matched controls, and ten healthy controls. All cases were evaluated for coronary artery calcium scoring and Framingham risk score. Statistical Analysis: Qualitative data were analyzed using the Chi-square test. In addition, demographics and CACS are summarized graphically or in a table. Results: SCH cases had higher thyroglobulin, while there was a trend toward an increase in total cholesterol, low-density lipoprotein (LDL, very LDL, and decrease in HDL levels. All participants had low-risk FRS (10-year FRS < 10%. The mean CACS in SCH was significantly higher than simple obese and healthy controls (47.17 vs. 2.67 vs. 0.00. Conclusion: This study suggests that SCH is an independent risk factor for coronary artery disease in apparently healthy controls. The risk of occult coronary artery disease is increased in SCH cases.

  18. Activation of myocardial phosphoinositide-3-kinase p110α ameliorates cardiac dysfunction and improves survival in polymicrobial sepsis.

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    Chuanfu Li

    Full Text Available Phosphoinositide-3-kinase (PI3K/Akt dependent signaling has been shown to improve outcome in sepsis/septic shock. There is also ample evidence that PI3K/Akt dependent signaling plays a crucial role in maintaining normal cardiac function. We hypothesized that PI3K/Akt signaling may ameliorate septic shock by attenuating sepsis-induced cardiac dysfunction. Cardiac function and survival were evaluated in transgenic mice with cardiac myocyte specific expression of constitutively active PI3K isoform, p110α (caPI3K Tg. caPI3K Tg and wild type (WT mice were subjected to cecal ligation/puncture (CLP induced sepsis. Wild type CLP mice showed dramatic cardiac dysfunction at 6 hrs. Septic cardiomyopathy was significantly attenuated in caPI3K CLP mice. The time to 100% mortality was 46 hrs in WT CLP mice. In contrast, 80% of the caPI3K mice survived at 46 hrs after CLP (p30 days (p<0.01. Cardiac caPI3K expression prevented expression of an inflammatory phenotype in CLP sepsis. Organ neutrophil infiltration and lung apoptosis were also effectively inhibited by cardiac PI3k p110α expression. Cardiac high mobility group box-1 (HMGB-1 translocation was also inhibited by caPI3K p110α expression. We conclude that cardiac specific activation of PI3k/Akt dependent signaling can significantly modify the morbidity and mortality associated with sepsis. Our data also indicate that myocardial function/dysfunction plays a prominent role in the pathogenesis of sepsis and that maintenance of cardiac function during sepsis is essential. Finally, these data suggest that modulation of the PI3K/p110α signaling pathway may be beneficial in the prevention and/or management of septic cardiomyopathy and septic shock.

  19. Effect of PⅠCP/PⅢNP on assessing cardiac diastolic dysfunction and collagen remodeling

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    Jin-song LI

    2016-09-01

    Full Text Available Objective  To explore the changes of serum procollagen Ⅰcarboxyl peptide (PⅠCP/procollagen Ⅲamino-terminal peptide (PⅢNP levels in cardiac diastolic dysfunction rabbit model, and the relationship with cardiac diastolic dysfunction and collagen remodeling. Methods  Sixty rabbits were randomly divided into control group (control, myocardial infarction group (MI and left ventricular hypertrophy group (LVH(20 each. E/e' ratio was detected by flow Doppler and tissue Doppler imaging, and ELISA was performed to detect the PⅠCP/PⅢNP level at the 2nd, 4th, 8th and 12th week. The collagen volume fraction (CVF and Ⅰ/Ⅲcollagen ratio were detected with polarized light through picric-acid Sirius red staining at the 12th week. Results  The PⅠCP and PⅢNP levels increased in MI group and LVH group than in control group with statistically significant difference (P<0.05, and the PⅠCPand PⅢNP levels were also increased in MI group than in LVH group (P<0.05 in a time-dependent manner; The E/e' ratio increased in MI group and LVH group than in control group with statistically significant difference (P<0.05 in a time-dependent manner; The CVF increased in MI group and LVH group than in control group with statistically significant difference (P<0.05. The PⅠCPand PⅢNP levels were positively correlated with the E/e' ratio (P<0.05, and the PⅠCP/PⅢNP ratio was positively correlated with the Ⅰ/Ⅲcollagen ratio (P<0.05. Conclusion  The PⅠCP and PⅢNP levels can be used to evaluate the changes of cardiac diastolic function and myocardial collagen remodeling in different pathological conditions. DOI: 10.11855/j.issn.0577-7402.2016.08.06

  20. Circulating dipeptidyl peptidase IV activity correlates with cardiac dysfunction in human and experimental heart failure.

    Science.gov (United States)

    dos Santos, Leonardo; Salles, Thiago A; Arruda-Junior, Daniel F; Campos, Luciene C G; Pereira, Alexandre C; Barreto, Ana Luiza T; Antonio, Ednei L; Mansur, Alfredo J; Tucci, Paulo J F; Krieger, José E; Girardi, Adriana C C

    2013-09-01

    The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated. Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of ≈130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (≈50%) and heart tissue (≈3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion. Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.

  1. Cardiac-specific overexpression of thioredoxin 1 attenuates mitochondrial and myocardial dysfunction in septic mice.

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    Sánchez-Villamil, Juana P; D'Annunzio, Verónica; Finocchietto, Paola; Holod, Silvia; Rebagliati, Inés; Pérez, Hernán; Peralta, Jorge G; Gelpi, Ricardo J; Poderoso, Juan J; Carreras, María C

    2016-12-01

    Sepsis-induced myocardial dysfunction is associated with increased oxidative stress and mitochondrial dysfunction. Current evidence suggests a protective role of thioredoxin-1 (Trx1) in the pathogenesis of cardiovascular diseases. However, it is unknown yet a putative role of Trx1 in sepsis-induced myocardial dysfunction, in which oxidative stress is an underlying cause. Transgenic male mice with Trx1 cardiac-specific overexpression (Trx1-Tg) and its wild-type control (wt) were subjected to cecal ligation and puncture or sham surgery. After 6, 18, and 24h, cardiac contractility, antioxidant enzymes, protein oxidation, and mitochondrial function were evaluated. Trx1 overexpression improved the average life expectancy (Trx1-Tg: 36, wt: 28h; p=0.0204). Sepsis induced a decrease in left ventricular developed pressure in both groups, while the contractile reserve, estimated as the response to β-adrenergic stimulus, was higher in Trx1-Tg in relation to wt, after 6h of the procedure. Trx1 overexpression attenuated complex I inhibition, protein carbonylation, and loss of membrane potential, and preserved Mn superoxide dismutase activity at 24h. Ultrastructural alterations in mitochondrial cristae were accompanied by reduced optic atrophy 1 (OPA1) fusion protein, and activation of dynamin-related protein 1 (Drp1) (fission protein) in wt mice at 24h, suggesting mitochondrial fusion/fission imbalance. PGC-1α gene expression showed a 2.5-fold increase in Trx1-Tg at 24h, suggesting mitochondrial biogenesis induction. Autophagy, demonstrated by electron microscopy and increased LC3-II/LC3-I ratio, was observed earlier in Trx1-Tg. In conclusion, Trx1 overexpression extends antioxidant protection, attenuates mitochondrial damage, and activates mitochondrial turnover (mitophagy and biogenesis), preserves contractile reserve and prolongs survival during sepsis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Cardiac fibroblast GSK-3β regulates ventricular remodeling and dysfunction in ischemic heart

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    Lal, Hind; Ahmad, Firdos; Zhou, Jibin; Yu, Justine E.; Vagnozzi, Ronald J.; Guo, Yuanjun; Yu, Daohai; Tsai, Emily J.; Woodgett, James; Gao, Erhe; Force, Thomas

    2014-01-01

    Background Myocardial infarction-induced remodeling includes chamber dilatation, contractile dysfunction, and fibrosis. Of these, fibrosis is the least understood. Following MI, activated cardiac fibroblasts (CFs) deposit extracellular matrix. Current therapies to prevent fibrosis are inadequate and new molecular targets are needed. Methods and Results Herein we report that GSK-3β is phosphorylated (inhibited) in fibrotic tissues from ischemic human and mouse heart. Using two fibroblast-specific GSK-3β knockout mouse models, we show that deletion of GSK-3β in CFs leads to fibrogenesis, left ventricular dysfunction and excessive scarring in the ischemic heart. Deletion of GSK-3β induces a pro-fibrotic myofibroblast phenotype in isolated CFs, in post-MI hearts, and in MEFs deleted for GSK-3β. Mechanistically, GSK-3β inhibits pro-fibrotic TGF-β1-SMAD-3 signaling via interactions with SMAD-3. Moreover, deletion of GSK-3β resulted in the suppression of SMAD-3 transcriptional activity. This pathway is central to the pathology since a small molecule inhibitor of SMAD-3 largely prevented fibrosis and limited LV remodeling. Conclusion These studies support targeting GSK-3β in myocardial fibrotic disorders and establish critical roles of CFs in remodeling and ventricular dysfunction. PMID:24899689

  3. The incidence and prognostic significance of cardiac arrhythmias and conduction abnormalities in patients with acute coronary syndromes and renal dysfunction.

    Science.gov (United States)

    Lisowska, Anna; Tycińska, Agnieszka; Knapp, Małgorzata; Lisowski, Piotr; Musiał, Włodzimierz J

    2011-01-01

    The incidence of cardiac arrhythmias, including atrial fibrillation (AF) in chronic kidney disease, is unknown, although AF is several times more common in patients with end-stage kidney disease than in the general population. To assess the incidence, types and management of cardiac arrhythmias and conduction abnormalities in patients with acute coronary syndromes (ACS) and renal dysfunction. We also evaluated the prognostic significance of arrhythmias in this patient group. We analysed 86 patients with renal dysfunction (GFR Cardiac arrhythmias were observed in 44 (51.1%) patients with AF being the most common (27 patients, 31.4%), predominantly in the paroxysmal form (21.4%). A total of 14 (16.3%) patients had cardiac arrhythmias requiring temporary or permanent pacing. Only 4 (4.6%) patients showed transient conduction abnormalities due to hyperkalaemia in the course of renal failure, while the remaining 10 (11.6%) patients demonstrated conduction abnormalities due to ACS. A total of 3 (3.5%) patients had other arrhythmias (atrial tachycardia, ventricular arrhythmias). During the follow-up period (mean duration: 14.3 months) 7 out of 44 patients (15.9%) with renal dysfunction and arrhythmia and 2 out of 42 patients (4.7%) without arrhythmia died (p Cardiac arrhythmias occur more often in patients with ACS if renal dysfunction is also present and are associated with poor prognosis.

  4. Changes in cardiac heparan sulfate proteoglycan expression and streptozotocin-induced diastolic dysfunction in rats

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    Cestari Ismar N

    2011-04-01

    Full Text Available Abstract Background Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ-induced diabetes. Methods Diabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection, after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression. Results In vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E diastolic filling and isovolumic relaxation time (IVRT indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis. Conclusion Our data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles.

  5. Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis.

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    Dorbala, Sharmila; Vangala, Divya; Bruyere, John; Quarta, Christina; Kruger, Jenna; Padera, Robert; Foster, Courtney; Hanley, Michael; Di Carli, Marcelo F; Falk, Rodney

    2014-08-01

    The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis. Effort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD). Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product. Compared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (coronary vasodilator function. Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment.

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    Elenkova, Atanaska; Shabani, Rabhat; Kalinov, Krassimir; Zacharieva, Sabina

    2012-07-01

    In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited. To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy. Case-control study. A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls. Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17-4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22-5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects. Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

  7. Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction?

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    Hothi, S S; Tan, D K; Partridge, G; Tan, L B

    2015-04-01

    Low peak O2 consumption (VO2max/kg) has been widely used as an indirect indicator of poor cardiac fitness, and often guides management of patients with severe heart failure (HF). We hypothesized that it should be as good an indicator of cardiac dysfunction in obese and non-obese HF patients. We compared the cardiopulmonary exercise performance and non-invasive hemodynamics of 152 obese (BMI>34 kg.m(-2)) and 173 non-obese (BMI≤32) male HF patients in NYHA classes II and III, with reference to 101 healthy male controls. Their physical and cardiac functional reserves were measured during treadmill exercise testing with standard respiratory gas analyses and CO2 rebreathing to measure cardiac output non-invasively during peak exercise. Data are given as mean ± SD. Obese HF patients with BMI 40.9 ± 7.5 kg·m(-2) (age 56.1 ± 14.0 years, NYHA 2.5 ± 0.5) exercised to acceptable cardiopulmonary limits (peak RER=1.07 ± 0.12), and achieved a mean VO2max/kg of 18.6 ± 5.2 ml·kg(-1)·min(-1), significantly lower than in non-obese HF counterparts (19.9 ± 5.6 ml·kg(-1)·min(-1), P=0.02, age 55.8 ± 10.6 years, BMI 26.6 ± 3.1, NYHA 2.4 ± 0.5, peak RER=1.07 ± 0.09), with both lower than controls (38.5 ± 9.7 ml·kg(-1)·min(-1), PVO2max was higher in obese (2.31 ± 0.69 ml·min(-1)) than non-obese HF patients (1.61 ± 0.49 ml·min(-1), PVO2max/kg is not a generally reliable indicator of cardiac fitness in all patients. Instead, we found that despite having lower VO2max/kg, obese HF patients had stronger hearts capable of generating greater cardiac power than non-obese HF patients of equivalent clinical HF status. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Successful Fontan conversion combined with cardiac resynchronization therapy for a case of failing Fontan circulation with ventricular dysfunction.

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    Takeuchi, Daiji; Asagai, Seiji; Ishihara, Kazuaki; Nakanishi, Toshio

    2014-11-01

    Although Fontan conversion combined with cardiac resynchronization therapy appears to be an effective surgical solution for the management of failing Fontan circulation with refractory atrial arrhythmia and cardiac dysfunction due to dyssynchronous ventricular wall motion, limited data are available on the mid- to long-term results of this treatment. We report our successful experience with Fontan conversion combined with cardiac resynchronization therapy in a male patient with failing Fontan circulation who showed favourable outcomes 5 years after the operation. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  9. Two-Dimensional Speckle Tracking Echocardiography Detects Subclinical Left Ventricular Systolic Dysfunction among Adult Survivors of Childhood, Adolescent, and Young Adult Cancer

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    Anthony F. Yu

    2016-01-01

    Full Text Available Two-dimensional speckle tracking echocardiography (2DSTE provides a sensitive measure of left ventricular (LV systolic function and may aid in the diagnosis of cardiotoxicity. 2DSTE was performed in a cross-sectional study of 134 patients (mean age: 31.4±8.8 years; 55% male; mean time since diagnosis: 15.4±9.4 years previously treated with anthracyclines (mean cumulative dose: 320±124 mg/m2, with (n=52 or without (n=82 mediastinal radiotherapy. The prevalence of LV systolic dysfunction, defined as fractional shortening < 27%, LV ejection fraction (LVEF < 55%, and global longitudinal strain (GLS ≤ 16%, was 5.2%, 6.0%, and 23.1%, respectively. Abnormal GLS was observed in 24 (18% patients despite a normal LVEF. Indices of LV systolic function were similar regardless of anthracycline dose. However, GLS was worse (18.0 versus 19.0, p=0.003 and prevalence of abnormal GLS was higher (36.5% versus 14.6%, p=0.004 in patients treated with mediastinal radiotherapy. Mediastinal radiotherapy was associated with reduced GLS (p=0.040 after adjusting for sex, age, and cumulative anthracycline dose. In adult survivors of childhood, adolescent, and young adult cancer, 2DSTE frequently detects LV systolic dysfunction despite a normal LVEF and may be useful for the long-term cardiac surveillance of adult cancer survivors.

  10. Advanced glycation end product cross-link breaker attenuates diabetes-induced cardiac dysfunction by improving sarcoplasmic reticulum calcium handling

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    Allyson eKranstuber

    2012-07-01

    Full Text Available Diabetic heart disease is a distinct clinical entity that can progress to heart failure and sudden death. However, the mechanisms responsible for the alterations in excitation-contraction coupling leading to cardiac dysfunction during diabetes are not well known. Hyperglycemia, the landmark of diabetes, leads to the formation of advanced glycation end products (AGE on long-lived proteins, including SR Ca2+ regulatory proteins. However, their pathogenic role on SR Ca2+ handling in cardiac myocytes is unknown. Therefore, we investigated whether an AGE cross-link breaker could prevent the alterations in SR Ca2+ cycling that lead to in vivo cardiac dysfunction during diabetes. Streptozotocin-induced diabetic rats were treated with Alagebrium Chloride (ALT-711 for 8 weeks and compared to age-matched placebo-treated diabetic rats and healthy rats. Cardiac function was assessed by echocardiographic examination. Ventricular myocytes were isolated to assess SR Ca2+ cycling by confocal imaging and quantitative Western blots. Diabetes resulted in in vivo cardiac dysfunction and ALT-711 therapy partially alleviated diastolic dysfunction by decreasing isovolumetric relaxation time and myocardial performance index (by 27 and 41% vs. untreated diabetic rats, respectively, P<0.05. In cardiac myocytes, diabetes induced prolongation of cytosolic Ca2+ transient clearance by 43% and decreased SR Ca2+ load by 25% (P<0.05; these parameters were partially improved after ALT-711 therapy. SERCA2a and RyR2 protein expression was significantly decreased in the myocardium of untreated diabetic rats (by 64 and 36% vs. controls, respectively, P<0.05, but preserved in the treated diabetic group compared to controls. Collectively, our result suggest that, in a model of type 1 diabetes, AGE accumulation primarily impairs SR Ca2+ reuptake in cardiac myocytes and that long term treatment with an AGE cross-link breaker partially normalized SR Ca2+ handling and improved diabetic

  11. Celastrol-Induced Suppression of the MiR-21/ERK Signalling Pathway Attenuates Cardiac Fibrosis and Dysfunction

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    Mian Cheng

    2016-05-01

    Full Text Available Backgroud: Myocardial fibrosis results in myocardial remodelling and dysfunction. Celastrol, a traditional oriental medicine, has been suggested to have cardioprotective effects. However, its underlying mechanism is unknown. This study investigated the ability of celastrol to prevent cardiac fibrosis and dysfunction and explored the underlying mechanisms. Methods: Animal and cell models of cardiac fibrosis were used in this study. Myocardial fibrosis was induced by transverse aortic constriction (TAC in mice. Cardiac hypertrophy and fibrosis were evaluated based on histological and biochemical measurements. Cardiac function was evaluated by echocardiography. The levels of transforming growth factor beta 1 (TGF-β1, extracellular signal regulated kinases 1/2 (ERK1/2 signalling were measured using Western blotting, while the expression of miR-21was analyzed by real-time qRT-PCR in vitro and in vivo. In vitro studies, cultured cardiac fibroblasts (CFs were treated with TGF-β1 and transfected with microRNA-21(miR21. Results: Celastrol treatment reduced the increased collagen deposition and down-regulated α-smooth muscle actin (α-SMA, atrial natriuretic peptide (ANP, brain natriuretic peptides (BNP, beta-myosin heavy chain (β-MHC, miR-21 and p-ERK/ERK. Cardiac dysfunction was significantly attenuated by celastrol treatment in the TAC mice model. Celastrol treatment reduced myocardial fibroblast viability and collagen content and down-regulated α-SMA in cultured CFs in vitro. Celastrol also inhibited the miR-21/ERK signalling pathway. Celastrol attenuated miR-21 up-regulation by TGF-β1 and decreased elevated p-ERK/ERK levels in CFs transfected with miR-21. Conclusion: MiR-21/ERK signalling could be a potential therapeutic pathway for the prevention of myocardial fibrosis. Celastrol ameliorates myocardial fibrosis and cardiac dysfunction, these probably related to miR-21/ERK signaling pathways in vitro and in vivo.

  12. Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Congying [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Dong, Ruolan [Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Chen, Chen [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hong, E-mail: hong.wang1988@yahoo.com [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Dao Wen, E-mail: dwwang@tjh.tjmu.edu.cn [Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-12-25

    Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejection fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling. - Highlights: • ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction. • ACOT1 can regulate PPARa/PGC1a signaling pathway. • We first generate the transgenic mice with cardiomyocyte specific expression of ACOT1.

  13. Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner.

    Science.gov (United States)

    Redfors, Bjorn; Ali, Anwar; Shao, Yangzhen; Lundgren, Joel; Gan, Li-Ming; Omerovic, Elmir

    2014-06-15

    Takotsubo cardiomyopathy (TCM) is characterized by regional left ventricular dysfunction that cannot be explained by an occlusive lesion in a coronary artery. Catecholamines are implicated in the pathogenesis of TCM but the mechanisms involved are unknown. Because the endogenous and the most commonly used exogenous catecholamines have well defined adrenoceptor subtype affinities, inferences can be made about the importance of each adrenoceptor subtype based on the ability of different catecholamines to induce TCM. We therefore studied which of five well-known catecholamines, that differ in receptor subtype affinity, are able to induce TCM-like cardiac dysfunction in the rat. 255 rats received intraperitoneally isoprenaline (β1/β2-adrenoceptor agonist), epinephrine (β1/β2/α-adrenoceptor agonist), norepinephrine (β1/α-adrenoceptor agonist), dopamine (α/β1/β2-adrenoceptor agonist) or phenylephrine (α-adrenoceptor agonist). Each catecholamine was given in five different doses. We measured blood pressure through a catheter inserted in the right carotid artery and studied cardiac morphology and function by echocardiography. All catecholamines induced takotsubo-like cardiac dysfunction. Isoprenaline induced low blood pressure and predominantly apical dysfunction whereas the other catecholamines induced high blood pressure and basal dysfunction. In another set of experiments, we continuously infused hydralazine or nitroprusside to rats that received epinephrine or norepinephrine to maintain systolic blood pressure 120 mm Hg after isoprenaline administration prevented apical TCM-like dysfunction. Catecholamine-induced takotsubo-like cardiac dysfunction appears to be afterload dependent rather than depend on stimulation of a specific adrenergic receptor subtype. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Correlation between changes in diastolic dysfunction and health-related quality of life after cardiac rehabilitation program in dilated cardiomyopathy

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    Sherin H.M. Mehani

    2013-03-01

    Full Text Available Chronic heart failure (CHF is a complex syndrome characterized by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Left ventricular diastolic dysfunction plays a major role in CHF and progression of most cardiac diseases. The current recommended goals can theoretically be accomplished via exercise and pharmacological therapy so the aim of the present study was to evaluate the impact of cardiac rehabilitation program on diastolic dysfunction and health related quality of life and to determine the correlation between changes in left ventricular diastolic dysfunction and domains of health-related quality of life (HRQoL. Forty patients with chronic heart failure were diagnosed as having dilated cardiomyopathy (DCM with systolic and diastolic dysfunction. The patients were equally and randomly divided into training and control groups. Only 30 of them completed the study duration. The training group participated in rehabilitation program in the form of circuit-interval aerobic training adjusted according to 55–80% of heart rate reserve for a period of 7 months. Circuit training improved both diastolic and systolic dysfunction in the training group. On the other hand, only a significant correlation was found between improvement in diastolic dysfunction and health related quality of life measured by Kansas City Cardiomyopathy Questionnaire. It was concluded that improvement in diastolic dysfunction as a result of rehabilitation program is one of the important underlying mechanisms responsible for improvement in health-related quality of life in DCM patients.

  15. [Relationship between blood pressure, heart rate and cardiac autonomic dysfunction in non-diabetic obese patients].

    Science.gov (United States)

    Banu, I; Nguyen, M T; Hamo-Tchatchouang, E; Cosson, E; Valensi, P

    2015-06-01

    Some studies suggest that a high heart rate (HR) would be predictive of the incidence of an elevated blood pressure (BP). Cardiac autonomic dysfunction (CAD) affects a high proportion of obese patients. CAD could be involved in BP increase. Our aim was to examine the relationship between CAD, HR and BP in obese patients without known diabetes. We included 428 overweight or obese patients. CAD was assessed by analyzing HR variations during three standard tests (Valsalva, deep breathing, lying-to-standing), which are mostly dependent on vagal control. An oral load in glucose was performed and the Matsuda index was calculated. The population was separated in 4 groups according to the grade of CAD (no or only one abnormal test, 2 or 3 abnormal tests) and HR (heart rate, which is indicative of a more marked insulin resistance and probably an excess in sympathetic activity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats

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    Francis Lopes Pacagnelli

    2016-01-01

    Full Text Available Abstract Background: Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. Objective: To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Methods: Male Wistar rats were divided into 2 groups: control (C; n = 8 and monocrotaline-induced pulmonary arterial hypertension (M; n = 8. Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test, and the groups were compared with non-paired Student t test or Mann Whitney test (p < 0.05. Results: Higher fractal dimension values were observed in group M as compared to group C (1.39 ± 0.05 vs. 1.37 ± 0.04; p < 0.05. Echocardiography showed lower pulmonary artery flow velocity, pulmonary acceleration time and ejection time values in group M, suggesting function worsening in those animals. Conclusion: The changes observed confirm pulmonary-arterial-hypertension-induced cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction.

  17. Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis.

    Science.gov (United States)

    Tonial, Cristian T; Garcia, Pedro Celiny R; Schweitzer, Louise Cardoso; Costa, Caroline A D; Bruno, Francisco; Fiori, Humberto H; Einloft, Paulo R; Garcia, Ricardo Branco; Piva, Jefferson Pedro

    The aim of this study was to verify the association of echocardiogram, ferritin, C-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis. A prospective cohort study was carried out from March to December 2014, with pediatric critical care patients aged between 28 days and 18 years. Inclusion criteria were diagnosis of sepsis, need for mechanical ventilation for more than 48h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected on the first day (D0), 24h (D1), and 72h (D3) after recruitment. Patients underwent transthoracic echocardiography to determine the ejection fraction of the left ventricle on D1 and D3. The outcomes measured were length of hospital stay and in the pediatric intensive care unit, mechanical ventilation duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality. Twenty patients completed the study. Patients with elevated ferritin levels on D0 had also fewer ventilator-free hours (p=0.046) and higher maximum inotropic score (p=0.009). Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay (p=0.047), pediatric intensive care unit stay (p=0.020), duration of mechanical ventilation (p=0.011), maximum inotropic score (p=0.001), and fewer ventilator-free hours (p=0.020). Cardiac dysfunction by echocardiography and serum ferritin value was significantly associated with unfavorable outcomes in pediatric patients with sepsis. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  18. Use of natriuretic peptides for detecting cardiac dysfunction in long-term disease-free breast cancer survivors

    NARCIS (Netherlands)

    Perik, PJ; De Vries, EGE; Boomsma, F; Van Der Graaf, WTA; Sleijfer, DT; Van Veldhuisen, DJ; Gietema, JA

    2005-01-01

    Background: Plasma natriuretic peptides are increased in patients with cardiac dysfunction. N-terminal (NT-ANP) and B-type (BNP) natriuretic peptides were measured in disease-free breast cancer survivors, during long-term follow-up after epirubicin (360 mg/m(2) or 450 mg/m(2) cumulatively) and chest

  19. Induced Pluripotent Stem Cells-Derived Mesenchymal Stem Cells Attenuate Cigarette Smoke-Induced Cardiac Remodeling and Dysfunction

    Directory of Open Access Journals (Sweden)

    Yingmin Liang

    2017-07-01

    Full Text Available The strong relationship between cigarette smoking and cardiovascular disease (CVD has been well-documented, but the mechanisms by which smoking increases CVD risk appear to be multifactorial and incompletely understood. Mesenchymal stem cells (MSCs are regarded as an important candidate for cell-based therapy in CVD. We hypothesized that MSCs derived from induced pluripotent stem cell (iPSC-MSCs or bone marrow (BM-MSCs might alleviate cigarette smoke (CS-induced cardiac injury. This study aimed to investigate the effects of BM-MSCs or iPSC-MSCs on CS-induced changes in serum and cardiac lipid profiles, oxidative stress and inflammation as well as cardiac function in a rat model of passive smoking. Male Sprague-Dawley rats were randomly selected for exposure to either sham air (SA as control or 4% CS for 1 h per day for 56 days. On day 29 and 43, human adult BM-MSCs, iPSC-MSCs or PBS were administered intravenously to CS-exposed rats. Results from echocardiography, serum and cardiac lipid profiles, cardiac antioxidant capacity, cardiac pro- and anti-inflammatory cytokines and cardiac morphological changes were evaluated at the end of treatment. iPSC-MSC-treated group showed a greater effect in the improvement of CS-induced cardiac dysfunction over BM-MSCs-treated group as shown by increased percentage left ventricular ejection fraction and percentage fractional shortening, in line with the greater reversal of cardiac lipid abnormality. In addition, iPSC-MSCs administration attenuated CS-induced elevation of cardiac pro-inflammatory cytokines as well as restoration of anti-inflammatory cytokines and anti-oxidative markers, leading to ameliorate cardiac morphological abnormalities. These data suggest that iPSC-MSCs on one hand may restore CS-induced cardiac lipid abnormality and on the other hand may attenuate cardiac oxidative stress and inflammation via inhibition of CS-induced NF-κB activation, leading to improvement of cardiac remodeling and

  20. Cardiac remodeling and dysfunction in childhood obesity: a cardiovascular magnetic resonance study.

    Science.gov (United States)

    Jing, Linyuan; Binkley, Cassi M; Suever, Jonathan D; Umasankar, Nivedita; Haggerty, Christopher M; Rich, Jennifer; Wehner, Gregory J; Hamlet, Sean M; Powell, David K; Radulescu, Aurelia; Kirchner, H Lester; Epstein, Frederick H; Fornwalt, Brandon K

    2016-05-11

    Obesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children. Forty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index was 23 % greater (27 ± 4 g/m(2.7) vs 22 ± 3 g/m(2.7), p obese/overweight children. This evidence of cardiac remodeling was present in obese children as young as age 8. Twenty four percent of obese/overweight children had concentric hypertrophy, 59 % had normal geometry and 17 % had either eccentric hypertrophy or concentric remodeling. LV mass index, thickness, ejection fraction and peak longitudinal and circumferential strains all correlated with epicardial adipose tissue after adjusting for height and gender (all p remodeling, and were most impaired in children with concentric hypertrophy (p Obese children show evidence of significant cardiac remodeling and dysfunction, which begins as young as age 8. Obese children with concentric hypertrophy and impaired strain may represent a particularly high risk subgroup that demands further investigation.

  1. High-sugar intake does not exacerbate metabolic abnormalities or cardiac dysfunction in genetic cardiomyopathy.

    Science.gov (United States)

    Hecker, Peter A; Galvao, Tatiana F; O'Shea, Karen M; Brown, Bethany H; Henderson, Reney; Riggle, Heather; Gupte, Sachin A; Stanley, William C

    2012-05-01

    A high-sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development by increased reactive oxygen species (ROS). Glucose-6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH) for superoxide generation by NADPH oxidase. Conversely, G6PD also facilitates ROS scavenging using the glutathione pathway. We hypothesized that a high-sugar intake would increase flux through G6PD to increase myocardial NADPH and ROS and accelerate cardiac dysfunction and death. Six-week-old TO-2 hamsters, a non-hypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of high starch or high sugar (57% of energy from sucrose plus fructose). After 24 wk, the δ-sarcoglycan-deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control 68.7 ± 4.5%, TO-2 starch 46.1 ± 3.7%, P sugar 58.0 ± 4.2%, NS, versus TO-2 starch or control; median survival: TO-2 starch 278 d, TO-2 sugar 318 d, P = 0.133). Although the high-sugar intake was expected to exacerbate cardiomyopathy, surprisingly, there was no further decrease in ejection fraction or survival with high sugar compared with starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (increased serum lipids and glucose and decreased myocardial oxidative enzymes) that were unaffected by diet. The high-sugar intake increased myocardial superoxide, but NADPH and lipid peroxidation were unaffected. A sugar-enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in superoxide production. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Radiotherapy-Induced Cardiac Implantable Electronic Device Dysfunction in Patients With Cancer.

    Science.gov (United States)

    Bagur, Rodrigo; Chamula, Mathilde; Brouillard, Émilie; Lavoie, Caroline; Nombela-Franco, Luis; Julien, Anne-Sophie; Archambault, Louis; Varfalvy, Nicolas; Gaudreault, Valérie; Joncas, Sébastien X; Israeli, Zeev; Parviz, Yasir; Mamas, Mamas A; Lavi, Shahar

    2017-01-15

    Radiotherapy can affect the electronic components of a cardiac implantable electronic device (CIED) resulting in malfunction and/or damage. We sought to assess the incidence, predictors, and clinical impact of CIED dysfunction (CIED-D) after radiotherapy for cancer treatment. Clinical characteristics, cancer, different types of CIEDs, and radiation dose were evaluated. The investigation identified 230 patients, mean age 78 ± 8 years and 70% were men. A total of 199 patients had pacemakers (59% dual chamber), 21 (9%) cardioverter-defibrillators, and 10 (4%) resynchronizators or defibrillators. The left pectoral (n = 192, 83%) was the most common CIED location. Sixteen patients (7%) experienced 18 events of CIED-D after radiotherapy. Reset to backup pacing mode was the most common encountered dysfunction, and only 1 (6%) patient of those with CIED-D experienced symptoms of atrioventricular dyssynchrony. Those who had CIED-D tended to have a shorter device age at the time of radiotherapy compared to those who did not (2.5 ± 1.5 vs 3.8 ± 3.4 years, p = 0.09). The total dose prescribed to the tumor was significantly greater among those who had CIED-D (66 ± 30 vs 42 ± 23 Gy, p radiotherapy for cancer treatment, the occurrence of newly diagnosed CIED-D was 7%, and the reset to backup pacing mode was the most common encountered dysfunction. The total dose prescribed to the tumor was a predictor of CIED-D. Importantly, although the unpredictability of CIEDs under radiotherapy is still an issue, none of our patients experienced significant symptoms, life-threatening arrhythmias, or conduction disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Cardiac magnetic resonance determinants of functional mitral regurgitation in ischemic and non ischemic left ventricular dysfunction.

    Science.gov (United States)

    Fernández-Golfín, Covadonga; De Agustin, Alberto; Manzano, M Carmen; Bustos, Ana; Sánchez, Tibisay; Pérez de Isla, Leopoldo; Fuentes, Manuel; Macaya, Carlos; Zamorano, José

    2011-04-01

    Functional mitral regurgitation (FMR) is frequent in left ventricular (LV) dilatation/dysfunction. Echocardiographic predictors of FMR are known. However, cardiac magnetic resonance (CMR) predictors of FMR have not been fully addressed. The aim of the study was to evaluate CMR mitral valve (MV) parameters associated with FMR in ischemic and non ischemic LV dysfunction. 80 patients with LV ejection fraction below 45% and/or left ventricular dilatation of ischemic and non ischemic etiology were included. Cine-MR images (steady state free-precession) were acquired in a short-axis and 4 chambers views where MV evaluation was performed. Delayed enhancement was performed as well. Significant FMR was established as more than mild MR according to the echocardiographic report. Mean age was 59 years, males 79%. FMR was detected in 20 patients (25%) Significant differences were noted in LV functional parameters and in most MV parameters according to the presence of significant FMR. However, differences were noted between ischemic and non ischemic groups. In the first, differences in most MV parameters remained significant while in the non ischemic, only systolic and diastolic interpapillary muscle distance (1.60 vs. 2.19 cm, P = 0.001; 2. 51 vs. 3.04, P = 0.008) were predictors of FMR. FMR is associated with a more severe LV dilatation/dysfunction in the overall population. CMR MV parameters are associated with the presence of significant FMR and are different between ischemic and non ischemic patients. CMR evaluation of these patients may help in risk stratification as well as in surgical candidate selection.

  4. Cardiac Risk and Disordered Eating: Decreased R Wave Amplitude in Women with Bulimia Nervosa and Women with Subclinical Binge/Purge Symptoms.

    Science.gov (United States)

    Green, Melinda; Rogers, Jennifer; Nguyen, Christine; Blasko, Katherine; Martin, Amanda; Hudson, Dominique; Fernandez-Kong, Kristen; Kaza-Amlak, Zauditu; Thimmesch, Brandon; Thorne, Tyler

    2016-11-01

    The purpose of the present study was threefold. First, we examined whether women with bulimia nervosa (n = 12) and women with subthreshold binge/purge symptoms (n = 20) showed decreased mean R wave amplitude, an indicator of cardiac risk, on electrocardiograph compared to asymptomatic women (n = 20). Second, we examined whether this marker was pervasive across experimental paradigms, including before and after sympathetic challenge tasks. Third, we investigated behavioural predictors of this marker, including binge frequency and purge frequency assessed by subtype (dietary restriction, excessive exercise, self-induced vomiting, and laxative abuse). Results of a 3 (ED symptom status) × 5 (experimental condition) mixed factorial ANCOVA (covariates: body mass index, age) indicated women with bulimia nervosa and women with subclinical binge/purge symptoms demonstrated significantly reduced mean R wave amplitude compared to asymptomatic women; this effect was pervasive across experimental conditions. Multiple regression analyses showed binge and purge behaviours, most notably laxative abuse as a purge method, predicted decreased R wave amplitude across all experimental conditions. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  5. Relationship between epicardial adipose tissue and subclinical coronary artery disease in patients with extra-cardiac arterial disease.

    Science.gov (United States)

    den Dekker, M A M; Takashima, R; van den Heuvel, E R; van den Dungen, J J A M; Tio, R A; Oudkerk, M; Vliegenthart, R

    2014-01-01

    Epicardial adipose tissue (EAT) and mediastinal adipose tissue (MAT) are linked to coronary artery disease (CAD). The association between EAT, MAT, and severity of CAD in known extra-cardiac arterial disease was investigated. Sixty-five cardiac asymptomatic patients (mean age 65 ± 8 years, 69% male) with peripheral arterial disease, carotid stenosis, or aortic aneurysm underwent coronary computed tomography angiography. Patients were divided into non-significant (cardiovascular risk factors. Median EAT was 99.5, 98.0, and 112.0 cm(3) (P = 0.38) and median MAT was 66.0, 90.0, and 81.0 cm(3) (P = 0.53) for non-significant, single vessel, and multi-vessel CAD, respectively. In age- and gender-adjusted analysis, only EAT was significantly associated with CAD (odds ratio [OR] 1.12 [95% confidence interval, 1.01-1.25] per 10 cm(3) increase in EAT; P = 0.04). This remained in multivariate-adjusted analysis (OR 1.21 [1.04-1.39]; P = 0.01). In patients with known extra-cardiac arterial disease, CAD is correlated with EAT, but not with MAT. These results suggest that EAT has a local effect on coronary atherosclerosis, apart from the endocrine effect of visceral fat. © 2013 The Obesity Society.

  6. Safety and efficacy of landiolol hydrochloride for prevention of atrial fibrillation after cardiac surgery in patients with left ventricular dysfunction: Prevention of Atrial Fibrillation After Cardiac Surgery With Landiolol Hydrochloride for Left Ventricular Dysfunction (PLATON) trial.

    Science.gov (United States)

    Sezai, Akira; Osaka, Shunji; Yaoita, Hiroko; Ishii, Yusuke; Arimoto, Munehito; Hata, Hiroaki; Shiono, Motomi

    2015-10-01

    We previously conducted a prospective study of landiolol hydrochloride (INN landiolol), an ultrashort-acting β-blocker, and reported that it could prevent atrial fibrillation after cardiac surgery. This trial was performed to investigate the safety and efficacy of landiolol hydrochloride in patients with left ventricular dysfunction undergoing cardiac surgery. Sixty patients with a preoperative left ventricular ejection fraction of less than 35% were randomly assigned to 2 groups before cardiac surgery and then received intravenous infusion with landiolol hydrochloride (landiolol group) or without landiolol (control group). The primary end point was occurrence of atrial fibrillation as much as 1 week postoperatively. The secondary end points were blood pressure, heart rate, intensive care unit and hospital stays, ventilation time, ejection fraction, biomarkers of ischemia, and brain natriuretic peptide. Atrial fibrillation occurred in 3 patients (10%) in the landiolol group versus 12 (40%) in the control group, and its frequency was significantly lower in the landiolol group (P = .002). During the early postoperative period, levels of brain natriuretic peptide and ischemic biomarkers were significantly lower in the landiolol group than the control group. The landiolol group also had a significantly shorter hospital stay (P = .019). Intravenous infusion was not discontinued for hypotension or bradycardia in either group. Low-dose infusion of landiolol hydrochloride prevented atrial fibrillation after cardiac surgery in patients with cardiac dysfunction and was safe, with no effect on blood pressure. This intravenous β-blocker seems useful for perioperative management of cardiac surgical patients with left ventricular dysfunction. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  7. Effect of Commiphora mukul extract on cardiac dysfunction and ventricular function in isoproterenol-induced myocardial infarction.

    Science.gov (United States)

    Ojha, Shreesh K; Nandave, Mukesh; Arora, Sachin; Mehra, Raj D; Joshi, Sujata; Narang, Rajiv; Arya, D S

    2008-09-01

    In present study, hydroalcoholic extract of C. mukul significantly improved the cardiac function and prevented myocardial ischemic impairment manifested in the form of increased heart rate, decreased arterial pressure, increased left ventricular end diastolic pressure, and altered myocardial contractility indices. C. mukul treatment additionally also produced a significant increase in lactate dehydrogenase levels and prevented decline of protein content in heart. C. mukul preserved the structural integrity of myocardium. Reduced leakage of myocyte enzyme lactate dehydrogenase and maintenance of structural integrity of myocardium along with favorable modulation of cardiac function and improved cardiac performance indicate the salvage of myocardium with C. mukul treatment. Guggulsterones which are considered to be responsible for most of the therapeutic properties of C. mukul may underlie the observed cardioprotective effect of C. mukul against cardiac dysfunction in isoproterenol-induced ischemic rats.

  8. Treatment of subclinical hyperthyroidism

    DEFF Research Database (Denmark)

    Mark, Peter D; Andreassen, Mikkel; Petersen, Claus L

    2015-01-01

    PURPOSE: The aim of this study was to investigate structure and function of the heart in subclinical hyperthyroidism (SH) before and after obtaining euthyroidism by radioactive iodine treatment, using high precision and observer-independent magnetic resonance imaging (MRI) technology. METHODS......: Cardiac MRI was performed before and after euthyroidism was obtained by radioactive iodine treatment in 12 otherwise healthy patients (11 women and one man, mean age 59 years, range 44-71 years) with a nodular goiter and SH, and compared with eight healthy controls investigated at baseline. Cardiac data...... were expressed as an index, as per body surface area, except for heart rate (HR) and ejection fraction. RESULTS: Post-treatment cardiac MRI was performed in median 139 days after a normalized serum TSH value had been recorded. During treatment, serum TSH increased from (median (range)) 0.01 (0...

  9. The subclinical effect of celiac disease on the heart and the effect of gluten-free diet on cardiac functions.

    Science.gov (United States)

    Karadaş, Ulaş; Eliaçık, Kayı; Baran, Maşallah; Kanık, Ali; Özdemir, Nihal; İnce, Osman Tolga; Bakiler, Ali Rahmi

    2016-01-01

    This study aimed to investigate the effects of celiac disease (CD) on cardiac function in children by using conventional transthoracic echocardiography (TTE) and tissue Doppler echocardiography (TDE). Forty-nine patients diagnosed with CD were enrolled into the study. Group 1 consisted of 26 (53%) patients who had recently been diagnosed and had not been on gluten-free diet whereas Group 2 consisted of 23 (47%) patients who had been on regular gluten-free diet for at least 10 months. 20 healthy children were enrolled into the study as the control group. The deceleration time (DT) and the left ventricle (LV) isovolumetric relaxation time (IVRT) were significantly shorter in Group 1 compared to Group 2 and the control group (p=0.002, p=0.015). Mitral valve E/E' ratio was significantly lower in Group 1 and 2 when compared to the control group (p < 0.001). The study demonstrated that evaluation of these parameters by using TDE could be beneficial in the early diagnosis of cardiac involvement in children with CD.

  10. Hemodynamic changes after levothyroxine treatment in subclinical hypothyroidism

    DEFF Research Database (Denmark)

    Faber, J; Petersen, L; Wiinberg, N

    2002-01-01

    In hypothyroidism, lack of thyroid hormones results in reduced cardiac function (cardiac output [CO]), and an increase of systemic vascular resistance (SVR). We speculated whether hemodynamic regulation in subjects with subclinical hypothyroidism (SH) (defined as mildly elevated thyrotropin [TSH...

  11. In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients.

    Science.gov (United States)

    Sasse, Michael; Dziuba, Friederike; Jack, Thomas; Köditz, Harald; Kaussen, Torsten; Bertram, Harald; Beerbaum, Philipp; Boehne, Martin

    2015-08-01

    Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused particles may exacerbate inflammatory syndromes since they activate the coagulation cascade and alter inflammatory response or microvascular perfusion. In a randomized, controlled, prospective trial, we have previously shown that particle-retentive in-line filtration prevented major complications in critically ill children. Now, we investigated the effect of in-line filtration on major complications in the subgroup of cardiac patients. Children admitted to tertiary pediatric intensive care unit were randomized to either control or filter group obtaining in-line filtration throughout complete infusion therapy. Risk differences and 95 % confidence intervals (CI) of several complications such as SIRS, sepsis, mortality, various organ failure and dysfunction were compared between both groups using the Wald method. 305 children (n = 150 control, n = 155 filter group) with cardiac diseases were finally analyzed. The majority was admitted after cardiac surgery with CPB. Risk of SIRS (-11.3 %; 95 % CI -21.8 to -0.5 %), renal (-10.0 %; 95 % CI -17.0 to -3.0 %) and hematologic (-8.1 %; 95 % CI -14.2 to -0.2 %) dysfunction were significantly decreased within the filter group. No risk differences were demonstrated for occurrence of sepsis, any other organ failure or dysfunctions between both groups. Infused particles might aggravate a systemic hypercoagulability and inflammation with subsequent organ malfunction in pediatric cardiac intensive care patients. Particle-retentive in-line filtration might be effective in preventing SIRS and maintaining renal and hematologic function. In-line filtration offers a novel therapeutic option to decrease morbidity in cardiac intensive care.

  12. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Benter

    2013-01-01

    Full Text Available Aims. We evaluated the effects of RU28318 (RU, a selective mineralocorticoid receptor (MR antagonist, Captopril (Capt, an angiotensin converting enzyme inhibitor, and Losartan (Los, an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R- induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I followed by a period of 30 min of reperfusion (R. Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple. Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving -dP/dt (a measure of diastolic function when administered to diabetic hearts after ischemia.

  13. Secoisolariciresinol diglucoside attenuates cardiac hypertrophy and oxidative stress in monocrotaline-induced right heart dysfunction.

    Science.gov (United States)

    Puukila, Stephanie; Fernandes, Rafael Oliveira; Türck, Patrick; Carraro, Cristina Campos; Bonetto, Jéssica Hellen Poletto; de Lima-Seolin, Bruna Gazzi; da Rosa Araujo, Alex Sander; Belló-Klein, Adriane; Boreham, Douglas; Khaper, Neelam

    2017-08-01

    Pulmonary arterial hypertension (PAH) occurs when remodeling of pulmonary vessels leads to increased pulmonary vascular resistance resulting in increased pulmonary arterial pressure. Increased pulmonary arterial pressure results in right ventricle hypertrophy and eventually heart failure. Oxidative stress has been implicated in the pathogenesis of PAH and may play a role in the regulation of cellular signaling involved in cardiac response to pressure overload. Secoisolariciresinol diglucoside (SDG), a component from flaxseed, has been shown to reduce cardiac oxidative stress in various pathophysiological conditions. We investigated the potential protective effects of SDG in a monocrotaline-induced model of PAH. Five- to six-week-old male Wistar rats were given a single intraperitoneal injection of monocrotaline (60 mg/kg) and sacrificed 21 days later where heart, lung, and plasma were collected. SDG (25 mg/kg) was given via gavage as either a 21-day co-treatment or pre-treatment of 14 days before monocrotaline administration and continued for 21 days. Monocrotaline led to right ventricle hypertrophy, increased lipid peroxidation, and elevated plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). Co-treatment with SDG did not attenuate hypertrophy or ALT and AST levels but decreased reactive oxygen species (ROS) levels and catalase and superoxide dismutase activity compared to the monocrotaline-treated group. Pre-treatment with SDG decreased right ventricle hypertrophy, ROS levels, lipid peroxidation, catalase, superoxide dismutase, and glutathione peroxidase activity and plasma levels of ALT and AST when compared to the monocrotaline group. These findings indicate that pre-treatment with SDG provided better protection than co-treatment in this model of right heart dysfunction, suggesting an important role for SDG in PAH and right ventricular remodeling.

  14. Elevated level of pro-inflammatory eicosanoids and EPC dysfunction in diabetic patients with cardiac ischemia

    Science.gov (United States)

    Issan, Yossi; Hochhauser, Edith; Guo, Austin; Gotlinger, Katherine H.; Kornowski, Ran; Leshem-Lev, Dorit; Lev, Eli; Porat, Eyal; Snir, Eitan; Thompson, Carl I.; Abraham, Nader G.; Laniado-Schwartzman, Michal

    2015-01-01

    Background Circulating endothelial progenitor cells (EPCs) are recruited from the blood system to sites of ischemia and endothelial damage, where they contribute to the repair and development of blood vessels. Since numerous eicosanoids including leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) have been shown to exert potent pro-inflammatory activities, we examined their levels in chronic diabetic patients with severe cardiac ischemia in conjunction with the level and function of EPCs. Results Lipidomic analysis revealed a diabetes-specific increase (p<0.05) in inflammatory and angiogenic eicosanoids including the 5-lipoxygenase-derived LTB4 (4.11±1.17 vs 0.96±0.27 ng/ml), the lipoxygenase/CYP-derived 12-HETE (117.08±35.05 vs 24.34±10.03 ng/ml), 12-HETrE (17.56±4.43 vs 4.15±2.07 ng/ml), and the CYP-derived 20-HETE (0.32±0.04 vs 0.06±0.05 ng/ml) the level of which correlated with BMI (p=0.0027). In contrast, levels of the CYP-derived EETs were not significantly (p= 0.36) different between these two groups. EPC levels and their colony forming units were lower (p<0.05) with a reduced viability in diabetic patients compared with non-diabetics. EPC function (Colony-Forming Units (CFUs) and MTT assay) also negatively correlated with the circulating levels of HgA1C. Conclusion This study demonstrates a close association between elevated levels of highly pro-inflammatory eicosonoids, diabetes and EPC dysfunction in patients with cardiac ischemia, indicating that chronic inflammation impact negatively on EPC function and angiogenic capacity in diabetes. PMID:23291334

  15. Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure.

    Science.gov (United States)

    Pellicori, Pierpaolo; Cleland, John G F; Zhang, Jufen; Kallvikbacka-Bennett, Anna; Urbinati, Alessia; Shah, Parin; Kazmi, Syed; Clark, Andrew L

    2016-12-01

    Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513-1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

  16. Phenotypic patterns of right ventricular dysfunction: analysis by cardiac magnetic imaging

    Directory of Open Access Journals (Sweden)

    Esther Zorio-Grima

    2013-01-01

    Full Text Available The aim of this study was to use magnetic resonance imaging (MRI to classify the morphological changes and remodeling of the right ventricle (RV that occur in different clinical situations and that have an impact on RV function. Most literature has traditionally focused on the left ventricle (LV and as a result, few studies analyze RV behavior and remodeling. The study evaluated all cardiac MRI performed at our center from 2008 to 2010. We retrospectively identified 159 patients who had some sign of right ventricular dysfunction (RVD based on MRI findings. We classified patients according to a combination of criteria for RVD and the presence of left ventricle dysfunction (LVD. We considered RVD as any of the following abnormalities: i depressed RV function; ii RV dilatation; iii RV hypertrophy. LVD was considered when there was atrial dilatation, LV hypertrophy, LV dilatation and/or depressed LV function. We obtained 6 pathophysiological patterns: RV pressure overload (1.9%, RV volume overload (15.7%, RV volume overload + LVD (32.7%, depressed RV function + LVD (42.1%, mixed RV overload + LVD (6.9% and other (0.6%. The most frequent etiology was congenital heart disease (33.3%, followed by idiopathic dilated cardiomyopathy (18.2%, left valvular disease (17.6%, ischemic heart disease (15%, pulmonary disease (9.8%, and other (6.1%. This study helps to classify the different patterns that RV can adopt in different clinical situations and can, therefore, help us to understand the RV pathophysiology.

  17. Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction.

    Science.gov (United States)

    Schumacher, Sarah M; Gao, Erhe; Zhu, Weizhong; Chen, Xiongwen; Chuprun, J Kurt; Feldman, Arthur M; Tesmer, John J G; Koch, Walter J

    2015-03-04

    Heart failure (HF) is a disease of epidemic proportion and is associated with exceedingly high health care costs. G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) kinase 2 (GRK2), which is up-regulated in the failing human heart, appears to play a critical role in HF progression in part because enhanced GRK2 activity promotes dysfunctional adrenergic signaling and myocyte death. Recently, we found that the selective serotonin reuptake inhibitor (SSRI) paroxetine could inhibit GRK2 with selectivity over other GRKs. Wild-type mice were treated for 4 weeks with paroxetine starting at 2 weeks after myocardial infarction (MI). These mice were compared with mice treated with fluoxetine, which does not inhibit GRK2, to control for the SSRI effects of paroxetine. All mice exhibited similar left ventricular (LV) dysfunction before treatment; however, although the control and fluoxetine groups had continued degradation of function, the paroxetine group had considerably improved LV function and structure, and several hallmarks of HF were either inhibited or reversed. Use of genetically engineered mice indicated that paroxetine was working through GRK2 inhibition. The beneficial effects of paroxetine were markedly greater than those of β-blocker therapy, a current standard of care in human HF. These data demonstrate that paroxetine-mediated inhibition of GRK2 improves cardiac function after MI and represents a potential repurposing of this drug, as well as a starting point for innovative small-molecule GRK2 inhibitor development. Copyright © 2015, American Association for the Advancement of Science.

  18. Discriminating between cardiac and pulmonary dysfunction in the general population with dyspnea by plasma pro-B-type natriuretic peptide

    DEFF Research Database (Denmark)

    Mogelvang, R; Goetze, JP; Schnohr, P

    2007-01-01

    OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac...... the expected concentration of plasma proBNP based on age and gender was established for dyspneic subjects: an actual plasma proBNP concentration below half of the expected value ruled out left ventricular systolic and diastolic dysfunction (sensitivity 100%, 95% CI 100% to 100%; specificity 15%, 95% CI 12...

  19. Protective effects of ulinastatin on cardiac dysfunction in mice with heat stroke and its mechanism

    Directory of Open Access Journals (Sweden)

    Jing-jing JI

    2017-06-01

    Full Text Available Objective To examine the effects of ulinastatin (UTI on cardiac dysfunction in mice with heat stroke and its possible mechanism. Methods 20 mice were divided into four groups randomly: room temperature plus normal saline (Sham+NS, room temperature plus UTI (Sham+UTI, heat stress plus normal saline (HS+NS, heat stress plus UTI (HS+UTI, 5 each. 105U/kg UTI was delivered by intraperitoneal injection before the onset of the heat stress. Room temperature groups were housed at room temperature (23.0±0.5℃, while heat stress groups were kept in an incubator at 36.5±0.5℃ and humidity of 65.0%±2.0%. The rectal temperature (Tr reaching 42℃ was taken as severe heat stroke, and the time in two heat stress groups was recorded. The mice were transferred to the room temperature (23.0±0.5℃ for natural cooling after the heat stroke onset. 6 hours after the treatment, cardiac output (CO was ultrasonographically detected, the myocardium was separated for histopathological examination and the expression of total p38 and phosphorylated p38 (p-p38 was determined by Western blotting. Results The time to reach 42℃ in HS+UTI group was significantly prolonged (P=0.044. Compared with the Sham+NS group, the CO in HS+NS and HS+UTI group decreased significantly (P=0.017, and the score of myocardial inflammation (P<0.001 and p-p38/p38 ratio (P<0.001 increased. The CO was significantly higher in HS+UTI group than in HS+NS group (P=0.030, and the score of myocardial inflammation (P<0.001 and p-p38/p38 ratio (P=0.001 were significantly lower. Conclusion Ulinastatin might improve the cardiac function in mice with heat stroke by decreasing the p-p38 and alleviating the inflammation response. DOI: 10.11855/j.issn.0577-7402.2017.04.04

  20. Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Sogaard, Peter; Pedersen, Sune A

    2009-01-01

    ; P=0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third...... parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function....

  1. Cardiac fibroblasts contribute to myocardial dysfunction in mice with sepsis: the role of NLRP3 inflammasome activation.

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    Wenbo Zhang

    Full Text Available Myocardial contractile dysfunction in sepsis is associated with the increased morbidity and mortality. Although the underlying mechanisms of the cardiac depression have not been fully elucidated, an exaggerated inflammatory response is believed to be responsible. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3 inflammasome is an intracellular platform that is involved in the maturation and release of interleukin (IL-1β. The aim of the present study is to evaluate whether sepsis activates NLRP3 inflammasome/caspase-1/IL-1β pathway in cardiac fibroblasts (CFs and whether this cytokine can subsequently impact the function of cardiomyocytes (cardiac fibroblast-myocyte cross-talk. We show that treatment of CFs with lipopolysaccharide (LPS induces upregulation of NLRP3, activation of caspase-1, as well as the maturation (activation and release of IL-1β. In addition, the genetic (small interfering ribonucleic acid [siRNA] and pharmacological (glyburide inhibition of the NLRP3 inflammasome in CFs can block this signaling pathway. Furthermore, the inhibition of the NLRP3 inflammasome in cardiac fibroblasts ameliorated the ability of LPS-challenged CFs to impact cardiomyocyte function as assessed by intracellular cyclic adenosine monophosphate (cAMP responses in cardiomyocytes. Salient features of this the NLP3 inflammasome/ caspase-1 pathway were confirmed in in vivo models of endotoxemia/sepsis. We found that inhibition of the NLRP3 inflammasome attenuated myocardial dysfunction in mice with LPS and increased the survival rate in mice with feces-induced peritonitis. Our results indicate that the activation of the NLRP3 inflammasome in cardiac fibroblasts is pivotal in the induction of myocardial dysfunction in sepsis.

  2. Serum from Diesel Exhaust-Exposed Rats with Cardiac Dysfunction Alters Aortic Endothelial Cell Function In Vitro: Circulating Mediators as Causative Factors?

    Science.gov (United States)

    Although circulating inflammatory mediators are strongly associated with adverse cardiovascular outcomes triggered by inhaled air pollution, direct cause-effect linkage has not been established. Given that endothelial toxicity often precedes and precipitates cardiac dysfunction, ...

  3. Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

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    Mohammad T. Elnakish

    2015-01-01

    Full Text Available Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models.

  4. Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

    Science.gov (United States)

    Elnakish, Mohammad T.; Ahmed, Amany A. E.; Mohler, Peter J.; Janssen, Paul M. L.

    2015-01-01

    Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID:26146529

  5. Low Molecular Weight Fucoidan Alleviates Cardiac Dysfunction in Diabetic Goto-Kakizaki Rats by Reducing Oxidative Stress and Cardiomyocyte Apoptosis

    Directory of Open Access Journals (Sweden)

    Xinfeng Yu

    2014-01-01

    Full Text Available Diabetic cardiomyopathy (DCM is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase C β, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.

  6. Mice lacking the Cβ subunit of PKA are resistant to angiotensin II-induced cardiac hypertrophy and dysfunction.

    Science.gov (United States)

    Enns, Linda C; Bible, Kenneth L; Emond, Mary J; Ladiges, Warren C

    2010-11-16

    PKA is a ubiquitous, multi-subunit cellular kinase that regulates a number of different physiological responses in response to cAMP, including metabolism, cell division, and cardiac function. Numerous studies have implicated altered PKA signaling in cardiac dysfunction. Recently, it has been shown that mice lacking the catalytic β subunit of PKA (PKA Cβ) are protected from age-related problems such as weight gain and enlarged livers, and we hypothesized that these mice might also be resistant to cardiomyopathy. Angiotensin II (ang II) induced hypertension in both PKA Cβ null mice and their WT littermates. However, PKA Cβ null mice were resistant to a number of ang II-induced, cardiopathological effects observed in the WT mice, including hypertrophy, decreased diastolic performance, and enlarged left atria. The Cβ subunit of PKA plays an important role in angiotensin-induced cardiac dysfunction. The Cβ null mouse highlights the potential of the PKA Cβ subunit as a pharmaceutical target for hypertrophic cardiac disease.

  7. Subclinical hypothyroidism

    DEFF Research Database (Denmark)

    Bak, Peter; Hjortshøj, Cristel S; Gaede, Peter

    2018-01-01

    OBJECTIVE: Cyanotic congenital heart disease is a systemic disease, with effects on multiple organ systems. A high prevalence of subclinical hypothyroidism (SCH) has been reported in a small cohort of cyanotic congenital heart disease patients. Subclinical hypothyroidism has been associated...... with various adverse cardiovascular effects, as well as an increased risk of progression to overt hypothyroidism. The aim of this study was to examine the prevalence of SCH in cyanotic congenital heart disease patients, consider possible etiologies, and evaluate thyroid function over time. METHODS: First, 90...... follow-up (6.5 ± 1.0 years), SCH (defined as ≥2 consecutive elevated thyroid-stimulating hormone values) was present in 26%. Three patients progressed to overt hypothyroidism. Patients with SCH were younger (34 ± 12 vs 42 ± 16 years; P = .01) and had a lower oxygen saturation (80 ± 5 vs 84 ± 6%; P = .03...

  8. Prophylactic furosemide infusion decreasing early major postoperative renal dysfunction in on-pump adult cardiac surgery: a randomized clinical trial

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    Fakhari S

    2017-01-01

    Full Text Available Solmaz Fakhari,1 Fariba Mirzaei Bavil,2 Eissa Bilehjani,1 Sona Abolhasani,3 Moussa Mirinazhad,2 Bahman Naghipour2 1Department of Anesthesiology, 2Department of Physiology, 3Tabriz University of Medical Sciences, Tabriz, Iran Introduction: Acute renal dysfunction is a common complication of cardiac surgery. Furosemide is used in prevention, or treatment, of acute renal dysfunction. This study was conducted to evaluate the protective effects of intra- and early postoperative furosemide infusion on preventing acute renal dysfunction in elective adult cardiac surgery. Methods: Eighty-one patients, candidates of elective cardiac surgery, were enrolled in this study in either the furosemide (n=41 or placebo (n=40 group. Furosemide (2 mg/h or 0.9% saline was administered and continued up to 12 hours postoperatively. We measured serum creatinine (Scr at preoperative and on the second and fifth postoperative days. Then calculated estimated glomerular filtration rate (eGFR at these times. An increase in Scr of >0.5 mg/dL and/or >25%–50%, compared to preoperative values, was considered as acute kidney injury (AKI. In contrast, an increase in Scr by >50% and/or the need for hemodialysis was regarded as acute renal failure (ARF. At the end we compared the AKI or ARF incidence between the two groups. Results: On the second and fifth postoperative days, Scr was lower, and the eGFR was higher in the furosemide group. AKI incidence was similar in the two groups (11 vs 12 cases; P-value 0.622; however, ARF rate was lower in furosemide group (1 vs 6 cases; P-value 0.044. During the study period, Scr was more stable in the furosemide group, however in the placebo group, Scr initially increased and then decreased to its preoperative value after a few days. Conclusion: This study showed that intra- and early postoperative furosemide infusion has a renal protective effect in adult cardiac surgery with cardiopulmonary bypass. Although this protective effect cannot

  9. Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity.

    Science.gov (United States)

    Li, Wei; Tang, Renqiao; Ouyang, Shengrong; Ma, Feifei; Liu, Zhuo; Wu, Jianxin

    2017-01-01

    Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

  10. Milrinone for cardiac dysfunction in critically ill adult patients : a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

    NARCIS (Netherlands)

    Koster, Geert; Bekema, Hanneke J.; Wetterslev, Jorn; Gluud, Christian; Keus, Frederik; van der Horst, Iwan C. C.

    Milrinone is an inotrope widely used for treatment of cardiac failure. Because previous meta-analyses had methodological flaws, we decided to conduct a systematic review of the effect of milrinone in critically ill adult patients with cardiac dysfunction. This systematic review was performed

  11. Evaluation of endothelial function in exogenous subclinical hyperthyroidism and the effect of treatment

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    Sayed Mohammad Hosseini

    2016-01-01

    Conclusions: This study demonstrated that FMD decreased in exogenous subclinical hyperthyroid patients which could be partially restored by treatment. These findings suggest that treatment of subclinical hyperthyroid state could improve endothelial dysfunction and at the end decreased the cardiovascular complications.

  12. History of alcohol abuse after major non-cardiac surgery and postoperative cognitive dysfunction.

    Science.gov (United States)

    Gvozdenović, Ljiljana; Antanasković, Ana

    2015-11-01

    The risk factors for postoperative cognitive dysfunction (POCD) after non-cardiac surgery include advanced age and preexisting cognitive impairment. Data was collected in a prospective manner on 220 patients of both genders. Patients were triaged into three groups, with American Society of Anesthesiologists-ASA Physical Classification System levels I-IV. Patients were 55 years of age and older, with self-reported alcohol abuse and were matched to age-, sex-, and education-matched nonalcoholic controls. They were tested using a neurocognitive battery before and two weeks after elective surgery or after a corresponding time interval without surgery. Verbal memory, visuospatial memory, and executive functions were assessed. Neurologic examination was performed in order to exclude subjects with potential cerebrovascular damage. Standard laboratory analyses were done and findings recorded. Significant predisposing factors for developing POCD were noted. From the total number of participants involved in the study, 135 (67.5%) patients belonged to ASA class III. Among all patients, 168 (84%) patients were chronic alcohol users. Pearson's χ(2) test shows a statistically significant difference regarding the use of alcohol (χ(2)=19.220, df=1, p=0.000, palcoholic group decreased after surgery. In the study by Mason which involved 255 elderly patients that were postoperatively admitted to the intensive care unit following a major abdominal surgery, development of POCD was two times greater in urgent cases (~40% of cases), when compared to elective interventions. Our results complement the data given by the World Health Organization and results of similar studies. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  13. The regulation of NLRP3 inflammasome expression during the development of cardiac contractile dysfunction in chronic kidney disease.

    Science.gov (United States)

    Chin, Li-Han; Hsu, Yu-Juei; Hsu, Shih-Che; Chen, Yen-Hui; Chang, Yung-Lung; Huang, Shih-Ming; Tsai, Chien-Sung; Lin, Chih-Yuan

    2017-12-26

    Chronic inflammation plays a crucial role in the long-term complications in patients with chronic kidney disease (CKD). This study aimed to assess the role of NLR pyrin domain-containing protein (NLRP3) inflammasome in cardiac contractile dysfunctions in CKD. The cardiac contractile function was evaluated and the expression of NLRP3 inflammasome and related cytokines in the heart was assessed in a murine sham-operated and 5/6 nephrectomy CKD model in vivo . In vitro , H9c2 cells were treated with uremic toxin indoxyl sulfate (IS), with or without NLRP3 inflammasome inhibition, which was achieved by using small interfering RNA (siRNA)-mediated knockdown of the NLRP3 gene. Moreover, the activation of nuclear factor κB (NF-κB) signaling and apoptosis marker levels were assessed in the IS-treated H9c2 cells. The results demonstrated that CKD can lead to the development of cardiac contractile dysfunction in vivo associated with the upregulation of NLRP3 inflammasome, IL-1β, IL-18, and contribute to the myocardial apoptosis. In vitro experiments showed the upregulation of inflammasome, IL-1β, and IL-18 levels, and cell apoptosis in the IS-treated H9c2 cells through the activation of NF-κB signaling pathway. The transfection of cells with si-NLRP3 was shown to alleviate IL-1β, IL-18, and cell apoptosis. Moreover, decreased cell viability induced by IS was shown to be attenuated by IL-1β or IL-18-neutralizing antibody. In summary, CKD can result in the development of cardiac contractile dysfunction associated with the upregulation of NLRP3 inflammasome/IL-1β/IL-18 axis induced by the uremic toxins.

  14. Reactive oxygen species damage drives cardiac and mitochondrial dysfunction following acute nano-titanium dioxide inhalation exposure.

    Science.gov (United States)

    Nichols, Cody E; Shepherd, Danielle L; Hathaway, Quincy A; Durr, Andrya J; Thapa, Dharendra; Abukabda, Alaeddin; Yi, Jinghai; Nurkiewicz, Timothy R; Hollander, John M

    2017-12-15

    Nanotechnology offers innovation in products from cosmetics to drug delivery, leading to increased engineered nanomaterial (ENM) exposure. Unfortunately, health impacts of ENM are not fully realized. Titanium dioxide (TiO2) is among the most widely produced ENM due to its use in numerous applications. Extrapulmonary effects following pulmonary exposure have been identified and may involve reactive oxygen species (ROS). The goal of this study was to determine the extent of ROS involvement on cardiac function and the mitochondrion following nano-TiO2 exposure. To address this question, we utilized a transgenic mouse model with overexpression of a novel mitochondrially-targeted antioxidant enzyme (phospholipid hydroperoxide glutathione peroxidase; mPHGPx) which provides protection against oxidative stress to lipid membranes. MPHGPx mice and littermate controls were exposed to nano-TiO2 aerosols (Evonik, P25) to provide a calculated pulmonary deposition of 11 µg/mouse. Twenty-four hours following exposure, we observed diastolic dysfunction as evidenced by E/A ratios greater than 2 and increased radial strain during diastole in wild-type mice (p < 0.05 for both), indicative of restrictive filling. Overexpression of mPHGPx mitigated the contractile deficits resulting from nano-TiO2 exposure. To investigate the cellular mechanisms associated with the observed cardiac dysfunction, we focused our attention on the mitochondrion. We observed a significant increase in ROS production (p < 0.05) and decreased mitochondrial respiratory function (p < 0.05) following nano-TiO2 exposure which were attenuated in mPHGPx transgenic mice. In summary, nano-TiO2 inhalation exposure is associated with cardiac diastolic dysfunction and mitochondrial functional alterations, which can be mitigated by the overexpression of mPHGPx, suggesting ROS contribution in the development of contractile and bioenergetic dysfunction.

  15. Impact of Ambulatory Blood Pressure on Early Cardiac and Renal Dysfunction in Hypertensive Patients without Clinically Apparent Target Organ Damage.

    Science.gov (United States)

    Kim, Darae; Shim, Chi Young; Hong, Geu Ru; Park, Sungha; Cho, In Jeong; Chang, Hyuk Jae; Ha, Jong Won; Chung, Namsik

    2018-03-01

    Impaired left ventricular (LV) global longitudinal strain (GLS) and the presence of microalbuminuria indicate early cardiac and renal dysfunction. We aimed to determine the relationships among 24-h ambulatory blood pressure (BP) variables, LV GLS, and urine albumin creatinine ratio (UACR) in hypertensive patients. A total of 130 hypertensive patients (mean age 53 years; 59 men) underwent 24-h ambulatory BP monitoring, measurements of peripheral and central BPs, and transthoracic echocardiography. Patients with apparent LV systolic dysfunction (LV ejection fraction <50%) or chronic kidney disease were not included. LV GLS was calculated using two-dimensional speckle tracking, and UACR was analyzed from spot urine samples. In simple correlation analysis, LV GLS showed the most significant correlation with mean daytime diastolic BP (DBP) (r=0.427, p<0.001) among the various BP variables analyzed. UACR revealed a significant correlation only with night-time mean systolic BP (SBP) (r=0.253, p=0.019). In multiple regression analysis, daytime mean DBP and night-time mean SBP were independent determinants for LV GLS (β=0.35, p=0.028) and log UACR (β=0.49, p=0.007), respectively, after controlling for confounding factors. Daytime mean DBP showed better diagnostic performance for impaired LV GLS than did peripheral or central DBPs, which were not diagnostic. Night-time mean SBP showed satisfactory diagnostic performance for microalbuminuria. There are different associations for daytime and night-time BP with early cardiac and renal dysfunction. Ambulatory BP monitoring provides more relevant BP parameters than do peripheral or central BPs regarding early cardiac and renal dysfunction in hypertensive patients.

  16. Effect of a low glycemic index diet versus a high-cereal fibre diet on markers of subclinical cardiac injury in healthy individuals with type 2 diabetes mellitus: An exploratory analysis of a randomized dietary trial.

    Science.gov (United States)

    Ha, Vanessa; Viguiliouk, Effie; Kendall, Cyril W C; Balachandran, Bashyam; Jenkins, David J A; Kavsak, Peter A; Sievenpiper, John L

    2017-12-01

    Markers of subclinical cardiac injury are elevated in individuals with type 2 diabetes mellitus (T2DM) compared to healthy individuals. Low glycemic index (LGI) diets may improve both diabetes and cardiovascular risk but their effects on cardiac injury and fibrosis have not been previously studied. To test the effect of a LGI diet on markers of subclinical cardiac injury and fibrosis, we assessed the effect of a LGI compared with a high-cereal fibre diet on high-sensitivity cardiac troponin I (hs-cTnI) and galectin-3 in otherwise healthy individuals with T2DM in an exploratory analysis of a completed randomized trial. A total of 201 participants completed the trial and had measurements of hs-cTnI and galectin-3 at baseline and at trial completion. Participants were randomized to follow a LGI or a high-cereal fibre diet over a 6-month period. Treatment differences were tested using Analysis of Covariance (ANCOVA) with sex, baseline values, and diet x sex interaction included as covariates. In a completer's analysis, no significant differences were observed for change in hs-cTnI (-0.16ng/L vs. -0.22ng/L, p=0.713) and galectin-3 levels (0.64μg/L vs. 0.14μg/L, p=0.166) when a LGI diet was compared to a high-cereal fibre diet. The effect of a LGI diet was similar to a high-cereal fibre diet on hs-cTnI and galectin-3 levels in otherwise healthy individuals with T2DM over a 6-month period. Nevertheless, in the absence of any adverse effects, LGI diets remain an option for diabetes and cardiovascular disease risk management. ClinicalTrials.gov identifier: NCT00438698. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. Subclinical Diabetes

    Directory of Open Access Journals (Sweden)

    LUÍS M.T.R. LIMA

    Full Text Available ABSTRACT Type 2 diabetes mellitus (T2DM is increasing in prevalence worldwide, and those non-diagnosed or misdiagnosed comprise a significant group compared to those diagnosed. Accumulated scientific evidence indicate that the current diagnostic markers (fasting glycemia, 2h glycemia after an oral glucose load and HbA1c are indeed late diagnostic criteria when considering the incidence of diabetes-related complications and comorbidities, which are also at high risk in some groups among normoglycemic individuals. Additionally, the earlier identification of future risk of diabetes is desirable since it would allow better adherence to preventive actions such as lifestyle intervention, ultimately avoiding complications and minimizing the economic impact/burden on health care expenses. Insulin resistance and hyperhormonemia (insulin, amylin, glucagon are non-disputable hallmarks of T2DM, which already takes place among these normoglycemic, otherwise health subjects, characterizing a state of subclinical diabetes. Insulin resistance and hyperinsulinemia can be computed from fasting plasma insulin as an independent variable in normoglycemia. An overview of the current diagnostic criteria, disease onset, complications, comorbidities and perspectives on lifestyle interventions are presented. A proposal for early detection of subclinical diabetes from routine evaluation of fasting plasma insulin, which is affordable and robust and thus applicable for the general population, is further suggested.

  18. Experimental mild renal insufficiency mediates early cardiac apoptosis, fibrosis, and diastolic dysfunction: a kidney-heart connection.

    Science.gov (United States)

    Martin, Fernando L; McKie, Paul M; Cataliotti, Alessandro; Sangaralingham, S Jeson; Korinek, Josef; Huntley, Brenda K; Oehler, Elise A; Harders, Gerald E; Ichiki, Tomoko; Mangiafico, Sarah; Nath, Karl A; Redfield, Margaret M; Chen, Horng H; Burnett, John C

    2012-01-15

    Impaired renal function with loss of nephron number in chronic renal disease (CKD) is associated with increased cardiovascular morbidity and mortality. However, the structural and functional cardiac response to early and mild reduction in renal mass is poorly defined. We hypothesized that mild renal impairment produced by unilateral nephrectomy (UNX) would result in early cardiac fibrosis and impaired diastolic function, which would progress to a more global left ventricular (LV) dysfunction. Cardiorenal function and structure were assessed in rats at 4 and 16 wk following UNX or sham operation (Sham); (n = 10 per group). At 4 wk, blood pressure (BP), aldosterone, glomerular filtration rate (GFR), proteinuria, and plasma B-type natriuretic peptide (BNP) were not altered by UNX, representing a model of mild early CKD. However, UNX was associated with significantly greater LV myocardial fibrosis compared with Sham. Importantly, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed increased apoptosis in the LV myocardium. Further, diastolic dysfunction, assessed by strain echocardiography, but with preserved LVEF, was observed. Changes in genes related to the TGF-β and apoptosis pathways in the LV myocardium were also observed. At 16 wk post-UNX, we observed persistent LV fibrosis and impairment in LV diastolic function. In addition, LV mass significantly increased, as did LVEDd, while there was a reduction in LVEF. Aldosterone, BNP, and proteinuria were increased, while GFR was decreased. The myocardial, structural, and functional alterations were associated with persistent changes in the TGF-β pathway and even more widespread changes in the LV apoptotic pathway. These studies demonstrate that mild renal insufficiency in the rat results in early cardiac fibrosis and impaired diastolic function, which progresses to more global LV remodeling and dysfunction. Thus, these studies importantly advance the concept of a kidney

  19. Subclinical Detection of Diabetic Cardiomyopathy with MicroRNAs: Challenges and Perspectives

    Directory of Open Access Journals (Sweden)

    Luis E. León

    2016-01-01

    Full Text Available The prevalence of cardiac diabetic diseases has been increased around the world, being the most common cause of death and disability among diabetic patients. In particular, diabetic cardiomyopathy is characterized with a diastolic dysfunction and cardiac remodelling without signs of hypertension and coronary artery diseases. In an early stage, it is an asymptomatic disease; however, clinical studies demonstrate that diabetic myocardia are more vulnerable to injury derived by acute myocardial infarct and are the worst prognosis for rehabilitation. Currently, biochemical and imaging diagnostic methods are unable to detect subclinical manifestation of the disease (prior to diastolic dysfunction. In this review, we elaborately discuss the current scientific evidences to propose circulating microRNAs as promising biomarkers for early detection of diabetic cardiomyopathy and, then, to identify patients at high risk of diabetic cardiomyopathy development. Moreover, here we summarise the research strategies to identify miRNAs as potential biomarkers, present limitations, challenges, and future perspectives.

  20. Effect of left ventricular dysfunction and viral load on risk of sudden cardiac death in patients with human immunodeficiency virus.

    Science.gov (United States)

    Moyers, Brian S; Secemsky, Eric A; Vittinghoff, Eric; Wong, Joseph K; Havlir, Diane V; Hsue, Priscilla Y; Tseng, Zian H

    2014-04-01

    Human immunodeficiency virus (HIV)-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EFdeath. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, pdeath, even after adjusting for EF. The association between EFHIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p=0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Cardiac specific expression of threonine 5 to alanine mutant sarcolipin results in structural remodeling and diastolic dysfunction.

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    Mayilvahanan Shanmugam

    Full Text Available The functional importance of threonine 5 (T5 in modulating the activity of sarcolipin (SLN, a key regulator of sarco/endoplasmic reticulum (SR Ca2+ ATPase (SERCA pump was studied using a transgenic mouse model with cardiac specific expression of threonine 5 to alanine mutant SLN (SLNT5A. In these transgenic mice, the SLNT5A protein replaces the endogenous SLN in atria, while maintaining the total SLN content. The cardiac specific expression of SLNT5A results in severe cardiac structural remodeling accompanied by bi-atrial enlargement. Biochemical analyses reveal a selective downregulation of SR Ca2+ handling proteins and a reduced SR Ca2+ uptake both in atria and in the ventricles. Optical mapping analysis shows slower action potential propagation in the transgenic mice atria. Doppler echocardiography and hemodynamic measurements demonstrate a reduced atrial contractility and an impaired diastolic function. Together, these findings suggest that threonine 5 plays an important role in modulating SLN function in the heart. Furthermore, our studies suggest that alteration in SLN function can cause abnormal Ca2+ handling and subsequent cardiac remodeling and dysfunction.

  2. Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu [Tokyo Medical Coll. (Japan)

    2001-05-01

    We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52{+-}15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m{sup 2} or higher were assigned to the high dose group and those given doses under 300 mg/m{sup 2} to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3{+-}218.2 mg/m{sup 2}. In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m{sup 2} appeared to be the borderline dose beyond

  3. Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor.

    Science.gov (United States)

    Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

    2017-01-01

    Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, preceptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, preceptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure.

  4. Bigger is not better: cortisol-induced cardiac growth and dysfunction in salmonids

    DEFF Research Database (Denmark)

    Johansen, Ida B.; Sandblom, Erik; Skov, Peter Vilhelm

    2017-01-01

    effect of the otherwise catabolic steroid hormone cortisol is probably implied, but has to date not been established experimentally. Furthermore, whereas cardiac growth is associated with failure of the mammalian heart, pathological cardiac hypertrophy has not previously been described in fish. Here, we......Stress and elevated cortisol levels are associated with pathological heart growth and cardiovascular disease in humans and other mammals. We recently established a link between heritable variation in post-stress cortisol production and cardiac growth in salmonid fish too. A conserved stimulatory...... show that rainbow trout (Oncorhynchus mykiss) treated with cortisol in the diet for 45 days have enlarged hearts with lower maximum stroke volume and cardiac output. In accordance with impaired cardiac performance, overall circulatory oxygen-transporting capacity was diminished as indicated by reduced...

  5. Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats.

    Science.gov (United States)

    Zhang, Rong; Niu, Huifang; Kang, Xiaohui; Ban, Tao; Hong, Hong; Ai, Jing

    2015-01-01

    The purpose of the present study was to clarify whether chronically elevated plasma neuropeptide Y (NPY) might affect heart function and cardiac remodeling in rats. Male Wistar rats were administered NPY (85 μg for 30 days) by mini-osmotic pump subcutaneously implanted between the scapulae. Associated indices for heart function, cardiac remodeling and hypertrophy were evaluated. Compared to the sham group, the baseline systolic blood pressure (SBP) in rats administered NPY was significantly increased; cardiac function was significantly decreased, as indicated by reduced ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (± dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed markedly increased expressions of β-myosin heavy chain (β-MHC), calcineurin (CaN) and phosphorylated p38 proteins, while no changes were found in the expressions of p38 total protein and the phosphorylations of JNK and ERK. This study reported for the first time that long-term elevated plasma concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and this phenomenon could, in part, be mediated by the Ca2+/CaM-dependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats. © 2015 S. Karger AG, Basel.

  6. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage.

    Directory of Open Access Journals (Sweden)

    Ana Garcia-Alvarez

    Full Text Available INTRODUCTION: Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP in the early identification of cardiac involvement in Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-four patients divided into 3 groups--group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32, group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14, and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction 37 pg/ml were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27 ± 26 vs. 11 ± 8 pg/ml, p = 0.03. CONCLUSION/SIGNIFICANCE: In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

  7. Palmitate diet-induced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction.

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    Catherine J Knowles

    Full Text Available Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate, and MCT diet (21% medium-chain triglycerides, no palmitate. We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.

  8. Patients without myocardial accumulation of {sup 123}I-metaiodobenzylguanidine. Does it always reflect cardiac adrenergic dysfunction?

    Energy Technology Data Exchange (ETDEWEB)

    Narita, Michihiro; Kurihara, Tadashi; Honda, Minoru; Hohjoh, Osamu [Sumitomo Hospital, Osaka (Japan)

    1994-12-01

    Since December 1992 to March 1994, we have performed myocardial imaging with {sup 123}I-metaiodobenzylguanidine ({sup 123}I-MIBG) in 110 patients to examine myocardial sympathetic integrity. Among them 11 patients (10%) showed no accumulation of {sup 123}I-MIBG in the heart. So we have examined the mechanisms of no myocardial {sup 123}I-MIBG accumulation. {sup 123}I-MIBG imaging was obtained at 20 min and 3 h after intravenous injection of {sup 123}I-MIBG (148 MBq) at rest. In addition to routine tomography, anterior planar imaging of the heart and the whole body imaging were performed. Eleven patients without myocardial {sup 123}I-MIBG accumulation consisted of 5 patients with orthostatic hypotension (including 3 patients with diabetic neuropathy). four patients with hypertrophic cardiomyopathy (HCM), one patient with hypertension and one normal subject. In patients with orthostatic hypotension, standing test showed cardiac sympathetic dysfunction. In addition to no myocardial {sup 123}I-MIBG accumulation, accumulation of {sup 123}I-MIBG in the salivary glands was not found in all them. These indicated that in patients with orthostatic hypotension, generalized sympathetic dysfunction caused no myocardial {sup 123}I-MIBG accumulation. But in other 6 patients there was no evidence which suggested the cardiac sympathetic nerve dysfunction. Age, sex, serum norepinephrine level, myocardial perfusion and the medication were not different between the patients with and without myocardial {sup 123}I-MIBG accumulation. So the mechanism of no myocardial {sup 123}I-MIBG accumulation was not clear in these patients. But it was noteworthy that in patients with HCM, no myocardial {sup 123}I-MIBG accumulation appeared in 17% (4/24), and the frequency of no myocardial {sup 123}I-MIBG accumulation in HCM was significantly (p<0.05) higher than in other disease entities when patients with orthostatic hypotension were excluded. (author).

  9. Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction.

    Science.gov (United States)

    Rodrigues, Bruno; Jorge, Luciana; Mostarda, Cristiano T; Rosa, Kaleizu T; Medeiros, Alessandra; Malfitano, Christiane; de Souza, Alcione L; Viegas, Katia Aparecida da Silva; Lacchini, Silvia; Curi, Rui; Brum, Patricia C; De Angelis, Kátia; Irigoyen, Maria Cláudia

    2012-09-01

    Exercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI. Male Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO(2)max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-α mRNA, and Ca(2+) handling proteins were measured. MI area was reduced in TDI (21 ± 4%) compared with SDI (38 ± 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca(2+) handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals. ET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO(2)max and survival after MI. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Latent cardiac dysfunction as assessed by echocardiography in bed-bound patients following cerebrovascular accidents: comparison with nutritional status.

    Science.gov (United States)

    Masugata, Hisashi; Senda, Shoichi; Goda, Fuminori; Yoshihara, Yumiko; Yoshikawa, Kay; Fujita, Norihiro; Himoto, Takashi; Okuyama, Hiroyuki; Taoka, Teruhisa; Imai, Masanobu; Kohno, Masakazu

    2007-07-01

    The aim of this study was to elucidate the cardiac function in bed-bound patients following cerebrovascular accidents. In accord with the criteria for activities of daily living (ADL) of the Japanese Ministry of Health, Labour and Welfare, 51 age-matched poststroke patients without heart disease were classified into 3 groups: rank A (house-bound) (n = 16, age, 85 +/- 6 years), rank B (chair-bound) (n = 16, age, 84 +/- 8 years), and rank C (bed-bound) (n = 19, age, 85 +/- 9 years). Using echocardiography, the left ventricular (LV) diastolic function was assessed by the ratio of early filling (E) and atrial contraction (A) transmitral flow velocities (E/A) of LV inflow. LV systolic function was assessed by LV ejection fraction (LVEF), and the Tei index was also measured to assess both LV systolic and diastolic function. No difference was observed in the E/A and LVEF among the 3 groups. The Tei index was higher in rank C (0.56 +/- 0.17) than in rank A (0.39 +/- 0.06) and rank B (0.48 +/- 0.17), and a statistically significant difference was observed between rank A and rank C (P cerebrovascular accidents. The Tei index may be a useful index of cardiac dysfunction in bed-bound patients because it is independent of the cardiac loading condition.

  11. The amelioration of cardiac dysfunction after myocardial infarction by the injection of keratin biomaterials derived from human hair.

    Science.gov (United States)

    Shen, Deliang; Wang, Xiaofang; Zhang, Li; Zhao, Xiaoyan; Li, Jingyi; Cheng, Ke; Zhang, Jinying

    2011-12-01

    Cardiac dysfunction following acute myocardial infarction is a major cause of advanced cardiomyopathy. Conventional pharmacological therapies rely on prompt reperfusion and prevention of repetitive maladaptive pathways. Keratin biomaterials can be manufactured in an autologous fashion and are effective in various models of tissue regeneration. However, its potential application in cardiac regeneration has not been tested. Keratin biomaterials were derived from human hair and its structure morphology, carryover of beneficial factors, biocompatibility with cardiomyocytes, and in vivo degradation profile were characterized. After delivery into infarcted rat hearts, the keratin scaffolds were efficiently infiltrated by cardiomyocytes and endothelial cells. Injection of keratin biomaterials promotes angiogenesis but does not exacerbate inflammation in the post-MI hearts. Compared to control-injected animals, keratin biomaterials-injected animals exhibited preservation of cardiac function and attenuation of adverse ventricular remodeling over the 8 week following time course. Tissue western blot analysis revealed up-regulation of beneficial factors (BMP4, NGF, TGF-beta) in the keratin-injected hearts. The salient functional benefits, the simplicity of manufacturing and the potentially autologous nature of this biomaterial provide impetus for further translation to the clinic. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. [Nitrid oxide, levosimendan and sildenafile in a patient with right ventricle dysfunction and severe pulmonary hypertension after cardiac surgery].

    Science.gov (United States)

    Aleixandre, L; Cortell, J; Vicente, R; Herrera, P; Loro, J M; Valera, F

    2014-11-01

    Pulmonary hypertension (PHT) and the resulting right ventricle dysfunction are important risk factors in patients who undergo cardiac surgery. The treatment of PHT and right ventricle dysfunction should be focused on maintaining the correct right ventricle after load, improving right ventricle function and reducing the right ventricle pre-load and therefore reducing pulmonary vascular resistance by means of vasodilators. A combined therapy of vasodilators and medicines which have different mechanisms of action, is becoming an option for the treatment of PHT. We present a 65 year old woman that suffered from mitral regurgitation, aortic valve disease, tricuspid and ascending aortic dilation with 115mmHg of pulmonary artery pressure (by ultrasound evaluation). The patient was operated on of mitral, aortic valve and tricuspid plastia and proximal aortic artery plastia as well. Previosly to surgery the patient suffered right ventricle dysfunction and PHT and was treated with nitric oxide, intravenous sildenafil and levosimendan. Subsequent evolution was satisfactory, PHT being controlled, without arterial hypotension nor respiratory alterations. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. The implication of tissue Doppler echocardiography and cardiopulmonary exercise in early detection of cardiac dysfunction in systemic lupus erythematosus patients.

    Science.gov (United States)

    Elnady, Basant M; Abdelghafar, Ayman Saeed Mohamed; Khalik, El Shazly Abdul; Algethami, Mohammed Mesfer; Basiony, A S; Al-Otaibi, Mona Dhaif Allah; Al-Otaibi, Maram Eidhah

    2016-09-01

    , and there was a statistical difference between SLE groups Ia and Ib; also, S wave was lower in group Ib than in group Ia. RV diastolic dysfunction in the form of lower E' and A' values was observed for the SLE group compared to the control group, especially in the medial annulus of the tricuspid valve. A higher A wave velocity with PWD of mitral and tricuspid inflows was observed in the patient group compared to the control group. SLE patients have an increased prevalence of subclinical systolic and diastolic LV and RV dysfunction. This result advocates for regular follow-up and early screening of SLE patients. Accordingly, treatment focused on improving diastolic heart function may have a role in enhancing QoL and improving the prognosis of SLE patients.

  14. Silencing nox4 in the paraventricular nucleus improves myocardial infarction-induced cardiac dysfunction by attenuating sympathoexcitation and periinfarct apoptosis.

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    Infanger, David W; Cao, Xian; Butler, Scott D; Burmeister, Melissa A; Zhou, Yi; Stupinski, John A; Sharma, Ram V; Davisson, Robin L

    2010-06-11

    Myocardial infarction (MI)-induced heart failure is characterized by central nervous system-driven sympathoexcitation and deteriorating cardiac function. The paraventricular nucleus (PVN) of the hypothalamus is a key regulator of sympathetic nerve activity and is implicated in heart failure. Redox signaling in the PVN and other central nervous system sites is a primary mechanism of neuro-cardiovascular regulation, and excessive oxidant production by activation of NADPH oxidases (Noxs) is implicated in some neuro-cardiovascular diseases. We tested the hypothesis that Nox-mediated redox signaling in the PVN contributes to MI-induced sympathoexcitation and cardiac dysfunction in mice. Real-time PCR revealed that Nox4 was the most abundantly expressed Nox in PVN under basal conditions. Coronary arterial ligation (MI) caused a selective upregulation of this homolog compared to Nox1 and Nox2. Adenoviral gene transfer of Nox4 (AdsiNox4) to PVN (bilateral) attenuated MI-induced superoxide formation in this brain region (day 14) to the same level as that produced by PVN-targeted gene transfer of cytoplasmic superoxide dismutase (AdCu/ZnSOD). MI mice treated with AdsiNox4 or AdCu/ZnSOD in the PVN showed marked improvement in cardiac function as assessed by echocardiography and left ventricular hemodynamic analysis. This was accompanied by significantly diminished sympathetic outflow and apoptosis in the periinfarct region of the heart. These results suggest that MI causes dysregulation of Nox4-mediated redox signaling in the PVN, which leads to sympathetic overactivation and a decline in cardiac function. Targeted inhibition of oxidant signaling in the PVN could provide a novel treatment for MI-induced heart failure.

  15. Dysfunctional Hyperpolarization-Activated Cyclic Nucleotide-gated Ion Channels in Cardiac Diseases

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    Xiaoqi Zhao

    Full Text Available Abstract Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are reverse voltage-dependent, and their activation depends on the hyperpolarization of the membrane and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP or other signal-transduction cascades. The distribution, quantity and activation states of HCN channels differ in tissues throughout the body. Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. They may constitute promising drug targets in the treatment of these cardiac diseases. Pharmacological treatment targeting HCN channels is of benefit to these cardiac conditions.

  16. C-C Motif Chemokine Receptor 9 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction.

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    Xu, Zhengxi; Mei, Fanghua; Liu, Hanning; Sun, Cheng; Zheng, Zhe

    2016-05-04

    Maladaptive cardiac hypertrophy is a major risk factor for heart failure, which is the leading cause of death worldwide. C-C motif chemokine receptor 9 (CCR9), a subfamily of the G protein-coupled receptor supergene family, has been highlighted as an immunologic regulator in the development and homing of immune cells and in immune-related diseases. Recently, CCR9 was found to be involved in the pathogenesis of other diseases such as cardiovascular diseases; however, the effects that CCR9 exerts in cardiac hypertrophy remain elusive. We observed significantly increased CCR9 protein levels in failing human hearts and in a mouse or cardiomyocyte hypertrophy model. In loss- and gain-of-function experiments, we found that pressure overload-induced hypertrophy was greatly attenuated by CCR9 deficiency in cardiac-specific CCR9 knockout mice, whereas CCR9 overexpression in cardiac-specific transgenic mice strikingly enhanced cardiac hypertrophy. The prohypertrophic effects of CCR9 were also tested in vitro, and a similar phenomenon was observed. Consequently, we identified a causal role for CCR9 in pathological cardiac hypertrophy. Mechanistically, we revealed a lack of difference in the expression levels of mitogen-activated protein kinases between groups, whereas the phosphorylation of AKT/protein kinase B and downstream effectors significantly decreased in CCR9 knockout mice and increased in CCR9 transgenic mice after aortic binding surgery. The prohypertrophic effects of CCR9 were not attributable to the mitogen-activated protein kinase signaling pathway but rather to the AKT-mammalian target of rapamycin-glycogen synthase kinase 3β signaling cascade. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. ICD function and dysfunction in patients with arrhythmogenic cardiac diseases: the role of home monitoring

    NARCIS (Netherlands)

    Asmundis, C. de; Ricciardi, D.; Namdar, M.; Pappaert, G.; Rodriguez-Manero, M.; Wauters, K.; Casado-Arroyo, R.; Rao, J.J.; Bayrak, F.; Chierchia, G.B.; Sarkozy, A.; Brugada, P.

    2013-01-01

    BACKGROUND: Since their implementation in clinical practice, remote home monitoring systems (HM) have undoubtedly become an added value in patients with implantable devices for cardiac rhythm management. The aim of this study was to investigate the impact of HM on clinical management and outcome in

  18. Cardiac diastolic dysfunction and metabolic syndrome in young women after placental syndrome.

    NARCIS (Netherlands)

    Zandstra, M.; Stekkinger, E.; Vlugt, M.J. van der; Dijk, A.P.J. van; Lotgering, F.K.; Spaanderman, M.E.A.

    2010-01-01

    OBJECTIVE: To estimate whether women with a recent history of a placental syndrome and concomitant metabolic syndrome have reduced cardiac diastolic function. METHODS: In this cohort study, women with a history of a placental syndrome were included. We assessed body mass index, blood pressure,

  19. Mineralocorticoid Receptor Deficiency in T Cells Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction Through Modulating T-Cell Activation.

    Science.gov (United States)

    Li, Chao; Sun, Xue-Nan; Zeng, Meng-Ru; Zheng, Xiao-Jun; Zhang, Yu-Yao; Wan, Qiangyou; Zhang, Wu-Chang; Shi, Chaoji; Du, Lin-Juan; Ai, Tang-Jun; Liu, Yuan; Liu, Yan; Du, Li-Li; Yi, Yi; Yu, Ying; Duan, Sheng-Zhong

    2017-07-01

    Although antagonists of mineralocorticoid receptor (MR) have been widely used to treat heart failure, the underlying mechanisms are incompletely understood. Recent reports show that T cells play important roles in pathologic cardiac hypertrophy and heart failure. However, it is unclear whether and how MR functions in T cells under these pathologic conditions. We found that MR antagonist suppressed abdominal aortic constriction-induced cardiac hypertrophy and decreased the accumulation and activation of CD4 + and CD8 + T cells in mouse heart. T-cell MR knockout mice manifested suppressed cardiac hypertrophy, fibrosis, and dysfunction compared with littermate control mice after abdominal aortic constriction. T-cell MR knockout mice had less cardiac inflammatory response, which was illustrated by decreased accumulation of myeloid cells and reduced expression of inflammatory cytokines. Less amounts and activation of T cells were observed in the heart of T-cell MR knockout mice after abdominal aortic constriction. In vitro studies showed that both MR antagonism and deficiency repressed activation of T cells, whereas MR overexpression elevated activation of T cells. These results demonstrated that MR blockade in T cells protected against abdominal aortic constriction-induced cardiac hypertrophy and dysfunction. Mechanistically, MR directly regulated T-cell activation and modulated cardiac inflammation. Targeting MR in T cells specifically may be a feasible strategy for more effective treatment of pathologic cardiac hypertrophy and heart failure. © 2017 American Heart Association, Inc.

  20. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis

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    Kain Vasundhara

    2011-11-01

    Full Text Available Abstract Background Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. Methods This study was designed to examine the effect of long-acting calcium channel blocker (CCB, Azelnidipine (AZL on contractile dysfunction, intracellular calcium (Ca2+ cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP injection of streptozotocin (STZ. Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS, time-to-PS (TPS, time-to-relengthening (TR90, maximal velocity of shortening/relengthening (± dL/dt and intracellular Ca2+ fluorescence. Results Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD, calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. Conclusion Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property.

  1. Coronary microvascular dysfunction is an early feature of cardiac involvement in patients with Anderson-Fabry disease.

    Science.gov (United States)

    Tomberli, Benedetta; Cecchi, Franco; Sciagrà, Roberto; Berti, Valentina; Lisi, Francesca; Torricelli, Francesca; Morrone, Amelia; Castelli, Gabriele; Yacoub, Magdi H; Olivotto, Iacopo

    2013-12-01

    Male patients with Anderson-Fabry disease (AFD) often exhibit cardiac involvement, characterized by LV hypertrophy (LVH), associated with severe coronary microvascular dysfunction (CMD). Whether CMD is present in patients without LVH, particularly when female, remains unresolved. The aim of the study was to investigate the presence of CMD by positron emission tomography (PET) in AFD patients of both genders, with and without evidence of LVH. We assessed myocardial blood flow following dipyridamole infusion (Dip-MBF) with 13N-labelled ammonia by PET in 30 AFD patients (age 51 ± 13 years; 18 females) and in 24 healthy controls. LVH was defined as echocardiographic maximal LV wall thickness ≥13 mm. LVH was present in 67% of patients (n = 20; 10 males and 10 females). Dip-MBF was reduced in all patients compared with controls (1.8 ± 0.5 and 3.2 ± 0.5 mL/min/g, respectively, P Coronary microvascular function is markedly impaired in AFD patients irrespective of LVH and gender. CMD may represent the only sign of cardiac involvement in AFD patients, with potentially important implications for clinical management.

  2. Cardiac Function and Diastolic Dysfunction in Behcet’s Disease: A Systematic Review and Meta-Analysis

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    Fawad Aslam

    2016-01-01

    Full Text Available Background. Cardiovascular involvement in Behcet’s disease (BD is reported and has variable manifestations. It is not clear if diastolic dysfunction (DD is increased in BD. Our objective was to evaluate the existing literature to determine if cardiac dysfunction, particularly DD, was more prevalent in these patients. Methods. A systematic review and meta-analysis of the available studies analyzing the echocardiographic findings in BD was conducted using a random-effects model. Mean differences were used to calculate the effect sizes of the echocardiographic parameters of interest. Results. A total of 22 studies with 1624 subjects were included in the analysis. Patients with BD had statistically significantly larger mean left atrial dimension (0.08, p=0.0008, greater aortic diameter (0.16, p=0.02, significantly reduced ejection fraction (−1.08, p<0.0001, significantly prolonged mitral deceleration time (14.20, p<0.0001, lower E/A ratio (−0.24, p=0.05, and increased isovolumetric relaxation time (7.29, p<0.00001. Conclusion. DD is increased in patients with BD by the presence of several echocardiographic parameters favoring DD as compared to controls. The meta-analysis also identified that LA dimension is increased in BD patients. EF has also been found to be lower in BD patients. Aortic diameter was also increased in BD patients as compared to controls.

  3. Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model.

    Science.gov (United States)

    Wei, Qin; Bian, Yeping; Yu, Fuchao; Zhang, Qiang; Zhang, Guanghao; Li, Yang; Song, Songsong; Ren, Xiaomei; Tong, Jiayi

    2016-11-01

    Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis. © 2016 by the Journal of Biomedical Research. All rights reserved.

  4. Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease.

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    Maria Köping

    Full Text Available Fabry disease (FD is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3 in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature.To examine hearing loss in patients with FD depending on cardiac and renal function.Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of Würzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA6 (0.5, 1, 2, 4, 6, 8 and HF-PTA (6, 8 kHz. Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.Sensorineural hearing loss was detected in 58.8% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05.High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.

  5. Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

    Science.gov (United States)

    Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

    2016-01-01

    The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

  6. Biomass fuel smoke exposure was associated with adverse cardiac remodeling and left ventricular dysfunction in Peru.

    Science.gov (United States)

    Burroughs Peña, M S; Velazquez, E J; Rivera, J D; Alenezi, F; Wong, C; Grigsby, M; Davila-Roman, V G; Gilman, R H; Miranda, J J; Checkley, W

    2017-07-01

    While household air pollution from biomass fuel combustion has been linked to cardiovascular disease, the effects on cardiac structure and function have not been well described. We sought to determine the association between biomass fuel smoke exposure and cardiac structure and function by transthoracic echocardiography. We identified a random sample of urban and rural residents living in the high-altitude region of Puno, Peru. Daily biomass fuel use was self-reported. Participants underwent transthoracic echocardiography. Multivariable linear regression was used to examine the relationship of biomass fuel use with echocardiographic measures of cardiac structure and function, adjusting for age, sex, height, body mass index, diabetes, physical activity, and tobacco use. One hundred and eighty-seven participants (80 biomass fuel users and 107 non-users) were included in this analysis (mean age 59 years, 58% women). After adjustment, daily exposure to biomass fuel smoke was associated with increased left ventricular internal diastolic diameter (P=.004), left atrial diameter (P=.03), left atrial area (four-chamber) (P=.004) and (two-chamber) (P=.03), septal E' (P=.006), and lateral E' (P=.04). Exposure to biomass fuel smoke was also associated with worse global longitudinal strain in the two-chamber view (P=.01). Daily biomass fuel use was associated with increased left ventricular size and decreased left ventricular systolic function by global longitudinal strain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Cardiac dysfunction and peri-weaning mortality in malonyl-coenzyme A decarboxylase (MCD) knockout mice as a consequence of restricting substrate plasticity.

    Science.gov (United States)

    Aksentijević, Dunja; McAndrew, Debra J; Karlstädt, Anja; Zervou, Sevasti; Sebag-Montefiore, Liam; Cross, Rebecca; Douglas, Gillian; Regitz-Zagrosek, Vera; Lopaschuk, Gary D; Neubauer, Stefan; Lygate, Craig A

    2014-10-01

    Inhibition of malonyl-coenzyme A decarboxylase (MCD) shifts metabolism from fatty acid towards glucose oxidation, which has therapeutic potential for obesity and myocardial ischemic injury. However, ~40% of patients with MCD deficiency are diagnosed with cardiomyopathy during infancy. To clarify the link between MCD deficiency and cardiac dysfunction in early life and to determine the contributing systemic and cardiac metabolic perturbations. MCD knockout mice ((-/-)) exhibited non-Mendelian genotype ratios (31% fewer MCD(-/-)) with deaths clustered around weaning. Immediately prior to weaning (18days) MCD(-/-) mice had lower body weights, elevated body fat, hepatic steatosis and glycogen depletion compared to wild-type littermates. MCD(-/-) plasma was hyperketonemic, hyperlipidemic, had 60% lower lactate levels and markers of cellular damage were elevated. MCD(-/-) hearts exhibited hypertrophy, impaired ejection fraction and were energetically compromised (32% lower total adenine nucleotide pool). However differences between WT and MCD(-/-) converged with age, suggesting that, in surviving MCD(-/-) mice, early cardiac dysfunction resolves over time. These observations were corroborated by in silico modelling of cardiomyocyte metabolism, which indicated improvement of the MCD(-/-) metabolic phenotype and improved cardiac efficiency when switched from a high-fat diet (representative of suckling) to a standard post-weaning diet, independent of any developmental changes. MCD(-/-) mice consistently exhibited cardiac dysfunction and severe metabolic perturbations while on a high-fat, low carbohydrate diet of maternal milk and these gradually resolved post-weaning. This suggests that dysfunction is a common feature of MCD deficiency during early development, but that severity is dependent on composition of dietary substrates. Copyright © 2014. Published by Elsevier Ltd.

  8. Prevalence, Diagnosis, Perioperative Monitoring and Treatment of Right Ventricular Dysfunction and/or Pulmonary Arterial Hypertension in Cardiac Surgical Patients in Germany-A Postal Survey.

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    Heringlake, Matthias; Schön, Julika; Pliet, Teresa; Haake, Nils; Reinecke, Alexander; Habicher, Marit; Sander, Michael; Markewitz, Andreas; Reuter, Daniel A; Groesdonk, Heinrich Volker; Trummer, Georg; Pilarzyk, Kevin; von der Brelie, Michael; Bein, Berthold; Schirmer, Uwe

    2017-12-01

    Background Sparse data are available on the prevalence of right ventricular dysfunction and/or pulmonary arterial hypertension in patients scheduled for cardiac surgery in Germany as well as on the intensity and modalities used for diagnosis, perioperative monitoring, and treatment of these comorbidities. Methods A postal survey including questions on the prevalence of preoperative right ventricular dysfunction and/or pulmonary arterial hypertension in patients undergoing cardiac surgery in 2009 was sent to 81 German heart centers. Total 47 of 81 (58%) heart centers returned the questionnaires. The centers reported data on 51,095 patients, and 49.8% of the procedures were isolated coronary artery bypass grafting. Results Data on the prevalence of preoperative pulmonary hypertension and/or right ventricular dysfunction were not available in 54% and 64.6% of centers. In the remaining hospitals, 19.5% of patients presented right heart dysfunction and 10% pulmonary arterial hypertension. Preoperative echocardiography was performed in only 45.3% of the coronary artery bypass grafting cases. Preoperative pharmacologic treatment of pulmonary hypertension or right ventricular dysfunction with oral sildenafil, inhaled prostanoids, or nitric oxide was initiated in 71% and 95.7% of the centers, respectively. Intra- and postoperative treatment was most frequently accomplished with phosphodiesterase-III inhibitors. Conclusion The prevalence of preoperative right heart dysfunction and pulmonary arterial hypertension in cardiac surgical patients in Germany seems to be substantial. However, in more than 50% of the patients, no preoperative data on right ventricular function and pulmonary arterial pressure are available. This may lead to underestimation of perioperative risk and inappropriate management of this high-risk population. Georg Thieme Verlag KG Stuttgart · New York.

  9. Wheat germ supplementation alleviates insulin resistance and cardiac mitochondrial dysfunction in an animal model of diet-induced obesity.

    Science.gov (United States)

    Ojo, Babajide; Simenson, Ashley J; O'Hara, Crystal; Wu, Lei; Gou, Xin; Peterson, Sandra K; Lin, Daniel; Smith, Brenda J; Lucas, Edralin A

    2017-08-01

    Obesity is strongly associated with insulin resistance (IR), along with mitochondrial dysfunction to metabolically active tissues and increased production of reactive O2 species (ROS). Foods rich in antioxidants such as wheat germ (WG), protect tissues from damage due to ROS and modulate some negative effects of obesity. This study examined the effects of WG supplementation on markers of IR, mitochondrial substrate metabolism and innate antioxidant markers in two metabolically active tissues (i.e. liver and heart) of C57BL/6 mice fed a high-fat-high-sucrose (HFS) diet. Male C57BL/6 mice, 6-week-old, were randomised into four dietary treatment groups (n 12 mice/group): control (C, 10 % fat kcal), C+10 % WG, HFS (60 % fat kcal) or HFS+10 % WG (HFS+WG). After 12 weeks of treatment, HFS+WG mice had significantly less visceral fat (-16 %, P=0·006) compared with the HFS group. WG significantly reduced serum insulin (P=0·009), the insulinotropic hormone, gastric inhibitory peptide (P=0·0003), and the surrogate measure of IR, homoeostatic model assessment of IR (P=0·006). HFS diet significantly elevated (45 %, P=0·02) cardiac complex 2 mitochondrial VO2, suggesting increased metabolic stress, whereas WG stabilised this effect to the level of control. Consequently, genes which mediate antioxidant defense and mitochondrial biogenesis (superoxide dismutase 2 (Sod2) and PPARγ coactivator 1-α (Pgc1a), respectively) were significantly reduced (Pheart of the HFS group, whereas WG supplementation tended to up-regulate both genes. WG significantly increased hepatic gene expression of Sod2 (P=0·048) but not Pgc1a. Together, these results showed that WG supplementation in HFS diet, reduced IR and improved cardiac mitochondrial metabolic functions.

  10. Overexpression myocardial inducible nitric oxide synthase exacerbates cardiac dysfunction and beta-adrenergic desensitization in experimental hypothyroidism.

    Science.gov (United States)

    Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping

    2016-02-01

    Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cardiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca(2+)]i transient ([Ca(2+)]iT), and β-adrenergic hyporesponsiveness. We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca(2+)]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400 W, 10(-5)mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca(2+)]iT. In hypothyroidism, isoproterenol (10(-8)M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca(2+)]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca(2+)]iT. Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cardiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism. Copyright © 2015 Elsevier

  11. Overexpression Myocardial Inducible Nitric Oxide Synthase Exacerbates Cardiac Dysfunction and Beta-Adrenergic Desensitization in Experimental Hypothyroidism☆,☆☆

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    Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F.; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping

    2015-01-01

    Background Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cadiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca2+]i transient ([Ca2+]iT), and β-adrenergic hyporesponsiveness. Methods and Results We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca2+]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400W, 10−5 mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca2+]iT. In hypothyroidism, isoproterenol (10−8 M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca2+]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca2+]iT. Conclusions Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cadiomyocyte iNOS may promote progressive cardiac dysfunction in

  12. Myocardial overexpression of Mecr, a gene of mitochondrial FAS II leads to cardiac dysfunction in mouse.

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    Zhijun Chen

    Full Text Available It has been recently recognized that mammalian mitochondria contain most, if not all, of the components of fatty acid synthesis type II (FAS II. Among the components identified is 2-enoyl thioester reductase/mitochondrial enoyl-CoA reductase (Etr1/Mecr, which catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters, generating saturated acyl-groups. Although the FAS type II pathway is highly conserved, its physiological role in fatty acid synthesis, which apparently occurs simultaneously with breakdown of fatty acids in the same subcellular compartment in mammals, has remained an enigma. To study the in vivo function of the mitochondrial FAS in mammals, with special reference to Mecr, we generated mice overexpressing Mecr under control of the mouse metallothionein-1 promoter. These Mecr transgenic mice developed cardiac abnormalities as demonstrated by echocardiography in vivo, heart perfusion ex vivo, and electron microscopy in situ. Moreover, the Mecr transgenic mice showed decreased performance in endurance exercise testing. Our results showed a ventricular dilatation behind impaired heart function upon Mecr overexpression, concurrent with appearance of dysmorphic mitochondria. Furthermore, the data suggested that inappropriate expression of genes of FAS II can result in the development of hereditary cardiomyopathy.

  13. Greater body mass index is a better predictor of subclinical cardiac damage at long-term follow-up in men than is insulin sensitivity

    DEFF Research Database (Denmark)

    Nielsen, Mette Lundgren; Pareek, Manan; Gerke, Oke

    2015-01-01

    BACKGROUND: To examine whether lower insulin sensitivity as determined by homeostatic model assessment (HOMA-%S) was associated with increased left ventricular mass (LVM) and presence of LV diastolic dysfunction at long-term follow-up, independently of body mass index (BMI), in middle-aged, other...

  14. Subclinical hypothyroidism ups the risk of vascular complications in ...

    African Journals Online (AJOL)

    The incidence of thyroid dysfunction in diabetic patients is higher than that of the general population. Undiagnosed thyroid dysfunction may affect the metabolic control and enhance cardiovascular, and other chronic complication risks in diabetic patients. Few studies have examined the relationship between subclinical ...

  15. When cardiac failure, kidney dysfunction, and kidney injury intersect in acute conditions: the case of cardiorenal syndrome.

    Science.gov (United States)

    Legrand, Matthieu; Mebazaa, Alexandre; Ronco, Claudio; Januzzi, James L

    2014-09-01

    To review and describe diagnostic and prognostic value of biomarkers of renal function and renal injury in the cardiorenal syndrome complicating acutely decompensated heart failure. PubMed search and review of relevant medical literature. Two reviewers screened and selected studies in English with diagnostic or prognostic assessment of biomarkers of renal injury. Narrative review of the medical literature. Cardiorenal syndrome has a complex pathophysiology and has a generally poor prognosis in patients with acutely decompensated heart failure. Among the methods to recognize risk for cardiorenal syndrome may be the use of circulating or urinary biomarkers, which may allow for more accurate early diagnosis and risk stratification; use of biomarkers may provide important pathophysiologic understanding beyond risk prediction. However, different phenotypes of patients with acute renal dysfunction may be present, which has ramifications with respect to response to treatment strategies. Addition of biomarkers of renal injury may provide additional prognostic value to biomarkers of renal or cardiac function, but more data are needed. Biomarkers reflecting renal function and injury are likely to better phenotype subgroups of patients with cardiorenal syndrome and to provide unique prognostic information. Future studies are needed relative to strategies using such biomarkers to guide care of affected patients.

  16. Cardiac diastolic dysfunction in high-fat diet fed mice is associated with lipotoxicity without impairment of cardiac energetics in vivo

    NARCIS (Netherlands)

    Abdurrachim, Desiree; Ciapaite, Jolita; Wessels, Bart; Nabben, Miranda; Luiken, Joost J. F. P.; Nicolay, Klaas; Prompers, Jeanine J.

    2014-01-01

    Obesity is often associated with abnormalities in cardiac morphology and function. This study tested the hypothesis that obesity-related cardiomyopathy is caused by impaired cardiac energetics. In a mouse model of high-fat diet (HFD)-induced obesity, we applied in vivo cardiac P-31 magnetic

  17. Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study

    Directory of Open Access Journals (Sweden)

    Kai O. Hensel

    2016-01-01

    Full Text Available Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM. 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5±3.1 years and mean disease duration 4.3±3.5 years and 44 age- and gender-matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal (p=0.019 and circumferential (p=0.016 strain rate both at rest and during exercise (p=0.021. This was more pronounced in T1DM patients with a longer disease duration (p=0.038. T1DM patients with serum HbA1c>9% showed impaired longitudinal (p=0.008 and circumferential strain (p=0.005 and a reduced E/A-ratio (p=0.018. In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment.

  18. Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study

    Science.gov (United States)

    Hensel, Kai O.; Grimmer, Franziska; Roskopf, Markus; Jenke, Andreas C.; Wirth, Stefan; Heusch, Andreas

    2016-01-01

    Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM). 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5 ± 3.1 years and mean disease duration 4.3 ± 3.5 years) and 44 age- and gender-matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate) during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal (p = 0.019) and circumferential (p = 0.016) strain rate both at rest and during exercise (p = 0.021). This was more pronounced in T1DM patients with a longer disease duration (p = 0.038). T1DM patients with serum HbA1c > 9% showed impaired longitudinal (p = 0.008) and circumferential strain (p = 0.005) and a reduced E/A-ratio (p = 0.018). In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment. PMID:26839891

  19. Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study.

    Science.gov (United States)

    Hensel, Kai O; Grimmer, Franziska; Roskopf, Markus; Jenke, Andreas C; Wirth, Stefan; Heusch, Andreas

    2016-01-01

    Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM). 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5 ± 3.1 years and mean disease duration 4.3 ± 3.5 years) and 44 age- and gender-matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate) during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal (p = 0.019) and circumferential (p = 0.016) strain rate both at rest and during exercise (p = 0.021). This was more pronounced in T1DM patients with a longer disease duration (p = 0.038). T1DM patients with serum HbA1c > 9% showed impaired longitudinal (p = 0.008) and circumferential strain (p = 0.005) and a reduced E/A-ratio (p = 0.018). In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment.

  20. Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

    Directory of Open Access Journals (Sweden)

    Smeding Lonneke

    2012-03-01

    Full Text Available Abstract Background Injurious mechanical ventilation (MV may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis. Methods Normal rats and intraperitoneal (i.p. lipopolysaccharide (LPS-treated rats were ventilated with low (6 ml/kg and high (19 ml/kg tidal volumes (Vt under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP, central venous pressure (CVP, cardiac output (CO and pulmonary plateau pressure (Pplat were measured. Ex vivo myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM-1 and edema were measured to evaluate endothelial inflammation and leakage. Results MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function ex vivo but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters ex vivo. Conclusion MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.

  1. Neuroendocrine and Cardiac Metabolic Dysfunction and NLRP3 Inflammasome Activation in Adipose Tissue and Pancreas following Chronic Spinal Cord Injury in the Mouse

    Directory of Open Access Journals (Sweden)

    Gregory E. Bigford

    2013-08-01

    Full Text Available CVD (cardiovascular disease represents a leading cause of mortality in chronic SCI (spinal cord injury. Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immunohistochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin and increased NPY (neuropeptide-Y expression in the hypothalamic ARC (arcuate nucleus and PVN (paraventricular nucleus, 1-month post-SCI. Long-form leptin receptor (Ob-Rb, JAK2 (Janus kinase/STAT3 (signal transducer and activator of transcription 3/p38 and RhoA/ROCK (Rho-associated kinase signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3 inflammasome in VAT (visceral adipose tissue and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

  2. Efficacy and effects on cardiac function of radiofrequency catheter ablation vs. direct current cardioversion of persistent atrial fibrillation with left ventricular systolic dysfunction.

    Directory of Open Access Journals (Sweden)

    Maojing Wang

    Full Text Available To evaluate the effect of catheter ablation vs. direct current synchronized cardioversion (DCC in patients with persistent atrial fibrillation (AF and left ventricular systolic dysfunction, and to define baseline features of patients that will get more benefit from ablation.From July 2013 to October 2014, 97 consecutive single-center patients with persistent AF and symptomatic heart failure (left ventricular ejection fraction (LVEF 20% or to over 55% in 31 (54.39% patients with worse baseline cardiac function and ventricular rate control.Catheter ablation relative to cardioversion of persistent AF with symptomatic heart failure yielded better 12-month SR maintenance and cardiac function. Compared with non-responders, patients with improved LVEF post-ablation had poorer ventricular rate control and cardiac function at baseline, suggesting a significant component of tachycardia-induced cardiomyopathy in this group.

  3. Bariatric Surgery Restores Cardiac and Sudomotor Autonomic C-Fiber Dysfunction towards Normal in Obese Subjects with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Carolina M Casellini

    shows that bariatric surgery can restore both cardiac and sudomotor autonomic C-fiber dysfunction in subjects with diabetes, potentially impacting morbidity and mortality.

  4. Subclinical myocardial impairment in SLE: insights from novel ultrasound techniques and clinical determinants.

    Science.gov (United States)

    Guşetu, Gabriel; Pop, Dana; Pamfil, Cristina; Bǎlaj, Raluca; Mureşan, Lucian; Cismaru, Gabriel; Matuz, Roxana; Roşu, Radu; Zdrenghea, Dumitru; Rednic, Simona

    2016-03-01

    Myocardial damage is frequent and often silent in systemic lupus erythematosus (SLE). The aim of the study was to determine the prevalence of myocardial damage by novel ultrasound techniques and to systematically assess the relationship between subclinical cardiac dysfunction and SLE-related clinical parameters. Seventy-five consecutive SLE patients without evidence of cardiac disease and seventy-three controls underwent standard transthoracic echocardiography using classical and novel ultrasound techniques: tissue Doppler imaging and speckle tracking echocardiography. Patient characteristics, cumulative organ damage and laboratory data were retrieved by medical chart review. Within the cohort, 89.3% of the patients were female; mean+/-SD age and median (IQR) disease duration were 43.2+/-12.5 years and 8.03(6.3) years, respectively. SLE patients exhibited a significant decrement in endocardial longitudinal strain (-18.4% vs 19.3%, p=0.001) compared with controls. Diastolic dysfunction was detected in 34 (45.3%) of SLE patients. Major determinants of systolic and diastolic dysfunction were hypertension (p=0.023 and pSLE patients who had better systolic longitudinal performance. Neither disease activity, nor specific organ involvement, were associated with myocardial impairment. Systolic longitudinal and diastolic performance impairments are frequent findings in SLE patients without overt cardiovascular disease. Cumulative organ damage, disease duration, APS, and hypertension are major determinants for early heart involvement in SLE patients.

  5. Post-procedural hemodiafiltration in acute coronary syndrome patients with associated renal and cardiac dysfunction undergoing urgent and emergency coronary angiography.

    Science.gov (United States)

    Marenzi, Giancarlo; Mazzotta, Gianfranco; Londrino, Francesco; Gistri, Roberto; Moltrasio, Marco; Cabiati, Angelo; Assanelli, Emilio; Veglia, Fabrizio; Rombolà, Giuseppe

    2015-02-15

    We investigated the use of a 3-hr treatment with hemodiafiltration, initiated soon after emergency or urgent coronary angiography in acute coronary syndrome (ACS) patients with associated severe renal and cardiac dysfunction. Patients with ACS and severe combined renal and cardiac dysfunction have a particularly high mortality risk. In them, the ideal strategy to both optimize treatment of coronary disease and minimize renal injury risk is currently unknown. This was an interventional study. ACS patients (STEMI and NSTEMI) with associated severe renal (eGFR ≤30 ml/min/1.73 m(2) ) and cardiac (LVEF ≤40%) dysfunction, admitted at La Spezia Hospital <24 hr from symptoms onset, underwent a prophylactic 3-hr hemodiafiltration treatment, which was started soon after urgent or emergency coronary procedure. Controls were patients matched for age, gender, Mehran's risk score, and kind of ACS, admitted at the Centro Cardiologico Monzino Milan. In-hospital and 1-year outcomes were evaluated. Sixty patients (30% STEMI), 30 hemodiafiltration-treated patients and 30 controls, with similar baseline characteristics, were included. In-hospital and cumulative 1-year mortality rates were significantly lower in hemodiafiltration-treated patients than in controls (3% vs. 23%; P = 0.05, and 10% vs. 53%; P < 0.001, respectively). Moreover, they had a lower incidence of severe AKI (10% vs. 40%; P = 0.015) and lower need for rescue renal replacement therapy during hospitalization (7% vs. 27%; P = 0.04). Our pilot study suggests that, in ACS patients with severe renal and cardiac insufficiency, treatment with an aggressive prophylactic hemodiafiltration session after urgent or emergency coronary angiography seems to be associated with a relevant improvement in survival. © 2014 Wiley Periodicals, Inc.

  6. Evolution of subclinical myocardial dysfunction detected by two-dimensional and three-dimensional speckle tracking in asymptomatic type 1 diabetic patients: a long‑term follow-up study.

    Science.gov (United States)

    Ringle, Anne; Dornhorst, Anne; Rehman, Michaela B; Ruisanchez, Cristina; Nihoyannopoulos, Petros

    2017-12-01

    We sought to assess the long-term evolution of left ventricular (LV) function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy, in asymptomatic type 1 diabetic patients, over a 6-year follow-up. Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular risk factors were compared to 26 matched healthy controls. Conventional, 2D and 3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year follow-up evaluation. At baseline, diabetic patients had similar LV ejection fraction (60 vs 61%; P  = NS), but impaired longitudinal function, as assessed by 2D-global longitudinal strain (GLS) (-18.9 ± 2 vs -20.5 ± 2; P  = 0.0002) and 3D-GLS (-17.5 ± 2 vs -19 ± 2; P  = 0.003). At follow-up, diabetic patients had worsened longitudinal function compared to baseline (2D-GLS: -18.4 ± 1 vs -19.2 ± 1; P  = 0.03). Global circumferential (GCS) and radial (GRS) strains were unchanged at baseline and during follow-up. Metabolic status did not correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of a compensatory increase of circumferential and radial functions in advanced stages of the disease - long-term diabetes (GCS: -26 ± 3 vs -23.3 ± 3; P  = 0.008) and in the presence of microvascular complications (GRS: 38.8 ± 9 vs 34.3 ± 8; P  = 0.04). Subclinical myocardial dysfunction can be detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by a mild decrease in longitudinal function at the follow-up, but did not extend to a clinical expression of the disease, as no death or over heart failure was reported. © 2017 The authors.

  7. Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunction without affecting blood pressure in angiotensin II-high salt-induced hypertension.

    Science.gov (United States)

    González, Germán E; Rhaleb, Nour-Eddine; D'Ambrosio, Martin A; Nakagawa, Pablo; Liu, Yunhe; Leung, Pablo; Dai, Xiangguo; Yang, Xiao-Ping; Peterson, Edward L; Carretero, Oscar A

    2015-01-01

    Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II). Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks. Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio. In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.

  8. Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunction without affecting blood pressure in angiotensin II-high salt-induced hypertension

    Science.gov (United States)

    González, Germán E.; Rhaleb, Nour-Eddine; D’ambrosio, Martin A.; Nakagawa, Pablo; Liu, Yunhe; Leung, Pablo; Dai, Xiangguo; Yang, Xiao-Ping; Peterson, Edward L.; Carretero, Oscar A.

    2014-01-01

    Objective Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II). Methods Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks. Results Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio. Conclusion In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension. PMID:25304471

  9. Cardiac Myosin Binding Protein-C Autoantibodies Are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Thomas L. Lynch, IVPhD

    2017-04-01

    Full Text Available Summary: The degradation and release of cardiac myosin binding protein-C (cMyBP-C upon cardiac damage may stimulate an inflammatory response and autoantibody (AAb production. We determined whether the presence of cMyBP-C-AAbs associated with adverse cardiac function in cardiovascular disease patients. Importantly, cMyBP-C-AAbs were significantly detected in acute coronary syndrome patient sera upon arrival to the emergency department, particularly in ST-segment elevation myocardial infarction patients. Patients positive for cMyBP-C-AAbs had reduced left ventricular ejection fraction and elevated levels of clinical biomarkers of myocardial infarction. We conclude that cMyBP-C-AAbs may serve as early predictive indicators of deteriorating cardiac function and patient outcome in acute coronary syndrome patients prior to the infarction. Key Words: acute myocardial infarction, autoantibodies, cardiac myosin binding protein-c, cardiomyopathy

  10. Muscular, cardiac, ventilatory and metabolic dysfunction in patients with multiple sclerosis: Implications for screening, clinical care and endurance and resistance exercise therapy, a scoping review.

    Science.gov (United States)

    Wens, Inez; Eijnde, Bert O; Hansen, Dominique

    2016-08-15

    In the treatment of multiple sclerosis (MS), exercise training is now considered a cornerstone. However, most clinicians tend to focus on neurologic deficits only, and thus prefer to prescribe rehabilitation programs specifically to counteract these deficits. However, the present comprehensive review shows that patients with MS (pwMS) also experience significant muscular, cardiac, ventilatory and metabolic dysfunction, which significantly contribute, next to neurologic deficits, to exercise intolerance. In addition, these anomalies also might increase the risk for frequent hospitalization and morbidity and can reduce life expectancy. Unfortunately, the impact of exercise intervention on these anomalies in pwMS are mostly unknown. Therefore, it is suggested that pwMS should be screened systematically for muscular, cardiac, ventilatory and metabolic function during exercise testing. The detection of such anomalies should lead to adaptations and optimisation of exercise training prescription and clinical care/medical treatment of pwMS. In addition, future studies should focus on the impact of exercise intervention on muscular, cardiac, ventilatory and metabolic (dys)function in pwMS, to contribute to improved treatment and care. Copyright © 2016. Published by Elsevier B.V.

  11. Prolongation of heart rate-corrected QT interval is a predictor of cardiac autonomic dysfunction in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Nomura, Atsushi; Kishimoto, Mitsumasa; Takahashi, Osamu; Deshpande, Gautam A; Yamaguchi, Kenichi; Okada, Masato

    2014-05-01

    Heart rate-corrected QT interval duration (QTc) has been shown to be related to cardiac autonomic dysfunction in patients with diabetes mellitus, although this association has not been previously described in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed the medical records of 91 SLE patients and 144 non-SLE connective tissue disease patients visiting our clinic from November 2010 to April 2011. We compared ambulatory heart rate identified by pulse measured by automated machine in an outpatient waiting area versus resting heart rate identified on prior screening electrocardiogram. Heart rate differences were analyzed in relation to QTc interval and other characteristics. Ambulatory and resting heart rate differences were larger among SLE patients with QTc prolongation (QTc > 430 ms) than those without QTc prolongation (mean difference, 15.9 vs. 9.6, p = 0.001). In multivariate analysis, differences in heart rate were associated with QTc prolongation (OR 1.10, 95 % CI 1.01-1.21; p = 0.038), independent of age, duration of disease, immunosuppressant use, hydroxychloroquine use, diabetes mellitus, cardiac abnormality, anti-Ro/SS-A antibody positivity, or resting heart rate. Cardiac autonomic dysfunction is a common manifestation of SLE and may be related to QTc prolongation.

  12. Predictive Value of Beat-to-Beat QT Variability Index across the Continuum of Left Ventricular Dysfunction: Competing Risks of Non-cardiac or Cardiovascular Death, and Sudden or Non-Sudden Cardiac Death

    Science.gov (United States)

    Tereshchenko, Larisa G.; Cygankiewicz, Iwona; McNitt, Scott; Vazquez, Rafael; Bayes-Genis, Antoni; Han, Lichy; Sur, Sanjoli; Couderc, Jean-Philippe; Berger, Ronald D.; de Luna, Antoni Bayes; Zareba, Wojciech

    2012-01-01

    Background The goal of this study was to determine the predictive value of beat-to-beat QT variability in heart failure (HF) patients across the continuum of left ventricular dysfunction. Methods and Results Beat-to-beat QT variability index (QTVI), heart rate variance (LogHRV), normalized QT variance (QTVN), and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca (MUSIC) HF study (mean age 63.1±11.7; males 70.6%; LVEF >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance (IDEAL) database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death [hazard ratio (HR) 1.67(95%CI 1.14-2.47), P=0.009] and in particular with non-sudden cardiac death [HR 2.91(1.69-5.01), P<0.001]. Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular [HR 1.57(1.04-2.35), P=0.031], and non-sudden cardiac death in multivariate competing risk model [HR 2.58(1.13-3.78), P=0.001]. No interaction between QTVI and LVEF was found. QTVI predicted neither non-cardiac death (P=0.546) nor SCD (P=0.945). Decreased heart rate variability (HRV) rather than increased QT variability was the reason for increased QTVI in this study. Conclusions Increased QTVI due to depressed HRV predicts cardiovascular mortality and non-sudden cardiac death, but neither SCD nor excracardiac mortality in HF across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from HF patients at risk. PMID:22730411

  13. SUBCLINICAL HYPOTHYROIDISM IN METABOLIC SYNDROME AND ROLE OF CRP IN 50 ADULT PATIENTS

    Directory of Open Access Journals (Sweden)

    Pratik Shah

    2017-04-01

    Full Text Available BACKGROUND Metabolic Syndrome (MetS is generally characterised as a clustering of the abnormal levels of blood lipids (low HDL and high triglycerides, impaired fasting glucose, elevated blood pressure, and excess abdominal obesity. The objectives of the study areTo evaluate presence of Subclinical Hypothyroidism in the study population of the patients with metabolic syndrome. To find out relation between Subclinical Hypothyroidism and different parameters of metabolic syndrome. To evaluate whether patients of metabolic syndrome with raised hs-CRP have an increased risk of having hypothyroidism. MATERIALS AND METHODS A total of 50 adult patients who met with inclusion criteria were selected. Patients with metabolic syndrome (MetS who fulfilled the NCEP-ATP III criteria: 3 out of 5 criteria positive. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions (e.g. lithium, amiodarone or γ-interferon were excluded from the study. RESULTS A total of 50 patients of metabolic syndrome were enrolled. Out of which 36 were euthyroid, 3 were overt hypothyroid and 11 were subclinical hypothyroid. Out of 11 patients of subclinical hypothyroidism, 9 were female and 2 were male patients. Out of 28 females, 9 (32% were SCH while out of 22 males, 2 (9% were SCH. Out of 50 patients, 3 were overt hypothyroid. All 3 patients had BP >130/85, waist circumference was >88 cm and HDL of 130/85, HDL 150 mg/dL and fasting blood glucose of >100 mg/dL were more associated with male patients. CONCLUSION Subclinical Hypothyroidism was present in 22% of study population and more so in females having metabolic syndrome (32%. Hence, it will be worthwhile to screen female metabolic syndrome patients for thyroid function abnormality. Abnormal blood pressure, triglycerides and HDL cholesterol levels were more associated with subclinical hypothyroidism

  14. Haemodynamic changes following treatment of subclinical and overt hyperthyroidism

    DEFF Research Database (Denmark)

    Faber, J; Wiinberg, N; Schifter, S

    2001-01-01

    Hyperthyroidism has profound effects on the cardiovascular system, including reduced systemic vascular resistance (SVR) due to relaxation of vascular smooth muscle cells, enhanced heart rate (HR) and cardiac output (CO) due to an increase in cardiac diastolic relaxation, contractility and heart...... rate. Subclinical hyperthyroidism is characterised by reduced serum TSH levels despite free thyroxine (T4) and tri-iodothyronine (T3) estimates within the reference range, in subjects with no obvious symptoms of hyperthyroidism. We measured haemodynamic changes (using impedance cardiography......) in subjects with endogenous subclinical hyperthyroidism in order to elucidate whether these patients had signs of excess thyroid hormone at the tissue level....

  15. Thyroid dysfunction in the elderly

    African Journals Online (AJOL)

    1997-09-09

    Sep 9, 1997 ... hyperthyroidism and 7 of hypothyroidism. Subclinical disease was diagnosed in 40 subjects. The overall prevalence of thyroid dysfunction in this population was. 11.2%. In 22 (3.4%) this had previously been recognised, while in 50 (7.8%) the dysfunction was newly diagnosed by the current survey.

  16. Inflammation and microvascular dysfunction in cardiac syndrome X patients without conventional risk factors for coronary artery disease.

    Science.gov (United States)

    Recio-Mayoral, Alejandro; Rimoldi, Ornella E; Camici, Paolo G; Kaski, Juan Carlos

    2013-06-01

    The aim of this study was to ascertain whether coronary microvascular dysfunction (CMD) and inflammation are related in cardiac syndrome X (CSX). CMD can lead to CSX, defined as typical angina and transient myocardial ischemia despite normal coronary arteriograms. Inflammation has been suggested to play a role in the pathogenesis of myocardial ischemia in CSX. We assessed 21 CSX patients (age 52 ± 10 years; 17 women) without traditional cardiovascular risk factors and 21 matched apparently healthy control subjects. Positron emission tomography was used to measure myocardial blood flow (MBF) and coronary flow reserve (CFR) in response to intravenous adenosine, whereas high-sensitivity C-reactive protein (CRP) was measured to assess inflammation. Patients were subdivided a priori into 2 groups according to CRP concentrations at study entry (i.e., ≤3 or >3 mg/l). There were no differences in resting (1.20 ± 0.23 ml/min/g vs. 1.14 ± 0.20 ml/min/g; p = 0.32) or hyperemic MBF (3.28 ± 1.02 ml/min/g vs. 3.68 ± 0.89 ml/min/g; p = 0.18) between CSX patients and the control group, whereas CFR was mildly reduced in CSX patients compared with the control group (2.77 ± 0.80 vs. 3.38 ± 0.80; p = 0.02). Patients with CRP >3 mg/l had more severe impairment of CFR (2.14 ± 0.33 vs. 3.16 ± 0.76; p = 0.001) and more ischemic electrocardiographic changes during adenosine administration than patients with lower CRP, and a negative correlation between CRP levels and CFR (r = -0.49, p = 0.02) was found in CSX patients. CSX patients with elevated CRP levels had a significantly reduced CFR compared with the control group, which is indicative of CMD. Our study thus suggests a role for inflammation in the modulation of coronary microvascular responses in patients with CSX. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial

    Science.gov (United States)

    Zhong, Jia; Trevisi, Letizia; Urch, Bruce; Lin, Xinyi; Speck, Mary; Coull, Brent A.; Liss, Gary; Thompson, Aaron; Wu, Shaowei; Wilson, Ander; Koutrakis, Petros; Silverman, Frances; Gold, Diane R.; Baccarelli, Andrea A.

    2017-04-01

    Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5-induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.

  18. Cardiac Myosin Binding Protein-C Autoantibodies are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome.

    Science.gov (United States)

    Lynch, Thomas L; Kuster, Diederik W D; Gonzalez, Beverly; Balasubramanian, Neelam; Nair, Nandini; Day, Sharlene; Calvino, Jenna E; Tan, Yanli; Liebetrau, Christoph; Troidl, Christian; Hamm, Christian W; Güçlü, Ahmet; McDonough, Barbara; Marian, Ali J; van der Velden, Jolanda; Seidman, Christine E; Huggins, Gordon S; Sadayappan, Sakthivel

    2017-04-01

    The degradation and release of cardiac myosin binding protein-C (cMyBP-C) upon cardiac damage may stimulate an inflammatory response and autoantibody (AAb) production. We determined whether the presence of cMyBP-C-AAbs associated with adverse cardiac function in CVD patients. Importantly, cMyBP-C-AAbs were significantly detected in ACS patient sera upon arrival to the emergency department, particularly in STEMI patients. Patients positive for cMyBP-C-AAbs had a reduced LVEF and elevated levels of clinical biomarkers of MI. We conclude that cMyBP-C-AAbs may serve as early predictive indicators of deteriorating cardiac function and patient outcome in ACS patients prior to the infarction.

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

    Science.gov (United States)

    Heinonen, Suvi E; Merentie, Mari; Hedman, Marja; Mäkinen, Petri I; Loponen, Elina; Kholová, Ivana; Bosch, Fatima; Laakso, Markku; Ylä-Herttuala, Seppo

    2011-06-30

    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). 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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass.

    Science.gov (United States)

    Schulze, Costas J; Castro, Michele M; Kandasamy, Arulmozhi D; Cena, Jonathan; Bryden, Courtney; Wang, Shoa H; Koshal, Arvind; Tsuyuki, Ross T; Finegan, Barry A; Schulz, Richard

    2013-11-01

    Matrix metalloproteinase-2 proteolyzes intracellular proteins in the heart and induces acute myocardial contractile dysfunction in ischemia-reperfusion injury. Doxycycline, a matrix metalloproteinase inhibitor, prevented matrix metalloproteinase-2-induced troponin I cleavage in rat hearts and improved contractile function following ischemia-reperfusion. In patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass, increased atrial matrix metalloproteinase-2 activity was inversely correlated with cardiac mechanical function at 3 hours reperfusion. We performed a study in patients with coronary artery disease undergoing primary elective coronary artery bypass graft surgery with cardiopulmonary bypass to determine whether doxycycline reduces cardiac mechanical dysfunction, matrix metalloproteinase activity, and troponin I degradation after reperfusion. Randomized, double-blinded, placebo-controlled study. University of Alberta Hospital. Forty-two patients with coronary artery disease undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. Patients were randomized to receive either oral administration of 20 mg of doxycycline or matching placebo pill twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days. Left ventricular stroke work index was examined prior to cardiopulmonary bypass and at 24 hours reperfusion. Right atrial biopsies were collected before cardiopulmonary bypass and 10 minutes after aortic cross-clamp release to determine matrix metalloproteinase-2 activity and troponin I level. Blood was collected to determine matrix metalloproteinase activity and interleukin-6, C-reactive protein, and troponin I levels. Cardiac 72-kDa matrix metalloproteinase-2 activity was lower upon reperfusion in biopsies from the doxycycline group (p = 0.01), and the increase of matrix metalloproteinase-2 activity in the placebo group due to reperfusion did not appear in the

  2. Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats

    NARCIS (Netherlands)

    Ouwens, D.M.; de Boer, C.; Fodor, M.; Galan, P.; Heine, R.J.; Maassen, J.A.; Diamant, M.

    2005-01-01

    Aims/hypothesis: Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic

  3. Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

    Science.gov (United States)

    Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

  4. 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...... of sarco/endoplasmic reticulum calcium ATPase and phospholamban showed no difference between genotypes. To determine the role of mTOR in the development of cardiac hypertrophy, we treated Acsl1(H-/-) mice with rapamycin. Six to eight week old Acsl1(H-/-) mice and their littermate controls were given i.......p. tamoxifen to eliminate cardiac Acsl1, then concomitantly treated for 10weeks with i.p. rapamycin or vehicle alone. Rapamycin completely blocked the enhanced ventricular S6K phosphorylation and cardiac hypertrophy and attenuated the expression of hypertrophy-associated fetal genes, including α-skeletal actin...

  5. Cardiac {sup 31}P-MRS compared to echocardiographic findings in patients with hypertensive heart disease without overt systolic dysfunction-Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Burkhard, Thorsten [Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main (Germany)], E-mail: Thorsten.Burkhard@web.de; Herzog, Christopher [Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main (Germany)], E-mail: c.herzog@em.uni-frankfurt.de; Linzbach, Sven [Department of Internal Medicine III, University Hospital Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main (Germany)], E-mail: s.linzbach@arcor.de; Spyridopoulos, Ioakim [Department of Internal Medicine III, University Hospital Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main (Germany)], E-mail: spyridopoulos@em.uni-frankfurt.de; Huebner, Frank [Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main (Germany)], E-mail: Frank.Huebner@kgu.de; Vogl, Thomas J. [Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt/Main (Germany)], E-mail: t.vogl@em.uni-frankfurt.de

    2009-07-15

    Purpose: To evaluate changes in high energy phosphate (HEP) metabolism in patients with hypertension and diastolic dysfunction but with normal LVEF > 55% assessed by echocardiography and tissue Doppler. Material and methods: 20 patients (16 men and 4 women, mean age 57 {+-} 13 years) were studied with phosphorus magnetic resonance spectroscopy and echocardiography. MRS was performed at 1.5 T using an ECG-gated CSI sequence with nuclear Overhauser effect. According to echocardiographical findings 12 patients were found to have a diastolic dysfunction, whereas 8 patients were identified as normal, serving as control group in the following statistical analysis. All patients had normal systolic function (LVEF > 55%).Statistical analysis was made by using mean {+-} S.D. for description of the data, Spearman correlation and two-tailed Student's t-test for independent samples. Results: No differences were found in weight, age, LVEF, endsystolic volume, end-diastolic volume, cardiac output and BNP levels between patients and control group. Myocardial mass at end-diastole correlated significantly with PCr/ATP ratio (r = -0.66; p = 0.04) in patients and control group. Myocardial PCr/ATP ratio in patients was significantly decreased compared to controls (1.21 {+-} 0.22 vs. 1.54 {+-} 0.24; p = 0.006). Conclusions: Cardiac {sup 31}P-MRS might offer a noninvasive means for detecting early states of heart failure in hypertensive patients.

  6. Activation of the Nkx2.5–Calr–p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish

    Directory of Open Access Journals (Sweden)

    Yanyi Sun

    2017-10-01

    Full Text Available Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia. Echocardiography of the glucose-treated fish demonstrated diastolic dysfunction at an early stage and systolic dysfunction at a later stage, consistent with what is observed in diabetic patients. Enlarged hearts with decreased myocardial density, accompanied by decompensated cardiac function, indicated that apoptosis was critical in the pathological process. Significant upregulation of the expression of Nkx2.5 and its downstream targets calreticulin (Calr and p53 was noted in the glucose-treated fish. High-glucose stimulation in vitro evoked marked apoptosis of primary cardiomyocytes, which was rescued by the p53 inhibitor pifithrin-μ. In vitro experiments were performed using compound treatment and genetically via cell infection. Genetically, knockout of Nkx2.5 induced decreased expression of Nkx2.5, Calr and p53. Upregulation of Calr resulted in increased p53 expression, whereas the level of Nkx2.5 remained unchanged. An adult zebrafish model of hyperglycemia-induced cardiomyopathy was successfully established. Hyperglycemia-induced myocardial apoptosis was mediated, at least in part, by activation of the Nkx2.5–Calr–p53 pathway in vivo, resulting in cardiac dysfunction and hyperglycemia-induced cardiomyopathy.

  7. Daily exercise prevents diastolic dysfunction and oxidative stress in a female mouse model of western diet induced obesity by maintaining cardiac heme oxygenase-1 levels.

    Science.gov (United States)

    Bostick, Brian; Aroor, Annayya R; Habibi, Javad; Durante, William; Ma, Lixin; DeMarco, Vincent G; Garro, Mona; Hayden, Melvin R; Booth, Frank W; Sowers, James R

    2017-01-01

    Obesity is a global epidemic with profound cardiovascular disease (CVD) complications. Obese women are particularly vulnerable to CVD, suffering higher rates of CVD compared to non-obese females. Diastolic dysfunction is the earliest manifestation of CVD in obese women but remains poorly understood with no evidence-based therapies. We have shown early diastolic dysfunction in obesity is associated with oxidative stress and myocardial fibrosis. Recent evidence suggests exercise may increase levels of the antioxidant heme oxygenase-1 (HO-1). Accordingly, we hypothesized that diastolic dysfunction in female mice consuming a western diet (WD) could be prevented by daily volitional exercise with reductions in oxidative stress, myocardial fibrosis and maintenance of myocardial HO-1 levels. Four-week-old female C57BL/6J mice were fed a high-fat/high-fructose WD for 16weeks (N=8) alongside control diet fed mice (N=8). A separate cohort of WD fed females was allowed a running wheel for the entire study (N=7). Cardiac function was assessed at 20weeks by high-resolution cardiac magnetic resonance imaging (MRI). Functional assessment was followed by immunohistochemistry, transmission electron microscopy (TEM) and Western blotting to identify pathologic mechanisms and assess HO-1 protein levels. There was no significant body weight decrease in exercising mice, normalized body weight 14.3g/mm, compared to sedentary mice, normalized body weight 13.6g/mm (p=0.38). Total body fat was also unchanged in exercising, fat mass of 6.6g, compared to sedentary mice, fat mass 7.4g (p=0.55). Exercise prevented diastolic dysfunction with a significant reduction in left ventricular relaxation time to 23.8ms for exercising group compared to 33.0ms in sedentary group (pstress and myocardial fibrosis with improved mitochondrial architecture. HO-1 protein levels were increased in the hearts of exercising mice compared to sedentary WD fed females. This study provides seminal evidence that exercise

  8. Reversing dobutamine-induced tachycardia using ivabradine increases stroke volume with neutral effect on cardiac energetics in left ventricular post-ischaemia dysfunction.

    Science.gov (United States)

    Bakkehaug, J P; Naesheim, T; Torgersen Engstad, E; Kildal, A B; Myrmel, T; How, O-J

    2016-10-01

    Compensatory tachycardia can potentially be deleterious in acute heart failure. In this study, we tested a therapeutic strategy of combined inotropic support (dobutamine) and selective heart rate (HR) reduction through administration of ivabradine. In an open-chest pig model (n = 12) with left ventricular (LV) post-ischaemia dysfunction, cardiac function was assessed by LV pressure catheter and sonometric crystals. Coronary flow and blood samples from the coronary sinus were used to measure myocardial oxygen consumption (MVO2 ). LV energetics was assessed by comparing MVO2 with cardiac work at a wide range of workloads. In the post-ischaemia heart, dobutamine (5 μg kg(-1)  min(-1) ) increased cardiac output (CO) by increasing HR from 102 ± 21 to 131 ± 16 bpm (beats per min; P efficiency. Similar findings on efficiency and LV function were also seen using an ex vivo working mouse heart protocol. A combined infusion of dobutamine and ivabradine had a neutral effect on post-ischaemia LV efficiency and increased left ventricular output without an increase in HR. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  9. Subclinical renal abnormalities in young thalassemia major and ...

    African Journals Online (AJOL)

    Background: Limited data are available about renal involvement in thalassemia patients. Renal dysfunction in these patients seems to be multifactorial attributed mainly to long standing anemia, chronic hypoxia, iron overload and toxicity of iron chelators. Objective: To assess the frequency of subclinical glomerular and ...

  10. Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D; Tattersall, Matthew C; Volpe, Gustavo J; Ambale-Venkatesh, Bharath; Nasir, Khurram; Wu, Colin O; Polak, Joseph F; Korcarz, Claudia E; Stein, James H; Carr, James; Watson, Karol E; Bluemke, David A; Lima, João A C

    2015-04-01

    The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Disfunción ventricular izquierda subclínica en diabéticos tipo 1 con menos de 10 años de evolución de la diabetes Subclinical left ventricular dysfunction in type 1 diabetics with less than 10 years of evolution of diabetes

    Directory of Open Access Journals (Sweden)

    Manuel Licea Puig

    2001-04-01

    Full Text Available Se realizó un estudio transversal en 32 diabéticos tipo 1 con menos de 10 años de evolución de la enfermedad, edades entre 17 y 40 años, para conocer la frecuencia de disfunción ventricular izquierda (DVI subclínica y factores asociados a la misma. Se excluyeron los pacientes que presentaron valvulopatías, cardiopatía isquémica, hipertensión arterial y otras enfermedades que provocan miocardiopatías. Se les realizó una historia clínica completa y se les indicó: glucemia en ayunas, HbA1, colesterol total, triglicéridos totales, HDL-colesterol, excreción urinaria de albúmina (EUA, velocidad de conducción motora y sensitiva de los miembros inferiores, electrocardiograma y ecocardiograma modo M, bidimensional y con Doppler pulsado. Se adoptaron los criterios propuestos por la Sociedad Americana de Ecocardiografía para el diagnóstico ecocardiográfico de DVI. Se comprobó DVI en el 25 %. Las alteraciones estructurales cardíacas se observaron en el 6,2 %. La neuropatía periférica se presentó en 6 de 8 pacientes con DVI. Los niveles de EUA fueron significativamente mayores en los afectados de DVI (219,5 ± 170,2 mg/L vs. 66,9 ± 86,9 mg/L. En conclusión, se afirmó que la DVI es de observación relativamente frecuente en los diabéticos con menos de 10 años de evolución y los niveles de EUA pudieran constituir un marcador de riesgo para el desarrollo de esta complicación.A cross-sectional study in 32 type l diabetics aged 17-40 with less than 10 years of evolution of the disease was conducted to know the frequency of subclinical left ventricular dysfunction (LVD and its associated factors. Patients with valvulopathies, ischemic heart disease, arterial hypertension and other diseases causing myocardiopathies, were excluded. Complete medical histories were obtained and fasting glycemia, HbAl, total cholesterol, total triglycerides, HDL-cholesterol, urinary excretion of albumin (USA, velocity of motor and sensitive conduction

  12. Silencing Nox4 in the Paraventricular Nucleus Improves Myocardial Infarction-Induced Cardiac Dysfunction by Attenuating Sympathoexcitation and Peri-infarct Apoptosis

    Science.gov (United States)

    Infanger, David W.; Cao, Xian; Butler, Scott D.; Burmeister, Melissa A.; Zhou, Yi; Stupinski, John A.; Sharma, Ram V.; Davisson, Robin L.

    2010-01-01

    Rationale: Myocardial infarction (MI)-induced heart failure (HF) is characterized by central nervous system (CNS)-driven sympathoexcitation and deteriorating cardiac function. The paraventricular nucleus (PVN) of the hypothalamus is a key regulator of sympathetic nerve activity and is implicated in HF. Redox signaling in the PVN and other CNS sites is a primary mechanism of neuro-cardiovascular regulation, and excessive oxidant production by activation of NADPH oxidases (Nox) is implicated in some neuro-cardiovascular diseases. Objective: We tested the hypothesis that Nox-mediated redox signaling in the PVN contributes to MI-induced sympathoexcitation and cardiac dysfunction in mice. Methods and Results: Real-time PCR revealed that Nox4 was the most abundantly expressed Nox in PVN under basal conditions. Coronary arterial ligation (MI) caused a selective upregulation of this homologue compared to Nox1 and Nox2. Adenoviral gene transfer of Nox4 siRNA (AdsiNox4) to PVN (bilateral) attenuated MI-induced superoxide formation in this brain region (day 14) to the same level as that produced by PVN-targeted gene transfer of cytoplasmic superoxide dismutase (AdCu/ZnSOD). MI mice treated with AdsiNox4 or AdCu/ZnSOD in the PVN showed marked improvement in cardiac function as assessed by echocardiography and left ventricular hemodynamic analysis. This was accompanied by significantly diminished sympathetic outflow and apoptosis in the peri-infarct region of the heart. Conclusions: These results suggest that MI causes dysregulation of Nox4-mediated redox signaling in the PVN, which leads to sympathetic overactivation and a decline in cardiac function. Targeted inhibition of oxidant signaling in the PVN could provide a novel treatment for MI-induced HF. PMID:20413786

  13. Insulin and resveratrol act synergistically, preventing cardiac dysfunction in diabetes, but the advantage of resveratrol in diabetics with acute heart attack is antagonized by insulin.

    Science.gov (United States)

    Huang, Jiung-Pang; Huang, Shiang-Suo; Deng, Jen-Ying; Chang, Chih-Chun; Day, Yuan-Ji; Hung, Li-Man

    2010-12-01

    Resveratrol (RSV), a natural phenolic compound, has been found to display cardiovascular protective and insulin-sensitizing properties. In this study, the effects of RSV and its combination with insulin on mortality, hemodynamics, insulin signaling, and nitrosative stress were compared in streptozotocin (STZ)-induced diabetic rats with or without acute myocardial ischemia/reperfusion (I/R) injury. Under normoxic conditions, cardiac systolic and diastolic functions and insulin-mediated Akt/GLUT4 (glucose transporter 4) activation were impaired in STZ-diabetic rats. The combination of RSV and insulin significantly prevented the above diabetes-associated abnormalities. Notwithstanding that, the diabetic state rendered the animals more susceptible to myocardial I/R injury, and the mortality rate and inducible nitric oxide synthase (iNOS)/nitrotyrosine protein expression and superoxide anion production were also further increased in I/R-injured diabetic hearts. In contrast, RSV treatment alone resulted in a lower mortality rate (from 62.5 to 18%) and better cardiac systolic function than its combination with insulin. RSV also inhibited iNOS/nitrotyrosine protein overexpression and superoxide anion overproduction in I/R-injured diabetic myocardium. Hyperglycemia, impairment of insulin signaling, overexpression of iNOS/nitrotyrosine, and superoxide anion overproduction were markedly rescued by the combination treatment, which did not show an improvement in mortality rate (30%) or cardiac performance over RSV treatment alone. These results indicate that insulin and RSV synergistically prevented cardiac dysfunction in diabetes and this may be in parallel with activation of the insulin-mediated Akt/GLUT4 signaling pathway. Although activation of the protective signal (Akt/GLUT4) and suppression of the adverse markers (iNOS, nitrotyrosine, and superoxide anion) were simultaneously observed in insulin and RSV combination treatment, insulin counteracted the advantage of RSV in

  14. Dysregulation of microRNAs and renin-angiotensin system in high salt diet-induced cardiac dysfunction in uninephrectomized rats.

    Science.gov (United States)

    Amara, Venkateswara Rao; Surapaneni, Sunil Kumar; Tikoo, Kulbhushan

    2017-01-01

    Uninephrectomy is not associated with major adverse events in cardiovascular and renal functions of live kidney donors. The effect of high salt diet on the quality of life of live kidney donors is largely unknown. Hence in this study, we aimed to determine the effect of high salt diet on the alterations of renin-angiotensin system and microRNAs leading to CV and renal dysfunction in uninephrectomized rats. In order to mimic clinical scenario, uninephrectomized male Sprague Dawley rats were fed initially with normal pellet diet for 12 weeks and then for 20 weeks with high salt (10% w/w NaCl) diet. At the end of the study, biochemical, functional, histological and molecular parameters were measured. High salt diet feeding resulted in renal dysfunction & fibrosis, decreased baroreflex sensitivity, increased in vivo cardiovascular reactivity to angiotensin II owing to upregulation of angiotensin II type 1 receptors and L-type calcium channels leading to cardiovascular dysfunction in uninephrectomized rats (UNX+HSD) worse than that of normal (binephric) rats fed with high salt diet (HSD). Protein expression of functional and hypertrophic protein markers revealed decreased SERCA, p-AMPK and increased p-AKT. Interestingly, levels of miR-25, miR-451 and miR-155 increased and miR-99 decreased in heart of uninephrectomized rats fed with high salt. However, circulating miR-25 and miR-451 levels decreased and miR-99b increased in these animals. Our study points out that since tissue and circulating levels of miRNAs are not similar, caution must be exercised during the usage of miRs as diagnostic or prognostic biomarkers. To our knowledge, we are the first to show that epigenetic alterations result in cardiac dysfunction in uninephrectomized rats fed with high salt diet.

  15. Right Ventricular Systolic Dysfunction in Chagas Disease Defined by Speckle-Tracking Echocardiography: A Comparative Study with Cardiac Magnetic Resonance Imaging.

    Science.gov (United States)

    Moreira, Henrique T; Volpe, Gustavo J; Marin-Neto, José A; Nwabuo, Chike C; Ambale-Venkatesh, Bharath; Gali, Luis G; Almeida-Filho, Oswaldo C; Romano, Minna M D; Pazin-Filho, Antonio; Maciel, Benedito C; Lima, João A C; Schmidt, André

    2017-05-01

    Chagas disease leads to biventricular heart failure, usually with prominent systemic congestion. Although echocardiography is widely used in clinical routine, the utility of echocardiographic parameters to detect right ventricular (RV) systolic dysfunction in patients with Chagas disease is unknown. We sought to study the diagnostic value of echocardiography, including speckle-tracking parameters, to distinguish individuals with RV systolic dysfunction from those with normal RV systolic function in Chagas disease using cardiac magnetic resonance (CMR) as the reference method. In this cross-sectional study, 63 individuals with Chagas disease underwent echocardiography and CMR evaluations. Conventional echocardiographic parameters for RV functional evaluation were tricuspid annular plane systolic excursion, RV systolic excursion velocity, fractional area change, and RV index of myocardial performance. Strain and strain rate were obtained by two-dimensional speckle-tracking echocardiography and defined as "RV free wall," when based only in segments from RV free wall, or "RV free wall and septum," when segments from both free RV wall and interventricular septum were included. RV systolic dysfunction was defined as RV ejection fraction (RVEF) -22.5% for men and >-23.3% for women) exhibited the highest area under the receiver operating characteristic curve (area under the curve = 0.829) to differentiate the presence from the absence of RV systolic dysfunction in Chagas disease, with a sensitivity and specificity of 67% and 83%, respectively. RV free wall strain is an appropriate and superior echocardiographic variable for evaluating RV systolic function in Chagas disease, and it should be the method of choice for this purpose. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  16. Screening for subclinical atherosclerosis by noninvasive methods in asymptomatic patients with risk factors

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    Castellon X

    2013-05-01

    Full Text Available Xavier Castellon, Vera BogdanovaDepartment of Cardiology, Private Hospital Athis Mons, Paris, FranceAbstract: Atherosclerosis is a leading cause of cardiovascular death due to the increasing prevalence of the disease and the impact of risk factors such as diabetes, obesity or smoking. Sudden cardiac death is the primary consequence of coronary artery disease in 50% of men and 64% of women. Currently the only available strategy to reduce mortality in the at-risk population is primary prevention; the target population must receive screening for atherosclerosis. The value of screening for subclinical atherosclerosis is still relevant, it has become standard clinical practice with the emergence of new noninvasive techniques (radio frequency [RF] measurement of intima-media thickness [RFQIMT] and arterial stiffness [RFQAS], and flow-mediated vasodilatation [FMV], which have been used by our team since 2007 and are based on detection marker integrators which reflect the deleterious effect of risk factors on arterial remodeling before the onset of clinical events. These techniques allow the study of values according to age and diagnosis of the pathological value, the thickness of the intima media (RFQIMT, the speed of the pulse wave (RFQAS, and the degree of endothelial dysfunction (FMV. This screening is justified in asymptomatic patients with cardiovascular risk factors (hypertension, diabetes, obesity, dyslipidemia, and tobacco smoking. Studies conducted by RF coupled with two-dimensional echo since 2007 have led to a more detailed analysis of the state of the arterial wall. The various examinations allow an assessment of the degree of subclinical atherosclerosis and its impact on arterial remodeling and endothelial function. The use of noninvasive imaging in screening and early detection of subclinical atherosclerosis is reliable and reproducible and allows us to assess the susceptibility of our patients with risk factors and ensures better

  17. Cardiac Overexpression of Insulin-Like Growth Factor I (IGF-1) Attenuates Chronic Alcohol Intake-Induced Myocardial Contractile Dysfunction But Not Hypertrophy: Role of Akt, mTOR, GSK3β and PTEN

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    Zhang, Bingfang; Turdi, Subat; Li, Quan; Lopez, Faye L.; Eason, Anna R.; Anversa, Piero; Ren, Jun

    2010-01-01

    Chronic alcohol intake leads to the development of alcoholic cardiomyopathy manifested by cardiac hypertrophy and contractile dysfunction. This study was designed to examine the effect of transgenic overexpression of insulin-like growth factor I (IGF-1) on alcohol-induced cardiac contractile dysfunction. Wild-type FVB and cardiac-specific IGF-1 mice were placed on a 4% alcohol or control diet for 16 weeks. Cardiac geometry and mechanical function were evaluated by echocardiography, cardiomyocyte and intracellular Ca2+ properties. Histological analyses for cardiac fibrosis and apoptosis were evaluated by Masson trichrome staining and TUNEL assay, respectively. Expression and/or phosphorylation of Cu/Zn superoxide dismutase (SOD1), Ca2+ handling proteins, key signaling molecules for survival including Akt, mTOR, GSK3β, Foxo3a and the negative regulator of Akt phosphatase and tensin homolog on chromosome ten (PTEN) as well as mitochondrial proteins UCP-2 and PGC1α were evaluated by western blot analysis. Chronic alcohol intake led to cardiac hypertrophy, interstitial fibrosis, reduced mitochondrial number, compromised cardiac contractile function and intracellular Ca2+ handling, decreased SOD1 expression, elevated superoxide production and overt apoptosis, all of which with the exception of cardiac hypertrophy were abrogated by the IGF-1 transgene. Immunoblotting data showed reduced phosphorylation of Akt, mTOR, GSK3β and Foxo3a, upregulated Foxo3a and PTEN, as well as dampened SERCA2a, PGC1α and UCP-2 following alcohol intake. All these alcohol-induced changes in survival and mitochondrial proteins were alleviated by IGF-1. Taken together, these data favor a beneficial role of IGF-1 in alcohol-induced myocardial contractile dysfunction independent of cardiac hypertrophy. PMID:20678571

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

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    Maria E Danoviz

    Full Text Available BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6 cells isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C, or culture medium (ASC/M as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively. Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT and control groups (culture medium, fibrin, or collagen alone. Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW, a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  19. Increased H-FABP concentrations in nonalcoholic fatty liver disease. Possible marker for subclinical myocardial damage and subclinical atherosclerosis.

    Science.gov (United States)

    Başar, O; Akbal, E; Köklü, S; Tuna, Y; Koçak, E; Başar, N; Tok, D; Erbiş, H; Senes, M

    2013-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis. A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima-media thickness (CIMT) which was measured by high resolution B mode ultrasonography. H-FABP levels were elevated in patients with NAFLD (16.3 ± 4.0 ng/ml) when compared with healthy controls (13.8 ± 2.1 ng/ml; p  subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors.

  20. Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reperfusion Injury by Attenuating Mitochondrial Dysfunction in Testosterone-Deprived Rats

    Science.gov (United States)

    Pongkan, Wanpitak; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2015-01-01

    Background Although testosterone deficiency is associated with increased risks of heart disease, the benefits of testosterone therapy are controversial. Moreover, current understanding on the cardiac effect of testosterone during cardiac ischemia-reperfusion (I/R) periods is unclear. We tested the hypothesis that testosterone replacement attenuates the impairment of left ventricular (LV) function and heart rate variability (HRV), and reduces the infarct size and arrhythmias caused by I/R injury in orchiectomized (ORX) rats. Methodology ORX or sham-operated male Wistar rats (n = 24) were randomly divided and received either testosterone (2 mg/kg, subcutaneously administered) or the vehicle for 8 weeks. The ejection fraction (EF) and HRV were determined at baseline and the 4th and 8th week. I/R was performed by left anterior descending coronary artery ligation for 30 minutes, followed by a 120-minute reperfusion. LV pressure, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. Results Prior to I/R, EF and HRV were impaired in the ORX group, but were restored in the testosterone-treated group. During I/R, arrhythmia scores and the infarct size were greater, and cardiac mitochondrial function was impaired, whereas the time to 1st VT/VF onset and the LV end-systolic pressure were decreased in the ORX group when compared to the sham group. Testosterone replacement attenuated the impairment of these parameters in ORX rats during I/R injury, but did not show any benefit or adverse effect in non-ORX rats. Conclusions Testosterone replacement restores cardiac function and autonomic regulation, and exerts cardioprotective effects during the I/R period via mitochondrial protection in ORX rats. PMID:25822979

  1. Cardiac resynchronization therapy for exercise-induced left ventricular dysfunction in the setting of left bundle branch block: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    JoEllyn M. Abraham, MD

    2014-12-01

    Full Text Available Exercise-induced dyspnea is one of the most common symptoms that cause a patient to see a physician and a broad differential diagnosis is required. In this case report, we describe a patient with this complaint who had a left bundle branch block and preserved left ventricular function at rest. On stress echocardiography, she had significant exercise-induced left ventricular dysfunction and associated mitral regurgitation but a coronary angiogram demonstrated normal coronary arteries. Both of the echocardiographic findings, as well as her symptoms, improved with the placement of a bi-ventricular pacemaker. A brief review of the literature on cardiac resynchronization therapy for indications beyond the current guidelines is also provided.

  2. Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic Rats

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    Deng Jen-Ying

    2009-08-01

    Full Text Available Abstract In this study, we established systemic in-vivo evidence from molecular to organism level to explain how diabetes can aggravate myocardial ischemia-reperfusion (I/R injury and revealed the role of insulin signaling (with specific focus on Akt/GLUT4 signaling molecules. The myocardial I/R injury was induced by the left main coronary artery occlusion for 1 hr and then 3 hr reperfusion in control, streptozotocin (STZ-induced insulinopenic diabetes, and insulin-treated diabetic rats. The diabetic rats showed a significant decrease in heart rate, and a prolonged isovolumic relaxation (tau which lead to decrease in cardiac output (CO without changing total peripheral resistance (TPR. The phosphorylated Akt and glucose transporter 4 (GLUT 4 protein levels were dramatically reduced in both I/R and non-I/R diabetic rat hearts. Insulin treatment in diabetes showed improvement of contractile function as well as partially increased Akt phosphorylation and GLUT 4 protein levels. In the animals subjected to I/R, the mortality rates were 25%, 65%, and 33% in the control, diabetic, and insulin-treated diabetic group respectively. The I/R-induced arrhythmias and myocardial infarction did not differ significantly between the control and the diabetic groups. Consistent with its anti-hyperglycemic effects, insulin significantly reduced I/R-induced arrhythmias but had no effect on I/R-induced infarctions. Diabetic rat with I/R exhibited the worse hemodynamic outcome, which included systolic and diastolic dysfunctions. Insulin treatment only partially improved diastolic functions and elevated P-Akt and GLUT 4 protein levels. Our results indicate that cardiac contractile dysfunction caused by a defect in insulin-stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats.

  3. Erectile dysfunction

    Science.gov (United States)

    Yafi, Faysal A.; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M.; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J.; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P.; Hellstrom, Wayne J. G.

    2016-01-01

    Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man’s quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner’s sexual experience and the couple’s quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

  4. Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy.

    Science.gov (United States)

    Umbarkar, Prachi; Singh, Sarojini; Arkat, Silpa; Bodhankar, S L; Lohidasan, Sathiyanarayanan; Sitasawad, Sandhya L

    2015-10-01

    Oxidative stress is closely associated with the pathophysiology of diabetic cardiomyopathy (DCM). The mitochondrial flavoenzyme monoamine oxidase A (MAO-A) is an important source of oxidative stress in the myocardium. We sought to determine whether MAO-A plays a major role in modulating DCM. Diabetes was induced in Wistar rats by single intraperitoneal injection of streptozotocin (STZ). To investigate the role of MAO-A in the development of pathophysiological features of DCM, hyperglycemic and age-matched control rats were treated with or without the MAO-A-specific inhibitor clorgyline (CLG) at 1 mg/kg/day for 8 weeks. Diabetes upregulated MAO-A activity; elevated markers of oxidative stress such as cardiac lipid peroxidation, superoxide dismutase activity, and UCP3 protein expression; enhanced apoptotic cell death; and increased fibrosis. All these parameters were significantly attenuated by CLG treatment. In addition, treatment with CLG substantially prevented diabetes-induced cardiac contractile dysfunction as evidenced by decreased QRS, QT, and corrected QT intervals, measured by ECG, and LV systolic and LV end-diastolic pressure measured by microtip pressure transducer. These beneficial effects of CLG were seen despite the persistent hyperglycemic and hyperlipidemic environments in STZ-induced experimental diabetes. In summary, this study provides strong evidence that MAO-A is an important source of oxidative stress in the heart and that MAO-A-derived reactive oxygen species contribute to DCM. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Possible mechanisms of cardiac contractile dysfunction and electrical changes in ammonium chloride induced chronic metabolic acidosis in Wistar rats.

    Science.gov (United States)

    Lasheen, N N; Mohamed, G F

    2016-12-13

    Metabolic acidosis could occur due to either endogenous acids accumulation or bicarbonate loss from the gastrointestinal tract or commonly from the kidney. This study aimed to investigate the possible underlying mechanism(s) of chronic acidosis-induced cardiac contractile and electrical changes in rats. Twenty four adult Wistar rats, of both sexes, were randomly divided into control group and chronic metabolic acidosis group, which received orally 0.28 M NH(4)Cl in the drinking water for 2 weeks. At the end of experimental period, systolic and diastolic blood pressure values were measured. On the day of sacrifice, rats were anesthetized by i.p. pentobarbitone (40 mg/kg b.w.), transthoracic echocardiography and ECG were performed. Blood samples were obtained from abdominal aorta for complete blood count and determination of pH, bicarbonate, chloride, sodium, potassium, troponin I, CK-MB, IL-6, renin and aldosterone levels. Hearts from both groups were studied for cardiac tissue IL-6 and aldosterone in addition to histopathological examination. Compared to control group, chronic metabolic acidosis group showed anemia, significant systolic and diastolic hypotension accompanied by significant reduction of ejection fraction and fraction of shortening, significant bradycardia, prolonged QTc interval and higher widened T wave as well as significantly elevated plasma levels of renin, aldosterone, troponin I, CK-MB and IL-6, and cardiac tissue aldosterone and IL-6. The left ventricular wall of the acidosis group showed degenerated myocytes with fibrosis and apoptosis. Thus, chronic metabolic acidosis induced negative inotropic and chronotropic effects and cardiomyopathy, possibly by elevated aldosterone and IL-6 levels released from the cardiac tissue.

  6. Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.

    Science.gov (United States)

    Liang, Lei; Shou, Xi-Ling; Zhao, Hai-Kang; Ren, Gu-Qun; Wang, Jian-Bang; Wang, Xi-Hui; Ai, Wen-Ting; Maris, Jackie R; Hueckstaedt, Lindsay K; Ma, Ai-Qun; Zhang, Yingmei

    2015-02-01

    Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial

  7. [Perinatal outcome and cardiac dysfunction in preterm growth-restricted neonates in relation to placental impairment severity].

    Science.gov (United States)

    Candel Pau, Júlia; Castillo Salinas, Félix; Perapoch López, Josep; Carrascosa Lezcano, Antonio; Sánchez García, Olga; Llurba Olivé, Elisa

    2016-10-01

    Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants. To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation. Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed. IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan. Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Benefit of combining quantitative cardiac CT parameters with troponin I for predicting right ventricular dysfunction and adverse clinical events in patients with acute pulmonary embolism

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    Meyer, Mathias, E-mail: mr.meyer.mathias@gmail.com [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Fink, Christian, E-mail: Christian.Fink@umm.de [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Roeger, Susanne, E-mail: susanne.roeger@umm.de [1st Department of Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Apfaltrer, Paul, E-mail: Paul.Apfaltrer@umm.de [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Haghi, Dariush, E-mail: dariush.haghi@umm.de [1st Department of Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Kaminski, Wolfgang E., E-mail: wolfgang.kaminski@umm.de [Department of Clinical Chemistry, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Neumaier, Michael, E-mail: michael.neumaier@medma.uni-heidelberg.de [Department of Clinical Chemistry, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Schoenberg, Stefan O., E-mail: Stefan.Schoenberg@umm.de [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); and others

    2012-11-15

    Objective: To prospectively evaluate the diagnostic accuracy of quantitative cardiac CT parameters alone and in combination with troponin I for the assessment of right ventricular dysfunction (RVD) and adverse clinical events in patients with acute pulmonary embolism (PE). Materials and results: This prospective study had institutional review board approval and was HIPAA compliant. In total 83 patients with confirmed PE underwent echocardiography and troponin I serum level measurements within 24 h. Three established cardiac CT measurements for the assessment of RVD were obtained (RV/LV{sub axial}, RV/LV{sub 4-CH}, and RV/LV{sub volume}). CT measurements and troponin I serum levels were correlated with RVD found on echocardiography and adverse clinical events according to Management Strategies and Prognosis in Pulmonary Embolism Trial-3 (MAPPET-3 criteria. 31 of 83 patients with PE had RVD on echocardiography and 39 of 83 patients had adverse clinical events. A RV/LV{sub volume} ratio > 1.43 showed the highest area under the curve (AUC) (0.65) for the prediction of adverse clinical events when compared to RV/LV{sub axial}, RV/LV{sub 4Ch} and troponin I. The AUC for the detection of RVD of RV/LV{sub axial}, RV/LV{sub 4Ch}, RV/LV{sub volume}, and troponin I were 0.86, 0.86, 0.92, and 0.69, respectively. Combination of RV/LV{sub axial}, RV/LV{sub 4Ch}, RV/LV{sub volume} with troponin I increased the AUC to 0.87, 0.87 and 0.93, respectively. Conclusion: A combination of cardiac CT parameters and troponin I measurements improves the diagnostic accuracy for detecting RVD and predicting adverse clinical events if compared to either test alone.

  9. Targeted P2X7 R shRNA delivery attenuates sympathetic nerve sprouting and ameliorates cardiac dysfunction in rats with myocardial infarction.

    Science.gov (United States)

    Gao, Hongmei; Yin, Jie; Shi, Yugen; Hu, Hesheng; Li, Xiaolu; Xue, Mei; Cheng, Wenjuan; Wang, Ye; Li, Xinran; Li, Yongkang; Wang, Yu; Yan, Suhua

    2017-04-01

    Inflammation-dominated sympathetic sprouting adjacent to the necrotic region following myocardial infarction (MI) has been implicated in the etiology of arrhythmias resulting in sudden cardiac death; however, the mechanisms responsible remain to be elucidated. Although P2X7 R is a key immune mediator, its role has yet to be explored. We investigated whether P2X7 R regulates NF-κB and affects cardiac sympathetic reinnervation in rats undergoing MI. An adenoviral vector with a short hairpin RNA (shRNA) sequence inserted was adopted for the inhibition of P2X7 R in vivo. Myocardial infarction was induced by left coronary artery ligation, and immediately after that, recombinant P2X7 R-shRNA adenovirus, negative adenovirus (control), or normal saline solution (vehicle) was injected intramyocardially around the MI region and border areas. A high level of P2X7 R was activated in the infarcted tissue at an early stage. The administration of P2X7 R RNAi resulted in the inhibition of Akt and Erk1/2 phosphorylation and decreased the activation of NF-κB and macrophage infiltration, as well as attenuated the expression of nerve growth factor (NGF). Eventually, the NGF-induced sympathetic hyperinnervation was blunted, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP 43). At 7 days post-MI, the arrhythmia score of programmed electrical stimulation in the vehicle-treated infarcted rats was higher than the MI-shRNA group. Further amelioration of cardiac dysfunction was also detected. The administration of P2X7 R RNAi during the acute inflammatory response phase prevented the process of sympathetic hyperinnervation after MI, which was associated in part with inhibiting the Akt and ERK1/2 pathways and NF-κB activation. © 2016 John Wiley & Sons Ltd.

  10. Coronary microvascular dysfunction and diastolic load correlate with cardiac troponin T release measured by a highly sensitive assay in patients with nonischemic heart failure.

    Science.gov (United States)

    Takashio, Seiji; Yamamuro, Megumi; Izumiya, Yasuhiro; Sugiyama, Seigo; Kojima, Sunao; Yamamoto, Eiichiro; Tsujita, Kenichi; Tanaka, Tomoko; Tayama, Shinji; Kaikita, Koichi; Hokimoto, Seiji; Ogawa, Hisao

    2013-08-13

    This study investigated factors associated with cardiac troponin T (cTnT) release from failing myocardium. Persistent and modest elevation of serum cTnT is frequently observed in heart failure (HF) patients free of coronary artery disease, although the mechanisms underlying this finding remain unclear. We evaluated serum cTnT levels in the aortic root (Ao) and coronary sinus (CS) using a highly sensitive assay in 90 nonischemic HF patients and 47 non-HF patients. Transcardiac cTnT and plasma B-type natriuretic peptide (BNP) release were described as the differences between CS and Ao cTnT levels [ΔcTnT (CS-Ao)] and BNP levels [ΔBNP (CS-Ao)], respectively. Coronary flow reserve (CFR) was measured in 68 HF patients using an intracoronary Doppler guidewire. ΔcTnT (CS-Ao) levels were available in 76 HF patients and 28 non-HF patients (84% vs. 60%; p = 0.001), and higher in HF patients than non-HF patients (p Coronary microvascular dysfunction, diagnosed by CFR coronary microvascular dysfunction (4.8 [2.0 to 8.1] ng/l) than those without (2.0 [1.2 to 4.6] ng/l; p = 0.04). cTnT release from failing myocardium correlated with diastolic load and coronary microvascular dysfunction in nonischemic HF patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Management of subclinical hyperthyroidism.

    Science.gov (United States)

    Santos Palacios, Silvia; Pascual-Corrales, Eider; Galofre, Juan Carlos

    2012-01-01

    The ideal approach for adequate management of subclinical hyperthyroidism (low levels of thyroid-stimulating hormone [TSH] and normal thyroid hormone level) is a matter of intense debate among endocrinologists. The prevalence of low serum TSH levels ranges between 0.5% in children and 15% in the elderly population. Mild subclinical hyperthyroidism is more common than severe subclinical hyperthyroidism. Transient suppression of TSH secretion may occur because of several reasons; thus, corroboration of results from different assessments is essential in such cases. During differential diagnosis of hyperthyroidism, pituitary or hypothalamic disease, euthyroid sick syndrome, and drug-mediated suppression of TSH must be ruled out. A low plasma TSH value is also typically seen in the first trimester of gestation. Factitial or iatrogenic TSH inhibition caused by excessive intake of levothyroxine should be excluded by checking the patient's medication history. If these nonthyroidal causes are ruled out during differential diagnosis, either transient or long-term endogenous thyroid hormone excess, usually caused by Graves' disease or nodular goiter, should be considered as the cause of low circulating TSH levels. We recommend the following 6-step process for the assessment and treatment of this common hormonal disorder: 1) confirmation, 2) evaluation of severity, 3) investigation of the cause, 4) assessment of potential complications, 5) evaluation of the necessity of treatment, and 6) if necessary, selection of the most appropriate treatment. In conclusion, management of subclinical hyperthyroidism merits careful monitoring through regular assessment of thyroid function. Treatment is mandatory in older patients (> 65 years) or in presence of comorbidities (such as osteoporosis and atrial fibrillation).

  12. Management of Subclinical Hyperthyroidism

    Science.gov (United States)

    Santos Palacios, Silvia; Pascual-Corrales, Eider; Galofre, Juan Carlos

    2012-01-01

    The ideal approach for adequate management of subclinical hyperthyroidism (low levels of thyroid-stimulating hormone [TSH] and normal thyroid hormone level) is a matter of intense debate among endocrinologists. The prevalence of low serum TSH levels ranges between 0.5% in children and 15% in the elderly population. Mild subclinical hyperthyroidism is more common than severe subclinical hyperthyroidism. Transient suppression of TSH secretion may occur because of several reasons; thus, corroboration of results from different assessments is essential in such cases. During differential diagnosis of hyperthyroidism, pituitary or hypothalamic disease, euthyroid sick syndrome, and drug-mediated suppression of TSH must be ruled out. A low plasma TSH value is also typically seen in the first trimester of gestation. Factitial or iatrogenic TSH inhibition caused by excessive intake of levothyroxine should be excluded by checking the patient’s medication history. If these nonthyroidal causes are ruled out during differential diagnosis, either transient or long-term endogenous thyroid hormone excess, usually caused by Graves’ disease or nodular goiter, should be considered as the cause of low circulating TSH levels. We recommend the following 6-step process for the assessment and treatment of this common hormonal disorder: 1) confirmation, 2) evaluation of severity, 3) investigation of the cause, 4) assessment of potential complications, 5) evaluation of the necessity of treatment, and 6) if necessary, selection of the most appropriate treatment. In conclusion, management of subclinical hyperthyroidism merits careful monitoring through regular assessment of thyroid function. Treatment is mandatory in older patients (> 65 years) or in presence of comorbidities (such as osteoporosis and atrial fibrillation). PMID:23843809

  13. Subclinical Hyperthyroidism: When to Consider Treatment.

    Science.gov (United States)

    Donangelo, Ines; Suh, Se Young

    2017-06-01

    Subclinical hyperthyroidism is defined by a low or undetectable serum thyroid-stimulating hormone level, with normal free thyroxine and total or free triiodothyronine levels. It can be caused by increased endogenous production of thyroid hormone (e.g., in Graves disease, toxic nodular goiter, or transient thyroiditis), by administration of thyroid hormone to treat malignant thyroid disease, or by unintentional excessive replacement therapy. The prevalence of subclinical hyperthyroidism in the general population is about 1% to 2%; however, it may be higher in iodinedeficient areas. The rate of progression to overt hyperthyroidism is higher in persons with thyroid-stimulating hormone levels less than 0.1 mIU per L than in persons with low but detectable thyroid-stimulating hormone levels. Subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation and heart failure in older adults, increased cardiovascular and all-cause mortality, and decreased bone mineral density and increased bone fracture risk in postmenopausal women. However, the effectiveness of treatment in preventing these conditions is unclear. A possible association between subclinical hyperthyroidism and quality-of-life parameters and cognition is controversial. The U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for thyroid dysfunction in asymptomatic persons. The American Thyroid Association and the American Association of Clinical Endocrinologists recommend treating patients with thyroid-stimulating hormone levels less than 0.1 mIU per L if they are older than 65 years or have comorbidities such as heart disease or osteoporosis.

  14. Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction.

    Science.gov (United States)

    Zhou, Mi; Bao, Yuqian; Li, Haobo; Pan, Yong; Shu, Lingling; Xia, Zhengyuan; Wu, Donghai; Lam, Karen S L; Vanhoutte, Paul M; Xu, Aimin; Jia, Weiping; Hoo, Ruby L-C

    2015-10-01

    Clinical evidence shows that circulating levels of adipocyte fatty-acid-binding protein (A-FABP) are elevated in patients with diabetes and closely associated with ischaemic heart disease. Patients with diabetes are more susceptible to myocardial ischaemia/reperfusion (MI/R) injury. The experiments in the present study investigated the role of A-FABP in MI/R injury with or without diabetes. Non-diabetic and diabetic (streptozotocin-induced) A-FABP knockout and wild-type mice were subjected to MI/R or sham intervention. After MI/R, A-FABP knockout mice exhibited reductions in myocardial infarct size, apoptotic index, oxidative and nitrative stress, and inflammation. These reductions were accompanied by an improved left ventricular function compared with the relative controls under non-diabetic or diabetic conditions. After diabetes induction, A-FABP knockout mice exhibited a preserved cardiac function compared with that in wild-type mice. Endothelial cells, but not cardiomyocytes, were identified as the most likely source of cardiac A-FABP. Cardiac and circulating A-FABP levels were significantly increased in mice with diabetes or MI/R. Diabetes-induced superoxide anion production was significantly elevated in wild-type mice, but diminished in A-FABP knockout mice, and this elevation contributed to the exaggeration of MI/R-induced cardiac injury. Phosphorylation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were enhanced in both diabetic and non-diabetic A-FABP knockout mice after MI/R injury, but diminished in wild-type mice. The beneficial effects of A-FABP deficiency on MI/R injury were abolished by the NOS inhibitor N(G)-nitro-L-arginine methyl ester. Thus, A-FABP deficiency protects mice against MI/R-induced and/or diabetes-induced cardiac injury at least partially through activation of the eNOS/NO pathway and reduction in superoxide anion production. © 2015 Authors; published by Portland Press Limited.

  15. Adenosine A2A  receptor agonist prevents cardiac remodeling and dysfunction in spontaneously hypertensive male rats after myocardial infarction

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    da Silva JS

    2017-03-01

    Full Text Available Jaqueline S da Silva,1 Daniele Gabriel-Costa,1 Roberto T Sudo,1 Hao Wang,2 Leanne Groban,2 Emanuele B Ferraz,3 José Hamilton M Nascimento,3 Carlos Alberto M Fraga,1 Eliezer J Barreiro,1 Gisele Zapata-Sudo1 1Research Program Development of Drugs, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Background: This work evaluated the hypothesis that 3,4-methylenedioxybenzoyl-2- thienylhydrazone (LASSBio-294, an agonist of adenosine A2A  receptor, could be beneficial for preventing cardiac dysfunction due to hypertension associated with myocardial infarction (MI. Methods: Male spontaneously hypertensive rats (SHR were randomly divided into four groups (six animals per group: sham-operation (SHR-Sham, and myocardial infarction rats (SHR-MI were treated orally either with vehicle or LASSBio-294 (10 and 20 mg.kg-1.d-1 for 4 weeks. Echocardiography and in vivo hemodynamic parameters measured left ventricle (LV structure and function. Exercise tolerance was evaluated using a treadmill test. Cardiac remodeling was accessed by LV collagen deposition and tumor necrosis factor α expression. Results: Early mitral inflow velocity was significantly reduced in the SHR-MI group, and there was significant recovery in a dose-dependent manner after treatment with LASSBio-294. Exercise intolerance observed in the SHR-MI group was prevented by 10 mg.kg-1.d-1 of LASSBio-294, and exercise tolerance exceeded that of the SHR-Sham group at 20 mg.kg-1.d-1. LV end-diastolic pressure increased after MI, and this was prevented by 10 and 20 mg.kg-1.d-1 of LASSBio-294. Sarcoplasmic reticulum Ca2+ ATPase levels were restored in a dose-dependent manner after treatment with LASSBio-294. Fibrosis and inflammatory processes were also

  16. TLR4 knockout attenuated high fat diet-induced cardiac dysfunction via NF-κB/JNK-dependent activation of autophagy.

    Science.gov (United States)

    Hu, Nan; Zhang, Yingmei

    2017-08-01

    Obesity is commonly associated with a low grade systemic inflammation, which may contribute to the onset and development of myocardial remodeling and contractile dysfunction. Toll-like receptor 4 (TLR4) plays an important role in innate immunity and inflammation although its role in high fat diet-induced obesity cardiac dysfunction remains elusive. This study was designed to examine the effect of TLR4 ablation on high fat diet intake-induced cardiac anomalies, if any, and underlying mechanism(s) involved. Wild-type (WT) and TLR4 knockout mice were fed normal or high fat (60% calorie from fat) diet for 12weeks prior to assessment of mechanical and intracellular Ca(2+) properties. The inflammatory signaling proteins (TLR4, NF-κB, and JNK) and autophagic markers (Atg5, Atg12, LC3B and p62) were evaluated. Our results revealed that high fat diet intake promoted obesity, marked decrease in fractional shortening, and cardiomyocyte contractile capacity with dampened intracellular Ca(2+) release and clearance, elevated ROS generation and oxidative stress as measured by aconitase activity, the effects of which were significantly attenuated by TLR4 knockout. In addition, high fat intake downregulated levels of Atg5, Atg12 and LC3B, while increasing p62 accumulation. TLR4 knockout itself did not affect Atg5, Atg12, LC3B and p62 levels while it reconciled high fat diet intake-induced changes in autophagy. In addition, TLR4 knockout alleviated high fat diet-induced phosphorylation of IKKβ, JNK and mTOR. In vitro study revealed that palmitic acid suppressed cardiomyocyte contractile function, the effect of which was inhibited the TLR4 inhibitor CLI-095, the JNK inhibitor AS601245 or the NF-κB inhibitor Celastrol. Taken together, these data showed that TLR4 knockout ameliorated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies through inhibition of inflammation and ROS, possibly through a NF-κB/JNK-dependent activation of autophagy. This article is

  17. Cardiac autonomic testing and treating heart disease. 'A clinical perspective'

    Directory of Open Access Journals (Sweden)

    Nicholas L. DePace

    2014-12-01

    Full Text Available Background Coronary heart disease (CHD is a major health concern, affecting nearly half the middle-age population and responsible for nearly one-third of all deaths. Clinicians have several major responsibilities beyond diagnosing CHD, such as risk stratification of patients for major adverse cardiac events (MACE and treating risks, as well as the patient. This second of a two-part review series discusses treating risk factors, including autonomic dysfunction, and expected outcomes. Methods Therapies for treating cardiac mortality risks including cardiovascular autonomic neuropathy (CAN, are discussed. Results While risk factors effectively target high-risk patients, a large number of individuals who will develop complications from heart disease are not identified by current scoring systems. Many patients with heart conditions, who appear to be well-managed by traditional therapies, experience MACE. Parasympathetic and Sympathetic (P&S function testing provides more information and has the potential to further aid doctors in individualizing and titrating therapy to minimize risk. Advanced autonomic dysfunction (AAD and its more severe form cardiovascular autonomic neuropathy have been strongly associated with an elevated risk of cardiac mortality and are diagnosable through autonomic testing. This additional information includes patient-specific physiologic measures, such as sympathovagal balance (SB. Studies have shown that establishing and maintaining proper SB minimizes morbidity and mortality risk. Conclusions P&S testing promotes primary prevention, treating subclinical disease states, as well as secondary prevention, thereby improving patient outcomes through (1 maintaining wellness, (2 preventing symptoms and disorder and (3 treating subclinical manifestations (autonomic dysfunction, as well as (4 disease and symptoms (autonomic neuropathy.

  18. Dual-specificity phosphatase 14 protects the heart from aortic banding-induced cardiac hypertrophy and dysfunction through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway.

    Science.gov (United States)

    Li, Chang-Yi; Zhou, Qing; Yang, Ling-Chao; Chen, Yi-He; Hou, Jian-Wen; Guo, Kai; Wang, Yue-Peng; Li, Yi-Gang

    2016-03-01

    Dual-specificity phosphatase 14 (Dusp14), an important negative modulator of mitogen-activated protein kinase (MAPK) signaling pathways, has been implicated in inflammatory immune response, cancers, cell differentiation and proliferation. The role of Dusp14 in chronic pressure overload-induced cardiac hypertrophy has not been explored. Here we have shown that Dusp14-/- knockout mice and cardiac-specific Dusp14 transgenic mice were generated and subjected to aortic banding (AB) for 4 weeks. Our results demonstrated that genetic loss of Dusp14 significantly aggravated cardiac hypertrophy, fibrosis, ventricular dilation and dysfunction, whereas transgenic cardiac-specific Dusp14 overexpression significantly attenuated AB-induced cardiac dysfunction and remodeling. In vitro, adenoviral overexpression of constitutive Dusp14 blocked angiotensin II-induced hypertrophic growth of cardiomyocytes, while Dusp14 knockdown led to opposite effects. Mechanistically, excessive phosphorylation of TAK1, P38MAPK and JNK1/2 was evidenced in Dusp14-/- knockout mice post-AB and inactivation of TAK1-P38MAPK and -JNK1/2 signaling using TAK1 inhibitor 5Z-7-ox shares similar antihypertrophic effect as Dusp14 overexpression. Moreover, we show that Dusp14 directly interacted with TAK1. Results from present experiments indicate that Dusp14 protects the heart from AB-induced cardiac hypertrophy and dysfunction possibly through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway. Future studies are warranted to test the feasibility of overexpressing Dusp14 as a therapeutic strategy to attenuate cardiac hypertrophy and failure.

  19. Cardiac autonomic dysfunction in chronic stroke women is attenuated after submaximal exercise test, as evaluated by linear and nonlinear analysis.

    Science.gov (United States)

    Francica, Juliana Valente; Bigongiari, Aline; Mochizuki, Luís; Scapini, Kátia Bilhar; Moraes, Oscar Albuquerque; Mostarda, Cristiano; Caperuto, Erico Chagas; Irigoyen, Maria Cláudia; De Angelis, Katia; Rodrigues, Bruno

    2015-09-29

    We evaluated cardiac autonomic modulation in women with chronic ischemic stroke (at least 4 years post-stroke) at rest and in response to submaximal exercise test. Fourteen post-stroke women (S group) and 10 healthy women (C group) participated in this study. Autonomic modulation (using linear and nonlinear analysis), blood pressure and metabolic variables at rest were evaluated immediately after the exercise test and during the recovery period (20 min). All participants underwent submaximal exercise test on cycle ergometer with gas analysis. At rest, the S group displayed higher lactate concentration, systolic (SBP) and diastolic blood pressure (DBP) values when compared to C group. Furthermore, the S group had lower heart rate variability (HRV) in time domain (SDNN: S = 30 ± 5 vs. 40 ± 8 ms; rMSSD: S = 14 ± 2 vs. C = 34 ± 3 ms), decreased high frequency band of pulse interval (S = 8.4 ± 2 vs. 33.1 ± 9 %) and 2V pattern of symbolic analysis (S = 17.3 ± 1 vs. 30 ± 3 %) (both indicators of cardiac vagal modulation) when compared to C group. Immediately after exercise, S group presented higher values of lactate, SBP, DBP and double product when compared to C group, as well as decreased heart rate recovery (HRR) measured at the first, second and third minutes. At recovery time, all HRV parameters in time and frequency domains improved in the S group; however, HF band remained lower when compared to C group. After the exercise test, women with chronic stroke presented reduced heart rate variability, reduced cardiac vagal modulation, as well as reduced HRR, while displayed an improvement of heart rate variability and cardiac vagal modulation when compared to their baseline. These results reinforce the importance of a physically active lifestyle for cardiovascular autonomic disorders observed in chronic stroke women.

  20. Autoantibodies to the beta(1)-Adrenoceptor from Patients with Periodontitis as a Risk Factor for Cardiac Dysfunction

    OpenAIRE

    Segovia, Marcela; Reina, Silvia Lorena; Borda, Enri Santiago; Sterin, Leonor Josefina

    2017-01-01

    The presence of serum autoantibodies in periodontitis (P) patients against â(1)-adrenoceptor (â(1)-AR), using cardiac membranes or a synthetic â(1)-AR peptide corresponding to the second extracellular loop of human â(1)-AR as antigens, permit us to detect circulating antibody from 40 P patients but not in 20 normal individuals (control). Simultaneously, the P patients exhibited a decrease in HRV. Anti-â(1)-AR IgG titters correlated with the decrease in HRV of the same patients and the anti-â(...

  1. Low-dose vasopressin infusion results in increased mortality and cardiac dysfunction following ischemia-reperfusion injury in mice.

    Science.gov (United States)

    Indrambarya, Toonchai; Boyd, John H; Wang, Yingjin; McConechy, Melissa; Walley, Keith R

    2009-01-01

    Arginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component. However, the direct effect of arginine vasopressin on the function of the ischemia/reperfusion injured heart has not been clearly elucidated. We measured left ventricular ejection fraction using trans-thoracic echocardiography in C57B6 mice, both in normal controls and following ischemia/reperfusion injury induced by a one hour ligation of the left anterior descending coronary artery. Mice were treated with one of normal saline, dobutamine (8.33 microg/kg/min), or arginine vasopressin (0.00057 Units/kg/min, equivalent to 0.04 Units/min in a 70 kg human) delivered by an intraperitoneal micro-osmotic pump. Arterial blood pressure was measured using a micromanometer catheter. In addition, mortality was recorded and cardiac tissues processed for RNA and protein. Baseline left ventricular ejection fraction was 65.6% (60 to 72). In normal control mice, there was no difference in left ventricular ejection fraction according to infusion group. Following ischemia/reperfusion injury, AVP treatment significantly reduced day 1 left ventricular ejection fraction 46.2% (34.4 to 52.0), both in comparison with baseline and day 1 saline treated controls 56.9% (42.4 to 60.2). There were no significant differences in preload (left ventricular end diastolic volume), afterload (blood pressure) or heart rate to account for the effect of AVP on left ventricular ejection fraction. The seven-day mortality rate was highest in the arginine vasopressin group. Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression. Arginine vasopressin infusion significantly depressed the myocardial function in an ischemia/reperfusion model and increased mortality in comparison with both saline and dobutamine treated animals. The use of vasopressin may be contraindicated in non

  2. Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Suzuki, Yasuyuki; Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Takasaki, Gunma (Japan)

    2015-04-01

    Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct. (orig.)

  3. Clinical usefulness of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy in diabetic patients with cardiac sympathetic nerve dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Miyanaga, Hajime; Yoneyama, Satoshi; Kamitani, Tadaaki; Kawasaki, Shingo; Takahashi, Toru; Kunishige, Hiroshi [Matsushita Memorial Hospital, Osaka (Japan)

    1995-09-01

    To assess the clinical utility of {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy in evaluating cardiac sympathetic nerve disturbance in diabetic patients, we performed MIBG scintigraphy in 18 diabetic patients and 11 normal controls. Diabetic patients with symptomatic neuropathy (DM2) had a significantly lower heart to mediastinum uptake ratio than did those without neuropathy or normal controls in initial and delayed images (initial image, 1.90{+-}0.27 vs 2.32{+-}0.38, 2.41{+-}0.40, p<0.01; delayed image, 1.80{+-}0.31 vs 2.48{+-}0.35, 2.56{+-}0.28, p<001, respectively). Defect score, assessed visually, were higher in DM2 patients than in patients in the other two groups (initial image, 7{+-}2.6 vs 1.5{+-}1.9, 0.7{+-}0.9; delayed image 10.6{+-}3.3 vs 4.0{+-}2.5, 1.7{+-}1.6 p<0.01, respectively). The maximum washout rate in DM2 patients was also higher than those in patients in the other two groups. The findings of these indices obtained from MIBG scintigraphy coincided with the % low-frequency power extracted from heart rate fluctuations using a power spectral analysis and the results of the Schellong test, which were used to evaluate sympathetic function. These results suggest that MIBG scintigraphy may be useful for evaluating cardiac sympathetic nerve disturbance in patients with diabetes. (author).

  4. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects.

    Directory of Open Access Journals (Sweden)

    Viswanathan Rajagopalan

    Full Text Available A large body of evidence suggests that thyroid hormones (THs are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3 treatment in myocardial infarction (MI rats increased left ventricular (LV contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day was available in drinking water ad libitum immediately following MI and continuing for 2 month(s (mo. Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

  5. Thyroid dysfunction and pregnancy outcomes

    Directory of Open Access Journals (Sweden)

    Sima Nazarpour

    2015-07-01

    Full Text Available Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective, case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly

  6. Thyroid dysfunction and pregnancy outcomes

    Science.gov (United States)

    Nazarpour, Sima; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Azizi, Fereidoun

    2015-01-01

    Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long

  7. DETECTION OF OCCULT GLOMERULAR DYSFUNCTION IN GLUCOSE SIX PHOSPHATE DEHYDROGENASE DEFICIENCY ANEMIA

    Directory of Open Access Journals (Sweden)

    Gehan Abdel Hakeem

    2016-08-01

    G6PD deficiency anemia is associated with a variable degree of glomerular dysfunction during acute hemolytic episodes. This glomerular dysfunction can result in chronic subclinical or occult chronic kidney injury.

  8. Long-Term Outcome in Levothyroxine Treated Patients With Subclinical Hypothyroidism and Concomitant Heart Disease

    DEFF Research Database (Denmark)

    Andersen, Mette Nygaard; Olsen, Anne-Marie Schjerning; Madsen, Jesper Clausager

    2016-01-01

    CONTEXT: Subclinical hypothyroidism is a common condition that may lead to impaired cardiac function. OBJECTIVE: This study sought to examine the effects of levothyroxine treatment in patients with subclinical hypothyroidism and heart disease. DESIGN: This was a register-based historical cohort...... study. SETTING AND PARTICIPANTS: The study was composed of Danish primary care patients and hospital outpatients age 18 years and older with established heart disease who were diagnosed with subclinical hypothyroidism in 1997-2011. Patients were stratified according to whether they claimed a subsequent...... myocardial infaction and stroke, and all-cause hospital admissions. RESULTS: Of 61 611 patients with a diagnosis of cardiac disease having their first time thyroid function testing, 1192 patients with subclinical hypothyroidism (mean age 73.6 [SD ± 13.3] y, 63.8% female) were included, of whom 136 (11...

  9. Comparison of QT dispersion between subclinical hypothyroid and euthyroid patients

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    Muharrem Kıskaç

    2010-06-01

    Full Text Available Objectives: The aim of this study was to investigate the relationship between subclinical hypothyroid and QTc dispersionindicating local heterogeneity in repolarization of myocardium, which is well known as independent cardiac risk factor for sudden death and ventricular arrhythmia.Materials and Methods: We compared QTc dispersion of subclinical hypothyroid patients, after treatment and healthy control group. We included a total of 50 patients with 41 women and 9 men in the study group. Electrocardiographywith 12 derivations, thyroid hormones, serum electrolytes and basic biochemical parameters were measured.The control group consisted of 25 healthy individuals.QT distances were calculated by using Bazet formula. The difference between the longest QTc and the shortest QTc distance was accepted as QTc dispersion (QTcd.Results: Comparison of subclinical hypothyroid patients, their euthyroidic period after treatment and healthy controlgroup, gave no significant differences in age, body weight, body mass index and free thyroxin values. However,significant difference was found in durations of QTd and QTcd between the subclinical hypothyroid, the control and the euthyroidic groups (p0.05.Conclusion: Our results suggested that subclinical hypothyroidpatients had longer QTc dispersion compared to euthyroidic period and healthy subjects. However there was no QTcd difference between the euthyroidic period and healthy control group.

  10. Ferritin and body mass index predict cardiac dysfunction in female adolescents with anorexia of the restrictive type.

    Science.gov (United States)

    Docx, Martine K F; Weyler, Joost; Simons, Annik; Ramet, José; Mertens, Luc

    2015-08-01

    Decreased left ventricular mass index in anorexia nervosa is amply reported. The aim of this study is to identify non-burdensome predictors of reduced left yentricular mass/height (cLVM) in a cohort of adolescent restrictive anorexic girls. This is a retrospective study of all anorexic girls of the restrictive type referred to our tertiary eating disorder unit between September 2002 and December 2012, for somatic assessment of weig ht loss. All subjects fulfilled DMS-IV criteria, without a family history of cardiac or cardiovascular diseases. In all, 283 restrictive anorexic girls (age: 14.63 +/- 1.65 y; body mass index: 15.72 +/- 1.81 kg/m2) were included. Ferritin and body mass index were independent, statistically significant predictors of the corrected left ventricular mass (P anorexia nervosa of the restrictive type. Two factors predicted decreased cLVM in our population: ferritin and BMI.

  11. Subclinical hypothyroidism in childhood.

    LENUS (Irish Health Repository)

    O'Grady, M J

    2012-02-01

    Subclinical hypothyroidism (SH) is defined as an elevated thyroid stimulating hormone (TSH) in association with a normal total or free thyroxine (T4) or triiodothyronine (T3). It is frequently encountered in both neonatology and general paediatric practice; however, its clinical significance is widely debated. Currently there is no broad consensus on the investigation and treatment of these patients; specifically who to treat and what cut-off level of TSH should be used. This paper reviews the available evidence regarding investigation, treatments and outcomes reported for childhood SH.

  12. Netrin-1 abrogates ischemia/reperfusion-induced cardiac mitochondrial dysfunction via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS.

    Science.gov (United States)

    Siu, Kin Lung; Lotz, Christopher; Ping, Peipei; Cai, Hua

    2015-01-01

    Despite an established role of mitochondrial dysfunction in cardiac ischemia/reperfusion (I/R) injury, the upstream activators have remained incompletely defined. We have recently identified an innovative role of exogenously applied netrin-1 in cardioprotection, which is mediated by increased nitric oxide (NO) bioavailability. Here, we tested the hypothesis that this "pharmacological" treatment of netrin-1 preserves mitochondrial function via novel mechanisms that are NO dependent. Freshly isolated C57BL6 mouse hearts were perfused using a Langendorff system, and subjected to a 20min global ischemia/60min reperfusion, in the presence or absence of netrin-1. I/R induced marked increases in infarct size, total superoxide and hydrogen peroxide production, activity and protein abundance of NADPH oxidase (NOX) isoform 4 (NOX4), as well as impaired mitochondrial integrity and function, all of which were attenuated by netrin-1. This protective effect of netrin-1 is attributed to cGMP, a downstream effector of NO. The protein levels of NOX1 and NOX2 were however unaffected, and infarct size from NOX1 and NOX2 knockouts was not different from wild type animals. Scavenging of NO with PTIO reversed inhibitory effects of netrin-1 on NOX4, while NO donor attenuated NOX4 protein abundance. In vivo NOX4 RNAi, or sepiapterin perfusion, resulted in recoupling of NOS, decreased infarct size, and blockade of dysfunctional mitochondrial swelling and mitochondrial superoxide production. These data demonstrate that netrin-1 induces cardioprotection through inhibition of NOX4 activity, which leads to recoupling of NOS, augmented NO bioavailability, reduction in oxidative stress, and ultimately preservation of mitochondrial function. The NO-dependent NOX4 inhibition connects with our previously established pathway of DCC/ERK1/2/eNOS/NO/DCC feed-forward mechanism, to maintain NOS in the coupling state to attenuate oxidative stress to preserve mitochondrial function. These findings may

  13. Thyroid dysfunction in type 2 diabetics seen at the University ...

    African Journals Online (AJOL)

    Chigo Okwuosa

    %) of 36 non diabetic controls (P< 0.05). The prevalence of thyroid dysfunction is 32.4% in females and 25.9% in males. Secondary hypothyroidism was seen in 78.9%, sub-clinical hypothyroidism in 15.8%, and sub-clinical hyperthyroidism 5.2% ...

  14. CADUCEUS, SCIPIO, ALCADIA: Cell therapy trials using cardiac-°©‐derived cells for patients with post myocardial infarction LV dysfunction, still evolving

    Directory of Open Access Journals (Sweden)

    Magdi H Yacoub

    2012-03-01

    Full Text Available The early results of the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction study were recently published in the Lancet [1]. This study is a phase 1 prospective randomised study, performed at two centres. The study was designed to test the hypothesis that intracoronary infusion of autologous cardiac-derived cells following myocardial infarction can reduce the size of the infarct and increase the amount of viable myocardium. The eligible patients were randomised in a 2:1 ratio to receive CDCs or standard care. In all, 17 patients were randomised to cell therapy and 8 to standard care. The cell therapy consisted of an infusion of 25 million cells into the infarct related artery, 1.5–3 months after successful primary angioplasty in patients who developed LV dysfunction (EF less than 37 per cent. The cells were derived from RV endomyocardial biopsies performed within the previous 37 days. The number of cells was determined from previous experimental studies of the maximum number of cells which can be injected without inducing infarction. The study was not blinded because of ethical considerations regarding performing right ventricular biopsy on the controls. The exclusion criteria included patients who had evidence of right ventricular infarction, or could not have an MRI examination because of claustrophobia or prior insertion of devices. There was no death, myocardial infarction or serious arrhythmia reported in either group during the period of follow up, which was between 6-12 months. Serious adverse events were observed in 24 percent of the intervention group versus 12 per cent in the controls (p not significant.

  15. Implantable cardiac monitors in high-risk post-infarction patients with cardiac autonomic dysfunction and moderately reduced left ventricular ejection fraction: Design and rationale of the SMART-MI trial.

    Science.gov (United States)

    Hamm, Wolfgang; Rizas, Konstantinos D; Stülpnagel, Lukas von; Vdovin, Nikolay; Massberg, Steffen; Kääb, Stefan; Bauer, Axel

    2017-08-01

    Most deaths after myocardial infarction (MI) occur in patients with left ventricular ejection fraction (LVEF) >35%, for whom no specific prophylactic strategies exist. Deceleration capacity (DC) of heart rate and periodic repolarization dynamics (PRD) are noninvasive electrophysiological markers depending on the vagal and sympathetic tone. The combination of abnormal DC and/or PRD identifies a new high-risk group among postinfarction patients with LVEF 36%-50%. This new high-risk group has similar characteristics with respect to prognosis and patient numbers to those of the established high-risk group identified by LVEF ≤ 35%. The SMART-MI trial is an investigator-initiated randomized prospective multicenter trial that tests the efficacy of implantable cardiac monitors (ICM) in this new high-risk group. The study will enroll approximately 1,600 survivors of acute MI with sinus rhythm and an LVEF of 35%-50% in 17 centers in Germany who will be tested for presence of cardiac autonomic dysfunction. Four hundred patients with either abnormal DC (≤2.5 ms) and/or PRD (≥5.75deg2) will be randomized in a 1:1 fashion to intensive follow-up via telemonitoring using an ICM device (experimental arm) or conventional follow-up (control arm). For the ICM arm, specific treatment paths have been developed according to current guidelines. The primary end point is time to detection of predefined serious arrhythmic events during follow-up, including atrial fibrillation ≥6minutes, nonsustained ventricular tachycardia (cycle length≤320 ms; ≥40 beats), atrioventricular block ≥IIb, and sustained ventricular tachycardia/ventricular fibrillation. The median follow-up period is 18months with a minimum follow-up of 6months. The effect of remote monitoring on clinical outcomes will be tested as secondary outcome measure (ClinicalTrials.gov NCT02594488). Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients.

    Science.gov (United States)

    Halperin, Anthony; Pajuelo, Monica; Tornheim, Jeffrey A; Vu, Nancy; Carnero, Andrés M; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Camacho, Marilyn; Justiniano, Juan; Colanzi, Rony; Bowman, Natalie M; Morris, Tiffany; MacDougall, Hamish; Bern, Caryn; Moore, Steven T; Gilman, Robert H

    2016-06-01

    Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients. © The American Society of Tropical Medicine and Hygiene.

  17. BENEFICIAL EFFECTS OF LEVOTHYROXINE IN THE TREATMENT OF SUBCLINICAL HYPOTHYROIDISM

    Directory of Open Access Journals (Sweden)

    Mulic Mersudin

    2016-12-01

    Full Text Available Introduction:Increased cardiovascular risk in thyroid dysfunction is associated with disorders of lipid and lipoproteins, endothelial dysfunction, metabolic, hormonal, hemodynamic changes and coagulation disorders. Subclinical hypothyroidism is characterized by a suprarnormal level of TSH with normal levels of thyroid hormones. The correlation between subclinical hypothyroidism of the lipid profile and cardiovascular outcomes remains unclear. Several intervention studies assessed the effect of levothyroxine therapy on the lipid profile of patients with subclinical hypothyroidism and obtained conflicting results. The aim of the research is to determine whether subclinical hypothyroidism is associated with the atherogenic lipid profile and whether these changes are reversible after the introduction of the L-thyroxine replacement therapy. Method: The study included 51 patients over 50 years of age with subclinical hypothyroidism. All the participants were subjected to an examination programme which included a detailed anamnesis and physical examination, laboratory tests (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, T3, T4, TSH. After eight weeks of levothyroxine therapy, the same laboratory parameters were determined in the patients. Results: Subjects with subclinical hypothyroidism had high average values: TSH (12.77 + 2.78 mIU / ml, total cholesterol (7.55 ± 0.79 mmol / l, LDL cholesterol (5.03 ± 0.61 mmol / l, triglycerides (2.48 ± 1.01 mmol / l; and the average value of HDL cholesterol was within reference values (1.12 ± 0.21 mmol / l. After eight weeks of levothyroxine replacement therapy, there was a statistically significant reduction of average values (p <0.0001: TSH (3.83 ± 1.33 mIU / ml, total cholesterol (6.28 ± 0.96 mmol / l, LDL cholesterol ( 4.03 ± 0.70 mmol / mmol / l l, triglycerides (1.98 ± 0.87 mmol / l; and the average value of HDL cholesterol increased significantly (p <0.0001 (1.32 ± 0.22 mmol

  18. Oral treatment with Euterpe oleracea Mart. (açaí) extract improves cardiac dysfunction and exercise intolerance in rats subjected to myocardial infarction.

    Science.gov (United States)

    Zapata-Sudo, Gisele; da Silva, Jaqueline S; Pereira, Sharlene L; Souza, Pergentino J C; de Moura, Roberto S; Sudo, Roberto Takashi

    2014-07-08

    This study was designed to evaluate the cardioprotective effects of Euterpe oleracea Mart., popularly known as "açaí", on rats subjected to myocardial infarction (MI). Hydroalcoholic extracts of açaí were obtained from a decoction of the seeds. Two male Wistar rat groups were delineated: 1) the sham-operated group (control, n = 6), with no surgical amendment, and 2) the MI group (n = 12), in which the anterior descendent coronary artery was occluded during surgery. MI group was divided into two subgroups, in which rats were either treated with hydroalcoholic extract of Euterpe oleracea seeds (100 mg/kg/day p.o.) or received no treatment. Treatment began on the day of surgery, and lasted 4 weeks. Subsequently, rats were subject to an exercise test protocol, hemodynamic evaluation, and histological analysis of the left ventricle. Groups were compared using one-way analysis of variance (ANOVA), followed by Dunnett's test. The total running distance of sham rats was 1339.0 ± 276.6 m, MI rats was 177.6 ± 15.8 m (P Euterpe oleracea treatment of MI rats prevented the development of exercise intolerance, cardiac hypertrophy, fibrosis, and dysfunction.

  19. Apical left ventricular myocardial dysfunction is an early feature of cardiac involvement in myotonic dystrophy type 1.

    Science.gov (United States)

    Garcia, Rodrigue; Labarre, Quentin; Degand, Bruno; Ingrand, Pierre; Le Gal, François; Bonnet, Benjamin; Delaubier, Anne; Guillou, Claire; Gellen, Barnabas; Coisne, Damien; Bouleti, Claire; Christiaens, Luc

    2017-02-01

    Left ventricular (LV) dysfunction is a major prognostic determinant in myotonic dystrophy type 1 (DM1). Therefore, markers of early-stage LV impairment may be useful. The aim of this study was to evaluate 2D echocardiographic LV strain in a cohort of DM1 patients with preserved left ventricular ejection fraction (LVEF) and to compare the results with matched controls. This prospective single-center study included 33 consecutive DM1 patients between February 2014 and February 2015. Mean age was 38.2±12.9 years, and 17 (52%) were males. Exclusion criteria were LVEF 120 milliseconds, history of atrial fibrillation, and presence of a pacemaker with ventricular pacing. DM1 patients were matched to healthy controls according to sex and age. DM1 patients showed significant impairment of global longitudinal strain (GLS) as compared to controls (-18.0±1.9 vs -19.1±2.4; P=.03), characterized by a marked alteration at the apex (-20.0±3.3 vs -22.7±3.1; P<.001). DM1 patients had also global radial strain impairment (20.0±9.8 vs 27.5±14.9; P=.024) compared to controls while global circumferential strain was not statistically different between groups (P=.94). Intra- and inter-observer analysis showed good reproducibility of GLS. Despite preserved LVEF, DM1 patients exhibited significantly altered LV GLS, particularly at the apex, as compared with controls. The detection of impaired myocardial deformation at early stages of the disease might help to screen high-risk patients who need closer follow-up. © 2017, Wiley Periodicals, Inc.

  20. Sirtuin 1 protects the aging heart from contractile dysfunction mediated through the inhibition of endoplasmic reticulum stress-mediated apoptosis in cardiac-specific Sirtuin 1 knockout mouse model.

    Science.gov (United States)

    Hsu, Yu-Juei; Hsu, Shih-Che; Hsu, Chiao-Po; Chen, Yen-Hui; Chang, Yung-Lung; Sadoshima, Junichi; Huang, Shih-Ming; Tsai, Chien-Sung; Lin, Chih-Yuan

    2017-02-01

    The longevity regulator Sirtuin 1 is an NAD+-dependent histone deacetylase that regulates endoplasmic reticulum stress and influences cardiomyocyte apoptosis during cardiac contractile dysfunction induced by aging. The mechanism underlying Sirtuin 1 function in cardiac contractile dysfunction related to aging has not been completely elucidated. We evaluated cardiac contractile function, endoplasmic reticulum stress, apoptosis, and oxidative stress in 6- and 12month-old cardiac-specific Sirtuin 1 knockout (Sirt1-/-) and control (Sirt1f/f) mice using western blotting and immunohistochemistry. Mice were injected with a protein disulphide isomerase inhibitor. For in vitro analysis, cultured H9c2 cardiomyocytes were exposed to either a Sirtuin 1 inhibitor or activator, with or without a mitochondrial inhibitor, to evaluate the effects of Sirtuin 1 on endoplasmic reticulum stress, nitric oxide synthase expression, and apoptosis. The effects of protein disulphide isomerase inhibition on oxidative stress and ER stress-related apoptosis were also investigated. Compared with 6-month-old Sirt1f/f mice, marked impaired contractility was observed in 12-month-old Sirt1-/- mice. These findings were consistent with increased endoplasmic reticulum stress and apoptosis in the myocardium. Measures of oxidative stress and nitric oxide synthase expression were significantly higher in Sirt1-/- mice compared with those in Sirt1f/f mice at 6months. In vitro experiments revealed increased endoplasmic reticulum stress-mediated apoptosis in H9c2 cardiomyocytes treated with a Sirtuin 1 inhibitor; the effects were ameliorated by a Sirtuin 1 activator. Moreover, consistent with the in vitro findings, impaired cardiac contractility was demonstrated in Sirt1-/- mice injected with a protein disulphide isomerase inhibitor. The present study demonstrates that the aging heart is characterized by contractile dysfunction associated with increased oxidative stress and endoplasmic reticulum stress and

  1. Hemodynamic changes after levothyroxine treatment in subclinical hypothyroidism

    DEFF Research Database (Denmark)

    Faber, J; Petersen, L; Wiinberg, N

    2002-01-01

    In hypothyroidism, lack of thyroid hormones results in reduced cardiac function (cardiac output [CO]), and an increase of systemic vascular resistance (SVR). We speculated whether hemodynamic regulation in subjects with subclinical hypothyroidism (SH) (defined as mildly elevated thyrotropin [TSH.......05). These changes were qualitatively similar but quantitatively less pronounced than in 15 women with overt hypothyroidism, also studied. Taking the two groups together (n = 31), pretreatment thyroid function (expressed as either TSH or free T(4) estimate) correlated to CO and SVR as well as the changes induced...... by LT(4) (p hypothyroidism should...

  2. Cardiac autonomic neuropathy in patients with diabetes mellitus.

    Science.gov (United States)

    Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J

    2014-02-15

    Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.

  3. Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systolic dysfunction.

    Science.gov (United States)

    Pascual-Figal, Domingo A; Ordoñez-Llanos, Jordi; Tornel, Pedro L; Vázquez, Rafael; Puig, Teresa; Valdés, Mariano; Cinca, Juan; de Luna, Antoni Bayes; Bayes-Genis, Antoni

    2009-12-01

    We studied whether the measurement of the soluble form of ST2 (sST2), an interleukin-1 receptor family member, could identify heart failure (HF) patients at risk of sudden cardiac death (SCD). The prediction of SCD remains an important challenge in patients with mild-to-moderate chronic HF. Concentrations of sST2 have been found increased and related to worse long-term outcomes in patients with acute HF. Whether sST2 has a prognostic role in SCD is unknown. A nested case-control study was performed on 36 cases of SCD and 63 control patients (matched for age, sex, and left ventricular ejection fraction) obtained from the MUSIC (MUerte Súbita en Insuficiencia Cardíaca) registry, a 3-year multicenter registry of ambulatory HF patients (New York Heart Association functional class II to III, left ventricular ejection fraction < or =45%). Demographic, clinical, echocardiographic, electrical, and biochemical data were collected at enrollment. Concentrations of sST2 were greater among decedents (0.23 ng/ml [interquartile range 0.16 to 0.43 ng/ml] vs. 0.12 ng/ml [interquartile range 0.06 to 0.23 ng/ml], p = 0.001) and were predictive of experiencing SCD (+0.1 ng/ml, odds ratio: 1.39, 95% confidence interval: 1.09 to 1.78, p = 0.006). On the basis of a combined biomarker status, only 4% of patients experienced SCD for neither sST2 nor N-terminal pro-B-type natriuretic peptide (NT-proBNP) above receiver-operator characteristic-derived cut-off points (0.15 ng/ml and 2,000 ng/l, respectively), 34% for either biomarker above, and 71% for both biomarkers above (p < 0.001 for trend). This combined variable added incremental prognostic value to the multivariable regression model (p < 0.001). Elevated sST2 concentrations are predictive of SCD in patients with chronic HF and provide complementary information to NT-proBNP levels. A combined biomarker approach may have an impact on clinical decision-making.

  4. Cardiac catheterization

    Science.gov (United States)

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; ...

  5. mTOR Hyperactivation by Ablation of Tuberous Sclerosis Complex 2 in the Mouse Heart Induces Cardiac Dysfunction with the Increased Number of Small Mitochondria Mediated through the Down-Regulation of Autophagy.

    Directory of Open Access Journals (Sweden)

    Manabu Taneike

    Full Text Available Mammalian target of rapamycin complex 1 (mTORC1 is a key regulator of cell growth, proliferation and metabolism. mTORC1 regulates protein synthesis positively and autophagy negatively. Autophagy is a major system to manage bulk degradation and recycling of cytoplasmic components and organelles. Tuberous sclerosis complex (TSC 1 and 2 form a heterodimeric complex and inactivate Ras homolog enriched in brain, resulting in inhibition of mTORC1. Here, we investigated the effects of hyperactivation of mTORC1 on cardiac function and structure using cardiac-specific TSC2-deficient (TSC2-/- mice. TSC2-/- mice were born normally at the expected Mendelian ratio. However, the median life span of TSC2-/- mice was approximately 10 months and significantly shorter than that of control mice. TSC2-/- mice showed cardiac dysfunction and cardiomyocyte hypertrophy without considerable fibrosis, cell infiltration or apoptotic cardiomyocyte death. Ultrastructural analysis of TSC2-/- hearts revealed misalignment, aggregation and a decrease in the size and an increase in the number of mitochondria, but the mitochondrial function was maintained. Autophagic flux was inhibited, while the phosphorylation level of S6 or eukaryotic initiation factor 4E -binding protein 1, downstream of mTORC1, was increased. The upregulation of autophagic flux by trehalose treatment attenuated the cardiac phenotypes such as cardiac dysfunction and structural abnormalities of mitochondria in TSC2-/- hearts. The results suggest that autophagy via the TSC2-mTORC1 signaling pathway plays an important role in maintenance of cardiac function and mitochondrial quantity and size in the heart and could be a therapeutic target to maintain mitochondrial homeostasis in failing hearts.

  6. Subclinical heart failure in juvenile idiopathic arthritis: a consequence of chronic inflammation and subclinical atherosclerosis

    Directory of Open Access Journals (Sweden)

    Hamada S Ahmad

    2016-01-01

    Conclusion Our findings indicate the presence of subclinical heart failure in these patients. JIA patients with subclinical atherosclerosis, with systemic disease, and with active disease are at greatest risk of developing subclinical heart failure.

  7. Subclinical hyperthyroidism and pregnancy outcomes.

    Science.gov (United States)

    Casey, Brian M; Dashe, Jodi S; Wells, C Edward; McIntire, Donald D; Leveno, Kenneth J; Cunningham, F Gary

    2006-02-01

    Subclinical hyperthyroidism has long-term sequelae that include osteoporosis, cardiovascular morbidity, and progression to overt thyrotoxicosis or thyroid failure. The objective of this study was to evaluate pregnancy outcomes in women with suppressed thyroid-stimulating hormone (TSH) and normal free thyroxine (fT(4)) levels. All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, underwent thyroid screening by chemiluminescent TSH assay. Women with TSH values at or below the 2.5th percentile for gestational age and whose serum fT(4) levels were 1.75 ng/dL or less were identified to have subclinical hyperthyroidism. Those women screened and delivered of a singleton infant weighing 500 g or more were analyzed. Pregnancy outcomes in women identified with subclinical hyperthyroidism were compared with those in women whose TSH values were between the 5th and 95th percentiles. A total of 25,765 women underwent thyroid screening and were delivered of singleton infants. Of these, 433 (1.7%) were considered to have subclinical hyperthyroidism, which occurred more frequently in African-American and/or parous women. Pregnancies in women with subclinical hyperthyroidism were less likely to be complicated by hypertension (adjusted odds ratio 0.66, 95% confidence interval 0.44-0.98). All other pregnancy complications and perinatal morbidity or mortality were not increased in women with subclinical hyperthyroidism. Subclinical hyperthyroidism is not associated with adverse pregnancy outcomes. Our results indicate that identification of subclinical hyperthyroidism and treatment during pregnancy is unwarranted. II-2.

  8. In Vivo Post-Cardiac Arrest Myocardial Dysfunction Is Supported by Ca2+/Calmodulin-Dependent Protein Kinase II-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2.

    Science.gov (United States)

    Woods, Christopher; Shang, Ching; Taghavi, Fouad; Downey, Peter; Zalewski, Adrian; Rubio, Gabriel R; Liu, Jing; Homburger, Julian R; Grunwald, Zachary; Qi, Wei; Bollensdorff, Christian; Thanaporn, Porama; Ali, Ayyaz; Riemer, Kirk; Kohl, Peter; Mochly-Rosen, Daria; Gerstenfeld, Edward; Large, Stephen; Ali, Ziad; Ashley, Euan

    2016-09-27

    Survival after sudden cardiac arrest is limited by postarrest myocardial dysfunction, but understanding of this phenomenon is constrained by a lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. We developed rodent models of in vivo postarrest myocardial dysfunction using extracorporeal membrane oxygenation resuscitation followed by invasive hemodynamics measurement. In postarrest isolated cardiomyocytes, we assessed mechanical load and Ca(2) (+)-induced Ca(2+) release (CICR) simultaneously using the microcarbon fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel fiberoptic catheter imaging system and a genetically encoded calcium sensor, GCaMP6f, to image CICR in vivo. We found potentiation of CICR in isolated cells from this extracorporeal membrane oxygenation model and in cells isolated from an ischemia/reperfusion Langendorff model perfused with oxygenated blood from an arrested animal but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed after arrest was mediated by the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban, and ryanodine receptor 2 was detected in the postarrest period. Exogenous adrenergic activation in vivo recapitulated Ca(2+) potentiation but was associated with lesser CaMKII activation. Because oxidative stress and aldehydic adduct formation were high after arrest, we tested a small-molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and postarrest outcome in vivo. Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation, which

  9. Prevalence of Subclinical Hypothyroidism in Pregnant Women in Tehran-Iran

    Directory of Open Access Journals (Sweden)

    Fakhrolmolouk Yassaee

    2014-07-01

    Full Text Available Background: Maternal subclinical hypothyroidism during pregnancy is associated with various adverse outcomes. Recent consensus guidelines advocate universal thyroid function screening during pregnancy. There are no data from Iran about the prevalence of thyroid hypofunction in pregnancy. This study aims to find the prevalence of thyroid dysfunction. Materials and Methods: In this descriptive cross sectional study, thyrotropin (TSH was measured in 3158 pregnant women irrespective of gestational age from October 2008-March 2012. If TSH was more than 2.5 mIU/L in the first trimester or more than 3 mIU/L in the second or third trimester, free T4 was measured to diagnose subclinical / overt hypothyroidism. If serum free T4 was in the normal range (0.7-1.8 ng/dl the diagnosis was subclinical hypothyroidism and if below the normal range, overt hypothyroidism was diagnosed. Results: A total of 3158 pregnant women were evaluated. One hundred forty seven of them were diagnosed as hypothyroidism. Subclinical hypothyroidism and overt hypothyroidism were present in 131 (89.1% and 16 (10.9% women respectively. Prevalence of subclinical hypothyroidism was 4.15%. Most of the subclinical and overt hypothyroidism cases were diagnosed in the first trimester. Conclusion: It appears logical to check TSH during pregnancy due to the observed prevalence of subclinical hypothyroidism.

  10. Attenuation of cardiac dysfunction and remodeling of myocardial infarction by microRNA-130a are mediated by suppression of PTEN and activation of PI3K dependent signaling.

    Science.gov (United States)

    Lu, Chen; Wang, Xiaohui; Ha, Tuanzhu; Hu, Yuanping; Liu, Li; Zhang, Xia; Yu, Honghui; Miao, Jonathan; Kao, Race; Kalbfleisch, John; Williams, David; Li, Chuanfu

    2015-12-01

    Activation of PI3K/Akt signaling protects the myocardium from ischemia/reperfusion injury. MicroRNAs have been demonstrated to play an important role in the regulation of gene expression at the post-transcriptional level. In this study, we examined whether miR-130a will attenuate cardiac dysfunction and remodeling after myocardial infarction (MI) via PI3K/Akt dependent mechanism. To determine the role of miR-130a in the proliferation and migration of endothelial cells, HUVECs were transfected with miR-130a mimics before the cells were subjected to scratch-induced wound injury. Transfection of miR-130a mimics stimulated the migration of endothelial cells into the wound area and increased phospho-Akt levels. To examine the effect of miR-130a on cardiac dysfunction and remodeling after MI, Lentivirus expressing miR-130a (LmiR-130a) was delivered into mouse hearts seven days before the mice were subjected to MI. Cardiac function was assessed by echocardiography before and for up to 21 days after MI. Ejection fraction (EF%) and fractional shortening (FS%) in the LmiR-130a transfected MI hearts were significantly greater than in LmiR-control and untransfected control MI groups. LmiR-130a transfection increased capillary number and VEGF expression, and decreased collagen deposition in the infarcted myocardium. Importantly, LmiR-130a transfection significantly suppressed PTEN expression and increased the levels of phosphorylated Akt in the myocardium. However, treatment of LmiR-130a-transfected mice with LY294002, a PI3K inhibitor, completely abolished miR-130a-induced attenuation of cardiac dysfunction after MI. miR-130a plays a critical role in attenuation of cardiac dysfunction and remodeling after MI. The mechanisms involve activation of PI3K/Akt signaling via suppression of PTEN expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Attenuation of cardiac dysfunction and remodeling of myocardial infarction by microRNA-130a is mediated by suppression of PTEN and activation of PI3K dependent signaling

    Science.gov (United States)

    Lu, Chen; Wang, Xiaohui; Ha, Tuanzhu; Hu, Yuanping; Liu, Li; Zhang, Xia; Yu, Honghui; Miao, Jonathan; Kao, Race; Kalbfleisch, John; Williams, David; Li, Chuanfu

    2015-01-01

    Objective Activation of PI3K/Akt signaling protects the myocardium from ischemia/reperfusion injury. MicroRNAs have been demonstrated to play an important role in the regulation of gene expression at the post-transcriptional level. In this study, we examined whether miR-130a will attenuate cardiac dysfunction and remodeling after myocardial infarction (MI) via PI3K/Akt dependent mechanism. Approaches and Results To determine the role of miR-130a in the proliferation and migration of endothelial cells, HUVECs were transfected with miR-130a mimics before the cells were subjected to scratch-induced wound injury. Transfection of miR-130a mimics stimulated the migration of endothelial cells into the wound area and increased phosphor-Akt levels. To examine the effect of miR-130a on cardiac dysfunction and remodeling after MI, Lentivirus expressing miR-130a (LmiR-130a) was delivered into mouse hearts seven days before the mice were subjected to MI. Cardiac function was assessed by echocardiography before and for up to 21 days after MI. Ejection fraction (EF%) and fractional shortening (FS%) in the LmiR-130a transfected MI hearts were significantly greater than in LmiR-control and untransfected control MI groups. LmiR-130a transfection increased capillary number and VEGF expression, and decreased collagen deposition in the infarcted myocardium. Importantly, LmiR-130a transfection significantly suppressed PTEN expression and increased the levels of phosphorylated Akt in the myocardium. However, treatment of LmiR-130a-transfected mice with LY294002, a PI3K inhibitor, completely abolished miR-130a-induced attenuation of cardiac dysfunction after MI. Conclusions miR-130a plays a critical role in attenuation of cardiac dysfunction and remodeling after MI. The mechanisms involve activation of PI3K/Akt signaling via suppression of PTEN expression. PMID:26458524

  12. Role of Micronutrients on Subclinical Atherosclerosis Micronutrients in Subclinical Atherosclerosis.

    Science.gov (United States)

    Kocyigit, Duygu; Gurses, Kadri Murat; Yalcin, Muhammed Ulvi; Tokgozoglu, Lale

    2016-01-01

    Atherosclerotic cardiovascular disease (CVD) leading to coronary heart disease is the leading cause of morbidity and mortality in the world. Nutrition is one of the key factors in the etiology of atherosclerosis. Micronutrient supplements are widely used to prevent many chronic diseases including atherosclerosis. However, scientific evidence regarding this issue is still insufficient and current data on the association of dietary micronutrients and CVD risk is contradictory. Most of the randomized studies have failed to demonstrate beneficial effects of micronutrient supplementation on markers of subclinical atherosclerosis. In this review, role of each micronutrient on subclinical atherosclerosis will be evaluated thoroughly.

  13. Subclinical markers of cardiovascular disease predict adverse outcomes in chronic kidney disease patients with normal left ventricular ejection fraction.

    Science.gov (United States)

    Sulemane, Samir; Panoulas, Vasileios F; Bratsas, Athanasios; Grapsa, Julia; Brown, Edwina A; Nihoyannopoulos, Petros

    2017-05-01

    Emerging cardiovascular biomarkers, such as speckle tracking echocardiography (STE) and aortic pulse wave velocity (aPWV), have recently demonstrated the presence of subclinical left ventricular dysfunction and arterial stiffening in patients with chronic kidney disease (CKD) and no previous cardiovascular history. However, limited information exists on the prognostic impact of these biomarkers. We aimed to investigate whether STE and aPWV predict major adverse cardiac events (MACE) in this patient population. In this cohort study we prospectively analysed 106 CKD patients with no overt cardiovascular disease (CVD) and normal left ventricular ejection fraction. Cardiac deformation was measured using STE while aPWV was measured using arterial tonometry. The primary end-point was the composite of all-cause mortality, acute coronary syndrome, stable angina requiring revascularization (either using percutaneous coronary intervention or coronary artery bypass surgery), hospitalization for heart failure and stroke. Over a median follow up period of 49 months (interquartile range 11-63 months), 26 patients (24.5%) reached the primary endpoint. In a multivariable Cox hazards model, global longitudinal strain (GLS) (HR 1.12, 95% CI 1.02-1.29, p = 0.041) and aPWV (HR 1.31, 95% CI 1.05-1.41, p = 0.021) were significant, independent predictors of MACE. GLS and aPWV independently predict MACE in CKD patients with normal EF and no clinically overt CVD.

  14. Intrahepatic cholestasis in subclinical and overt hyperthyroidism: two case reports

    Directory of Open Access Journals (Sweden)

    Soylu Aliye

    2008-04-01

    Full Text Available Abstract Introduction Non-specific abnormalities in liver function tests might accompany the clinical course of hyperthyroidism. Hyperthyroidism can cause the elevation of hepatic enzymes and bilirubin. Jaundice is rare in overt hyperthyroidism, especially in subclinical hyperthyroidism. On the other hand, the use of anti-thyroid drugs has rarely been associated with toxic hepatitis and cholestatic jaundice. Case presentation Here we present two cases of cholestasis that accompanied two distinct forms of clinical hyperthyroidism. The first patient had a clinical presentation of severe cholestasis in the absence of congestive failure related to hyperthyroidism. The second case had developed intrahepatic cholestasis in the presence of subclinical hyperthyroidism, and improved with rifampicin treatment. Conclusion Hyperthyroidism should be a consideration in non-specific liver dysfunction.

  15. Evaluation of LDL-Cholesterol / HDL-Cholesterol Ratio as Predictor of Dyslipidemia in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Smita S. Kottagi

    2014-01-01

    Full Text Available Background: Subclinical hypothyroidism is defined as a serum TSH concentration above the upper limit of the reference range when serum T3 and T4 concentrations are within reference ranges. Subclinical thyroid disease is a laboratory diagnosis. Patients with subclinical disease have few or no definitive clinical signs or symptoms of thyroid dysfunction. It has been associated with higher levels of some cardiovascular risk factors. Despite some conflicting results, many studies have found that subjects with subclinical hypothyroidism have total cholesterol and low density lipoprotein cholesterol levels higher than euthyroid subjects. The association between subclinical hypothyroidism and dyslipidemia is well known. Aims and Objectives: This study is an attempt to find the importance of Low Density Lipoprotein – Cholesterol / Higher Density Lipoprotein - Cholesterol (LDL-C/HDL-C ratio rather than measurement of individual lipid profile parameters in bringing to light the dyslipidemic state associated with subclinical hypothyroidism. Materials and Methods: We studied 30 subclinical hypothyroid cases with age above 35 yrs and 30 age matched euthyroid controls. Serum T3, T4, TSH were estimated by ELISA method, serum total cholesterol, HDL Cholesterol by enzymatic CHOD-PAP method, and LDL cholesterol using Friedewald formula. Results: We found the significant increase in the serum levels of TSH (p < 0.001, Total cholesterol (p<0.001, LDL cholesterol (p<0.001, and LDL-C/HDL-C (p<0.001, Systolic blood pressure and diastolic blood pressure (p<0.001. There was no significant change in the levels of serum T3, T4, HDL- cholesterol. Conclusion: Increased levels of total cholesterol, LDL cholesterol and increased LDL-C/HDL-C ratio are seen in patients with subclinical hypothyroidism. LDL-C/HDLC ratio is a better indicator for dyslipidemia in subclinical hypothyroid cases.

  16. Thyroid Dysfunction among Young Adults in Uganda | Galukande ...

    African Journals Online (AJOL)

    Background: Most studies on thyroid dysfunction have been on patients refereed for treatment, little is known about the prevalence in the general populations. The importance of knowing such prevalence data lies in that fact that subclinical thyroid dysfunction is an important risk on development of heart disease, ...

  17. Subclinical organ damage and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Sehestedt, Thomas; Olsen, Michael H

    2010-01-01

    Traditional cardiovascular risk factors have poor prognostic value for individuals and screening for subclinical organ damage has been recommended in hypertension in recent guidelines. The aim of this review was to investigate the clinical impact of the additive prognostic information provided...... by measuring subclinical organ damage. We have (i) reviewed recent studies linking markers of subclinical organ damage in the heart, blood vessels and kidney to cardiovascular risk; (ii) discussed the evidence for improvement in cardiovascular risk prediction using markers of subclinical organ damage; (iii...... for risk discrimination, calibration and reclassification; and (ii) the economic costs and health benefits associated with measuring markers of subclinical organ damage....

  18. EAMJ May Subclinical.indd

    African Journals Online (AJOL)

    2009-05-02

    May 2, 2009 ... EL-Safty, I.A.M., GadalIah, M., Shouman, A.E. and. Nessim, D.E. Subclinical nephrotoxicity caused by smoking and occupational silica exposure among. Egyptian industrial workers. Arch. Med. Res. 2003;. 34: 415-421. 4. Ivandic, M., Hofmann, W. and Guder, W.G. The use of knowledge-based systems to ...

  19. Cardiac Resynchronization Therapy Relieves Intractable Angina Due to Exercise-Induced Left Bundle Branch Block Without Left Ventricular Systolic Dysfunction: A Detailed Case Study.

    Science.gov (United States)

    Czuriga, Daniel; Lim, Pitt O

    2016-05-01

    Exercise-induced left bundle branch block is rare and can be demonstrated with exercise testing. When the heart rate reaches a certain threshold, the QRS widens into left bundle branch block. This paper describes a patient with exercise-induced left bundle branch block related angina and dyspnea, who responded to cardiac resynchronization therapy. We documented the potential benefits of cardiac resynchronization therapy with a left ventricular rapid pacing study prior to its implantation. Although exercise-induced left bundle branch block is not a current indication for cardiac resynchronization therapy in patients such as ours, it could be considered when conventional drug therapy fails. © 2016 Wiley Periodicals, Inc.

  20. Myocardial ultrasonic tissue characterization in patients with thyroid dysfunction

    Directory of Open Access Journals (Sweden)

    Schmidt André

    2010-04-01

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

  1. In vivo Post-Cardiac Arrest Myocardial Dysfunction is Supported by CaMKII-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2

    Science.gov (United States)

    Downey, Peter; Zalewski, Adrian; Rubio, Gabriel R.; Liu, Jing; Homburger, Julian R.; Grunwald, Zachary; Qi, Wei; Bollensdorff, Christian; Thanaporn, Porama; Ali, Ayyaz; Riemer, Kirk; Kohl, Peter; Mochly-Rosen, Daria; Gerstenfeld, Edward; Large, Stephen; Ali, Ziad; Ashley, Euan

    2016-01-01

    Background Survival after sudden cardiac arrest is limited by post-arrest myocardial dysfunction but understanding of this phenomenon is constrained by lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. Methods We developed rodent models of in vivo post-arrest myocardial dysfunction using extra-corporeal membrane oxygenation (ECMO) resuscitation followed by invasive hemodynamics measurement. In post-arrest isolated cardiomyocytes, we assessed mechanical load and Ca2+ induced Ca2+ release (CICR) simultaneously using the micro-carbon-fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel-designed fiber optic catheter imaging system, and a genetically encoded calcium sensor GCaMP6f, to image CICR in vivo. Results We found potentiation of CICR in isolated cells from this ECMO model and also in cells isolated from an ischemia-reperfusion Langendorff model perfused with oxygenated blood from an arrested animal, but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed post-arrest was mediated by the activation of Ca2+/calmodulin kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban and ryanodine receptor 2 (RyR2) was detected in the post-arrest period. Exogenous adrenergic activation in vivo recapitulated Ca2+ potentiation but was associated with lesser CaMKII activation. Since oxidative stress and aldehydic adduct formation were high post arrest, we tested a small molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and post-arrest outcome in vivo. Conclusions Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation

  2. Modulation of metabolic and cardiac dysfunctions by swimming in overweight rats on a high cholesterol and fructose diet: possible role of adiponectin.

    Science.gov (United States)

    Sakr, H F

    2013-04-01

    Western diet rich in cholesterol and sucrose with decreased physical activity cause overweight and metabolic syndrome. The aim of the present study was to investigate the effect of swimming on the cardiac adiponectin mRNA expression in high cholesterol and fructose fed rats. Forty Sprague-Dawley male rats divided into 2 equal groups. First group - control, that was fed with chow diet for 15 weeks. Second group was fed with high cholesterol and fructose diet (HCFD) for 15 weeks. Ten rats from both groups performed swimming during the last 4 weeks. After 15 weeks serum glucose, insulin, lipogram, leptin, resistin, adiponectin, and cardiac enzymes (lactate dehydrogenase and creatine kinase - MB) levels were measured. HOMA-IR index was calculated, evaluation of cardiac adiponectin gene expression using RT-PCR and cardiac histopathological examination were studied. Left ventricular developed pressure (LVDP), dp/dtmax and -dp/dtmax were measured by isolated Langendorff-perfused heart. Swimming exercise in rats fed HCFD resulted in improvement of the glucose homeostasis and lipogram with decreased leptin, resistin and HOMA-IR index with elevation in serum adiponectin. Also, there was an over-expression of down-expressed cardiac adiponectin gene. Also, ventricular functions were ameliorated by swimming exercise training. Swimming exercise partially improved the ventricular function that could be possibly explained through increased the cardiac expression of adiponectin.

  3. Cardiovascular autonomic neuropathy and subclinical cardiovascular disease in normoalbuminuric type 1 diabetic patients

    DEFF Research Database (Denmark)

    Mogensen, Ulrik Madvig; Jensen, Tonny; Køber, Lars

    2012-01-01

    Cardiovascular autonomic neuropathy (CAN) is associated with increased mortality in diabetes. Since CAN often develops in parallel with diabetic nephropathy as a confounder, we aimed to investigate the isolated impact of CAN on cardiovascular disease in normoalbuminuric patients. Fifty......-six normoalbuminuric, type 1 diabetic patients were divided into 26 with (+) and 30 without (-) CAN according to tests of their autonomic nerve function. Coronary artery plaque burden and coronary artery calcium score (CACS) were evaluated using computed tomography. Left ventricular function was evaluated using...... with increased CACS, subclinical left ventricular dysfunction, and increased pulse pressure. In conclusion, CAN in normoalbuminuric type 1 diabetic patients is associated with distinct signs of subclinical cardiovascular disease....

  4. Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction. A National Heart, Lung, and Blood Institute-sponsored study from the Women's Ischemia Syndrome Evaluation.

    Science.gov (United States)

    Thomson, Louise E J; Wei, Janet; Agarwal, Megha; Haft-Baradaran, Afsaneh; Shufelt, Chrisandra; Mehta, Puja K; Gill, Edward B; Johnson, B Delia; Kenkre, Tanya; Handberg, Eileen M; Li, Debiao; Sharif, Behzad; Berman, Daniel S; Petersen, John W; Pepine, Carl J; Bairey Merz, C Noel

    2015-04-01

    Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). Although traditional noninvasive stress imaging is often normal in CMD, cardiac MRI may be able to detect CMD in this population. Vasodilator stress cardiac MRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi-quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression, and sensitivity/specificity. Symptomatic women had lower mean pharmacological stress MPRI compared with reference subjects (1.71±0.43 versus 2.23±0.37; P<0.0001). Lower MPRI was predictive of ≥1 abnormal CRT variables (odds ratio =0.78 [0.70, 0.88], P<0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%. Noninvasive cardiac MRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the noninvasive identification and management of CMD patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00832702. © 2015 American Heart Association, Inc.

  5. Association of exhaled carbon monoxide with subclinical cardiovascular disease and their conjoint impact on the incidence of cardiovascular outcomes

    Science.gov (United States)

    Cheng, Susan; Enserro, Danielle; Xanthakis, Vanessa; Sullivan, Lisa M.; Murabito, Joanne M.; Benjamin, Emelia J.; Polak, Joseph F.; O'Donnell, Christopher J.; Wolf, Philip A.; O'Connor, George T.; Keaney, John F.; Vasan, Ramachandran S.

    2014-01-01

    Aims Whereas endogenous carbon monoxide (CO) is cytoprotective at physiologic levels, excess CO concentrations are associated with cardiometabolic risk and may represent an important marker of progression from subclinical to clinical cardiovascular disease (CVD). Methods and results In 1926 participants of the Framingham Offspring Study (aged 57 ± 10 years, 46% women), we investigated the relationship of exhaled CO, a surrogate of blood CO concentration, with both prevalent subclinical CVD and incident clinical CVD events. Presence of subclinical CVD was determined using a comprehensive panel of diagnostic tests used to assess cardiac and vascular structure and function. Individuals with the highest (>5 p.p.m.) compared with lowest (≤4 p.p.m.) CO exposure were more likely to have subclinical CVD [odds ratios (OR): 1.67, 95% CI: 1.32–2.12; P < 0.001]. During the follow-up period (mean 5 ± 3 years), 193 individuals developed overt CVD. Individuals with both high CO levels and any baseline subclinical CVD developed overt CVD at an almost four-fold higher rate compared with those with low CO levels and no subclinical disease (22.1 vs. 6.3%). Notably, elevated CO was associated with incident CVD in the presence [hazards ration (HR): 1.83, 95% CI: 1.08–3.11; P = 0.026] but not in the absence (HR: 0.80, 95% CI: 0.42–1.53; P = 0.51) of subclinical CVD (Pinteraction = 0.019). Similarly, subclinical CVD was associated with incident CVD in the presence of high but not low CO exposure. Conclusion Our findings in a community-based sample suggest that elevated CO is a marker of greater subclinical CVD burden and, furthermore, a potential key component in the progression from subclinical to clinical CVD. PMID:24574370

  6. Reduced end-systolic pressure-volume ratio response to exercise: a marker of subclinical myocardial disease in type 2 diabetes.

    Science.gov (United States)

    Jellis, Christine L; Jenkins, Carly; Leano, Rodel; Martin, Jennifer H; Marwick, Thomas H

    2010-07-01

    Limitations in the predictive value of negative exercise echocardiography in type 2 diabetes mellitus has been linked to a reduced end-systolic pressure-volume response (ESPVR). We sought whether abnormal ESPVR reflected subclinical diabetic heart disease by examining the association between the ESPVR and markers of myocardial dysfunction and to establish if the change (Delta) or peak systolic blood pressure/end-systolic left ventricular volume ratio (SP/ESV) is a better marker of contractile reserve in type 2 diabetes mellitus. Resting and exercise echocardiography was performed in 167 apparently healthy patients with type 2 diabetes mellitus (97 men; age, 55+/-10 years) without ischemia, other cardiac disease, or noncardiac complications of diabetes. Standard echocardiographic and color tissue Doppler measures (early diastolic tissue velocity, strain, and strain rate) were acquired at baseline and peak stress in apical long-axis views. Calibrated integrated backscatter was calculated from a resting parasternal long-axis view. DeltaSP/ESV was calculated as [(peak stress SP/ESV)-(rest SP/ESV)]. The 83 subjects who demonstrated a DeltaSP/ESV exercise were older and had lower peak heart rate, resting diastolic and stress systolic tissue velocity, stress ejection fraction, and exercise capacity than the remainder. There was no significant association between DeltaSP/ESV and metabolic derangement or echocardiographic measures of deformation or backscatter. Change in Sm and stress ejection fraction were independent correlates of DeltaSP/ESV. DeltaSP/ESV ratio is associated with established features of subclinical diabetic heart disease as well as determinants of contractile reserve (peak hemodynamic response and stress systolic function). Peak ESPVR is poorly associated with markers of myocardial dysfunction.

  7. Subclinical hypothyroidism in childhood and adolescense.

    Science.gov (United States)

    Catli, Gonul; Abaci, Ayhan; Büyükgebiz, Atilla; Bober, Ece

    2014-11-01

    Subclinical hypothyroidism (SH) is defined as a serum thyroid-stimulating hormone (TSH) level above the reference range with normal serum free thyroxin (sT4) and free triiodothyronine (sT3) levels. The prevalence of SH in children and adolescents is reported between 1.7% and 9.5%. Hashimoto's thyroiditis is the most prevalent cause of SH in children. Although it has been suggested that SH is entirely an asymptomatic laboratory diagnosis, typical hypothyroid symptoms as well have been reported in some patients. Results of the adult studies on SH revealed that SH had unfavorable effects on cardiovascular system (atherosclerosis); metabolic parameters (dyslipidemia, insulin resistance, etc.); neuromuscular system; and cognitive functions in the long term. The number of studies investigating the effect of childhood SH on growth, bone maturation, lipid parameters, carbohydrate metabolism, neuromuscular system, and cognitive and cardiac function is limited. Knowledge about the natural history of SH is unclear even though there are numerous studies upon this subject. In children and adults, treatment of SH with L-T₄ is still a matter of debate, and there is no consensus on this issue yet.

  8. Subclinical organ damage and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Sehestedt, Thomas; Olsen, Michael H

    2010-01-01

    Traditional cardiovascular risk factors have poor prognostic value for individuals and screening for subclinical organ damage has been recommended in hypertension in recent guidelines. The aim of this review was to investigate the clinical impact of the additive prognostic information provided...... by measuring subclinical organ damage. We have (i) reviewed recent studies linking markers of subclinical organ damage in the heart, blood vessels and kidney to cardiovascular risk; (ii) discussed the evidence for improvement in cardiovascular risk prediction using markers of subclinical organ damage; (iii......) investigated which and how many markers to measure and (iv) finally discussed whether measuring subclinical organ damage provided benefits beyond risk prediction. In conclusion, more studies and if possible randomized studies are needed to investigate (i) the importance of markers of subclinical organ damage...

  9. Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction.

    Science.gov (United States)

    Chen, Ailan; Li, Wanglin; Chen, Xinyu; Shen, Yuechun; Dai, Wenjun; Dong, Qi; Li, Xinchun; Ou, Caiwen; Chen, Minsheng

    2016-11-17

    Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling. A rat model of abdominal aortic constriction (AAC)-induced cardiac pressure overload was induced. These rats were grouped as the AAC (no treatment) or TMZ group according to whether oral trimetazidine (TMZ, 40 mg/kg/d, for 5 days) was administered. Changes in cardiac structures were sequentially evaluated via echocardiography. The myocardial ADP/ATP ratio was determined to reflect the metabolic status, and changes in serum neuropeptide Y systems were evaluated. Myocardial metabolic disorder was acutely induced as evidenced by an increased ADP/ATP ratio within 7 days of AAC before the morphological changes in the myocardium, accompanied by up-regulation of serum oxidative stress markers and expression of fetal genes related to hypertrophy. Moreover, the serum NPY and myocardial NPY-1R, 2R, and 5R levels were increased within the acute phase of AAC-induced cardiac pressure overload. Pretreatment with TMZ could partly attenuate myocardial energy metabolic homeostasis, decrease serum levels of oxidative stress markers, attenuate the induction of hypertrophy-related myocardial fetal genes, inhibit the up-regulation of serum NPY levels, and further increase the myocardial expression of NPY receptors. Cardiac metabolic remodeling is an early change in the myocardium before the presence of typical morphological ventricular remodeling following cardiac pressure overload, and pretreatment with TMZ may at least partly reverse the acute metabolic disturbance

  10. Disfunción ventricular izquierda subclínica en diabéticos tipo I con 10 o más años de evolución de la diabetes Disfunción ventricular izquierda subclínica en diabéticos tipo I con 10 o más años de evolución de la diabetes Subclinical left ventricular dysfunction in type 1 diabetics with 10 or more years of diabetes progression

    Directory of Open Access Journals (Sweden)

    Omar Singh Linares

    2001-08-01

    Full Text Available Se realizó un estudio transversal en 32 diabéticos tipo 1 con 10 o más años de evolución, con edades entre 17 y 40 años, para conocer la frecuencia de disfunción ventricular izquierda (DVI subclínica y sus factores asociados. Se excluyeron los pacientes que presentaban valvulopatía, cardiopatía isquémica, hipertensión arterial y otras enfermedades que provocan miocardiopatía. A todos se les realizó una historia clínica completa y se les indicó: glucemia en ayunas, hemoglobina glucosilada (HbA1, colesterol total, triglicéridos totales, lipoproteína de alta densidad (HDL-colesterol, excreción urinaria de albúmina (EUA, velocidad de conducción nerviosa motora y sensitiva en los miembros inferiores, electrocardiograma y ecocardiograma a modo M, bidimensional y con Doppler pulsado. Para el diagnóstico ecocardiográfico de DVI se adoptaron los criterios propuestos por la Sociedad Americana de Ecocardiografía. Se comprobó DVI en el 34,3 %. Se observaron alteraciones estructurales cardíacas en el 18,75 %. Se presentó neuropatía periférica en 8/11 pacientes con DVI (72,7 %. Los niveles de EUA fueron significativamente mayores en los afectados de DVI (233,4 ± 176 mg/L. El engrosamiento de septum interventricular y de la pared posterior fue significativamente mayor en pacientes con DVI. Se concluyó que la DVI es una complicación frecuente en el diabético tipo 1, lo que obliga a su búsqueda sistemática en este grupo de pacientesA cross-sectional study of 32 type 1 diabetics aged 17-40 years, with 10 or more years of diabetes profession was conducted to find out the frequency of subclinical left ventricular dysfunction (LVD and its associated factors. Those patients presenting with valvulopathy, ischemic heart disease, blood hypertension and other diseases leading to myocardiopathy, were excluded. Their complete medical histories were made and they were indicated the following: glycemia in fasting conditions, glycosylated

  11. [Cardiac amyloidosis].

    Science.gov (United States)

    Boussabah, Elhem; Zakhama, Lilia; Ksontini, Iméne; Ibn Elhadj, Zied; Boukhris, Besma; Naffeti, Sana; Thameur, Moez; Ben Youssef, Soraya

    2008-09-01

    PREREQUIS: Amyloidosis is a rare infiltrative disease characterized by multiple clinical features. Various organs are involved and the cardiovascular system is a common target of amyloidosis. Cardiac involvement may occur with or without clinical manifestations and is considered as a major prognostic factor. To analyze the clinical features of cardiac involvement, to review actual knowledgement concerning echocardiographic diagnostic and to evaluate recent advances in treatment of the disease. An electronic search of the relevant literature was carried out using Medline and Pubmed. Keys words used for the final search were amyloidosis, cardiopathy and echocardiography. We considered for analysis reviews, studies and articles between 1990 and 2007. Amyloidosis represents 5 to 10% of non ischemic cardiomyoparhies. Cardiac involvement is the first cause of restrictive cardiomyopathy witch must be evoked in front of every inexplained cardiopathy after the age of forty. The amyloid nature of cardiopathy is suggered if some manifestations were associated as a peripheric neuropathy, a carpal tunnel sydrome and proteinuria > 3g/day. Echocardiography shows dilated atria, a granular sparkling appearance of myocardium, diastolic dysfunction and thickened left ventricle contrasting with a low electric voltage. The proof of amyloidosis is brought by an extra-cardiac biopsy, the indications of endomyocardial biopsy are very limited. The identification of the amyloid nature of cardiopathy has an direct therapeutic implication: it indicates the use of digitalis, calcium channel blockers and beta-blockers. Today the treatment of amyloidosis remains very unsatisfactory especially in the cardiac involvement. An early diagnosis before the cardiac damage may facilitate therapy and improve prognosis.

  12. The Association Between Endocan Levels and Subclinical Atherosclerosis in Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Lv, Yaya; Zhang, Yaqiong; Shi, Weiya; Liu, Juxiang; Li, Yonghong; Zhou, Zubang; He, Qijuan; Wei, Suhong; Liu, Jing; Quan, Jinxing

    2017-05-01

    Proinflammatory conditions induced by circulating factors in diabetes play a pivotal role in endothelial dysfunction and related vascular complications. Endothelial cell-specific molecule-1 or endocan is a dermatan sulfate proteoglycan secreted primarily by the vascular endothelium. Although endocan has been shown to be a potential biomarker in coronary heart disease, its role in the pathogenesis of atherosclerosis (AS) in diabetes remains unclear. In this study, we investigated the correlation between serum endocan levels and subclinical AS in patients with type 2 diabetes mellitus (T2DM). Patients (n = 69) with T2DM were included. All the patients were stratified based on the absence (n = 42) or presence (n = 27) of subclinical AS. Healthy subjects (n = 28) served as controls. Serum levels of endocan, fasting blood glucose, glycosylated hemoglobin A1, high-sensitivity C-reactive protein and carotid intima-media thickness (cIMT) were measured. Endocan levels were significantly elevated in both the T2DM (0.89 ± 0.28ng/mL) and T2DM with subclinical AS (1.20 ± 0.33ng/mL) groups relative to the control group (0.68 ± 0.24ng/mL) (P subclinical AS (odds ratio = 1.98, 95% CI: 1.43-2.73, P subclinical AS in patients with T2DM. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  13. Overt and subclinical hypothyroidism among Bangladeshi pregnant women and its effect on fetomaternal outcome.

    Science.gov (United States)

    Sharmeen, M; Shamsunnahar, P A; Laita, T R; Chowdhury, S B

    2014-08-01

    Thyroid disorders are among the common endocrine problems in pregnant women. It is now well established that not only overt but subclinical thyroid dysfunction also has adverse effects on maternal and fetal outcome. There are few data from Bangladesh about the prevalence of thyroid dysfunction in pregnancy. With this background, this study aims to find out thyroid dysfunction (both overt and subclinical hypothyroidism) in pregnancy and its impact on obstetrical outcome. We studied the evaluation of 50 admitted pregnancies corresponding to 29 women with subclinical hypothyroidism and rest 21 was overt hypothyroidism. Detailed history and examination were performed. Apart from routine obstetrical investigations, Thyroid Stimulating Hormone (TSH) estimation was done. Their obstetrical and perinatal outcomes were noted. Overt hypothyroidism was significantly (p hypothyroidism patients. In sub clinical hypothyroidism 86.2% conceived firstly within 2 years and 66.7% in overt hypothyroidism patients conceived firstly in between 3 to 5 years after marriage. Overt hypothyroids were prone to have pregnancy-induced hypertension 42.9%, intrauterine growth restriction (P = 0.001) and gestational diabetes (38.1%) as compared to subclinical cases. Neonatal complications were significantly more in overt hypothyroidism group. Mean TSH level was significantly (p hypothyroidism patients but mean FT4 level was almost similar in both groups. Majority of the patient underwent caesarean section in both groups due to associated medical and obstetrical complications. None of the babies showed hypothyroidism by cord blood tests. In this analysis our results showed that overt hypothyroidism among Bangladeshi pregnant women are associated with more maternal complication & adverse parental outcome than subclinical hypothyroidism. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications

  14. Subclinical hypothyroidism in obese children

    Directory of Open Access Journals (Sweden)

    Aleksandra Januszek-Trzciąkowska

    2013-08-01

    Full Text Available Subclinical hypothyroidism (SH is defined as an elevated thyroid stimulating hormone (TSH associated with normal levels of free thyroxine. In obese persons prevalence of SH is significantly higher than in general population. SH is of particular interest in children with respect to the crucial role of thyroid hormones in the development of central nervous system and linear growth. Currently there is no general consensus on the treatment of SH with L-tyroxine. It is suggested that this hormonal state is rather a consequence that the cause of the overweight status.

  15. [Subclinical hypothyroidism in obese children].

    Science.gov (United States)

    Januszek-Trzciąkowska, Aleksandra; Małecka-Tendera, Ewa

    2013-08-05

    Subclinical hypothyroidism (SH) is defined as an elevated thyroid stimulating hormone (TSH) associated with normal levels of free thyroxine. In obese persons prevalence of SH is significantly higher than in general population. SH is of particular interest in children with respect to the crucial role of thyroid hormones in the development of central nervous system and linear growth. Currently there is no general consensus on the treatment of SH with L-tyroxine. It is suggested that this hormonal state is rather a consequence that the cause of the overweight status.

  16. Subclinical Hypercorticism: the Necessity of Diagnostic Search

    Directory of Open Access Journals (Sweden)

    А.N. Kvacheniuk

    2016-02-01

    Full Text Available Considering certain difficulties in subclinical hypercorticism diagnosis, the object of this work is to focus attention of doctors in different areas on the necessity of thorough examination of patients with pathological conditions that may be the manifestation of Cushing’s syndrome (arterial hypertension, obesity, impaired carbohydrate metabolism and osteoporosis. The laboratory diagnosis is the instrument for early subclinical hypercorticism detection.

  17. Cold Pressor Stress Cardiac Magnetic Resonance Myocardial Flow Reserve Is Not Useful for Detection of Coronary Endothelial Dysfunction in Women with Signs and Symptoms of Ischemia and No Obstructive CAD.

    Directory of Open Access Journals (Sweden)

    Sofy Landes

    Full Text Available Coronary endothelial function testing using acetylcholine is not routinely available, while non-pharmacological cold pressor testing (CPT is considered an endothelial stressor. Noninvasive cardiac magnetic resonance imaging (CMRI myocardial perfusion reserve index (MPRI can detect coronary microvascular dysfunction (CMD. We evaluated if CPT stress CMRI MPRI could detect invasive coronary endothelial dysfunction.Coronary reactivity testing was performed in 189 women with symptoms and signs of ischemic but no obstructive coronary artery disease as previously described plus CPT stress. Subjects also underwent pharmacologic and CPT stress during CMRI (1.5 T. Statistical analysis comparing CPT MPRI between groups was performed by Welch`s t-test and Mann-Whitney where appropriate. Anderson-Darling test and Levene test were considered to verify the normality and homogeneity of variances assumptions. Correlation analyses between CPT MPRI and both invasive and noninvasive measures of CMD were performed using Spearman correlation.While CPT MPRI correlated with pharmacological stress MPRI, it did not correlate with invasive measures of CMD including invasively measured responses to intracoronary (IC adenosine, IC acetylcholine, CPT, or IC nitroglycerin. Additionally CPT MPRI was not significantly different between subjects with normal compared to abnormal pharm stress MPRI or normal compared to abnormal invasive CMD parameters.Despite correlation with pharmacological stress MPRI, non-invasive CPT MPRI does not appear to be useful for detecting CMD in symptomatic women.

  18. Cold Pressor Stress Cardiac Magnetic Resonance Myocardial Flow Reserve Is Not Useful for Detection of Coronary Endothelial Dysfunction in Women with Signs and Symptoms of Ischemia and No Obstructive CAD.

    Science.gov (United States)

    Landes, Sofy; Dela Cruz, Sherwin; Wei, Janet; AlBadri, Ahmed; Shufelt, Chrisandra; Mehta, Puja; Thomson, Louise E; Diniz, Marcio A; Zhang, Xiao; Petersen, John W; Anderson, R David; Pepine, Carl J; Berman, Daniel S; Bairey Merz, C Noel

    2017-01-01

    Coronary endothelial function testing using acetylcholine is not routinely available, while non-pharmacological cold pressor testing (CPT) is considered an endothelial stressor. Noninvasive cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) can detect coronary microvascular dysfunction (CMD). We evaluated if CPT stress CMRI MPRI could detect invasive coronary endothelial dysfunction. Coronary reactivity testing was performed in 189 women with symptoms and signs of ischemic but no obstructive coronary artery disease as previously described plus CPT stress. Subjects also underwent pharmacologic and CPT stress during CMRI (1.5 T). Statistical analysis comparing CPT MPRI between groups was performed by Welch`s t-test and Mann-Whitney where appropriate. Anderson-Darling test and Levene test were considered to verify the normality and homogeneity of variances assumptions. Correlation analyses between CPT MPRI and both invasive and noninvasive measures of CMD were performed using Spearman correlation. While CPT MPRI correlated with pharmacological stress MPRI, it did not correlate with invasive measures of CMD including invasively measured responses to intracoronary (IC) adenosine, IC acetylcholine, CPT, or IC nitroglycerin. Additionally CPT MPRI was not significantly different between subjects with normal compared to abnormal pharm stress MPRI or normal compared to abnormal invasive CMD parameters. Despite correlation with pharmacological stress MPRI, non-invasive CPT MPRI does not appear to be useful for detecting CMD in symptomatic women.

  19. Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction

    OpenAIRE

    Chen, Ailan; Li, Wanglin; Chen, Xinyu; Shen, Yuechun; Dai, Wenjun; Dong, Qi; Li, Xinchun; Ou, Caiwen; Chen, Minsheng

    2016-01-01

    Background Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine ...

  20. Cardiac sympathetic innervation assessed with (123)I-MIBG retains prognostic utility in diabetic patients with severe left ventricular dysfunction evaluated for primary prevention implantable cardioverter-defibrillator.

    Science.gov (United States)

    García-González, P; Fabregat-Andrés, Ó; Cozar-Santiago, P; Sánchez-Jurado, R; Estornell-Erill, J; Valle-Muñoz, A; Quesada-Dorador, A; Payá-Serrano, R; Ferrer-Rebolleda, J; Ridocci-Soriano, F

    2016-01-01

    Scintigraphy with iodine-123-metaiodobenzylguanidine ((123)I-MIBG) is a non-invasive tool for the assessment of cardiac sympathetic innervation (CSI) that has proven to be an independent predictor of survival. Recent studies have shown that diabetic patients with heart failure (HF) have a higher deterioration in CSI. It is unknown if (123)I-MIBG has the same predictive value for diabetic and non-diabetic patients with advanced HF. An analysis is performed to determine whether CSI with (123)I-MIBG retains prognostic utility in diabetic patients with HF, evaluated for a primary prevention implantable cardioverter-defibrillator (ICD). Seventy-eight consecutive HF patients (48 diabetic) evaluated for primary prevention ICD implantation were prospectively enrolled and underwent (123)I-MIBG to assess CSI (heart-to-mediastinum ratio - HMR). A Cox proportional hazards multivariate analysis was used to determine the influence of (123)I-MIBG images for prediction of cardiac events in both diabetic and non-diabetic patients. The primary end-point was a composite of arrhythmic event, cardiac death, or admission due to HF. During a mean follow-up of 19.5 [9.3-29.3] months, the primary end-point occurred in 24 (31%) patients. Late HMR was significantly lower in diabetic patients (1.30 vs. 1.41, p=0.014). Late HMR≤1.30 was an independent predictor of cardiac events in diabetic (hazard ratio 4.53; p=0.012) and non-diabetic patients (hazard ratio 12.31; p=0.023). Diabetic patients with HF evaluated for primary prevention ICD show a higher deterioration in CSI than non-diabetics; nevertheless (123)I-MIBG imaging retained prognostic utility for both diabetic and non-diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  1. Level of systemic inflammation and endothelial injury is associated with cardiovascular dysfunction and vasopressor support in post-cardiac arrest patients

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Johansson, Pär I; Kjaergaard, Jesper

    2017-01-01

    AIM: Post-cardiac arrest syndrome (PCAS) is characterized by a sepsis-like inflammatory response and hemodynamic instability. We investigated the associations between systemic inflammation, endothelial damage and hemodynamic parameters including vasopressor support in patients with out...... survivors after OHCA, increasing systemic inflammation and endothelial injury was associated with increased need of vasopressor support. Systemic inflammation, in particular IL-6, was consistently associated with vasopressor support, however endothelial injury may also play a role in PCAS associated...

  2. Cardiovascular dysfunction in infants with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Armstrong, Katey

    2012-04-01

    Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2\\/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.

  3. Early detection of cardiac involvement in Miyoshi myopathy: 2D strain echocardiography and late gadolinium enhancement cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Kim Byoung

    2010-05-01

    Full Text Available Abstract Background Miyoshi myopathy (MM is an autosomal recessive distal myopathy characterized by early adult onset. Cardiomyopathy is a major clinical manifestation in other muscular dystrophies and an important prognostic factor. Although dysferlin is highly expressed in cardiac muscle, the effect of dysferlin deficiency in cardiac muscle has not been studied. We hypothesized that early myocardial dysfunction could be detected by 2D strain echocardiography and late gadolinium enhancement (LGE cardiovascular magnetic resonance (CMR. Method Five consecutive MM patients (3 male in whom we detected the DYSF gene mutation and age-matched healthy control subjects were included. None of the patients had history of cardiac disease or signs and symptoms of overt heart failure. Patients were studied using 2D strain echocardiography and CMR, with 2D strain being obtained using the Automated Function Imaging technique. Results All patients had preserved left ventricular systolic function. However, segmental Peak Systolic Longitudinal Strain (PSLS was decreased in 3 patients. Global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005. Basal anterior septum, basal inferior septum, mid anterior, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects (P Conclusions Patients with MM showed subclinical involvement of the heart. 2D strain and LGE are sensitive methods for detecting myocardial dysfunction prior to the development of cardiovascular symptoms. The prognostic significance of these findings warrants further longitudinal follow-up.

  4. Subclinical coronary atherosclerosis: racial profiling is necessary!

    Science.gov (United States)

    Orakzai, Sarwar H; Orakzai, Raza H; Nasir, Khurram; Santos, Raul D; Edmundowicz, Daniel; Budoff, Matthew J; Blumenthal, Roger S

    2006-11-01

    We aim to review the studies comparing coronary calcification across different ethnic groups. There is still uncertainty regarding ethnic differences in the prevalence, progression, and risk of coronary artery disease. Clues to possible racial differences in rates of coronary heart disease (CHD) may be found by identifying subclinical disease. Coronary artery calcification (CAC) can be used to predict risk of CHD in both symptomatic and asymptomatic subjects. Online databases were searched for studies assessing racial differences in CAC. Most of the published studies have shown that racial differences exist in the prevalence and severity of CAC. Whites have a higher prevalence of CAC as compared to African Americans and other ethnic groups even after adjustment for risk factors. These differences in CAC are even more pronounced in men and in the elderly. Data regarding the distribution of CAC in ethnic groups outside the United States are limited. Emerging evidence indicates that while several ethnic groups outside the United States tend to have a greater prevalence of CHD risk factors, their prevalence of CAC is lower, as compared with Americans. Thus, the data obtained in the United States may not be able to be fully extrapolated to populations outside the United States for assessment of CHD risk. The presence and extent of CAC varies among different racial groups within and outside the United States. The relationship between calcification and the incidence of CHD in these ethnic groups needs further exploration. Thus, it is important to develop ethnic specific CAC nomograms to more accurately determine the underlying CHD risk associated with CAC in these individuals. It will also be imperative to obtain outcome data and relate it to baseline levels of CAC to help us put in perspective the significance of racial differences in CAC and how they impact on cardiac risk prediction.

  5. Impact of subclinical haemorrhage on the pituitary gland in patients with pituitary adenomas.

    Science.gov (United States)

    Kinoshita, Yasuyuki; Tominaga, Atsushi; Usui, Satoshi; Arita, Kazunori; Sugiyama, Kazuhiko; Kurisu, Kaoru

    2014-05-01

    Advanced magnetic resonance imaging (MRI) and optical instruments for surgery frequently demonstrate subclinical haemorrhage in pituitary adenomas; however, the effects of subclinical haemorrhage on pituitary glands remain unclear. We sought to clarify the pituitary function in patients with subclinical pituitary adenoma haemorrhage (SPAH). Between January 2006 and December 2012, we retrospectively reviewed 328 consecutive patients who underwent surgery for pituitary adenoma. SPAH was defined as an intratumoral haemorrhage based on both 3 tesla MRI and operative findings, with no clinical symptoms of acute pituitary adenoma apoplexy. The pituitary dysfunction assessed using pre- and postoperative provocative tests was investigated in patients categorized into three groups: nonapoplectic adenoma, adenoma with SPAH and adenoma with clinical apoplexy. The main outcome measure was the incidence of pituitary dysfunction. The overall incidence of nonapoplectic adenomas, adenomas with SPAH and adenomas with clinical apoplexy was 82·3%, 14·3% and 3·4%, respectively. Clinical pituitary apoplexy frequently occurred in male patients with large nonfunctioning adenomas, causing pituitary dysfunction. Contrastingly, the incidence of SPAH was significantly higher in the patients with prolactinoma (P = 0·0260), including those with relatively small adenomas (P = 0·0007). No medications, such as dopamine agonists or somatostatin analogues, were observed to affect the occurrence of SPAH. No deterioration of the pituitary function was observed in the SPAH patients in comparison with the patients with nonapoplectic adenoma, and the size of the haematoma occupying the pituitary adenoma did not exhibit any relationships with the deterioration of the pituitary function. Furthermore, SPAH caused no deterioration of the pituitary function after a surgery based on the postoperative provocation tests. Subclinical pituitary adenoma haemorrhage does not cause any added dysfunction in

  6. Reactivity to Social Stress in Subclinical Social Anxiety: Emotional Experience, Cognitive Appraisals, Behavior, and Physiology

    OpenAIRE

    Liviu George Crisan; Romana eVulturar; Mircea eMiclea; Miu, Andrei C.

    2016-01-01

    Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in t...

  7. Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

    Science.gov (United States)

    Sanz-Ruiz, Ricardo; Casado Plasencia, Ana; Borlado, Luis R; Fernández-Santos, María Eugenia; Al-Daccak, Reem; Claus, Piet; Palacios, Itziar; Sádaba, Rafael; Charron, Dominique; Bogaert, Jan; Mulet, Miguel; Yotti, Raquel; Gilaberte, Immaculada; Bernad, Antonio; Bermejo, Javier; Janssens, Stefan; Fernández-Avilés, Franciso

    2017-06-23

    Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398. © 2017 American Heart Association, Inc.

  8. Impact of a nurse-led home and clinic-based secondary prevention programme to prevent progressive cardiac dysfunction in high-risk individuals: the Nurse-led Intervention for Less Chronic Heart Failure (NIL-CHF) randomized controlled study.

    Science.gov (United States)

    Stewart, Simon; Chan, Yih-Kai; Wong, Chiew; Jennings, Garry; Scuffham, Paul; Esterman, Adrian; Carrington, Melinda

    2015-06-01

    The aim of this study was to determine the effectiveness of a long-term, nurse-led, multidisciplinary programme of home/clinic visits in preventing progressive cardiac dysfunction in individuals at risk of developing de novo chronic heart failure (CHF). A pragmatic, single-centre (tertiary-referral hospital with specialist cardiological services), open-label, randomized controlled trial with blinded endpoint adjudication was carried out. In total, 624 cardiac inpatients (66 ± 11 years, 71% male, and 70% with CAD) were randomly allocated (1:1) to standard care or the study intervention. The intention-to-treat cohort comprised 310 standard care and 301 intervention participants. During 51.0 ± 8.2 months follow-up, 38/310 (12%) standard care [mean event-free survival 1865 days, 95% confidence interval (CI) 1817-1913 days] vs. 41/301 (14%) intervention participants (1855 days, 95% CI 1804-1906 days) experienced the primary composite endpoint of de novo CHF hospitalization or all-cause mortality (P = 0.574). Although there were no statistically significant differences in the rate of cardiovascular-related and emergency hospitalizations, the NIL-CHF (Nurse-led Intervention for Less Chronic Heart Failure) group accumulated 478 (0.214 ± 0.70 vs. 0.095 ± 0.284 days/participant/month; P = 0.052) and 1097 fewer days of hospital stay (0.391 ± 1.80 vs. 0.199 ± 0.47 days/participant/month; P = 0.023), respectively, compared with standard care. The intervention group also showed better cardiac recovery on echocardiography at 3 years [81/226 (35.8%) vs. 56/225 (24.9%), odds ratio 1.44, 95% CI 1.08-1.92, P = 0.011]. Relative to a high level of standard care, the NIL-CHF intervention was ineffective in preventing CHF and rehospitalization. On the other hand, it was associated with reduced hospital stay and improved cardiac function over the long term. Australian New Zealand Clinical Trials Registry (No. 12608000022369). © 2015 The Authors. European Journal of Heart Failure

  9. Exogenous heat shock cognate protein 70 pretreatment attenuates cardiac and hepatic dysfunction with associated anti-inflammatory responses in experimental septic shock.

    Science.gov (United States)

    Hsu, Jong-Hau; Yang, Rei-Cheng; Lin, Shih-Jen; Liou, Shu-Fen; Dai, Zen-Kong; Yeh, Jwu-Lai; Wu, Jiunn-Ren

    2014-12-01

    It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction because of its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, and myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 μg/kg, i.v.) attenuated LPS-induced hypotension and tachycardia by 21% and 23%, respectively (P shock cognate protein 70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, P shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic, and systemic derangements, with associated inhibition of proinflammatory mediators including tumor necrosis factor α, nitric oxide, cyclooxygenase 2, and matrix metalloproteinase 9, through mitogen-activated protein kinase/nuclear factor κB signaling pathways. Therefore, extracellular HSC70 may have a promising role in the prophylactic treatment of sepsis.

  10. Subclinical hypothyroidism after vascular complicated pregnancy.

    Science.gov (United States)

    van der Zanden, Moniek; Hop-de Groot, Rianne J; Sweep, Fred C G J; Ross, H Alec; den Heijer, Martin; Spaanderman, Marc E A

    2013-01-01

    Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions. In 372 women with a history of vascular complicated pregnancy, we assessed thyroid function. Subclinical hypothyroidism was diagnosed in 73/372 women (19.6%). It occurred more often when pregnancy ended before 32 weeks of gestation (p = 0.008). In this cohort, subclinical hypothyroidism is more common after very preterm delivery. It may contribute to the elevated risk of remote cardiovascular disease.

  11. Selective Endothelin-1 Receptor type-A Inhibition in Cardiac Surgery Subjects with Pre-Existing LV Dysfunction: Influence on Early Post-Operative Hemodynamics

    Science.gov (United States)

    Toole, John M.; Ikonomidis, John S.; Szeto, Wilson Y.; Zellner, James L.; Mulcahy, John; Deardorff, Rachael L.; Spinale, Francis G.

    2010-01-01

    Background and Objective A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor LV function (reduced ejection fraction; EF). Accordingly, this study tested the hypothesis that a selective ET-AR antagonist (ET-ARA) administered peri-operatively would favorably affect post-CPB hemodynamic profiles in patients with a pre-existing poor LVEF. Methods and Results Patients (n=29; 66±2 yrs) with a reduced LVEF (37±2%) were prospectively randomized, in a blinded fashion, at the time of elective coronary revascularization and/or valve replacement requiring CPB, to infusion of the highly-selective and potent ET-ARA, sitaxsentan at 1 or 2 mg/kg (IV bolus; n=9, 10 respectively) or vehicle (saline; n=10). Infusion of the ET-ARA/vehicle was performed immediately prior to separation from CPB and again at 12 hrs post-CPB. ET and hemodynamic measurements were performed at baseline, at separation from CPB (Time 0) and at 0.5, 6, 12, 24 hrs post-CPB. Baseline plasma ET (4.0±0.3 fmol/mL) was identical across all 3 groups, but when compared to pre-operative, baseline values obtained from age matched subjects with a normal LVEF (n=37;LVEF>50%), were significantly increased (2.9±0.2 fmol/mL, pTime 0, SVR changed in an equivalent fashion in the post-CPB period, but a significant ET-ARA effect was observed for PVR (ANOVA; p<0.05). For example at 24 hrs post-CPB, PVR increased by 40 d.scm-5 in the vehicle group, but directionally decreased by over 40 d·s·cm-5 in the 2 mg/kg ETARA group (p<0.05). Total adverse events were equivalently distributed across the ET-ARA/placebo groups. Conclusions These unique findings demonstrated that infusion of an ET-ARA in high risk cardiac surgery patients was not associated with significant hemodynamic compromise. Moreover, ET-ARA favorably affected PVR in the

  12. 1,25(OH)2D3improves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR-related mechanisms in type 1 diabetes.

    Science.gov (United States)

    Qu, Hua; Lin, Ke; Wang, Hang; Wei, Huili; Ji, Baolan; Yang, Zengsong; Peng, Chuan; Xiao, Xiaoqiu; Deng, Huacong

    2017-05-01

    Diabetic cardiomyopathy is one of the most important cardiac complications associated with diabetes. However, the mechanisms underlying diabetic cardiomyopathy remain unclear. The PARP1, SIRT1, and mTOR pathways have been implicated in cardiac diseases, and they are also associated with diabetes. 1,25(OH) 2 D 3 was recently recognized as a potential PARP1inhibitor in a macrophage cell line. The aim of our study was to investigate whether 1,25(OH) 2 D 3 can improve diabetic cardiomyopathy through a vitamin D receptor (VDR)-dependent mechanism associated with the PARP1/SIRT1/mTOR pathway. 1,25(OH) 2 D 3 -treated diabetic rats displayed improved left ventricular wall thickness and end-diastolic/systolic diameter, end-diastolic/systolic volume, left ventricular ejection fraction, fractional shortening, atrial natriuretic peptide, and brain natriuretic peptide gene expression, and interstitial fibrosis compared with untreated diabetic rats, while silencing the VDR gene in DM rats blocked the above results. 1,25(OH) 2 D 3 treatment also decreased PARP1 and increased SIRT1 expression levels and repressed the phosphorylation of mTOR. Treating neonatal cardiomyocytes with 1,25(OH) 2 D 3 and a PARP1 inhibitor decreased PARP1 and increased SIRT1 protein expression. The present study demonstrates that 1,25(OH) 2 D 3 treatment has the potential to improve diabetic cardiomyopathy in rats and suggests that VD-VDR signaling induces this protective effect against diabetic cardiomyopathy might partly through the PARP1/SIRT1/mTOR pathway. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Hepatic mitochondrial dysfunction in Friedreich Ataxia

    Directory of Open Access Journals (Sweden)

    Stüwe Sven H

    2011-11-01

    Full Text Available Abstract Background Mitochondrial dysfunction due to respiratory chain impairment is a key feature in pathogenesis of Friedreich ataxia. Friedreich ataxia affects the nervous system, heart and pancreas. Methods We assessed hepatic mitochondrial function by 13C-methionine-breath-test in 16 Friedreich ataxia patients and matched healthy controls. Results Patients exhaled significantly smaller amounts of 13CO2 over 90 minutes. Maximal exhaled percentage dose of 13CO2 recovery was reduced compared to controls. Conclusions 13C-methionine-breath-test indicates subclinical hepatic mitochondrial dysfunction in Friedreich ataxia but did not correlate with GAA repeat lengths, disease duration or disease severity.

  14. Right ventricular dysfunction in patients with end-stage renal disease on regular hemodialysis

    Directory of Open Access Journals (Sweden)

    Mohamed Momtaz

    2013-01-01

    Conclusion Subclinical RV dysfunction - as estimated by RV function indices; tricuspid plane systolic excursion, right ventricle fractional area change, and LTDISº - is increased among HD patients. A high prevalence of pulmonary hypertension was found among HD patients and this was not associated significantly with RV or left ventricular dysfunction in these patients.

  15. Subclinical hypothyroidism after vascular complicated pregnancy

    NARCIS (Netherlands)

    Zanden, M. van der; Hop-de Groot, R.J.; Sweep, F.C.; Ross, H.A.; Heijer, M. den; Spaanderman, M.E.A.

    2013-01-01

    OBJECTIVE: Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions.

  16. Predictive value of beat-to-beat QT variability index across the continuum of left ventricular dysfunction: competing risks of noncardiac or cardiovascular death and sudden or nonsudden cardiac death.

    Science.gov (United States)

    Tereshchenko, Larisa G; Cygankiewicz, Iwona; McNitt, Scott; Vazquez, Rafael; Bayes-Genis, Antoni; Han, Lichy; Sur, Sanjoli; Couderc, Jean-Philippe; Berger, Ronald D; de Luna, Antoni Bayes; Zareba, Wojciech

    2012-08-01

    The goal of the present study was to determine the predictive value of beat-to-beat QT variability in heart failure patients across the continuum of left ventricular dysfunction. Beat-to-beat QT variability index (QTVI), log-transformed heart rate variance, normalized QT variance, and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca heart failure study (mean age, 63.1±11.7; men, 70.6%; left ventricular ejection fraction >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death (subhazard ratio, 1.67 [95% CI, 1.14-2.47]; P=0.009) and, in particular, with non-SCD (subhazard ratio, 2.91 [1.69-5.01]; P<0.001). Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular (subhazard ratio, 1.57 [1.04-2.35]; P=0.031) and non-SCD in multivariate competing risk model (subhazard ratio, 2.58 [1.13-3.78]; P=0.001). No interaction between QTVI and left ventricular ejection fraction was found. QTVI predicted neither noncardiac death (P=0.546) nor SCD (P=0.945). Decreased heart rate variability rather than increased QT variability was the reason for increased QTVI in the present study. Increased QTVI because of depressed heart rate variability predicts cardiovascular mortality and non-SCD but neither SCD nor extracardiac mortality in heart failure across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from heart failure patients at risk.

  17. Interventions for clinical and subclinical hypothyroidism in pregnancy.

    Science.gov (United States)

    Reid, Sally M; Middleton, Philippa; Cossich, Mary C; Crowther, Caroline A

    2010-07-07

    Over the last decade there has been enhanced awareness of the appreciable morbidity of thyroid dysfunction, particularly thyroid deficiency. Since treating clinical and subclinical hypothyroidism may reduce adverse obstetric outcomes, it is crucial to identify which interventions are safe and effective. To identify interventions used in the management of hypothyroidism and subclinical hypothyroidism in pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2009). Randomised controlled trials (RCTs) that compared a pharmacological intervention for hypothyroidism and subclinical hypothyroidism in pregnancy with another intervention or placebo. Two review authors assessed trial eligibility and quality and extracted the data. We included three RCTs of moderate risk of bias involving 314 women. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). One trial of 30 hypothyroid women compared levothyroxine doses, but only reported biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia (RR 1.44; 95% CI 0.25 to 8.38) or preterm birth (RR 0.96; 95% CI 0.20 to 4.61). None of the three trials reported on childhood neurodevelopmental delay.There was a non-significant trend towards fewer miscarriages with levothyroxine, and selenium showed some favourable impact on postpartum thyroid function and decreased incidence of moderate to advanced postpartum thyroiditis. Levothyroxine treatment of clinical hypothyroidism in pregnancy is already standard

  18. Selective endothelin-1 receptor type A inhibition in subjects undergoing cardiac surgery with preexisting left ventricular dysfunction: Influence on early postoperative hemodynamics.

    Science.gov (United States)

    Toole, John M; Ikonomidis, John S; Szeto, Wilson Y; Zellner, James L; Mulcahy, John; Deardorff, Rachael L; Spinale, Francis G

    2010-03-01

    A robust release of endothelin-1 with subsequent endothelin-A subtype receptor activation occurs in patients after cardiac surgery requiring cardiopulmonary bypass. Increased endothelin-A subtype receptor activation has been identified in patients with poor left ventricular function (reduced ejection fraction). Accordingly, this study tested the hypothesis that a selective endothelin-A subtype receptor antagonist administered perioperatively would favorably affect post-cardiopulmonary bypass hemodynamic profiles in patients with a preexisting poor left ventricular ejection fraction. Patients (n = 29; 66 +/- 2 years) with a reduced left ventricular ejection fraction (37% +/- 2%) were prospectively randomized in a blinded fashion, at the time of elective coronary revascularization or valve replacement requiring cardiopulmonary bypass, to infusion of the highly selective and potent endothelin-A subtype receptor antagonist sitaxsentan at 1 or 2 mg/kg (intravenous bolus; n = 9, 10 respectively) or vehicle (saline; n = 10). Infusion of the endothelin-A subtype receptor antagonist/vehicle was performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass. Endothelin and hemodynamic measurements were performed at baseline, at separation from cardiopulmonary bypass (time 0), and at 0.5, 6, 12, and 24 hours after cardiopulmonary bypass. Baseline plasma endothelin (4.0 +/- 0.3 fmol/mL) was identical across all 3 groups, but when compared with preoperative values, baseline values obtained from age-matched subjects with a normal left ventricular ejection fraction (n = 37; left ventricular ejection fraction > 50%) were significantly increased (2.9 +/- 0.2 fmol/mL, P time 0, systemic vascular resistance changed in an equivalent fashion in the post-cardiopulmonary bypass period, but a significant endothelin-A subtype receptor antagonist effect was observed for pulmonary vascular resistance (analysis of variance; P < .05). For

  19. Cardiac Dysautonomia in Huntington's Disease.

    Science.gov (United States)

    Abildtrup, Mads; Shattock, Michael

    2013-01-01

    Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

  20. Technological advances shed light on left ventricular cardiac disturbances in cystic fibrosis.

    Science.gov (United States)

    Sayyid, Zahra N; Sellers, Zachary M

    2017-07-01

    Cystic fibrosis (CF), the most common autosomal recessive lethal disease in Caucasians, causes chronic pulmonary disease and can lead to cor pulmonale with right ventricular dysfunction. The presence of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiac myocardia has prompted debate regarding possible defective ion channel-induced cardiomyopathy. Clinical heart disease in CF is considered rare and is restricted to case reports. It has been unclear if this is due to the lack of physiological importance of CFTR in the heart, the relatively short lifespan of those with CF, or a technical inability to detect subclinical disease. Extensive echocardiographic investigations have yielded contradictory results, leading to the dogma that left ventricular defects in CF occur secondary to lung disease. In this review, we consider why studies examining heart function in CF have not provided clarity on this topic. We then focus on data from new echocardiographic and magnetic resonance imaging technology, which are providing greater insight into cardiac function in CF and demonstrating that, in addition to secondary effects from pulmonary disease, there may be an intrinsic primary defect in the CF heart. With advancing lifespans and activity levels, understanding the risk of cardiac disease is vital to minimizing morbidity in adults with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Partial deletion of eNOS gene causes hyperinsulinemic state, unbalance of cardiac insulin signaling pathways and coronary dysfunction independently of high fat diet.

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    Cecilia Vecoli

    Full Text Available Abnormalities in eNOS gene, possibly interacting with high fat diet (HFD, affect peripheral vascular function and glucose metabolism. The relative role of eNOS gene, HFD and metabolic derangement on coronary function has not been fully elucidated. We test whether eNOS gene deficiency per se or in association with HFD modulates coronary function through mechanisms involving molecular pathways related to insulin signaling. Wild type (WT, eNOS-/- and eNOS+/- mice were studied. WT and eNOS+/- mice were fed with either standard or HF diet for 16 weeks and compared with standard diet fed eNOS-/-. Glucose and insulin tolerance tests were performed during the last week of diet. Coronary resistance (CR was measured at baseline and during infusions of acetylcholine (Ach or sodium-nitroprusside (SNP to evaluate endothelium-dependent or independent vasodilation, in the Langendorff isolated hearts. Cardiac expression of Akt and ERK genes as evaluation of two major insulin-regulated signaling pathways involved in the control of vascular tone were assessed by western blot. HFD-fed mice developed an overt diabetic state. Conversely, chow-fed genetically modified mice (in particular eNOS-/- showed a metabolic pattern characterized by normoglycemia and hyperinsulinemia with a limited degree of insulin resistance. CR was significantly higher in animals with eNOS gene deletions than in WT, independently of diet. Percent decrease in CR, during Ach infusion, was significantly lower in both eNOS-/- and eNOS+/- mice than in WT, independently of diet. SNP reduced CR in all groups except eNOS-/-. The cardiac ERK1-2/Akt ratio, increased in animals with eNOS gene deletions compared with WT, independently of diet. These results suggest that the eNOS genetic deficiency, associated or not with HFD, has a relevant effect on coronary vascular function, possibly mediated by increase in blood insulin levels and unbalance in insulin-dependent signaling in coronary vessels

  2. High dose folic acid pre-treatment blunts cardiac dysfunction during ischemia coupled to maintenance of high energy phosphates and reduces post-reperfusion injury

    Science.gov (United States)

    Moens, An L.; Champion, Hunter C.; Claeys, Marc J.; Tavazzi, Barbara; Kaminki, Pawel M.; Wolin, Michael S.; Borgonjon, Dirk; Van Nassauw, Luc; Haile, Azeb; Zviman, Muz; Bedja, Djahida; Wuyts, Floris L.; Elsaesser, Rebecca S.; Cos, Paul; Gabrielson, Kathy L.; Lazzarino, Giuseppe; Paolocci, Nazareno; Timmermans, Jean-Pierre; Vrints, Christiaan J.; Kass, David A.

    2008-01-01

    Background The B-vitamin folic acid (FA) is important to mitochondrial protein and nucleic acid synthesis, is an anti-oxidant, and enhances nitric oxide synthase activity. Here, we tested whether FA reduces myocardial ischemic dysfunction and post-reperfusion injury. Methods Wistar rats were pretreated with either FA (10mg/d) or placebo for 1-wk, and then underwent in vivo transient left coronary artery occlusion for 30min with or without 90min reperfusion (total:n=131; sub-groups used for various analyses). FA (4.5•10-6M i.c) pretreatment and global ischemia/reperfusion (30 min/30min), was also performed in vitro (n=28). Results After 30min ischemia, global function declined more in controls than FA-pretreated rats (ΔdP/dtmax -878±586 mmHg/s vs. placebo -1956±351 mmHg/s, p=0.03), and regional thickening was better preserved (37.3±5.3% vs. 5.1±0.6%-placebo, p=0.004). Anterior-wall perfusion fell similarly (-78.4±9.3% vs. -71.2±13.8%-placebo at 30 min); yet myocardial high energy phosphates ATP and ADP reduced by ischemia in controls were better preserved by FA-pretreatment (e.g. ATP: control: 2740±58; ischemia: 947±55; ischemia+FA: 1332±101 nmol/g, p=0.02). Basal oxypurines (xanthine, hypoxanthine, and urate) rose with FA-pretreatment, but increased less during ischemia than in controls. Ischemic superoxide generation declined (3124±280 FA vs. 5898±474 placebo, cpm/mg, p=0.001). After reperfusion, FA-treated hearts had smaller infarcts (3.8±1.2% vs 60.3±4.1%-placebo area at risk, p<0.002), less contraction band necrosis, TUNEL-positivity, superoxide, and nitric oxide synthase uncoupling. Infarct size declined similarly with 1 mg/d FA as well. Conclusion FA-pretreatment blunts myocardial dysfunction during ischemia, and ameliorates post-reperfusion injury. This is coupled to preservation of high energy phosphates, reducing subsequent ROS-generation, eNOS-uncoupling and post-reperfusion cell death. PMID:18362233

  3. High-dose folic acid pretreatment blunts cardiac dysfunction during ischemia coupled to maintenance of high-energy phosphates and reduces postreperfusion injury.

    Science.gov (United States)

    Moens, An L; Champion, Hunter C; Claeys, Marc J; Tavazzi, Barbara; Kaminski, Pawel M; Wolin, Michael S; Borgonjon, Dirk J; Van Nassauw, Luc; Haile, Azeb; Zviman, Muz; Bedja, Djahida; Wuyts, Floris L; Elsaesser, Rebecca S; Cos, Paul; Gabrielson, Kathy L; Lazzarino, Giuseppe; Paolocci, Nazareno; Timmermans, Jean-Pierre; Vrints, Christiaan J; Kass, David A

    2008-04-08

    The B vitamin folic acid (FA) is important to mitochondrial protein and nucleic acid synthesis, is an antioxidant, and enhances nitric oxide synthase activity. Here, we tested whether FA reduces myocardial ischemic dysfunction and postreperfusion injury. Wistar rats were pretreated with either FA (10 mg/d) or placebo for 1 week and then underwent in vivo transient left coronary artery occlusion for 30 minutes with or without 90 minutes of reperfusion (total n=131; subgroups used for various analyses). FA (4.5x10(-6) mol/L i.c.) pretreatment and global ischemia/reperfusion (30 minutes/30 minutes) also were performed in vitro (n=28). After 30 minutes of ischemia, global function declined more in controls than in FA-pretreated rats (Delta dP/dtmax, -878+/-586 versus -1956+/-351 mm Hg/s placebo; P=0.03), and regional thickening was better preserved (37.3+/-5.3% versus 5.1+/-0.6% placebo; P=0.004). Anterior wall perfusion fell similarly (-78.4+/-9.3% versus -71.2+/-13.8% placebo at 30 minutes), yet myocardial high-energy phosphates ATP and ADP reduced by ischemia in controls were better preserved by FA pretreatment (ATP: control, 2740+/-58 nmol/g; ischemia, 947+/-55 nmol/g; ischemia plus FA, 1332+/-101 nmol/g; P=0.02). Basal oxypurines (xanthine, hypoxanthine, and urate) rose with FA pretreatment but increased less during ischemia than in controls. Ischemic superoxide generation declined (3124+/-280 cpm/mg FA versus 5898+/-474 cpm/mg placebo; P=0.001). After reperfusion, FA-treated hearts had smaller infarcts (3.8+/-1.2% versus 60.3+/-4.1% placebo area at risk; P<0.002) and less contraction band necrosis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positivity, superoxide, and nitric oxide synthase uncoupling. Infarct size declined similarly with 1 mg/d FA. FA pretreatment blunts myocardial dysfunction during ischemia and ameliorates postreperfusion injury. This is coupled to preservation of high-energy phosphates, reducing subsequent reactive

  4. Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: primary results from the T-wave alternans sudden cardiac death in heart failure trial substudy.

    Science.gov (United States)

    Gold, Michael R; Ip, John H; Costantini, Otto; Poole, Jeanne E; McNulty, Steven; Mark, Daniel B; Lee, Kerry L; Bardy, Gust H

    2008-11-11

    Sudden cardiac death remains a leading cause of mortality despite advances in medical treatment for the prevention of ischemic heart disease and heart failure. Recent studies showed a benefit of implantable cardioverter defibrillator implantation, but appropriate shocks for ventricular tachyarrhythmias were noted only in a minority of patients during 4 to 5 years of follow-up. Accordingly, better risk stratification is needed to optimize patient selection. In this regard, microvolt T-wave alternans (TWA) has emerged as a potentially useful measure of arrhythmia vulnerability, but it has not been evaluated previously in a prospective, randomized trial of implantable cardioverter defibrillator therapy. This investigation was a prospective substudy of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) that included 490 patients at 37 clinical sites. TWA tests were classified by blinded readers as positive (37%), negative (22%), or indeterminate (41%) by standard criteria. The composite primary end point was the first occurrence of any of the following events: sudden cardiac death, sustained ventricular tachycardia/fibrillation, or appropriate implantable cardioverter defibrillator discharge. During a median follow-up of 30 months, no significant differences in event rates were found between TWA-positive or -negative patients (hazard ratio 1.24, 95% confidence interval 0.60 to 2.59, P=0.56) or TWA-negative and nonnegative (positive and indeterminate) subjects (hazard ratio 1.28, 95% confidence interval 0.65 to 2.53, P=0.46). Similar results were obtained with the inclusion or exclusion of patients randomized to amiodarone in the analyses. TWA testing did not predict arrhythmic events or mortality in SCD-HeFT, although a small reduction in events (20% to 25%) among TWA-negative patients cannot be excluded given the sample size of this study. Accordingly, these results suggest that TWA is not useful as an aid in clinical decision making on implantable

  5. The prognostic value of cardiac dysfunction assessed by bedside echocardiography in critically ill patients with COPD requiring mechanical ventilation: a study protocol

    Science.gov (United States)

    Zhang, Zhongheng; Chen, Lin; Chen, Kun; Ni, Hongying

    2014-01-01

    Introduction Chronic obstructive lung disease is not only a major cause of morbidity and mortality, but is also the major reason for intensive care unit (ICU) admission. Cardiac function is often impaired in this disease, but its association with clinical outcome has not been fully established. Methods and analysis This is a prospective observational study conducted in a 47-bed mixed ICU of a tertiary academic teaching hospital. The study will be performed from January 2014 to December 2015. All patients meeting the diagnostic criteria of acute exacerbation of chronic obstructive pulmonary disease and admitted to the ICU are potentially eligible for the present study. The relevant demographics and laboratory measurements have been obtained. Transthoracic echocardiography was performed immediately after ICU admission by experienced intensivists. The Cox proportional hazard regression model has been fitted by using a stepwise forward selection and backward elimination technique. If linear assumption is not satisfied, the linear spline function will be used. Ethics and dissemination The study protocol was approved by the ethics committee of Jinhua municipal central hospital. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial registration number The study protocol is registered at ClinicalTrials.gov (NCT02099279). PMID:25256186

  6. Lack of effects of pioglitazone on cardiac function in patients with type 2 diabetes and evidence of left ventricular diastolic dysfunction: a tissue doppler imaging study

    Directory of Open Access Journals (Sweden)

    Katsouras Christos S

    2010-09-01

    Full Text Available Abstract Background Thiazolidinediones, used for the treatment of patients with type 2 diabetes mellitus (DM2, are associated with an increased incidence of heart failure. We sought to investigate the effects of pioglitazone on novel echocardiographic indices of left ventricular (LV diastolic function in DM2 patients with LV diastolic dysfunction (LVDD. Methods Eighty-eight asymptomatic DM2 patients on metformin and/or sulfonylureas, aged 64.5 ± 7.7 years, without known cardiovascular disease, with normal LV systolic function and evidence of LVDD were randomly assigned to pioglitazone 30 mg/day (n = 42 or an increase in dose of other oral agents (n = 39 for 6 months. All patients underwent transthoracic conventional and Tissue Doppler Imaging echocardiography at baseline and follow-up. The primary end-point was change in early diastolic velocity of the mitral annulus (E'. Results Improvement of glycaemic control was similar in the 2 groups. A significant difference (p Conclusions In asymptomatic DM2 patients with LVDD, the addition of pioglitazone to oral conventional treatment for 6 months does not induce any adverse or favorable changes in LV diastolic or systolic function despite improvements in glycaemic control, insulin sensitivity, lipid profile, and blood pressure.

  7. Behavioral, psychological, and physical characteristics of female athletes with subclinical eating disorders.

    Science.gov (United States)

    Beals, K A; Manore, M M

    2000-06-01

    The purpose of this study was to delineate and further define the behavioral, psychological, and physical characteristics of female athletes with subclinical eating disorders. Subjects consisted of 24 athletes with subclinical eating disorders (SCED) and 24 control athletes. Group classification was determined by scores on the Eating Disorder Inventory (EDI), the Body Shape Questionnaire (BSQ), and a symptom checklist for eating disorders (EDI-SC). Characteristics representative of the female athletes with subclinical eating disorders were derived from an extensive health and dieting history questionnaire and an in-depth interview (the Eating Disorder Examination). Energy intake and expenditure (kcal/d) were estimated using 7-day weighed food records and activity logs. The characteristics most common in the female athletes with subclinical eating disorders included: (a) preoccupation with food, energy intake, and body weight; (b) distorted body image and body weight dissatisfaction; (c) undue influence of body weight on self-evaluation; (d) intense fear of gaining weight even though at or slightly below ( approximately 5%) normal weight; (e) attempts to lose weight using one or more pathogenic weight control methods; (g) food intake governed by self-hatred upon breaking a rule; (h) absence of medical disorder to explain energy restriction, weight loss, or maintenance of low body weight; and (i) menstrual dysfunction. Awareness of these characteristics may aid in more timely identification and treatment of female athletes with disordered eating patterns and, perhaps, prevent the development of more serious, clinical eating disorders.

  8. Natural Course of Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    J P Sytch

    2005-03-01

    Full Text Available Objectives of this retrospective study were to evaluate the natural course of subclinical hypothyroidism (SH and to estimate possible predictable factors of overt hypothyroidism. Population of the study was selected from the patients with spontaneously elevated thyrotropin (TSH and normal free thyroxin (fT4 levels. Overall 87 patients (12 male, 75 female with SH without any therapy with thyroid hormones or iodide drugs or without previous thyroid surgery, thyrostatic therapy, or radioactive iodine therapy were included in the analysis. Results: the main risk factors of overt hypothyroidism in this population were positive thyroid antibodies (odds ratio = 3.99 and high initial level of TSH (>8 mU/l (odds ratio = 4.77. Patient’s age, gender or duration of SH did not affect significantly the risk of overt hypothyroidism. Conclusions: rational substitutive therapy with thyroid hormones was not discussed in this study, however the data suggest that positive thyroid antibodies and relatively high TSH level may be useful to decide upon such therapy in individuals with SH. Key words: hypothyroidism, Hashimotos, thyroiditis, thyrotropin.

  9. Weight History and Subclinical Myocardial Damage.

    Science.gov (United States)

    Ndumele, Chiadi E; Cobb, Laura; Lazo, Mariana; Bello, Natalie A; Shah, Amil; Nambi, Vijay; Blumenthal, Roger S; Gerstenblith, Gary; Solomon, Scott D; Ballantyne, Christie M; Selvin, Elizabeth; Coresh, Josef

    2017-11-20

    Excess weight is associated with subclinical myocardial damage, as reflected by high-sensitivity cardiac troponin T (hs-cTnT) concentrations, which portends high heart failure risk. However, the association between weight history and myocardial damage is unknown. We evaluated 9062 Atherosclerosis Risk in Communities (ARIC) visit 4 (1996-1999) participants with a body mass index (BMI) ≥ 18.5 kg/m(2) and no previous cardiovascular disease. We cross-tabulated visit 4 ("current") BMI categories of normal weight, overweight, and obese with those at visit 1 (1987-1989) and with BMI categories calculated from self-reported weight at age 25 years. Duration of obesity was calculated in years. A cumulative weight measure of "excess BMI-years" was also calculated [product of mean BMI (centered at 25 kg/m(2)) over all ARIC time points × follow-up duration]. We used logistic regression to estimate associations of weight history metrics with increased hs-cTnT (≥14 ng/L) at visit 4. Overall, 623 individuals (7%) had increased hs-cTnT at visit 4. Within each current BMI category, previous excess weight was associated with increased hs-cTnT, with the strongest associations for those with past and current obesity [odds ratio (OR), 3.85; 95% CI, 2.51-5.90 for obesity at age 25 years and visit 4]. Each 10-year longer obesity duration was associated with increased hs-cTnT (OR, 1.26; 95% CI, 1.17-1.35). Each 100 higher excess BMI-years was also progressively associated with increased hs-cTnT (OR, 1.21; 95% CI, 1.14-1.27). Previous obesity and greater cumulative weight from young adulthood increase the likelihood of myocardial damage, indicating long-term toxic effects of adiposity on the myocardium and the need for weight maintenance strategies targeting the entire life span. © 2017 American Association for Clinical Chemistry.

  10. Early Liver and Kidney Dysfunction Associated with Occupational Exposure to Sub-Threshold Limit Value Levels of Benzene, Toluene, and Xylenes in Unleaded Petrol

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    Masoud Neghab

    2015-12-01

    Conclusion: The average exposure of petrol station workers to BTX did not exceed the current threshold limit values (TLVs for these chemicals. However, evidence of subtle, subclinical and prepathologic early liver and kidney dysfunction was evident in exposed individuals.

  11. NT-proBNP as Early Marker of Subclinical Late Cardiotoxicity after Doxorubicin Therapy and Mediastinal Irradiation in Childhood Cancer Survivors

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    Amal Zidan

    2015-01-01

    Full Text Available Background. Childhood cancer survivors treated with anthracyclines and mediastinal irradiation are at risk for late onset cardiotoxicity. Aims of the Study. To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP and tissue Doppler imaging (TDI as early predictors of late onset cardiotoxicity in asymptomatic survivors of childhood cancer treated with doxorubicin with or without mediastinal irradiation. Methods. A cross-sectional study on 58 asymptomatic survivors of childhood cancer who received doxorubicin in their treatment protocols and 32 asymptomatic Hodgkin’s lymphoma survivors who received anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and conventional echocardiography were determined. Results. Thirty percent of survivors had abnormal NT-proBNP levels. It was significantly related to age at diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI detected myocardial affection in 20% more than conventional echocardiography. Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy. Conclusions. TDI could detect early cardiac dysfunction even in those with normal conventional echocardiography. Measurement of NT-proBNP represents an interesting strategy for detecting subclinical cardiotoxicity. We recommend prospective and multicenter studies to validate the role of NT-proBNP as an early marker for late onset doxorubicin-induced cardiotoxicity.

  12. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

    NARCIS (Netherlands)

    Natarajan, Pradeep; Bis, Joshua C; Bielak, Lawrence F; Cox, Amanda J; Dörr, Marcus; Feitosa, Mary F; Franceschini, Nora; Guo, Xiuqing; Hwang, Shih-Jen; Isaacs, Aaron; Jhun, Min A; Kavousi, Maryam; Li-Gao, Ruifang; Lyytikäinen, Leo-Pekka; Marioni, Riccardo E; Schminke, Ulf; Stitziel, Nathan O; Tada, Hayato; van Setten, Jessica|info:eu-repo/dai/nl/345493990; Smith, Albert V; Vojinovic, Dina; Yanek, Lisa R; Yao, Jie; Yerges-Armstrong, Laura M; Amin, Najaf; Baber, Usman; Borecki, Ingrid B; Carr, J Jeffrey; Chen, Yii-Der Ida; Cupples, L Adrienne; de Jong, Pim A|info:eu-repo/dai/nl/287955672; de Koning, Harry; de Vos, Bob D|info:eu-repo/dai/nl/413986004; Demirkan, Ayse; Fuster, Valentin; Franco, Oscar H; Goodarzi, Mark O; Harris, Tamara B; Heckbert, Susan R; Heiss, Gerardo; Hoffmann, Udo; Hofman, Albert; Išgum, Ivana|info:eu-repo/dai/nl/31484984X; Jukema, J Wouter; Kähönen, Mika; Kardia, Sharon L R; Kral, Brian G; Launer, Lenore J; Massaro, Joseph; Mehran, Roxana; Mitchell, Braxton D; Mosley, Thomas H; de Mutsert, Renée; Newman, Anne B; Nguyen, Khanh-Dung; North, Kari E; O'Connell, Jeffrey R; Oudkerk, Matthijs; Pankow, James S; Peloso, Gina M; Post, Wendy; Province, Michael A; Raffield, Laura M; Raitakari, Olli T; Reilly, Dermot F; Rivadeneira, Fernando; Rosendaal, Frits; Sartori, Samantha; Taylor, Kent D; Teumer, Alexander; Trompet, Stella; Turner, Stephen T; Uitterlinden, André G; Vaidya, Dhananjay; van der Lugt, Aad; Völker, Uwe; Wardlaw, Joanna M; Wassel, Christina L; Weiss, Stefan; Wojczynski, Mary K; Becker, Diane M; Becker, Lewis C; Boerwinkle, Eric; Bowden, Donald W; Deary, Ian J; Dehghan, Abbas; Felix, Stephan B; Gudnason, Vilmundur; Lehtimäki, Terho; Mathias, Rasika; Mook-Kanamori, Dennis O; Psaty, Bruce M; Rader, Daniel J; Rotter, Jerome I; Wilson, James G; van Duijn, Cornelia M; Völzke, Henry; Kathiresan, Sekar; Peyser, Patricia A; O'Donnell, Christopher J

    2016-01-01

    BACKGROUND: -The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease (CHD). We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the

  13. Association of Mild-to-Moderate Reduction in Glomerular Filtration Rate with Subclinical Atherosclerosis in Postmenopausal Women.

    Science.gov (United States)

    Parv, Florina; Beceanu, Andrei; Avram, Rodica; Timar, Romulus Zorin; Timar, Bogdan; Gadalean, Florica

    2017-05-24

    Due to loss of hormonal protective effects, postmenopausal women have an increased cardiovascular (CV) risk. Chronic kidney disease (CKD) is a well-established risk factor for CV disease, but little is known whether mild-to-moderate kidney dysfunction is associated with atherosclerosis burden in the postmenopausal asymptomatic women. Subclinical atherosclerosis was evaluated in 125 postmenopausal women with no clinical form of atherosclerosis, by carotid and femoral ultrasonography, ankle-brachial index (ABI), and flow-mediated dilation (FMD). Carotid and femoral atherosclerosis were defined as increased intima-media thickness (IMT) and/or the presence of plaques. Endothelial function was assessed by endothelial dependent (flow-mediated dilation at 1 minute [FMD1]) and independent (flow-mediated dilation after nitroglycerin [FMDNTG]) vasodilation. Classical CV risk factors (age, smoking, obesity, diabetes, blood pressure, and lipids) were evaluated. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Univariate linear regression and multivariate logistic regressions were used to evaluate the independent associations between kidney function and markers of subclinical atherosclerosis. In the unadjusted linear analysis, eGFR showed a significant negative association with markers of subclinical atherosclerosis: carotid IMT (R(2) = 0.305; p subclinical atherosclerosis, independent of traditional CV risk factors. It is important to detect renal function decline, even if it is mild, to improve risk stratification of subclinical atherosclerosis in postmenopausal women.

  14. Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy.

    Science.gov (United States)

    Akram, Frida Hosseini; Johansson, Bengt; Möllerström, Gunnar; Landgren, Britt-Marie; Stavreus-Evers, Anneli; Skjöldebrand-Sparre, Lottie

    2017-11-01

    Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy. In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n = 611), one low-risk group comprising women without risk factors for thyroid disorder (n = 511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n = 88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed. The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p = 0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0 mIU/L. High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since ∼10% of women with SCH or hypothyroidism could not be diagnosed in this way.

  15. Relationship between two-dimensional speckle-tracking septal strain and response to cardiac resynchronization therapy in patients with left ventricular dysfunction and left bundle branch block: a prospective pilot study.

    Science.gov (United States)

    Maréchaux, Sylvestre; Guiot, Aurélie; Castel, Anne Laure; Guyomar, Yves; Semichon, Marc; Delelis, François; Heuls, Sebastien; Ennezat, Pierre-Vladimir; Graux, Pierre; Tribouilloy, Christophe

    2014-05-01

    Previous studies have demonstrated variable patterns of longitudinal septal deformation in patients with left ventricular (LV) dysfunction and left bundle branch block. This prospective single center study was designed to assess the relationship between septal deformation patterns obtained by two-dimensional speckle-tracking echocardiography and response to cardiac resynchronization therapy (CRT). One hundred one patients with New York Heart Association class II to IV heart failure, LV ejection fractions ≤ 35%, and left bundle branch block underwent echocardiography before CRT. Longitudinal two-dimensional speckle-tracking strain analysis in the apical four-chamber view identified three patterns: double-peaked systolic shortening (pattern 1), early pre-ejection shortening peak followed by prominent systolic stretch (pattern 2), and pseudonormal shortening with a late systolic shortening peak and less pronounced end-systolic stretch (pattern 3). CRT response was defined as a relative reduction in LV end-systolic volume of ≥ 15% at 9-month follow-up. CRT super-response was defined as an absolute LV ejection fraction of ≥ 50% associated with a relative reduction in LV end-systolic volume of ≥ 15% and an improvement in New York Heart Association functional class. Cardiac death or hospitalization for heart failure during follow-up was systematically investigated. Ninety-two percent of patients with pattern 1 or 2 were responders to CRT compared with 59% with pattern 3 (P < .0001). Thirty-six percent of patients with pattern 1 were super-responders compared with 15% of those with pattern 2 and 12% of those with pattern 3 (P = .037). The improvement in LV volumes, LV ejection fraction, and global longitudinal strain after CRT was better in patients with pattern 1 or 2 compared with those with pattern 3 (P < .0001 for all). Eighteen-month outcomes were excellent in patients with pattern 1 or 2, with event-free survival of 95 ± 3% compared with 75 ± 7% in patients

  16. Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease.

    Science.gov (United States)

    Levelt, Eylem; Piechnik, Stefan K; Liu, Alexander; Wijesurendra, Rohan S; Mahmod, Masliza; Ariga, Rina; Francis, Jane M; Greiser, Andreas; Clarke, Kieran; Neubauer, Stefan; Ferreira, Vanessa M; Karamitsos, Theodoros D

    2017-10-25

    Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention.

  17. The regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy patients with or without left ventricular outflow tract obstruction: Assessment with first-pass perfusion imaging using 3.0-T cardiac magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hua-yan [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Yang, Zhi-gang, E-mail: yangzg666@163.com [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Sun, Jia-yu; Wen, Ling-yi; Zhang, Ge; Zhang, Shuai [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Guo, Ying-kun [Department of Radiology, West China Second University Hospital, Sichuan University (China)

    2014-04-15

    Purpose: To assess regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy (HCM) patients with or without left ventricular outflow tract obstruction using 3.0-T cardiac magnetic resonance (CMR) first-pass perfusion imaging. Materials and methods: Forty-two HCM patients, including 25 HCM patients with left ventricular outflow tract obstruction (HOCM), 17 HCM patients without left ventricular outflow tract obstruction (NOHCM), and 14 healthy subjects underwent CMR. The left ventricular (LV) function, left ventricular end-diastolic wall thickness (EDTH), and diameter of left ventricular outflow tract (LVOT) were measured and calculated. Based on the signal–time curve of the first-pass myocardium perfusion imaging, perfusion parameters including upslope, time to peak, and peak intensity, were assessed and compared by using one-way analysis of variance and independent t tests. Results: On the first-pass perfusion imaging, lower upslope and peak intensity and longer time to peak were found in HCM patients compared with normal subjects (all p < 0.05). In contrast to the NOHCM group, the average time to peak of the HOCM group was increased (13.30 ± 4.82 s vs 16.28 ± 4.90 s, p < 0.05), but first-pass perfusion upslope was reduced (4.96 ± 2.55 vs 2.58 ± 0.77, p < 0.05). According to the bull's-eye model, the HOCM group's average thickness of basal segments was thicker than the NOHCM group, especially the anteroseptal, inferolateral, and anterior wall values, with a corresponding lower first-pass perfusion upslope than the NOHCM group (all p < 0.05). A significant correlation was observed between first-pass perfusion upslope and LV EDTH (r = −0.551, p < 0.001) and LVOT diameter (r = 0.472, p < 0.001). Conclusions: The regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy (HCM) patients with or without left ventricular outflow tract obstruction can be detected with first-pass perfusion CMR

  18. Treatment of Subclinical Hypothyroidism in Obese Patients

    Directory of Open Access Journals (Sweden)

    T Demidova

    2008-03-01

    Full Text Available We observed 20 women suffering from adiposity and subclinical hypothyroidism. Lipid spectrum, carbohydrate metabolism, BP and insulinresistance, the extent and variants of fat tissue distribution, a test with physical exercise, all research in dynamics (in the beginning and 6 months after normalization of TSH level against the background of substitution therapy with L-T4 were evaluated. The positive shifts revealed during the afore mentioned research allow us to express our opinion in favour of carrying out substitution therapy with L-T4 at subclinical hypothyroidism .

  19. Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dalip Gupta

    2013-11-01

    Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.

  20. Erectile Dysfunction

    Science.gov (United States)

    ... of things can interfere with sexual feelings and cause or worsen erectile dysfunction. These include: Depression, anxiety or other mental health conditions Stress Relationship problems due to stress, poor communication or other concerns ...

  1. Erectile Dysfunction

    Science.gov (United States)

    ... Diabetes Association. http://www.diabetes.org/living-with-diabetes/treatment-and-care/men/erectile-dysfunction.html. Accessed Nov. ... medicine and a synthesis of the main available therapies. Diabetes & Metabolism. 2012;38:1. Nippoldt TB (expert opinion). ...

  2. Orgasmic dysfunction

    Science.gov (United States)

    ... dysfunction is when a woman either cannot reach orgasm, or has trouble reaching orgasm when she is sexually excited. When sex is ... to 15% of women have never had an orgasm. Surveys suggest that up to one half of ...

  3. Erectile dysfunction

    National Research Council Canada - National Science Library

    Giuliano, F; Droupy, S

    2013-01-01

    Erectile dysfunction (ED) is the most commonly studied sexual disorder. ED is defined by a consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual activity...

  4. Erectile Dysfunction

    Science.gov (United States)

    ... rigid. Medications The oral medications for erectile dysfunction, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), relax the muscles ... to begin working; the erection helping effects of sildenafil and vardenafil last for about 8 hours and ...

  5. Impact of bovine subclinical mastitis and effect of lactational treatment

    NARCIS (Netherlands)

    van den Borne, B.H.P.

    2010-01-01

    This thesis aimed to quantify the impact of subclinical mastitis in dairy cattle in the Netherlands and to explore the epidemiologic and economic effects of antimicrobial treatment of recently acquired subclinical mastitis during lactation. First, the occurrence of (sub)clinical mastitis was

  6. Prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mirta Centeno Maxzud

    2016-12-01

    Full Text Available Diabetes mellitus (DM and thyroid dysfunction (TD are two common endocrine disorders. The unrecognized subclinical TD may adversely affect metabolic control and increase cardiovascular risk. Our aim was to investigate the prevalence of TD in patients with type 2 diabetes mellitus in an observational cross-sectional study. Clinical and laboratory evaluation was performed to 205 consecutive outpatients at Endocrinology Diabetes and Nutrition Center in Concepcion City, Tucuman, Argentina. Thyroid dysfunction was classified as clinical hypothyroidism with TSH > 4.20 mUI / ml and FT4 4.20 mUI / ml and free T4 0.93 to 1.70 ng / dl. Subclinical hyperthyroidism was considered with TSH 1.70 mUI / ml. Autoimmunity was diagnosed with anti-TPO > 34 IU / ml. TD prevalence in type 2 diabetic patients was 48% (n = 92. In subjects who denied prior TD, the prevalence was 40% (n = 37, 15 with subclinical hypothyroidism (45%. In the whole study population prevalence of subclinical hypothyroidism was 8%. Globally, subclinical DT prevalence was 9% (n = 17 and anti-TPO 13% (n = 25. Early detection of thyroid dysfunction in patients with type 2 diabetes mellitus should be performed routinely, given the high rate of newly diagnosed cases, and increased cardiovascular risk associated with undiagnosed thyroid dysfunction.

  7. How frequently should a patient taking amiodarone be screened for thyroid dysfunction?

    Directory of Open Access Journals (Sweden)

    A. Pazin-Filho

    2009-08-01

    Full Text Available Amiodarone-induced thyroid dysfunction (AITD is a common complication of amiodarone therapy and its prevalence varies according to iodine intake, subclinical thyroid disorders and the definition of AITD. There is no consensus about the frequency of screening for this condition. We evaluated 121 patients on chronic regular intake of amiodarone (mean intake = 248.5 ± 89 mg; duration of treatment = 5.3 ± 3.9 years, range = 0.57-17 years and with stable baseline cardiac condition. Those with no AITD were followed up for a median period of 3.2 years (range: 0.6-6.7 and the incidence rate of AITD, defined by clinical and laboratorial findings as proposed by international guidelines, was obtained (62.8 per 1000 patients/year. We applied the Cox proportional hazard model to adjust for potential confounding factors and used sensitivity analysis to identify the best screening time for follow-up. We detected thyroid dysfunction in 59 (48.7% of the 121 patients, amiodarone-induced hypothyroidism in 50 (41.3% and hyperthyroidism in 9 (7.5%. Compared with patients without AITD, there was no difference regarding dosage or duration of therapy, heart rhythm disorder or baseline cardiac condition. During the follow-up of the 62 patients without AITD at baseline evaluation, 11 developed AITD (interquartile range, IR: 62.8 (95%CI: 31.3-112.3 cases per 1000 patients/year, 9 of them with hypothyroidism - IR: 11.4 (95%CI: 1.38-41.2, and 2 hyperthyroidism - IR: 51.3 (95%CI: 23.4-97.5. Age, gender, dose, and duration of treatment were not significant after adjustment. During the first 6 months of follow-up the incidence rate for AITD was 39.3 (9.2-61.9 cases per 1000 patients/year. These data show that AITD is quite common, and support the need for screening at 6-month intervals, unless clinical follow-up dictates otherwise or further information regarding the prognosis of untreated subclinical AITD is available.

  8. [Thyroid dysfunction during pregnancy].

    Science.gov (United States)

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

    Energy Technology Data Exchange (ETDEWEB)

    Estorch, Montserrat; Carrio, Ignasi; Mena, Esther; Flotats, Albert; Camacho, Valle; Fuertes, Jordi [Autonomous University of Barcelona, Department of Nuclear Medicine, Hospital Sant Pau, Barcelona (Spain); Kulisewsky, Jaume [Autonomous University of Barcelona, Department of Neurology, Hospital Sant Pau, Barcelona (Spain); Narula, Jagat [Irvine College of Medicine, Division of Cardiology, University of California, Irvine, CA (United States)

    2004-12-01

    Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution. Six patients (aged 62-81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second {sup 123}I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration. After amitriptyline administration, there was a decrease in regional MIBG uptake in 10{+-}4 segments per patient [62/120 segments (52%): 37 segments with a 5-10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions. A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging. (orig.)

  10. 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)

  11. Sub-clinical Addison′s disease

    Directory of Open Access Journals (Sweden)

    Manash P Baruah

    2012-01-01

    Full Text Available As autoimmune adrenalitis is fast replacing tuberculosis as the most common etiology cause of adrenal insufficiency, subtler forms of the same are being recognised as subclinical addison′s disease. In this article, we review what is known about this entity till date.

  12. Subclinical pertussis in incompletely vaccinated and unvaccinated ...

    African Journals Online (AJOL)

    4-fold increase in IgG antibodies to. AGG2,3 and to either PT or FHA or both are shown in Figs. 1 - 3. The subclinical pertussis led to stimulation of antibody responses to multiple antigens of Bordetella perttjssis. Antibody levels attained were significantly higher for all pertussis antibody assays than those detected in' age-.

  13. [Subclinical hypothyroidism and cardiovascular risk factors].

    Science.gov (United States)

    Frías López, Ma del C; Tárraga López, P J; Rodríguez Montes, J A; Solera Albero, J; Celada Rodríguez, A; López Cara, M A; Gálvez, A

    2011-01-01

    To determine the prevalence of subclinical hypothyroidism in the general population of an urban health center and describe the clinical characteristics and cardiovascular risk factors in patients with subclinical hypothyroidism. An observational study, retrospective, reviewing the medical histories of patients sampled from June 2005 until July 2007. We analyzed the following variables; facts: age and sex. Family history thyroid disease and other diseases. Personal History: cardiovascular pulmonary autoimmune, alterations gynecology obstetric diabetes, hypertension (HT) dislipemia, obesity, psychiatric alterations and haematological. Laboratory data: novel TSH, free T4, antiperoxidase antibodies, total cholesterol and its fractions. The prevalence of the sample of 100 patients collected over 8 months was 3.8% in the general population over 14 years, of which 79 were women and 21 were men. 13% were type 2 diabetics, 23% had HT and 40% had dyslipidemia. Overweight and obesity were present in 26%. The average level of TSH was 6.92 ± 2.29 μU/ml and the average level of free T4 was 1.16 ± 0.16 ng/ml. Prevalence subclinical hypothyroidism was 3.8%. especially in women with a mean age of 46. The incidence of cardiovascular risk factors in the subjects studied is higher in DM (13%), similar to general population in terms of dyslipidemia (40%) and obesity (23%) and lowest in hypertension (23%). In our study we observed a common pattern in the management of subclinical hypothyroidism, requiring the implementation and promotion of practice guidelines in primary care.

  14. Altered anorectal function in rotating shift workers: Association with autonomic dysfunction and sleep disturbance

    Directory of Open Access Journals (Sweden)

    Jui-Sheng Hung

    2016-09-01

    Conclusion: Rotating shift workers have anorectal dysmotility and cardiac sympathetic hyperactivity. Anorectal dysmotility in RSW workers has a close relationship with cardiac autonomic dysfunction, sleep disturbance, and depression, but not with anxiety.

  15. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which...

  16. Early clinical and subclinical visual evoked potential and Humphrey's visual field defects in cryptococcal meningitis.

    Directory of Open Access Journals (Sweden)

    Anand Moodley

    Full Text Available Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM. Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP testing and 47 patients underwent Humphrey's visual field (HVF testing. Decreased best corrected visual acuity (BCVA was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9% right eyes and 50/74 (67.6% left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5 ms and 119.8 (±15.7 ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10 ms (p<0.001. Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6% right eyes and 32/45 (71.1% left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM.

  17. Ghrelin and orotic acid increased in subclinical mastitis.

    Science.gov (United States)

    Karatas, F; Aydin, S; Kaygusuzoglu, E; Yildiz, H; Erulas, F A; Ozkan, Y

    2008-07-01

    Hormone ghrelin and orotic acid accelerate wound healing as well as controlling inflammation and immunity. We have, therefore, investigated the serum and milk levels of ghrelin and orotic acid in dairy cows with (n = 21) or without (n = 21) subclinical mastitis. Acylated and des-acylated ghrelin as well as orotic acid concentration were detected by using high performance liquid chromatography (HPLC). The results revealed that ghrelin level in milk and serum was significantly higher in dairy cows with subclinical mastitis than that of dairy cows without subclinical mastitis. This was also the case when the orotic acid concentrations in dairy cows with subclinical mastitis were compared with those dairy cows without subclinical mastitis. In conclusion, ghrelin and orotic acid occur in particularly high concentrations in subclinical mastitis, and might, therefore, be required in greater amounts for tissue repair and may be also used as a indicator for subclinical mastitis.

  18. Comparison of high-sensitivity C-reactive protein and fetuin-A levels before and after treatment for subjects with subclinical hyperthyroidism.

    Science.gov (United States)

    Bilgir, Oktay; Bilgir, Ferda; Topcuoglu, Tuba; Calan, Mehmet; Calan, Ozlem

    2014-03-01

    This study was designed to show the effect of propylthiouracil treatment on sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels on subjects with subclinical hyperthyroidism. After checking sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels of 35 patients with subclinical hyperthyroidism, each was given 50 mg tablets of propylthiouracil three times daily. After 3 months, sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels were then compared to the levels before treatment. Although high-sensitivity C-reactive protein and sCD40L levels were normal in the subclinical hyperthyroidism patients compared to the healthy controls, fetuin-A levels were statistically significantly higher (*p = 0.022). After treatment, fetuin-A levels of subclinical hyperthyroidism patients decreased statistically significantly compared to the levels before treatment (**p = 0.026). sCD40L and high-sensitivity C-reactive protein levels did not have a statistically significant difference compared to the control group and post-propylthiouracil treatment. In subclinical hyperthyroidism patients, high fetuin-A levels before propylthiouracil treatment and decreases in these levels after treatment in cases with subclinical hyperthyroidism indicated the possibility of preventing long-term cardiac complications with propylthiouracil treatment.

  19. Subclinical peripheral neuropathy in type 1 diabetic adolescents and its relationship with metabolic control

    Directory of Open Access Journals (Sweden)

    Sajić Silvija

    2005-01-01

    Full Text Available Professional management of paediatric diabetology, according to consensus guidelines, involves the screening of micro-vascular complications at puberty. The subclinical form of peripheral neural dysfunction in diabetic teenagers is reported with a frequency of 50-88%, by different authors. The purpose of this study was to evaluate the frequency of subclinical distal neuropathy (DSMN in type 1 diabetic pediatric patients during the second decade of life, and its relationship with metabolic control. The Endocrinology Department and the Neurology-Physiology Laboratory of the Pediatric Clinic in Belgrade carried out a longitudinal follow-up study (lasting 18 months, beginning in November 2000 on a selection of patients with poor metabolic control. During routine clinical treatment, patients were evaluated using the electrophysiological diagnostic method on peripheral neural dysfunction, a subclinical form of neuropathy. Metabolic control was manifested through HbA1c levels, measured every 3 months, using ion-exchange chromatography. Finally, here is the data collected from the clinical follow-up investigation of 60 children, aged 13-19 (median 1S.S±2.2, with duration of diabetes from 2-16 years (median b.3±3.b, and on the following therapies: 43 CT-conventional and 17 IIT-intensive, and insulin dose/day, median 1.02 (0.6-2.1 U/kg. Detected DSMN parameters at the beginning and at the end of the study were also noted. DSMN frequency was positive, at 64% for HbA1c of 9.44; DSMN dysfunction was reversed in 5% of the patients, for HbA1c of 10.17; the worst result was the progression of DSMN at 6.7% for HbA1c of 10.52; 6.7% had negative DSMN, with improved metabolic control, for HbA1c of 8.4; 15% of the examinations were unfinished (+/*. ANOVA statistical analysis showed a significant statistical relationship between metabolic control (HbA1c levels and DSMN neuropathy (sig. 0.043, p<0.05. There was no significant relationship between the reversion of

  20. Laryngeal Dysfunction

    DEFF Research Database (Denmark)

    Hull, James H; Backer, Vibeke; Gibson, Peter G

    2016-01-01

    The larynx is one of the most highly innervated organs in humans and serves a number of vitally important, complex, and highly evolved biological functions. On a day-to-day basis, the larynx functions autonomously, addressing several roles including airway protection, swallowing, and phonation....... In some situations the larynx appears to adopt a functional state that could be considered maladaptive or "dysfunctional." This laryngeal dysfunction can underpin and account for a number of respiratory symptoms that otherwise appear incongruous with a clinical disease state and/or contribute...

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

    Science.gov (United States)

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

    2017-05-01

    Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine-a late sodium current inhibitor-improves diastolic function in animal models and subjects with obstructive coronary artery disease (CAD). We hypothesized that ranolazine would beneficially alter diastolic function in CMD. To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD and from 43 healthy reference controls. Diastolic strain rate was impaired in CMD vs controls (circumferential diastolic strain rate: 99.9% ± 2.5%/s vs 120.1% ± 4.0%/s, P = 0.0003; radial diastolic strain rate: -199.5% ± 5.5%/s vs -243.1% ± 9.6%/s, P = 0.0008, case vs control). Moreover, peak systolic circumferential strain (CS) and radial strain (RS) were also impaired in cases vs controls (CS: -18.8% ± 0.3% vs -20.7% ± 0.3%; RS: 35.8% ± 0.7% vs 41.4% ± 0.9%; respectively; both P CMD cases after 2 weeks of ranolazine vs placebo. The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have subclinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD. © 2016 Wiley Periodicals, Inc.

  2. Cardiac catheterization - discharge

    Science.gov (United States)

    Catheterization - cardiac - discharge; Heart catheterization - discharge: Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization discharge; CAD - cardiac catheterization discharge; Coronary ...

  3. Sleeping and resting respiratory rates in dogs with subclinical heart disease.

    Science.gov (United States)

    Ohad, Dan G; Rishniw, Mark; Ljungvall, Ingrid; Porciello, Francesco; Häggström, Jens

    2013-09-15

    To characterize sleeping respiratory rates (SRRs) and resting respiratory rates (RRRs), collected in the home environment, of dogs with subclinical heart disease that could result in left-sided congestive heart failure. Prospective cross-sectional study. 190 adult dogs with subclinical left-sided heart disease. Most dogs had mitral valve disease or dilated cardiomyopathy of various severities. Clients collected ten 1-minute SRRs or RRRs during a period ranging from 1 week to 6 months. Clinicians provided echocardiographic and medical data on each patient. The within-dog mean SRR (SRRmean; 16 breaths/min) was significantly lower than the within-dog mean RRR (RRRmean; 21 breaths/min). Seven dogs had SRRmean and 33 dogs had RRRmean > 25 breaths/min; 1 dog had SRRmean and 12 dogs had RRRmean > 30 breaths/min; these dogs mostly had a left atrial (LA)-to-aortic ratio > 1.8. Dogs with moderate LA enlargement had a significantly higher SRRmean than did other dogs. However, median SRRmean for each of 4 levels of LA enlargement was dog SRR and RRR remained stable for 10 consecutive measurements. Treatment with cardiac medications or presence of pulmonary hypertension was not associated with SRRmean or RRRmean. Results suggested that dogs with confirmed subclinical left-sided heart disease of various severities generally had SRRmean dog SRRmean or RRRmean.

  4. Serum cholesterol and triglyceride concentrations in diabetic patients with subclinical hypothyroidism.

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    Díez, Juan J; Iglesias, Pedro

    2014-10-01

    To assess whether subclinical hypothyroidism is associated to elevations in serum cholesterol and triglyceride levels in patients with type 2 diabetes. From a total population of 1,112 patients with type 2 diabetes screened for thyroid dysfunction (thyrotropin measurement), a group of 325 patients with normal thyroid function and another group of 29 patients with subclinical hypothyroidism were selected. No patient had known dyslipidemia or was taking lipid lowering medication. Patients with subclinical hypothyroidism had serum levels of total cholesterol (4.88 ± 0.74 mmol/L), HDL cholesterol (1.37 ± 0.34 mmol/L), LDL cholesterol (2.94 ± 0.58 mmol/L), and triglycerides (1.05 [0.88-1.41] mmol/L) that did not significantly differ from those found in euthyroid patients (4.79 ± 0.83, 1.33 ± 0.36, 2.87 ± 0.76, and 1.11 [0.81-1.43] mmol/L, respectively). Multiple regression analysis showed no association between TSH and serum lipid levels. These results suggest that, in our population, there are no significant differences in serum cholesterol and triglyceride levels between diabetic patients with normal and reduced thyroid function. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  5. Erectile dysfunction.

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    Khera, Mohit; Goldstein, Irwin

    2011-06-29

    Erectile dysfunction may affect 30% to 50% of men aged 40 to 70 years, with age, smoking, and obesity being the main risk factors, although 20% of cases have psychological causes. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of phosphodiesterase inhibitors on erectile dysfunction in men with diabetes, with cardiovascular disease, with spinal cord injury, and with prostate cancer or undergoing prostatectomy? What are the effects of drug treatments other than phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of devices, psychological/behavioural treatments, and alternative treatments in men with erectile dysfunction of any cause? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 81 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: alprostadil (intracavernosal, intraurethral, topical), cognitive behavioural therapy, ginseng, papaverine, papaverine plus phentolamine (bimix), papaverine plus phentolamine plus alprostadil (trimix), penile prostheses, phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil), psychosexual counselling, vacuum devices, and yohimbine.

  6. Outcome of adrenalectomy for subclinical hypercortisolism and Cushing syndrome.

    Science.gov (United States)

    Raffaelli, Marco; De Crea, Carmela; D'Amato, Gerardo; Gallucci, Pierpaolo; Lombardi, Celestino P; Bellantone, Rocco

    2017-01-01

    We compared operative and metabolic outcomes in patients with subclinical Cushing syndrome and Cushing syndrome caused by unilateral adrenal lesion, aiming to clarify the role of glucocorticoid replacement treatment in patients with subclinical Cushing syndrome after adrenalectomy. The medical records of all the patients who underwent unilateral adrenalectomy for subclinical Cushing syndrome or Cushing syndrome were reviewed. Diagnostic criteria for subclinical Cushing syndrome were a pathologic dexamethasone suppression test plus 2 additional criteria. Twenty-nine patients with subclinical Cushing syndrome and 50 with Cushing syndrome were identified. No significant difference was found between patients with subclinical Cushing syndrome and Cushing syndrome regarding lesion size, operative time, and hospital stay. Two patients out of 29 with subclinical Cushing syndrome and 3 out of 50 patients with Cushing syndrome experienced Clavien-Dindo grade II complications (P = .87). All the patients required postoperative glucocorticoid replacement that was discontinued within 6 months in 28 of the 29 patients with subclinical Cushing syndrome and in 3 out of 50 Cushing syndrome patients (P Cushing syndrome and Cushing syndrome. Hypercortisolism was resolved in all the cases. Operative and metabolic outcomes of adrenalectomy are similar in subclinical Cushing syndrome and Cushing syndrome. Postoperative glucocorticoid replacement treatment is advisable in all patients with subclinical Cushing syndrome. Prolonged adrenal insufficiency is more frequent in Cushing syndrome patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Assessment of left atrial mechanical functions in thyroid dysfunction.

    Science.gov (United States)

    Karabag, Turgut; Dogan, Sait M; Bayraktaroğlu, Taner; Sayin, Muhammet R; Buyukuysal, Cagatay; Akpinar, Ibrahim; Aydin, Mustafa

    2013-01-01

     Thyroid hormone deficiency can lead to the impairment of cardiac function.  The aim of the study was to determine the left atrial (LA) mechanical function in patients with subclinical hypothyroidism (SHT) and overt hypothyroidism (OHT) and investigate associations of LA mechanical function with diastolic function.   Twenty‑six patients with newly diagnosed SHT (mean age, 42.2 ±12.5 years), 21 patients with OHT (40.2 ±8.5 years) and 28 healthy volunteers (42.4 ±11.2 years) were enrolled in this study. Patients were evaluated by standard M‑mode echocardiographic measurements, mitral Doppler flow analysis, and tissue Doppler parameters at the lateral, septal, and right ventricular annuli. LA volumes were measured using the disc method, and the parameters of LA mechanical function were calculated.   The active emptying volume (AEV) and active emptying fraction (AEF) were significantly higher in the OHT and SHT groups compared with controls. The passive emptying volume and passive emptying fraction were lower in the OHT and SHT groups compared with controls, but the differences were not significant. The conduit volume and the E/A ratio were significantly lower in the OHT and SHT groups compared with controls. The lateral and septal E/Em were significantly higher in the OHT and SHT groups than in the control group, but the septal Em/Am was significantly lower. Diastolic function parameters showed significant associations with AEV and AEF.   LA mechanical function is impaired in patients with thyroid dysfunction. Our findings suggest that this impairment is secondary to that of the left ventricular diastolic function.

  8. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  9. Is There Any Effect on Smell and Taste Functions with Levothyroxine Treatment in Subclinical Hypothyroidism?

    Science.gov (United States)

    Baskoy, Kamil; Ay, Seyid Ahmet; Altundag, Aytug; Kurt, Onuralp; Salihoglu, Murat; Deniz, Ferhat; Tekeli, Hakan; Yonem, Arif; Hummel, Thomas

    2016-01-01

    Subclinical hypothyroidism has been accused for coronary heart disease, lipid metabolism disorders, neuropsychiatric disorders, infertility or pregnancy related problems with various strength of evidence. Currently there is insufficient knowledge about olfaction and taste functions in subclinical hypothyroidism. Aim of the present study is to investigate the degree of smell and taste dysfunction in patients with subclinical hypothyroidism. 28 subclinical hypothyroid patients, and 31 controls enrolled in the prospective study in Istanbul, Turkey. Subclinical hypothyroid patients were treated with L-thyroxine for 3 months. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens ("Sniffin' Sticks", Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Patients scored lower on psychophysical olfactory tests than controls (odor thresholds:8.1±1.0 vs 8.9±1.1, p = 0.007; odor discrimination:12.4±1.3 vs 13.1±0.9, p = 0.016; odor identification:13.1±0.9 vs 14.0±1.1, p = 0.001; TDI score: 33.8±2.4 vs 36.9±2.1, p = 0.001). In contrast, results from psychophysical gustatory tests showed only a decreased score for "bitter" in patients, but not for other tastes (5.9±1.8 vs 6.6±1.0, p = 0.045). Three month after onset of treatment olfactory test scores already indicated improvement (odor thresholds:8.1±1.0 vs 8.6±0.6, psmell and taste, with thyroid function test were also evaluated. TSH, fT4 were found have no correlation with smell and taste changes with treatment. However bitter taste found positively correlated with T3 with treatment(r: 0.445, p: 0.018). Subclinical hypothyroid patients exhibited a significantly decreased olfactory sensitivity; in addition, bitter taste was significantly affected. Most importantly, these deficits can be remedied on average within 3 months with adequate treatment.

  10. Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity.

    Science.gov (United States)

    Hughes, Michael; Lilleker, James B; Herrick, Ariane L; Chinoy, Hector

    2015-05-01

    Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease. Accurate biomarkers are thus required to screen for cardiac disease, to better inform both therapeutic decision-making and treatment response. The widespread uptake of cardiac troponin testing has revolutionised the management of acute coronary syndromes. While cardiac troponin I (cTnI) appears specific to the myocardium, cardiac troponin T (cTnT) is also expressed by skeletal muscle, including regenerating skeletal muscle tissue. There is increasing interest about the role of cardiac troponins as a putative biomarker of primary cardiac involvement in IIM and SSc-spectrum disorders. Herewith we discuss subclinical cardiac disease in IIM and SSc-spectrum disorders, the respective roles of cTnI and cTnT testing, and the re-expression of cTnT within regenerating skeletal muscle tissue. There remains wide variation in access to cardiac troponin testing nationally and internationally. We propose two pragmatic clinical pathways using cardiac troponins, preferably measuring concomitant cTnT followed by confirmatory (cardiac) cTnI to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity, and also an agenda for future research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Exercise training in adverse cardiac remodeling.

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    Duncker, Dirk J; van Deel, Elza D; de Waard, Monique C; de Boer, Martine; Merkus, Daphne; van der Velden, Jolanda

    2014-06-01

    Cardiac remodeling in response to a myocardial infarction or chronic pressure-overload is an independent risk factor for the development of heart failure. In contrast, cardiac remodeling produced by regular physical exercise is associated with a decreased risk for heart failure. There is evidence that exercise training has a beneficial effect on disease progression and survival in patients with cardiac remodeling and dysfunction, but concern has also been expressed that exercise training may aggravate pathological remodeling and dysfunction. Here we present studies from our laboratory into the effects of exercise training on pathological cardiac remodeling and dysfunction in mice. The results indicate that even in the presence of a large infarct, exercise training exerts beneficial effects on the heart. These effects were mimicked in part by endothelial nitric oxide synthase (eNOS) overexpression and abrogated by eNOS deficiency, demonstrating the importance of nitric oxide signaling in mediating the cardiac effects of exercise. Exercise prior to a myocardial infarction was also cardioprotective. In contrast, exercise tended to aggravate pathological cardiac remodeling and dysfunction in the setting of pressure-overload produced by an aortic stenosis. These observations emphasize the critical importance of the underlying pathological stimulus for cardiac hypertrophy and remodeling, in determining the effects of exercise training. Future studies are needed to define the influence of exercise type, intensity and duration in different models and severities of pathological cardiac remodeling. Together such studies will aid in optimizing the therapy of exercise training in the setting of cardiovascular disease.

  12. SUBCLINICAL HYPOTHYROIDISM CURRENT CONCEPTS & M ANAGEMENT STRATEGEIES

    Directory of Open Access Journals (Sweden)

    Radha Krishnan

    2015-05-01

    Full Text Available Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone ( TSH and normal free T3 & T4 , without clinical features of hypothyroidism . Clinical significance of SCH remains uncertain and controversial . Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms . There are still controversies surrounding SCH and associated risk of various cardiovascular diseases ( CVDs , pregnancy outcomes , neuropsychiatric issues , metabolic syndrome , and dyslipidemia . This review will summarize the current data related to the effects of SCH on cardiovascular risk , SCH in pregnancy , in dyslipedemia and clinical guidelines on management of this condition . The evidence has been updated by a Pub med search on the risks and treatment of subclinical hypothyroidism of most recent articles published until March 2015

  13. Should Subclinical Hypothyroidism Be an Exclusion Criterion for the Diagnosis of Polycystic Ovary Syndrome?

    Science.gov (United States)

    de-Medeiros, Sebastião Freitas; Yamamoto, Márcia Marly Winck; de-Medeiros, Matheus Antônio Souto; Barbosa, Jacklyne Silva; Norman, Robert John

    2017-01-01

    The purpose of the study was to examine whether patients with subclinical hypothyroidism (SCH) should be excluded before making a diagnosis of polycystic ovary syndrome (PCOS). Seven hundred sixteen patients, 462 with true PCOS, 31 with PCOS-SCH, and 223 normal cycling women were enrolled. Clinical, metabolic, and hormonal parameters among the groups were investigated. Continuous variables were compared by one-way analysis of variance. Proportions were compared using Z test. Fisher test was used to compare categorical variables. Simple correlation was performed using Spearman's coefficient. Correlation between thyroid stimulating hormone (TSH) and dependent variables were performed using backward multiple regression. The significance level was set at 0.05. True polycystic ovary and polycystic ovary with subclinical hypothyroidism patients presented similar anthropometrical parameters. C-peptide was higher in polycystic ovary patients than in the other groups (p=0.014). Prevalence of glucose intolerance (p=0.186) and insulin resistance (p=0.293) was not statistically different in polycystic ovary and polycystic ovary with subclinical hypothyroidism. TSH levels showed positive correlation with lean body mass (p=0.032), total cholesterol (p=0.046, insulin (p=0.048) and prolactin (p=0.047). Backward multiple regression model retained TC, insulin, and PRL as predictors of TSH levels (p=0.011). Anthropometric parameters and ovary morphology were similar in both PCOS and PCOS-with-SCH patients. Regarding hormones, only C-peptide was higher in PCOS group. TSH correlated with total cholesterol, insulin, and prolactin. Before PCOS diagnosis, the exclusion criterion thyroid dysfunction should be standardized and subclinical hypothyroidism should not exclude a diagnosis of PCOS.

  14. Subclinical hypothyroidism and myocardial function in obese children.

    Science.gov (United States)

    Brienza, C; Grandone, A; Di Salvo, G; Corona, A M; Di Sessa, A; Pascotto, C; Calabrò, R; Toraldo, R; Perrone, L; del Giudice, E Miraglia

    2013-09-01

    Pediatric obesity is an important health problem representing a major public health concern worldwide in the last decades. An isolated elevation of Thyroid Stimulating Hormone (TSH) with normal levels of thyroid hormones is frequently found in obese children. It has been named Isolated Hyperthyreotropinemia or Subclinical Hypothyroidism (SCH) and may be considered a consequence of obesity. Evidence exists that SCH is related to impairment of both systolic and diastolic myocardial function in the adult population. The aim of our study is to establish if obesity-related SCH influences myocardial function in children. We examined 34 obese children and adolescents with SCH and 60 obese children with normal TSH levels who underwent Doppler echocardiographic to evaluate myocardial function. Global systolic function as assessed by Ejection Fraction (EF) was comparable between groups, however Right Ventricle pressure global systolic function and pressure were significantly reduced in SCH group. Mitral annulus peak systolic (MAPSE) excursion lateral and MAPSE septum resulted significantly reduced in SCH group. Tissue Doppler imaging peak systolic motion (TDI-S) was reduced in SCH group. Diastolic function also showed significant modifications in SCH group. These results suggest possible involvement of cardiac function in obese children with SCH resulting in both abnormal diastolic function and reduced longitudinal systolic function. This new insight into cardiovascular consequences of obesity-related SCH in children could influence clinical approach to such patients by pediatric endocrinologists. Copyright © 2012 Elsevier B.V. All rights reserved.