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Sample records for affect heart function

  1. Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice.

    PubMed

    Ruiz, Lina M; Salazar, Celia; Jensen, Erik; Ruiz, Paula A; Tiznado, William; Quintanilla, Rodrigo A; Barreto, Marlen; Elorza, Alvaro A

    2015-01-01

    Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2 (∙-) production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined. PMID:26106459

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  3. Short-Term Exposure to Ozone Does Not Impair Vascular Function or Affect Heart Rate Variability in Healthy Young Men

    PubMed Central

    Barath, Stefan; Langrish, Jeremy P.; Blomberg, Anders

    2013-01-01

    Air pollution exposure is associated with cardiovascular morbidity and mortality, yet the role of individual pollutants remains unclear. In particular, there is uncertainty regarding the acute effect of ozone exposure on cardiovascular disease. In these studies, we aimed to determine the effect of ozone exposure on vascular function, fibrinolysis, and the autonomic regulation of the heart. Thirty-six healthy men were exposed to ozone (300 ppb) and filtered air for 75min on two occasions in randomized double-blind crossover studies. Bilateral forearm blood flow (FBF) was measured using forearm venous occlusion plethysmography before and during intra-arterial infusions of vasodilators 2–4 and 6–8h after each exposure. Heart rhythm and heart rate variability (HRV) were monitored during and 24h after exposure. Compared with filtered air, ozone exposure did not alter heart rate, blood pressure, or resting FBF at either 2 or 6h. There was a dose-dependent increase in FBF with all vasodilators that was similar after both exposures at 2–4h. Ozone exposure did not impair vasomotor or fibrinolytic function at 6–8h but rather increased vasodilatation to acetylcholine (p = .015) and sodium nitroprusside (p = .005). Ozone did not affect measures of HRV during or after the exposure. Our findings do not support a direct rapid effect of ozone on vascular function or cardiac autonomic control although we cannot exclude an effect of chronic exposure or an interaction between ozone and alternative air pollutants that may be responsible for the adverse cardiovascular health effects attributed to ozone. PMID:23872581

  4. A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy

    PubMed Central

    Zeng, Xianxu; Tate, Rebecca E.; McKee, Mary L.; Capen, Diane E.; Zhang, Zhan; Tanzi, Rudolph E.; Zhou, Chao

    2015-01-01

    Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential

  5. A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy.

    PubMed

    Alex, Aneesh; Li, Airong; Zeng, Xianxu; Tate, Rebecca E; McKee, Mary L; Capen, Diane E; Zhang, Zhan; Tanzi, Rudolph E; Zhou, Chao

    2015-01-01

    Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential

  6. The Genetic Response to Short-term Interventions Affecting Cardiovascular Function: Rationale and Design of the HAPI Heart Study

    PubMed Central

    Mitchell, Braxton D.; McArdle, Patrick F.; Shen, Haiqing; Rampersaud, Evadnie; Pollin, Toni I.; Bielak, Lawrence F.; Jaquish, Cashell; Douglas, Julie A.; Roy-Gagnon, Marie-Hélène; Sack, Paul; Naglieri, Rosalie; Hines, Scott; Horenstein, Richard B.; Chang, Yen-Pei C.; Post, Wendy; Ryan, Kathleen A.; Brereton, Nga Hong; Pakyz, Ruth E.; Sorkin, John; Damcott, Coleen M.; O’Connell, Jeffrey R.; Mangano, Charles; Corretti, Mary; Vogel, Robert; Herzog, William; Weir, Matthew R.; Peyser, Patricia A.; Shuldiner, Alan R.

    2008-01-01

    Background The etiology of cardiovascular disease (CVD) is multifactorial. Efforts to identify genes influencing CVD risk have met with limited success to date, likely due to the small effect sizes of common CVD risk alleles and the presence of gene by gene and gene by environment interactions. Methods The Heredity and Phenotype Intervention (HAPI) Heart Study was initiated in 2002 to measure the cardiovascular response to four short-term interventions affecting cardiovascular risk factors and to identify the genetic and environmental determinants of these responses. The measurements included blood pressure responses to the cold pressor stress test and to a high salt diet, triglyceride excursion in response to a high fat challenge, and response in platelet aggregation to aspirin therapy. Results The interventions were carried out in 868 relatively healthy Amish adults from large families. The heritabilities of selected response traits for each intervention ranged from 8–38%, suggesting that some of the variation associated with response to each intervention can be attributed to the additive effects of genes. Conclusions Identifying these response genes may identify new mechanisms influencing CVD and may lead to individualized preventive strategies and improved early detection of high-risk individuals. PMID:18440328

  7. Right heart function in COPD.

    PubMed

    Macnee, William

    2010-06-01

    Pulmonary hypertension is a common complication in patients with severe hypoxic COPD, but the elevation in pulmonary arterial pressure (PAP) is usually relatively mild, although its presence indicates a poor prognosis. A minority of patients have severe pulmonary hypertension, whose prognosis is very poor with the development of right heart failure. Pulmonary hypertension in COPD is thought to result from hypoxic pulmonary vasoconstriction leading to structural remodeling of all layers of the pulmonary arterial walls. The simple hypothesis that hypoxemia in patients with chronic lung disease results in pulmonary hypertension, which adversely affects right ventricular function and hence increases morbidity and decreases exercise tolerance, leading to the development of peripheral edema and increased mortality, is still somewhat controversial. Whether therapeutic interventions that directly affect PAP or right ventricular function have a significant effect on long-term survival in patients with pulmonary hypertension secondary to hypoxic lung disease is still a matter of debate. Furthermore, whether such interventions will have an effect on symptoms or exercise tolerance remains unproven. Present therapies are limited to the correction of hypoxemia over the long term, which has been shown to have proven benefits on survival. Further studies are required of more specific pulmonary vasodilators or therapies to improve right ventricular function in these patients. PMID:20496299

  8. Diastolic function in heart failure.

    PubMed

    Kovács, Sándor J

    2015-01-01

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

  9. Diastolic Function in Heart Failure

    PubMed Central

    Kovács, Sándor J

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction. PMID:26306682

  11. Reduction of homocysteine in elderly with heart failure improved vascular function and blood pressure control but did not affect inflammatory activity.

    PubMed

    Andersson, Sven E; Edvinsson, Marie-Louise; Edvinsson, Lars

    2005-11-01

    We have previously shown that hyperhomocysteinaemia is common in elderly heart failure patients, and is associated with endothelial dysfunction, impaired vasodilatory capacity and a low-grade inflammation. In the present study we examined if supplementation with B6, B12 and folate could normalize the hyperhomocysteinaemia and if so, in turn, would improve the associated parameters. This was an open study without placebo control on heart failure patients with plasma homocysteine > 15 microM. Measurements of cutaneous vascular reactivity, blood pressure, inflammatory activity and endothelial function were performed before and after intervention with intra-individual comparisons. The treatment reduced homocysteine to near normal values and enhanced the hyperaemic response to acetylcholine related to the response to heat. The mean arterial blood pressure and pulse rate was reduced. There was no effect on inflammatory activity, plasma levels of von Willebrand factor, subjective health quality or the hyperaemic responses to sodium nitroprusside or local warming. Hyperhomocysteinaemia in heart failure patients is multifactorial in origin. Folate deficiency, inflammatory activity and reduced renal function could be contributing. It is suggested that supplementation with B-vitamins can improve the vasodilatory capacity and reduce the blood pressure but additional studies are required to confirm this. PMID:16236143

  12. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... percent of smokers begin before age 18. Middle-Aged Women: At menopause, a woman's heart disease risk ... risk of developing high blood pressure for women aged 55 is about 90 percent. Beginning at age ...

  13. Factors affecting survival in total artificial heart recipients before transplantation.

    PubMed

    Kawaguchi, A T; Gandjbakhch, I; Pavie, A; Muneretto, C; Solis, E; Bors, V; Leger, P; Vaissier, E; Levasseur, J P; Szefner, J

    1990-11-01

    To identify factors affecting the successful bridge to transplantation, experience with 32 recipients of the Jarvik-7 artificial heart was reviewed. Between patients with and without a successful bridge, there were no significant differences in preoperative hepatorenal function or postoperative hemodynamics, but there were significant differences in body size. When recipients were divided according to body surface areas of less than or greater than 1.8 m2, the smaller patients more frequently developed respirator dependence (73% vs. 18%, p less than 0.01), renal failure (53% vs. 18%, p less than 0.05), and hepatic failure and sepsis, resulting in less frequent qualification for transplantation (20% vs. 65%, p less than 0.05). There were no successful bridge operations in seven patients with body surface areas of less than 1.7 m2, and only one success in nine patients who were less than 170 cm in height, despite use of a smaller stroke volume model. The smaller patients had poorer ventricular filling, which was largely compensated for by the drive controls set for significantly longer diastole and higher vacuum, resulting in similar hemodynamics between the groups. The results suggest that device fitting as manifested by body size is an important factor affecting major organ recovery and subsequent transplantation in recipients of the Jarvik-7 artificial heart. A paracorporeal device may be advisable for patients with body surface areas of less than 1.8 m2 or who were less than 175 cm in height until an even smaller model with a better fit in the thorax becomes available. PMID:2225424

  14. Functional Assessment for Congenital Heart Disease

    PubMed Central

    2014-01-01

    Significant improvement in survival of children with congenital cardiac malformations has resulted in an increasing population of adolescent and adult patients with congenital heart disease. Of the long-term cardiac problems, ventricular dysfunction remains an important issue of concern. Despite corrective or palliative repair of congenital heart lesions, the right ventricle, which may be the subpulmonary or systemic ventricular chamber, and the functional single ventricle are particularly vulnerable to functional impairment. Regular assessment of cardiac function constitutes an important aspect in the long-term follow up of patients with congenital heart disease. Echocardiography remains the most useful imaging modality for longitudinal monitoring of cardiac function. Conventional echocardiographic assessment has focused primarily on quantification of changes in ventricular size and blood flow velocities during the cardiac cycles. Advances in echocardiographic technologies including tissue Doppler imaging and speckle tracking echocardiography have enabled direct interrogation of myocardial deformation. In this review, the issues of ventricular dysfunction in congenital heart disease, conventional echocardiographic and novel myocardial deformation imaging techniques, and clinical applications of these techniques in the functional assessment of congenital heart disease are discussed. PMID:24653734

  15. ON THE BIOMECHANICS OF HEART VALVE FUNCTION

    PubMed Central

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

    2009-01-01

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

  16. My head says yes but my heart says no: cognitive and affective attraction as a function of similarity to the ideal self.

    PubMed

    Herbst, Kenneth C; Gaertner, Lowell; Insko, Chester A

    2003-06-01

    The authors hypothesized that similarity to the ideal self (IS) simultaneously generates attraction and repulsion. Attraction research has suggested that a person likes individuals who are similar to his or her IS. Social comparison research has suggested that upward social comparison threatens self-evaluation. In Experiment 1, attraction to a partner increased and then decreased as the partner became more similar to and then surpassed the participant's IS. In Experiment 2, the cognitive and affective components of attraction increased and decreased, respectively, as the partner approached and surpassed the participant's IS to the extent that the dimension of comparison was meaningful and participants andicipated meeting their partner. Similarity to the IS generates opposing cognitive and affective reactions when the self-evaluative threat of upward comparison intensifies. PMID:12793585

  17. Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts.

    PubMed

    Verma, Sunil K; Deshmukh, Vaibhav; Nutter, Curtis A; Jaworski, Elizabeth; Jin, Wenhao; Wadhwa, Lalita; Abata, Joshua; Ricci, Marco; Lincoln, Joy; Martin, James F; Yeo, Gene W; Kuyumcu-Martinez, Muge N

    2016-01-01

    Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart failure. Genome-wide transcriptome changes have been identified at early stages in the right ventricle (RV) of infants with HLHS, although the molecular mechanisms remain unknown. Here, we demonstrate that the RNA binding protein Rbfox2, which is mutated in HLHS patients, is a contributor to transcriptome changes in HLHS patient RVs. Our results indicate that majority of transcripts differentially expressed in HLHS patient hearts have validated Rbfox2 binding sites. We show that Rbfox2 regulates mRNA levels of targets with 3'UTR binding sites contributing to aberrant gene expression in HLHS patients. Strikingly, the Rbfox2 nonsense mutation identified in HLHS patients truncates the protein, impairs its subcellular distribution and adversely affects its function in RNA metabolism. Overall, our findings uncover a novel role for Rbfox2 in controlling transcriptome in HLHS. PMID:27485310

  18. Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts

    PubMed Central

    Verma, Sunil K.; Deshmukh, Vaibhav; Nutter, Curtis A.; Jaworski, Elizabeth; Jin, Wenhao; Wadhwa, Lalita; Abata, Joshua; Ricci, Marco; Lincoln, Joy; Martin, James F.; Yeo, Gene W.; Kuyumcu-Martinez, Muge N.

    2016-01-01

    Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart failure. Genome-wide transcriptome changes have been identified at early stages in the right ventricle (RV) of infants with HLHS, although the molecular mechanisms remain unknown. Here, we demonstrate that the RNA binding protein Rbfox2, which is mutated in HLHS patients, is a contributor to transcriptome changes in HLHS patient RVs. Our results indicate that majority of transcripts differentially expressed in HLHS patient hearts have validated Rbfox2 binding sites. We show that Rbfox2 regulates mRNA levels of targets with 3’UTR binding sites contributing to aberrant gene expression in HLHS patients. Strikingly, the Rbfox2 nonsense mutation identified in HLHS patients truncates the protein, impairs its subcellular distribution and adversely affects its function in RNA metabolism. Overall, our findings uncover a novel role for Rbfox2 in controlling transcriptome in HLHS. PMID:27485310

  19. Congenital heart disease

    MedlinePlus

    Congenital heart disease is a problem with the heart's structure and function that is present at birth. ... Congenital heart disease (CHD) can describe a number of different problems affecting the heart. It is the most common ...

  20. Interplay between cardiac function and heart development.

    PubMed

    Andrés-Delgado, Laura; Mercader, Nadia

    2016-07-01

    Mechanotransduction refers to the conversion of mechanical forces into biochemical or electrical signals that initiate structural and functional remodeling in cells and tissues. The heart is a kinetic organ whose form changes considerably during development and disease. This requires cardiomyocytes to be mechanically durable and able to mount coordinated responses to a variety of environmental signals on different time scales, including cardiac pressure loading and electrical and hemodynamic forces. During physiological growth, myocytes, endocardial and epicardial cells have to adaptively remodel to these mechanical forces. Here we review some of the recent advances in the understanding of how mechanical forces influence cardiac development, with a focus on fluid flow forces. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26952935

  1. [The effect of droperidol on heart function].

    PubMed

    Chernikov, V S; Bakuleva, N P; Kostava, V T

    1992-01-01

    The effect of droperidol (3.3 x 10(-6) M) on the functional capacities of the isolated heart has been studied. The drug inhibited myocardial contractility. The effect manifested directly after the introduction of droperidol into perfusate (prompt phase). Afterwards the progress of the drug inhibitory effect was slow (slow phase). It is assumed that the difficulties in the use of droperidol in the critical cardiosurgical patients are associated with the attenuation in the realization of the regulatory effects of the central nervous system. PMID:1416194

  2. [Changes of heart function after different cell type stem cell transplantation in chronic heart failure].

    PubMed

    Fan, Zhongcai; Chen, Mao; Deng, Juelin; Liu, Xiaojing; Zhang, Li; Rao, Li; Yang, Qing; Huang, Dejia

    2006-12-01

    To investigate the feasibility of introcoronary cell infusion into nonischemic heart failure (HF) heart and whether different types of stem cell transplantation would affect heart function to a similar degree. Japanese white ears rabbits were used as HF models by intravenous injection adriamycin. Autologous bone marrow mononuclear cells(BMCs), bone marrow stromal cells (MSCs), skeletal myoblasts (SMs) or culture medium were infused into coronary arteries respectively by occluding the root of ascending aorta. The mortality during and 4 weeks after the procedure the mortality was 7.1% and 16.7% respectively. After 4 weeks, the ejection fraction (EF) in BMCs group had significant improvement (P < 0.05, n=8). No significant difference was seen in MSCs (n =8), SMs (n=6) and sham groups (n=8) compared with pretransplantation (P > 0.05). In sham group,the left ventricular endostolic diameter (LVED) had significant enlargement (P < 0.05), No significant difference was seen in MBCs, MSCs and SMs groups compared with pretransplantation (P > 0.05). Immunofluorescence revealed de novo expression of cardiac troponin I in BMCs and MSCs groups, cardiac troponin I was not detected in SMs group. In conclusions, intracoronary cell transplantation could provide effective cell delivery into dilated cardiomyopathy hearts and could be a useful strategy for treating CHF, BMCs cell transplantation may be the first choice in all the above cell types. PMID:17228727

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

    ERIC Educational Resources Information Center

    Moore, Crystal Dea

    2010-01-01

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

  4. Factors affecting the heart rate during self-paced walking.

    PubMed

    Bassey, E J; Macdonald, I A; Patrick, J M

    1982-01-01

    The results of 277 self-paced walking tests have been analysed for the effects of body composition, sex and age using step-up multiple regression analysis. Equations are given for the influence of the significant factors on chosen walking speeds and on heart rate (fc) (standardised at 4.8 km . h-1 by interpolation from points recorded at three walking speeds). The basic equations are: Normal speed (km . h-1) = 1.72 + 2.13 stature (m) - 0.008 age (years) Fast speed (km . h-1) = 0.54 + 3.69 stature (m) - 0.016 age (years) For men: fc4.8 (beat . min-1) = 161 - 50.7 stature (m) + 0.223 body weight (kg) For women: fc4.8 (beat . min-1) = 161 - 50.7 stature (m) + 0.223 body weight (kg) + 4.43 The significant factors affecting freely chosen walking speeds are stature and age. When estimates of body composition are available, percentage fat is found to be the most influential single factor affecting fc, while sex no longer has a significant effect, and age now has a negative influence. When allowance is made for these factors the effects of customary physical activity can be seen more clearly. PMID:7199445

  5. [Association between function of selenium and heart disease].

    PubMed

    Hiraoka, Yuji

    2016-07-01

    An excessive oxidative stress is considered to be responsible for the development and progression of heart disease. Deficiency of trace elements with antioxidative activities is present in patients with heart disease. Selenium (Se) is an integral part of the enzyme glutathione peroxidase(GPx), one of the central players of the heart's antioxidant system, and it's deficiency is implicated in certain types of heart disease. Our study suggests that myocardial oxidative stress in chronic heart failure may be augmented at least in part by concomitant GPx deficiency, and that the administration of Se could rescue the exhaustion of this selenoprotein, resulting in improved left ventricular function. PMID:27455811

  6. Protective Mechanisms of Mitochondria and Heart Function in Diabetes

    PubMed Central

    Tocchetti, Carlo G.; Bhatt, Niraj; Paolocci, Nazareno; Cortassa, Sonia

    2015-01-01

    Abstract Significance: The heart depends on continuous mitochondrial ATP supply and maintained redox balance to properly develop force, particularly under increased workload. During diabetes, however, myocardial energetic-redox balance is perturbed, contributing to the systolic and diastolic dysfunction known as diabetic cardiomyopathy (DC). Critical Issues: How these energetic and redox alterations intertwine to influence the DC progression is still poorly understood. Excessive bioavailability of both glucose and fatty acids (FAs) play a central role, leading, among other effects, to mitochondrial dysfunction. However, where and how this nutrient excess affects mitochondrial and cytoplasmic energetic/redox crossroads remains to be defined in greater detail. Recent Advances: We review how high glucose alters cellular redox balance and affects mitochondrial DNA. Next, we address how lipid excess, either stored in lipid droplets or utilized by mitochondria, affects performance in diabetic hearts by influencing cardiac energetic and redox assets. Finally, we examine how the reciprocal energetic/redox influence between mitochondrial and cytoplasmic compartments shapes myocardial mechanical activity during the course of DC, focusing especially on the glutathione and thioredoxin systems. Future Directions: Protecting mitochondria from losing their ability to generate energy, and to control their own reactive oxygen species emission is essential to prevent the onset and/or to slow down DC progression. We highlight mechanisms enforced by the diabetic heart to counteract glucose/FAs surplus-induced damage, such as lipid storage, enhanced mitochondria-lipid droplet interaction, and upregulation of key antioxidant enzymes. Learning more on the nature and location of mechanisms sheltering mitochondrial functions would certainly help in further optimizing therapies for human DC. Antioxid. Redox Signal. 22, 1563–1586. PMID:25674814

  7. Functions for the cardiomyokine, MANF, in cardioprotection, hypertrophy and heart failure

    PubMed Central

    Glembotski, Christopher C.

    2013-01-01

    We define cardiomyokines as heart-derived secreted proteins that affect cardiovascular function via autocrine, paracrine and/or endocrine mechanisms. The subject of this review is the cardiomyokine, mesencephalic astrocyte-derived neurotrophic factor (MANF). The expression of MANF is increased in the ischemic heart, in part, through activation of ER stress, a condition that drastically impairs the expression and secretion of most cardiomyokines. This novel function of MANF suggests that it may have important roles in the ER stressed, ischemic heart. Consistent with this are recent findings showing that MANF protects against ischemic damage, and that it is anti-hypertrophic. Accordingly, in light of its function as a potentially secreted cardiomyokine, MANF has translational potential as a novel therapy for ischemic heart disease. This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure. PMID:20970425

  8. Placebo Sleep Affects Cognitive Functioning

    ERIC Educational Resources Information Center

    Draganich, Christina; Erdal, Kristi

    2014-01-01

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

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

    SciTech Connect

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

    1994-09-01

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

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

    PubMed

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

    2014-05-01

    With approximately 7000 species, snakes and lizards, collectively known as squamates, are by far the most species-rich group of reptiles. It was from reptile-like ancestors that mammals and birds evolved and squamates can be viewed as phylogenetically positioned between them and fishes. Hence, their hearts have been studied for more than a century yielding insights into the group itself and into the independent evolution of the fully divided four-chambered hearts of mammals and birds. Structurally the heart is complex and debates persist on rudimentary issues such as identifying structures critical to understanding ventricle function. In seeking to resolve these controversies we have generated three-dimensional (3D) models in portable digital format (pdf) of the anaconda and anole lizard hearts ('typical' squamate hearts) and the uniquely specialized python heart with comprehensive annotations of structures and cavities. We review the anatomy and physiology of squamate hearts in general and emphasize the unique features of pythonid and varanid lizard hearts that endow them with mammal-like blood pressures. Excluding pythons and varanid lizards it is concluded that the squamate heart has a highly consistent design including a disproportionately large right side (systemic venous) probably due to prevailing pulmonary bypass (intraventricular shunting). Unfortunately, investigations on rudimentary features are sparse. We therefore point out gaps in our knowledge, such as the size and functional importance of the coronary vasculature and of the first cardiac chamber, the sinus venosus, and highlight areas with implications for vertebrate cardiac evolution. PMID:23998743

  11. Functional requirements of a mathematical model of the heart.

    PubMed

    Palladino, Joseph L; Noordergraaf, Abraham

    2009-01-01

    Functional descriptions of the heart, especially the left ventricle, are often based on the measured variables pressure and ventricular outflow, embodied as a time-varying elastance. The fundamental difficulty of describing the mechanical properties of the heart with a time-varying elastance function that is set a priori is described. As an alternative, a new functional model of the heart is presented, which characterizes the ventricle's contractile state with parameters, rather than variables. Each chamber is treated as a pressure generator that is time and volume dependent. The heart's complex dynamics develop from a single equation based on the formation and relaxation of crossbridge bonds. This equation permits the calculation of ventricular elastance via E(v) = partial differentialp(v)/ partial differentialV(v). This heart model is defined independently from load properties, and ventricular elastance is dynamic and reflects changing numbers of crossbridge bonds. In this paper, the functionality of this new heart model is presented via computed work loops that demonstrate the Frank-Starling mechanism and the effects of preload, the effects of afterload, inotropic changes, and varied heart rate, as well as the interdependence of these effects. Results suggest the origin of the equivalent of Hill's force-velocity relation in the ventricle. PMID:19964370

  12. Myoglobin function evaluated in working heart tissue.

    PubMed

    Gardner, J D; Schubert, R W

    1998-01-01

    Previous modeling efforts suggest that myoglobin-facilitated diffusion contributes very little to oxygen transport in a Krebs-Henseleit perfused isolated heart when literature-derived values for the diffusion coefficient of myoglobin (DMb) were used. Simulations have strongly suggested that the contractile mechanisms of muscle may augment diffusion in working preparations. Myoglobin-facilitated oxygen diffusion may be augmented by the same mechanism. In this study, parameters of an oxygen transport to tissue model are optimized to investigate the possibility of elevated diffusion coefficients for oxygen and myoglobin in working heart tissue. The Radially-Averaged, Axially-Distributed (RAAD) model considers axial diffusion of oxygen in tissue, myoglobin facilitation of oxygen transport, and pO2-dependent oxygen consumption (Michaelis-Menten kinetics). Models are solved numerically using a variable-mesh finite-difference scheme. Parameters are optimized using a Nelder-Mead simplex routine and are chosen to minimize the sum-of-squares error (SSE) between model oxygen partial pressure (pO2) predictions and experimental pO2 data. Models are solved both with and without myoglobin facilitation. Myoglobin was found to have little effect on the oxygen distribution predicted by the models. Optimized values for the oxygen diffusion coefficient remained elevated. However, optimized values for myoglobin diffusion coefficient were found to be less than measured values. The RAAD model optimization results suggest that myoglobin does not significantly facilitate oxygen diffusion to tissue in the steady state and that myoglobin diffusion is not elevated in working heart. PMID:9889930

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

    ERIC Educational Resources Information Center

    McLeod, Susan H.

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

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

    NASA Astrophysics Data System (ADS)

    Johnson, Brennan; Garrity, Deborah; Dasi, Lakshmi

    2012-11-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

    Johns, Julia; Patt, Antonia; Hillmann, Edna

    2015-01-01

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

  17. Phosphoinositide-Dependent Kinase 1 and mTORC2 Synergistically Maintain Postnatal Heart Growth and Heart Function in Mice

    PubMed Central

    Zhao, Xia; Lu, Shuangshuang; Nie, Junwei; Hu, Xiaoshan; Luo, Wen; Wu, Xiangqi; Liu, Hailang; Feng, Qiuting; Chang, Zai; Liu, Yaoqiu; Cao, Yunshan; Sun, Haixiang; Li, Xinli; Hu, Yali

    2014-01-01

    The protein kinase Akt plays a critical role in heart function and is activated by phosphorylation of threonine 308 (T308) and serine 473 (S473). While phosphoinositide-dependent kinase 1 (PDK1) is responsible for Akt T308 phosphorylation, the identities of the kinases for Akt S473 phosphorylation in the heart remain controversial. Here, we disrupted mTOR complex 2 (mTORC2) through deletion of Rictor in the heart and found normal heart growth and function. Rictor deletion caused significant reduction of Akt S473 phosphorylation but enhanced Akt T308 phosphorylation, suggesting that a high level of Akt T308 phosphorylation maintains Akt activity and heart function. Deletion of Pdk1 in the heart caused significantly enhanced Akt S473 phosphorylation that was suppressed by removal of Rictor, leading to worsened dilated cardiomyopathy (DCM) and accelerated heart failure in Pdk1-deficient mice. In addition, we found that increasing Akt S473 phosphorylation through deletion of Pten or chemical inhibition of PTEN reversed DCM and heart failure in Pdk1-deficient mice. Investigation of heart samples from human DCM patients revealed changes similar to those in the mouse models. These results demonstrated that PDK1 and mTORC2 synergistically promote postnatal heart growth and maintain heart function in postnatal mice. PMID:24662050

  18. Functions of miRNAs during Mammalian Heart Development

    PubMed Central

    Yan, Shun; Jiao, Kai

    2016-01-01

    MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest cells. Recent data have identified various miRNAs as critical regulators of the proper differentiation, proliferation, and survival of these cell types. In this review, we briefly introduce the contemporary understanding of mammalian cardiac development. We also focus on recent developments in the field of cardiac miRNAs and their functions during the development of different cell types. PMID:27213371

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

    PubMed Central

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

    2015-01-01

    Reduced cardiovascular responses to psychological stressors have been found to be associated with both obesity and negative affect in adults, but have been less well studied in children and adolescent populations. These findings have most often been interpreted as reflecting reduced sympathetic nervous system response, perhaps associated with heightened baseline sympathetic activation among the obese and those manifesting negative affect. However, obesity and negative affect may themselves be correlated, raising the question of whether they both independently affect cardiovascular reactivity. The present study thus examined the separate effects of obesity and negative affect on both cardiovascular and skin conductance responses to stress (e.g., during a serial subtraction math task) in adolescents, while controlling for baseline levels of autonomic activity during rest. Both obesity and negative affect had independent and negative associations with cardiovascular reactivity, such that reduced stress responses were apparent for obese adolescents and those with high levels of negative affect. In contrast, neither obesity nor negative affect was related to skin conductance responses to stress, implicating specifically noradrenergic mechanisms rather than sympathetic mechanisms generally as being deficient. Moreover, baseline heart rate was unrelated to obesity in this sample, which suggests that heightened baseline of sympathetic activity is not necessary for the reduced cardiovascular reactivity to stress. PMID:26049136

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

    NASA Technical Reports Server (NTRS)

    Kuipers, Andre; Cork, Michael; LeGouic, Marine

    2002-01-01

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

  1. How mental stress affects endothelial function.

    PubMed

    Toda, Noboru; Nakanishi-Toda, Megumi

    2011-12-01

    Mental stress is an important factor contributing to recognized mechanisms underlying cardiovascular events. Among these, stress-related endothelial dysfunction is an early risk factor that predicts future development of severe cardiovascular disorders. Acute mental stress by a variety of tests impairs endothelial function in humans, although the opposite results have been reported by some investigators. Chronic stress always deteriorates endothelial function in humans and experimental animals. Stress hormones, such as glucocorticoids and pro-inflammatory cytokines, and endothelin-1 liberated in response to mental stress participate in endothelial dysfunction possibly via downregulation of endothelial nitric oxide synthase (eNOS) expression, eNOS inactivation, decreased nitric oxide (NO) actions, and increased NO degradation, together with vasoconstriction counteracting against NO-induced vasodilatation. Catecholamines do not directly affect endothelial function but impair its function when blood pressure elevation by the amines is sustained. Endogenous opioids favorably affect endothelial function, which counteract deteriorating effects of other stress hormones and mediators. Inhibition of cortisol and endothelin-1 production, prevention of pro-inflammatory mediator accumulation, hypnotics, mirthful laughter, humor orientation, and lifestyle modification would contribute to the prevention and treatment for stress-related endothelial dysfunction and future serious cardiovascular disease. PMID:21947555

  2. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. Estrogen treatment affects brain functioning after menopause.

    PubMed

    Bayer, Ulrike; Hausmann, Markus

    2011-12-01

    Sex hormones have powerful neuromodulatory effects on functional brain organization and cognitive functioning. This paper reviews findings from studies investigating the influence of sex hormones in postmenopausal women with and without hormone therapy (HT). Functional brain organization was investigated using different behavioural tasks in postmenopausal women using either estrogen therapy or combined estrogen plus gestagen therapy and age- and IQ-matched postmenopausal women not taking HT. The results revealed HT-related modulations in specific aspects of functional brain organization including functional cerebral asymmetries and interhemispheric interaction. In contrast to younger women during the menstrual cycle, however, it seems that HT, and especially estrogen therapy, after menopause affects intrahemispheric processing rather than interhemispheric interaction. This might be explained by a faster and more pronounced age-related decline in intrahemispheric relative to interhemispheric functioning, which might be associated with higher sensitivity to HT. Taken together, the findings suggest that the female brain retains its plasticity even after reproductive age and remains susceptible to the effects of sex hormones throughout the lifetime, which might help to discover new clinical approaches in the hormonal treatment of neurological and psychiatric disorders. PMID:22120942

  5. 2D imaging of functional structures in perfused pig heart

    NASA Astrophysics Data System (ADS)

    Kessler, Manfred D.; Cristea, Paul D.; Hiller, Michael; Trinks, Tobias

    2002-06-01

    In 2000 by 2D-imaging we were able for the first time to visualize in subcellular space functional structures of myocardium. For these experiments we used hemoglobin-free perfused pig hearts in our lab. Step by step we learned to understand the meaning of subcellular structures. Principally, the experiment revealed that in subcellular space very fast changes of light scattering can occur. Furthermore, coefficients of different parameters were determined on the basis of multicomponent system theory.

  6. Current aspects of thiamine deficiency on heart function.

    PubMed

    Roman-Campos, Danilo; Cruz, Jader Santos

    2014-03-01

    Beriberi is a disease caused by thiamine deficiency (TD), which may lead to heart problems, including heart failure. Despite the fact that thiamine prevalence is reduced in the industrialized world, it remains a health hazard especially due to chronic alcohol consumption. Diagnosing the presence of TD based on both electrocardiogram and echocardiogram exams is particularly challenging because of its non-specific symptoms. TD diagnosis is unique, which then leads to determination of its severity. If thiamine infusion abrogates its symptomology, only then can the case be definitely diagnosed as TD. Another condition eliciting increased likelihood of developing TD in humans is furosemide administration to heart failure patients. Furosemide administration worsens heart failure due to heightened TD. However, literature data provided are contradictory and require clarification. Up until now, the rat has been the preferred TD animal model. However, the results are even more contradictory than those in humans. It seems that if the rat TD models are separated into two distinct groups, according to animal age, the results appear to be more consistent: younger rats are more prone to develop TD signs similar to those found in humans. Their symptoms stem from changes in cardiac myocyte function that are reversed after thiamine supplementation. However, it remains an open question as to why only younger rats are able to develop human-like symptoms and deserve further investigation. PMID:24398040

  7. Pulmonary function differences in patients with chronic right heart failure secondary to pulmonary arterial hypertension and chronic left heart failure

    PubMed Central

    Liu, Wei-Hua; Luo, Qin; Liu, Zhi-Hong; Zhao, Qing; Xi, Qun-Ying; Xue, Hai-Feng; Zhao, Zhi-Hui

    2014-01-01

    Background Pulmonary abnormalities are found in both chronic heart failure (CHF) and pulmonary arterial hypertension (PAH). The differences of pulmonary function in chronic left heart failure and chronic right heart failure are not fully understood. Material/Methods We evaluated 120 patients with stable CHF (60 with chronic left heart failure and 60 with chronic right heart failure). All patients had pulmonary function testing, including pulmonary function testing at rest and incremental cardiopulmonary exercise testing (CPX). Results Patients with right heart failure had a significantly lower end-tidal partial pressure of CO2 (PetCO2), higher end-tidal partial pressure of O2 (PetO2) and minute ventilation/CO2 production (VE/VCO2) at rest. Patients with right heart failure had a lower peak PetCO2, and a higher peak dead space volume/tidal volume (VD/VT) ratio, peak PetO2, peak VE/VCO2, and VE/VCO2 slope during exercise. Patients with right heart failure had more changes in ΔPetCO2 and ΔVE/VCO2, from rest to exercise. Conclusions Patients with right heart failure had worse pulmonary function at rest and exercise, which was due to severe ventilation/perfusion (V/Q) mismatching, severe ventilation inefficiency, and gas exchange abnormality. PMID:24916204

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

    PubMed Central

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

    2013-01-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities. PMID:24271490

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

    PubMed

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

    2014-02-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities. PMID:24271490

  10. Can lifestyle modification affect men's erectile function?

    PubMed

    Hehemann, Marah C; Kashanian, James A

    2016-04-01

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

  11. Left ventricular function in adult patients with atrial septal defect: implication for development of heart failure after transcatheter closure.

    PubMed

    Masutani, Satoshi; Senzaki, Hideaki

    2011-11-01

    Despite advances in device closure for atrial septal defect (ASD), post-closure heart failure observed in adult patients remains a clinical problem. Although right heart volume overload is the fundamental pathophysiology in ASD, the post-closure heart failure characterized by acute pulmonary congestion is likely because of age-related left ventricular diastolic dysfunction, which is manifested by acute volume loading with ASD closure. Aging also appears to play important roles in the pathophysiology of heart failure through several mechanisms other than diastolic dysfunction, including ventricular systolic and vascular stiffening and increased incidence of comorbidities that significantly affect cardiovascular function. Recent studies suggested that accurate assessment of preclosure diastolic function, such as test ASD occlusion, may help identify high-risk patients for post-closure heart failure. Anti-heart failure therapy before device closure or the use of fenestrated device appears to be effective in preventing post-closure heart failure in the high-risk patients. However, the long-term outcome of such patients remains to be elucidated. Future studies are warranted to construct an algorithm to identify and treat patients at high risk for heart failure after device closure of ASD. PMID:22041334

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

    PubMed

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

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders. PMID:26712328

  13. Gap junction modulation and its implications for heart function

    PubMed Central

    Kurtenbach, Stefan; Kurtenbach, Sarah; Zoidl, Georg

    2014-01-01

    Gap junction communication (GJC) mediated by connexins is critical for heart function. To gain insight into the causal relationship of molecular mechanisms of disease pathology, it is important to understand which mechanisms contribute to impairment of gap junctional communication. Here, we present an update on the known modulators of connexins, including various interaction partners, kinases, and signaling cascades. This gap junction network (GJN) can serve as a blueprint for data mining approaches exploring the growing number of publicly available data sets from experimental and clinical studies. PMID:24578694

  14. Does lung diffusion impairment affect exercise capacity in patients with heart failure?

    PubMed Central

    Agostoni, P G; Bussotti, M; Palermo, P; Guazzi, M

    2002-01-01

    Objective: To determine whether there is a relation between impairment of lung diffusion and reduced exercise capacity in chronic heart failure. Design: 40 patients with heart failure in stable clinical condition and 40 controls participated in the study. All subjects underwent standard pulmonary function tests plus measurements of resting lung diffusion (carbon monoxide transfer, Tlco), pulmonary capillary volume (Vc), and membrane resistance (Dm), and maximal cardiopulmonary exercise testing. In 20 patients and controls, the following investigations were also done: (1) resting and constant work rate Tlco; (2) maximal cardiopulmonary exercise testing with inspiratory O2 fractions of 0.21 and 0.16; and (3) rest and peak exercise blood gases. The other subjects underwent Tlco, Dm, and Vc measurements during constant work rate exercise. Results: In normoxia, exercise induced reductions of haemoglobin O2 saturation never occurred. With hypoxia, peak exercise uptake (peak V̇o2) decreased from (mean (SD)) 1285 (395) to 1081 (396) ml/min (p < 0.01) in patients, and from 1861 (563) to 1771 (457) ml/min (p < 0.05) in controls. Resting Tlco correlated with peak V̇o2 in heart failure (normoxia < hypoxia). In heart failure patients and normal subjects, Tlco and peak V̇o2 correlated with O2 arterial content at rest and during peak exercise in both normoxia and hypoxia. Tlco, Vc, and Dm increased during exercise. The increase in Tlco was greater in patients who had a smaller reduction of exercise capacity with hypoxia. Alveolar–arterial O2 gradient at peak correlated with exercise capacity in heart failure during normoxia and, to a greater extent, during hypoxia. Conclusions: Lung diffusion impairment is related to exercise capacity in heart failure. PMID:12381630

  15. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

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

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype. PMID:26919895

  16. Heart Valve Structure and Function in Development and Disease

    PubMed Central

    Hinton, Robert B.; Yutzey, Katherine E.

    2014-01-01

    The mature heart valves are made up of highly organized extracellular matrix (ECM) and valve interstitial cells (VIC) surrounded by an endothelial cell layer. The ECM of the valves is stratified into elastin-, proteoglycan- and collagen-rich layers that confer distinct biomechanical properties to the leaflets and supporting structures. Signaling pathways have critical functions in primary valvulogenesis as well as maintenance of valve structure and function over time. Animal models provide powerful tools to study valve development and disease processes. Valve disease is a significant public health problem and increasing evidence implicates aberrant developmental mechanisms underlying pathogenesis. Further studies are necessary to determine regulatory pathway interactions underlying pathogenesis in order to generate new avenues for novel therapeutics. PMID:20809794

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

    PubMed

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

    2015-11-01

    Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n=8) having values of 23-29 °C, and high-temperature group (n=18) having values of 32-36 °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4 °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2 °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50 ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology. PMID:26340855

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

    PubMed

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

    2015-10-01

    High frequency heart rate variability (HRV) is a measure of neurocardiac communication thought to reflect predominantly parasympathetic cardiac regulation. Low HRV has been associated empirically with clinical and subclinical levels of anxiety and depression and, more recently, high levels of HRV have been associated with better performance on some measures of executive functioning (EF). These findings have offered support for theories proposing HRV as an index measure of a broad, self-regulatory capacity underlying aspects of emotion regulation and executive control. This study sought to test that proposition by using a structural equation modeling approach to examine the relationships of HRV to negative affect (NA) and EF in a large sample of U.S. adults ages 30s-80s. HRV was modeled as a predictor of an NA factor (self-reported trait anxiety and depression symptoms) and an EF factor (performance on three neuropsychological tests tapping facets of executive abilities). Alternative models also were tested to determine the utility of HRV for predicting NA and EF, with and without statistical control of demographic and health-related covariates. In the initial structural model, HRV showed a significant positive relationship to EF and a nonsignificant relationship to NA. In a covariate-adjusted model, HRV's associations with both constructs were nonsignificant. Age emerged as the only significant predictor of NA and EF in the final model, showing inverse relationships to both. Findings may reflect population and methodological differences from prior research; they also suggest refinements to the interpretations of earlier findings and theoretical claims regarding HRV. PMID:26168884

  19. Left atrial booster function in valvular heart disease

    PubMed Central

    Heidenreich, Fred P.; Shaver, James A.; Thompson, Mark E.; Leonard, James J.

    1970-01-01

    This study was designed to assess atrial booster pump action in valvular heart disease and to dissect booster pump from reservoir-conduit functions. In five patients with aortic stenosis and six with mitral stenosis, sequential atrioventricular (A-V) pacing was instituted during the course of diagnostic cardiac catheterization. Continuous recording of valvular gradient allowed estimation of flow for each cardiac cycle by transposition of the Gorlin formula. Left ventricular ejection time and left ventricular stroke work in aortic stenosis or left ventricular mean systolic pressure in mitral stenosis were also determined. Control observations were recorded during sequential A-V pacing with well-timed atrial systole. Cardiac cycles were then produced with no atrial contraction but undisturbed atrial reservoir function by intermittently interrupting the atrial pacing stimulus during sequential A-V pacing. This intervention significantly reduced valvular gradient, flow, left ventricular ejection time, and left ventricular mean systolic pressure or stroke work. Cardiac cycles were then produced with atrial booster action eliminated by instituting synchronous A-V pacing. The resultant simultaneous contraction of the atrium and ventricle not only eliminated effective atrial systole but also placed atrial systole during the normal period of atrial reservoir function. This also significantly reduced all the hemodynamic measurements. However, comparison of the magnitude of change from these two different pacing interventions showed no greater impairment of hemodynamic state when both booster pump action and reservoir function were impaired than when booster pump action alone was impaired. The study confirms the potential benefit of well placed atrial booster pump action in valvular heart disease in man. PMID:5449701

  20. CoQ₁₀ Function and Role in Heart Failure and Ischemic Heart Disease.

    PubMed

    Ayer, Anita; Macdonald, Peter; Stocker, Roland

    2015-01-01

    Coenzyme Q (CoQ) is an essential lipid of cells present in all cellular compartments. The functions of CoQ in mitochondrial respiration and as an antioxidant are established, although the lipid likely has additional, presently unknown, roles. While the therapeutic utility of CoQ10 supplements is recognized in the rare cases of primary CoQ10 deficiencies, a potential role for CoQ10 supplements in cardiovascular disease, particularly heart failure, has also been studied for over 40 years. This review summarizes our current knowledge in these areas derived from animal studies and human trials. Current evidence for a benefit of CoQ10 supplements in diseases other than primary CoQ10 deficiencies is insufficient. PMID:25974695

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

    SciTech Connect

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

    1984-02-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Mendler, Luca; Braun, Thomas; Müller, Stefan

    2016-01-01

    SUMOylation is a ubiquitin-related transient posttranslational modification pathway catalyzing the conjugation of small ubiquitin-like modifier (SUMO) proteins (SUMO1, SUMO2, and SUMO3) to lysine residues of proteins. SUMOylation targets a wide variety of cellular regulators and thereby affects a multitude of different cellular processes. SUMO/sentrin-specific proteases are able to remove SUMOs from targets, contributing to a tight control of SUMOylated proteins. Genetic and cell biological experiments indicate a critical role of balanced SUMOylation/deSUMOylation for proper cardiac development, metabolism, and stress adaptation. Here, we review the current knowledge about SUMOylation/deSUMOylation in the heart and provide an integrated picture of cardiac functions of the SUMO system under physiologic or pathologic conditions. We also describe potential therapeutic approaches targeting the SUMO machinery to combat heart disease. PMID:26837744

  5. Fish Consumption, Sleep, Daily Functioning, and Heart Rate Variability

    PubMed Central

    Hansen, Anita L.; Dahl, Lisbeth; Olson, Gina; Thornton, David; Graff, Ingvild E.; Frøyland, Livar; Thayer, Julian F.; Pallesen, Staale

    2014-01-01

    Study Objectives: This study investigated the effects of fatty fish on sleep, daily functioning and biomarkers such as heart rate variability (HRV), vitamin D status (serum 25-hydroxyvitamin D (25OHD), and eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3) in red blood cells. Moreover the relationship among sleep, daily functioning, HRV, vitamin D status, and levels of EPA+DHA was investigated. Methods: Ninety-five male forensic patients from a secure forensic inpatient facility in the USA were randomly assigned into a Fish or a Control group. The Fish group received Atlantic salmon three times per week from September to February, and the Control group was provided an alternative meal (e.g., chicken, pork, beef), but with the same nutritional value as their habitual diet, three times per week during the same period. Sleep (sleep latency, sleep efficiency, actual sleep time, and actual wake time), self-perceived sleep quality and daily functioning, as well as vitamin D status, EPA+DHA, and HRV, were assessed pre- and post-intervention period. Results: There was a significant increase in sleep latency from pre- to post-test in the Control group. The Fish group reported better daily functioning than the Control group during post-test. Fish consumption throughout the wintertime had also an effect on resting HRV and EPA+DHA, but not on vitamin D status. However, at post-test, the vitamin D status in the Fish group was still closer to the level regarded as optimal compared to the Control group. Vitamin D status correlated negatively with actual wake time and positively with sleep efficiency during pre-test, as well as positively with daily functioning and sleep quality during post-test. Finally, HRV correlated negatively with sleep latency and positively with daily functioning. Conclusions: Fish consumption seemed to have a positive impact on sleep in general and also on daily functioning, which may be related to vitamin D status and HRV. Citation

  6. Effect of Renal Function on Prognosis in Chronic Heart Failure

    PubMed Central

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

    2014-01-01

    Renal dysfunction (RD) is associated with increased mortality in heart failure (HF). The aim of this study was to identify whether worsened or improved renal function during mid-term follow-up is associated with worsened outcomes in chronic HF patients. 892 participants from a multicenter cohort study of chronic HF were followed over 3.1±1.9 years of enrollment. Worsened and improved renal function were tested with multivariable models as independent predictors of HF hospitalization and mortality. While 12% of subjects experienced a ≥25% decrease in estimated glomerular filtration rate (eGFR), 17% experienced a ≥25% increase in eGFR, and there was stability of kidney function observed in the cohort as a whole. The quartile with the worst RD at any point in time had increased risk of HF hospitalization and mortality. Worsened eGFR was associated with HF outcomes in the unadjusted (HR=1.71 (95%CI 1.04-2.81), p=0.035), but not the adjusted analysis. Improvement in eGFR was not associated with outcome (p=0.453). In chronic HF, the severity of RD predicts risk of poor outcome better than changes in renal function during mid-term follow-up. This suggests that in patients with appropriately treated chronic HF, worsening renal function in itself does not yield useful prognostic information and may not reflect poor outcome. PMID:25465925

  7. Dynamic heart-in-thorax phantom for functional SPECT

    SciTech Connect

    Celler, A.; Lyster, D.; Farncombe, T.

    1996-12-31

    We have designed and built a dynamic heart-in-thorax phantom to be used as a primary tool during the experimental verification of the performance of the quantitative dynamic functional imaging method we are developing for standard rotating single photon emission computed tomography (SPECT) cameras. The phantom consists of two independent parts (i) a dynamic heart model with the possibility of mounting {open_quotes}defects{close_quotes} inside it and (ii) a non-uniform thorax model with lungs and spinal cord, and uses the fact that the washout of a tracer by dilution is governed by a linear first order equation, the same type of equation as is used to model time-activity distribution in myocardial viability studies. Tests of the dynamic performance of the phantom in planar scanning mode have confirmed the validity of these assumptions. Also the preliminary results obtained in SPECT mode show that the values of characteristic times could be experimentally determined and that these values agreed well with the values preset on the phantom. We consider that the phantom is ready for extensive use in studies into development of the dynamic SPECT method.

  8. Preserved Left Ventricular, Systolic Function in Clinical Congestive Heart Failure

    PubMed Central

    Lee, Bang Hun; Kim, Jeong Hyun; Lim, Heon Kil; Lee, Chung Kyun

    1987-01-01

    Although clinical congestive heart failure (CHF) is associated with significant left ventricular (LV) systolic dysfunction, recently it has been recognized that LV diastolic dysfunction also may occur in the absence of abnormal systolic performance. A retrospective study evaluated 23 patients with myocardial infarction and CHF who had undergone multigated blood pool scintigraphy and were found to have normal LV ejection fraction (≥ 50%). Average rapid filling velocity (RFV) and slow filling velocity (SFV) were both significantly reduced in CHF patients (5.1 ± 1.3 unit/s, 2.2 ± 1.4 unit/s respectively) compared with normal control group (3.9 ± 1.2 unit/s, 1.3 ± 0.8 unit/s respectively). Rapid filling time and total diastolic time were also significantly prolonged in CHF patients (p<0.01, p<0.05 respectively). There were no significant changes in heart rate and blood pressure between two groups. Thus, normal systolic LV function is encountered in patients with CHF and it appears to be prudent to evaluate diastolic performance as well for optimal therapeutic strategies for CHF patients. PMID:3154818

  9. Cardiac cytoarchitecture - why the "hardware" is important for heart function!

    PubMed

    Ehler, Elisabeth

    2016-07-01

    Cells that constitute fully differentiated tissues are characterised by an architecture that makes them perfectly suited for the job they have to do. This is especially obvious for cardiomyocytes, which have an extremely regular shape and display a paracrystalline arrangement of their cytoplasmic components. This article will focus on the two major cytoskeletal multiprotein complexes that are found in cardiomyocytes, the myofibrils, which are responsible for contraction and the intercalated disc, which mediates mechanical and electrochemical contact between individual cardiomyocytes. Recent studies have revealed that these two sites are also crucial in sensing excessive mechanical strain. Signalling processes will be triggered that## lead to changes in gene expression and eventually lead to an altered cardiac cytoarchitecture in the diseased heart, which results in a compromised function. Thus, understanding these changes and the signals that lead to them is crucial to design treatment strategies that can attenuate these processes. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26577135

  10. Recompensation of heart and kidney function after treatment with peritoneal dialysis in a case of congestive heart failure.

    PubMed

    Kihm, Lars P; Hankel, Vinzent; Zugck, Christian; Remppis, Andrew; Schwenger, Vedat

    2011-01-01

    We report the case of a 57-year-old woman suffering from congestive heart failure. Due to refractory congestions despite optimised medical treatment, the patient was listed for heart transplantation and peritoneal dialysis was initiated. Peritoneal dialysis led to a significant weight loss, reduction of hyperhydration and extracellular water obtained by bioimpedance measurement, and a significant improvement in clinical and echocardiographic examination. Furthermore, residual kidney function increased during the long-term followup, and subsequently peritoneal dialysis was ceased. Pulmonary artery pressure and left ventricular ejection fraction remained stable and the patient did well. This case demonstrates the possibility of treating hyperhydration due to congestive heart failure with peritoneal dialysis resulting in recompensation of both heart and kidney functions. PMID:22162698

  11. Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure.

    PubMed

    Coggan, Andrew R; Peterson, Linda R

    2016-08-01

    Heart failure (HF) patients suffer from exercise intolerance that diminishes their ability to perform normal activities of daily living and hence compromises their quality of life. This is due largely to detrimental changes in skeletal muscle mass, structure, metabolism, and function. This includes an impairment of muscle contractile performance, i.e., a decline in the maximal force, speed, and power of muscle shortening. Although numerous mechanisms underlie this reduction in contractility, one contributing factor may be a decrease in nitric oxide (NO) bioavailability. Consistent with this, recent data demonstrate that acute ingestion of NO3 (-)-rich beetroot juice, a source of NO via the NO synthase-independent enterosalivary pathway, markedly increases maximal muscle speed and power in HF patients. This review discusses the role of muscle contractile dysfunction in the exercise intolerance characteristic of HF, and the evidence that dietary NO3 (-) supplementation may represent a novel and simple therapy for this currently underappreciated problem. PMID:27271563

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Sex Differences in Patients With Acute Decompensated Heart Failure: Insights From the Heart Function Assessment Registry Trial in Saudi Arabia.

    PubMed

    AlFaleh, Hussam F; Thalib, Lukman; Kashour, Tarek; Hersi, Ahmad; Mimish, Layth; Elasfar, Abdelfatah A; Almasood, Ali; Al Ghamdi, Saleh; Ghabashi, Abdullah; Malik, Asif; Hussein, Gamal A; Al-Murayeh, Mushabab; Abuosa, Ahmed; Al Habeeb, Waleed; Al Habib, Khalid F

    2016-08-01

    We assessed sex-specific differences in clinical features and outcomes of patients with acute heart failure (AHF). The Heart function Assessment Registry Trial in Saudi Arabia (HEARTS), a prospective registry, enrolled 2609 patients with AHF (34.2% women) between 2009 and 2010. Women were older and more likely to have risk factors for atherosclerosis, history of heart failure (HF), and rheumatic heart and valve disease. Ischemic heart disease was the prime cause for HF in men and women but more so in men (P < .001). Women had higher rates of hypertensive heart disease and primary valve disease (P < .001, for both comparisons). Men were more likely to have severe left ventricular systolic dysfunction. On discharge, a higher use of angiotensin-converting enzyme inhibitors, β-blockers, and aldosterone inhibitors was observed in men (P < .001 for all comparisons). Apart from higher atrial fibrillation in women and higher ventricular arrhythmias in men, no differences were observed in hospital outcomes. The overall survival did not differ between men and women (hazard ratio: 1.0, 95% confidence interval: 0.8-1.2, P = .981). Men and women with AHF differ significantly in baseline clinical characteristics and management but not in adverse outcomes. PMID:26438635

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

    EPA Science Inventory

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

  16. Does iron deficiency anemia affect olfactory function?

    PubMed

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

    2016-07-01

    Conclusion This study found a negative effect of IDA on olfactory function. IDA leads to a reduction in olfactory function, and decreases in hemoglobin levels result in further reduction in olfactory function. Objective This study examined the effects of iron-deficiency anemia (IDA) on olfactory function. Method The study enrolled 50 IDA patients and 50 healthy subjects. Olfactory function was evaluated using the Sniffin' Sticks olfactory test. The diagnosis of IDA was made according to World Health Organization (WHO) criteria. Results Patients with IDA had a significantly lower threshold, discrimination, and identification (TDI) value, and a lower threshold compared with the control group. However, there were no significant differences between the groups in terms of smell selectivity values. PMID:26963317

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

    PubMed

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

    2014-11-01

    The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-β signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm. PMID:25282101

  18. Prevalence of Isolated Atrial Amyloidosis in Young Patients Affected by Congestive Heart Failure

    PubMed Central

    Millucci, Lia; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Tanganelli, Piero; Santucci, Annalisa

    2012-01-01

    Atrial natriuretic peptide (ANP), whose amyloid is responsible of isolated atrial amyloidosis (IAA), is known to play an important role in the pathophysiology of congestive heart failure (CHF). We provide here the microscopic examination of atrial biopsies from 36 young (mean 40 years) CHF patients distinguished in idiopathic dilated cardiomyopathy (DC) affected and hypertrophic Cardiomyopathy (HC) affected, endorsing the presumptive association of early CHF with IAA. We utilized a multiple method, using Congo red (CR) staining, CR fluorescence (CRF), and immunohistochemistry to assess the presence of IAA in CHF. Immunostaining showed a moderate deposition of IAA in the atrium surrounding working myocardium with small intracellular deposits. Our findings suggest a monitoring of young CHF cases for the development of IAA. Our study also demonstrated how the concurrent use of immunohistochemistry, CR, and CRF may greatly enhance the detection of low-grade amyloid deposits. PMID:22536133

  19. Prevalence of isolated atrial amyloidosis in young patients affected by congestive heart failure.

    PubMed

    Millucci, Lia; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Tanganelli, Piero; Santucci, Annalisa

    2012-01-01

    Atrial natriuretic peptide (ANP), whose amyloid is responsible of isolated atrial amyloidosis (IAA), is known to play an important role in the pathophysiology of congestive heart failure (CHF). We provide here the microscopic examination of atrial biopsies from 36 young (mean 40 years) CHF patients distinguished in idiopathic dilated cardiomyopathy (DC) affected and hypertrophic Cardiomyopathy (HC) affected, endorsing the presumptive association of early CHF with IAA. We utilized a multiple method, using Congo red (CR) staining, CR fluorescence (CRF), and immunohistochemistry to assess the presence of IAA in CHF. Immunostaining showed a moderate deposition of IAA in the atrium surrounding working myocardium with small intracellular deposits. Our findings suggest a monitoring of young CHF cases for the development of IAA. Our study also demonstrated how the concurrent use of immunohistochemistry, CR, and CRF may greatly enhance the detection of low-grade amyloid deposits. PMID:22536133

  20. Dynamic heart phantom with functional mitral and aortic valves

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  1. American Heart Association’s Life’s Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function

    PubMed Central

    Folsom, Aaron R.; Shah, Amil M.; Lutsey, Pamela L.; Roetker, Nicholas S.; Alonso, Alvaro; Avery, Christy L.; Miedema, Michael D.; Konety, Suma; Chang, Patricia P.; Solomon, Scott D.

    2015-01-01

    BACKGROUND Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association’s Life’s Simple 7 guidelines -- on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose -- is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults aged 45-64 years in 1987-89. From the 1987-89 risk factor measurements, we created a Life’s Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2,218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4,855 participants free of clinical cardiovascular disease in 2011-13, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS One in four participants (25.5%) developed heart failure through age 85. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life’s Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life’s Simple 7 score compared with an inadequate score. CONCLUSIONS Greater achievement of American Heart Association’s Life’s Simple 7 in middle-age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. PMID:25908393

  2. [Structure and function of the heart according to body weight in men of working age].

    PubMed

    Dudar, L V; Honcharenko, L I; Ovdiĭ, M O

    2014-01-01

    The scientific structure and function heart in 65 working age men according to weight and body composition. The shown that the excess body weight observed a significant increase in the size and volume left ventricle of the heart and myocardial mass. The percentage of muscle mass in the body of the patients positively correlated with systolic function of the heart, while the percentage of body fat had a negative correlation with this index. The shown that the individualization of health exercise should take into account the percentage of the active body weight and fat mass in the body, since the high content of fat intense exercise can lead to heart and remodeling worsening left ventricular systolic function heart, while increasing BMI due to muscle does not contribute to the structural and functional reorganization of the heart. PMID:24908966

  3. A phenotypic in vitro model for the main determinants of human whole heart function.

    PubMed

    Stancescu, Maria; Molnar, Peter; McAleer, Christopher W; McLamb, William; Long, Christopher J; Oleaga, Carlota; Prot, Jean-Matthieu; Hickman, James J

    2015-08-01

    This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems. PMID:25978005

  4. A phenotypic in vitro model for the main determinants of human whole heart function

    PubMed Central

    Stancescu, Maria; Molnar, Peter; McAleer, Christopher W.; McLamb, William; Long, Christopher J.; Oleaga, Carlota; Prot, Jean-Matthieu; Hickman, James J.

    2015-01-01

    This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model featured a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems. PMID:25978005

  5. Hydrodynamic function of polyurethane prosthetic heart valves: influences of Young's modulus and leaflet thickness.

    PubMed

    Bernacca, Gillian M; O'Connor, Bernard; Williams, David F; Wheatley, David J

    2002-01-01

    The development of flexible polyurethane heart valves has been hindered by material degradation in vivo. Low modulus polyurethane leaflets are regarded as desirable to achieve good hydrodynamic function. However, low modulus materials may suffer high strain accumulation, hence poor durability. Higher modulus materials may improve durability, but may have poor hydrodynamic function. This study examines the hydrodynamic behaviour of biostable polyurethane valves, varying Young's modulus from 5 to 63.6 MPa and mean leaflet thickness from 48-238 microm. Parameters studied included mean pressure gradient, energy losses and regurgitation over 5 equivalent cardiac outputs (3.6, 4.9, 6.4, 8.0 and 9.61 min(-1)) At low cardiac output, modulus was not significantly correlated with any parameter of valve opening. At 9.61 min(-1), modulus significantly influenced mean pressure gradient (p = 0.033). Mean leaflet thickness significantly correlated with mean pressure gradient and energy losses during forward flow at all cardiac outputs (p<0.001). This study demonstrates that, over a wide range of moduli, valve hydrodynamic function is not affected significantly by the material modulus. Leaflet thickness is a highly significant factor. Higher modulus elastomers in a range up to 32.5 MPa may be useful in prosthetic heart valve leaflet manufacture, retaining good hydrodynamic function while potentially extending the lifetime of the valve. PMID:11762853

  6. Miniature implantable instrument measures and transmits heart function data

    NASA Technical Reports Server (NTRS)

    Lee, R. D.

    1971-01-01

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

  7. Exercise training affects age-induced changes in SOD and heat shock protein expression in rat heart.

    PubMed

    Rinaldi, Barbara; Corbi, Graziamaria; Boccuti, Silvia; Filippelli, Walter; Rengo, Giuseppe; Leosco, Dario; Rossi, Francesco; Filippelli, Amelia; Ferrara, Nicola

    2006-08-01

    The aim of this study was to test the effects of age and chronic exercise training on antioxidant and heat shock protein (Hsp) expression by comparing the hearts of young (Y), sedentary old (SO) and trained old (TO) rats. In SO rats, there were: (a) changes in myocardial structure and function; (b) increased malondialdehyde levels; (c) no changes in superoxide-dismutase (SOD) enzymes; (d) reduced Hsp70 expression; and (e) increased Hsp27 expression. In TO rats, SOD enzymes and Hsp70 expression were increased and Hsp27 was further increased. Malondialdehyde level did not differ between TO and SO rats, which shows that chronic exercise did not affect the peroxidation index. In summary, by increasing Hsp27 and Hs70 levels, prolonged exercise partially counterbalanced the heart age-related effects in the antioxidant system without altering peroxidation levels. These findings suggest that the beneficial effects on aged-related cardiovascular changes could be connected to the "anti-oxidant" effects of prolonged exercise training. PMID:16822632

  8. Anomalies of left coronary artery origin affecting surgical repair of hypoplastic left heart syndrome and Shone complex.

    PubMed

    Saroli, Tania; Gelehrter, Sarah; Gomez-Fifer, Carlen A; van der Velde, Mary E; Bove, Edward L; Ensing, Gregory J

    2008-08-01

    There has traditionally been less concern regarding coronary anomalies with left-sided congenital heart lesions such as hypoplastic left heart syndrome (HLHS)or Shone complex than with other lesions. However, coronary anomalies in this setting can profoundly affect surgical intervention, particularly when surgical repair involves the ascending aorta. We describe four patients with congenital left-sided heart lesions in which left coronary artery (LCA) anomalies substantially affected intervention and outcome. In the first two cases, the coronary anomalies were not identified prospectively and resulted in surgical injury directly to the coronary or to its surrounding region. In the latter two cases, successful identification of the coronary anomaly preoperatively allowed for modification of surgical technique and/or intervention. We conclude that detailed coronary artery assessment should be part of the routine echocardiographic evaluation of congenital left-sided heart lesions that require surgery. PMID:18445061

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

    PubMed

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

    2016-03-01

    Implantation of a total artificial heart (TAH) is one of the therapeutic options for the treatment of patients with end-stage biventricular heart failure. There is no report on the hemodynamics of the functional centrifugal-flow TAH with functional atrial contraction (fCFTAH). We evaluated the effects of pulsatile flow by atrial contraction in acute animal models. The goats received fCFTAH that we created from two centrifugal-flow ventricular assist devices. Some hemodynamic parameters maintained acceptable levels: heart rate 115.5 ± 26.3 bpm, aortic pressure 83.5 ± 10.1 mmHg, left atrial pressure 18.0 ± 5.9 mmHg, pulmonary pressure 28.5 ± 9.7 mmHg, right atrial pressure 13.6 ± 5.2 mmHg, pump flow 4.0 ± 1.1 L/min (left) 3.9 ± 1.1 L/min (right), and cardiac index 2.13 ± 0.14 L/min/m(2). fCFTAH with atrial contraction was able to maintain the TAH circulation by forming a pulsatile flow in acute animal experiments. Taking the left and right flow rate balance using the low internal pressure loss of the VAD pumps may be easier than by other pumps having considerable internal pressure loss. We showed that the remnant atrial contraction effected the flow rate change of the centrifugal pump, and the atrial contraction waves reflected the heart rate. These results indicate that remnant atria had the possibility to preserve autonomic function in fCFTAH. We may control fCFTAH by reflecting the autonomic function, which is estimated with the flow rate change of the centrifugal pump. PMID:26198448

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-09-01

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

  12. Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

    PubMed Central

    Polegato, Bertha F.; Minicucci, Marcos F.; Azevedo, Paula S.; Gonçalves, Andréa F.; Lima, Aline F.; Martinez, Paula F.; Okoshi, Marina P.; Okoshi, Katashi; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Background Heart failure prediction after acute myocardial infarction may have important clinical implications. Objective To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. Methods The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. Results Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. Conclusion In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset. PMID:26815462

  13. Factors affecting regional pulmonary blood flow in chronic ischemic heart disease

    SciTech Connect

    Pistolesi, M.; Miniati, M.; Bonsignore, M.; Andreotti, F.; Di Ricco, G.; Marini, C.; Rindi, M.; Biagini, A.; Milne, E.N.; Giuntini, C.

    1988-07-01

    To assess the effect of left heart disease on pulmonary blood flow distribution, we measured mean pulmonary arterial and wedge pressures, cardiac output, pulmonary vascular resistance, pulmonary blood volume, and arterial oxygen tension before and after treatment in 13 patients with longstanding ischemic heart failure and pulmonary edema. Pulmonary edema was evaluated by a radiographic score, and regional lung perfusion was quantified on a lung scan by the upper to lower third ratio (U:L ratio) of pulmonary blood flow per unit of lung volume. In all cases, redistribution of lung perfusion toward the apical regions was observed; this pattern was not affected by treatment. After treatment, pulmonary vascular pressures, resistance, and edema were reduced, while pulmonary blood volume did not change. At this time, pulmonary vascular resistance showed a positive correlation with the U:L ratio (r = 0.78; P less than 0.01), whereas no correlation was observed between U:L ratio and wedge pressure, pulmonary edema, or arterial oxygen tension. Hence, redistribution of pulmonary blood flow, in these patients, reflects chronic structural vascular changes prevailing in the dependent lung regions.

  14. Factors affecting nurses' intent to assess for depression in heart failure patients.

    PubMed

    Lea, Patricia

    2014-01-01

    The association between depression and cardiovascular disease has been well established and has been shown to decrease patients' quality of life and increase the risk of mortality, frequency and duration of hospitalization, and health care costs. The inpatient setting provides a potentially valuable opportunity to assess and treat depression among patients with acute cardiac illness, allowing for daily monitoring of treatment side effects. Although systematic depression screening appears to be feasible, efficient, and well accepted on inpatient cardiac units, the current lack of consistent inpatient assessment for depression in heart failure patients suggests the presence of barriers influencing the effective diagnosis and treatment of depression among inpatients with heart failure. The theory of planned behavior describes the cognitive mechanism by which behavioral intent is formed, giving some insight into how nurses' attitudes and beliefs affect their performance of routine depression screening. In addition, application of this cognitive theory suggests that nurses may be influenced to adopt more positive attitudes and beliefs about depression through educational intervention, leading to greater likelihood of routine assessment for depression, ultimately leading to more timely diagnosis and treatment and improved patient outcomes. PMID:25280199

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

    PubMed

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

    2016-06-27

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. PMID:27353089

  16. Executive Dysfunction is Independently Associated with Reduced Functional Independence in Heart Failure

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Raz, Naftali; Cohen, Ronald; Sweet, Lawrence H.; Colbert, Lisa H.; Josephson, Richard; van Dulmen, Manfred; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Aims and Objectives To examine the independent association between executive function with instrumental activities of daily living and health behaviors in older adults with heart failure. Background Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision-making, planning, organizing, and behavioral monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined. Design Cross-sectional analyses. Methods 175 heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton-Brody instrumental activities of daily living scale and reported current cigarette use. Results Hierarchical regressions revealed reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed executive dysfunction was associated with current cigarette use. Conclusions Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviors in heart failure. Future studies should examine whether heart failure patients benefit from formal organization schemae (i.e., pill organizers) to maintain independence. Relevance to Clinical Practice Screening of executive function in heart failure patients may provide key insight into their ability to perform daily tasks, including management of treatment recommendations. PMID:23650879

  17. Assessment of systolic and diastolic function in heart failure using ambulatory monitoring with acoustic cardiography.

    PubMed

    Dillier, Roger; Zuber, Michel; Arand, Patricia; Erne, Susanne; Erne, Paul

    2011-08-01

    INTRODUCTION. The circadian variation of heart function and heart sounds in patients with and without heart failure (HF) is poorly understood. We hypothesized HF patients would exhibit less circadian variation with worsened cardiac function and sleep apnea. METHODS. We studied 67 HF patients (age 67.4 ± 8.2 years; 42% acute HF) and 63 asymptomatic control subjects with no history of HF (age 61.6 ± 7.7 years). Subjects wore a heart sound/ECG/respiratory monitor. The data were analyzed for sleep apnea, diastolic heart sounds, and systolic time intervals. RESULTS. The HF group had significantly greater prevalence of the third heart sound and prolongation of electro-mechanical activation time, while the control group had an age-related increase in the prevalence of the fourth heart sound. The control group showed more circadian variation in cardiac function. The HF subjects had more sleep apnea and higher occurrence of heart rate non-dipping. CONCLUSIONS. The control subjects demonstrated an increasing incidence of diastolic dysfunction with age, while systolic function was mostly unchanged with aging. Parameters related to systolic function were significantly worse in the HF group with little diurnal variation, indicating a constant stimulation of sympathetic tone in HF and reduction of diurnal regulation. PMID:21361859

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

    NASA Astrophysics Data System (ADS)

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

    2005-05-01

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

  19. [The effect of argan oil on heart function during ischemia and reperfusion].

    PubMed

    Benajiba, N; Morel, S; De Leiris, J; Boucher, F; Charrouf, Z; Mokhtar, N; Aguenaou, H

    2002-01-01

    The aim of this study was to evaluate the effect of organ oil on isolated heart function before and after ischemia and on the activity of cardiac antioxidant enzymes. 16 Wistar rats were divided into 2 groups; control group and treated group receiving 5 mL/kg/day of organ oil. After 8 weeks of treatment, hearts were perfused and subjected to a global ischemia followed by reperfusion. Activity of cardiac antioxidant enzymes was assessed in freeze-clamped hearts at the end of reperfusion. Results showed that organ oil induces: 1--damage to heart function during the preischemic period, 2--decreased functional recovery during reperfusion and 3--significant increase in catalase activity. It seems that, in our experimental conditions, organ oil increases heart sensitivity to ischemia and reperfusion. However, the mechanism involved has yet to be understood. PMID:12422535

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

    PubMed Central

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

    2015-01-01

    The precise contributions of afferent feedback to cardiovascular and respiratory responses to exercise are still unclear. The aim of this crossover study was to assess whether and how autonomic cardiovascular and respiratory control differed in response to dynamic (DYN) and isometric contractions (ISO) at a similar, low heart rate (HR) level. Therefore, 22 healthy males (26.7 ± 3.6 yrs) performed two kinds of voluntary exercises at similar HR: ISO and DYN of the right quadriceps femoris muscle. Although HR was eqivalent (82 ± 8 bpm for DYN and ISO, respectively), rating of exertion, blood pressures, and rate pressure product were higher, whereas breathing frequency, minute ventilation, oxygen uptake and carbon dioxide output were significantly lower during ISO. Tidal volume, end-tidal partial pressures of O2 and CO2, respiratory exchange ratio and capillary blood lactate concentration were comparable between both contraction modes. Heart rate variability (HRV) indicators, SDNN, HF-Power and LF-Power, representing both vagal and sympathetic influences, were significantly higher during ISO. Sample entropy, a non-linear measure of HRV was also significantly affected by contraction mode. It can be concluded that, despite the same net effect on HR, the quality of cardiovascular control during low intensity exercise is significantly different between DYN and ISO. HRV analysis indicated a sympatho-vagal coactivation during ISO. Whether mechanoreceptor feedback alone, a change in central command, or the interaction of both mechanisms is the main contributor of the distinct autonomic responses to the different exercise modes remains to be elucidated. PMID:26042047

  1. Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure

    PubMed Central

    Millucci, Lia; Paccagnini, Eugenio; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Laschi, Marcella; Consumi, Marco; Spreafico, Adriano; Tanganelli, Piero; Lupetti, Pietro; Magnani, Agnese; Santucci, Annalisa

    2011-01-01

    Aims Atrial Natriuretic Peptide (ANP)-containing amyloid is frequently found in the elderly heart. No data exist regarding ANP aggregation process and its link to pathologies. Our aims were: i) to experimentally prove the presumptive association of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby elucidating IAA implication in the CHF pathogenesis. Methods and Results A significant prevalence (85%) of IAA was immunohistochemically proven ex vivo in biopsies from CHF patients. We investigated in vitro (using Congo Red, Thioflavin T, SDS-PAGE, transmission electron microscopy, infrared spectroscopy) ANP fibrillogenesis, starting from α-ANP as well as the ability of dimeric β-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing β-ANP prevalence in CHF. Our results defined the uncommon rapidity of α-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the onset of a fibrillization process subsequently proceeding at physiological pH. Interestingly, CHF-like conditions induced the production of the most stable and time-resistant ANP fibrils suggesting that CHF affected people may be prone to develop IAA. Conclusions We established a link between IAA and CHF by ex vivo examination and assessed that β-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that β-ANP plays a crucial role in ANP amyloid deposition under physiopathological CHF conditions. Overall, our findings indicate that early IAA-related ANP deposition may occur in CHF and suggest that these latter patients should be monitored for the development of cardiac amyloidosis. PMID:21814559

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Wohlgemuth, Serene L.; Pilgrim, David B.

    2015-01-01

    The vertebrate sarcomere is a complex and highly organized contractile structure whose assembly and function requires the coordination of hundreds of proteins. Proteins require proper folding and incorporation into the sarcomere by assembly factors, and they must also be maintained and replaced due to the constant physical stress of muscle contraction. Zebrafish mutants affecting muscle assembly and maintenance have proven to be an ideal tool for identification and analysis of factors necessary for these processes. The still heart mutant was identified due to motility defects and a nonfunctional heart. The cognate gene for the mutant was shown to be smyd1b and the still heart mutation results in an early nonsense codon. SMYD1 mutants show a lack of heart looping and chamber definition due to a lack of expression of heart morphogenesis factors gata4, gata5 and hand2. On a cellular level, fast muscle fibers in homozygous mutants do not form mature sarcomeres due to the lack of fast muscle myosin incorporation by SMYD1b when sarcomeres are first being assembled (19hpf), supporting SMYD1b as an assembly protein during sarcomere formation. PMID:26544721

  4. The relationships among heart rate variability, executive functions, and clinical variables in patients with panic disorder.

    PubMed

    Hovland, Anders; Pallesen, Ståle; Hammar, Åsa; Hansen, Anita Lill; Thayer, Julian F; Tarvainen, Mika P; Nordhus, Inger Hilde

    2012-12-01

    Heart rate variability (HRV) is reduced in patients who suffer from panic disorder (PD). Reduced HRV is related to hypoactivity in the prefrontal cortex (PFC), which negatively affects executive functioning. The present study assessed the relationships between vagally mediated HRV at baseline and measures of executive functioning in 36 patients with PD. Associations between these physiological and cognitive measures and panic-related variables were also investigated. HRV was measured using HF-power (ms(2)), and executive functions were assessed with the Wisconsin Card Sorting Test (WCST) and the Color-Word Interference Test (CWIT) from the Delis-Kaplan Executive Function System (D-KEFS). Panic-related variables comprised panic frequency, panic-related distress, and duration of PD. Performance on the neuropsychological measures correlated significantly with HRV. Both panic-related distress and duration of PD were inversely related with measures of HRV and cognitive inhibition. The current findings support the purported relationship between HRV and executive functions involving the PFC. PMID:23069273

  5. Social functioning and age across affective and non-affective psychoses

    PubMed Central

    Martin, Elizabeth A.; Öngür, Dost; Cohen, Bruce M.; Lewandowski, Kathryn E.

    2014-01-01

    Both non-affective and affective psychoses are associated with deficits in social functioning across the course of the illness. However, it is not clear how social functioning varies among diagnostic groups as a function of age. The current study examined the relationship between social functioning and age in schizophrenia (SZ), schizoaffective disorder (SZA), and psychotic bipolar disorder (PBD). We found that individuals with PBD had the highest functioning while individuals with SZ had the poorest. The functioning of individuals with SZA fell in between the other groups. We also found that older ages were associated with poorer functioning. Although there was not a significant diagnostic group by age interaction, visual inspection of our data suggests a subtly steeper trajectory of decline in PBD. These results indicate that a decline in social functioning with may be an important area of unmet need in treatment across psychotic disorders. PMID:25503785

  6. Expert system for heart function based on artificial neural networks and fuzzy theory

    NASA Astrophysics Data System (ADS)

    Yu, Wei; Li, Xiaoying; Yu, Daoyin; Mao, Yi; Hua, Qi

    1998-09-01

    In this paper, a computer-aided diagnosis system for heart function based on artificial neural networks and fuzzy logic is introduced. Typical parameters reflecting heart function, provided by echocardiography, were used as input of neural networks and their corresponding heart functions as output. To obtain an analytic and discrimination model closer to brain, we combined fuzzy theory with neural network technology, and input parameters are fuzzily treated. During distinguishing morbid style, we used fuzzy interval, fuzzy number and its related possibility distribution concepts, and selected appropriate operator, and so get its corresponding membership, meanwhile membership was put out of interval of linguistic to consist with language expression. The network selected was BP, and back- propagation algorithm was used to train the network. After studying the result evaluated by expert, the neural network was used to appreciate 150 testees' heart function, of which 90.7% was consistent with experts' diagnosis.

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

    PubMed

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

    2016-01-01

    Perilla frutescens L. due to its aromatic, antibacterial, anti-inflammatory and antioxidant traits has been traditionally used as medicinal plant in Eastern Asia. Alterations of mitochondria are interconnected with many chronic diseases. Bioactives of herbal extracts can modulate mitochondrial effects and be beneficial in prevention of mitochondrial related chronic diseases. Direct effects of the red-leaf form P. frutescens extract (PFE) and the green-leaf form P. frutescens var. crispa f. viridis extract (PCE) were evaluated investigating activities on the oxidative phosphorylation and antioxidant activity in the rat heart mitochondria in vitro. HPLC-MS analysis was applied for the identification of phenolic compounds. Cell with a Clark-type oxygen electrode was used for mitochondrial respiration measurement. The generation of reactive oxygen species was estimated in isolated rat heart mitochondria and determined fluorimetrically. State 3 respiration rate was not affected by lower concentrations, however, it was inhibited at higher concentrations by 22-70% for PFE and by 45-55% for PCE. PFE containing anthocyanins induced the concentration-dependent stimulation (by 23-76%) of the State 4 respiration rate after addition of cytochrome c due to reducing properties. Significant reduction of H₂O₂ pro- duction was observed with investigated concentrations of rosmarinic acid and both perilla extracts. Our results demonstrate that the effect of PFE and PCE extracts on rat heart mitochondria depend on the qualitative characteristics of complex of biologically active compounds. Selective effects on mitochondrial function could enable the regulation of apoptosis or another mechanisms occurring in cells. PMID:27008808

  8. Using en-face optical coherence tomography to analyse gene function in Drosophila Melanogaster larval heart

    NASA Astrophysics Data System (ADS)

    Bradu, Adrian; Ma, Lisha; Bloor, Jim; Podoleanu, Adrian

    2008-09-01

    In-vivo Optical Coherence Tomography (OCT) imaging of the fruit fly Drosophila Melanogaster larval heart allows non invasive visualizations and assessment of its cardiac function. In order to image Drosophila heart, we have developed a dedicated imaging instrument able to provide simultaneous OCT and Laser Scanning Confocal Microscopy (LSCM) images. With this dual imaging system, the heart can easily be located and visualised within the specimen and the change of the heart shape in a cardiac cycle monitored. Here we have used targeted gene expression to knockdown the myospheroid (mys) gene in the larval heart using a specific RNAi construct. By knocking down a β integrin subunit encoded by mys we have recorded an enlarged heart chamber in both diastolic and systolic states. Also, the fraction of reduction of the chamber diameter was smaller in the knockdown heart. These phenotypic differences indicate that impaired cardiac contractility occurs in the heart where the integrin gene express level is reduced. At our knowledge, this is for the first time when it is shown that integrins have a direct relationship to a dilated heart defect.

  9. Does exposure to an artificial ULF magnetic field affect blood pressure, heart rate variability and mood?

    PubMed

    Mitsutake, Gen; Otsuka, Kuniaki; Oinuma, Sachiko; Ferguson, Ian; Cornélissen, Germaine; Wanliss, James; Halberg, Franz

    2004-10-01

    The aim of this study was to determine whether an artificial magnetic field with an amplitude and frequency equivalent to those of geomagnetic pulsations during geomagnetic storms could affect physiology and psychology. Three healthy volunteers wore anambulatory BP monitor and an ECG recorder around the clock for 12 consecutive weekends in Winnipeg, Manitoba, Canada. In a room shielded against ELF and VLF waves, they were exposed for 8 hours per week to either a 50 nT 0.0016 Hz or a sham magnetic field at one of six circadian stages. Real exposure randomly alternated with sham exposure. They provided saliva and recorded mood and reaction time every 4 hours while awake. Systolic (S) and diastolic (D) blood pressure (BP), and heart rate (HR) were recorded every 30 minutes. Spectral analysis of HR variability (HRV) was performed using the maximum entropy method and a complex demodulation method. For these variables, daily means were compared between real and sham exposure, using paired t-tests. Their circadian MESOR, amplitude, and acrophase were analyzed and summarized using single cosinor and population-mean cosinor. Circadian rhythms were demonstrated for HR, SBP, DBP for sham exposure, salivary flow rate, positive affect, vigor, and subjective alertness (p < 0.001, -0.02). One participant showed higher HR, lower LF, HF, and VLF powers, and a steeper power-law slope (p < 0.005, -0.0001) in an early night exposure to the real magnetic field, but not in other circadian stages. There was no significant difference between circadian responses to real and sham exposure in any variable at any circadian stage. PMID:15754834

  10. Lightning and the Heart: Fractal Behavior in Cardiac Function

    PubMed Central

    BASSINGTHWAIGHTE, JAMES B.; van BEEK, J. H. G. M.

    2010-01-01

    Physical systems, from galactic clusters to diffusing molecules, often show fractal behavior. Likewise, living systems might often be well described by fractal algorithms. Such fractal descriptions in space and time imply that there is order in chaos, or put the other way around, chaotic dynamical systems in biology are more constrained and orderly than seen at first glance. The vascular network, the syncytium of cells, the processes of diffusion and transmembrane transport might be fractal features of the heart. These fractal features provide a basis which enables one to understand certain aspects of more global behavior such as atrial or ventricular fibrillation and perfusion heterogeneity. The heart might be regarded as a prototypical organ from these points of view. A particular example of the use of fractal geometry is in explaining myocardial flow heterogeneity via delivery of blood through an asymmetrical fractal branching network. PMID:21938081

  11. [The heart pumping function and the systemic regulation of blood circulation in groups of heart surgery patients].

    PubMed

    Knyshov, H V; Palets', B L; Nastenko, Ie A; Maksymenko, V B

    1996-01-01

    General properties of cardiovascular system functioning in the groups of postoperative patients in the cardiac surgery clinic were studied using the information technology (IT), combined the methods of cluster and nonlinear regression analysis and computer simulation. It was shown, that in all five separated groups of observations (clusters) the direct dependency of cardiac (CI) and stroke (SI) indexes on central venous pressure (CVP) was determined by the variations of total peripheral resistance and reactions of venous tone (u), contractility (E) and heart rate (HR), oriented on the stabilisation of mean aortic pressure (AP) on approximately the same level. Significant differences between the characteristics CI(CVP), SI(CVP) in the groups were determined by the level of E (especially of the right ventricle) and diastolic tone of the heart. Correlation of the cardiac (E,HR) and vascular (u) components of Ap regulation changed correspondingly the heart functional state. Proposed approach and IT may be used in such clinical and experimental research where considerable volume of observations is combined with the great variation of data and, correspondingly, a poor definition level of system behavior. PMID:9044808

  12. Frontal brain electrical activity (EEG) and heart rate in response to affective infant-directed (ID) speech in 9-month-old infants.

    PubMed

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

    2007-10-01

    Many studies have shown that infants prefer infant-directed (ID) speech to adult-directed (AD) speech. ID speech functions to aid language learning, obtain and/or maintain an infant's attention, and create emotional communication between the infant and caregiver. We examined psychophysiological responses to ID speech that varied in affective content (i.e., love/comfort, surprise, fear) in a group of typically developing 9-month-old infants. Regional EEG and heart rate were collected continuously during stimulus presentation. We found the pattern of overall frontal EEG power was linearly related to affective intensity of the ID speech, such that EEG power was greatest in response to fear, than surprise than love/comfort; this linear pattern was specific to the frontal region. We also noted that heart rate decelerated to ID speech independent of affective content. As well, infants who were reported by their mothers as temperamentally distressed tended to exhibit greater relative right frontal EEG activity during baseline and in response to affective ID speech, consistent with previous work with visual stimuli and extending it to the auditory modality. Findings are discussed in terms of how increases in frontal EEG power in response to different affective intensity may reflect the cognitive aspects of emotional processing across sensory domains in infancy. PMID:17659820

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

    ERIC Educational Resources Information Center

    Lam, Gigi

    2015-01-01

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

  14. Beyond ejection fraction: an integrative approach for assessment of cardiac structure and function in heart failure.

    PubMed

    Cikes, Maja; Solomon, Scott D

    2016-06-01

    Left ventricular ejection fraction (LVEF) has been the central parameter used for diagnosis and management in patients with heart failure. A good predictor of adverse outcomes in heart failure when below ∼45%, LVEF is less useful as a marker of risk as it approaches normal. As a measure of cardiac function, ejection fraction has several important limitations. Calculated as the stroke volume divided by end-diastolic volume, the estimation of ejection fraction is generally based on geometric assumptions that allow for assessment of volumes based on linear or two-dimensional measurements. Left ventricular ejection fraction is both preload- and afterload-dependent, can change substantially based on loading conditions, is only moderately reproducible, and represents only a single measure of risk in patients with heart failure. Moreover, the relationship between ejection fraction and risk in patients with heart failure is modified by factors such as hypertension, diabetes, and renal function. A more complete evaluation and understanding of left ventricular function in patients with heart failure requires a more comprehensive assessment: we conceptualize an integrative approach that incorporates measures of left and right ventricular function, left ventricular geometry, left atrial size, and valvular function, as well as non-imaging factors (such as clinical parameters and biomarkers), providing a comprehensive and accurate prediction of risk in heart failure. PMID:26417058

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

    PubMed Central

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

    2016-01-01

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

  16. Sarcoplasmic reticulum function and carnitine palmitoyltransferase-1 inhibition during progression of heart failure

    PubMed Central

    Rupp, Heinz; Vetter, Roland

    2000-01-01

    Failing cardiac hypertrophy is associated with an inadequate sarcoplasmic reticulum (SR) function. The hypothesis was examined that pressure overloaded hearts fail to increase SR Ca2+ uptake rate proportionally to the hypertrophy and that carnitine palmitoyltransferase-1 inhibition by etomoxir ((±)-ethyl 2[6(4-chlorophenoxy)hexyl] oxirane-2-carboxylate) can counteract this process. Severe left ventricular pressure overload was induced in rats by constricting the ascending aorta for 8, 10, 14 and 28 weeks leading to cardiac hypertrophy (+62–+103% of sham-operated rats) and pulmonary congestion. Homogenate oxalate-facilitated SR Ca2+ uptake rate g wet wt−1 was reduced (P<0.05) by 29.9±1.8% irrespective of phospholamban phosphorylation (in the presence of catalytic subunit of protein kinase A) and inhibition of SR Ca2+ release channel by ruthenium red. SERCA2 protein level was reduced (P<0.05) by 30.4±0.8%. SR Ca2+ uptake rate was inversely correlated (P<0.05) with left ventricular weight but was not affected by the occurrence of pulmonary congestion. Because SR Ca2+ uptake rate of whole ventricles was not reduced, a hypertrophy proportional dilution of SR Ca2+ uptake has to be inferred which precedes pulmonary congestion. Treatment with etomoxir (15 mg kg body wt−1 day−1 for 10 weeks) did not affect left ventricular weight but decreased (P<0.05) the right ventricular hypertrophy related to pulmonary congestion. In parallel, SR Ca2+ uptake rate of left ventricle and myosin isozyme V1 were increased (P<0.05). Etomoxir represents a candidate approach for prevention of heart failure by inducing a hypertrophy proportional increase in SR Ca2+ uptake rate. PMID:11139455

  17. Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study

    PubMed Central

    2011-01-01

    Background Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF. Methods Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period. Results Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after treatment (p = 0.74) and in the metoprolol succinate group 1.82 ± 0.29 and 2.10 ± 0.37 before and after treatment, respectively (p = 0.27). Diurnal blood pressures as well as heart rate were also unchanged by changing from carvedilol to metoprolol tartrate or metoprolol succinate. Conclusion Endothelial function remained unchanged when switching the beta blocker treatment from carvedilol to either metoprolol tartrate or metoprolol succinate in this study, where blood pressure and heart rate also remained unchanged in patients with mild HF. Trial registration Current Controlled Trials NCT00497003 PMID:21999413

  18. Relationship of depressive symptoms to functional status in women with heart failure

    PubMed Central

    Song, Eun Kyeung; Moser, Debra K.; Lennie, Terry A.

    2010-01-01

    Background Among patients with heart failure, women have worse functional status than do men, but little research has focused on determining factors that influence functional status in either sex. Objectives To compare factors that influence functional status in men and women with heart failure and to test whether depressive symptoms mediate the relationship between physical symptoms and functional status. Methods A cross-sectional, descriptive study design was used. A total of 231 patients, 133 men and 98 women, were recruited from an inpatient heart failure clinic in South Korea. Functional status (the Korean Activity Scale/Index), physical symptoms (the Symptom Status Questionnaire), depressive symptoms (the Beck Depression Inventory), and situational factors (living status, socioeconomic status) were measured. Hierarchical multiple regression and mediation analysis were used for data analysis. Results Women (mean score, 24.5; SD, 17.3) had worse functional status than did men (mean score, 31.9; SD, 20.1; P=.004). Dyspnea on exertion (β = −0.16), ankle swelling (β = −0.19), fatigue (β = −0.20), and depressive symptoms (β = −0.19) were independently associated with functional status in women, whereas only dyspnea on exertion (β = −0.30) influenced functional status of men in hierarchical multiple regression analysis. Mediation analysis indicated that depressive symptoms mediated the relationship between physical symptoms and functional status in women with heart failure, but not in men. Conclusions Distinct physical and psychological symptoms influence functional status in women with heart failure. A systematic multidimensional intervention may be required to target depressive symptoms to improve functional status in women with heart failure. PMID:19556413

  19. Vinculin network–mediated cytoskeletal remodeling regulates contractile function in the aging heart

    PubMed Central

    Kaushik, Gaurav; Spenlehauer, Alice; Sessions, Ayla O.; Trujillo, Adriana S.; Fuhrmann, Alexander; Fu, Zongming; Venkatraman, Vidya; Pohl, Danielle; Tuler, Jeremy; Wang, Mingyi; Lakatta, Edward G.; Ocorr, Karen; Bodmer, Rolf; Bernstein, Sanford I.; Van Eyk, Jennifer E.; Cammarato, Anthony; Engler, Adam J.

    2015-01-01

    The human heart is capable of functioning for decades despite minimal cell turnover or regeneration, suggesting that molecular alterations help sustain heart function with age. However, identification of compensatory remodeling events in the aging heart remains elusive. We present the cardiac proteomes of young and old rhesus monkeys and rats, from which we show that certain age-associated remodeling events within the cardiomyocyte cytoskeleton are highly conserved and beneficial rather than deleterious. Targeted transcriptomic analysis in Drosophila confirmed conservation and implicated vinculin as a unique molecular regulator of cardiac function during aging. Cardiac-restricted vinculin overexpression reinforced the cortical cytoskeleton and enhanced myofilament organization, leading to improved contractility and hemodynamic stress tolerance in healthy and myosin-deficient fly hearts. Moreover, cardiac-specific vinculin overexpression increased median life span by more than 150% in flies. A broad array of potential therapeutic targets and regulators of age-associated modifications, specifically for vinculin, are presented. These findings suggest that the heart has molecular mechanisms to sustain performance and promote longevity, which may be assisted by therapeutic intervention to ameliorate the decline of function in aging patient hearts. PMID:26084806

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

    PubMed

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

    2015-03-01

    This study was initiated to assess the temporal trends of renal function, and define risk factors associated with worsening renal function in pediatric heart transplant recipients in the immediate post-operative period. We performed a single-center retrospective study in children ≤18 yr receiving OHT (1993-2012). The AKIN's validated, three-tiered AKI staging system was used to categorize the degree of WRF. One hundred sixty-four patients qualified for inclusion. Forty-seven patients (28%) were classified as having WRF after OHT. Nineteen patients (11%) required dialysis after heart transplantation. There was a sustained and steady improvement in renal function in children following heart transplantation in all age groups, irrespective of underlying disease process. The significant factors associated with risk of WRF included body surface area (OR: 1.89 for 0.5 unit increase, 95% CI: 1.29-2.76, p = 0.001) and use of ECMO prior to and/or after heart transplantation (OR: 3.50, 95% CI: 1.51-8.13, p = 0.004). Use of VAD prior to heart transplantation was not associated with WRF (OR: 0.50, 95% CI: 0.17-1.51, p = 0.22). On the basis of these data, we demonstrate that worsening renal function improves early after orthotopic heart transplantation. PMID:25484128

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

    PubMed

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

    2012-08-24

    The three isoforms of vertebrate troponin T (TnT) are normally expressed in a muscle type-specific manner. Here we report an exception that the cardiac muscle of toad (Bufo) expresses exclusively slow skeletal muscle TnT (ssTnT) together with cardiac forms of troponin I and myosin as determined using immunoblotting, cDNA cloning, and/or LC-MS/MS. Using RT-PCR and 3'- and 5'-rapid amplification of cDNA ends on toad cardiac mRNA, we cloned full-length cDNAs encoding two alternatively spliced variants of ssTnT. Expression of the cloned cDNAs in Escherichia coli confirmed that the toad cardiac muscle expresses solely ssTnT, predominantly the low molecular weight variant with the exon 5-encoded NH(2)-terminal segment spliced out. Functional studies were performed in ex vivo working toad hearts and compared with the frog (Rana) hearts. The results showed that toad hearts had higher contractile and relaxation velocities and were able to work against a significantly higher afterload than that of frog hearts. Therefore, the unique evolutionary adaptation of utilizing exclusively ssTnT in toad cardiac muscle corresponded to a fitness value from improving systolic function of the heart. The data demonstrated a physiological importance of the functional diversity of TnT isoforms. The structure-function relationship of TnT may be explored for the development of new treatment of heart failure. PMID:22778265

  2. [Effect of exogenously administered ATP on heart function and energy status].

    PubMed

    Chernikov, V S; Darbinian, T M; Bakuleva, N P

    1993-01-01

    It has been shown that ATP (24.10(-6) M) administered once into the circulating solution improved strength and speed characteristics of aerobically perfused hearts. The increasing demands of the hearts in oxygen and energy substrates were satisfied due to coronary vessels dilatation without harming the energy status of the myocardium. When the functional parameters of the hearts in the test and control groups did not differ, an exogenously administered ATP was included into the energy metabolism and increased considerably ATP and CP tissue levels, the sum of high-energy phosphates and ATP/ADP ratio. Artificial supplementation of tissue energy resources was accompanied by a decrease in energy-dependent end-diastolic pressure and diastolic left ventricular elasticity and by increased extensibility of the heart muscle, which may improve functional parameters. PMID:8185075

  3. Strategies to Enhance the Effectiveness of Adult Stem Cell Therapy for Ischemic Heart Diseases Affecting the Elderly Patients

    PubMed Central

    Khatiwala, Roshni

    2016-01-01

    Myocardial infarctions and chronic ischemic heart disease both commonly and disproportionately affect elderly patients more than any other patient population. Despite available treatments, heart tissue is often permanently damaged as a result of cardiac injury. This review aims to summarize recent literature proposing the use of modified autologous adult stem cells to promote healing of post-infarct cardiac tissue. This novel cellular treatment involves isolation of adult stem cells from the patient, in vitro manipulation of these stem cells, and subsequent transplantation back into the patient’s own heart to accelerate healing. One of the hindrances affecting this process is that cardiac issues are increasingly common in elderly patients, and stem cells recovered from their tissues tend to be pre-senescent or already in senescence. As a result, harsh in vitro manipulations can cause the aged stem cells to undergo massive in vivo apoptosis after transplantation. The consensus in literature is that inhibition or reversal of senescence onset in adult stem cells would be of utmost benefit. In fact, it is believed that this strategy may lower stem cell mortality and coerce aged stem cells into adopting more resilient phenotypes similar to that of their younger counterparts. This review will discuss a selection of the most efficient and most-recent strategies used experimentally to enhance the effectiveness of current stem cell therapies for ischemic heart diseases. PMID:26779896

  4. Heart Attack

    MedlinePlus

    ... have a heart attack. About half of them die. Many people have permanent heart damage or die because they don't get help immediately. It's ... few hours causes the affected heart muscle to die. NIH: National Heart, Lung, and Blood Institute

  5. Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction

    PubMed Central

    Gori, Mauro; Senni, Michele; Gupta, Deepak K.; Charytan, David M.; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M.; Santos, Angela B. S.; Zile, Michael R.; Voors, Adriaan A.; McMurray, John J. V.; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D.

    2014-01-01

    Aim Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. Methods We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m2 and/or albuminuria] and cardiovascular structure/function. Results The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Conclusion Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. PMID:24980489

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

    PubMed Central

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

    2011-01-01

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

  7. Arginylation regulates myofibrils to maintain heart function and prevent dilated cardiomyopathy

    PubMed Central

    Kurosaka, Satoshi; Leu, N. Adrian; Pavlov, Ivan; Han, Xuemei; Ribeiro, Paula Aver Bretanha; Xu, Tao; Bunte, Ralph; Saha, Sougata; Wang, Junling; Cornachione, Anabelle; Mai, Wilfried; Yates, John R; Rassier, Dilson E.; Kashina, Anna

    2012-01-01

    Protein arginylation mediated by arginyltransferase (ATE1) is essential for heart formation during embryogenesis, however its cell-autonomous role in cardiomyocytes and the differentiated heart muscle has never been investigated. To address this question, we generated cardiac muscle-specific Ate1 knockout mice, in which Ate1 deletion was driven by α-myosin heavy chain promoter (αMHC-Ate1 mouse). These mice were initially viable, but developed severe cardiac contractility defects, dilated cardiomyopathy, and thrombosis over time, resulting in high rates of lethality after 6 months of age. These symptoms were accompanied by severe ultrastructural defects in cardiac myofibrils, seen in the newborns and far preceding the onset of cardiomyopathy, suggesting that these defects were primary and likely underlay the development of the future heart defects. Several major sarcomeric proteins were arginylated in vivo. Moreover, Ate1 deletion in the hearts resulted in a significant reduction of active and passive myofibril forces, suggesting that arginylation is critical for both myofibril structural integrity and contractility. Thus, arginylation is essential for maintaining the heart function by regulation of the major myofibril proteins and myofibril forces, and its absence in the heart muscle leads to progressive heart failure through cardiomyocyte-specific defects. PMID:22626847

  8. How to interpret liver function tests in heart failure patients?

    PubMed

    Çağlı, Kumral; Başar, Fatma Nurcan; Tok, Derya; Turak, Osman; Başar, Ömer

    2015-05-01

    Cardiac hepatopathy has generally been used to describe any liver damage caused by cardiac disorders in the absence of other possible causes of liver damage. Although there is no consensus on the terminology used, cardiac hepatopathy can be examined as congestive hepatopathy (CH) and acute cardiogenic liver injury (ACLI). CH is caused by passive venous congestion of the liver that generally occurs in the setting of chronic cardiac conditions such as chronic HF, constrictive pericarditis, tricuspid regurgitation, or right-sided heart failure (HF) of any cause, and ACLI is most commonly associated with acute cardiocirculatory failure resulting from acute myocardial infarction, acute decompensated HF, or myocarditis. Histologically, CH is characterized by sinusoidal dilation, replacement of hepatocytes with red blood cells extravasating from the sinusoids, and necrosis/apoptosis of zone 3 of the Rappaport acinus, and it could progress to cirrhosis in advanced cases. In ACLI, however, massive necrosis of zone 3 is the main histological finding. Primary laboratory findings of CH are elevated serum cholestasis markers including bilirubin, alkaline phosphatase, and γ-glutamyl-transpeptidase levels, whereas those of ACLI are a striking elevation in transaminase and lactate dehydrogenase levels. Both CH and ACLI have a prognostic value for identifying cardiovascular events and mortality and have some special implications in the management of patients undergoing ventricular assist device implantation or cardiac transplantation. There is no specific treatment for CH or ACLI other than treatment of the underlying cardiac disorder. PMID:26006191

  9. Heart rate variability and cognitive function: effects of physical effort.

    PubMed

    Luft, Caroline Di Bernardi; Takase, Emílio; Darby, David

    2009-10-01

    This study investigated alterations in heart rate variability (HRV) and cognitive performance before and after physical effort, for 30 high-level track and field athletes (23 males and 7 females). Interbeat intervals were assessed at the baseline and during each task of a CogState cognitive battery (simple reaction time, choice reaction time, working memory, short-term memory and sustained attention). Time and frequency domain measures of HRV were compared between conditions and between tasks. The results indicated differences in HRV between executive and non-executive tasks. There was a significant increase in sympathetic-modulation-related indices after physical effort. The differences between executive and non-executive tasks were the same in post-test. Correlations were found between HRV and cognitive performance, which differed by speed and accuracy. We conclude that HRV is related to cognitive demand and that the correlation between HRV and cognitive performance seems to be stronger after physical exercise. The results raise questions about the psychophysiological meaning of different HRV signals and this has implications for future research about the relationship between HRV and cognition. PMID:19632295

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

    PubMed

    Bunzel, B; Wollenek, G; Grundböck, A

    1992-10-01

    Heart transplantation has become an accepted therapy for patients suffering from terminal heart disease for whom neither standard forms of medication nor the usual surgery are of any benefit. Although results regarding postoperative quantity and quality of life are encouraging, it must not be overlooked that the patient and his family face, and have to overcome, profound psychosocial problems. The main stressors were identified in interviews with 47 heart transplant patients. The main preoperative problems were: the way of being informed about the diagnosis, the waiting period for transplantation, anguishing doubts about the decision to have a transplant, being a body without heart ('zombie'), guilt and shame regarding the donor, the reactions of others. Postoperatively the patients have to cope with: re-entering social systems, reactions of friends, neighbours and colleagues, rejection episodes, death of a fellow patient, the need to redesign family life. All the problems reported by the patients interviewed are discussed regarding their psychosocial implications, and hints are given on how to minimize them. PMID:1299462

  11. DOES FEEDBACK FROM A NEST AFFECT PERIPARTURIENT BEHAVIOUR, HORMONES AND HEART RATE IN GILTS?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine the effects of feedback from a farrowing nest on sow welfare, as determined by behaviour, hormones and heart rate, 20 gilts housed in central-nest-farrowing-pens were permitted to build a nest of peat, straw and branches. Ten sows then had their nest removed (NR) 10h after the onset of ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Downstream of homeotic genes: in the heart of Hox function.

    PubMed

    Monier, Bruno; Tevy, Maria Florencia; Perrin, Laurent; Capovilla, Maria; Sémériva, Michel

    2007-01-01

    A functional organ is constituted of diverse cell types. Each one occupies a distinct position and is associated to specific morphological and physiological functions. The identification of the genetic programs controlling these elaborated and highly precise features of organogenesis is crucial to understand how a mature organ works under normal conditions, and how pathologies can develop. Recently, a number of studies have reported a critical role for Hox genes in one example of organogenesis: cardiogenesis in Drosophila. Beyond the interest in understanding the molecular basis of functional cardiogenesis, this system might provide a model for proposing new paradigms of how Hox genes achieve their action throughout development. PMID:18820463

  14. Drug-like actions of autoantibodies against receptors of the autonomous nervous system and their impact on human heart function

    PubMed Central

    Herda, LR; Felix, SB; Boege, F

    2012-01-01

    Antibodies against cholinergic and adrenergic receptors (adrenoceptors) are frequent in serum of patients with chronic heart failure. Their prevalence is associated with Chagas' disease, idiopathic dilated cardiomyopathy (DCM), and ischaemic heart disease. Among the epitopes targeted are first and second extracellular loops of the β-adrenergic (β-adrenoceptor) and M2 muscarinic receptor. β1-adrenoceptor autoantibodies affect radioligand binding and cardiomyocyte function similar to agonists. Corresponding rodent immunizations induce symptoms compatible with chronic heart failure that are reversible upon removal of the antibodies, transferable via the serum and abrogated by adrenergic antagonists. In DCM patients, prevalence and stimulatory efficacy of β1-adrenoceptor autoantibodies are correlated to the decline in cardiac function, ventricular arrhythmia and higher incidence of cardiac death. In conclusion, such autoantibodies seem to cause or promote chronic human left ventricular dysfunction by acting on their receptor targets in a drug-like fashion. However, the pharmacology of this interaction is poorly understood. It is unclear how the autoantibodies trigger changes in receptor activity and second messenger coupling and how that is related to the pathogenesis and severity of the associated diseases. Here, we summarize the available evidence regarding these issues and discuss these findings in the light of recent knowledge about the conformational activation of the human β2-adrenoceptor and the properties of bona fide cardiopathogenic autoantibodies derived from immune-adsorption therapy of DCM patients. These considerations might contribute to the conception of therapy regimen aimed at counteracting or neutralizing cardiopathogenic receptor autoantibodies. PMID:22220626

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

    ERIC Educational Resources Information Center

    Atoofi, Saeid

    2013-01-01

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

  16. Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged Mdx mice.

    PubMed

    Bostick, Brian; Yue, Yongping; Long, Chun; Marschalk, Nate; Fine, Deborah M; Chen, Jing; Duan, Dongsheng

    2009-02-01

    Duchenne muscular dystrophy (DMD) affects both skeletal and cardiac muscle. It is currently unclear whether the strategies developed for skeletal muscle can ameliorate cardiomyopathy. Synthetic mini-/micro-dystrophin genes have yielded impressive skeletal muscle protection in animal models. The 6-kb DeltaH2-R19 minigene is particularly promising because it completely restores skeletal muscle force to wild-type levels. Here, we examined whether expressing this minigene in the heart, but not skeletal muscle, could normalize cardiac function in the mdx model of DMD cardiomyopathy. Transgenic mdx mice were generated to express the DeltaH2-R19 minigene under the control of the alpha-myosin heavy-chain promoter. Heart structure and function were examined in adult and very old mice. The DeltaH2-R19 minigene enhanced cardiomyocyte sarcolemmal strength and prevented myocardial fibrosis. It also restored the dobutamine response and enhanced treadmill performance. Surprisingly, heart-restricted DeltaH2-R19 minigene expression did not completely normalize electrocardiogram and hemodynamic abnormalities. Overall, systolic function and ejection fraction were restored to normal levels but stroke volume and cardiac output remained suboptimal. Our results demonstrate that the skeletal muscle-proven DeltaH2-R19 minigene can correct cardiac histopathology but cannot fully normalize heart function. Novel strategies must be developed to completely restore heart function in DMD. PMID:19066599

  17. Reduced Cognitive Function Predicts Functional Decline in Patients with Heart Failure over 12 months

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Colbert, Lisa H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Background Impaired activities of daily living (ADL) are common in heart failure (HF) patients and contribute to the elevated mortality and hospitalization rates in this population. Cognitive impairment is also prevalent in HF, though its ability to predict functional decline over time is unknown. Aims This study examined the longitudinal pattern of activities of daily living in HF persons and whether reduced baseline cognitive status predicts functional decline in this population. Methods 110 persons with HF completed the Lawton-Brody Activities of Daily Living Scale and were administered the Modified Mini-Mental Status Examination (3MS) at baseline and a 12-month follow-up. Three composite scores were derived from the Lawton-Brody, including total, instrumental, and basic ADLs. Results HF patients reported high rates of baseline impairments in instrumental ADLs, including shopping, food preparation, housekeeping duties, laundry, among others. Repeated measures analyses showed significant declines in total and instrumental ADLs from baseline to the 12-month follow-up in HF (p < .05). Hierarchical regression analyses showed that poorer baseline performance on the 3MS predicted worse total ADL performance at 12-months (β = .15, p = .049), including greater dependence in shopping, driving, feeding, and physical ambulation (p < .05 for all). Conclusion The current results show that HF patients report significant functional decline over a 12-month period and brief cognitive tests can identify those patients at highest risk for decline. If replicated, such findings encourage the use of cognitive screening measures to identify HF patients most likely to require assistance with ADL tasks. PMID:23754840

  18. Lifetime affect and midlife cognitive function: prospective birth cohort study

    PubMed Central

    Richards, M.; Barnett, J. H.; Xu, M. K.; Croudace, T. J.; Gaysina, D.; Kuh, D.; Jones, P. B.

    2014-01-01

    Background Recurrent affective problems are predictive of cognitive impairment, but the timing and directionality, and the nature of the cognitive impairment, are unclear. Aims To test prospective associations between life-course affective symptoms and cognitive function in late middle age. Method A total of 1668 men and women were drawn from the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort). Longitudinal affective symptoms spanning age 13-53 years served as predictors; outcomes consisted of self-reported memory problems at 60-64 years and decline in memory and information processing from age 53 to 60-64 years. Results Regression analyses revealed no clear pattern of association between longitudinal affective symptoms and decline in cognitive test scores, after adjusting for gender, childhood cognitive ability, education and midlife socioeconomic status. In contrast, affective symptoms were strongly, diffusely and independently associated with self-reported memory problems. Conclusions Affective symptoms are more clearly associated with self-reported memory problems in late midlife than with objectively measured cognitive performance. PMID:24357571

  19. Does Subacromial Osteolysis Affect Shoulder Function after Clavicle Hook Plating?

    PubMed Central

    Sun, Siwei; Gan, Minfeng; Sun, Han; Wu, Guizhong; Yang, Huilin; Zhou, Feng

    2016-01-01

    Purpose. To evaluate whether subacromial osteolysis, one of the major complications of the clavicle hook plate procedure, affects shoulder function. Methods. We had performed a retrospective study of 72 patients diagnosed with a Neer II lateral clavicle fracture or Degree-III acromioclavicular joint dislocation in our hospital from July 2012 to December 2013. All these patients had undergone surgery with clavicle hook plate and were divided into two groups based on the occurrence of subacromial osteolysis. By using the Constant-Murley at the first follow-up visit after plates removal, we evaluated patients' shoulder function to judge if it has been affected by subacromial osteolysis. Results. We have analyzed clinical data for these 72 patients, which shows that there is no significant difference between group A (39 patients) and group B (33 patients) in age, gender, injury types or side, and shoulder function (the Constant-Murley scores are 93.38 ± 3.56 versus 94.24 ± 3.60, P > 0.05). Conclusion. The occurrence of subacromial osteolysis is not rare, and also it does not significantly affect shoulder function. PMID:27034937

  20. Pharmacological inhibition of IK1 by PA-6 in isolated rat hearts affects ventricular repolarization and refractoriness.

    PubMed

    Skarsfeldt, Mark A; Carstensen, Helena; Skibsbye, Lasse; Tang, Chuyi; Buhl, Rikke; Bentzen, Bo H; Jespersen, Thomas

    2016-04-01

    The inwardly rectifying potassium current (IK 1) conducted through Kir2.X channels contribute to repolarization of the cardiac action potential and to stabilization of the resting membrane potential in cardiomyocytes. Our aim was to investigate the effect of the recently discovered IK 1 inhibitor PA-6 on action potential repolarization and refractoriness in isolated rat hearts. Transiently transfected HEK-293 cells expressing IK 1 were voltage-clamped with ramp protocols. Langendorff-perfused heart experiments were performed on male Sprague-Dawley rats, effective refractory period, Wenckebach cycle length, and ventricular effective refractory period were determined following 200 nmol/L PA-6 perfusion. 200 nmol/L PA-6 resulted in a significant time-latency in drug effect on the IK 1 current expressed in HEK-293 cells, giving rise to a maximal effect at 20 min. In the Langendorff-perfused heart experiments, PA-6 prolonged the ventricular action potential duration at 90% repolarization (from 41.8 ± 6.5 msec to 72.6 ± 21.1 msec, 74% compared to baseline, P < 0.01, n = 6). In parallel, PA-6 significantly prolonged the ventricular effective refractory period compared to baseline (from 34.8 ± 4.6 msec to 58.1 ± 14.7 msec, 67%, P < 0.01, n = 6). PA-6 increased the short-term beat-to-beat variability and ventricular fibrillation was observed in two of six hearts. Neither atrial ERP nor duration of atrial fibrillation was altered following PA-6 application. The results show that pharmacological inhibition of cardiac IK 1 affects ventricular action potential repolarization and refractoriness and increases the risk of ventricular arrhythmia in isolated rat hearts. PMID:27117805

  1. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

    PubMed

    Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

    2013-10-01

    Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

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

    SciTech Connect

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

    1985-01-01

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

  3. Impact of cold ischemia on mitochondrial function in porcine hearts and blood vessels.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Factors affecting the supply of glucose to the heart of the rat, in vivo.

    PubMed Central

    Daniel, P M; Love, E R; Pratt, O E

    1980-01-01

    1. The influx of glucose into the heart of intact, living, anaesthetized rats was measured when the levels of insulin the blood were (a) low (as a result of fasting), (b) normal, and (c) high (as a result of injecting insulin). The findings showed that the transport of glucose into cardiac cells is carrier-mediated and is strongly insulin-independent. 2. The major barrier to the supply glucose to the heart from the circulating blood is at the surface membrane of the cardiac cells, rather than at the endothelium of the cardiac capillaries. 3. The extracellular space of the heart was measured and was found to be approximately 25% of the cardiac tissue. 4. During life, glucose, as well as its analogue, 3-O-methylglucose passes across the membranes of the cells of the heart by means of a transport system which is strongly dependent upon insulin and appears to be carried-mediated. A likely explanation for the effect of insulin is that it increases considerably the affinity of the transport carrier for glucose. Saturation of the carrier takes place when the levels of insulin and of glucose in the blood are high. However, when the concentration of insulin is low, e.g. during a fast, the affinity of the carrier for glucose is reduced so that saturation cannot be demonstrated. 5. It is suggested that the low level of insulin that is found in the blood in the early morning, which is due to the night fast, may lead to the cardiac dysfunction which often develops at that time. PMID:6788938

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

    NASA Astrophysics Data System (ADS)

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

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

  7. Dysferlin deficiency blunts β-adrenergic-dependent lusitropic function of mouse heart.

    PubMed

    Wei, Bin; Wei, Hongguang; Jin, J-P

    2015-12-01

    Dysferlin is a cell membrane bound protein with a role in the repair of skeletal and cardiac muscle cells. Deficiency of dysferlin leads to limb-girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy. In cardiac muscle, dysferlin is located at the intercalated disc and transverse tubule membranes. Loss of dysferlin causes death of cardiomyocytes, notably in ageing hearts, leading to dilated cardiomyopathy and heart failure in LGM2B patients. To understand the primary pathogenesis and pathophysiology of dysferlin cardiomyopathy, we studied cardiac phenotypes of young adult dysferlin knockout mice and found early myocardial hypertrophy with largely compensated baseline cardiac function. Cardiomyocytes isolated from dysferlin-deficient mice showed normal shortening and re-lengthening velocities in the absence of external load with normal peak systolic Ca(2+) but slower Ca(2+) re-sequestration than wild-type controls. The effects of isoproterenol on relaxation velocity, left ventricular systolic pressure and stroke volume were blunted in dysferlin-deficient mouse hearts compared with that in wild-type hearts. Young dysferlin-deficient mouse hearts expressed normal isoforms of myofilament proteins whereas the phosphorylation of ventricular myosin light chain 2 was significantly increased, implying a molecular response to the impaired lusitropic function. These early phenotypes of diastolic cardiac dysfunction and blunted lusitropic response of cardiac muscle to β-adrenergic stimulation indicate a novel pathogenic mechanism of dysferlin cardiomyopathy. PMID:26415898

  8. Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart

    PubMed Central

    Foster, Simon R.; Porrello, Enzo R.; Purdue, Brooke; Chan, Hsiu-Wen; Voigt, Anja; Frenzel, Sabine; Hannan, Ross D.; Moritz, Karen M.; Simmons, David G.; Molenaar, Peter; Roura, Eugeni; Boehm, Ulrich; Meyerhof, Wolfgang; Thomas, Walter G.

    2013-01-01

    G protein-coupled receptors (GPCRs) are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2) as well as Tas1r1 and Tas1r3 (comprising the umami receptor) are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and by in situ hybridization can be visualized across the myocardium in isolated cardiac cells. Tas1r1 gene-targeted mice (Tas1r1Cre/Rosa26tdRFP) strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart. PMID:23696900

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. Electrophysiological Remodeling in Heart Failure

    PubMed Central

    Wang, Yanggan; Hill, Joseph A.

    2010-01-01

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

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

    PubMed

    Dong, Shan; Jacob, Tim J C

    2016-03-15

    Bright light therapy has been shown to have a positive impact on seasonal affective disorder (SAD), depression and anxiety. Smell has also has been shown to have effects on mood, stress, anxiety and depression. The objective of this study was to investigate the effect of the combination of light and smell in a non-adaptive cycle. Human subjects were given smell (lemon, lavender or peppermint) and light stimuli in a triangular wave (60scycle) for 15min. Blood pressure and heart rate were monitored before and after each session for 5 consecutive days and a Profile of Mood States (POMS) test was administered before and after the sensory stimulation on days 1, 3 and 5. The light-smell stimulus lowered blood pressure, both systolic and diastolic, and reduced heart rate for all odours compared to control. Of the two sensory stimuli, the odour stimulus contributed most to this effect. The different aromas in the light-smell combinations could be distinguished by their different effects on the mood factors with lemon inducing the greatest mood changes in Dejection-Depression, Anger-Hostility, Tension-Anxiety. In conclusion, combined light and smell stimulation was effective in lowering blood pressure, reducing heart rate and improving mood. The combination was more effective than either smell or light stimuli alone, suggesting that a light-smell combination would be a more robust and efficacious alternative treatment for depression, anxiety and stress. PMID:26780148

  14. Functional significance of preserved affect recognition in schizophrenia

    PubMed Central

    Fiszdon, Joanna M.; Johannesen, Jason K.

    2009-01-01

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

  15. Age-associated Pro-inflammatory Remodeling and Functional Phenotype in the Heart and Large Arteries

    PubMed Central

    Wang, Mingyi; Shah, Ajay M

    2015-01-01

    The aging population is increasing dramatically. Aging–associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure. PMID:25665458

  16. Galnt1 Is Required for Normal Heart Valve Development and Cardiac Function

    PubMed Central

    Tian, E; Stevens, Sharon R.; Guan, Yu; Springer, Danielle A.; Anderson, Stasia A.; Starost, Matthew F.; Patel, Vyomesh; Ten Hagen, Kelly G.; Tabak, Lawrence A.

    2015-01-01

    Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc-Ts) responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals. The underlying phenotype is aberrant valve formation caused by increased cell proliferation within the outflow tract cushion of developing hearts, which is first detected at developmental stage E11.5. Developing valves from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1 and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels of other extracellular matrix proteins. We also observed increased BMP and MAPK signaling. Taken together, the ablation of Galnt1 appears to disrupt the formation/remodeling of the extracellular matrix and alters conserved signaling pathways that regulate cell proliferation. Our study provides insight into the role of this conserved protein modification in cardiac valve development and may represent a new model for idiopathic valve disease. PMID:25615642

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  18. Cognitive and behavioral functioning of children listed for heart and/or lung transplantation.

    PubMed

    Wray, J; Radley-Smith, R

    2010-11-01

    The objective of the study was to assess cognitive function and behavior in a group of children listed for heart and/or lung transplantation. Ninety-nine children (3.7-16.8 years) listed for heart and/or lung transplant for congenital heart disease (CHD), cardiomyopathy (CM), cystic fibrosis (CF) or primary pulmonary hypertension (PPH) were evaluated with standardized measures of cognitive function, academic ability and behavior. Results were compared with a historical cohort of healthy children and comparisons were made between the four diagnostic subgroups. Mean subtest scores, overall IQ and achievement scores were within the normal range for the total group but were significantly lower than those of the healthy group. Although there were few significant differences between the diagnostic subgroups children with CHD or CF tended to perform at a lower level than those with CM or PPH. There were some significant issues with behavior for all diagnostic subgroups, particularly in the domain of social competence. Patients with end-stage heart or lung disease are at increased risk for cognitive and/or behavioral problems, particularly those with CHD. Follow-up of these patients after transplant is important to determine the role that psychological functioning prior to surgery has in the longer term after surgery. PMID:20977644

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

    PubMed Central

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

    1992-01-01

    We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition. Images PMID:1601992

  20. Effect of anemia on cardiac function, microvascular structure, and capillary hematocrit in rat hearts.

    PubMed

    Rakusan, K; Cicutti, N; Kolar, F

    2001-03-01

    The effect of anemia on the coronary microcirculation was studied in young male rats. Chronic anemia resulted in increased left ventricular end-diastolic pressure and decreased functional reserve. Cardiac mass in anemic animals increased by 25%. Capillary and arteriolar densities in these hearts remained unchanged, indicating angiogenesis in this experimental situation (estimated aggregate capillary length in the left ventricle of anemic hearts was 3.06 km compared with 2.35 km in control hearts). Capillary hematocrit was decreased in chronic anemia less than systemic hematocrit: from 25 to 18% in anemia versus 45 to 28% in controls. Capillary hematocrit and red blood cell spacing were also studied after acute blood withdrawal. Here, capillary hematocrit was preserved even more: 22 versus 24% in systemic hematocrit. Finally, the same was studied in isolated hearts perfused with solutions of various hematocrits. After perfusion with low-hematocrit solution (14%), the capillary hematocrit (24%) was even higher than the perfusate hematocrit! In conclusion, we found evidence of angiogenesis in cardiomegaly induced by chronic anemia. Microvascular growth was accompanied by advantageous regulation of red blood cell spacing within these vessels. This was even more pronounced during acute hemodilution and in isolated perfused hearts. PMID:11179091

  1. The stretch-activation response may be critical to the proper functioning of the mammalian heart

    PubMed Central

    Vemuri, Ramesh; Lankford, Edward B.; Poetter, Karl; Hassanzadeh, Shahin; Takeda, Kazuyo; Yu, Zu-Xi; Ferrans, Victor J.; Epstein, Neal D.

    1999-01-01

    The “stretch-activation” response is essential to the generation of the oscillatory power required for the beating of insect wings. It has been conjectured but not previously shown that a stretch-activation response contributes to the performance of a beating heart. Here, we generated transgenic mice that express a human mutant myosin essential light chain derived from a family with an inherited cardiac hypertrophy. These mice faithfully replicate the cardiac disease of the patients with this mutant allele. They provide the opportunity to study the stretch-activation response before the hearts are distorted by the hypertrophic process. Studies disclose a mismatch between the physiologic heart rate and resonant frequency of the cardiac papillary muscles expressing the mutant essential light chain. This discordance reduces oscillatory power at frequencies that correspond to physiologic heart-rates and is followed by subsequent hypertrophy. It appears, therefore, that the stretch-activation response, first described in insect flight muscle, may play a role in the mammalian heart, and its further study may suggest a new way to modulate human cardiac function. PMID:9927691

  2. Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart

    PubMed Central

    Hosoyama, Tohru; Samura, Makoto; Kudo, Tomoaki; Nishimoto, Arata; Ueno, Koji; Murata, Tomoaki; Ohama, Takashi; Sato, Koichi; Mikamo, Akihito; Yoshimura, Koichi; Li, Tao-Sheng; Hamano, Kimikazu

    2015-01-01

    Cardiosphere-derived cells (CDCs) isolated from postnatal heart tissue are a convenient and efficientresource for the treatment of myocardial infarction. However, poor retention of CDCs in infarcted hearts often causes less than ideal therapeutic outcomes. Cell sheet technology has been developed as a means of permitting longer retention of graft cells, and this therapeutic strategy has opened new avenues of cell-based therapy for severe ischemic diseases. However, there is still scope for improvement before this treatment can be routinely applied in clinical settings. In this study, we investigated whether hypoxic preconditioning enhances the therapeutic efficacy of CDC monolayer sheets. To induce hypoxia priming, CDC monolayer sheets were placed in an incubator adjusted to 2% oxygen for 24 hours, and then preconditioned mouse CDC sheets were implanted into the infarcted heart of old myocardial infarction mouse models. Hypoxic preconditioning of CDC sheets remarkably increased the expression of vascular endothelial growth factor through the PI3-kinase/Akt signaling pathway. Implantation of preconditioned CDC sheets improved left ventricular function inchronically infarcted hearts and reduced fibrosis. The therapeutic efficacy of preconditioned CDC sheets was higher than the CDC sheets that were cultured under normaxia condition. These results suggest that hypoxic preconditioning augments the therapeutic angiogenic and anti-fibrotic activity of CDC sheets. A combination of cell sheets and hypoxic preconditioning offers an attractive therapeutic protocol for CDC transplantation into chronically infarcted hearts. PMID:26885271

  3. Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart.

    PubMed

    Hosoyama, Tohru; Samura, Makoto; Kudo, Tomoaki; Nishimoto, Arata; Ueno, Koji; Murata, Tomoaki; Ohama, Takashi; Sato, Koichi; Mikamo, Akihito; Yoshimura, Koichi; Li, Tao-Sheng; Hamano, Kimikazu

    2015-01-01

    Cardiosphere-derived cells (CDCs) isolated from postnatal heart tissue are a convenient and efficientresource for the treatment of myocardial infarction. However, poor retention of CDCs in infarcted hearts often causes less than ideal therapeutic outcomes. Cell sheet technology has been developed as a means of permitting longer retention of graft cells, and this therapeutic strategy has opened new avenues of cell-based therapy for severe ischemic diseases. However, there is still scope for improvement before this treatment can be routinely applied in clinical settings. In this study, we investigated whether hypoxic preconditioning enhances the therapeutic efficacy of CDC monolayer sheets. To induce hypoxia priming, CDC monolayer sheets were placed in an incubator adjusted to 2% oxygen for 24 hours, and then preconditioned mouse CDC sheets were implanted into the infarcted heart of old myocardial infarction mouse models. Hypoxic preconditioning of CDC sheets remarkably increased the expression of vascular endothelial growth factor through the PI3-kinase/Akt signaling pathway. Implantation of preconditioned CDC sheets improved left ventricular function inchronically infarcted hearts and reduced fibrosis. The therapeutic efficacy of preconditioned CDC sheets was higher than the CDC sheets that were cultured under normaxia condition. These results suggest that hypoxic preconditioning augments the therapeutic angiogenic and anti-fibrotic activity of CDC sheets. A combination of cell sheets and hypoxic preconditioning offers an attractive therapeutic protocol for CDC transplantation into chronically infarcted hearts. PMID:26885271

  4. Stirring the hearts of followers: charismatic leadership as the transferal of affect.

    PubMed

    Erez, Amir; Misangyi, Vilmos F; Johnson, Diane E; LePine, Marcie A; Halverson, Kent C

    2008-05-01

    In 2 studies, the authors found that leader charisma was positively associated with followers' positive affect and negatively associated with followers' negative affect. The authors hypothesized that leaders' positive affect, positive expression, and aroused behavior will mediate these relationships. The results of their lab study suggest that leaders' positive expression and aroused behavior mediated these relationships. A field study showed that firefighters under the command of a charismatic officer were happier than those under the command of a non-charismatic officer and that these relationships were mediated by the leader's positive affect and a tendency to express positivity. PMID:18457489

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

    PubMed Central

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

    2015-01-01

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

  6. Factors affecting sexual function in menopause: A review article.

    PubMed

    Nazarpour, Soheila; Simbar, Masoumeh; Tehrani, Fahimeh Ramezani

    2016-08-01

    This study aimed to systematically review the articles on factors affecting sexual function during menopause. Searching articles indexed in Pubmed, Science Direct, Iranmedex, EMBASE, Scopus, and Scientific Information Database databases, a total number of 42 studies published between 2003 and 2013 were selected. Age, estrogen deficiency, type of menopause, chronic medical problems, partner's sex problems, severity of menopause symptoms, dystocia history, and health status were the physical factors influencing sexual function of menopausal women. There were conflicting results regarding the amount of androgens, hormonal therapy, exercise/physical activity, and obstetric history. In the mental-emotional area, all studies confirmed the impact of depression and anxiety. Social factors, including smoking, alcohol consumption, the quality of relationship with husband, partner's loyalty, sexual knowledge, access to health care, a history of divorce or the death of a husband, living apart from a spouse, and a negative understanding of women's health were found to affect sexual function; however, there were conflicting results regarding the effects of education, occupation, socioeconomic status, marital duration, and frequency of sexual intercourse. PMID:27590367

  7. Microbial composition affects the functioning of estuarine sediments

    PubMed Central

    Reed, Heather E; Martiny, Jennifer BH

    2013-01-01

    Although microorganisms largely drive many ecosystem processes, the relationship between microbial composition and their functioning remains unclear. To tease apart the effects of composition and the environment directly, microbial composition must be manipulated and maintained, ideally in a natural ecosystem. In this study, we aimed to test whether variability in microbial composition affects functional processes in a field setting, by reciprocally transplanting riverbed sediments between low- and high-salinity locations along the Nonesuch River (Maine, USA). We placed the sediments into microbial ‘cages' to prevent the migration of microorganisms, while allowing the sediments to experience the abiotic conditions of the surroundings. We performed two experiments, short- (1 week) and long-term (7 weeks) reciprocal transplants, after which we assayed a variety of functional processes in the cages. In both experiments, we examined the composition of bacteria generally (targeting the 16S rDNA gene) and sulfate-reducing bacteria (SRB) specifically (targeting the dsrAB gene) using terminal restriction fragment length polymorphism (T-RFLP). In the short-term experiment, sediment processes (CO2 production, CH4 flux, nitrification and enzyme activities) depended on both the sediment's origin (reflecting differences in microbial composition between salt and freshwater sediments) and the surrounding environment. In the long-term experiment, general bacterial composition (but not SRB composition) shifted in response to their new environment, and this composition was significantly correlated with sediment functioning. Further, sediment origin had a diminished effect, relative to the short-term experiment, on sediment processes. Overall, this study provides direct evidence that microbial composition directly affects functional processes in these sediments. PMID:23235294

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

    PubMed

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

    1985-01-01

    To elucidate the characteristics of measures of function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearman's rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579), and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand, correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease. PMID:4008592

  9. The role of regret minimisation in lifestyle choices affecting the risk of coronary heart disease.

    PubMed

    Boeri, Marco; Longo, Alberto; Grisolía, José M; Hutchinson, W George; Kee, Frank

    2013-01-01

    This paper introduces the discrete choice model-paradigm of Random Regret Minimisation (RRM) to the field of health economics. The RRM is a regret-based model that explores a driver of choice different from the traditional utility-based Random Utility Maximisation (RUM). The RRM approach is based on the idea that, when choosing, individuals aim to minimise their regret-regret being defined as what one experiences when a non-chosen alternative in a choice set performs better than a chosen one in relation to one or more attributes. Analysing data from a discrete choice experiment on diet, physical activity and risk of a fatal heart attack in the next ten years administered to a sample of the Northern Ireland population, we find that the combined use of RUM and RRM models offer additional information, providing useful behavioural insights for better informed policy appraisal. PMID:23228950

  10. Acute heart inflammation: ultrastructural and functional aspects of macrophages elicited by Trypanosoma cruzi infection

    PubMed Central

    Melo, Rossana C N

    2009-01-01

    Abstract The heart is the main target organ of the parasite Trypanosoma cruzi, the causal agent of Chagas' disease, a significant public health issue and still a major cause of morbidity and mortality in Latin America. During the acute disease, tissue damage in the heart is related to the intense myocardium parasitism. To control parasite multiplication, cells of the monocytic lineage are highly mobilized. In response to inflammatory and immune stimulation, an intense migration and extravasation of monocytes occurs from the bloodstream into heart. Monocyte differentiation leads to the formation of tissue phagocytosing macrophages, which are strongly activated and direct host defence. Newly elicited monocyte-derived macrophages both undergo profound physiological changes and display morphological heterogeneity that greatly differs from originally non-inflammatory macrophages, and underlie their functional activities as potent inflammatory cells. Thus, activated macrophages play a critical role in the outcome of parasite infection. This review covers functional and ultrastructural aspects of heart inflammatory macrophages triggered by the acute Chagas' disease, including recent discoveries on morphologically distinct, inflammation-related organelles, termed lipid bodies, which are actively formed in vivo within macrophages in response to T. cruzi infection. These findings are defining a broader role for lipid bodies as key markers of macrophage activation during innate immune responses to infectious diseases and attractive targets for novel anti-inflammatory therapies. Modulation of macrophage activation may be central in providing therapeutic benefits for Chagas' disease control. PMID:18624767

  11. Cyclin D2 rescues size and function of GATA4 haplo-insufficient hearts

    PubMed Central

    Yamak, Abir; Temsah, Rana; Maharsy, Wael; Caron, Sophie; Paradis, Pierre; Aries, Anne

    2012-01-01

    Transcription factor GATA4 is a key regulator of cardiomyocyte growth, and differentiation and 50% reduction in GATA4 levels results in hypoplastic hearts. Search for GATA4 targets/effectors revealed cyclin D2 (CD2), a member of the D-type cyclins (D1, D2, and D3) that play a vital role in cell growth and differentiation as a direct transcriptional target and a mediator of GATA4 growth in postnatal cardiomyocytes. GATA4 associates with the CD2 promoter in cardiomyocytes and is sufficient to induce endogenous CD2 transcription and to dose-dependently activate the CD2 promoter in heterologous cells. Cardiomyocyte-specific overexpression of CD2 results in enhanced postnatal cardiac growth because of increased cardiomyocyte proliferation. When these transgenic mice are crossed with Gata4 heterozygote mice, they rescue the hypoplastic cardiac phenotype of Gata4+/− mice and enhance cardiomyocyte survival and heart function. The data uncover a role for CD2 in the postnatal heart as an effector of GATA4 in myocyte growth and survival. The finding that postnatal upregulation of a cell-cycle gene in GATA4 haplo-insufficient hearts may be protective opens new avenues for maintaining or restoring cardiac function in GATA4-dependent cardiac disease. PMID:22923619

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Norton, Katelyn N.; Badrov, Mark B.; Barron, Carly C.; Suskin, Neville; Heinecke, Armin

    2015-01-01

    This study tested the hypothesis that coronary artery disease (CAD) alters the cortical circuitry associated with exercise. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 23 control subjects [control; 8 women; 63 ± 11 yr; mean arterial pressure (MAP): 90 ± 9 mmHg] (mean ± SD) and 17 similarly aged CAD patients (4 women; 59 ± 9 yr; MAP: 87 ± 10 mmHg). Four repeated bouts each of 30%, 40%, and 50% of maximal voluntary contraction (MVC) force (LAB session), and seven repeated bouts of isometric handgrip (IHG) at 40% MVC force (fMRI session), were performed, with each contraction lasting 20 s and separated by 40 s of rest. There was a main effect of group (P = 0.03) on HR responses across all IHG intensities. Compared with control, CAD demonstrated less task-dependent deactivation in the posterior cingulate cortex and medial prefrontal cortex, and reduced activation in the right anterior insula, bilateral precentral cortex, and occipital lobe (P < 0.05). When correlated with HR, CAD demonstrated reduced activation in the bilateral insula and posterior cingulate cortex, and reduced deactivation in the dorsal anterior cingulate cortex, and bilateral precentral cortex (P < 0.05). The increased variability in expected autonomic regions and decrease in total cortical activation in response to the IHG task are associated with a diminished HR response to volitional effort in CAD. Therefore, relative to similarly aged and healthy individuals, CAD impairs the heart rate response and modifies the cortical patterns associated with cardiovascular control during IHG. PMID:25972576

  14. Quality of life and cardiorespiratory function in chronic heart failure: effects of 12 months' aerobic training.

    PubMed Central

    Kavanagh, T.; Myers, M. G.; Baigrie, R. S.; Mertens, D. J.; Sawyer, P.; Shephard, R. J.

    1996-01-01

    OBJECTIVE: To examine the long-term benefits and safety of aerobic training in patients with chronic heart failure. DESIGN: Non-randomised control trial with 52 weeks follow up. SETTING: Outpatient cardiac rehabilitation referral centre. PATIENTS: Patients with compensated chronic heart failure (mean (SD) age 62 (6) years, New York Heart Association stage III, initial resting ejection fraction 22 (7)%). Experimental group of 17 men, 4 women; control group 8 men, 1 woman. INTERVENTIONS: Experimental group: progressive, supervised aerobic walking programme for 52 weeks. Control group: standard medical treatment. MAIN OUTCOME MEASURES: Six-minute walk distance, progressive cycle ergometer test to subjective exhaustion, disease-specific quality of life questionnaire, and standard gamble test, all measured at entry, 4, 8, 12, 16, 26, and 52 weeks. RESULTS: Control data showed no changes except a small trend to improved emotional function (P = 0.02 at 12 weeks only). Fifteen of the 21 patients completed all 52 weeks of aerobic training; two withdrew for non-cardiac reasons (16, 52 weeks). Three were withdrawn because of worsening cardiac failure unrelated to their exercise participation (4, 4, 8 weeks), and one had a non-fatal cardiac arrest while shopping (16 weeks). Gains of cardiorespiratory function plateaued at 16-26 weeks, with 10-15% improvement in six-minute walk, peak power output, and peak oxygen intake linked to gains in oxygen pulse and ventilatory threshold and reductions in resting heart rate. Marked improvements in quality of life followed a parallel course. CONCLUSIONS: Aerobic training is safe and beneficial in compensated chronic heart failure. Gains in aerobic function and quality of life persisted over a programme lasting 52 weeks. PMID:8774326

  15. Vascular Endothelial Growth Factor Prevents Apoptosis and Preserves Contractile Function in Hypertrophied Infant Heart

    PubMed Central

    Friehs, Ingeborg; Barillas, Rodrigo; Vasilyev, Nikolay V.; Roy, Nathalie; McGowan, Francis X.; del Nido, Pedro J.

    2012-01-01

    Background Cardiac hypertrophy is an adaptive response to increased workload that, if unrelieved, leads to heart failure. It has been reported that cardiomyocyte apoptosis contributes to failure, and that vascular endothelial growth factor (VEGF) treatment of hypertrophied myocardium increases capillary density and improves myocardial perfusion. In this study we hypothesized that VEGF treatment reduces cardiomyocyte apoptosis and thereby preserves myocardial contractile function. Methods and Results Newborn rabbits underwent aortic banding. At 4 and 6 weeks of age, hypertrophied animals were treated with intrapericardial administration of recombinant VEGF protein. Three groups of animals were investigated: age-matched controls (C), untreated hypertrophied (H), and VEGF-treated hypertrophied hearts (T). Cardiomyocyte apoptosis was determined by TUNEL staining and PARP cleavage (immunoblotting of nuclear extracts) and cardiac function by transthoracic echocardiography. Death attributable to severe heart failure occurred in 14 of 43 untreated and 2 of 29 VEGF-treated animals (P<0.01). TUNEL-positive cardiomyocyte nuclei (n/1000 nuclei) were significantly increased in untreated hearts at 5 weeks (H: 10±1.8 versus T: 3±0.7) and at 7 weeks (H: 13±3.6 versus T: 5±1.5; P<0.05). Increased apoptosis in untreated hypertrophy was also confirmed by the presence of PARP cleavage (H: 74±7 versus T: 41±4 arbitrary densitometry units; P<0.05). VEGF treatment preserved left ventricular mass, prevented dilation (T: 1.01±0.06 versus H: 0.77±0.07; P<0.05), and preserved contractility indices compared with untreated hearts. Conclusions Lack of adaptive capillary growth impairs myocardial perfusion and substrate delivery in hypertrophying myocardium. VEGF treatment reduces myocardial apoptosis and prolongs survival in a model of severe progressive left ventricular hypertrophy. Promoting capillary growth with VEGF reduces apoptosis, preserves myocardial contractile function, and

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  17. [Improved kidney function with intravenous prostaglandin E1 in patients with terminal heart failure].

    PubMed

    Wutte, M; Hülsmann, M; Berger, R; Rödler, S; Frey, B; Stanek, B; Pacher, R

    1998-07-31

    In end stage congestive heart failure activation of a series of compensatory mechanisms increase renal vascular resistance and impair renal function. Prostaglandin E1 is increasingly used in the treatment of severe heart failure for its vasodilating actions. In various experimental settings prostaglandin E analogues are known to improve renal function by modulating renal filtration pressure and redistribution of renal blood flow. However, prostaglandin E1 decreases systemic blood pressure and thus, also renal perfusion pressure, a fact by which renal function might be further compromized in heart failure patients. The aim of the study was to evaluate the effects of prostaglandin E1 on excretory renal function in patients with end stage heart failure and to prove the hypothesis, that the well known local actions of prostaglandins on renal microcirculation might outweigh the negative impact of an expected decrease in perfusion pressure. 25 patients with terminal congestive heart failure were investigated. 13 patients received prostaglandin E1 at a dose of 13.5 +/- 1.9 ng/kg/min in combination with constant rates of dopamine and dobutamine (group A), 12 patients received prostaglandin E1 at a dose of 10.3 +/- 1.7 ng/kg/min without catecholamines (group B). There was no significant difference in prostaglandin dosages between groups. Kidney function was assessed by measuring plasma creatinine and urea nitrogen, urinary output, creatinine clearance, osmotic and free water clearance at baseline and after 72 h of infusion therapy. Hemodynamic parameters were measured by using a balloon tipped pulmonary arterial catheter. Hemodynamic measurements during infusion showed a significant improvement in all patients. At the same time as expected mean arterial pressure decreased in both groups (p < 0.001). Nevertheless, in both groups a significant increase of creatinine clearance during infusion was observed (in group A from 45 ml/min to 78 ml/min., p < 0.05, in group B from 59

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

    NASA Astrophysics Data System (ADS)

    Lee, Chen-Ting; Repasky, Elizabeth A.

    2011-03-01

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

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

    PubMed

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

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts. PMID:24284259

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

    PubMed

    Khraiche, Diala; Ben Moussa, Nidhal

    2016-02-01

    Postoperative impairment of right ventricular (RV) systolic function can appear after surgical repair of complex congenital heart defects, such as tetralogy of Fallot; it is caused by chronic volume and/or pressure overload due to pulmonary regurgitation and/or stenosis. RV dysfunction is strongly associated with prognosis in these patients. Cardiac magnetic resonance imaging is the gold standard for quantification of RV volumes and ejection fraction in patients with congenital heart diseases; however, it is costly and is not widely available. Echocardiography is the imaging modality that is most available and most frequently used to assess RV systolic function. However, RV ejection fraction cannot be measured accurately by standard two-dimensional echocardiography because of its pyramidal shape. Surrogate parameters of RV systolic function are mostly used in routine practice. New techniques of two-dimensional strain and three-dimensional quantification of RV volumes and ejection fraction have been developed in recent years. The aim of this article is to show the pertinence of each variable of RV systolic function measured by echocardiography in patients with repaired congenital heart disease and residual chronic RV overload. PMID:26774976

  1. Trbp regulates heart function through miRNA-mediated Sox6 repression

    PubMed Central

    Ding, Jian; Chen, Jinghai; Wang, Yanqun; Kataoka, Masaharu; Ma, Lixin; Zhou, Pingzhu; Hu, Xiaoyun; Lin, Zhiqiang; Nie, Mao; Deng, Zhong-Liang; Pu, William T; Wang, Da-Zhi

    2015-01-01

    Cardiomyopathy is associated with altered expression of genes encoding contractile proteins. Here we show that Trbp (Tarbp2), an RNA binding protein, is required for normal heart function. Cardiac-specific inactivation of Trbp (TrbpcKO) caused progressive cardiomyopathy and lethal heart failure. Trbp loss of function resulted in upregulation of Sox6, repression of genes encoding normal cardiac slow-twitch myofiber proteins, and pathologically increased expression of skeletal fast-twitch myofiber genes. Remarkably, knockdown of Sox6 fully rescued the Trbp mutant phenotype, whereas Sox6 overexpression phenocopied the TrbpcKO phenotype. Trbp inactivation was mechanistically linked to Sox6 upregulation through altered processing of miR-208a, which is a direct inhibitor of Sox6. Transgenic overexpression of miR-208a sufficiently repressed Sox6, restored the balance of fast- and slow- twitch myofiber gene expression, and rescued cardiac function in TrbpcKO mice. Together, our studies reveal a novel Trbp-mediated microRNA processing mechanism in regulating a linear genetic cascade essential for normal heart function. PMID:26029872

  2. Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart

    PubMed Central

    Khan, Mahmood; Meduru, Sarath; Mohan, Iyyapu K.; Kuppusamy, M. Lakshmi; Wisel, Sheik; Kulkarni, Aditi; Rivera, Brian K.; Hamlin, Robert L.; Kuppusamy, Periannan

    2009-01-01

    A major limitation to the application of stem-cell therapy to repair ischemic heart damage is the low survival of transplanted cells in the heart, possibly due to poor oxygenation. We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant treatment to augment stem-cell therapy. Therefore, the goal of this study was to evaluate the effect of HBO on the engraftment of rat bone-marrow-derived mesenchymal stem cells (MSCs) transplanted in infarct rat hearts. Myocardial infarction (MI) was induced in Fisher-344 rats by permanently ligating the left-anterior-descending coronary artery. MSCs, labeled with fluorescent superparamagnetic iron oxide (SPIO) particles, were transplanted in the infarct and peri-infarct regions of the MI hearts. HBO (100% oxygen at 2 ATA for 90 min) was administered daily for 2 weeks. Four MI groups were used: untreated (MI); HBO; MSC; MSC+HBO. Echocardiography, electro-vectorcardiography, and magnetic resonance imaging were used for functional evaluations. The engraftment of transplanted MSCs in the heart was confirmed by SPIO fluorescence and Prussian-blue staining. Immunohistochemical staining was used to identify key cellular and molecular markers including CD29, troponin-T, connexin-43, VEGF, α-smooth-muscle actin, and von-Willebrand factor in the tissue. Compared to MI and MSC groups, the MSC+HBO group showed a significantly increased recovery of cardiac function including left-ventricular (LV) ejection fraction, fraction-shortening, LV wall-thickness, and QRS vector. Further, HBO treatment significantly increased the engraftment of CD29-positive cells, expression of connexin-43, troponin-T and VEGF, and angiogenesis in the infarct tissue. Thus, HBO appears to be a potential and clinically-viable adjuvant treatment for myocardial stem-cell therapy. PMID:19376124

  3. Out of mind, out of heart: attention affects duration of emotional experience.

    PubMed

    Freund, Alexandra M; Keil, Andreas

    2013-01-01

    It has been suggested that the extent to which a person maintains attention to pleasant versus unpleasant aspects of a given stimulus has an effect on the self-reported affective state. This assumption was empirically tested in two experiments. In Study 1, participants received the instruction either to focus on a positive emotion-eliciting event (winning a tournament chess game) or to focus their attention on an affectively neutral distraction task (describing drawings). Study 2 used negative performance feedback in a cognitive task to induce unpleasant affect and included three experimental groups (waiting condition, continuing with the same cognitive task, distraction by a different cognitive task). Results converged to show that distracting attention away from the emotion-eliciting event leads to a shorter duration of the emotional experience. These findings support the attention-focus hypothesis. PMID:22963519

  4. Bisphenol A affects androgen receptor function via multiple mechanisms

    PubMed Central

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

    2013-01-01

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. PMID:23562765

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

    PubMed

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

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. PMID:23562765

  6. New York Heart Association functional class predicts exercise parameters in the current era

    PubMed Central

    Russell, Stuart D.; Saval, Matthew A.; Robbins, Jennifer L.; Ellestad, Myrvin H.; Gottlieb, Stephen S.; Handberg, Eileen M.; Zhou, Yi; Chandler, Bleakley

    2009-01-01

    The New York Heart Association (NYHA) functional class is a subjective estimate of a patient's functional ability based on symptoms that does not always correlate with the objective estimate of functional capacity, peak oxygen consumption (peak VO2). Additionally, relationships between these two measurements have not been examined in the current medical era when patients are using beta blockers, aldosterone antagonists, and cardiac resynchronization therapy (CRT). Using baseline data from the HF-ACTION (Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing) study, we examined this relationship. Methods 1758 patients underwent a symptom limited metabolic stress test and stopped exercise due to dyspnea or fatigue. The relationship between NYHA functional class and peak VO2 was examined. Additionally, the effects of beta blockers, aldosterone antagonists, and CRT therapy on these relationships were compared. Results NYHA II patients have a significantly higher peak VO2 (16.1 ± 4.6 vs. 13.0 ± 4.2 ml/kg/min), a lower Ve/VCO2 slope (32.8 ± 7.7 versus 36.8 ± 10.4), and a longer duration of exercise (11.0 ± 3.9 versus 8.0 ± 3.4 minutes) than NYHA III/IV patients. Within each functional class, there is no difference in any of the exercise parameters between patients on or off of beta blockers, aldosterone antagonists, or CRT therapy. Finally, with increasing age a significant difference in peak VO2, Ve/VCO2 slope, and exercise time was found. Conclusion For patients being treated with current medical therapy, there still is a difference in true functional capacity between NYHA functional class II and III/IV patients. However, within each NYHA functional class, the presence or absence or contemporary heart failure therapies does not alter exercise parameters. PMID:19782785

  7. Acute Mountain Sickness, Hypoxia, Hypobaria and Exercise Duration each Affect Heart Rate.

    PubMed

    DiPasquale, D M; Strangman, G E; Harris, N S; Muza, S R

    2015-07-01

    In this study, we quantified the changes in post-exercise resting heart rate (HRrst) associated with acute mountain sickness (AMS), and compared the effects of hypobaric hypoxia (HH) and normobaric hypoxia (NH) on HRrst. We also examined the modulating roles of exercise duration and exposure time on HRrst. Each subject participated in 2 of 6 conditions: normobaric normoxia (NN), NH, or HH (4 400 m altitude equivalent) combined with either 10 or 60 min of moderate cycling at the beginning of an 8-h exposure. AMS was associated with a 2 bpm higher HRrst than when not sick, after taking into account the ambient environment, exercise duration, and SpO2. In addition, HRrst was elevated in both NH and HH compared to NN with HRrst being 50% higher in HH than in NH. Participating in long duration exercise led to elevated resting HRs (0.8-1.4 bpm higher) compared with short exercise, while short exercise caused a progressive increase in HRrst over the exposure period in both NH and HH (0.77-1.2 bpm/h of exposure). This data suggests that AMS, NH, HH, exercise duration, time of exposure, and SpO2 have independent effects on HRrst. It further suggests that hypobaria exerts its own effect on HRrst in hypoxia. Thus NH and HH may not be interchangeable environments. PMID:25837245

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

    PubMed

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

    2015-01-01

    Longevity and quality of life for left ventricular assist device (LVAD) patients are plagued by driveline exit site infections. Ultraviolet (UV) radiation, a current treatment in wound healing clinics, could potentially treat LVAD exit site infections. However, the effect of UV radiation on the tensile properties of HeartMate II (HMII) driveline material is unknown. The sleeve of a single HMII driveline was distributed into six exposure groups (n = 10/group). The six groups were further divided into two treatment cohorts designed to replicate wound treatment schedules of postimplant LVAD patients. Strip biaxial tensile tests were performed on both unexposed and exposed samples to analyze changes in material elasticity (Young's modulus), point of deformation (yield strength), and breaking point. Our data suggest that UV exposure changes the elasticity of the HMII driveline. However, the material endured aberrantly large forces and the properties remained within the safety threshold of device performance. This study warrants further examination of the effect of UV light on driveline material, to determine safety, reliability, and efficacy of UV treatment on exit site infections. PMID:26102175

  9. Investigation of factors affecting fluorometric quantitation of cytosolic [Ca2+] in perfused hearts.

    PubMed Central

    Brandes, R; Figueredo, V M; Camacho, S A; Baker, A J; Weiner, M W

    1993-01-01

    The goal of these studies was to examine the effects of several factors that may artifactually influence quantitation of cytosolic [Ca2+], [Ca2+]c, while using the fluorescent calcium indicator Indo-1. The following factors were investigated: 1) a possible fluorescence contribution from unhydrolized Indo-1/AM (by Mn2+ quenching), 2) Ca2+ buffering by Indo-1 (by varying [Indo-1]), 3) endothelial and mitochondrial Indo-1 loading (by bradykinin stimulation and calculations), and 4) effects of changing tissue fluorescence (predominantly NAD(P)H) on calculated [Ca2+]c during hypoxia (by a new method which allowed simultaneous determination of [Ca2+]c and changes in [NAD(P)H]). No significant contribution of Indo-1/AM was found. With increasing [Indo-1], calculated systolic [Ca2+]c fell significantly. Indo-1 incorporation (< 18%) into endothelial cells, caused a slight underestimation of systolic [Ca2+]c, while mitochondrial Indo-1 loading may cause overestimation of [Ca2+]c. With increased tissue fluorescence, during hypoxia, systolic [Ca2+]c may be underestimated by approximately 27% (for Indo-1 loading factors three to five times original tissue fluorescence). These studies suggest conditions in which experimental artifacts could be minimized to allow reliable quantitation of [Ca2+]c in intact perfused hearts using Indo-1 fluorometry. The major problem of obtaining reliable results depended on the ability to correct for changing NAD(P)H fluorescence while keeping [Indo-1] low. PMID:8298028

  10. Radiation from wireless technology affects the blood, the heart, and the autonomic nervous system.

    PubMed

    Havas, Magda

    2013-01-01

    Exposure to electrosmog generated by electric, electronic, and wireless technology is accelerating to the point that a portion of the population is experiencing adverse reactions when they are exposed. The symptoms of electrohypersensitivity (EHS), best described as rapid aging syndrome, experienced by adults and children resemble symptoms experienced by radar operators in the 1940s to the 1960s and are well described in the literature. An increasingly common response includes clumping (rouleau formation) of the red blood cells, heart palpitations, pain or pressure in the chest accompanied by anxiety, and an upregulation of the sympathetic nervous system coincident with a downregulation of the parasympathetic nervous system typical of the "fight-or-flight" response. Provocation studies presented in this article demonstrate that the response to electrosmog is physiologic and not psychosomatic. Those who experience prolonged and severe EHS may develop psychologic problems as a consequence of their inability to work, their limited ability to travel in our highly technologic environment, and the social stigma that their symptoms are imagined rather than real. PMID:24192494

  11. [The effect of transvenous laser therapy on lipid peroxidation function in patients with ischemic heart disease].

    PubMed

    Vakhliaev, V D; Smirnova, I E; Uchaĭkina, L V; Barsel', V A; Aksiutina, M S; Matveeva, S A; Paramonova, M A; Shchedrina, I S; Syrkin, A L

    1992-07-01

    The papers deals with changes in the levels of lipid peroxidation products in patients with stable angina of effort, which occurred with intravenous helium-neon blood irradiation. The therapy was highly effective in patients with lower functional classes and persons with normal circulation, resulting in a reduction in lipid peroxidation intensity. Predictors are recommended to determine the efficiency and expediency of laser therapy in patients with coronary heart disease. PMID:1487878

  12. Effects of Exercise Training on Autonomic Function in Chronic Heart Failure: Systematic Review

    PubMed Central

    Hsu, Chung-Yin; Hsieh, Ping-Lun; Hsiao, Shu-Fang; Chien, Meng-Yueh

    2015-01-01

    Objectives. Cardiac autonomic imbalance accompanies the progression of chronic heart failure (CHF). It is unclear whether exercise training could modulate autonomic control in CHF. This study aimed to review systematically the effects of exercise training on heart rate recovery (HRR) and heart rate variability (HRV) in patients with CHF. Methods. Literatures were systematically searched in electronic databases and relevant references. Only published randomized controlled trials (RCTs) focusing on exercise training for CHF were eligible for inclusion. Outcome measurements included HRR and HRV parameters. Results. Eight RCTs were eligible for inclusion and provided data on 280 participants (186 men). The participants were 52–70 years of age with New York Heart Association functional class II-III of CHF. Each study examined either aerobic or resistance exercise. Two trials addressed outcome of HRR and six HRV among these studies. Two RCTs showed that moderate aerobic exercise could improve HRR at 2 minutes after exercise training in CHF. Five of six RCTs demonstrated positive effects of exercise training on HRV which revealed the increments in high frequency (HF) and decrements in LF (low frequency)/HF ratio after training. Conclusion. Participation in an exercise training program has positive effects on cardiac autonomic balance in patients with CHF. PMID:26543861

  13. SRC-2 Coactivator Deficiency Decreases Functional Reserve in Response to Pressure Overload of Mouse Heart

    PubMed Central

    Reineke, Erin L.; York, Brian; Stashi, Erin; Chen, Xian; Tsimelzon, Anna; Xu, Jianming; Newgard, Christopher B.; Taffet, George E.; Taegtmeyer, Heinrich; Entman, Mark L.; O’Malley, Bert W.

    2012-01-01

    A major component of the cardiac stress response is the simultaneous activation of several gene regulatory networks. Interestingly, the transcriptional regulator steroid receptor coactivator-2, SRC-2 is often decreased during cardiac failure in humans. We postulated that SRC-2 suppression plays a mechanistic role in the stress response and that SRC-2 activity is an important regulator of the adult heart gene expression profile. Genome-wide microarray analysis, confirmed with targeted gene expression analyses revealed that genetic ablation of SRC-2 activates the “fetal gene program” in adult mice as manifested by shifts in expression of a) metabolic and b) sarcomeric genes, as well as associated modulating transcription factors. While these gene expression changes were not accompanied by changes in left ventricular weight or cardiac function, imposition of transverse aortic constriction (TAC) predisposed SRC-2 knockout (KO) mice to stress-induced cardiac dysfunction. In addition, SRC-2 KO mice lacked the normal ventricular hypertrophic response as indicated through heart weight, left ventricular wall thickness, and blunted molecular signaling known to activate hypertrophy. Our results indicate that SRC-2 is involved in maintenance of the steady-state adult heart transcriptional profile, with its ablation inducing transcriptional changes that mimic a stressed heart. These results further suggest that SRC-2 deletion interferes with the timing and integration needed to respond efficiently to stress through disruption of metabolic and sarcomeric gene expression and hypertrophic signaling, the three key stress responsive pathways. PMID:23300926

  14. Somatic, but not cognitive–affective, symptoms are associated with reduced heart rate variability in individuals with dysphoria

    PubMed Central

    Benvenuti, Simone Messerotti; Buodo, Giulia; Mennella, Rocco; Palomba, Daniela

    2015-01-01

    Background: Somatic, but not cognitive–affective, symptoms of depression have been associated with reduced heart rate variability (HRV), and with poor prognosis in cardiovascular patients. However, factors concomitant with cardiovascular diseases may confound the relationship between somatic symptoms of depression and reduced HRV. Therefore, this study examined whether reduced HRV was differentially associated with cognitive–affective and somatic symptoms of depression in medically healthy individuals with and without dysphoria. Methods: Self-reported cognitive–affective and somatic symptoms as measured with the Beck Depression Inventory-II questionnaire and time and frequency domain parameters of HRV were collected in 62 medically healthy individuals, of whom 25 with and 37 without dysphoria. Results: Somatic, but not cognitive–affective, symptoms of depression were inversely associated with SD of NN intervals (β = -0.476, p < 0.05), number of interval differences of successive NN intervals greater than 50 ms (NN50; β = -0.498, p < 0.03), and HRV total power (β = -0.494, p < 0.04) in the group with dysphoria, after controlling for sex, anxiety, and lifestyle factors. Cognitive–affective and somatic symptoms were not related to any of the HRV parameters in the group without dysphoria (all ps > 0.24). Conclusion: By showing that the relationship between somatic depressive symptoms and reduced HRV extends to medically healthy individuals with dysphoria, the present findings suggest that this association is independent of factors concomitant with cardiovascular diseases. The present study also suggests that individuals with somatic rather than cognitive–affective subsets of depressive symptoms may be at greater risk for developing cardiovascular diseases. PMID:25999905

  15. Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion.

    PubMed

    Senthamizhselvan, Oomaidurai; Manivannan, Jeganathan; Silambarasan, Thangarasu; Raja, Boobalan

    2014-08-01

    Reperfusion of ischemic tissue leads to the generation of oxygen derived free radicals which plays an important role in cellular damage. Objective of the current study is to evaluate the cardio-protective and antioxidant effect of diosmin on ischemia-reperfusion related cardiac dysfunction, oxidative stress and apoptosis. Diosmin (50 and 100 mg/kg body weight (bw)) was given every day to the rats orally throughout the experimental period. Ischemia/reperfusion protocol was carried out ex vivo using langendorff perfusion method and the cardiac functional recovery was assessed in terms of percentage rate pressure product. Coronary effluents of LDH and CK-MB activities, antioxidant enzyme activities, lipid peroxidation products, activity of TCA cycle enzymes were evaluated. Moreover, in vitro superoxide anion and hydroxyl radical scavenging potential of diosmin was also quantified. Finally, quantitative real-time PCR was used for assessing Bcl-2 mRNA expression in heart. Cardiac functional recovery was impaired after reperfusion compared with continuously perfused heart. It was significantly prevented by diosmin treatment. Impaired antioxidant enzyme activities and elevated lipid peroxidation products level were also significantly suppressed. The activity of TCA cycle enzymes was protected against reperfusion stress. Down regulated Bcl-2 was also significantly increased. This study concluded that diosmin pretreatment prevents all the impaired patterns including cardiac function, oxidative stress and apoptosis associated with reperfusion in control heart by its antioxidant role. PMID:24769512

  16. Physical Exercise Improves The Functional Capacity and Quality of Life in Patients With Heart Failure

    PubMed Central

    Bocalini, Danilo Sales; dos Santos, Leonardo; Serra, Andrey Jorge

    2008-01-01

    OBJECTIVE The purpose of this study was to investigate the effects of physical exercise on the functional capacity and quality of life in heart failure patients. METHODS Forty-two patients of both sexes with heart failure of NYHA class II and III with different etiologies were randomly divided into untrained or trained groups. The six-month exercise program consisted of aerobic training, muscle strength training, agility and joint flexibility activities. Physical fitness was evaluated by testing the performance on these trained components. Quality of life was evaluated by scored answers to a standardized questionnaire involving multiple domains. RESULTS Baseline values did not differ between groups. Improvement in the trained group was identified in all components of functional capacity when compared to the untrained group (p < 0.001). Quality of life improved in the trained patients concerning physical, psychological, social and environmental domains (p < 0.001), whereas no significant change was found in the untrained patients. CONCLUSIONS Guided and monitored physical exercise is safe and has the potential to improve functional capacity and quality of life in heart failure patients with multiple etiologies. PMID:18719752

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

    PubMed Central

    Hehemann, Marah C.

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  19. Scorpion venom components that affect ion-channels function

    PubMed Central

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

    2014-01-01

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

  20. Posture and Gender Differentially Affect Heart Rate Variability of Symptomatic Mitral Valve Prolapse and Normal Adults

    PubMed Central

    Chang, Chien-Jung; Chen, Ya-Chu; Lee, Chih-Hsien; Yang, Ing-Fang; Yang, Ten-Fang

    2016-01-01

    Background Heart rate variability (HRV) has been shown to be a useful measure of autonomic activity in healthy and mitral valve prolapsed (MVP) subjects. However, the effects of posture and gender on HRV in symptomatic MVP and normal adults had not been elucidated in Taiwan. Methods A total of 118 MVP patients (7 males, 39 ± 7 years old; and 111 females, 42 ± 13 years old) and 148 healthy control (54 males, 28 ± 4 years old; and 94 females, 26 ± 6 years old) were investigated. The diagnosis of MVP was confirmed by cross-sectional echocardiography. A locally developed Taiwanese machine was used to record the HRV parameters for MVP and control groups in three stationary positions. Thereafter, the HRV time-domain parameters, and the frequency-domain parameters derived from fast Fourier transform or autoregressive methods were analyzed. Results The MVP group showed a decrease in time domain parameters and obtunded postural effects on frequency domain parameters moreso than the control group. Though the parasympathetic tone was dominant in female (higher RMSSD, nHF and lower nLF vs. male), the sympathetic outflow was higher in MVP female (lower SDNN, NN50 and higher nLF vs. normal female). While the parasympathetic activity was lower in male, sympathetic outflow was dominant in MVP male (lower nHF and higher nLF vs. normal male). Conclusions Both MVP female and male subjects had elevated levels of sympathetic outflow. The obtunded postural effects on frequency domain measures testified to the autonomic dysregulation of MVP subjects. PMID:27471360

  1. Integrating Negative Affect Measures in a Measurement Model: Assessing the Function of Negative Affect as Interference to Self-Regulation

    ERIC Educational Resources Information Center

    Magno, Carlo

    2010-01-01

    The present study investigated the composition of negative affect and its function as inhibitory to thought processes such as self-regulation. Negative affect in the present study were composed of anxiety, worry, thought suppression, and fear of negative evaluation. These four factors were selected based on the criteria of negative affect by…

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

    PubMed

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

    2015-03-15

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

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

    PubMed Central

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

    2015-01-01

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

  4. Effect of cardiac resynchronization therapy on pulmonary function in patients with heart failure.

    PubMed

    Cundrle, Ivan; Johnson, Bruce D; Somers, Virend K; Scott, Christopher G; Rea, Robert F; Olson, Lyle J

    2013-09-15

    Pulmonary congestion due to heart failure causes abnormal lung function. Cardiac resynchronization therapy (CRT) is a proven effective treatment for heart failure. The aim of this study was to test the hypothesis that CRT promotes increased lung volumes, bronchial conductance, and gas diffusion. Forty-four consecutive patients with heart failure were prospectively investigated before and after CRT. Spirometry, gas diffusion (diffusing capacity for carbon monoxide), cardiopulmonary exercise testing, New York Heart Association class, brain natriuretic peptide, the left ventricular ejection fraction, left atrial volume, and right ventricular systolic pressure were assessed before and 4 to 6 months after CRT. Pre- and post-CRT measures were compared using either paired Student's t tests or Wilcoxon's matched-pair test; p values <0.05 were considered significant. Improved New York Heart Association class, left ventricular ejection fraction, left atrial volume, right ventricular systolic pressure, and brain natriuretic peptide were observed after CRT (p <0.05 for all). Spirometry after CRT demonstrated increased percentage predicted total lung capacity (90 ± 17% vs 96 ± 15%, p <0.01) and percentage predicted forced vital capacity (80 ± 19% vs 90 ± 19%, p <0.01). Increased percentage predicted total lung capacity was significantly correlated with increased peak exercise end-tidal carbon dioxide (r = 0.43, p = 0.05). Increased percentage predicted forced vital capacity was significantly correlated with decreased right ventricular systolic pressure (r = -0.30, p = 0.05), body mass index (r = -0.35, p = 0.02) and creatinine (r = -0.49, p = 0.02), consistent with an association of improved bronchial conductance and decreased congestion. Diffusing capacity for carbon monoxide did not significantly change. In conclusion, increased lung volumes and bronchial conductance due to decreased pulmonary congestion and increased intrathoracic space contribute to an improved

  5. Functional Amyloid Signaling via the Inflammasome, Necrosome, and Signalosome: New Therapeutic Targets in Heart Failure.

    PubMed

    Parry, Traci L; Melehani, Jason H; Ranek, Mark J; Willis, Monte S

    2015-01-01

    As the most common cause of death and disability, globally, heart disease remains an incompletely understood enigma. A growing number of cardiac diseases are being characterized by the presence of misfolded proteins underlying their pathophysiology, including cardiac amyloidosis and dilated cardiomyopathy (DCM). At least nine precursor proteins have been implicated in the development of cardiac amyloidosis, most commonly caused by multiple myeloma light chain disease and disease-causing mutant or wildtype transthyretin (TTR). Similarly, aggregates with PSEN1 and COFILIN-2 have been identified in up to one-third of idiopathic DCM cases studied, indicating the potential predominance of misfolded proteins in heart failure. In this review, we present recent evidence linking misfolded proteins mechanistically with heart failure and present multiple lines of new therapeutic approaches that target the prevention of misfolded proteins in cardiac TTR amyloid disease. These include multiple small molecule pharmacological chaperones now in clinical trials designed specifically to support TTR folding by rational design, such as tafamidis, and chaperones previously developed for other purposes, such as doxycycline and tauroursodeoxycholic acid. Last, we present newly discovered non-pathological "functional" amyloid structures, such as the inflammasome and necrosome signaling complexes, which can be activated directly by amyloid. These may represent future targets to successfully attenuate amyloid-induced proteotoxicity in heart failure, as the inflammasome, for example, is being therapeutically inhibited experimentally in autoimmune disease. Together, these studies demonstrate multiple novel points in which new therapies may be used to primarily prevent misfolded proteins or to inhibit their downstream amyloid-mediated effectors, such as the inflammasome, to prevent proteotoxicity in heart failure. PMID:26664897

  6. The influence of muscle action on heart rate, RPE, and affective responses after upper-body resistance exercise.

    PubMed

    Miller, Paul C; Hall, Eric E; Chmelo, Elizabeth A; Morrison, Jeffrey M; DeWitt, Rachel E; Kostura, Christine M

    2009-03-01

    Ratings of perceived exertion (RPE) are routinely used to monitor, assess, and prescribe aerobic exercise. Heart rate (HR) is another measure used to evaluate exercise intensity. Additionally, affective responses to aerobic exercise have been studied and seem to be influenced by the intensity of the exercise. The perceptual, HR, and affective responses to resistance exercise have not been effectively established. The purpose of this study was to examine whether differences in affect, RPE, and HR exist among college-aged women (n = 31) performing three different modes of resistance training: concentric (CE), eccentric (EE), and traditional concentric/eccentric (TE) performed at varying resistances. The women were asked to complete four sessions of resistance training on variable resistance machines: chest press, seated row, overhead press, and biceps curl. The first session was used to establish the 10-repetition maximum (RM) load for each station. Subsequent sessions involved the execution of training in one of the three test conditions: CE, EE, or TE. The participants performed three sets of each lift at 80% 10-RM, 100% 10-RM, and 120% 10-RM. The data revealed lower RPE during EE than the other test conditions. Similarly, EE elicited more mild HR response than either CE or TE. This finding is potentially important for the establishment of training programs, especially for those individuals recovering from an illness, who had been previously sedentary, and who are involved in rehabilitation of an injury. PMID:19204573

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

    PubMed

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

    2003-06-01

    We examined the development of infants' regional electrocortical (EEG) and heart rate (ECG) responses to affective musical stimuli during the first 12 months of post-natal life. Separate groups of infants were seen at 3 (n=33), 6 (n=42), 9 (n=52), and 12 (n=40) months of age at which time regional EEG and ECG responses were continuously recorded during a baseline condition and during the presentation of three orchestral pieces that were known to vary in affective valence and intensity (happy, sad, fear). Overall, there were two important findings. First, we found that although the overall amount of EEG 4-8 Hz power increased between 3 and 12 months, the distribution of EEG power changed across age, with the younger infants (3- and 6-month-olds) showing no difference between frontal and parietal regions, but the older infants (9- and 12-month-olds) showing relatively more activation at frontal than at parietal sites. This development likely reflects the maturation of frontal lobe function. Second, we found that the presentation of affective music significantly increased brain activity at 3 months of age, had seemingly little effect at 6 and 9 months, and significantly attenuated brain activity at 12 months. Findings suggest that there is a clear developmental change in the effect of music on brain activity in the first year, with music having a "calming" influence on infants by the end of the first year of life. PMID:12812802

  8. Remote at-home detection and monitoring of functional chronotropic incompetence in heart failure patients.

    PubMed

    Katra, Rodolphe P; Chakravarthy, Niranjan; Libbus, Imad

    2011-02-01

    Chronotropic incompetence (CI) is common in heart failure (HF) patients and is associated with worsening outcome. Detecting and tracking functional CI during activities of daily living could provide insight into its contribution to HF symptoms and facilitate effective HF patient management. HF patients (n = 180, NYHA Class III/IV, ejection fraction (EF) ≤40%) were enrolled in a multi-center prospective monitoring study and had an external multi-sensor system applied to the chest and replaced weekly during a 90-day study. Medical information was collected at baseline and study close. Heart rate, respiration, activity, and body fluid data from the system were transmitted at regular intervals and used for offline analysis. Patients were primarily male (70%), with 61 ± 13 years mean age, 25 ± 5 kg/m(2) BMI, and 28 ± 7% EF. By correlating age-adjusted activity level and heart rate adaptation with a proprietary algorithm, functional CI was detected in 45% and ruled out in 29% of patients under conditions of daily living. In the remaining patients (26%), functional CI assessment was indeterminate due to insufficient age-adjusted activity level. Functional CI and No-CI groups were not significantly different in terms of baseline demographics, characteristics or HF outcome over the study period. β-blocker use was 16% in the CI group and 82% in the no-CI group (p < 0.001), and therefore, could not explain the manifestation of functional CI. This proof-of-concept study suggests that a chronotropic response that may be functionally debilitating during activities of daily living in HF patients can be detected and tracked in a point-of-care telemonitoring approach using a non-invasive, adherent device. PMID:20931310

  9. Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors.

    PubMed

    Pustovit, Ksenia B; Kuzmin, Vladislav S; Abramochkin, Denis V

    2016-03-01

    Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart. PMID:26680209

  10. Grape polyphenols do not affect vascular function in healthy men.

    PubMed

    van Mierlo, Linda A J; Zock, Peter L; van der Knaap, Henk C M; Draijer, Richard

    2010-10-01

    Data suggest that polyphenol-rich products may improve endothelial function and other cardiovascular health risk factors. Grape and wine contain high amounts of polyphenols, but effects of these polyphenols have hardly been investigated in isolation in randomized controlled studies. Our objective in this study was to test the chronic effect of polyphenol-rich solids derived from either a wine grape mix or grape seed on flow-mediated dilation (FMD). Blood pressure and other vascular function measures, platelet function, and blood lipids were secondary outcomes. Thirty-five healthy males were randomized in a double-blind, placebo-controlled crossover study consisting of three 2-wk intervention periods separated by 1-wk washout periods. The test products, containing 800 mg of polyphenols, were consumed as capsules. At the end of each intervention period, effects were measured after consumption of a low-fat breakfast (~751 kJ, 25% fat) and a high-fat lunch (~3136 kJ, 78% fat). After the low-fat breakfast, the treatments did not significantly affect FMD. The absolute difference after the wine grape solid treatment was -0.4% (95% CI = -1.8 to 0.9; P = 0.77) and after grape seed solids, 0.2% (95% CI = -1.2 to 1.5; P = 0.94) compared with after the placebo treatment. FMD effects after the high-fat lunch and effects on secondary outcomes also showed no consistent differences between both of the grape solids and placebo treatment. In conclusion, consumption of grape polyphenols has no major impact on FMD in healthy men. Future studies should address whether grape polyphenols can improve FMD and other cardiovascular health risk factors in populations with increased cardiovascular risk. PMID:20702747

  11. Does Bowel Preparation for Colonoscopy Affect Cognitive Function?

    PubMed Central

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

    2015-01-01

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

  12. Does Bowel Preparation for Colonoscopy Affect Cognitive Function?

    PubMed

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

    2015-11-01

    Colonoscopy is a common procedure used in the diagnosis and treatment of a range of bowel disorders. Prior preparation involving potent laxatives is a necessary stage to ensure adequate visualization of the bowel wall. It is known that the sedatives given to most patients during the colonoscopy cause a temporary impairment in cognitive function; however, the potential for bowel preparation to affect cognitive function has not previously been investigated. To assess the effect of bowel preparation for colonoscopy on cognitive function. This was a prospective, nonrandomized controlled study of cognitive function in patients who had bowel preparation for colonoscopy compared with those having gastroscopy and therefore no bowel preparation. Cognitive function was assessed using the Modified Mini Mental State Examination (MMMSE) and selected tests from the Cambridge Neuropsychological Test Automated Battery. Individual test scores and changes between initial and subsequent tests were compared between the groups. Age, gender, and weight were also compared. Forty-three colonoscopy and 25 gastroscopy patients were recruited. The 2 groups were similar for age and gender; however, patients having gastroscopy were heavier. MMMSE scores for colonoscopy and gastroscopy groups, respectively, were 28.6 and 29.5 (P = 0.24) at baseline, 28.7 and 29.8 (P = 0.32) at test 2, 28.1 and 28.5 (P = 0.76) at test 3. Motor screening scores for colonoscopy and gastroscopy groups, respectively, were 349.3 and 354.1 (P = 0.97) at baseline, 307.5 and 199.7 (P = 0.06) at test 2, 212.0 and 183.2 (P = 0.33) at test 3. Spatial working memory scores for colonoscopy and gastroscopy groups, respectively, were 14.4 and 6.7 (P = 0.29) at baseline, 9.7 and 4.3 (P = 0.27) at test 2, 10 and 4.5 (P = 0.33) at test 3. Digit Symbol Substitution Test scores for colonoscopy and gastroscopy groups, respectively, were 36.3 and 37.8 (P = 0.84) at baseline, 36.4 and 40.0 (P

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

    SciTech Connect

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

    1988-07-01

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

  14. In vitro assessment of mitral valve function in cyclically pressurized porcine hearts.

    PubMed

    Vismara, Riccardo; Leopaldi, Alberto M; Piola, Marco; Asselta, Chiara; Lemma, Massimo; Antona, Carlo; Redaelli, Alberto; van de Vosse, Frans; Rutten, Marcel; Fiore, Gianfranco B

    2016-04-01

    Recent approaches to the in vitro experimental study of cardiac fluid mechanics involve the use of whole biological structures to investigate in the lab novel therapeutic approaches for the treatment of heart pathologies. To enhance reliability and repeatability, the influence of the actuation strategy of the experimental apparatuses on the biomechanics of biological structures needs to be assessed. Using echography and intracardiac high-speed imaging, we compared the mitral valve (MV) anatomo-functional features (coaptation areas/lengths, papillary muscles-valvular plane distances) in two passive-beating-heart mock loops with internal (IPML) or external (EPML) pressurization of the ventricular chamber. Both apparatuses showed fluid dynamic conditions that closely resembled the physiology. The MVs analyzed in the EPML presented coaptation areas and lengths that were systematically higher, and exhibited greater variability from early-to peak-systole, as compared to those in the IPML. Moreover, in the EPML, the MV leaflets exhibited a convexity with high curvature toward the atrium. With the IPML, MV coaptation lengths ranged similar to available clinical data and the papillary muscles-valve plane distances were more stable throughout systole. In conclusion, both the apparatuses allow for reproducing in vitro the left heart hemodynamics, in terms of flow rates and pressures, with proper mitral valve continence. Results suggest that the IPML is more suitable for replicating the physiological MV functioning, while the EPML may have more potential as a model for the study of MV pathologies. PMID:26908180

  15. Functional decorations: post-translational modifications and heart disease delineated by targeted proteomics

    PubMed Central

    2013-01-01

    The more than 300 currently identified post-translational modifications (PTMs) provides great scope for subtle or dramatic alteration of protein structure and function. Furthermore, the rapid and transient nature of many PTMs allows efficient signal transmission in response to internal and environmental stimuli. PTMs are predominantly added by enzymes, and the enzymes responsible (such as kinases) are thus attractive targets for therapeutic interventions. Modifications can be grouped according to their stability or transience (reversible versus irreversible): irreversible types (such as irreversible redox modifications or protein deamidation) are often associated with aging or tissue injury, whereas transient modifications are associated with signal propagation and regulation. This is particularly important in the setting of heart disease, which comprises a diverse range of acute (such as ischemia/reperfusion), chronic (such as heart failure, dilated cardiomyopathy) and genetic (such as hypertrophic cardiomyopathy) disease states, all of which have been associated with protein PTM. Recently the interplay between diverse PTMs has been suggested to also influence cellular function, with cooperation or competition for sites of modification possible. Here we discuss the utility of proteomics for examining PTMs in the context of the molecular mechanisms of heart disease. PMID:23445784

  16. Mechanisms Linking Energy Substrate Metabolism to the Function of the Heart

    PubMed Central

    Carley, Andrew N.; Taegtmeyer, Heinrich; Lewandowski, E. Douglas

    2015-01-01

    Metabolic signaling mechanisms are increasingly recognized to mediate the cellular response to alterations in workload demand, as a consequence of physiological and pathophysiological challenges. Thus, an understanding of the metabolic mechanisms coordinating activity in the cytosol with the energy-providing pathways in the mitochondrial matrix becomes critical for deepening our insights into the pathogenic changes that occur in the stressed cardiomyocyte. Processes that exchange both metabolic intermediates and cations between the cytosol and mitochondria enable transduction of dynamic changes in contractile state to the mitochondrial compartment of the cell. Disruption of such metabolic transduction pathways has severe consequences for the energetic support of contractile function in the heart and is implicated in the pathogenesis of heart failure. Deficiencies in metabolic reserve and impaired metabolic transduction in the cardiomyocyte can result from inherent deficiencies in metabolic phenotype or maladaptive changes in metabolic enzyme expression and regulation in the response to pathogenic stress. This review examines both current and emerging concepts of the functional linkage between the cytosol and the mitochondrial matrix with a specific focus on metabolic reserve and energetic efficiency. These principles of exchange and transport mechanisms across the mitochondrial membrane are reviewed for the failing heart from the perspectives of chronic pressure overload and diabetes mellitus. PMID:24526677

  17. In Sickness and in Health: a Literature Review about Function of Social Support within Anxiety and Heart Disease Association

    PubMed Central

    Zarbo, Cristina; Compare, Angelo; Baldassari, Elena; Bonardi, Alberto; Romagnoni, Claudia

    2013-01-01

    A narrative review of the major evidence concerning the relationship between anxiety, social support and cardiac disease was conducted. Literature demonstrates that a strict relationship between anxiety, social support and cardiac disease outcomes subsists. However, the function of social support within anxiety and heart disease association remains unclear and needs to further researches to be established. Moreover evidence suggests that it’s the quality of close relationships to play an important role in affecting psychological and physiological health status. The main components that the literature suggests for a better quality of social support and close relationship, and the main assessment measure are presented. Evidence about cardiac rehabilitation programs and the need to assess and intervene on psychological and psychosocial factors is discussed. PMID:24403952

  18. Extraction of heart rate from functional near-infrared spectroscopy in infants

    NASA Astrophysics Data System (ADS)

    Perdue, Katherine L.; Westerlund, Alissa; McCormick, Sarah A.; Nelson, Charles A.

    2014-06-01

    Changes in heart rate are a useful physiological measure in infant studies. We present an algorithm for calculating the heart rate (HR) from oxyhemoglobin pulsation in functional near-infrared spectroscopy (fNIRS) signals. The algorithm is applied to data collected from 10 infants, and the HR derived from the fNIRS signals is compared against the HR as calculated by electrocardiography. We show high agreement between the two HR signals for all infants (r>0.90), and also compare stimulus-related HR responses as measured by the two methods and find good agreement despite high levels of movement in the infants. This algorithm can be used to measure changes in HR in infants participating in fNIRS studies without the need for additional HR sensors.

  19. Long-Time Autocorrelation Function of ECG Signal for Healthy versus Diseased Human Heart

    NASA Astrophysics Data System (ADS)

    Kulessa, B.; Srokowski, T.; Drozdz, S.

    2003-01-01

    Long-time ECG time series for healthy subjects and diseased patients are analysed. In the first case, the power spectrum has the 1/f shape in a broad frequency range. However, its behaviour for very low and very high frequency is different and the entire spectrum is integrable. For patients with post-ictal heart rate oscillation in partial epilepsy the 1/f noise is not present. We determine the power spectrum by evaluating the Fourier transform of the signal in both cases and calculate the signal autocorrelation function. It falls with time faster for diseased patients then for healthy people. The presented method can serve as a diagnostic tool of some heart diseases.

  20. Extraction of heart rate from functional near-infrared spectroscopy in infants

    PubMed Central

    Perdue, Katherine L.; Westerlund, Alissa; McCormick, Sarah A.; Nelson, Charles A.

    2014-01-01

    Abstract. Changes in heart rate are a useful physiological measure in infant studies. We present an algorithm for calculating the heart rate (HR) from oxyhemoglobin pulsation in functional near-infrared spectroscopy (fNIRS) signals. The algorithm is applied to data collected from 10 infants, and the HR derived from the fNIRS signals is compared against the HR as calculated by electrocardiography. We show high agreement between the two HR signals for all infants (r>0.90), and also compare stimulus-related HR responses as measured by the two methods and find good agreement despite high levels of movement in the infants. This algorithm can be used to measure changes in HR in infants participating in fNIRS studies without the need for additional HR sensors. PMID:24972361

  1. Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart.

    PubMed

    Hansen, Katrina J; Favreau, John T; Guyette, Jacques P; Tao, Ze-Wei; Coffin, Spencer T; Cunha-Gavidia, Anny; D'Amore, Brian; Perreault, Luke R; Fitzpatrick, John P; DeMartino, Angelica; Gaudette, Glenn R

    2016-01-01

    Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW) and systolic area of contraction (SAC) and global parameters derived from the pressure waveform. MI (n = 6) significantly decreased RSW (0.026 ± 0.011) and SAC (0.022 ± 0.015) when compared with sham operation (RSW: 0.141 ± 0.009; SAC: 0.166 ± 0.005, n = 6) (p < 0.05). The delivery of unseeded biological sutures to the infarcted hearts did not change regional mechanical function compared with the infarcted hearts (RSW: 0.032 ± 0.004, SAC: 0.037 ± 0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend toward increase of regional mechanical function compared with the infarcted heart (RSW: 0.057 ± 0.011; SAC: 0.051 ± 0.014, n = 6). Global function showed no significant differences between any group (p > 0.05); however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0% ± 2.2%), where unseeded (3.8% ± 0.6%) and hMSC-seeded (3.7% ± 0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining suture area was

  2. Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart

    PubMed Central

    Hansen, Katrina J.; Favreau, John T.; Guyette, Jacques P.; Tao, Ze-Wei; Coffin, Spencer T.; Cunha-Gavidia, Anny; D'Amore, Brian; Perreault, Luke R.; Fitzpatrick, John P.; DeMartino, Angelica; Gaudette, Glenn R.

    2016-01-01

    Abstract Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW) and systolic area of contraction (SAC) and global parameters derived from the pressure waveform. MI (n = 6) significantly decreased RSW (0.026 ± 0.011) and SAC (0.022 ± 0.015) when compared with sham operation (RSW: 0.141 ± 0.009; SAC: 0.166 ± 0.005, n = 6) (p < 0.05). The delivery of unseeded biological sutures to the infarcted hearts did not change regional mechanical function compared with the infarcted hearts (RSW: 0.032 ± 0.004, SAC: 0.037 ± 0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend toward increase of regional mechanical function compared with the infarcted heart (RSW: 0.057 ± 0.011; SAC: 0.051 ± 0.014, n = 6). Global function showed no significant differences between any group (p > 0.05); however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0% ± 2.2%), where unseeded (3.8% ± 0.6%) and hMSC-seeded (3.7% ± 0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining suture area

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

    SciTech Connect

    Umetani, K.; Fukushima, K.

    2013-03-15

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

  4. Cardiac autonomic function measured by heart rate variability and turbulence in pre-hypertensive subjects.

    PubMed

    Erdem, Alim; Uenishi, Masahiro; Küçükdurmaz, Zekeriya; Matsumoto, Kazuo; Kato, Ritsushi; Hara, Motoki; Yazıcı, Mehmet

    2013-01-01

    Non-dipping blood pressure pattern was shown to be associated with increased cardiovascular events. In addition, cardiac autonomic dysfunction was found to be associated with non-dipper phenomenon. In this study, we aimed to evaluate the cardiac autonomic functions in dipper and non-dipper pre-hypertensive subjects. A total of 65 pre-hypertensive subjects were enrolled in this study. They were divided into two groups as non-dippers (40 subjects, 52% female) and dippers (25 subjects, 52.5% female). Cardiac autonomic functions of the two groups were compared with the aid of heart rate variability, heart rate turbulence (HRT), atrial premature contractions (APCs), ventricular premature contractions (VPCs), and mean heart rate (MHR). There was no significant difference between non-dippers and dippers in basal characteristics. The two parameters of HRT, turbulence onset and turbulence slope, were found to be significantly abnormal in non-dippers than in dippers (P < .011 and P < .002, respectively). Heart rate variability parameters, including SDNN, SDANN, RMSSD, and pNN50, were found to be similar in dipper and non-dipper pre-hypertensive subjects (P < .998, P < .453, P < .205, and P < .788, respectively). APCs, VPCs, and MHR were compared, and there were statistical differences between the groups (APCs 5.80 ± 4.55, 9.14 ± 7.33, P < .024; VPCs 8.48 ± 8.83, 13.23 ± 9.68, P < .044; and MHR 70.16 ± 11.08, 76.26 ± 11.31, P < .035; respectively). This study demonstrated a possible cardiac autonomic dysfunction in pre-hypertensive subjects with non-dipper pattern. This may be a basis for future studies related to pre-hypertension and non-dipping BP pattern. PMID:22676318

  5. Eprosartan improves cardiac function in swine working heart model of ischemia-reperfusion injury

    PubMed Central

    Weymann, Alexander; Sabashnikov, Anton; Patil, Nikhil P.; Konertz, Wolfgang; Modersohn, Diethelm; Dohmen, Pascal M.

    2014-01-01

    Background Eprosartan is an angiotensin II receptor antagonist used as an antihypertensive. We sought to evaluate the regional effect of Eprosartan on postinfarct ventricular remodeling and myocardial function in an isolated swine working heart model of ischemia-reperfusion injury. Material/Methods 22 swine hearts were perfused with the Langendorff perfusion apparatus under standard experimental conditions. Myocardial ischemia was induced by a 10-min left anterior descending artery ligation. Hearts were reperfused with either saline (control group, n=11), or Eprosartan (treatment group, n=11). Left ventricular pressure (LVP) and regional heart parameters such as intramyocardial pressure (IMP), wall thickening rate (WTh), and pressure-length-loops (PLL) were measured at baseline and after 30 min of reperfusion. Results Measured parameters were statistically similar between the 2 groups at baseline. The administration of Eprosartan led to a significantly better recovery of IMP and WTh: 44.4±2.5 mmHg vs. 51.2±3.3 mmHg, p<0.001 and 3.8±0.4 μm vs. 4.4±0.3 μm, p=0.001, respectively. PLL were also significantly higher in the treatment group following reperfusion (21694±3259 units vs. 31267±3429 units, p<0.01). There was no difference in the LVP response to Eprosartan versus controls (63.6±3.0 mmHg vs. 62.5±3.1 mmHg, p=0.400). Conclusions Pre-treatment with Eprosartan is associated with a significant improvement in regional cardiac function under ischemic conditions. Pharmacological treatment with eprosartan may exert a direct cardioprotective effect on ischemic myocardium. PMID:24762635

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

    NASA Astrophysics Data System (ADS)

    Umetani, K.; Fukushima, K.

    2013-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  8. Cognitive function in ambulatory patients with systolic heart failure: insights from the warfarin versus aspirin in reduced cardiac ejection fraction (WARCEF) trial.

    PubMed

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

    2014-01-01

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

  9. The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

    PubMed Central

    Reid, Ryan; Ezekowitz, Justin A.; Brown, Paul M.; McAlister, Finlay A.; Rowe, Brian H.; Braam, Branko

    2015-01-01

    Background Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. Objectives The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. Methods 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID:26380982

  10. Physical exercise affects slow cycling cells in the rat heart and reveals a new potential niche area in the atrioventricular junction.

    PubMed

    Vukusic, Kristina; Asp, Julia; Henriksson, Helena Barreto; Brisby, Helena; Lindahl, Anders; Sandstedt, Joakim

    2015-10-01

    Physical exercise has several beneficial effects on the heart. In other tissues it has been shown to activate endogenous stem cells. There is however a lack of knowledge how exercise affects the distribution of progenitor cells as well as overall cell turnover within the heart. Therefore, proliferating cells were identified using BrdU DNA labeling in a rat exercise model. Slow cycling cells were identified by label retention. BrdU+ nuclei were counted in apex, ventricle and atrioventricular junction (AV junction), as well as in skin tissue where label retaining cells (LRC) have been described previously. After 13 weeks of chasing, the cells with the highest intensity were identified and considered as LRC. Heart tissue showed slower proliferation compared to skin. The highest number of BrdU+ cells was found in the AV junction. Here, a sub region in close proximity to the valvular insertion point was observed, where density of BrdU+ cells was high at all time points. Physical exercise increased proliferation in AV junction at the early stage. Furthermore, the sub region was found to harbor a significant higher number of LRC compared to other regions of the heart in the exercised animals. Progenitor markers MDR1 and Sca-1 were detected in the same area by immunohistochemistry. In conclusions, our data shows that physical exercise affects cell turnover and distribution of LRC in the heart. Furthermore, it reveals a region within the AV junction of the heart that shows features of a stem cell niche. PMID:26047663

  11. SIRT3 deficiency impairs mitochondrial and contractile function in the heart.

    PubMed

    Koentges, Christoph; Pfeil, Katharina; Schnick, Tilman; Wiese, Sebastian; Dahlbock, Rabea; Cimolai, Maria C; Meyer-Steenbuck, Maximilian; Cenkerova, Katarina; Hoffmann, Michael M; Jaeger, Carsten; Odening, Katja E; Kammerer, Bernd; Hein, Lutz; Bode, Christoph; Bugger, Heiko

    2015-01-01

    Sirtuin 3 (SIRT3) is a mitochondrial NAD(+)-dependent deacetylase that regulates energy metabolic enzymes by reversible protein lysine acetylation in various extracardiac tissues. The role of SIRT3 in myocardial energetics and in the development of mitochondrial dysfunction in cardiac pathologies, such as the failing heart, remains to be elucidated. To investigate the role of SIRT3 in the regulation of myocardial energetics and function SIRT3(-/-) mice developed progressive age-related deterioration of cardiac function, as evidenced by a decrease in ejection fraction and an increase in enddiastolic volume at 24 but not 8 weeks of age using echocardiography. Four weeks following transverse aortic constriction, ejection fraction was further decreased in SIRT3(-/-) mice compared to WT mice, accompanied by a greater degree of cardiac hypertrophy and fibrosis. In isolated working hearts, a decrease in cardiac function in SIRT3(-/-) mice was accompanied by a decrease in palmitate oxidation, glucose oxidation, and oxygen consumption, whereas rates of glycolysis were increased. Respiratory capacity and ATP synthesis were decreased in cardiac mitochondria of SIRT3(-/-) mice. HPLC measurements revealed a decrease of the myocardial ATP/AMP ratio and of myocardial energy charge. Using LC-MS/MS, we identified increased acetylation of 84 mitochondrial proteins, including 6 enzymes of fatty acid import and oxidation, 50 subunits of the electron transport chain, and 3 enzymes of the tricarboxylic acid cycle. Lack of SIRT3 impairs mitochondrial and contractile function in the heart, likely due to increased acetylation of various energy metabolic proteins and subsequent myocardial energy depletion. PMID:25962702

  12. Genetic lineage tracing defines myofibroblast origin and function in the injured heart.

    PubMed

    Kanisicak, Onur; Khalil, Hadi; Ivey, Malina J; Karch, Jason; Maliken, Bryan D; Correll, Robert N; Brody, Matthew J; J Lin, Suh-Chin; Aronow, Bruce J; Tallquist, Michelle D; Molkentin, Jeffery D

    2016-01-01

    Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction (MI) and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell type in terms of their origins and functional effects in vivo. Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen-inducible Cre for cellular lineage-tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Lineage tracing with four additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin(+) myofibroblasts reduces collagen production and scar formation after MI. Periostin-traced myofibroblasts also revert back to a less-activated state upon injury resolution. Our results define the myofibroblast as a periostin-expressing cell type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21(+) tissue-resident fibroblasts. PMID:27447449

  13. [Heart valves after 22 years - good long-term function of aortic homograft, advanced impairment in function of atrioventricular valves].

    PubMed

    Michalski, Błazej; Chrzanowski, Lukasz; Krzemińska-Pakula, Maria; Kasprzak, Jarosław D

    2010-03-01

    We report a case of a 61-year-old female patient with a history of aortic valve replacement, who was admitted to our hospital with symptoms and signs of decompensated heart failure (NYHA class III). Transthoracic echocardiogram revealed mitral valve and tricuspid valve regurgitation (III grade) with normal function of aortic valve homograft implanted 22 years ago. The patient underwent cardiosurgical mitral valve replacement and tricuspid valve annuloplasty with very good result. An aortic valve homograft may be the best alternative to a mechanical valves for a young female patients. PMID:20411462

  14. Echocardiographic features of impaired left ventricular diastolic function in Chagas's heart disease.

    PubMed Central

    Combellas, I; Puigbo, J J; Acquatella, H; Tortoledo, F; Gomez, J R

    1985-01-01

    To study left ventricular diastolic function in Chagas's disease, simultaneous echocardiograms, phonocardiograms, and apexcardiograms were recorded in 20 asymptomatic patients with positive Chagas's serology and no signs of heart disease (group 1), 12 with Chagas's heart disease and symptoms of ventricular arrhythmia but no heart failure (group 2), 20 normal subjects (group 3), and 12 patients with left ventricular hypertrophy (group 4). The recordings were digitised to determine left ventricular isovolumic relaxation time and the rate and duration of left ventricular cavity dimension increase and wall thinning. In groups 1 and 2 (a) aortic valve closure (A2) and mitral valve opening were significantly delayed relative to minimum dimension and were associated with prolonged isovolumic relaxation, (b) left ventricular cavity size was abnormally increased during isovolumic relaxation and abnormally reduced during isovolumic contraction, and (c) peak rate of posterior wall thinning and dimension increase were significantly reduced and duration of posterior wall thinning was significantly prolonged; both of these abnormalities occurred at the onset of diastolic filling. These abnormalities were more pronounced in group 2 and were accompanied by an increase in the height of the apexcardiogram "a" wave, an indication of pronounced atrial systole secondary to end diastolic filling impairment due to reduced left ventricular distensibility. Group 4, which had an established pattern of diastolic abnormalities, showed changes similar to those in group 2; however, the delay in aortic valve closure (A2) and in mitral valve opening and the degree of dimension change were greater in the latter group. Thus early isovolumic relaxation and left ventricular abnormalities were pronounced in the patients with Chagas's heart disease and may precede systolic compromise, which may become apparent in later stages of the disease. The digitised method is valuable in the early detection of

  15. Left Atrial Size and Function in a Canine Model of Chronic Atrial Fibrillation and Heart Failure

    PubMed Central

    Goldberg, Adam; Kusunose, Kenya; Qamruddin, Salima; Rodriguez, L. Leonardo; Mazgalev, Todor N.; Griffin, Brian P.; Van Wagoner, David R.; Zhang, Youhua; Popović, Zoran B.

    2016-01-01

    Background Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS). Methods HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 μs, 20 Hz, 3–7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms. Results RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p<0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p <0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals. Conclusions In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration. PMID:26771573

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

    PubMed Central

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

    2015-01-01

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

  17. Children's Sleep and Autonomic Function: Low Sleep Quality Has an Impact on Heart Rate Variability

    PubMed Central

    Michels, Nathalie; Clays, Els; De Buyzere, Marc; Vanaelst, Barbara; De Henauw, Stefaan; Sioen, Isabelle

    2013-01-01

    Objectives: Short sleep duration and poor sleep quality in children have been associated with concentration, problem behavior, and emotional instability, but recently also with disrupted autonomic nervous function, which predicts cardiovascular health. Heart rate variability (HRV) was used as noninvasive indicator of autonomic function to examine the influence of sleep. Design: Cross-sectional and longitudinal observational study on the effect of sleep on HRV Participants: Belgian children (5-11 years) of the ChiBS study in 2010 (N = 334) and 2011 (N = 293). Interventions: N/A. Methods: Sleep duration was reported and in a subgroup sleep quality (efficiency, latency, awakenings) was measured with accelerometry. High-frequency (HF) power and autonomic balance (LF/HF) were calculated on supine 5-minute HRV measurements. Stress was measured by emotion and problem behavior questionnaires. Sleep duration and quality were used as HRV predictors in corrected cross-sectional and longitudinal regressions. Stress was tested as mediator (intermediate pathway) or moderator (interaction) in sleep-HRV associations. Results: In both cross-sectional and longitudinal analyses, long sleep latency could predict lower HF (parasympathetic activity), while nocturnal awakenings, sleep latency, low sleep efficiency, and low corrected sleep duration were related to higher LF/HF (sympathetic/parasympathetic balance). Parental reported sleep duration was not associated with HRV. The significances remained after correction for stress. Stress was not a mediator, but a moderator (enhancer) in the relationship between sleep quality and HRV. Conclusions: Low sleep quality but not parent-reported low sleep duration leads to an unhealthier heart rate variability pattern (sympathetic over parasympathetic dominance). This stresses the importance of good sleep quality for cardiovascular health in children. Citation: Michels N; Clays E; De Buyzere M; Vanaelst B; De Henauw S; Sioen I. Children's sleep

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

    PubMed

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

    2015-02-01

    The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity "in vitro" was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC's fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components. PMID:25532475

  19. Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice.

    PubMed

    Li, Quanxi; Davila, Juanmahel; Kannan, Athilakshmi; Flaws, Jodi A; Bagchi, Milan K; Bagchi, Indrani C

    2016-05-01

    Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plastics and epoxy resins, has received much attention in female reproductive health due to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study, we addressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:27022677

  20. Origin of Heart Rate Variability and Turbulence: An Appraisal of Autonomic Modulation of Cardiovascular Function

    PubMed Central

    Lombardi, Federico; Stein, Phyllis K.

    2011-01-01

    Heart period constantly changes on a beat to beat basis, due to autonomic influences on the sinoatrial node, and changes can be quantified as heart rate variability (HRV). In addition, after a premature ventricular beat, there are reproducible variations in RR interval, also due to baroreflex mediated autonomic influences on the sinoatrial node, that can be measured as heart rate turbulence (HRT). Impaired autonomic function as measured by HRV and HRT has proven to predict adverse outcomes in clinical settings. The ability of reduced HRV and HRT to predict adverse outcomes has been explained by their dependency on vagal mechanisms that could reflect an increased sympathetic and a reduced vagal modulation of sinus node, thus favoring cardiac electrical instability. Analysis of non-linear dynamics of HRV has also been utilized to describe the fractal like characteristic of the variability signal and proven effective in identify patients at risk for sudden cardiac death. Despite the clinical validity of these measures, it has also been evident that the relationship between neural input and sinus node responsiveness is extremely complex and variable in different clinical conditions. Thus, abnormal HRV or HRT on a clinical Holter recordings may reflect non-neural as well as autonomic mechanisms, and this also needs to be taken into account when interpreting any findings. However, under controlled conditions, the computation of the low and high frequency components of HRV and of their normalized powers or ratio seems capable of providing valid information on sympatho-vagal balance in normal subjects, as well as in most patients with a preserved left ventricular function. Thus, analysis of HRV does provide a unique tool to specifically assess autonomic control mechanisms in association with various perturbations. In conclusion, HRV measures are of substantial utility to identify patients with an increased cardiac mortality and to evaluate autonomic control mechanisms, but

  1. Origin of heart rate variability and turbulence: an appraisal of autonomic modulation of cardiovascular function.

    PubMed

    Lombardi, Federico; Stein, Phyllis K

    2011-01-01

    Heart period constantly changes on a beat to beat basis, due to autonomic influences on the sinoatrial node, and changes can be quantified as heart rate variability (HRV). In addition, after a premature ventricular beat, there are reproducible variations in RR interval, also due to baroreflex mediated autonomic influences on the sinoatrial node, that can be measured as heart rate turbulence (HRT). Impaired autonomic function as measured by HRV and HRT has proven to predict adverse outcomes in clinical settings. The ability of reduced HRV and HRT to predict adverse outcomes has been explained by their dependency on vagal mechanisms that could reflect an increased sympathetic and a reduced vagal modulation of sinus node, thus favoring cardiac electrical instability. Analysis of non-linear dynamics of HRV has also been utilized to describe the fractal like characteristic of the variability signal and proven effective in identify patients at risk for sudden cardiac death. Despite the clinical validity of these measures, it has also been evident that the relationship between neural input and sinus node responsiveness is extremely complex and variable in different clinical conditions. Thus, abnormal HRV or HRT on a clinical Holter recordings may reflect non-neural as well as autonomic mechanisms, and this also needs to be taken into account when interpreting any findings. However, under controlled conditions, the computation of the low and high frequency components of HRV and of their normalized powers or ratio seems capable of providing valid information on sympatho-vagal balance in normal subjects, as well as in most patients with a preserved left ventricular function. Thus, analysis of HRV does provide a unique tool to specifically assess autonomic control mechanisms in association with various perturbations. In conclusion, HRV measures are of substantial utility to identify patients with an increased cardiac mortality and to evaluate autonomic control mechanisms, but

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

    PubMed

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

    2012-09-01

    Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes. PMID:22691878

  3. Adverse effects of AMP-activated protein kinase alpha2-subunit deletion and high-fat diet on heart function and ischemic tolerance in aged female mice.

    PubMed

    Slámová, K; Papoušek, F; Janovská, P; Kopecký, J; Kolář, F

    2016-03-14

    AMP-activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK alpha2-subunit deletion affects heart function and ischemic tolerance of adult and aged mice. AMPK alpha2(-/-) (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK alpha2-subunit protein level, but no difference in AMPK alpha1-subunit was detected between the strains. Both alpha1- and alpha2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK alpha2-subunit deletion and high-fat feeding on heart function and myocardial ischemic tolerance in aged female mice are not additive. PMID:26596312

  4. Mechanics of the Functionally Univentricular Heart-How Little Do We Understand and Why Does It Matter?

    PubMed

    Grattan, Michael; Mertens, Luc

    2016-08-01

    Despite improved surgical techniques, preoperative and postoperative care, patients with functionally univentricular hearts (UVH) continue to have high morbidity and mortality and a decreased lifespan. Ventricular systolic and diastolic dysfunction is a major contributing factor to Fontan patient outcome. The evaluation of ventricular function in patients with UVH is particularly challenging. At a cellular and ultrastructural level, there are inherent differences between single and biventricular right and left ventricles. In addition, there are variable loading conditions throughout the stages of single ventricle palliation as well as variable ventricular remodelling in response to these changes. We will discuss the traditional and newer, advanced echocardiographic techniques that have been applied to evaluate ventricular function in patients with UVH. Each method has inherent advantages and disadvantages when applied to this population. The use of novel techniques including deformational imaging and 3-dimensional echocardiography will hopefully provide a more comprehensive understanding of the performance of the single ventricle, and how ventricular dysfunction affects the clinical status of patients after Fontan palliation. PMID:26919793

  5. Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia.

    PubMed

    Del Viso, Florencia; Huang, Fang; Myers, Jordan; Chalfant, Madeleine; Zhang, Yongdeng; Reza, Nooreen; Bewersdorf, Joerg; Lusk, C Patrick; Khokha, Mustafa K

    2016-09-12

    Human genomics is identifying candidate genes for congenital heart disease (CHD), but discovering the underlying mechanisms remains challenging. In a patient with CHD and heterotaxy (Htx), a disorder of left-right patterning, we previously identified a duplication in Nup188. However, a mechanism to explain how a component of the nuclear pore complex (NPC) could cause Htx/CHD was undefined. Here, we show that knockdown of Nup188 or its binding partner Nup93 leads to a loss of cilia during embryonic development while leaving NPC function largely intact. Many data, including the localization of endogenous Nup188/93 at cilia bases, support their direct role at cilia. Super-resolution imaging of Nup188 shows two barrel-like structures with dimensions and organization incompatible with an NPC-like ring, arguing against a proposed "ciliary pore complex." We suggest that the nanoscale organization and function of nucleoporins are context dependent in a way that is required for the structure of the heart. PMID:27593162

  6. Heart Failure

    MedlinePlus

    ... blood the way it should. It can affect one or both sides of the heart. The weakening of the heart's pumping ability causes Blood and fluid to back up into the lungs The buildup of fluid in the feet, ankles and legs - called edema Tiredness and shortness of breath Common causes of ...

  7. Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men—the British Regional Heart Study

    PubMed Central

    Wannamethee, S Goya; Shaper, A Gerald; Papacosta, Olia; Lennon, Lucy; Welsh, Paul; Whincup, Peter H

    2016-01-01

    Aims The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men. Methods and results Prospective study of 3242 men aged 60–79 years without prevalent HF or myocardial infarction followed up for an average period of 13 years, in whom 211 incident HF cases occurred. Incident HF was examined in relation to % predicted FEV1 and FVC. The Global Initiative on Obstructive Lung Diseases spirometry criteria were used to define airway obstruction. Reduced FEV1, but not FVC in the normal range, was significantly associated with increased risk of HF after adjustment for established HF risk factors including inflammation. The adjusted HRs comparing men in the 6–24th percentile with the highest quartile were 1.91 (1.24 to 2.94) and 1.30 (0.86 to 1.96) for FEV1 and FVC, respectively. FEV1 and FVC were inversely associated with NT-proBNP and cTnT, although the association between FEV1 and incident HF remained after adjustment for NT-proBNP and cTnT. Compared with normal subjects (FEV1/FVC ≥0.70 and FVC≥80%), moderate or severe (FEV1/FVC <0.70 and FEV1 <80%) airflow obstruction was independently associated with HF ((adjusted relative risk 1.59 (1.08 to 2.33)). Airflow restriction (FEV1/FVC ≥0.70 and FVC <80%) was not independently associated with HF. Conclusions Reduced FEV1 reflecting airflow obstruction is associated with cardiac dysfunction and increased risk of incident HF in older men. PMID:26811343

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  10. Unique functions of Gata4 in mouse liver induction and heart development.

    PubMed

    Borok, Matthew J; Papaioannou, Virginia E; Sussel, Lori

    2016-02-15

    Gata4 and Gata6 are closely related transcription factors that are essential for the development of a number of embryonic tissues. While they have nearly identical DNA-binding domains and similar patterns of expression, Gata4 and Gata6 null embryos have strikingly different embryonic lethal phenotypes. To determine whether the lack of redundancy is due to differences in protein function or Gata4 and Gata6 expression domains, we generated mice that contained the Gata6 cDNA in place of the Gata4 genomic locus. Gata4(Gata6/Gata6) embryos survived through embryonic day (E)12.5 and successfully underwent ventral folding morphogenesis, demonstrating that Gata6 is able to replace Gata4 function in extraembryonic tissues. Surprisingly, Gata6 is unable to replace Gata4 function in the septum transversum mesenchyme or the epicardium, leading to liver agenesis and lethal heart defects in Gata4(Gata6/Gata6) embryos. These studies suggest that Gata4 has evolved distinct functions in the development of these tissues that cannot be performed by Gata6, even when it is provided in the identical expression domain. Our work has important implications for the respective mechanisms of Gata function during development, as well as the functional evolution of these essential transcription factors. PMID:26687508

  11. Temperature acclimation of mitochondria function from the hearts of a temperate wrasse (Notolabrus celidotus).

    PubMed

    Iftikar, F I; Morash, A J; Cook, D G; Herbert, N A; Hickey, A J R

    2015-06-01

    Understanding how mitochondrial function alters with acclimation may provide insight to the limits these organelles place on temperate fish hearts facing seasonal temperature fluctuations. This investigation determined if compromised cardiac mitochondrial function contributed to heart failure (HF) in the New Zealand wrasse Notolabrus celidotus acclimated at their mean summer and winter ocean temperatures. To test this hypothesis, fish were acclimated to cold (CA, 15°C) and warm (WA, 21°C) temperatures. The temperature of HF was determined by Doppler sonography and mitochondrial function in permeabilised cardiac fibres was tested using high resolution respirometry. Heat stress mediated HF occurred at a THF of 26.7±0.4°C for CA fish, and at 28.2±0.6°C for WA fish. Biochemical analyses also revealed that WA fish had elevated resting plasma lactate indicating an increased dependence on anaerobic pathways. When cardiac fibres were tested with increasing temperatures, apparent breakpoints in the respiratory control ratio (RCR-I) with substrates supporting complex I (CI) oxygen flux occurred below the THF for both acclimated groups. While WA cardiac mitochondria were less sensitive to increasing temperature for respirational flux supported by CI, Complex II, and chemically uncoupled flux, CA fish maintained higher RCRs at higher temperatures. We conclude that while acclimation to summer temperatures does alter cardiac mitochondrial function in N. celidotus, these changes need not be beneficial in terms of oxidative phosphorylation efficiency and may come at an energetic cost, which would be detrimental in the face of further habitat warming. PMID:25645295

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

    PubMed

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

    2016-01-15

    Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications. PMID:26561645

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

    PubMed Central

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

    2010-01-01

    We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload. PMID:19933421

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-15

    Heart failure with preserved ejection fraction (HFpEF) has been described as a disease of elderly subjects with female predominance and hypertension. Our clinical experience suggests patients with HFpEF from an urban population are far more heterogenous, with greater co-morbidities and significant inhospital morbidity. There are limited data on the hospitalization course and outcomes in acute decompensated HFpEF. Hospitalizations for acute heart failure at our institution from July 2011 to June 2012 were identified by International Classification of Diseases, Ninth Revision, codes and physician review for left ventricular ejection fraction ≥50% and were reviewed for patient characteristics and clinical outcomes. Worsening renal function (WRF) was defined as creatinine increase of ≥0.3 mg/dl by 72 hours after admission. Hospital readmission and mortality data were captured from electronic medical records and the Social Security Death Index. Of 434 heart failure admissions, 206 patients (47%) with HFpEF were identified. WRF developed in 40%, the highest reported in HFpEF to date, and was associated with higher blood pressure and lower volume of diuresis. Compared to previous reports, hospitalized patients with HFpEF were younger (mean age 63.2 ± 13.6 years), predominantly black (74%), and had more frequent and severe co-morbidities: hypertension (89%), diabetes (56%), and chronic kidney disease (55%). There were no significant differences in 1- and 12-month outcomes by gender, race, or WRF. In conclusion, we found hospitalized patients with HFpEF from an urban population develop a high rate of WRF are younger than previous cohorts, often black, and have greater co-morbidities than previously described. PMID:26410603

  16. Prevalence, implication, and determinants of worsening renal function after surgery for congenital heart disease.

    PubMed

    Saiki, Hirofumi; Kuwata, Seiko; Kurishima, Clara; Iwamoto, Yoichi; Ishido, Hirotaka; Masutani, Satoshi; Senzaki, Hideaki

    2016-08-01

    Accumulating data in adults indicate the prognostic importance of worsening renal function (WRF) during treatment of acute heart failure. Venous congestion appears to play a dominant role in WRF; however, data regarding WRF in children with congenital heart disease (CHD) are limited. The present study was conducted to elucidate the prevalence and characteristics of WRF after surgery for CHD in children. We also tested our hypothesis that, similar to adult heart failure, venous congestion is an important determinant of WRF independent of cardiac output in this population. Fifty-five consecutive pediatric patients who underwent cardiovascular surgery for CHD were studied (median age 0.7 years; range 3 days to 17 years). The degree of WRF was assessed by the difference between the maximum levels of postoperative serum creatinine (Cr) and preoperative serum Cr. There was a high prevalence of WRF in the present cohort: an increase in Cr level was observed in 47 patients (85 %) and a Cr increase ≥0.3 mg/dL was seen in 23 (42 %). Importantly, WRF was significantly associated with a worse clinical outcome of a longer stay in the intensive care unit and hospital (both p < 0.05), even after controlling for age and operative factors. In addition, multivariate regression analysis revealed that central venous pressure, rather than cardiac output, was an independent determinant of WRF. Postoperative management to relieve venous congestion may help ameliorate or prevent WRF and thereby improve outcomes in patients with CHD. PMID:26266633

  17. Heart Failure

    MedlinePlus

    ... together. About Rise Above HF Rise Above Heart Failure seeks to increase the dialogue about HF and improve the lives of people affected by the condition through awareness, education and support. Through the initiative, AHA strives to ...

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

    PubMed Central

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

    2014-01-01

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

  19. The effect of K201 on isolated working rabbit heart mechanical function during pharmacologically induced Ca2+ overload

    PubMed Central

    Kelly, A; Elliott, EB; Matsuda, R; Kaneko, N; Smith, GL; Loughrey, CM

    2012-01-01

    BACKGROUND AND PURPOSE Reduced cardiac contractility has been associated with disrupted myocardial Ca2+ signalling. The 1,4 benzothiazepine K201 (JTV-519) acts on several Ca2+ handling proteins and improves cardiac contractility in vivo in a variety of animal models of myocardial dysfunction. However, it is unclear whether this improvement depends on the systemic effects of K201 or if K201 reverses the effects of Ca2+ dysregulation, regardless of the cause. EXPERIMENTAL APPROACH The effect of K201 on cardiac mechanical function was assessed in isolated working hearts from adult rabbits, using a ventricular pressure-volume catheter. In separate experiments, the effect of K201 was investigated in hearts following pharmacologically induced Ca2+ overload using elevated extracellular [Ca2+] ([Ca2+]o) and β-adrenoceptor stimulation. KEY RESULTS K201 induced a concentration-dependent decline in systolic function (peak pressure, dP/dtmax and preload recruitable stroke work), lusitropy (reduced dP/dtmin and increased end diastolic pressure) and stroke volume, independent of decreased heart rate. In separate experiments, mechanical function in hearts exposed to 4.5 mmol·L−1[Ca2+]o and 150 nmol·L−1 isoprenaline declined until cessation of aortic flow (in 6 out of 11 hearts). However, all hearts perfused with the addition of 1 µmol·L−1 K201 maintained aortic flow and demonstrated significantly improved peak systolic pressures, dP/dtmax and dP/dtmin. CONCLUSIONS AND IMPLICATIONS K201 significantly improved mechanical function of the heart during Ca2+ overload. This suggests that K201 can limit the detrimental effects of elevated intracellular Ca2+ and exert beneficial effects on cardiac contractile function, independent of systemic effects previously observed in vivo. PMID:21658026

  20. Concomitant gastroparesis negatively affects children with functional gallbladder disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. Perturbations of heart development and function in cardiomyocytes from human embryonic stem cells with trisomy 21.

    PubMed

    Bosman, Alexis; Letourneau, Audrey; Sartiani, Laura; Del Lungo, Martina; Ronzoni, Flavio; Kuziakiv, Rostyslav; Tohonen, Virpi; Zucchelli, Marco; Santoni, Federico; Guipponi, Michel; Dumevska, Biljana; Hovatta, Outi; Antonarakis, Stylianos E; Jaconi, Marisa E

    2015-05-01

    Congenital heart defects (CHD) occur in approximately 50% of patients with Down syndrome (DS); the mechanisms for this occurrence however remain unknown. In order to understand how these defects evolve in early development in DS, we focused on the earliest stages of cardiogenesis to ascertain perturbations in development leading to CHD. Using a trisomy 21 (T21) sibling human embryonic stem cell (hESC) model of DS, we show that T21-hESC display many significant differences in expression of genes and cell populations associated with mesodermal, and more notably, secondary heart field (SHF) development, in particular a reduced number of ISL1(+) progenitor cells. Furthermore, we provide evidence for two candidate genes located on chromosome 21, ETS2 and ERG, whose overexpression during cardiac commitment likely account for the disruption of SHF development, as revealed by downregulation or overexpression experiments. Additionally, we uncover an abnormal electrophysiological phenotype in functional T21 cardiomyocytes, a result further supported by mRNA expression data acquired using RNA-Seq. These data, in combination, revealed a cardiomyocyte-specific phenotype in T21 cardiomyocytes, likely due to the overexpression of genes such as RYR2, NCX, and L-type Ca(2+) channel. These results contribute to the understanding of the mechanisms involved in the development of CHD. Stem Cells 2015;33:1434-1446. PMID:25645121

  2. Heart Failure Functional Class Associated with Depression Severity But Not Anxiety Severity

    PubMed Central

    Celik, Etem; Cay, Serkan; Sensoy, Baris; Murat, Sani; Oksuz, Fatih; Cankurt, Tayyar; Ali Mendi, Mehmet

    2016-01-01

    Background Depression and anxiety are common in heart failure (HF) patients and associated with adverse clinical outcomes. However, there are little or no published data that focuses on the relationship between these commonly observed situations and HF classes. The aim of this study was to evaluate the relationship between these psychiatric co-morbidities and HF symptom classes. As a second objective of our study, the associations between patient characteristics and depression severity were also assessed. Methods Our study enrolled a total of 420 HF study participants. The severity of depressive and anxiety symptoms was evaluated by Beck’s depression and anxiety. The measured total scores were used to grade depression severity and anxiety as minimal/mild and moderate/severe. Results According to NYHA Functional Classification, 228 patients (51%) had class I symptoms, 101 (23%) had class II symptoms, 31 (7%) had class III symptoms, and class IV symptoms were noted in the remaining 60 patients (19%). The mean Beck’s depression and anxiety scores were 12.4 ± 11.1 and 13.4 ± 9.0, respectively. While no association between HF symptom classes and anxiety severity was observed, a significant positive relation between HF symptom class and depression score was found. Conclusions The results of our study suggested that HF symptom class was positively associated with severity of depression. On the other hand, there was no association between HF symptom class and anxiety score in a wide population of heart failure patients. PMID:27122931

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

    PubMed

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

    2014-02-01

    Currently available heart valve replacements are limited in long-term performance or fail due to leaflet thickening, lack of growth or remodeling potential. In order to address these issues, it is necessary to mimic multiple factors of the native valvular extracellular matrix (ECM) such as architecture, mechanical behavior and biochemical signals. Here, we successfully generated an electrospun PEGdma-PLA scaffold adapted to the structure and mechanical properties of native valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells (VECs) were seeded on the scaffold and when cultured under physiological conditions in a bioreactor, the construct performed like a native leaflet. Atomic force microscopy (AFM) was employed to obtain detailed mechanical information from the leaflets, which enabled the first layer-specific measurement of the Young's modulus. Interestingly, spongiosa stiffness was much lower compared to the fibrosa and ventricularis. Moreover, investigations into human fetal heart valve development identified collagen type I and versican as important structural proteins. As a proof of principle, these proteins were introduced to the scaffold, demonstrating the ability to bio-functionalize the hybrid valve based on natures' blueprint. PMID:24333025

  4. Initial emergency department systolic blood pressure predicts left ventricular systolic function in acute decompensated heart failure.

    PubMed

    Styron, Joseph F; Jois-Bilowich, Preeti; Starling, Randall; Hobbs, Robert E; Kontos, Michael C; Pang, Peter S; Peacock, W Frank

    2009-01-01

    Ejection fraction (EF) is often unknown in patients who present with acute decompensated heart failure (ADHF). The objective of this study was to determine whether a patient's systolic blood pressure is associated with their left ventricular EF. This study was a retrospective chart review of all patients admitted to an emergency department (ED) observation unit from January 2002 to December 2004. A low EF was defined as <40%. Among 475 patients, the median age was 72 years, 53% were men, 40% were white, 59% were black, and 59% had a low EF. Patients with low EFs were more likely male ( P<.0001), with prior congestive heart disease ( P<.0001), longer QRS duration ( P<.0001), left bundle branch block ( P<.0001), and higher B-type natriuretic peptide ( P<.0001). The low EF group was less likely to have diabetes ( P<.0001). Adjusted odds ratios for an EF >or=40% were significant at all systolic blood pressure readings >120 mm Hg. Having an ED systolic BP >120 mm Hg is associated with significantly higher rates of preserved left ventricular systolic function in patients with ADHF. PMID:19187401

  5. [The function of the heart changes in implementation of the diving reactions in humans].

    PubMed

    Baranova, T I; Berlov, D N; Zavarina, L B; Minigalin, A D; Smith, N Y; Xu, S; Yanvareva, I N

    2015-03-01

    The changes of chronotropic function of the heart and of the myocardium in the implementation of the diving response in humans were studied by the electrocardiographic method. The study involved 80 students aged 18-20 years. Diving simulation was performed by immersing the face in cold water during breath-hold exhale. When the water temperature was 12.3 +/- 2.3 degrees C, average duration of apnea was 31 +/- 11 s. The oxygen content in the exhaled air after apnea was 98.8 +/- 8.7 mm Hg, carbon dioxide--49.1 +/- 3.5 mm Hg. It was observed slowing of the heart rate, mainly due to the increasing of diastole in 41 of the 80 surveyed during simulating diving. But it also can be observed symptoms of conduction deterioration: atrioventricular block type I (22% of reactive type and 29% of the highly reactive type subjects), and exceeds standards QTc-interval prolongation (at 7.5% of the subjects). These responses are adaptive in nature and disappear in the recovery process. But the fact abnormalities of conduction in the myocardium must be considered when using the diving reflex in medical practice, as may be due to a predisposition to a certain pathology of the cardiovascular system. PMID:26016327

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

    PubMed

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

    2016-08-01

    OBJECTIVE To assess platelet closure time (CT), mean platelet component (MPC) concentration, and platelet component distribution width (PCDW) in dogs with subclinical chronic valvular heart disease. ANIMALS 89 Cavalier King Charles Spaniels (CKCSs) and 39 control dogs (not CKCSs). PROCEDURES Platelet count, MPC concentration, PCDW, and Hct were measured by use of a hematology analyzer, and CT was measured by use of a platelet function analyzer. Murmur grade and echocardiographic variables (mitral valve regurgitant jet size relative to left atrial area, left atrial-to-aortic diameter ratio, and left ventricular internal dimensions) were recorded. Associations between explanatory variables (sex, age, murmur grade, echocardiographic variables, platelet count, and Hct) and outcomes (CT, MPC concentration, and PCDW) were examined by use of multivariate regression models. RESULTS A model with 5 variables best explained variation in CT (R(2), 0.74), with > 60% of the variance of CT explained by mitral valve regurgitant jet size. The model of best fit to explain variation in MPC concentration included only platelet count (R(2), 0.24). The model of best fit to explain variation in PCDW included platelet count and sex (R(2), 0.25). CONCLUSIONS AND CLINICAL RELEVANCE In this study, a significant effect of mitral valve regurgitant jet size on CT was consistent with platelet dysfunction. However, platelet activation, as assessed on the basis of the MPC concentration and PCDW, was not a feature of subclinical chronic valvular heart disease in CKCSs. PMID:27463549

  7. Isolation and expansion of functionally-competent cardiac progenitor cells directly from heart biopsies

    PubMed Central

    Davis, Darryl R; Kizana, Eddy; Terrovitis, John; Barth, Andreas S.; Zhang, Yiqiang; Smith, Rachel Ruckdeschel; Miake, Junichiro; Marbán, Eduardo

    2010-01-01

    The adult heart contains reservoirs of progenitor cells that express embryonic and stem cell-related antigens. While these antigenically-purified cells are promising candidates for autologous cell therapy, clinical application is hampered by their limited abundance and tedious isolation methods. Methods that involve an intermediate cardiosphere-forming step have proven successful and are being tested clinically, but it is unclear whether the cardiosphere step is necessary. Accordingly, we investigated the molecular profile and functional benefit of cells that spontaneously emigrate from cardiac tissue in primary culture. Adult Wistar-Kyoto rat hearts were minced, digested and cultured as separate anatomical regions. Loosely-adherent cells that surround the plated tissue were harvested weekly for a total of five harvests. Genetic lineage tracing demonstrated that a small proportion of the direct outgrowth from cardiac samples originates from myocardial cells. This outgrowth contains sub-populations of cells expressing embryonic (SSEA-1) and stem cell-related antigens (c-Kit, abcg2) that varied with time in culture but not with the cardiac chamber of origin. This direct outgrowth, and its expanded progeny, underwent marked in vitro angiogenic/cardiogenic differentiation and cytokine secretion (IGF-1, VGEF). In vivo effects included long-term functional benefits as gauged by MRI following cell injection in a rat model of myocardial infarction. Outgrowth cells afforded equivalent functional benefits to cardiosphere-derived cells, which require more processing steps to manufacture. These results provide the basis for a simplified and efficient process to generate autologous cardiac progenitor cells (and mesenchymal supporting cells) to augment clinically-relevant approaches for myocardial repair. PMID:20211627

  8. Effect of Permanent Atrial Fibrillation on Cognitive Function in Patients With Chronic Heart Failure.

    PubMed

    Coma, Maria; González-Moneo, Maria Jesús; Enjuanes, Cristina; Velázquez, Paula Poveda; Espargaró, Deva Bas; Pérez, Bernardo Andrés; Tajes, Marta; Garcia-Elias, Anna; Farré, Núria; Sánchez-Benavides, Gonzalo; Martí-Almor, Julio; Comin-Colet, Josep; Benito, Begoña

    2016-01-15

    In patients with chronic heart failure (HF), cognitive impairment (CI) is associated with poorer treatment adherence and higher readmission and mortality rates. Previous studies suggest that atrial fibrillation (AF) could impair cognitive function. This study sought to assess the association between permanent AF (permAF) and CI in patients with HF. We evaluated cognitive function in 881 patients with stable HF (73 ± 11 years, 44% women, 48% with preserved ejection fraction) using the Mini-Mental State Examination test (n = 876) and the Pfeiffer's Short Portable Mental Status Questionnaire (n = 848). CI was defined as a Mini-Mental State Examination score <24 or Short Portable Mental Status Questionnaire (errors) >2. The independent association between permAF and CI was assessed by binary logistic regression analysis. A total of 295 patients (33.5%) had CI, in 5.1% of cases moderate/severe. Patients with permAF had more frequently any degree of CI (43% vs 31%), and moderate/severe CI (8% vs 5%). In the multivariate analysis, CI was associated with permAF (odds ratio 1.54, 95% C.I. 1.05 to 2.28), an older age, female gender, diabetes mellitus, chronic kidney disease, previous stroke, New York Heart Association class III/IV, and lower systolic blood pressure. No interaction was found for AF and CI between patients with reduced and preserved ejection fraction. In conclusion, the presence of permAF is independently associated with CI in patients with HF, both with reduced and preserved ejection fraction. Given the clinical impact of CI in the HF population, active assessment of cognitive function is particularly warranted in patients with HF with permAF. PMID:26686573

  9. [Individual heart functioning variability under exposure to equal physical factors in patients with different vegetative system tone].

    PubMed

    Dudnk, E N; Kalita, A V; Dibrova, E A; Fedorov, S M; Karimova, I M; Glazachev, O S; Sudakov, K V

    2007-01-01

    The article describes changes in heart rhythm variability (HRV) as a response to equal complex physical factors (hyperthermia of 60 degrees C with low relative humidity of 8 to 15%, air ionization, thalasso, and relaxing music). The subjects of the study were 28 individuals having no verified chronic diseases, who underwent a course of five recovery procedures using exposure to a complex of weak physical factors realized in Ionic House technology (Japan). The study found that changes in heart functioning as a response to equal physical factors depended on the initial vegetative system tone. Patients with normotonic and sympathicotonic heart regulation displayed the activation of parasympathetic vegetative nervous system as a result of a single exposure to a complex of physical factors, whereas in vagotonic patients sympathetic heart regulation was activated under the same conditions. PMID:17500213

  10. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

    PubMed

    Giugliano, Francesca M; Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-04-26

    Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients. PMID:27148425

  11. The relationship between resting heart rate variability and erectile tumescence among men with normal erectile function

    PubMed Central

    Harte, Christopher B.

    2013-01-01

    Introduction Individuals with erectile dysfunction have been shown to display lower heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. No studies have explored whether HRV is predictive of erectile response among men with clinically normal erectile function. Aim To examine associations between resting HRV and objective measures of genital response (i.e., resting penile circumference; erectile tumescence) and self-reported sexual function. Methods The sample comprised 59 male community volunteers (mean age = 20.15 years; SD = 2.52) selected from the control conditions of two previously published studies. Participants reported erectile function in the normal range (scoring ≥ 26 on the International Index of Erectile Function [IIEF]) and had no history of cardiovascular disease or myocardial infarct. During a laboratory visit, self-report, anthropometric, cardiovascular, and electrocardiographic data were assessed, as well as resting penile circumference and erectile tumescence in response to viewing an erotic film. Main Outcome Measures Resting penile responses, erectile tumescence (circumferential change via penile plethysmography), self-reported sexual function per the IIEF, and both time-domain (standard deviation of beat-to-beat [NN] intervals [SDNN], square root of the mean squared difference of successive NN intervals [RMSSD], and percent of NN intervals for which successive heartbeat intervals differed by at least 50 msec [pNN50]) and frequency-domain (low frequency [LF], high frequency [HF], LF/HF ratio) parameters of HRV were assessed. Results Higher resting HF power and lower resting LF/HF ratio were associated with greater erectile tumescence. There were marginally significant positive associations between mean NN interval and pNN50 and penile tumescence. HRV was not associated with self-reported sexual function or with resting penile circumference. Conclusions Results suggested that, among men without erectile

  12. Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells.

    PubMed

    Pannella, Micaela; Caliceti, Cristiana; Fortini, Francesca; Aquila, Giorgio; Vieceli Dalla Sega, Francesco; Pannuti, Antonio; Fortini, Cinzia; Morelli, Marco Bruno; Fucili, Alessandro; Francolini, Gloria; Voltan, Rebecca; Secchiero, Paola; Dinelli, Giovanni; Leoncini, Emanuela; Ferracin, Manuela; Hrelia, Silvana; Miele, Lucio; Rizzo, Paola

    2016-12-01

    It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4. We found a higher number of closed tubes in HUVECs treated with advanced HF patients serum in comparison with cells treated with serum from mild HF patients or controls. Furthermore, as indicated by the reduction of the active form of Notch4 (N4IC) and of Jagged1, advanced HF patients serum inhibited Notch signalling in HUVECs in comparison with mild HF patients' serum and controls. The circulating levels of NT-proBNP (N-terminal of the pro-hormone brain natriuretic peptide), a marker for the detection and evalutation of HF, were positively correlated with the number of closed tubes (r = 0.485) and negatively with Notch4IC and Jagged1 levels in sera-treated cells (r = -0.526 and r = -0.604, respectively). In conclusion, we found that sera from advanced HF patients promote sprouting angiogenesis and dysregulate Notch signaling in HUVECs. Our study provides in vitro evidence of an angiogenic stimulus arising during HF progression and suggests a role for the Notch pathway in it. J. Cell. Physiol. 231: 2700-2710, 2016. © 2016 Wiley Periodicals, Inc. PMID:26987674

  13. Better Adherence to Treatment Recommendations in Heart Failure Predicts Improved Cognitive Function at a One Year Follow Up

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Introduction Treatment non-adherence is common in heart failure and associated with poor health outcomes in this population. Recent cross-sectional work in heart failure and past work in other medical populations suggests cognitive function is a key determinant of patient’s ability to adhere to treatment recommendations. However, it is also possible that treatment adherence is an important modifier and predictor of cognitive function, though no study has examined this possibility and we sought to do so in a sample of heart failure patients. Methods 115 patients with heart failure self-reported adherence to treatment recommendations. The Modified Mini Mental State Examination (3MS), Trail Making Test parts A and B, and the California Verbal Learning Test-II (CVLT-II) assessed cognitive function. These procedures were performed at baseline and a 12-month follow-up. Results Global cognition and memory abilities improved over the 12-month period. Regression analyses controlling for baseline and medical and demographic factors showed better baseline treatment adherence predicted improved 12-month performances on the 3MS and CVLT-II. Adherence to medication and diet regimens and smoking abstinence emerged as the most important contributors. Conclusions Better treatment adherence predicted improved cognition one-year later in HF. Prospective studies that utilize objective assessments of treatment adherence are needed to confirm our findings and examine whether improved treatment adherence preserves cognitive function in heart failure. PMID:25352233

  14. SUMO1 Affects Synaptic Function, Spine Density and Memory

    PubMed Central

    Matsuzaki, Shinsuke; Lee, Linda; Knock, Erin; Srikumar, Tharan; Sakurai, Mikako; Hazrati, Lili-Naz; Katayama, Taiichi; Staniszewski, Agnieszka; Raught, Brian; Arancio, Ottavio; Fraser, Paul E.

    2015-01-01

    Small ubiquitin-like modifier-1 (SUMO1) plays a number of roles in cellular events and recent evidence has given momentum for its contributions to neuronal development and function. Here, we have generated a SUMO1 transgenic mouse model with exclusive overexpression in neurons in an effort to identify in vivo conjugation targets and the functional consequences of their SUMOylation. A high-expressing line was examined which displayed elevated levels of mono-SUMO1 and increased high molecular weight conjugates in all brain regions. Immunoprecipitation of SUMOylated proteins from total brain extract and proteomic analysis revealed ~95 candidate proteins from a variety of functional classes, including a number of synaptic and cytoskeletal proteins. SUMO1 modification of synaptotagmin-1 was found to be elevated as compared to non-transgenic mice. This observation was associated with an age-dependent reduction in basal synaptic transmission and impaired presynaptic function as shown by altered paired pulse facilitation, as well as a decrease in spine density. The changes in neuronal function and morphology were also associated with a specific impairment in learning and memory while other behavioral features remained unchanged. These findings point to a significant contribution of SUMO1 modification on neuronal function which may have implications for mechanisms involved in mental retardation and neurodegeneration. PMID:26022678

  15. Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture.

    PubMed

    Beste, Christian; Ocklenburg, Sebastian; von der Hagen, Maja; Di Donato, Nataliya

    2016-06-01

    Cortical development is a complex process where a multitude of factors, including cadherins, plays an important role and where disruptions are known to have far reaching effects in neural development and cortical patterning. Cadherins play a central role in structural left-right differentiation during brain and body development, but their effect on a functional level remains elusive. We addressed this question by examining functional cerebral asymmetries in a patient with Van Maldergem Syndrome (VMS) (MIM#601390), which is caused by mutations in DCHS1-FAT4 cadherins, using a dichotic listening task. Using neurophysiological (EEG) data, we show that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. Basic perceptual processing of biaurally presented auditory stimuli was unaffected. This suggests that the strength and emergence of functional cerebral asymmetries is a direct function of proliferation and differentiation of neuronal stem cells. Moreover, these results support the recent assumption that the molecular mechanisms establishing early left-right differentiation are an important factor in the ontogenesis of functional lateralization. PMID:25930014

  16. SUMO1 Affects Synaptic Function, Spine Density and Memory.

    PubMed

    Matsuzaki, Shinsuke; Lee, Linda; Knock, Erin; Srikumar, Tharan; Sakurai, Mikako; Hazrati, Lili-Naz; Katayama, Taiichi; Staniszewski, Agnieszka; Raught, Brian; Arancio, Ottavio; Fraser, Paul E

    2015-01-01

    Small ubiquitin-like modifier-1 (SUMO1) plays a number of roles in cellular events and recent evidence has given momentum for its contributions to neuronal development and function. Here, we have generated a SUMO1 transgenic mouse model with exclusive overexpression in neurons in an effort to identify in vivo conjugation targets and the functional consequences of their SUMOylation. A high-expressing line was examined which displayed elevated levels of mono-SUMO1 and increased high molecular weight conjugates in all brain regions. Immunoprecipitation of SUMOylated proteins from total brain extract and proteomic analysis revealed ~95 candidate proteins from a variety of functional classes, including a number of synaptic and cytoskeletal proteins. SUMO1 modification of synaptotagmin-1 was found to be elevated as compared to non-transgenic mice. This observation was associated with an age-dependent reduction in basal synaptic transmission and impaired presynaptic function as shown by altered paired pulse facilitation, as well as a decrease in spine density. The changes in neuronal function and morphology were also associated with a specific impairment in learning and memory while other behavioral features remained unchanged. These findings point to a significant contribution of SUMO1 modification on neuronal function which may have implications for mechanisms involved in mental retardation and neurodegeneration. PMID:26022678

  17. Keeping the heart in balance: the functional interactions of myoglobin with nitrogen oxides.

    PubMed

    Flögel, Ulrich; Fago, Angela; Rassaf, Tienush

    2010-08-15

    Myoglobin (Mb) is an important intracellular oxygen-binding hemoprotein found in the cytoplasm of skeletal and cardiac muscle tissue playing a well-known role in O(2) storage and delivery. Within the last decade the knowledge about Mb's function has been considerably extended by the generation of myoglobin-deficient (myo(-/-)) mice, which for the first time enabled the analysis of Mb's role in physiology without pharmacological intervention. Utilizing the myo(-/-) mice, it has been demonstrated that beyond its function in O(2) supply Mb substantially contributes to nitric oxide (NO) homeostasis in the heart. By a dynamic cycle, in which a decrease in tissue O(2) tension drives the conversion of Mb from being a NO scavenger under normoxia to a NO producer during hypoxia, mitochondrial respiration is reversibly adapted to the intracellular O(2) tension. Therefore, Mb may act as an important O(2) sensor through which NO can regulate muscle energetics and function. As Mb is widespread throughout the fauna, the diverse oxygen-dependent interactions between Mb and nitrogen oxides may not only be of relevance for mammals but also for other vertebrates as evidenced by comparable phenotypes of 'artificial' (myo(-/-) mice) and 'natural' Mb knockouts (icefish and amphibians). In conclusion, it seems likely that Mb's multifunctional properties create an environment characterized by a tightly adapted aerobic mitochondrial respiration and low levels of free radicals, and thus serve an essential and beneficial role within the myocardium, which appears to be functionally important over a wide range of species. PMID:20675541

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

    PubMed

    Calderon, Johanna; Bellinger, David C

    2015-10-01

    It is widely recognised that children with congenital heart disease (CHD) are at high risk for neurodevelopmental impairments including attention deficit hyperactivity disorder and autism spectrum disorder symptoms. Executive function impairments are one of the most prominent neurodevelopmental features associated with CHD. These deficits can have widespread debilitating repercussions in children's neurocognitive, behavioural, and psycho-social development. There is a crucial gap in research regarding the efficacy of preventive or treatment strategies for these important cognitive morbidities. Executive functions are complex neurocognitive skills highly amenable to improvement. Evidence-based interventions have shown promising results in other paediatric populations, strongly suggesting that they might also benefit the growing population of children with CHD. In this review, we summarise the available data on executive function impairments in children and adolescents with CHD. We underline the important co-morbidity of executive dysfunction with other cognitive and psychiatric issues in CHD, which raises awareness of the crucial need to prevent or at least mitigate these deficits. Finally, we summarise future avenues for research in terms of interventions that may help reduce executive function impairments in youth with CHD. PMID:26082199

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

    PubMed

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

    2015-09-01

    We analyzed the clinical presentation and outcomes (from 2003 to 2013) of heart failure (HF) with apparently normal systolic function (HFPEF). Based on the echocardiographic left ventricular ejection fraction (LVEF), patients were divided into 2 groups, group 1 (<50%) and group 2 (≥50%). Of 2212 patients with HF, 20% were in group 2. Patients in group 2 were more likely to be older, females, Arabs, hypertensive, and obese (P = .001). Patients in group 1 were mostly Asians and had more troponin-T positivity (P = .001). Inhospital cardiac arrest, shock, and deaths were significantly greater in group 1. On multivariate analysis, age, ST-segment elevation myocardial infarction, lack of on-admission β-blockers, and angiotensin-converting enzyme inhibitors use were independent predictors of mortality. HFPEF is associated with less mortality compared to those who presented with reduced LVEF. On admission, use of evidence-based medications could in part predict this difference in the hospital outcome. PMID:25248442

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

    PubMed

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

    2014-06-01

    We analyzed parameters of the pumping function of the heart in rats subjected to enhanced motor activity after a preliminary 70-day hypokinesia under conditions of α- and β-adrenergic receptor stimulation with norepinephrine followed by blockade of β-adrenergic receptor with propranolol (obsidian) and α1-adrenergic receptors with doxazosin. After norepinephrine administration, the HR and cardiac output were higher in rats with enhanced physical activity after preliminary hypokinesia than in rats with low physical activity. After propranolol administration, stroke volume and cardiac output in 100-day-old rats with limited activity were lower, and HR higher was than in rats with enhanced physical activity after preliminary 70-day hypokinesia. After administration of doxazosin, rats with limited motor activity demonstrated more pronounced changes in HR than rats with enhanced physical activity after preliminary 70-day hypokinesia. PMID:24970234

  1. Intracrine angiotensin II functions originate from noncanonical pathways in the human heart.

    PubMed

    Ferrario, Carlos M; Ahmad, Sarfaraz; Varagic, Jasmina; Cheng, Che Ping; Groban, Leanne; Wang, Hao; Collawn, James F; Dell Italia, Louis J

    2016-08-01

    Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1-12) [Ang-(1-12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1-12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions. PMID:27233763

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

    SciTech Connect

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

    2008-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

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

    PubMed

    Waldum-Grevbo, Bård

    2015-01-01

    The majority of outpatients with heart failure (HF) have chronic kidney disease (CKD) as an important comorbidity. Both glomerular filtration rate and abnormal urinary albumin excretion are major predictors of outcome in HF patients. Despite this, patients with renal dysfunction have been systematically excluded from the large randomized HF trials. There is lack of evidence for optimal treatment in these cardiorenal patients and treatment nihilism may account in part for their bad prognosis. Identifying and monitoring the progression of renal disease and making an effort to preserve renal function should be an important task in the management of all patients with HF. In this review, the current understanding of the pathophysiology of renal dysfunction in outpatients with HF will be summarized. Furthermore, important principles of the identification and management of cardiorenal patients will be described in order to make the physician more capable of managing outpatients with HF and renal dysfunction. PMID:25966919

  5. Temperament Affects Sympathetic Nervous Function in a Normal Population

    PubMed Central

    Kim, Bora; Lee, Jae-Hon; Kang, Eun-Ho

    2012-01-01

    Objective Although specific temperaments have been known to be related to autonomic nervous function in some psychiatric disorders, there are few studies that have examined the relationship between temperaments and autonomic nervous function in a normal population. In this study, we examined the effect of temperament on the sympathetic nervous function in a normal population. Methods Sixty eight healthy subjects participated in the present study. Temperament was assessed using the Korean version of the Cloninger Temperament and Character Inventory (TCI). Autonomic nervous function was determined by measuring skin temperature in a resting state, which was recorded for 5 minutes from the palmar surface of the left 5th digit using a thermistor secured with a Velcro® band. Pearson's correlation analysis and multiple linear regression were used to examine the relationship between temperament and skin temperature. Results A higher harm avoidance score was correlated with a lower skin temperature (i.e. an increased sympathetic tone; r=-0.343, p=0.004) whereas a higher persistence score was correlated with a higher skin temperature (r=0.433, p=0.001). Hierarchical linear regression analysis revealed that harm avoidance was able to predict the variance of skin temperature independently, with a variance of 7.1% after controlling for sex, blood pressure and state anxiety and persistence was the factor predicting the variance of skin temperature with a variance of 5.0%. Conclusion These results suggest that high harm avoidance is related to an increased sympathetic nervous function whereas high persistence is related to decreased sympathetic nervous function in a normal population. PMID:22993530

  6. Fetal urinoma and prenatal hydronephrosis: how is renal function affected?

    PubMed Central

    Oktar, Tayfun; Salabaş, Emre; Kalelioğlu, İbrahim; Atar, Arda; Ander, Haluk; Ziylan, Orhan; Has, Recep; Yüksel, Atıl

    2013-01-01

    Objective: In our study, the functional prognosis of kidneys with prenatal urinomas were investigated. Material and methods: Between 2006 and 2010, fetal urinomas were detected in 19 fetuses using prenatal ultrasonography (US), and the medical records were reviewed retrospectively. Of the 19 cases, the follow-up data were available for 10 fetuses. The gestational age at diagnosis, prognosis of urinomas, clinical course and renal functions were recorded. Postnatal renal functions were assessed with renal scintigraphy. Results: Unilateral urinomas and increased parenchyma echogenicity in the ipsilateral kidney were detected in all of the fetuses. Of the 10 fetuses with follow-up data, the option of termination was offered in 6 cases of anhydramnios, including 3 cases with signs of infravesical obstruction (a possible posterior urethral valve (PUV) and poor prognostic factors and 3 cases with unilateral hydronephrosis and increased echogenicity in the contralateral kidney. Only one family agreed the termination. The other 5 fetuses died during the early postnatal period. The average postnatal follow-up period in the 4 surviving fetuses was 22.5 months (8–38 months). One patient with a PUV underwent ablation surgery during the early postnatal period. In the postnatal period, none of the 4 kidneys that were ipsilateral to the urinoma were functional on scintigraphic evaluation. The urinomas disappeared in 3 cases. Nephrectomy was performed in one case due to recurrent urinary tract infections. Conclusion: In our study, no function was detected in the ipsilateral kidney of surviving patients with urinomas. Upper urinary tract dilatation accompanied by a urinoma is a poor prognostic factor for renal function. PMID:26328088

  7. Failure of platelet parameters and biomarkers to correlate platelet function to severity and etiology of heart failure in patients enrolled in the EPCOT trial. With special reference to the Hemodyne hemostatic analyzer. Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure.

    PubMed

    Serebruany, Victor L; McKenzie, Marcus E; Meister, Andrew F; Fuzaylov, Sergey Y; Gurbel, Paul A; Atar, Dan; Gattis, Wendy A; O'Connor, Christopher M

    2002-01-01

    Data from small studies have suggested the presence of platelet abnormalities in patients with congestive heart failure (CHF). We sought to characterize the diagnostic utility of different platelet parameters and platelet-endothelial biomarkers in a random outpatient CHF population investigated in the EPCOT ('Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure') Trial. Blood samples were obtained for measurement of platelet contractile force (PCF), whole blood aggregation, shear-induced closure time, expression of glycoprotein (GP) IIb/IIIa, and P-selectin in 100 consecutive patients with CHF. Substantial interindividual variability of platelet characteristics exists in patients with CHF. There were no statistically significant differences when patients were grouped according to incidence of vascular events, emergency revascularization needs, survival, or etiology of heart failure. Aspirin use did not affect instrument readings either. PCF correlates very poorly with whole blood aggregometry (r(2) = 0.023), closure time (r(2) = 0.028), platelet GP IIb/IIIa (r(2) = 0.0028), and P-selectin (r(2) = 0.002) expression. Furthermore, there was no correlation with brain natriuretic peptide concentrations, a marker of severity and prognosis in heart failure reflecting the neurohumoral status. Patients with heart failure enrolled in the EPCOT Trial exhibited a marginal, sometimes oppositely directed change in platelet function, challenging the diagnostic utility of these platelet parameters and biomarkers to serve as useful tools for the identification of platelet abnormalities, for predicting clinical outcomes, or for monitoring antiplatelet strategies in this population. The usefulness of these measurements for assessing platelets in the different clinical settings remains to be explored. Taken together, opposite to our expectations, major clinical characteristics of heart failure did not correlate well with

  8. Effects of chronic methamphetamine exposure on heart function in uninfected and retrovirus-infected mice.

    PubMed

    Yu, Qianli; Montes, Sergio; Larson, Douglas F; Watson, Ronald R

    2002-07-12

    Methamphetamine (MA) increases catecholamine levels, which have detrimental effects on heart function through vasoconstriction, myocardial hypertrophy, and fibrosis. Murine retrovirus infection induces dilated cardiomyopathy (DCM). The present study investigated the cardiovascular effects of chronic MA treatment on uninfected and retrovirus-infected mice. C57BL/6 mice were studied after 12 weeks treatment. The four study groups were (group I) uninfected, MA placebo; (group II) infected, MA placebo; (group III) uninfected, MA treatment; and (group IV) infected and MA treatment. MA injections were given i.p. once a day for 5 days/week with a increasing dose from 15 mg/kg to 40 mg/kg. Left ventricular mechanics were measured in situ a using Millar conductance catheter system for pressure-volume loop analysis. Cardiac pathology was determined with histological analysis. In the uninfected mice, the load independent contractile parameters, pre-load recruitable stroke work (PRSW) and dP/dt(max) vs. Ved, significantly decreased by 32% and 35% in MA treated mice when compared to the saline injected mice. In retrovirus-infected mice, although there were no significant difference in Ees, PRSW, and dP/dt(max) vs. Ved due to MA treatment, they were increased 45%, 15% and 42% respectively when compared to saline treated mice. No further lowered heart function during murine AIDS may be due to the counteraction of the retroviral DCM and the MA induced myocardial fibrosis and hypertrophy (thickening of the ventricular walls). This is supported by increases in the End-diastolic volume (Ved, 38%) and End-systolic volume (Ves, 84%) in the retrovirus-infected saline injected mice, the decreases of 33% and 17% in the uninfected MA-treated mice, but no significant changes in the retrovirus-infected MA treated mice when compared to uninfected saline injected mice. These data suggest that MA induced myocardial cellular changes compensate for retrovirus induced DCM. PMID:12084392

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2016-03-01

    The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders. PMID:26840706

  11. Thrombocytosis in the Setting of Isomerism and a Functionally Univentricular Heart

    PubMed Central

    2015-01-01

    Introduction Bodily isomerism, also known as heterotaxy, is a unique entity in which there is mirror imagery in various organ systems. Those with isomerism will often have congenital malformations of the heart requiring functionally univentricular palliation. Anecdotally, thrombocytosis has been noted with higher frequency in patients with isomerism. This study aimed to determine the prevalence of thrombocytosis at different stages and identify independent predictors of thrombocytosis. Methods We identified patients with isomerism and a functionally univentricular heart who received care at our institution between January 1998 and January 2014. Clinical data regarding these patients was collected via chart review. Platelet counts were collected before initial surgical palliation, the day prior to second surgical palliation, and the day prior to the third surgical palliation. Platelet counts from the first postoperative day following all three surgical palliations was also collected. Mean platelet counts were compared between consecutive stages as well as to the initial platelet count. The frequency of thrombocytosis was also calculated at each point with a binomial logistic regression conducted to determine independent risk factors of thrombocytosis at each time point. Results A total of 57 patients were included in the analysis. The mean platelet count before initial surgical palliation was 349.21 x 109/L and decreased with age. Thrombocytosis was noted in 15.8% prior to initial surgical palliation and 23.6% prior to second surgical palliation. Thrombocytosis was no longer noted after second surgical palliation. No independent risk factors for thrombocytosis were identified. Conclusion Thrombocytosis is not infrequent during the first year of life in those with isomerism. It is important to be vigilant of platelet counts in this population as thrombocytosis may lead to increased thromboembolic events, particularly in the setting of a Blalock-Taussig shunt

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

    PubMed Central

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

    2016-01-01

    The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R 2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders. PMID:26840706

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

    PubMed

    Mavrodi, Alexandra; Paraskevas, George

    2014-03-01

    According to their writings, ancient Greek physicians had explored the anatomy of the heart. Although pre-Hippocratic medicine, which relied on religion and mysticism, has nothing more to present than implausible theories and speculations, younger physicians thanks to their animal dissections were able to depict the heart with detail. Hippocratic "On the Heart", Aristotle's, Herophilus', Erasistratus' and Galen's writings provide us with the necessary data to take a look at the anatomy of the heart as it was described back then. Despite of some confusing passages in their writings and some erroneous notions, the heart was described with relative accuracy. In the years after antiquity and in the Middle Age the only information about the anatomy of the heart could be derived from the ancient Greek works and only anatomists of the Renaissance managed to displace them. In this paper we present the knowledge of all known ancient Greek physicians about the heart, with emphasis on its anatomy. PMID:24447741

  14. Drying process strongly affects probiotics viability and functionalities.

    PubMed

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

    2015-11-20

    Probiotic formulations are widely used and are proposed to have a variety of beneficial effects, depending on the probiotic strains present in the product. The impact of drying processes on the viability of probiotics is well documented. However, the impact of these processes on probiotics functionality remains unclear. In this work, we investigated variations in seven different bacterial markers after various desiccation processes. Markers were composed of four different viability evaluation (combining two growth abilities and two cytometric measurements) and in three in vitro functionalities: stimulation of IL-10 and IL-12 production by PBMCs (immunomodulation) and bacterial adhesion to hexadecane. We measured the impact of three drying processes (air-drying, freeze-drying and spray-drying), without the use of protective agents, on three types of probiotic bacteria: Bifidobacterium bifidum, Lactobacillus plantarum and Lactobacillus zeae. Our results show that the bacteria respond differently to the three different drying processes, in terms of viability and functionality. Drying methods produce important variations in bacterial immunomodulation and hydrophobicity, which are correlated. We also show that adherence can be stimulated (air-drying) or inhibited (spray-drying) by drying processes. Results of a multivariate analysis show no direct correlation between bacterial survival and functionality, but do show a correlation between probiotic responses to desiccation-rewetting and the process used to dry the bacteria. PMID:26325197

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

    ERIC Educational Resources Information Center

    Richardson, T.; Kester, J. J.

    1984-01-01

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

  16. Suppression of cerebral hemodynamics is associated with reduced functional capacity in patients with heart failure

    PubMed Central

    Fu, Tieh-Cheng; Wang, Chao-Hung; Hsu, Chih-Chin; Cherng, Wen-Jin; Huang, Shu-Chun

    2011-01-01

    This investigation elucidated the underlying mechanisms of functional impairments in patients with heart failure (HF) by simultaneously comparing cardiac-cerebral-muscle hemodynamic and ventilatory responses to exercise among HF patients with various functional capacities. One hundred one patients with HF [New York Heart Association HF functional class II (HF-II, n = 53) and functional class III (HF-III, n = 48) patients] and 71 normal subjects [older control (O-C, n = 39) and younger control (Y-C, n = 32) adults] performed an incremental exercise test using a bicycle ergometer. A recently developed noninvasive bioreactance device was adopted to measure cardiac hemodynamics, and near-infrared spectroscopy was employed to assess perfusions in the frontal cerebral lobe (Δ[THb]FC) and vastus lateralis muscle (Δ[THb]VL). The results demonstrated that the Y-C group had higher levels of cardiac output, Δ[THb]FC, and Δ[THb]VL during exercise than the O-C group. Moreover, these cardiac/peripheral hemodynamic responses to exercise in HF-III group were smaller than those in both HF-II and O-C groups. Although the change of cardiac output caused by exercise was normalized, the amounts of blood distributed to frontal cerebral lobe and vastus lateralis muscle in the HF-III group significantly declined during exercise. The HF-III patients had lower oxygen-uptake efficiency slopes (OUES) and greater V̇e-V̇o2 slopes than the HF-II patients and age-matched controls. However, neither hemodynamic nor ventilatory response to exercise differed significantly between the HF-II and O-C groups. Cardiac output, Δ[THb]FC, and Δ[THb]VL during exercise were directly related to the OUES and V̇o2peak and inversely related to the V̇e-V̇co2 slope. Moreover, cardiac output or Δ[THb]FC was an effect modifier, which modulated the correlation status between Δ[THb]VL and V̇e-V̇co2 slope. We concluded that the suppression of cerebral/muscle hemodynamics during exercise is associated with

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

    Discoidin domain receptor 2 (DDR2) is a fibrillar collagen receptor that is expressed in mesenchymal cells throughout the body. In the heart, DDR2 is selectively expressed on cardiac fibroblasts. We generated a germline DDR2 knockout mouse and used this mouse to examine the role of DDR2 deletion on heart structure and function. Echocardiographic measurements from null mice were consistent with those from a smaller heart, with reduced left ventricular chamber dimensions and little change in wall thickness. Fractional shortening appeared normal. Left ventricular pressure measurements revealed mild inotropic and lusitropic abnormalities that were accentuated by dobutamine infusion. Both body and heart weights from 10-wk-old male mice were ∼20% smaller in null mice. The reduced heart size was not simply due to reduced body weight, since cardiomyocyte lengths were atypically shorter in null mice. Although normalized cardiac collagen mass (assayed by hydroxyproline content) was not different in null mice, the collagen area fraction was statistically higher, suggesting a reduced collagen density from altered collagen deposition and cross-linking. Cultured cardiac fibroblasts from null mice deposited collagen at a slower rate than wild-type littermates, possibly due to the expression of lower prolyl 4-hydroxylase α-isoform 1 enzyme levels. We conclude that genetic deletion of the DDR2 collagen receptor alters cardiac fibroblast function. The resulting perturbations in collagen deposition can influence the structure and function of mature cardiomyocytes. PMID:24993042

  19. An integrated approach for the systematic identification and characterization of heart-enriched genes with unknown functions

    PubMed Central

    Uchida, Shizuka; Schneider, André; Wiesnet, Marion; Jungblut, Benno; Zarjitskaya, Polina; Jenniches, Katharina; Kreymborg, Karsten grosse; Seeger, Werner; Braun, Thomas

    2009-01-01

    Background High throughput techniques have generated a huge set of biological data, which are deposited in various databases. Efficient exploitation of these databases is often hampered by a lack of appropriate tools, which allow easy and reliable identification of genes that miss functional characterization but are correlated with specific biological conditions (e.g. organotypic expression). Results We have developed a simple algorithm (DGSA = Database-dependent Gene Selection and Analysis) to identify genes with unknown functions involved in organ development concentrating on the heart. Using our approach, we identified a large number of yet uncharacterized genes, which are expressed during heart development. An initial functional characterization of genes by loss-of-function analysis employing morpholino injections into zebrafish embryos disclosed severe developmental defects indicating a decisive function of selected genes for developmental processes. Conclusion We conclude that DGSA is a versatile tool for database mining allowing efficient selection of uncharacterized genes for functional analysis. PMID:19267916

  20. Left ventricular angiography on exercise. A new method of assessing left ventricular function in ischaemic heart disease.

    PubMed Central

    Sharma, B; Goodwin, J F; Raphael, M J; Steiner, R E; Rainbow, R G; Taylor, S H

    1976-01-01

    Left ventricular function was studied in 17 patients with ischaemic heart disease and compared with 4 patients with normal left ventricular function. The patients in the homogeneous group of ischaemic heart disease were further subdivided into those 'without angina' (n=5) and those 'with angina' (n=12), depending upon the presence of angina during supine leg exercise at the time of definitive study. At rest there was no significant difference in the heart rate, cardiac output, stroke volume, and left ventricular end-diastolic pressure (LVEDP) in the three groups. During exercise the cardiac output and stroke volume were significantly depressed and LVEDP was significantly raised in the ischaemic heart disease group as a whole but within this group failed to show any significant difference in patients with and without angina. The left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) measurements showed clear separation of these three groups only on exercise. On exercise, there was decrease in LVEDV and LVESV (P less than 0.05; P less than 0.02) in the group with normal left ventricular function, no change in the group with ischaemic heart disease without angina, and striking increase in LVEDV and LVESV in the group with ischaemic heart disease and angina (P less than 0.01 and P less than 0.02, respectively). This angiographic method of assessing left ventricular function shows clear separation of the three groups and also highlights the significance of angina. Ejection fraction (EF), a commonly measured parameter of left ventricular function, failed to reflect consistent changes on exercise as compared to values at rest which emphasizes the limitations of the measurement of ejection fraction at rest. Images PMID:1082766

  1. Modulation of Serotonin Transporter Function during Fetal Development Causes Dilated Heart Cardiomyopathy and Lifelong Behavioral Abnormalities

    PubMed Central

    Noorlander, Cornelle W.; Ververs, Frederique F. T.; Nikkels, Peter G. J.; van Echteld, Cees J. A.; Visser, Gerard H. A.; Smidt, Marten P.

    2008-01-01

    Background Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. Methodology/Principal Findings In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. Conclusions These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher

  2. Heart regeneration.

    PubMed

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26597703

  3. SLE-associated risk factors affect DC function

    PubMed Central

    Son, Myoungsun; Kim, Sun Jung; Diamond, Betty

    2016-01-01

    Numerous risk alleles for systemic lupus erythematosus (SLE) have now been identified. Analysis of the expression of genes with risk alleles in cells of hematopoietic origin demonstrates them to be most abundantly expressed in B cells and dendritic cells (DCs), suggesting that these cell types may be the drivers of the inflammatory changes seen in SLE. DCs are of particular interest as they act to connect the innate and the adaptive immune response. Thus, DCs can transform inflammation into autoimmunity, and autoantibodies are the hallmark of SLE. In this review, we focus on mechanisms of tolerance that maintain DCs in a non-activated, non-immunogenic state. We demonstrate, using examples from our own studies, how alterations in DC function stemming from either DC-intrinsic abnormalities or DC-extrinsic regulators of function can predispose to autoimmunity. PMID:26683148

  4. RIGHT HEMISPHERIC FUNCTION IN NORMALS, AFFECTIVE DISORDER AND SCHIZOPHRENIA

    PubMed Central

    Borde, Milind; Roy, Amal; Davis, Elizabeth J.B.; Davis, Rachel

    1996-01-01

    The happy-sad chimeric faces test has been established as a useful test of right hemispheric function. It is known to elicit a left hemifacial bias (LHF bias) in right handed subjects. 41 normals and 19 manic, depressive and schizophrenic patients each were tested. All subjects were strictly right handed. Normals and depressives showed significant LHF bias. Monies and schizophrenics did not show significant LHF Bias. This suggests right hemispheric dysfunction in both mania and schizophrenia. PMID:21584135

  5. Nuclear cyclophilins affect spliceosome assembly and function in vitro

    PubMed Central

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

    2015-01-01

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

  6. Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

    PubMed Central

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

    2015-01-01

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

  7. Prenatal drug exposure affects neonatal brain functional connectivity.

    PubMed

    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

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

  8. Aerobic Exercise as an Adjunct Therapy for Improving Cognitive Function in Heart Failure

    PubMed Central

    Gary, Rebecca A.; Brunn, Kathryn

    2014-01-01

    Persons with heart failure (HF) are typically older and are at a much higher risk for developing cognitive impairment (CI) than persons without HF. Increasingly, CI is recognized as a significant, independent predictor of worse clinical outcomes, more frequent hospital readmissions, and higher mortality rates in persons with HF. CI can have devastating effects on ability to carry out HF effective self-care behaviors. If CI occurs, however, there are currently no evidence based guidelines on how to manage or improve cognitive function in this population. Improvement in cognition has been reported following some therapies in HF and is thought to be the consequence of enhanced cerebral perfusion and oxygenation, suggesting that CI may be amenable to intervention. Because there is substantial neuronal loss with dementia and no effective restorative therapies, interventions that slow, reverse, or prevent cognitive decline are essential. Aerobic exercise is documented to increase cerebral perfusion and oxygenation by promoting neuroplasticity and neurogenesis and, in turn, cognitive functioning. Few studies have examined exercise as a potential adjunct therapy for attenuating or alleviating cognitive decline in HF. In this review, the potential benefit of aerobic exercise on cognitive functioning in HF is presented along with future research directions. PMID:25105053

  9. Non-Invasive Evaluation of Heart Function with Four-Dimensional Echocardiography

    PubMed Central

    Chen, Ran; Zhu, Meihua; Sahn, David J.; Ashraf, Muhammad

    2016-01-01

    Background The aim of this study is to assess the accuracy and feasibility of left ventricular systolic function determined by four-dimensional echocardiography (4DE). Methods Latex balloons were sewn into the left ventricle (LV) of 20 freshly harvested pig hearts which were then passively driven by a pulsatile pump apparatus. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and left ventricular ejection fraction (LVEF) derived from 4DEand two-dimensional echocardiography (2DE)-derived LVEF were quantified at different stroke volumes (SV) 30–70 ml and correlated with sonomicrometry data. Results In all comparisons, GLS, GCS, GAS, 2DE-LVEF, and 4DE-LVEF demonstrated strong correlations with sonomicrometry data (r = 0.77, r = 0.89, r = 0.79, r = 0.93, r = 0.96, all P <0.001). Bland-Altman analyses showed slight overestimations of echo-derived GLS, GCS, 2DE-LVEF and 3DE-LVEF over sonomicrometry values (bias = 2.88, bias = 3.99, bias = 3.37, bias = 2.78, respectively). Furthermore, there is better agreement between GCS, 4D LVEF and sonomicrometry values compared with GLS and 2D LVEF. Conclusion Four-dimensional echocardiography accurately assesses LV function. GCS derived by 4DE is a potential alternative parameter to quantify LV systolic function. PMID:27144844

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

    PubMed

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

    2002-01-01

    It is thought that changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca(2+) uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca(2+) uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca(2+) uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca(2+) handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression. PMID:11744638

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  13. Novel heart rate parameters for the assessment of autonomic nervous system function in premature infants.

    PubMed

    Lucchini, M; Fifer, W P; Sahni, R; Signorini, M G

    2016-09-01

    Autonomic nervous system (ANS) balance is a key factor in homeostatic control of cardiac activity, breathing and certain reflex reactions such as coughing, sneezing and swallowing and thus plays a crucial role for survival. ANS impairment has been related to many neonatal pathologies, including sudden infant death syndrome (SIDS). Moreover, some conditions have been identified as risk factors for SIDS, such as prone sleep position. There is an urgent need for timely and non-invasive assessment of ANS function in at-risk infants. Systematic measurement of heart rate variability (HRV) offers an optimal approach to access indirectly both sympathetic and parasympathetic influences on ANS functioning. In this paper, data from premature infants collected in a sleep physiology laboratory in the NICU are presented: traditional and novel approaches to HRV analyses are applied and compared in order to evaluate their relative merits in the assessment of ANS activity and the influence of sleep position. Indices from time domain and nonlinear approaches contributed as markers of physiological development in premature infants. Moreover, significant differences were observed as a function of sleep position. PMID:27480495

  14. The effect of negative affect on cognition: Anxiety, not anger, impairs executive function.

    PubMed

    Shields, Grant S; Moons, Wesley G; Tewell, Carl A; Yonelinas, Andrew P

    2016-09-01

    It is often assumed that negative affect impairs the executive functions that underlie our ability to control and focus our thoughts. However, support for this claim has been mixed. Recent work has suggested that different negative affective states like anxiety and anger may reflect physiologically separable states with distinct effects on cognition. However, the effects of these 2 affective states on executive function have never been assessed. As such, we induced anxiety or anger in participants and examined the effects on executive function. We found that anger did not impair executive function relative to a neutral mood, whereas anxiety did. In addition, self-reports of induced anxiety, but not anger, predicted impairments in executive function. These results support functional models of affect and cognition, and highlight the need to consider differences between anxiety and anger when investigating the influence of negative affect on fundamental cognitive processes such as memory and executive function. (PsycINFO Database Record PMID:27100367

  15. 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

    SciTech Connect

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

    2013-11-15

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

  16. Yersinia enterocolitica Affects Intestinal Barrier Function in the Colon.

    PubMed

    Hering, Nina A; Fromm, Anja; Kikhney, Judith; Lee, In-Fah M; Moter, Annette; Schulzke, Jörg D; Bücker, Roland

    2016-04-01

    Infection with Yersinia enterocolitica causes acute diarrhea in early childhood. A mouse infection model presents new findings on pathological mechanisms in the colon. Symptoms involve diarrhea with watery feces and weight loss that have their functional correlates in decreased transepithelial electrical resistance and increased fluorescein permeability. Y. enterocolitica was present within the murine mucosa of both ileum and colon. Here, the bacterial insult was of focal nature and led to changes in tight junction protein expression and architecture. These findings are in concordance with observations from former cell culture studies and suggest a leak flux mechanism of diarrhea. PMID:26621910

  17. Dietary supplementation with either saturated or unsaturated fatty acids does not affect the mechanoenergetics of the isolated rat heart

    PubMed Central

    Goo, Soyeon; Han, June‐Chiew; Nisbet, Linley A.; LeGrice, Ian J.; Taberner, Andrew J.; Loiselle, Denis S.

    2014-01-01

    Abstract It is generally recognized that increased consumption of polyunsaturated fatty acids, fish oil (FO) in particular, is beneficial to cardiac and cardiovascular health, whereas equivalent consumption of saturated fats is deleterious. In this study, we explore this divergence, adopting a limited purview: The effect of dietary fatty acids on the mechanoenergetics of the isolated heart per se. Mechanical indices of interest include left‐ventricular (LV) developed pressure, stroke work, cardiac output, coronary perfusion, and LV power. The principal energetic index is whole‐heart oxygen consumption, which we subdivide into its active and basal moieties. The primary mechanoenergetic index of interest is cardiac efficiency, the ratio of work performance to metabolic energy expenditure. Wistar rats were divided into three Diet groups and fed, ad libitum, reference (REF), fish oil‐supplemented (FO), or saturated fatty acid‐supplemented (SFA) food for 6 weeks. At the end of the dietary period, hearts were excised, mounted in a working‐heart rig, and their mechanoenergetic performance quantified over a range of preloads and afterloads. Analyses of Variance revealed no difference in any of the individual mechanoenergetic indices among the three Diet groups. In particular, we found no effect of prior dietary supplementation with either saturated or unsaturated fatty acids on the global efficiency of the heart. PMID:24760525

  18. Cardiac Rehabilitation is Associated with Lasting Improvements in Cognitive Function in Older Adults with Heart Failure

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Objective Heart failure (HF) is a known risk factor for cognitive impairment. Cardiac rehabilitation (CR) may attenuate poor neurocognitive outcomes in HF via improved physical fitness—a significant promoter of cognitive function. However, no study has examined the possible acute and lasting benefits of CR on cognitive function in persons with HF. Methods and Results 52 patients with HF completed a 12-week Phase II CR program. All participants were administered neuropsychological testing and completed a brief physical fitness assessment at baseline, completion of CR (i.e. 12-weeks), and 12-month follow-up. Repeated measures analyses showed a significant time effect for both attention/executive function and memory (p < 0.05). Attention/executive function performance increased from baseline to 12-weeks and these gains remained up to 12-months; memory was unchanged from baseline to 12-weeks, but then improved between the 12-week and 12-month time points. Physical fitness improved from baseline to 12-weeks and these benefits were maintained 12-months later. Changes in physical fitness and cognitive function over time did not reach a statistically significant association, though poorer physical fitness was associated with decreased cognitive performance at the baseline and 12-month time points. Conclusions CR is associated with both acute and lasting cognitive benefits in patients with HF. Prospective studies with extended follow-ups are needed to clarify the mechanisms that underpin cognitive improvements following CR (e.g., improved cerebral perfusion) and whether CR can ultimately reduce risk for cognitive decline and conditions like Alzheimer’s disease in HF. PMID:25181916

  19. DiGeorge Syndrome Gene tbx1 Functions through wnt11r to Regulate Heart Looping and Differentiation

    PubMed Central

    Choudhry, Priya; Trede, Nikolaus S.

    2013-01-01

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

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

    PubMed

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

    2015-08-01

    Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients. PMID:25979518

  1. Assessing structural and functional responses of murine hearts to acute and sustained β-adrenergic stimulation in vivo

    PubMed Central

    Puhl, Sarah-Lena; Weeks, Kate L.; Ranieri, Antonella; Avkiran, Metin

    2016-01-01

    Introduction Given the importance of β-adrenoceptor signalling in regulating cardiac structure and function, robust protocols are required to assess potential alterations in such regulation in murine models in vivo. Methods Echocardiography was performed in naïve and stressed (isoprenaline; 30 μg/g/day s.c. for up to 14 days) mice, in the absence or presence of acute β-adrenergic stimulation (dobutamine 0.75 μg/g, i.p.). Controls received saline infusion and/or injection. Hearts were additionally analysed gravimetrically, histologically and biochemically. Results In naïve mice, acute β-adrenoceptor stimulation with dobutamine increased heart rate, left ventricular (LV) fractional shortening (LVFS), ejection fraction (LVEF) and wall thickness and decreased LV diameter (p < 0.05). In stressed mice, dobutamine failed to induce further inotropic and chronotropic responses. Furthermore, following dobutamine injection, these mice exhibited lower LVEF and LVFS at identical heart rates, relative to corresponding controls. Sustained isoprenaline infusion induced LV hypertrophy (increased heart weight, heart weight/body weight ratio, heart weight/tibia length ratio and LV wall thickness (p < 0.05)) by 3 days, with little further change at 14 days. In contrast, increases in LVEF and LVFS were seen only at 14 days (p < 0.05). Discussion We describe protocols for and illustrative data from the assessment of murine cardiac responses to acute and sustained β-adrenergic stimulation in vivo, which would be of value in determining the impact of genetic or pharmacological interventions on such responses. Additionally, our data indicate that acute dobutamine stimulation unmasks early signs of LV dysfunction in the remodelled heart, even at a stage when basal function is enhanced. PMID:26836145

  2. The Development of Functional Overreaching Is Associated with a Faster Heart Rate Recovery in Endurance Athletes

    PubMed Central

    Aubry, Anaël; Hausswirth, Christophe; Louis, Julien; Coutts, Aaron J.

    2015-01-01

    Purpose The aim of the study was to investigate whether heart rate recovery (HRR) may represent an effective marker of functional overreaching (f-OR) in endurance athletes. Methods and Results Thirty-one experienced male triathletes were tested (10 control and 21 overload subjects) before (Pre), and immediately after an overload training period (Mid) and after a 2-week taper (Post). Physiological responses were assessed during an incremental cycling protocol to exhaustion, including heart rate, catecholamine release and blood lactate concentration. Ten participants from the overload group developed signs of f-OR at Mid (i.e. -2.1 ± 0.8% change in performance associated with concomitant high perceived fatigue). Additionally, only the f-OR group demonstrated a 99% chance of increase in HRR during the overload period (+8 ± 5 bpm, large effect size). Concomitantly, this group also revealed a >80% chance of decreasing blood lactate (-11 ± 14%, large), plasma norepinephrine (-12 ± 37%, small) and plasma epinephrine peak concentrations (-51 ± 22%, moderate). These blood measures returned to baseline levels at Post. HRR change was negatively correlated to changes in performance, peak HR and peak blood metabolites concentrations. Conclusion These findings suggest that i) a faster HRR is not systematically associated with improved physical performance, ii) changes in HRR should be interpreted in the context of the specific training phase, the athletes perceived level of fatigue and the performance response; and, iii) the faster HRR associated with f-OR may be induced by a decreased central command and by a lower chemoreflex activity. PMID:26488766

  3. Mitochondrial depolarization and asystole in the globally ischemic rabbit heart: coordinated response to interventions affecting energy balance

    PubMed Central

    Venable, Paul W.; Sciuto, Katie J.; Warren, Mark; Taylor, Tyson G.; Garg, Vivek; Shibayama, Junko

    2014-01-01

    Mitochondrial membrane potential (ΔΨm) depolarization has been implicated in the loss of excitability (asystole) during global ischemia, which is relevant for the success of defibrillation and resuscitation after cardiac arrest. However, the relationship between ΔΨm depolarization and asystole during no-flow ischemia remains unknown. We applied spatial Fourier analysis to confocally recorded fluorescence emitted by ΔΨm-sensitive dye tetramethylrhodamine methyl ester. The time of ischemic ΔΨm depolarization (tmito_depol) was defined as the time of 50% decrease in the magnitude of spectral peaks reflecting ΔΨm. The time of asystole (tasys) was determined as the time when spontaneous and induced ventricular activity ceased to exist. Interventions included tachypacing (150 ms), myosin II ATPase inhibitor blebbistatin (heart immobilizer), and the combination of blebbistatin and the inhibitor of glycolysis iodoacetate. In the absence of blebbistatin, confocal images were obtained during brief perfusion with hyperkalemic solution and after the contraction failed between 7 and 15 min of ischemia. In control, tmito_depol and tasys were 24.4 ± 6.0 and 26.0 ± 5.0 min, respectively. Tachypacing did not significantly affect either parameter. Blebbistatin dramatically delayed tmito_depol and tasys (51.4 ± 8.6 and 45.7 ± 5.3 min, respectively; both P < 0.0001 vs. control). Iodoacetate combined with blebbistatin accelerated both events (tmito_depol, 12.7 ± 1.8 min; and tasys, 6.5 ± 1.1 min; both P < 0.03 vs. control). In all groups pooled together, tasys was strongly correlated with tmito_depol (R2 = 0.845; P < 0.0001). These data may indicate a causal relationship between ΔΨm depolarization and asystole or a similar dependence of the two events on energy depletion during ischemia. Our results urge caution against the use of blebbistatin in studies addressing pathophysiology of myocardial ischemia. PMID:25552307

  4. Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function

    MedlinePlus

    ... for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...

  5. Does Vitamin C Deficiency Affect Cognitive Development and Function?

    PubMed Central

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

    2014-01-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(−/−) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies. PMID:25244370

  6. Mevalonate availability affects human and rat resistance vessel function.

    PubMed Central

    Roullet, J B; Xue, H; Roullet, C M; Fletcher, W S; Cipolla, M J; Harker, C T; McCarron, D A

    1995-01-01

    Previous data in rat conductance vessels indicated that cellular mevalonate contributes to vascular tone and systemic blood pressure control. Using exogenous mevalonate (M) or lovastatin, a 3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitor (L), we characterized the role of mevalonate availability in resistance artery function, both in experimental animals and humans. Rat mesenteric artery resistance vessels (MARV, n = 9) were incubated for 48 h with either L, M, L + M, or vehicle (V) and tested for reactivity to NE, serotonin, acetylcholine, atrial natriuretic peptide, and sodium nitroprusside (SNP). Lovastatin increased sensitivity to NE (P < 0.03) and serotonin (P < 0.003), and significantly impaired the response to all three vasodilators. These effects were reversed by co-incubation with mevalonate. Mevalonate alone had no effect. In separate experiments, intravascular free Ca2+ concentration (ivfCa2+) was determined in fura-2AM loaded MARV. Basal ivfCa2+ was increased after a 48-h exposure to L (52.7 +/- 4.6 nM, L, vs. 29.7 +/- 2.4 nM, V, n = 12, P < 0.003), as were ivfCa2+ levels following stimulation with low (100 nM) NE concentrations. Similar ivfCa2+ concentrations were achieved during maximum contraction with NE (10 mM) in both groups. Human resistance arteries of human adipose tissue were also studied. Lovastatin increased the sensitivity to NE (ED50 = 372 +/- 56 nM, V, and 99 +/- 33 nM, L, P < 0.001) and significantly decreased the relaxation to acetylcholine and SNP of human vessels. We conclude that mevalonate availability directly contribute to resistance vessel function and vascular signal transduction systems in both experimental animals and humans. The study calls for the identification of non-sterol, mevalonate-derived vasoactive metabolites, and suggests that disorders of the mevalonate pathway can alter vascular tone and cause hypertension. PMID:7615793

  7. Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction

    PubMed Central

    Richards, A; Nicholls, M; Yandle, T; Ikram, H; Espiner, E; Turner, J; Buttimore, R; Lainchbury, J; Elliott, J; Frampton, C; Crozier, I; Smyth, D

    1999-01-01

    independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

 Keywords: cardiac natriuretic peptides; noradrenaline; myocardial infarction; heart failure PMID:9922344

  8. Correlation of heart rate variability with cardiac functional and metabolic variables in cyclists with training induced left ventricular hypertrophy

    PubMed Central

    Pluim, B; Swenne, C; Zwinderman, A; Maan, A; van der Laarse, A; Doornbos, J; Van der Wall, E E

    1999-01-01

    OBJECTIVE—To examine the correlation between heart rate variability and left ventricular mass in cyclists with an athlete's heart.
METHODS—Left ventricular mass and diastolic function were determined at rest and myocardial high energy phosphates were quantified at rest and during atropine-dobutamine stress in 12 male cyclists and 10 control subjects, using magnetic resonance techniques. Ambulatory 24 hour ECG recordings were obtained, and time and frequency domain heart rate variability indices were computed.
RESULTS—In the cyclists, the mean of all RR intervals between normal beats (meanNN), the SD of the RR intervals, and their coefficient of variation were significantly greater than in control subjects (p < 0.01, p < 0.01, and p < 0.05, respectively). For cyclists and control subjects, only meanNN correlated with left ventricular mass (r = 0.48, p = 0.038). The heart rate variability indices that correlated with functional or metabolic variables were: meanNN v E/A peak (the ratio of peak early and peak atrial filling rate) (r = 0.48, p = 0.039); the root mean square of successive differences in RR intervals among successive normal beats v E/A area (ratio of peak early and peak atrial filling volume) (r = 0.48, p = 0.040); percentage of successive RR intervals differing by more than 50 ms v the phosphocreatine to ATP ratio at rest (r = 0.54, p = 0.017); and the SD of the average RR intervals during all five minute periods v the phosphocreatine to ATP ratio during stress (r = 0.60, p = 0.007).
CONCLUSIONS—Highly trained cyclists have increased heart rate variability indices, reflecting increased cardiac vagal control compared with control subjects. Left ventricular mass has no major influence on heart rate variability, but heart rate variability is significantly correlated with high energy phosphate metabolism and diastolic function.


Keywords: heart rate variability; left ventricular mass; hypertrophy; athlete

  9. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy

    PubMed Central

    Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-01-01

    Abstract Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three‐dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity‐modulated radiotherapy appears to be the appropriate treatment in heart‐transplanted oncologic patients. PMID:27148425

  10. Cardiac function, microvascular structure, and capillary hematocrit in hearts of polycythemic rats.

    PubMed

    Rakusan, K; Cicutti, N; Kolar, F

    2001-12-01

    The effect of polycythemia on the coronary microcirculation was studied in young male rats. Two experimental models of polycythemia were employed: cobalt-induced polycythemia, which mimics hypoxia-induced changes, and erythropoietin-induced polycythemia, which circumvents these changes. In both models, baseline left ventricular function was normal, whereas maximal systolic and developed pressures were decreased. In cobalt-treated rats the left ventricular functional reserve was also compromised. Morphometric analysis of the left ventricle confirmed previously described improved geometric conditions for oxygen supply at the distal portions of capillaries (smaller domain areas and shorter capillary segments). In cobalt-treated but not in erythropoietin-treated rats, increased capillary angiogenesis was also detected. In the hearts from rats with both types of polycythemia, a small but significant increase in the formation of arterioles was found. Capillary linear hematocrit was within the normal range in both types of polycythemia despite sizeable increases in systemic hematocrit. Significant differences in red blood cell distribution within capillaries were found between proximal and distal portions in all experimental groups. PMID:11709408

  11. Decomposition of Heart Rate Variability Spectrum into a Power-Law Function and a Residual Spectrum

    PubMed Central

    Kuo, Jane; Kuo, Cheng-Deng

    2016-01-01

    The power spectral density (PSD) of heart rate variability (HRV) contains a power-law relationship that can be obtained by plotting the logarithm of PSD against the logarithm of frequency. The PSD of HRV can be decomposed mathematically into a power-law function and a residual HRV (rHRV) spectrum. Almost all rHRV measures are significantly smaller than their corresponding HRV measures except the normalized high-frequency power (nrHFP). The power-law function can be characterized by the slope and Y-intercept of linear regression. Almost all HRV measures except the normalized low-frequency power have significant correlations with the Y-intercept, while almost all rHRV measures except the total power [residual total power (rTP)] do not. Though some rHRV measures still correlate significantly with the age of the subjects, the rTP, high-frequency power (rHFP), nrHFP, and low-/high-frequency power ratio (rLHR) do not. In conclusion, the clinical significances of rHRV measures might be different from those of traditional HRV measures. The Y-intercept might be a better HRV measure for clinical use because it is independent of almost all rHRV measures. The rTP, rHFP, nrHFP, and rLHR might be more suitable for the study of age-independent autonomic nervous modulation of the subjects. PMID:27314001

  12. Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association.

    PubMed

    Murphy, Elizabeth; Ardehali, Hossein; Balaban, Robert S; DiLisa, Fabio; Dorn, Gerald W; Kitsis, Richard N; Otsu, Kinya; Ping, Peipei; Rizzuto, Rosario; Sack, Michael N; Wallace, Douglas; Youle, Richard J

    2016-06-10

    Cardiovascular disease is a major leading cause of morbidity and mortality in the United States and elsewhere. Alterations in mitochondrial function are increasingly being recognized as a contributing factor in myocardial infarction and in patients presenting with cardiomyopathy. Recent understanding of the complex interaction of the mitochondria in regulating metabolism and cell death can provide novel insight and therapeutic targets. The purpose of this statement is to better define the potential role of mitochondria in the genesis of cardiovascular disease such as ischemia and heart failure. To accomplish this, we will define the key mitochondrial processes that play a role in cardiovascular disease that are potential targets for novel therapeutic interventions. This is an exciting time in mitochondrial research. The past decade has provided novel insight into the role of mitochondria function and their importance in complex diseases. This statement will define the key roles that mitochondria play in cardiovascular physiology and disease and provide insight into how mitochondrial defects can contribute to cardiovascular disease; it will also discuss potential biomarkers of mitochondrial disease and suggest potential novel therapeutic approaches. PMID:27126807

  13. Advanced Echocardiography in Adult Zebrafish Reveals Delayed Recovery of Heart Function after Myocardial Cryoinjury

    PubMed Central

    Kossack, Mandy; Juergensen, Lonny; Fuchs, Dieter; Katus, Hugo A.; Hassel, David

    2015-01-01

    Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited. We here present a standardized examination protocol to broadly assess cardiac performance in adult zebrafish by advancing conventional echocardiography with modern speckle-tracking analyses. This allows accurate detection of changes in cardiac performance and further enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution. Combining conventional echocardiography measurements with radial and longitudinal velocity, displacement, strain, strain rate and myocardial wall delay rates after myocardial cryoinjury permitted to non-invasively determine injury dimensions and to longitudinally follow functional recovery during cardiac regeneration. We show that functional recovery of cryoinjured hearts occurs in three distinct phases. Importantly, the regeneration process after cryoinjury extends far beyond the proposed 45 days described for ventricular resection with reconstitution of myocardial performance up to 180 days post-injury (dpi). The imaging modalities evaluated here allow sensitive cardiac phenotyping and contribute to further establish adult zebrafish as valuable cardiac disease model beyond the larval developmental stage. PMID:25853735

  14. CHANGES IN HEART RATE VARIABILITY AND LUNG FUNCTION OBSERVED IN NC PATROL TROOPERS EXPOSED TO PM AND AIR TOXICS

    EPA Science Inventory

    Changes in Heart Rate Variability and Lung Function in NC Patrol Troopers exposed to PM and Air Toxics

    Michael Riediker1, Wayne E Cascio1, Robert B Devlin2, Thomas Griggs1&4, Margaret Herbst1, Ronald W Williams3, Steve P McCorquodale4, Philip A Bromberg1
    1) University o...

  15. [MORPHO-FUNCTIONAL CHANGES OF THYMUS TISSUES IN CHILDREN WITH CONGENITAL HEART DISEASE].

    PubMed

    Loginova, N P; Chetvertnykh, V A; Chemurziyeva, N V

    2016-01-01

    Biopsy specimens of the thymus were studied in children aged under 11 months (n = 77) with congenital heart defects and circulatory hypoxia of varying severity. Histological sections were stained with hematoxylin-eosin and Shubich's method (to demonstrate mast cells). The expression of Ki-67, CD3 and CD34 was assessed by immunohistochemistry. The ultrastructure of thymic tissues was also examined. It was found that the severity of hypoxia determined the morphological changes in the organ associated with a development of large complex of tissue reactions. A disruption of internal structure and a loss of integrity of epithelio-reticular cells and thymocytes were demonstrated in ultrathin sections. Thymocyte proliferation index (Ki-67) and thymocytopoiesis intensity (CD3+) were reduced in all the zones of the thymus. The degree of hypoxia affected the redistribution of CD3+ lymphocytes leading to their accumulation in the medulla. The processes of endogenous regeneration took place which involved the cells of fibroblastic line and progenitor cells (CD34+) together with active formation of new blood vessels. These findings suggest that the morphological changes identified in the tissues of the thymus are a manifestation of tissue adaptation to hypoxia of varying severity under conditions of endogenous regeneration, simultaneously reflecting the processes of substitution cytogenesis. PMID:27487665

  16. Neonatal SSRI exposure improves mitochondrial function and antioxidant defense in rat heart.

    PubMed

    Braz, Glauber Ruda F; Freitas, Cristiane M; Nascimento, Luciana; Pedroza, Anderson A; da Silva, Aline Isabel; Lagranha, Claudia

    2016-04-01

    Protein restriction during prenatal, postnatal, or in both periods has a close relationship with subsequent development of cardiovascular disease in adulthood. Elevated brain levels of serotonin and its metabolites have been found in malnourished states. The aim in the present study was to investigate whether treatment with fluoxetine (Fx), a selective serotonin reuptake inhibitor, mimics the detrimental effect of low-protein diet during the perinatal period on the male rat heart. Our hypothesis is that increased circulating serotonin as a result of pharmacologic treatment with Fx leads to cardiac dysfunction similar to that observed in protein-restricted rats. Male Wistar rat pups received daily subcutaneous injection of Fx or vehicle from postnatal day 1 to postnatal day 21. Male rats were euthanized at 60 days of age and the following parameters were evaluated in the cardiac tissue: mitochondrial respiratory capacity, respiratory control ratio, reactive oxygen species (ROS) production, mitochondrial membrane potential, and biomarkers of oxidative stress and antioxidant defense. We found that Fx treatment increased mitochondrial respiratory capacity (123%) and membrane potential (212%) and decreased ROS production (55%). In addition we observed an increase in the antioxidant capacity (elevation in catalase activity (5-fold) and glutathione peroxidase (4.6-fold)). Taken together, our results suggest that Fx treatment in the developmental period positively affects the mitochondrial bioenergetics and antioxidant defense in the cardiac tissue. PMID:26939042

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

    PubMed Central

    Nowobilski, Roman; Dropinski, Jerzy; Kotula-Horowitz, Katarzyna; Laskowicz, Bartosz; Stanisz, Andrzej; Lelakowski, Jacek

    2015-01-01

    Background and Aims Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function. Design and Methods The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters. Results Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24–5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07–29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24–66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03–1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001–1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96–0.99; p = 0.02). MetS subjects had significantly lower values of certain

  18. Consumption of bee pollen affects rat ovarian functions.

    PubMed

    Kolesarova, A; Bakova, Z; Capcarova, M; Galik, B; Juracek, M; Simko, M; Toman, R; Sirotkin, A V

    2013-12-01

    The aim of this study was to examine possible effects of bee pollen added to the feed mixture (FM) on rat ovarian functions (secretion activity and apoptosis). We evaluated the bee pollen effect on the release of insulin-like growth factor I (IGF-I) and steroid hormones (progesterone and estradiol), as well as on the expression of markers of apoptosis (Bcl-2, Bax and caspase-3) in rat ovarian fragments. Female rats (n = 15) were fed during 90 days by FM without or with rape seed bee pollen in dose either 3 kg/1000 kg FM or 5 kg/1000 kg FM. Fragments of ovaries isolated from rats of each group (totally 72 pieces) were incubated for 24 h. Hormonal secretion into the culture medium was detected by RIA. The markers of apoptosis were evaluated by Western blotting. It was observed that IGF-I release by rat ovarian fragments was significantly (p < 0.05) decreased; on the other hand, progesterone and estradiol secretion was increased after bee pollen treatment at dose 5 kg/1000 kg FM but not at 3 kg/1000 FM. Accumulation of Bcl-2 was increased by bee pollen added at 3 kg/1000 kg FM, but not at higher dose. Accumulation of Bax was increased in ovaries of rats fed by bee pollen at doses either 3 or 5 kg/1000 kg FM, whilst accumulation of caspase-3 increased after feeding with bee pollen at dose 5 kg/1000 kg FM, but not at 3 kg/1000 kg FM. Our results contribute to new insights regarding the effect of bee pollen on both secretion activity (release of growth factor IGF-I and steroid hormones progesterone and estradiol) and apoptosis (anti- and pro-apoptotic markers Bcl-2, Bax and caspase-3). Bee pollen is shown to be a potent regulator of rat ovarian functions. PMID:23137268

  19. Light-emitting diode therapy (LEDT) improves functional capacity in rats with heart failure.

    PubMed

    Capalonga, Lucas; Karsten, Marlus; Hentschke, Vítor Scotta; Rossato, Douglas Dalcin; Dornelles, Maurício Pinto; Sonza, Anelise; Bagnato, Vanderlei Salvador; Ferraresi, Cleber; Parizotto, Nivaldo Antonio; Dal Lago, Pedro

    2016-07-01

    The syndrome of heart failure (HF) promotes central and peripheral dysfunctions that result in functional capacity decrease, leading to fatigue, dyspnea, and exercise intolerance. The use of light-emitting diode therapy (LEDT) has shown good results reducing fatigue and exercise intolerance, when applied on skeletal muscles before or after exercises. Thereby, the aim of this study was to compare the effects of LEDT on functional capacity, aerobic power, and hemodynamic function in HF rats. Male Wistar rats (230-260 g) were randomly allocated into three experimental groups: Sham (n = 6), Control-HF (n = 4), and LEDT-HF (n = 6). The animals were subjected to an exercise performance test (ET) with gas analysis coupled in a metabolic chamber for rats performed two times (6 and 14 weeks after myocardial infarction). On the day after the baseline aerobic capacity test, the animals were submitted during 8 weeks to the phototherapy protocol, five times/week, 60 s of irradiation, 6 J delivered per muscle group. Statistical analysis was performed by one- and two-way ANOVAs with repeated measures and Student-Newman-Keuls post hoc tests (p ≤ 0.05). Comparing the percentage difference (Δ) between baseline and the final ET, there was no significant difference for the VO2max variable considering all groups. However, Sham and LEDT-HF groups showed higher relative values than the Control-HF group, respectively, for distance covered (27.7 and 32.5 %), time of exercise test (17.7 and 20.5 %), and speed (13.6 and 12.2 %). In conclusion, LEDT was able to increase the functional capacity evaluated by distance covered, time, and speed of exercise in rats with HF. PMID:27059227

  20. Pathophysiology of Heart Failure.

    PubMed

    Tanai, Edit; Frantz, Stefan

    2015-01-01

    Heart failure is considered an epidemic disease in the modern world affecting approximately 1% to 2% of adult population. It presents a multifactorial, systemic disease, in which--after cardiac injury--structural, neurohumoral, cellular, and molecular mechanisms are activated and act as a network to maintain physiological functioning. These coordinated, complex processes lead to excessive volume overload, increased sympathetic activity, circulation redistribution, and result in different, parallel developing clinical signs and symptoms. These signs and symptoms sum up to an unspecific clinical picture; thus invasive and noninvasive diagnostic tools are used to get an accurate diagnosis and to specify the underlying cause. The most important, outcome determining factor in heart failure is its constant progression. Constant optimizing of pharmatherapeutical regimes, novel targets, and fine regulation of these processes try to keep these compensatory mechanisms in a physiological range. Beside pharmacological therapy, interventional and surgical therapy options give new chances in the management of heart failure. For the optimization and establishment of these and novel therapeutical approaches, complete and comprehensive understanding of the underlying mechanisms is essentially needed. Besides diagnosis and treatment, efforts should be made for better prevention in heart failure by treatment of risk factors, or identifying and following risk groups. This summary of the pathophysiology of heart failure tries to give a compact overview of basic mechanisms and of the novel unfolding, progressive theory of heart failure to contribute to a more comprehensive knowledge of the disease. PMID:26756631

  1. Cigarette smoke extract affects mitochondrial function in alveolar epithelial cells.

    PubMed

    Ballweg, Korbinian; Mutze, Kathrin; Königshoff, Melanie; Eickelberg, Oliver; Meiners, Silke

    2014-12-01

    Cigarette smoke is the main risk factor for chronic obstructive pulmonary disease (COPD). Exposure of cells to cigarette smoke induces an initial adaptive cellular stress response involving increased oxidative stress and induction of inflammatory signaling pathways. Exposure of mitochondria to cellular stress alters their fusion/fission dynamics. Whereas mild stress induces a prosurvival response termed stress-induced mitochondrial hyperfusion, severe stress results in mitochondrial fragmentation and mitophagy. In the present study, we analyzed the mitochondrial response to mild and nontoxic doses of cigarette smoke extract (CSE) in alveolar epithelial cells. We characterized mitochondrial morphology, expression of mitochondrial fusion and fission genes, markers of mitochondrial proteostasis, as well as mitochondrial functions such as membrane potential and oxygen consumption. Murine lung epithelial (MLE)12 and primary mouse alveolar epithelial cells revealed pronounced mitochondrial hyperfusion upon treatment with CSE, accompanied by increased expression of the mitochondrial fusion protein mitofusin 2 and increased metabolic activity. We did not observe any alterations in mitochondrial proteostasis, i.e., induction of the mitochondrial unfolded protein response or mitophagy. Therefore, our data indicate an adaptive prosurvival response of mitochondria of alveolar epithelial cells to nontoxic concentrations of CSE. A hyperfused mitochondrial network, however, renders the cell more vulnerable to additional stress, such as sustained cigarette smoke exposure. As such, cigarette smoke-induced mitochondrial hyperfusion, although part of a beneficial adaptive stress response in the first place, may contribute to the pathogenesis of COPD. PMID:25326581

  2. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

    SciTech Connect

    Benderitter, M.; Assem, M.; Maupoil, V.

    1995-10-01

    During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab.

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

    ERIC Educational Resources Information Center

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

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

  4. Functional TLR5 genetic variants affect human colorectal cancer survival.

    PubMed

    Klimosch, Sascha N; Försti, Asta; Eckert, Jana; Knezevic, Jelena; Bevier, Melanie; von Schönfels, Witigo; Heits, Nils; Walter, Jessica; Hinz, Sebastian; Lascorz, Jesus; Hampe, Jochen; Hartl, Dominik; Frick, Julia-Stefanie; Hemminki, Kari; Schafmayer, Clemens; Weber, Alexander N R

    2013-12-15

    Toll-like receptors (TLR) are overexpressed on many types of cancer cells, including colorectal cancer cells, but little is known about the functional relevance of these immune regulatory molecules in malignant settings. Here, we report frequent single-nucleotide polymorphisms (SNP) in the flagellin receptor TLR5 and the TLR downstream effector molecules MyD88 and TIRAP that are associated with altered survival in a large cohort of Caucasian patients with colorectal cancer (n = 613). MYD88 rs4988453, a SNP that maps to a promoter region shared with the acetyl coenzyme-A acyl-transferase-1 (ACAA1), was associated with decreased survival of patients with colorectal cancer and altered transcriptional activity of the proximal genes. In the TLR5 gene, rs5744174/F616L was associated with increased survival, whereas rs2072493/N592S was associated with decreased survival. Both rs2072493/N592S and rs5744174/F616L modulated TLR5 signaling in response to flagellin or to different commensal and pathogenic intestinal bacteria. Notably, we observed a reduction in flagellin-induced p38 phosphorylation, CD62L shedding, and elevated expression of interleukin (IL)-6 and IL-1β mRNA in human primary immune cells from TLR5 616LL homozygote carriers, as compared with 616FF carriers. This finding suggested that the well-documented effect of cytokines like IL-6 on colorectal cancer progression might be mediated by TLR5 genotype-dependent flagellin sensing. Our results establish an important link between TLR signaling and human colorectal cancer with relevance for biomarker and therapy development. PMID:24154872

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  6. Phosphate Ions Affect the Water Structure at Functionalized Membrane Surfaces.

    PubMed

    Barrett, Aliyah; Imbrogno, Joseph; Belfort, Georges; Petersen, Poul B

    2016-09-01

    Antifouling surfaces improve function, efficiency, and safety in products such as water filtration membranes, marine vehicle coatings, and medical implants by resisting protein and biofilm adhesion. Understanding the role of water structure at these materials in preventing protein adhesion and biofilm formation is critical to designing more effective coatings. Such fouling experiments are typically performed under biological conditions using isotonic aqueous buffers. Previous studies have explored the structure of pure water at a few different antifouling surfaces, but the effect of electrolytes and ionic strength (I) on the water structure at antifouling surfaces is not well studied. Here sum frequency generation (SFG) spectroscopy is used to characterize the interfacial water structure at poly(ether sulfone) (PES) and two surface-modified PES films in contact with 0.01 M phosphate buffer with high and low salt (Ionic strength, I= 0.166 and 0.025 M, respectively). Unmodified PES, commonly used as a filtration membrane, and modified PES with a hydrophobic alkane (C18) and with a poly(ethylene glycol) (PEG) were used. In the low ionic strength phosphate buffer, water was strongly ordered near the surface of the PEG-modified PES film due to exclusion of phosphate ions and the creation of a surface potential resulting from charge separation between phosphate anions and sodium cations. However, in the high ionic strength phosphate buffer, the sodium and potassium chloride (138 and 3 mM, respectively) in the phosphate buffered saline screened this charge and substantially reduced water ordering. A much smaller water ordering and subsequent reduction upon salt addition was observed for the C18-modified PES, and little water structure change was seen for the unmodified PES. The large difference in water structuring with increasing ionic strength between widely used phosphate buffer and phosphate buffered saline at the PEG interface demonstrates the importance of studying

  7. DOES FEED-BACK FROM A NEST AFFECT PERIPARTURIENT BEHAVIOR, HEART RATE AND CIRCULATORY CORTISOL AND OXYTOCIN IN GILTS?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine the effects of feed-back from a farrowing nest on periparturient behaviour, heart rate and hormones, 20 primiparous sows housed in Schmid pens were permitted to build a nest of peat, straw and branches. Ten primiparous sows then had their nest removed (NR) 10 h after the onset of nest-b...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. Heart Health

    MedlinePlus

    ... Connected Home » Heart Health Heath and Aging Heart Health Your Heart Changes to Your Heart With ... are both taking steps toward heart health. Your Heart Your heart is a strong muscle about the ...

  11. High saturated fat feeding prevents left ventricular dysfunction and enhances mitochondrial function in heart failure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulation of lipids in the heart is associated with contractile dysfunction, and has been proposed to be a causative factor in mitochondrial dysfunction. We have previously shown that administration of a high saturated fat diet in heart failure (HF) increased mitochondrial respiration and ETC com...

  12. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    PubMed Central

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  13. Metrics of High-Density Lipoprotein Function and Hospital Mortality in Acute Heart Failure Patients

    PubMed Central

    Potočnjak, Ines; Degoricija, Vesna; Trbušić, Matias; Terešak, Sanda Dokoza; Radulović, Bojana; Pregartner, Gudrun; Berghold, Andrea; Tiran, Beate; Marsche, Gunther; Frank, Saša

    2016-01-01

    Objective The functionality of high-density lipoprotein (HDL) is impaired in chronic ischaemic heart failure (HF). However, the relationship between HDL functionality and outcomes in acute HF (AHF) has not been studied. The present study investigates whether the metrics of HDL functionality, including HDL cholesterol efflux capacity and HDL-associated paraoxonase (PON)-1 arylesterase (AE) activity are associated with hospital mortality in AHF patients. Methods and Results The study was performed as a prospective, single-centre, observational research on 152 patients, defined and categorised according to the ESC and ACCF/AHA Guidelines for HF by time of onset, final clinical presentation and ejection fraction. The mean age of the included patients (52% female) was 75.2 years (SD 10.3) and hospital mortality was 14.5%. HDL cholesterol efflux capacity was examined by measuring the capacity of apoB depleted serum to remove tritium-labelled cholesterol from cultured macrophages. The AE activity of the HDL fraction was examined by a photometric assay. In a univariable regression analysis, low cholesterol efflux, but not AE activity, was significantly associated with hospital mortality [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64–0.96, p = 0.019]. In multivariable analysis progressively adjusting for important clinical and laboratory parameters the association obtained for cholesterol efflux capacity and hospital mortality by univariable analysis, despite a stable OR, did not stay significant (p = 0.179). Conclusion Our results suggest that HDL cholesterol efflux capacity (but not AE activity) contributes to, but is not an independent risk factor for, hospital mortality in AHF patients. Larger studies are needed to draw firm conclusions. PMID:27304214

  14. Health literacy and global cognitive function predict e-mail but not internet use in heart failure patients.

    PubMed

    Schprechman, Jared P; Gathright, Emily C; Goldstein, Carly M; Guerini, Kate A; Dolansky, Mary A; Redle, Joseph; Hughes, Joel W

    2013-01-01

    Background. The internet offers a potential for improving patient knowledge, and e-mail may be used in patient communication with providers. However, barriers to internet and e-mail use, such as low health literacy and cognitive impairment, may prevent patients from using technological resources. Purpose. We investigated whether health literacy, heart failure knowledge, and cognitive function were related to internet and e-mail use in older adults with heart failure (HF). Methods. Older adults (N = 119) with heart failure (69.84 ± 9.09 years) completed measures of health literacy, heart failure knowledge, cognitive functioning, and internet use in a cross-sectional study. Results. Internet and e-mail use were reported in 78.2% and 71.4% of this sample of patients with HF, respectively. Controlling for age and education, logistic regression analyses indicated that higher health literacy predicted e-mail (P < .05) but not internet use. Global cognitive function predicted e-mail (P < .05) but not internet use. Only 45% used the Internet to obtain information on HF and internet use was not associated with greater HF knowledge. Conclusions. The majority of HF patients use the internet and e-mail, but poor health literacy and cognitive impairment may prevent some patients from accessing these resources. Future studies that examine specific internet and email interventions to increase HF knowledge are needed. PMID:24282634

  15. Health Literacy and Global Cognitive Function Predict E-Mail but Not Internet Use in Heart Failure Patients

    PubMed Central

    Schprechman, Jared P.; Gathright, Emily C.; Goldstein, Carly M.; Guerini, Kate A.; Dolansky, Mary A.; Redle, Joseph; Hughes, Joel W.

    2013-01-01

    Background. The internet offers a potential for improving patient knowledge, and e-mail may be used in patient communication with providers. However, barriers to internet and e-mail use, such as low health literacy and cognitive impairment, may prevent patients from using technological resources. Purpose. We investigated whether health literacy, heart failure knowledge, and cognitive function were related to internet and e-mail use in older adults with heart failure (HF). Methods. Older adults (N = 119) with heart failure (69.84 ± 9.09 years) completed measures of health literacy, heart failure knowledge, cognitive functioning, and internet use in a cross-sectional study. Results. Internet and e-mail use were reported in 78.2% and 71.4% of this sample of patients with HF, respectively. Controlling for age and education, logistic regression analyses indicated that higher health literacy predicted e-mail (P < .05) but not internet use. Global cognitive function predicted e-mail (P < .05) but not internet use. Only 45% used the Internet to obtain information on HF and internet use was not associated with greater HF knowledge. Conclusions. The majority of HF patients use the internet and e-mail, but poor health literacy and cognitive impairment may prevent some patients from accessing these resources. Future studies that examine specific internet and email interventions to increase HF knowledge are needed. PMID:24282634

  16. Cognitive Function in Heart Failure is Associated with Nonsomatic Symptoms of Depression but Not Somatic Symptoms

    PubMed Central

    Hawkins, Misty A. W.; Dolansky, Mary A.; Schaefer, Julie T.; Fulcher, Michael J.; Gunstad, John; Redle, Joseph D.; Josephson, Richard; Hughes, Joel W.

    2014-01-01

    Background Patients with heart failure (HF) have high rates of cognitive impairment and depressive symptoms. Depressive symptoms have been associated with greater cognitive impairments in HF; however, it is not known whether particular clusters of depressive symptoms are more detrimental to cognition than others. Objective To identify whether somatic and/or nonsomatic depressive symptom clusters were associated with cognitive function in persons with HF. Methods Participants were 326 HF patients (40.5% female, 26.7% race-ethnicity, aged 68.6±9.7 years). Depressive symptoms were measured using a depression questionnaire commonly used in medical populations: the Patient Health Questionnatire-9 (PHQ-9). Somatic and Nonsomatic subscales scores were created using previous factor analytic results. A neuropsychological battery tested attention, executive function, and memory. Composites were created using averages of age-adjusted scaled scores. Regressions adjusting for demographic and clinical factors were conducted. Results Regressions revealed that PHQ-9 Total was associated with Attention (β=−.14, p=.008) and Executive Function (β=−.17, p=.001). When analyzed separately, the Nonsomatic subscale – but not the Somatic symptoms subscale (ps ≥.092) – was associated with Attention scores (β=−.15, p=.004) and Memory (β=−.11, p=.044). Both Nonsomatic (β=−.18, p<.001) and Somatic symptoms (β=−.11, p=.048) were related to Executive Function. When included together, only the Nonsomatic symptom cluster was associated with Attention (β=−.15, p=.020) and Executive Function (β=−.19, p=.003). Conclusions Greater overall depressive symptom severity was associated with poorer performance on multiple cognitive domains, an effect driven primarily by the nonsomatic symptoms of depression. Clinical Implications These findings suggest that screening explicitly for nonsomatic depressive symptoms may be warranted and that the mechanisms underlying the

  17. Functional and anatomical characterization of brown adipose tissue in heart failure with blood oxygen level dependent magnetic resonance.

    PubMed

    Panagia, Marcello; Chen, Yin-Ching Iris; Chen, Howard H; Ernande, Laura; Chen, Chan; Chao, Wei; Kwong, Kenneth; Scherrer-Crosbie, Marielle; Sosnovik, David E

    2016-07-01

    Recent studies have suggested that brown adipose tissue (BAT) plays an important role in obesity, insulin resistance and heart failure. The characterization of BAT in vivo, however, has been challenging. No technique to comprehensively image BAT anatomy and function has been described. Moreover, the impact on BAT of the neuroendocrine activation seen in heart failure has only recently begun to be evaluated in vivo. The aim of this study was to use MRI to characterize the impact of heart failure on the morphology and function of BAT. Mice subjected to permanent ligation of the left coronary artery were imaged with MRI 6 weeks later. T2 weighted MRI of BAT volume and blood oxygen level dependent MRI of BAT function were performed. T2 * maps of BAT were obtained at multiple time points before and after administration of the β3 adrenergic agonist CL 316 243 (CL). Blood flow to BAT was studied after CL injection using the flow alternating inversion recovery (FAIR) approach. Excised BAT tissue was analyzed for lipid droplet content and for uncoupling protein 1 (UCP1) mRNA expression. BAT volume was significantly lower in heart failure (51 ± 1 mm(3) versus 65 ± 3 mm(3) ; p < 0.05), and characterized by a reduction in lipid globules and a fourfold increase in UCP1 mRNA (p < 0.05). CL injection increased BAT T2 * in healthy animals but not in mice with heart failure (24 ± 4% versus 6 ± 2%; p < 0.01), consistent with an increase in flow in control BAT. This was confirmed by a significant difference in the FAIR response in BAT in control and heart failure mice. Heart failure results in the chronic activation of BAT, decreased BAT lipid stores and decreased BAT volume, and it is associated with a marked decrease in ability to respond to acute physiological stimuli. This may have important implications for substrate utilization and overall metabolic homeostasis in heart failure. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27226402

  18. Dyads Affected by Chronic Heart Failure: A Randomized Study Evaluating Effects of Education and Psychosocial Support to Patients With Heart Failure and Their Partners

    PubMed Central

    ÅGREN, SUSANNA; EVANGELISTA, LORRAINE S.; HJELM, CARINA; STRÖMBERG, ANNA

    2012-01-01

    Background Chronic heart failure (CHF) causes great suffering for both patients and their partners. The aim of this study was to evaluate the effects of an integrated dyad care program with education and psychosocial support to patients with CHF and their partners during a postdischarge period after acute deterioration of CHF. Methods One hundred fifty-five patient-caregiver dyads were randomized to usual care (n = 71) or a psychoeducation intervention (n = 84) delivered in 3 modules through nurse-led face-to-face counseling, computer-based education, and other written teaching materials to assist dyads to develop problem-solving skills. Follow-up assessments were completed after 3 and 12 months to assess perceived control, perceived health, depressive symptoms, self-care, and caregiver burden. Results Baseline sociodemographic and clinical characteristics of dyads in the experimental and control groups were similar at baseline. Significant differences were observed in patients’ perceived control over the cardiac condition after 3 (P < .05) but not after 12 months, and no effect was seen for the caregivers. No group differences were observed over time in dyads’ health-related quality of life and depressive symptoms, patients’ self-care behaviors, and partners’ experiences of caregiver burden. Conclusions Integrated dyad care focusing on skill-building and problem-solving education and psychosocial support was effective in initially enhancing patients’ levels of perceived control. More frequent professional contact and ongoing skills training may be necessary to have a higher impact on dyad outcomes and warrants further research. PMID:22555264

  19. Wavelet Based Method for Congestive Heart Failure Recognition by Three Confirmation Functions.

    PubMed

    Daqrouq, K; Dobaie, A

    2016-01-01

    An investigation of the electrocardiogram (ECG) signals and arrhythmia characterization by wavelet energy is proposed. This study employs a wavelet based feature extraction method for congestive heart failure (CHF) obtained from the percentage energy (PE) of terminal wavelet packet transform (WPT) subsignals. In addition, the average framing percentage energy (AFE) technique is proposed, termed WAFE. A new classification method is introduced by three confirmation functions. The confirmation methods are based on three concepts: percentage root mean square difference error (PRD), logarithmic difference signal ratio (LDSR), and correlation coefficient (CC). The proposed method showed to be a potential effective discriminator in recognizing such clinical syndrome. ECG signals taken from MIT-BIH arrhythmia dataset and other databases are utilized to analyze different arrhythmias and normal ECGs. Several known methods were studied for comparison. The best recognition rate selection obtained was for WAFE. The recognition performance was accomplished as 92.60% accurate. The Receiver Operating Characteristic curve as a common tool for evaluating the diagnostic accuracy was illustrated, which indicated that the tests are reliable. The performance of the presented system was investigated in additive white Gaussian noise (AWGN) environment, where the recognition rate was 81.48% for 5 dB. PMID:26949412

  20. Physiologically inspired cardiac scaffolds for tailored in vivo function and heart regeneration

    PubMed Central

    Kaiser, Nicholas J; Coulombe, Kareen L K

    2015-01-01

    Tissue engineering is well suited for the treatment of cardiac disease due to the limited regenerative capacity of native cardiac tissue and the loss of function associated with endemic cardiac pathologies, such as myocardial infarction and congenital heart defects. However, the physiological complexity of the myocardium imposes extensive requirements on tissue therapies intended for these applications. In recent years, the field of cardiac tissue engineering has been characterized by great innovation and diversity in the fabrication of engineered tissue scaffolds for cardiac repair and regeneration to address these problems. From early approaches that attempted only to deliver cardiac cells in a hydrogel vessel, significant progress has been made in understanding the role of each major component of cardiac living tissue constructs (namely cells, scaffolds, and signaling mechanisms) as they relate to mechanical, biological, and electrical in vivo performance. This improved insight, accompanied by modern material science techniques, allows for the informed development of complex scaffold materials that are optimally designed for cardiac applications. This review provides a background on cardiac physiology as it relates to critical cardiac scaffold characteristics, the degree to which common cardiac scaffold materials fulfill these criteria, and finally an overview of recent in vivo studies that have employed this type of approach. PMID:25970645

  1. Microwave influence on the isolated heart function. 2: Combined effect of radiation and some drugs

    SciTech Connect

    Pakhomov, A.G.; Dubovick, B.V.; Degtyariov, I.G.; Pronkevich, A.N.

    1995-09-01

    The combined effects of microwave radiation and some drugs were studied in an isolated frog auricle preparation. The experiments established that exposure to pulse-modulated 915 Mhz microwaves for up to 40 min had no effect on either the rate or the amplitude of spontaneous auricle twitches, unless the average absorbed power was high enough to produce preparation heating. Treatment of the preparation with saline containing (0.6--3.0) 10{sup {minus}5} M of propranolol or (0.5--1.5) 10{sup {minus}7} M of atropine altered neither its pacemaker nor its contractile functions; these drugs also had no effect when they were combined with nonthermal microwave irradiation. Caffeine (1 mM) strongly increased the average heart power, which was calculated as the product of twitch rate ad amplitude. The caffeine effect appeared to be significantly augmented (by about 15%, P<0.02) under exposure to burst-type pulsed microwaves (pulse width, 1.5 msec; pause, 2.5 msec; 8 pulses/burst, 16 bursts/s; average SAR, 8--10 W/kg). By itself, this modulation was not effective; the heating of the preparation and saline during exposure was approximately 0.1 C, which could not account for the detected changes. The experimental results demonstrate that caffeine treatment increases the microwave sensitivity of the frog auricle preparation and reveals primarily subthreshold, nonthermal microwave effect.

  2. The influence of mannitol on renal function during and after open-heart surgery.

    PubMed

    Fisher, A R; Jones, P; Barlow, P; Kennington, S; Saville, S; Farrimond, J; Yacoub, M

    1998-05-01

    Mannitol is often included in the priming solution of the heart-lung machine used during cardiopulmonary bypass (CPB). This study was set up to evaluate the effect of different doses of mannitol on human patients. Patients receiving 10 g of mannitol (n = 18) had an increased diuresis only during the bypass period (mean time = 87 min) when compared with a control group (n = 19) who did not receive mannitol. Patients receiving 20 g of mannitol (n = 19) had a significantly greater diuresis than both the control group and the 10 g group and the diuresis continued on throughout the immediate postbypass period (total mean time approximately 3 h). Patients receiving 30 g of mannitol (n = 20) also had a significantly greater diuresis that continued on during the first hour in the intensive care unit (ICU) (total mean time approximately 4 h). After 6 h in the ICU, all three groups of mannitol-treated patients equally demonstrated a trend towards an increased diuresis over the control group, which became a significant increase by 12 h in the ICU (p = 0.001) despite indications that the mannitol had been cleared from the body. These results suggest that there is an improvement of renal function post-CPB if mannitol is included in the CPB prime which may be due to an amelioration of the ischaemic effects of bypass on the kidneys. PMID:9638715

  3. Wavelet Based Method for Congestive Heart Failure Recognition by Three Confirmation Functions

    PubMed Central

    Daqrouq, K.; Dobaie, A.

    2016-01-01

    An investigation of the electrocardiogram (ECG) signals and arrhythmia characterization by wavelet energy is proposed. This study employs a wavelet based feature extraction method for congestive heart failure (CHF) obtained from the percentage energy (PE) of terminal wavelet packet transform (WPT) subsignals. In addition, the average framing percentage energy (AFE) technique is proposed, termed WAFE. A new classification method is introduced by three confirmation functions. The confirmation methods are based on three concepts: percentage root mean square difference error (PRD), logarithmic difference signal ratio (LDSR), and correlation coefficient (CC). The proposed method showed to be a potential effective discriminator in recognizing such clinical syndrome. ECG signals taken from MIT-BIH arrhythmia dataset and other databases are utilized to analyze different arrhythmias and normal ECGs. Several known methods were studied for comparison. The best recognition rate selection obtained was for WAFE. The recognition performance was accomplished as 92.60% accurate. The Receiver Operating Characteristic curve as a common tool for evaluating the diagnostic accuracy was illustrated, which indicated that the tests are reliable. The performance of the presented system was investigated in additive white Gaussian noise (AWGN) environment, where the recognition rate was 81.48% for 5 dB. PMID:26949412

  4. Sequential delivery of angiogenic growth factors improves revascularization and heart function after myocardial infarction

    PubMed Central

    Awada, Hassan K.; Johnson, Noah R.; Wang, Yadong

    2015-01-01

    Treatment of ischemia through therapeutic angiogenesis faces significant challenges. Growth factor (GF)-based therapies can be more effective when concerns such as GF spatiotemporal presentation, bioactivity, bioavailability, and localization are addressed. During angiogenesis, vascular endothelial GF (VEGF) is required early to initiate neovessel formation while platelet-derived GF (PDGF-BB) is needed later to stabilize the neovessels. The spatiotemporal delivery of multiple bioactive GFs involved in angiogenesis, in a close mimic to physiological cues, holds great potential to treat ischemic diseases. To achieve sequential release of VEGF and PDGF, we embed VEGF in fibrin gel and PDGF in a heparin-based coacervate that is distributed in the same fibrin gel. In vitro, we show the benefits of this controlled delivery approach on cell proliferation, chemotaxis, and capillary formation. A rat myocardial infarction (MI) model demonstrated the effectiveness of this delivery system in improving cardiac function, ventricular wall thickness, angiogenesis, cardiac muscle survival, and reducing fibrosis and inflammation in the infarct zone compared to saline, empty vehicle, and free GFs. Collectively, our results show that this delivery approach mitigated the injury caused by MI and may serve as a new therapy to treat ischemic hearts pending further examination. PMID:25836592

  5. The Role of Mitochondrial Functional Proteins in ROS Production in Ischemic Heart Diseases

    PubMed Central

    Pei, Haifeng; Yang, Yi; Zhao, Heng; Li, Xiuchuan; Yang, Dachun; Li, De; Yang, Yongjian

    2016-01-01

    Ischemic heart diseases (IHD) have become the leading cause of death around the world, killing more than 7 million people annually. In IHD, the blockage of coronary vessels will cause irreversible cell injury and even death. As the “powerhouse” and “apoptosis center” in cardiomyocytes, mitochondria play critical roles in IHD. Ischemia insult can reduce myocardial ATP content, resulting in energy stress and overproduction of reactive oxygen species (ROS). Thus, mitochondrial abnormality has been identified as a hallmark of multiple cardiovascular disorders. To date, many studies have suggested that these mitochondrial proteins, such as electron transport chain (ETC) complexes, uncoupling proteins (UCPs), mitochondrial dynamic proteins, translocases of outer membrane (Tom) complex, and mitochondrial permeability transition pore (MPTP), can directly or indirectly influence mitochondria-originated ROS production, consequently determining the degree of mitochondrial dysfunction and myocardial impairment. Here, the focus of this review is to summarize the present understanding of the relationship between some mitochondrial functional proteins and ROS production in IHD. PMID:27119006

  6. The Friend of GATA proteins U-shaped, FOG-1, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila

    PubMed Central

    Fossett, Nancy; Tevosian, Sergei G.; Gajewski, Kathleen; Zhang, Qian; Orkin, Stuart H.; Schulz, Robert A.

    2001-01-01

    Friend of GATA (FOG) proteins regulate GATA factor-activated gene transcription. During vertebrate hematopoiesis, FOG and GATA proteins cooperate to promote erythrocyte and megakaryocyte differentiation. The Drosophila FOG homologue U-shaped (Ush) is expressed similarly in the blood cell anlage during embryogenesis. During hematopoiesis, the acute myeloid leukemia 1 homologue Lozenge and Glial cells missing are required for the production of crystal cells and plasmatocytes, respectively. However, additional factors have been predicted to control crystal cell proliferation. In this report, we show that Ush is expressed in hemocyte precursors and plasmatocytes throughout embryogenesis and larval development, and the GATA factor Serpent is essential for Ush embryonic expression. Furthermore, loss of ush function results in an overproduction of crystal cells, whereas forced expression of Ush reduces this cell population. Murine FOG-1 and FOG-2 also can repress crystal cell production, but a mutant version of FOG-2 lacking a conserved motif that binds the corepressor C-terminal binding protein fails to affect the cell lineage. The GATA factor Pannier (Pnr) is required for eye and heart development in Drosophila. When Ush, FOG-1, FOG-2, or mutant FOG-2 is coexpressed with Pnr during these developmental processes, severe eye and heart phenotypes result, consistent with a conserved negative regulation of Pnr function. These results indicate that the fly and mouse FOG proteins function similarly in three distinct cellular contexts in Drosophila, but may use different mechanisms to regulate genetic events in blood vs. cardial or eye cell lineages. PMID:11404479

  7. High Resolution ECG for Evaluation of Heart Function During Exposure to Subacute Hypobaric Hypoxia

    NASA Technical Reports Server (NTRS)

    Zupet, Petra; Finderle, Zarko; Schlegel, Todd T.; Princi, Tanja; Starc, Vito

    2010-01-01

    High altitude climbing presents a wide spectrum of health risks, including exposure to hypobaric hypoxia. Risks are also typically exacerbated by the difficulty in appropriately monitoring for early signs of organ dysfunction in remote areas. We investigated whether high resolution advanced ECG analysis might be helpful as a non-invasive and easy-to-use tool (e.g., instead of Doppler echocardiography) for evaluating early signs of heart overload in hypobaric hypoxia. Nine non-acclimatized healthy trained alpine rescuers (age 43.7 plus or minus 7.3 years) climbed in four days to the altitude of 4,200 m on Mount Ararat. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position on different days but at the same time of day at four different altitudes: 400 m (reference altitude), 1,700 m, 3,200 m and 4,200 m. Changes in conventional and advanced resting ECG parameters, including in beat-to-beat QT and RR variability, waveform complexity, signal-averaged, high-frequency and spatial/spatiotemporal ECG was estimated by calculation of the regression coefficients in independent linear regression models. A p-value of less than 0.05 was adopted as statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with trends k = -96 ms/1000 m with p = 0.000 and k = -9 ms/1000 m with p = 0.001, respectively. Significant changes were found in P-wave amplitude, which nearly doubled from the lowest to the highest altitude (k = 41.6 microvolt/1000 m with p = 0.000), and nearly significant changes in P-wave duration (k = 2.9 ms/1000 m with p = 0.059). Changes were less significant or non-significant in other studied parameters including those of waveform complexity, signal-averaged, high-frequency and spatial/spatiotemporal ECG. High resolution ECG analysis, particularly of the P wave, shows promise as a tool for monitoring early changes in heart function

  8. Cyanotic heart disease

    MedlinePlus

    ... or rhythms The treatment of choice for most congenital heart diseases is surgery to repair the defect . There are ... Some inherited factors may play a role in congenital heart disease. Many family members may be affected. If you ...

  9. Vitamin D Insufficiency Is Associated with Lower Physical Function in Patients with Heart Failure and Diabetes

    PubMed Central

    Lopes, M. R.; Ribeiro, Paula A. B.; Souza, Gabriela C.; Clausell, Nadine; Schaan, Beatriz D.

    2014-01-01

    Vitamin D deficiency is frequent among patients with heart failure (HF) and diabetes, disorders associated with exercise intolerance and muscle weakness. This study aims to search for associations between vitamin D sufficiency and physical function indexes in patients with HF and diabetes. A cross-sectional study of 146 HF patients, 39.7% with diabetes, at a Brazilian tertiary outpatient clinic was performed. Patients underwent clinical evaluation, 6-minute walk test (6 MWT), handgrip strength, physical activity level (IPAQ), and biochemical evaluations including serum 25-hydroxyvitamin D. Classification was done according to vitamin D status (≥30 ng/dL, sufficient) and presence/absence of diabetes in vitamin sufficient, no diabetes (DS-C, n = 25), vitamin sufficient, diabetes (DS-DM, n = 18), vitamin deficient, no diabetes (DD-C, n = 63), and vitamin deficient, diabetes (DD-DM, n = 40). Patients age was 55.4 ± 8 yrs; 70.5% had vitamin D deficiency. Clinical characteristics were similar among groups. Total time expended in physical activity was similar among groups (P = 0.26). DS-C covered higher distances in the 6 MWT (392 ± 60 m) versus DD-DM (309 ± 116 m); P = 0.024. Handgrip strength was similar among groups but tended to lower levels in DD-DM (P = 0.074) even after being adjusted to physical activity (P = 0.069). Vitamin D deficiency can influence physical function in HF diabetic patients. PMID:25243195

  10. Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease.

    PubMed

    Liang, Y; Li, Y P; He, F; Liu, X Q; Zhang, J Y

    2015-06-01

    Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34(+) monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34(+) endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells. PMID:25923462

  11. Interaction between worsening renal function and persistent congestion in acute decompensated heart failure.

    PubMed

    Wattad, Malak; Darawsha, Wisam; Solomonica, Amir; Hijazi, Maher; Kaplan, Marielle; Makhoul, Badira F; Abassi, Zaid A; Azzam, Zaher S; Aronson, Doron

    2015-04-01

    Worsening renal function (WRF) and congestion are inextricably related pathophysiologically, suggesting that WRF occurring in conjunction with persistent congestion would be associated with worse clinical outcome. We studied the interdependence between WRF and persistent congestion in 762 patients with acute decompensated heart failure (HF). WRF was defined as ≥0.3 mg/dl increase in serum creatinine above baseline at any time during hospitalization and persistent congestion as ≥1 sign of congestion at discharge. The primary end point was all-cause mortality with mean follow-up of 15 ± 9 months. Readmission for HF was a secondary end point. Persistent congestion was more common in patients with WRF than in patients with stable renal function (51.0% vs 26.6%, p <0.0001). Both persistent congestion and persistent WRF were significantly associated with mortality (both p <0.0001). There was a strong interaction (p = 0.003) between persistent WRF and congestion, such that the increased risk for mortality occurred predominantly with both WRF and persistent congestion. The adjusted hazard ratio for mortality in patients with persistent congestion as compared with those without was 4.16 (95% confidence interval [CI] 2.20 to 7.86) in patients with WRF and 1.50 (95% CI 1.16 to 1.93) in patients without WRF. In conclusion, persisted congestion is frequently associated with WRF. We have identified a substantial interaction between persistent congestion and WRF such that congestion portends increased mortality particularly when associated with WRF. PMID:25700802

  12. Equestrian expertise affecting physical fitness, body compositions, lactate, heart rate and calorie consumption of elite horse riding players.

    PubMed

    Sung, Bong-Ju; Jeon, Sang-Yong; Lim, Sung-Ro; Lee, Kyu-Eon; Jee, Hyunseok

    2015-06-01

    Horse riding (HR) is a sport harmonized with rider and horse. HR is renowned as an effective sport for young and old women and men. There is rare study regarding comparison between elite horse riders and amateurs. We aimed to investigate comprehensive ranges of parameters such as change of lactate, heart rate, calorie, VO2max, skeletal muscle mass, body water, body fat, etc between amateurs and professionals to emphasize HR not only as a sport training but also as a therapeutic aspect. We performed 3 experiments for comparing physical fitness, body compositions, lactate value, heart rate and calorie consumption change before and after riding between amateurs and elites. Around 3 yr riding experienced elites are preeminent at balance capability compared to 1 yr riding experienced amateurs. During 18 min horse riding, skeletal muscle mass and body fat were interestingly increased and decreased, respectively. Lactate response was more sensitive in elites rather than amateurs and its recovery was reversely reacted. Exercise intensity estimated from heart rate was significantly higher in elites (P<0.05). The similar pattern of calorie consumption during riding between amateurs and elites was shown. Horse riding possibly induces various physiological (muscle strength, balance, oxidative capability, flexibility, and metabolic control) changes within body and is thus highly recommended as combined exercise for women, children, and aged as therapeutic and leisure sport activity. PMID:26171385

  13. Equestrian expertise affecting physical fitness, body compositions, lactate, heart rate and calorie consumption of elite horse riding players

    PubMed Central

    Sung, Bong-Ju; Jeon, Sang-Yong; Lim, Sung-Ro; Lee, Kyu-Eon; Jee, Hyunseok

    2015-01-01

    Horse riding (HR) is a sport harmonized with rider and horse. HR is renowned as an effective sport for young and old women and men. There is rare study regarding comparison between elite horse riders and amateurs. We aimed to investigate comprehensive ranges of parameters such as change of lactate, heart rate, calorie, VO2max, skeletal muscle mass, body water, body fat, etc between amateurs and professionals to emphasize HR not only as a sport training but also as a therapeutic aspect. We performed 3 experiments for comparing physical fitness, body compositions, lactate value, heart rate and calorie consumption change before and after riding between amateurs and elites. Around 3 yr riding experienced elites are preeminent at balance capability compared to 1 yr riding experienced amateurs. During 18 min horse riding, skeletal muscle mass and body fat were interestingly increased and decreased, respectively. Lactate response was more sensitive in elites rather than amateurs and its recovery was reversely reacted. Exercise intensity estimated from heart rate was significantly higher in elites (P<0.05). The similar pattern of calorie consumption during riding between amateurs and elites was shown. Horse riding possibly induces various physiological (muscle strength, balance, oxidative capability, flexibility, and metabolic control) changes within body and is thus highly recommended as combined exercise for women, children, and aged as therapeutic and leisure sport activity. PMID:26171385

  14. Heart Health - Brave Heart

    MedlinePlus

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

  15. MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart

    PubMed Central

    Dakhlallah, Duaa; Zhang, Jianying; Yu, Lianbo; Marsh, Clay B.; Angelos, Mark G.; Khan, Mahmood

    2015-01-01

    Cardiovascular disease is the number one cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure (CHF). Cell therap (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA in the cardiac muscle and is down-regulated in patients with MI. We hypothesized that reprogramming MSCs using microRNA-mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs and the levels of miR-133a were measured by qRT-PCR. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic heart. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels and apoptosis related genes (Apaf-1, Capase-9 and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, qRT-PCR data demonstrated a significant decrease in expression of the pro-apoptotic genes; Apaf-1, caspase-9 and caspase-3 in the miR-133a mimic transplanted group. Further, luciferase reporter assay confirmed that miR- 133a is a direct target for Apaf-1. Overall, bioengineering of stem cells through miRNAs manipulation could potentially improve the therapeutic outcome of

  16. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    SciTech Connect

    Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Moros, Eduardo G.; Zheng, Junying; Hauer-Jensen, Martin; Boerma, Marjan

    2014-01-01

    Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

  17. Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart

    PubMed Central

    Lim, Byung-Kwan; Xiong, Dingding; Dorner, Andrea; Youn, Tae-Jin; Yung, Aaron; Liu, Taylor I.; Gu, Yusu; Dalton, Nancy D.; Wright, Adam T.; Evans, Sylvia M.; Chen, Ju; Peterson, Kirk L.; McCulloch, Andrew D.; Yajima, Toshitaka; Knowlton, Kirk U.

    2008-01-01

    The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that belongs to the family of adhesion molecules. In the postnatal heart, it is localized predominantly at the intercalated disc, where its function is not known. Here, we demonstrate that a first degree or complete block of atrioventricular (AV) conduction developed in the absence of CAR in the adult mouse heart and that prolongation of AV conduction occurred in the embryonic heart of the global CAR-KO mouse. In the cardiac-specific CAR-KO (CAR-cKO) mouse, we observed the loss of connexin 45 localization to the cell-cell junctions of the AV node but preservation of connexin 40 and 43 in contracting myocardial cells and connexin 30.2 in the AV node. There was also a marked decrease in β-catenin and zonula occludens-1 (ZO-1) localization to the intercalated discs of CAR-cKO mouse hearts at 8 weeks before the mice developed cardiomyopathy at 21 weeks of age. We also found that CAR formed a complex with connexin 45 via its PSD-95/DigA/ZO-1–binding (PDZ-binding) motifs. We conclude that CAR expression is required for normal AV-node conduction and cardiac function. Furthermore, localization of connexin 45 at the AV-node cell-cell junction and of β-catenin and ZO-1 at the ventricular intercalated disc are dependent on CAR. PMID:18636119

  18. High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

    PubMed Central

    Kang, Bong Jin; Park, Jinhyoung; Kim, Jieun; Kim, Hyung Ham; Lee, Changyang; Hwang, Jae Youn; Lien, Ching-Ling; Shung, K. Kirk

    2015-01-01

    Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s−1 with high accuracy (p-value = 0.974 > 0.05). In the in vivo study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example, E/Em < 10, E/A < 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation. PMID:25505135

  19. Predicting the accuracy of facial affect recognition: the interaction of child maltreatment and intellectual functioning.

    PubMed

    Shenk, Chad E; Putnam, Frank W; Noll, Jennie G

    2013-02-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying levels of intellectual functioning. A sample of maltreated (n=50) and nonmaltreated (n=56) adolescent females, 14 to 19 years of age, was recruited to participate in this study. Participants completed demographic and study-related questionnaires and interviews to control for potential psychological and psychiatric confounds such as symptoms of posttraumatic stress disorder, negative affect, and difficulties in emotion regulation. Participants also completed an experimental paradigm that recorded responses to facial affect displays starting in a neutral expression and changing into a full expression of one of six emotions: happiness, sadness, anger, disgust, fear, or surprise. Hierarchical multiple regression assessed the incremental advantage of evaluating the interaction between child maltreatment and intellectual functioning. Results indicated that the interaction term accounted for a significant amount of additional variance in the accurate identification of facial affect after controlling for relevant covariates and main effects. Specifically, maltreated females with lower levels of intellectual functioning were least accurate in identifying facial affect displays, whereas those with higher levels of intellectual functioning performed as well as nonmaltreated females. These results suggest that maltreatment and intellectual functioning interact to predict the recognition of facial affect, with potential long-term consequences for the interpersonal functioning of maltreated females. PMID:23036371

  20. Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure

    PubMed Central

    Sundararaman, S; Miller, T J; Pastore, J M; Kiedrowski, M; Aras, R; Penn, M S

    2011-01-01

    We previously demonstrated that transient stromal cell-derived factor-1 alpha (SDF-1) improved cardiac function when delivered via cell therapy in ischemic cardiomyopathy at a time remote from acute myocardial infarction (MI) rats. We hypothesized that non-viral gene transfer of naked plasmid DNA-expressing hSDF-1 could similarly improve cardiac function. To optimize plasmid delivery, we tested SDF-1 and luciferase plasmids driven by the cytomegalovirus (CMV) promoter with (pCMVe) or without (pCMV) translational enhancers or α myosin heavy chain (pMHC) promoter in a rodent model of heart failure. In vivo expression of pCMVe was 10-fold greater than pCMV and pMHC expression and continued over 30 days. We directly injected rat hearts with SDF-1 plasmid 1 month after MI and assessed heart function. At 4 weeks after plasmid injection, we observed a 35.97 and 32.65% decline in fractional shortening (FS) in control (saline) animals and pMHC-hSDF1 animals, respectively, which was sustained to 8 weeks. In contrast, we observed a significant 24.97% increase in animals injected with the pCMVe-hSDF1 vector. Immunohistochemistry of cardiac tissue revealed a significant increase in vessel density in the hSDF-1-treated animals compared with control animals. Increasing SDF-1 expression promoted angiogenesis and improved cardiac function in rats with ischemic heart failure along with evidence of scar remodeling with a trend toward decreased myocardial fibrosis. These data demonstrate that stand-alone non-viral hSDF-1 gene transfer is a strategy for improving cardiac function in ischemic cardiomyopathy. PMID:21472007

  1. Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study

    PubMed Central

    Weaver, Anne M.; Wellenius, Gregory A.; Wu, Wen-Chih; Hickson, DeMarc A.; Kamalesh, Masoor; Wang, Yi

    2016-01-01

    Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150–299 m, 1161 lived 300–999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans. PMID:27304962

  2. Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study.

    PubMed

    Weaver, Anne M; Wellenius, Gregory A; Wu, Wen-Chih; Hickson, DeMarc A; Kamalesh, Masoor; Wang, Yi

    2016-01-01

    Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150-299 m, 1161 lived 300-999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans. PMID:27304962

  3. Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death.

    PubMed

    White, C W; Ambrose, E; Müller, A; Li, Y; Le, H; Thliveris, J; Arora, R C; Lee, T W; Dixon, I M C; Tian, G; Nagendran, J; Hryshko, L V; Freed, D H

    2016-03-01

    The resuscitation of hearts donated after circulatory death (DCD) is gaining widespread interest; however, the method of initial reperfusion (IR) that optimizes functional recovery has not been elucidated. We sought to determine the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-min standoff period was observed and then hearts were reperfused for 3 min at three different temperatures (5°C; N = 6, 25°C; N = 5, and 35°C; N = 7) with a normokalemic adenosine-lidocaine crystalloid cardioplegia. Hearts then underwent normothermic EVHP for 6 h during which time myocardial function was assessed in a working mode. We found that IR coronary blood flow differed among treatment groups (5°C = 483 ± 53, 25°C = 722 ± 60, 35°C = 906 ± 36 mL/min, p < 0.01). During subsequent EVHP, less myocardial injury (troponin I: 5°C = 91 ± 6, 25°C = 64 ± 16, 35°C = 57 ± 7 pg/mL/g, p = 0.04) and greater preservation of endothelial cell integrity (electron microscopy injury score: 5°C = 3.2 ± 0.5, 25°C = 1.8 ± 0.2, 35°C = 1.7 ± 0.3, p = 0.01) were evident in hearts initially reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of myocardial function (cardiac index: 5°C = 3.9 ± 0.8, 25°C = 6.2 ± 0.4, 35°C = 6.5 ± 0.6 mL/minute/g, p = 0.03) during EVHP. We conclude that the avoidance of profound hypothermia during IR minimizes injury and improves the functional recovery of DCD hearts. PMID:26780159

  4. Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

    PubMed Central

    Åsvold, Bjørn O.; Vatten, Lars J.; Bjøro, Trine; Bauer, Douglas C.; Bremner, Alexandra; Cappola, Anne R.; Ceresini, Graziano; den Elzen, Wendy P. J.; Ferrucci, Luigi; Franco, Oscar H.; Franklyn, Jayne A.; Gussekloo, Jacobijn; Iervasi, Giorgio; Imaizumi, Misa; Kearney, Patricia M.; Khaw, Kay-Tee; Maciel, Rui M. B.; Newman, Anne. B.; Peeters, Robin P.; Psaty, Bruce M.; Razvi, Salman; Sgarbi, José A.; Stott, David J.; Trompet, Stella; Vanderpump, Mark P. J.; Völzke, Henry; Walsh, John P.; Westendorp, Rudi G. J.; Rodondi, Nicolas

    2016-01-01

    Importance Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). Objective To assess the association between differences in thyroid function within the reference range and CHD risk. Design, Setting, and Participants Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Exposures Thyroid function as expressed by serum thyrotropin levels at baseline. Mainoutcomes and Measures Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Results Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Conclusions and

  5. Angiotensin-converting enzyme and matrix metalloproteinase inhibition with developing heart failure: comparative effects on left ventricular function and geometry

    NASA Technical Reports Server (NTRS)

    McElmurray, J. H. 3rd; Mukherjee, R.; New, R. B.; Sampson, A. C.; King, M. K.; Hendrick, J. W.; Goldberg, A.; Peterson, T. J.; Hallak, H.; Zile, M. R.; Spinale, F. G.

    1999-01-01

    The progression of congestive heart failure (CHF) is left ventricular (LV) myocardial remodeling. The matrix metalloproteinases (MMPs) contribute to tissue remodeling and therefore MMP inhibition may serve as a useful therapeutic target in CHF. Angiotensin converting enzyme (ACE) inhibition favorably affects LV myocardial remodeling in CHF. This study examined the effects of specific MMP inhibition, ACE inhibition, and combined treatment on LV systolic and diastolic function in a model of CHF. Pigs were randomly assigned to five groups: 1) rapid atrial pacing (240 beats/min) for 3 weeks (n = 8); 2) ACE inhibition (fosinopril, 2.5 mg/kg b.i.d. orally) and rapid pacing (n = 8); 3) MMP inhibition (PD166793 2 mg/kg/day p.o.) and rapid pacing (n = 8); 4) combined ACE and MMP inhibition (2.5 mg/kg b.i.d. and 2 mg/kg/day, respectively) and rapid pacing (n = 8); and 5) controls (n = 9). LV peak wall stress increased by 2-fold with rapid pacing and was reduced in all treatment groups. LV fractional shortening fell by nearly 2-fold with rapid pacing and increased in all treatment groups. The circumferential fiber shortening-systolic stress relation was reduced with rapid pacing and increased in the ACE inhibition and combination groups. LV myocardial stiffness constant was unchanged in the rapid pacing group, increased nearly 2-fold in the MMP inhibition group, and was normalized in the ACE inhibition and combination treatment groups. Increased MMP activation contributes to the LV dilation and increased wall stress with pacing CHF and a contributory downstream mechanism of ACE inhibition is an effect on MMP activity.

  6. A Functional Coupling Between Carbon Monoxide and Nitric Oxide Contributes to Increased Vasopressin Neuronal Activity in Heart Failure rats.

    PubMed

    Reis, Wagner L; Biancardi, Vinicia C; Zhou, Yiqiang; Stern, Javier E

    2016-05-01

    Despite the pathophysiological importance of neurohumoral activation in patients with heart failure (HF), the precise underlying mechanisms contributing to elevated vasopressin (VP) activation in HF remains unknown. Carbon monoxide (CO) is a gaseous neurotransmitter in the central nervous system that stimulates VP neuronal firing activity. Recently, we showed that the excitatory effect of CO on VP neurons in the hypothalamic paraventricular nucleus (PVN) was mediated by inhibition of nitric oxide (NO). Given that previous studies showed that VP neuronal activity is enhanced, whereas NO inhibitory signaling is blunted in HF rats, we tested whether an enhanced endogenous CO availability within the PVN contributes to elevated VP neuronal activity and blunted NO signaling in HF rats. We found that both haeme-oxygenase 1 (the CO-synthesizing enzyme) protein and mRNA expression levels were enhanced in the PVN of HF compared with sham rats (∼18% and ∼38%, respectively). We report that in sham rats, bath application of a CO donor (tricarbonyldichlororuthenium dimer) increased the firing activity of identified PVN VP neurons (P < .05), whereas inhibition of endogenous CO production (Tin-protoporphyrin IX [SnPP]) failed to affect neuronal activity. In HF rats, however, SnPP decreased VP activity (P < .05), an effect that was occluded by previous NO synathase blockade NG-nitro-larginine methyl ester. Finally, we found that SnPP increased the mean frequency of γ-aminobutyric acid inhibitory postsynaptic currents in VP neurons in HF (P < .05) but not sham rats. Our results support an enhanced endogenous CO excitatory signaling in VP neurons, which likely contributes to blunted NO and γ-aminobutyric acid inhibitory function in HF rats. PMID:26982634

  7. Left ventricular end-diastolic pressure in anginal patients: lack of correlation with New York Heart Association's functional classification.

    PubMed

    Prakash, R; Aronow, W S; Khemka, M

    1975-02-01

    The New York Heart Association (NYHA) recently designated functional classifications I, II, and III, for angina. In the authors' series of 80 male anginal patients, observations were made on the mean left ventricular end-diastolic pressure (LVEDP) at rest and after left ventriculography and on the percentage of anginal patients with an abnormal LVEDP under these respective circumstances. The findings indicated no significant differences on the basis of NYHA classifications I, II, III. In the author's opinion, the NYHA functional classification cannot be used to distinguish the presence of abnormal left ventricular function in class I, II, and III anginal patients. PMID:1141626

  8. Impaired heart rate regulation and depression of cardiac chronotropic and dromotropic function in polymicrobial sepsis

    PubMed Central

    Hoover, Donald B.; Ozment, Tammy R.; Wondergem, Robert; Li, Chuanfu; Williams, David L.

    2014-01-01

    The scope of cardiac pathophysiology in sepsis has not been fully defined. Accordingly, we evaluated the effects of sepsis on heart rate (HR), HR variability, and conduction parameters in a murine model of sepsis. Electrocardiograms were recorded non-invasively from conscious mice before and after cecal ligation and puncture (CLP) or sham surgery. Responses of isolated atria to tyramine and isoproterenol were quantified to assess the functional state of sympathetic nerves and postjunctional sensitivity to adrenergic stimulation. CLP mice had lower HR compared to sham at 16-18 h post-surgery (Sham: 741±7 beats per min, CLP: 557±31 beats per min, n=6/group, P<0.001), and there was significant prolongation of the PR, QRS and QTc intervals. Slowing of HR and conduction developed within 4-6 h after CLP and were preceded by a decrease in HR variability. Treatment of CLP mice with isoproterenol (5 mg/kg, i.p.) at 25 h post-surgery failed to increase HR or decrease conduction intervals. The lack of in vivo response to isoproterenol cannot be attributed to hypothermia since robust chronotropic and inotropic responses to isoproterenol were evoked from isolated atria at 25 and 30° C. These findings demonstrate that impaired regulation of HR (i.e, reduced HR variability) develops before the onset of overt cardiac rate and conduction changes in septic mice. Subsequent time-dependent decreases in HR and cardiac conduction can be attributed to hypothermia and would contribute to decreased cardiac output and organ perfusion. Since isolated atria from septic mice showed normal responsiveness to adrenergic stimulation, we conclude that impaired effectiveness of isoproterenol in vivo can be attributed to reversible effects of systemic factors on adrenergic receptors and/or post-receptor signaling. PMID:25271380

  9. Heart transplant

    MedlinePlus

    ... 10 years. Alternative Names Cardiac transplant; Transplant - heart; Transplantation - heart Images Heart, section through the middle Heart, ... 28. Bernstein D. Pediatric heart and heart-lung transplantation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton ...

  10. Heart Failure

    MedlinePlus

    ... version of this page please turn Javascript on. Heart Failure What is Heart Failure? In heart failure, the heart cannot pump enough ... failure often experience tiredness and shortness of breath. Heart Failure is Serious Heart failure is a serious and ...

  11. Monitoring changes in heart tissue temperature and evaluation of graft function after coronary artery bypass grafting surgery.

    PubMed

    Lekas, Raimundas; Jakuska, Povilas; Krisciukaitis, Algimantas; Veikutis, Vincentas; Dzemyda, Gintautas; Mickevicius, Tomas; Morkūnaite, Kristina; Vilke, Alina; Treigys, Povilas; Civinskiene, Genuvaite; Andriuskevicius, Jonas; Vanagas, Tomas; Skauminas, Kestutis; Bernatoniene, Jurga

    2009-01-01

    Thermography is a relatively new contact-free method used in experimental and clinical studies and in cardiovascular surgery to investigate the myocardium and coronary artery function. Objects of complex study included mongrel dogs and patients with coronary artery disease who underwent cardiac surgery. For active dynamic thermography, we used a thermovision camera "A20V" (FLIR Systems, USA). Our data indicate that both experimental and clinical study performed on beating hearts could be an important approach to interoperation inspection of autovenous graft function. An infrared camera also can be successfully used to determine the extent of ischemic damage to the myocardium, heart, and blood vessels during surgery as a significant prognostic tool for evaluating outcome after cardiac operation. PMID:19357452

  12. Cardiac Structure and Function in Heart Failure with Preserved Ejection Fraction: Baseline Findings from the Echocardiographic Study of the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial

    PubMed Central

    Shah, Amil M.; Shah, Sanjiv J.; Anand, Inder S.; Sweitzer, Nancy K.; O’Meara, Eileen; Heitner, John F.; Sopko, George; Li, Guichu; Assmann, Susan F.; McKinlay, Sonja M.; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

    2016-01-01

    Background Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggests significant heterogeneity in this population. Methods and Results Echocardiograms were obtained from 935 patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial prior to initiation of randomized therapy. Average age was 70±10 years, 49% were female, 14% were of African descent, and co-morbidities were highly prevalent. Centralized quantitative analysis in a blinded core laboratory demonstrated a mean LVEF of 59.3±7.9%, with prevalent concentric LV remodeling (34%) and hypertrophy (43%), and left atrial (LA) enlargement (53%). Diastolic dysfunction was present in 66% of gradable participants, and was significantly associated with greater LV hypertrophy and a higher prevalence of LA enlargement. Doppler evidence of pulmonary hypertension was present in 36%. At least 1 measure of structural heart disease was present in 93% of patients. Conclusions Participants enrolled in TOPCAT demonstrated heterogeneous patterns of ventricular remodeling, with high prevalence of structural heart disease, including LV hypertrophy and LA enlargement, in addition to pulmonary hypertension, each of which has been associated with adverse outcomes in HFpEF. Diastolic function was normal in approximately one-third of gradable participants, highlighting the heterogeneity of the cardiac phenotype in this syndrome. These findings deepen our understanding of the TOPCAT trial population and expand our knowledge of the diversity of the cardiac phenotype in HFpEF. Clinical Trial Registration Clinicaltrials.gov Identifier NCT00094302 PMID:25122186

  13. Cardiac Structure and Function in Heart Failure with Preserved Ejection Fraction: Baseline Findings from the Echocardiographic Study of the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial

    PubMed Central

    Shah, Amil M.; Shah, Sanjiv J.; Anand, Inder S.; Sweitzer, Nancy K.; O’Meara, Eileen; Heitner, John F.; Sopko, George; Li, Guichu; Assmann, Susan F.; McKinlay, Sonja M.; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

    2014-01-01

    Background Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggests significant heterogeneity in this population. Methods and Results Echocardiograms were obtained from 935 patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial prior to initiation of randomized therapy. Average age was 70±10 years, 49% were female, 14% were of African descent, and co-morbidities were highly prevalent. Centralized quantitative analysis in a blinded core laboratory demonstrated a mean LVEF of 59.3±7.9%, with prevalent concentric LV remodeling (34%) and hypertrophy (43%), and left atrial (LA) enlargement (53%). Diastolic dysfunction was present in 66% of gradable participants, and was significantly associated with greater LV hypertrophy and a higher prevalence of LA enlargement. Doppler evidence of pulmonary hypertension was present in 36%. At least 1 measure of structural heart disease was present in 93% of patients. Conclusions Participants enrolled in TOPCAT demonstrated heterogeneous patterns of ventricular remodeling, with high prevalence of structural heart disease, including LV hypertrophy and LA enlargement, in addition to pulmonary hypertension, each of which has been associated with adverse outcomes in HFpEF. Diastolic function was normal in approximately one-third of gradable participants, highlighting the heterogeneity of the cardiac phenotype in this syndrome. These findings deepen our understanding of the TOPCAT trial population and expand our knowledge of the diversity of the cardiac phenotype in HFpEF. Clinical Trial Registration Clinicaltrials.gov Identifier NCT00094302 PMID:24249049

  14. Right ventricular diastolic function in dialysis patients could be affected by vascular access.

    PubMed

    Di Lullo, Luca; Floccari, Fulvio; Polito, Pasquale

    2011-01-01

    Tricuspid annular plane excursion (TAPSE) measurement in echocardiography is a measure of heart diastolic distensibility: a low TAPSE indicates reduced ventricular distensibility leading to diastolic dysfunction. It is a good prognostic index for cardiac mortality risk in congestive heart failure patients, adding significant prognostic information to the NYHA clinical classification. Our study was designed to evaluate the effect of a single hemodialysis (HD) session on diastolic function and TAPSE, focusing on the effects of vascular access typology. Twenty chronically uremic patients (age 51 ± 10 years, dialytic age 24 ± 8 months), without overt heart disease, underwent conventional two-dimensional and Doppler echocardiography immediately before starting and 15 min after ending a mid-week HD session. Ten patients had distal radiocephalic arterovenous fistula (AVF), and 10 had permanent central venous catheters (CVC). The amount of fluid removed by HD was 2,706 ± 1,047 g/session. HD led to a reduction in TAPSE, left ventricle end-diastole volume, left ventricle end-systole volume, right ventricle end-diastole diameter, peak early transmitral flow velocity, and the ratio of early to late Doppler velocities of diastolic mitral flow. AVF patients showed greater right ventricle diameters versus CVC patients, while TAPSE appeared higher in the latter. Only the AVF patient group showed TAPSE values <15 mm. Our data confirm the effects of terminal uremia on right ventricle function (chamber dilation, impaired diastolic function), showing that these abnormalities are more frequent in AVF patients as opposed to CVC patients. It is reasonable to explain these clinical features as the effect of preload increase operated by AVF. PMID:21196771

  15. Acquired deficiency of tafazzin in the adult heart: Impact on mitochondrial function and response to cardiac injury.

    PubMed

    Szczepanek, Karol; Allegood, Jeremy; Aluri, Hema; Hu, Ying; Chen, Qun; Lesnefsky, Edward J

    2016-04-01

    The content and composition of cardiolipin (CL) is critical for preservation of mitochondrial oxidative phosphorylation (OXPHOS) and inner membrane integrity. Tafazzin (Taz) is an enzyme responsible for remodeling of immature CL containing mixed acyl groups into the mature tetralinoleyl form (C18:2)4-CL. We hypothesized that acquired defects in Taz in the mature heart would impact remodeling of CL and augment cardiac injury. The role of acquired Taz deficiency was studied using the inducible Taz knockdown (TazKD) mouse. Taz-specific shRNA is induced by doxycycline (DOX). One day of DOX intake decreased Taz mRNA in the heart to 20% vs. DOX-treated WT. Knockdown was initiated at an adult age and was stable during long term feeding. CL phenotype was assessed by (C18:2)4-CL content and was reduced 40% vs. WT at two months of DOX. TazKD showed increased production of reactive oxygen species and increased susceptibility to permeability transition pore opening at baseline. However, OXPHOS measured using the rate of oxygen consumption was unchanged in the setting of acquired Taz deficiency. Infarct size, measured in isolated buffer-perfused Langendorff hearts following 25min. Stop flow ischemia and 60min. Reperfusion was not altered in TazKD hearts. Thus, impaired Taz-function with onset at adult age does not enhance susceptibility to ischemia-reperfusion injury. PMID:26692032

  16. A flexible home monitoring platform for patients affected by chronic heart failure directly integrated with the remote Hospital Information System

    NASA Astrophysics Data System (ADS)

    Donati, Massimiliano; Bacchillone, Tony; Saponara, Sergio; Fanucci, Luca

    2011-05-01

    Today Chronic Heart Failure (CHF) represents one of leading cause of hospitalization among chronic disease, especially for elderly citizens, with a consequent considerable impact on patient quality of life, resources congestion and healthcare costs for the National Sanitary System. The current healthcare model is mostly in-hospital based and consists of periodic visits, but unfortunately it does not allow to promptly detect exacerbations resulting in a large number of rehospitalization. Recently physicians and administrators identify telemonitoring systems as a strategy able to provide effective and cost efficient healthcare services for CHF patients, ensuring early diagnosis and treatments in case of necessity. This work presents a complete and integrated ICT solution to improve the management of chronic heart failure through the remote monitoring of vital signs at patient home, able to connect in-hospital care of acute syndrome with out-of-hospital follow-up. The proposed platform represents the patient's interface, acting as link between biomedical sensors and the data collection point at the Hospital Information System (HIS) in order to handle in transparent way the reception, analysis and forwarding of the main physiological parameters.

  17. Viewing Nature Scenes Positively Affects Recovery of Autonomic Function Following Acute-Mental Stress

    PubMed Central

    2013-01-01

    A randomized crossover study explored whether viewing different scenes prior to a stressor altered autonomic function during the recovery from the stressor. The two scenes were (a) nature (composed of trees, grass, fields) or (b) built (composed of man-made, urban scenes lacking natural characteristics) environments. Autonomic function was assessed using noninvasive techniques of heart rate variability; in particular, time domain analyses evaluated parasympathetic activity, using root-mean-square of successive differences (RMSSD). During stress, secondary cardiovascular markers (heart rate, systolic and diastolic blood pressure) showed significant increases from baseline which did not differ between the two viewing conditions. Parasympathetic activity, however, was significantly higher in recovery following the stressor in the viewing scenes of nature condition compared to viewing scenes depicting built environments (RMSSD; 50.0 ± 31.3 vs 34.8 ± 14.8 ms). Thus, viewing nature scenes prior to a stressor alters autonomic activity in the recovery period. The secondary aim was to examine autonomic function during viewing of the two scenes. Standard deviation of R-R intervals (SDRR), as change from baseline, during the first 5 min of viewing nature scenes was greater than during built scenes. Overall, this suggests that nature can elicit improvements in the recovery process following a stressor. PMID:23590163

  18. The mitochondrial uniporter controls fight or flight heart rate increases

    PubMed Central

    Wu, Yuejin; Rasmussen, Tyler P.; Koval, Olha M.; Joiner, Mei-ling A.; Hall, Duane D.; Chen, Biyi; Luczak, Elizabeth D.; Wang, Qiongling; Rokita, Adam G.; Wehrens, Xander H. T.; Song, Longsheng; Anderson, Mark E.

    2015-01-01

    Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant negative (DN) MCU. Here we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment prior to each heartbeat. Our findings show the MCU is necessary for complete physiological heart rate acceleration and suggest MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate. PMID:25603276

  19. Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

    NASA Technical Reports Server (NTRS)

    Meyerson, F. Z.; Kapelko, V. I.; Gorina, M. S.; Shchegolkov, A. N.; Larinov, N. P.

    1980-01-01

    Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart.

  20. Low-Dose Irradiation Affects Expression of Inflammatory Markers in the Heart of ApoE -/- Mice

    PubMed Central

    Mathias, Daniel; Mitchel, Ronald E. J.; Barclay, Mirela; Wyatt, Heather; Bugden, Michelle; Priest, Nicholas D.; Scholz, Markus; Hildebrandt, Guido; Kamprad, Manja; Glasow, Annegret

    2015-01-01

    Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025–0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025–2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05–2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and

  1. Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

    PubMed

    Mathias, Daniel; Mitchel, Ronald E J; Barclay, Mirela; Wyatt, Heather; Bugden, Michelle; Priest, Nicholas D; Whitman, Stewart C; Scholz, Markus; Hildebrandt, Guido; Kamprad, Manja; Glasow, Annegret

    2015-01-01

    Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention

  2. The expression of CG9940 affects the adaptation of cardiac function, mobility, and lifespan to exercise in aging Drosophila.

    PubMed

    Wen, Deng-Tai; Zheng, Lan; Ni, Liu; Wang, Hui; Feng, Yue; Zhang, Min

    2016-10-01

    The CG9940 gene, which encodes the NAD(+) synthase protein in Drosophila, is conserved in human, zebra fish, and mosquito. NAD(+) synthase is a homodimer, which catalyzes the final step in de novo nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, an amide transfer from either ammonia or glutamine to nicotinic acid adenine dinucleotide (NaAD). Both the CG9940 and exercise are closely relative to NAD(+) level, and NAD(+) plays important roles not only in energy metabolism and mitochondrial functions but also in aging. In our study, the expression of CG9940 was changed by UAS/GAL4 system in Drosophila. Flies were trained by a training device. Cardiac function was analyzed by M-mode traces, climbing index was measured through negative geotaxis assay, and lifespan was measured via lifespan assays. The important new findings from our present study included the following: (1) the expression of the CG9940 could affect cardiac function, mobility, and lifespan in Drosophila. Over-expression of the CG9940 gene had positive effects on Drosophila, such as enhanced aging cardiac output, reduced heart failure, delayed age-related mobility decline, and prolonged lifespan, but lower-expression of the CG9940 had negative effects on them. (2) Different expressions of the CG9940 resulted in different influences on the adaptation of cardiac function, mobility, and lifespan to exercise in aging Drosophila. Both normal-expression and over-expression of the CG9940 resulted in positive influences on the adaptation of cardiac functions, mobility, and lifespan to exercise in aging Drosophila such as exercise slowed age-related decline of cardiac function, mobility and extent of lifespan in these flies, while lower-expression of the CG9940 led to negative impacts on the adaptation of mobility and lifespan to exercise in Drosophila. PMID:27448710

  3. Mitoconfusion: Non-canonical functioning of dynamism factors in static mitochondria of the heart

    PubMed Central

    Song, Moshi; Dorn, Gerald W.

    2015-01-01

    Mitochondrial fitness is central to heart health. In many cell types mitochondria are dynamic, interconnected filamentous networks. By comparison, mitochondria of healthy post-mitotic adult cardiomyocytes are shortened, round, hypo-dynamic organelles. Mitochondrial networks are absent in cardiomyocytes; fission, fusion, and organelle mobility are not normally observed. Nevertheless, mitochondrial fission factor Drp1 and fusion factors Mfn1, Mfn2, and Opa1 are abundant and indispensable in adult hearts. Here, we review recent insights into roles for mitochondrial dynamics factors not strictly related to morphometric remodeling, advancing the argument that fission and fusion of cardiomyocyte mitochondria supports surveillance, sequestration, and mitophagic removal of damaged organelles. PMID:25651174

  4. Anatomic and functional imaging of congenital heart disease with digital subtraction angiography

    SciTech Connect

    Buonocore, E.; Pavlicek, W.; Modic, M.T.; Meaney, T.F.; O'Donovan, P.B.; Grossman, L.B.; Moodie, D.S.; Yiannikas, J.

    1983-06-01

    Digital subtraction angiography (DSA) of the heart was performed in 54 patients for the evaluation of congenital heart diagnostic images and accurate physiologic shunt data that compared favorably with catheter angiography and nuclear medicine studies. Retrospective analysis of this series of patients indicated that DSA studies contributed sufficient informantion to shorten significantly or modify cardiac catheterization in 85% (79/93) of the defects that were identified. Interatrial septal defects were particularly well diagnosed, with identification occurring in 10 of 10 cases, wheseas intraventricular septal defects were identified in only 6 of 9 patients. Evaluation of postsurgical patients was accurate in 19 of 20 cases.

  5. Mitochondrial structure and function are not different between nonfailing donor and end-stage failing human hearts.

    PubMed

    Holzem, Katherine M; Vinnakota, Kalyan C; Ravikumar, Vinod K; Madden, Eli J; Ewald, Gregory A; Dikranian, Krikor; Beard, Daniel A; Efimov, Igor R

    2016-08-01

    During human heart failure, the balance of cardiac energy use switches from predominantly fatty acids (FAs) to glucose. We hypothesized that this substrate shift was the result of mitochondrial degeneration; therefore, we examined mitochondrial oxidation and ultrastructure in the failing human heart by using respirometry, transmission electron microscopy, and gene expression studies of demographically matched donor and failing human heart left ventricular (LV) tissues. Surprisingly, respiratory capacities for failing LV isolated mitochondria (n = 9) were not significantly diminished compared with donor LV isolated mitochondria (n = 7) for glycolysis (pyruvate + malate)- or FA (palmitoylcarnitine)-derived substrates, and mitochondrial densities, assessed via citrate synthase activity, were consistent between groups. Transmission electron microscopy images also showed no ultrastructural remodeling for failing vs. donor mitochondria; however, the fraction of lipid droplets (LDs) in direct contact with a mitochondrion was reduced, and the average distance between an LD and its nearest neighboring mitochondrion was increased. Analysis of FA processing gene expression between donor and failing LVs revealed 0.64-fold reduced transcript levels for the mitochondrial-LD tether, perilipin 5, in the failing myocardium (P = 0.003). Thus, reduced FA use in heart failure may result from improper delivery, potentially via decreased perilipin 5 expression and mitochondrial-LD tethering, and not from intrinsic mitochondrial dysfunction.-Holzem, K. M., Vinnakota, K. C., Ravikumar, V. K., Madden, E. J., Ewald, G. A., Dikranian, K., Beard, D. A., Efimov, I. R. Mitochondrial structure and function are not different between nonfailing donor and end-stage failing human hearts. PMID:27075244

  6. Human Cardiosphere-Derived Cells From Advanced Heart Failure Patients Exhibit Augmented Functional Potency in Myocardial Repair

    PubMed Central

    Shen, Deliang; Sun, Baiming; Blusztajn, Agnieszka; Xie, Yucai; Ibrahim, Ahmed; Aminzadeh, Mohammad Amin; Liu, Weixin; Li, Tao-Sheng; De Robertis, Michele A.; Marbán, Linda; Czer, Lawrence S. C.; Trento, Alfredo; Marbán, Eduardo

    2014-01-01

    Objectives This study sought to compare the regenerative potency of cells derived from healthy and diseased human hearts. Background Results from pre-clinical studies and the CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial support the notion that cardiosphere-derived cells (CDCs) from normal and recently infarcted hearts are capable of regenerating healthy heart tissue after myocardial infarction (MI). It is unknown whether CDCs derived from advanced heart failure (HF) patients retain the same regenerative potency. Methods In a mouse model of acute MI, we compared the regenerative potential and functional benefits of CDCs derived from 3 groups: 1) non-failing (NF) donor: healthy donor hearts post-transplantation; 2) MI: patients who had an MI 9 to 35 days before biopsy; and 3) HF: advanced cardiomyopathy tissue explanted at cardiac transplantation. Results Cell growth and phenotype were identical in all 3 groups. Injection of HF CDCs led to the greatest therapeutic benefit in mice, with the highest left ventricular ejection fraction, thickest infarct wall, most viable tissue, and least scar 3 weeks after treatment. In vitro assays revealed that HF CDCs secreted higher levels of stromal cell-derived factor 1 (SDF-1), which may contribute to the cells’ augmented resistance to oxidative stress, enhanced angiogenesis, and improved myocyte survival. Histological analysis indicated that HF CDCs engrafted better, recruited more endogenous stem cells, and induced greater angiogenesis and cardiomyocyte cell-cycle re-entry. CDC-secreted SDF-1 levels correlated with decreases in scar mass over time in CADUCEUS patients treated with autologous CDCs. Conclusions CDCs from advanced HF patients exhibit augmented potency in ameliorating ventricular dysfunction post-MI, possibly through SDF-1–mediated mechanisms. PMID:24511463

  7. Positive Affect in the Midst of Distress: Implications for Role Functioning

    PubMed Central

    Moskowitz, Judith Tedlie; Shmueli-Blumberg, Dikla; Acree, Michael; Folkman, Susan

    2012-01-01

    Stress has been shown to deplete the self-regulation resources hypothesized to facilitate effective role functioning. However, recent research suggests that positive affect may help to replenish these vital self-regulation resources. Based on revised Stress and Coping theory and the Broaden-and-Build theory of positive emotion, three studies provide evidence of the potential adaptive function of positive affect in the performance of roles for participants experiencing stress. Participants were students (Study 1), caregivers of ill children (Study 2), and individuals recently diagnosed with HIV (Study 3). In cross sectional analyses, using role functioning as an indicator of self-regulation performance, we found that positive affect was significantly correlated with better self regulation performance, independent of the effects of negative affect. The effects were not as strong longitudinally, however, and there was little evidence of a reciprocal association between increases in positive affect and improvements in role functioning over time. The results provide some modest support for hypotheses stemming from the Broaden and Build model of positive emotion and revised Stress and Coping theory, both of which argue for unique adaptive functions of positive affect under stressful conditions. PMID:23175617

  8. Evolving hybrid approaches: the preservation of the 'neglected' pulmonary valve function in patients with congenital heart disease.

    PubMed

    Vida, Vladimiro L; Bacha, Emile; Stellin, Giovanni

    2016-07-01

    The involvement of the hemodynamic expertise in the operating room led to the development of new strategies aimed to improve both early and long-term outcome of patients with congenital heart disease. During the last decade, with the aim of preserving the pulmonary valve function, we embarked on a new surgical approach, which combines surgical and interventional techniques, which are performed in the operating room. We believe that the preservation of the pulmonary valve function can be extended to any patients with classic tetralogy of Fallot and other selected patients with congenital pulmonary valve hypoplasia and dysfunction. PMID:26950198

  9. The pathophysiology of heart failure.

    PubMed

    Kemp, Clinton D; Conte, John V

    2012-01-01

    Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. PMID:22227365

  10. Increasing tetrahydrobiopterin in cardiomyocytes adversely affects cardiac redox state and mitochondrial function independently of changes in NO production.

    PubMed

    Sethumadhavan, Savitha; Whitsett, Jennifer; Bennett, Brian; Ionova, Irina A; Pieper, Galen M; Vasquez-Vivar, Jeannette

    2016-04-01

    Tetrahydrobiopterin (BH4) represents a potential strategy for the treatment of cardiac remodeling, fibrosis and/or diastolic dysfunction. The effects of oral treatment with BH4 (Sapropterin™ or Kuvan™) are however dose-limiting with high dose negating functional improvements. Cardiomyocyte-specific overexpression of GTP cyclohydrolase I (mGCH) increases BH4 several-fold in the heart. Using this model, we aimed to establish the cardiomyocyte-specific responses to high levels of BH4. Quantification of BH4 and BH2 in mGCH transgenic hearts showed age-based variations in BH4:BH2 ratios. Hearts of mice (<6 months) have lower BH4:BH2 ratios than hearts of older mice while both GTPCH activity and tissue ascorbate levels were higher in hearts of young than older mice. No evident changes in nitric oxide (NO) production assessed by nitrite and endogenous iron-nitrosyl complexes were detected in any of the age groups. Increased BH4 production in cardiomyocytes resulted in a significant loss of mitochondrial function. Diminished oxygen consumption and reserve capacity was verified in mitochondria isolated from hearts of 12-month old compared to 3-month old mice, even though at 12 months an improved BH4:BH2 ratio is established. Accumulation of 4-hydroxynonenal (4-HNE) and decreased glutathione levels were found in the mGCH hearts and isolated mitochondria. Taken together, our results indicate that the ratio of BH4:BH2 does not predict changes in neither NO levels nor cellular redox state in the heart. The BH4 oxidation essentially limits the capacity of cardiomyocytes to reduce oxidant stress. Cardiomyocyte with chronically high levels of BH4 show a significant decline in redox state and mitochondrial function. PMID:26826575

  11. Comparison of muscle functional electrical stimulation to conventional bicycle exercise on endothelium and functional status indices in patients with heart failure.

    PubMed

    Deftereos, Spyridon; Giannopoulos, Georgios; Raisakis, Konstantinos; Kossyvakis, Charalampos; Kaoukis, Andreas; Driva, Metaxia; Pappas, Loukas; Panagopoulou, Vasiliki; Ntzouvara, Olga; Karavidas, Apostolos; Pyrgakis, Vlasios; Rentoukas, Ilias; Aggeli, Constadina; Stefanadis, Christodoulos

    2010-12-01

    The aim of this prospective, open-label, cohort study was to compare the effect of muscle functional electrical stimulation (FES) on endothelial function to that of conventional bicycle training. Eligible patients were those with New York Heart Association class II or III heart failure symptoms and ejection fractions ≤ 0.35. Two physical conditioning programs were delivered: FES of the muscles of the lower limbs and bicycle training, each lasting for 6 weeks, with a 6-week washout period between them. Brachial artery flow-mediated dilation (FMD) and other parameters were assessed before and after FES and the bicycle training program. FES resulted in a significant improvement in FMD, which increased from 5.9 ± 0.5% to 7.7 ± 0.5% (95% confidence interval for the difference 1.5% to 2.3%, p < 0.001). Bicycle training also resulted in a substantial improvement of endothelial function. FMD increased from 6.2 ± 0.4% to 9.2 ± 0.4% (95% confidence interval for the difference 2.5% to 3.5%, p < 0.001). FES was associated with a 41% relative increase in FMD, compared to 57% with bicycle exercise (95% confidence interval for the difference between the relative changes 1.2% to 30.5%, p = 0.034). This resulted in attaining a significantly higher FMD value after bicycle training compared to FES (9.2 ± 0.4% vs 7.7 ± 0.5%, p < 0.001). In conclusion, the effect of muscle FES in patients with heart failure on endothelial function, although not equivalent to that of conventional exercise, is substantial. Muscle FES protocols may prove very useful in the treatment of patients with heart failure who cannot or will not adhere to conventional exercise programs. PMID:21094364

  12. Short-term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats

    PubMed Central

    LI, YAN; XUAN, YAN-HUA; LIU, SHUANG-SHUANG; DONG, JING; LUO, JIA-YING; SUN, ZHI-JUN

    2015-01-01

    Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055

  13. LACK OF MYOGLOBIN FUNCTION IN THE ISOLATED PERFUSED BUFFALO SCULPIN (ENOPHRYS BISON) HEART

    EPA Science Inventory

    The contribution of myoglobin to cardiac performance and O2 consumption was investigated using an isolated perfused buffalo sculpin (Enophrys bison) heart preparation. ose-response studies at ambient (150 Torr)(l Torr=l33.322 Pa) O2 tensions were conducted as a means of selecting...

  14. THE CIRCADIAN CLOCK WITHIN THE HEART: POTENTIAL INFLUENCE ON MYOCARDIAL GENE EXPRESSION, METABOLISM, AND FUNCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is becoming increasingly clear that the intrinsic properties of both the heart and vasculature exhibit dramatic oscillations over the course of the day. Diurnal variations in the responsiveness of the cardiovascular system to environmental stimuli are mediated by a complex interplay between extra...

  15. Remote heart function monitoring: role of the CardioMEMS HF System.

    PubMed

    Vanoli, Emilio; D'Elia, Emilia; La Rovere, Maria T; Gronda, Edoardo

    2016-07-01

    Heart failure is a pandemic condition that is challenging cardiology today. The primary economical and social burden of this syndrome is hospitalization rate whose costs represent the highest ones within the entire healthcare management. Remote monitoring of physiological data, obtained through self-reporting via telephone calls or, automatically, using external devices is a potential novel approach to implement management of patients with heart failure and reduce hospitalization rates. Relatively large but, sometimes, contradicting information exists about the efficacy of remote monitoring via different noninvasive approaches to reduce the economical and social burden of heart failure management. This leaves still partly unaddressed this critical issue and generates the need for new approaches. In this context, the CardioMEMS device that can chronically monitor pulmonary pressures from a small microchip inserted transvenously in the pulmonary artery seems to represent an innovative tool to challenge hospitalization rates. Consecutive analyses from the CHAMPION study had indeed documented the efficacy of the CardioMEMS in the remote monitoring of the pulmonary circulation status of patients with heart failure and in providing adequate information to optimally manage such patients with the final result of a significant hospitalization rate reduction. The striking information here is that this appears to be true in patients with preserved left ventricular ejection fraction also. Overall, the reports from the CHAMPION study encourage the use of CardioMEMS but larger populations are needed to definitively prove its value. PMID:26881785

  16. Total heart volume as a function of clinical and anthropometric parameters in a population of external beam radiation therapy patients

    NASA Astrophysics Data System (ADS)

    Nadège Ilembe Badouna, Audrey; Veres, Cristina; Haddy, Nadia; Bidault, François; Lefkopoulos, Dimitri; Chavaudra, Jean; Bridier, André; de Vathaire, Florent; Diallo, Ibrahima

    2012-01-01

    The aim of this paper was to determine anthropometric parameters leading to the least uncertain estimate of heart size when connecting a computational phantom to an external beam radiation therapy (EBRT) patient. From computed tomography images, we segmented the heart and calculated its total volume (THV) in a population of 270 EBRT patients of both sexes, aged 0.7-83 years. Our data were fitted using logistic growth functions. The patient age, height, weight, body mass index and body surface area (BSA) were used as explanatory variables. For both genders, good fits were obtained with both weight (R2 = 0.89 for males and 0.83 for females) and BSA (R2 = 0.90 for males and 0.84 for females). These results demonstrate that, among anthropometric parameters, weight plays an important role in predicting THV. These findings should be taken into account when assigning a computational phantom to a patient.

  17. Functional Amyloid Signaling via the Inflammasome, Necrosome, and Signalosome: New Therapeutic Targets in Heart Failure

    PubMed Central

    Parry, Traci L.; Melehani, Jason H.; Ranek, Mark J.; Willis, Monte S.

    2015-01-01

    As the most common cause of death and disability, globally, heart disease remains an incompletely understood enigma. A growing number of cardiac diseases are being characterized by the presence of misfolded proteins underlying their pathophysiology, including cardiac amyloidosis and dilated cardiomyopathy (DCM). At least nine precursor proteins have been implicated in the development of cardiac amyloidosis, most commonly caused by multiple myeloma light chain disease and disease-causing mutant or wildtype transthyretin (TTR). Similarly, aggregates with PSEN1 and COFILIN-2 have been identified in up to one-third of idiopathic DCM cases studied, indicating the potential predominance of misfolded proteins in heart failure. In this review, we present recent evidence linking misfolded proteins mechanistically with heart failure and present multiple lines of new therapeutic approaches that target the prevention of misfolded proteins in cardiac TTR amyloid disease. These include multiple small molecule pharmacological chaperones now in clinical trials designed specifically to support TTR folding by rational design, such as tafamidis, and chaperones previously developed for other purposes, such as doxycycline and tauroursodeoxycholic acid. Last, we present newly discovered non-pathological “functional” amyloid structures, such as the inflammasome and necrosome signaling complexes, which can be activated directly by amyloid. These may represent future targets to successfully attenuate amyloid-induced proteotoxicity in heart failure, as the inflammasome, for example, is being therapeutically inhibited experimentally in autoimmune disease. Together, these studies demonstrate multiple novel points in which new therapies may be used to primarily prevent misfolded proteins or to inhibit their downstream amyloid-mediated effectors, such as the inflammasome, to prevent proteotoxicity in heart failure. PMID:26664897

  18. The bHLH Transcription Factor Hand Regulates the Expression of Genes Critical to Heart and Muscle Function in Drosophila melanogaster

    PubMed Central

    Hallier, Benjamin; Hoffmann, Julia; Roeder, Thomas; Tögel, Markus; Meyer, Heiko; Paululat, Achim

    2015-01-01

    Hand proteins belong to the highly conserved family of basic Helix-Loop-Helix transcription factors and are critical to distinct developmental processes, including cardiogenesis and neurogenesis in vertebrates. In Drosophila melanogaster a single orthologous hand gene is expressed with absence of the respective protein causing semilethality during early larval instars. Surviving adult animals suffer from shortened lifespan associated with a disorganized myofibrillar structure being apparent in the dorsal vessel, the wing hearts and in midgut tissue. Based on these data, the major biological significance of Hand seems to be related to muscle development, maintenance or function; however, up to now the physiological basis for Hand functionality remains elusive. Thus, the identification of genes whose expression is, directly or indirectly, regulated by Hand has considerable relevance with respect to understanding its biological functionality in flies and vertebrates. Beneficially, hand mutants are viable and exhibit affected tissues, which renders Drosophila an ideal model to investigate up- or downregulated target genes by a comparative microarray approach focusing on the respective tissues from mutant specimens. Our present work reveals for the first time that Drosophila Hand regulates the expression of numerous genes of diverse physiological relevancy, including distinct factors required for proper muscle development and function such as Zasp52 or Msp-300. These results relate Hand activity to muscle integrity and functionality and may thus be highly beneficial to the evaluation of corresponding hand phenotypes. PMID:26252215

  19. Maternal depression and the heart of parenting: respiratory sinus arrhythmia and affective dynamics during parent-adolescent interactions.

    PubMed

    Connell, Arin M; Hughes-Scalise, Abigail; Klostermann, Susan; Azem, Talla

    2011-10-01

    Maternal depression is associated with problematic parenting and the development of emotional and behavior problems in children and adolescents. While emotional regulatory abilities are likely to influence emotional exchanges between parents and teens, surprisingly little is known about the role of emotion regulation during parent-child interactions, particularly in high-risk families. Respiratory sinus arrhythmia (RSA) has been widely linked to emotion regulatory abilities in recent research, and the current study investigated RSA and maternal depression in relation to dyadic flexibility, as well as mutuality of negative and positive affect displayed during three discussion tasks between 59 mother-adolescent pairs (age 11-17 years). Dyadic flexibility was predicted by the interaction of maternal depression, maternal RSA, and teen RSA, with higher maternal RSA predicting greater dyadic flexibility, particularly in highest risk dyads (i.e., elevated maternal depression and lower teen RSA). Teen RSA interacted with maternal depression to predict mutual negative affect, serving as a protective factor. Finally, maternal and teen RSA interacted to predict mutual positive affect, with maternal RSA buffering against low teen RSA to predict higher mutual positive affect. Results support the role of RSA in affectively laden interactions between parents and adolescents, particularly in the face of maternal depression. PMID:21875198

  20. Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats

    PubMed Central

    Habibi, Parisa; Alihemmati, Alireza; NourAzar, Alireza; Yousefi, Hadi; Mortazavi, Safieh; Ahmadiasl, Nasser

    2016-01-01

    Objective(s): The beneficial and more potent role of exercise to prevent heart apoptosis in ovariectomized rats has been known. The aim of this study was to examine the effects of swimming training on cardiac expression of Bcl-2, and Mir-133 levels and glycogen changes in the myocyte. Materials and Methods: Forty animals were separated into four groups as control, sham, ovariectomy (OVX) and ovariectomized group with 8 weeks swimming training (OVX.E). Training effects were evaluated by measuring lipid profiles, Bcl-2 and Mir-133 expression levels in the cardiac tissue. Grafts were analyzed by reverse transcription–polymerase chain reaction for Bcl-2 mRNA and Mir-133 and by Western blot for Bcl-2 protein. Results: Ovariectomy down-regulated Bcl-2 and Mir-133 expression levels in the cardiac tissue, and swimming training up-regulated their expression significantly (P<0.05). Conclusion: Our results showed that regular exercise as a physical replacement therapy could prevent and improve the effects of estrogen deficiency in the cardia. PMID:27279981

  1. Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

    PubMed Central

    Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

  2. NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets

    PubMed Central

    Bouveret, Romaric; Waardenberg, Ashley J; Schonrock, Nicole; Ramialison, Mirana; Doan, Tram; de Jong, Danielle; Bondue, Antoine; Kaur, Gurpreet; Mohamed, Stephanie; Fonoudi, Hananeh; Chen, Chiann-mun; Wouters, Merridee A; Bhattacharya, Shoumo; Plachta, Nicolas; Dunwoodie, Sally L; Chapman, Gavin; Blanpain, Cédric; Harvey, Richard P

    2015-01-01

    We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off-targets", and retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease. DOI: http://dx.doi.org/10.7554/eLife.06942.001 PMID:26146939

  3. Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.

    PubMed

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

  4. FREEDOM, SYNTAX, FAME and FUNCTIONALITY: the future of surgical revascularization in stable ischemic heart disease.

    PubMed

    Ferguson, T Bruce; Chen, Cheng

    2014-01-01

    At the age of nearly 50 years, the procedure of coronary artery bypass grafting (CABG) now has the most solid evidence supporting its role in revascularization for stable ischemic heart disease in its history. In what is a relatively infrequent occurrence in medicine, the results from large-scale observational database analyses are now aligned with and supported by data from recent randomized trials, providing important contemporary evidence in support of CABG. However, even with strong evidence, the changing landscape of revascularization for stable ischemic heart disease threatens to make this evidence irrelevant in deciding which patients should be referred for CABG in the future. How the procedure of CABG could be modified and optimized for incorporation into this new landscape is discussed in this article. PMID:24344664

  5. Cardiac function estimation from MRI using a heart model and data assimilation: advances and difficulties.

    PubMed

    Sermesant, M; Moireau, P; Camara, O; Sainte-Marie, J; Andriantsimiavona, R; Cimrman, R; Hill, D L G; Chapelle, D; Razavi, R

    2006-08-01

    In this paper, we present a framework to estimate local ventricular myocardium contractility using clinical MRI, a heart model and data assimilation. First, we build a generic anatomical model of the ventricles including muscle fibre orientations and anatomical subdivisions. Then, this model is deformed to fit a clinical MRI, using a semi-automatic fuzzy segmentation, an affine registration method and a local deformable biomechanical model. An electromechanical model of the heart is then presented and simulated. Finally, a data assimilation procedure is described, and applied to this model. Data assimilation makes it possible to estimate local contractility from given displacements. Presented results on fitting to patient-specific anatomy and assimilation with simulated data are very promising. Current work on model calibration and estimation of patient parameters opens up possibilities to apply this framework in a clinical environment. PMID:16765630

  6. Affect and the Brain's Functional Organization: A Resting-State Connectivity Approach

    PubMed Central

    Rohr, Christiane S.; Okon-Singer, Hadas; Craddock, R. Cameron; Villringer, Arno; Margulies, Daniel S.

    2013-01-01

    The question of how affective processing is organized in the brain is still a matter of controversial discussions. Based on previous initial evidence, several suggestions have been put forward regarding the involved brain areas: (a) right-lateralized dominance in emotional processing, (b) hemispheric dominance according to positive or negative valence, (c) one network for all emotional processing and (d) region-specific discrete emotion matching. We examined these hypotheses by investigating intrinsic functional connectivity patterns that covary with results of the Positive and Negative Affective Schedule (PANAS) from 65 participants. This approach has the advantage of being able to test connectivity rather than activation, and not requiring a potentially confounding task. Voxelwise functional connectivity from 200 regions-of-interest covering the whole brain was assessed. Positive and negative affect covaried with functional connectivity involving a shared set of regions, including the medial prefrontal cortex, the anterior cingulate, the visual cortex and the cerebellum. In addition, each affective domain had unique connectivity patterns, and the lateralization index showed a right hemispheric dominance for negative affect. Therefore, our results suggest a predominantly right-hemispheric network with affect-specific elements as the underlying organization of emotional processes. PMID:23935850

  7. Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function-A Magnetic Resonance Image Study

    PubMed Central

    Lin, Lian-Yu; Su, Mao-Yuan M.; Pham, Van-Truong; Tran, Thi-Thao; Wang, Yung-Hung; Tseng, Wen-Yih I.; Lo, Men-Tzung; Lin, Jiunn-Lee

    2016-01-01

    Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function. PMID:26876005

  8. Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function--A Magnetic Resonance Image Study.

    PubMed

    Lin, Lian-Yu; Su, Mao-Yuan M; Pham, Van-Truong; Tran, Thi-Thao; Wang, Yung-Hung; Tseng, Wen-Yih I; Lo, Men-Tzung; Lin, Jiunn-Lee

    2016-01-01

    Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function. PMID:26876005

  9. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction).

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-05-01

    Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. PMID:27056419

  10. Optimization of a Model Corrected Blood Input Function from Dynamic FDG-PET Images of Small Animal Heart In Vivo.

    PubMed

    Zhong, Min; Kundu, Bijoy K

    2013-10-01

    Quantitative evaluation of dynamic Positron Emission Tomography (PET) of mouse heart in vivo is challenging due to the small size of the heart and limited intrinsic spatial resolution of the PET scanner. Here, we optimized a compartment model which can simultaneously correct for spill over and partial volume effects for both blood pool and the myocardium, compute kinetic rate parameters and generate model corrected blood input function (MCBIF) from ordered subset expectation maximization - maximum a posteriori (OSEM-MAP) cardiac and respiratory gated (18)F-FDG PET images of mouse heart with attenuation correction in vivo, without any invasive blood sampling. Arterial blood samples were collected from a single mouse to indicate the feasibility of the proposed method. In order to establish statistical significance, venous blood samples from n=6 mice were obtained at 2 late time points, when SP contamination from the tissue to the blood is maximum. We observed that correct bounds and initial guesses for the PV and SP coefficients accurately model the wash-in and wash-out dynamics of the tracer from mouse blood. The residual plot indicated an average difference of about 1.7% between the blood samples and MCBIF. The downstream rate of myocardial FDG influx constant, Ki (0.15±0.03 min(-1)), compared well with Ki obtained from arterial blood samples (P=0.716). In conclusion, the proposed methodology is not only quantitative but also reproducible. PMID:24741130

  11. Neonatal transfer of membrane-bound stem cell factor improves survival and heart function in aged mice after myocardial ischemia.

    PubMed

    Sun, Zhuo; Lee, Chyan-Jang; Mejia-Guerrero, Salvador; Zhang, Yuemei; Higuchi, Koji; Li, Ren-Ke; Medin, Jeffrey A

    2012-12-01

    Stem cell mobilization to injured tissue contributes to neovascularization, resulting in regeneration after myocardial infarction (MI). We previously showed that direct cardiac injection of a recombinant lentivirus (LV) that engineers expression of membrane-bound stem cell factor (mSCF) improves outcomes immediately after MI. In this study, we evaluated the effect of neonatal LV/mSCF transduction on MI outcomes in aged mice. We constructed a recombinant LV harboring an α-myosin heavy chain promoter that drives mSCF expression and injected it into the temporal vein of neonatal mice. One year later, sustained expression of mSCF in the adult mouse hearts was detected by genomic and quantitative RT-PCR and immunohistochemistry. To evaluate the contribution of neonatal LV/mSCF delivery to recovery from MI, we induced an MI in adult LV/mSCF-transduced, LV only-transduced, and nontransduced control mice. Strikingly, LV/mSCF transduction reduced infarct scar size, enhanced angiogenesis, improved ventricular function, and significantly increased survival of the mice. Regional overexpression of CD11b, a marker of monocytes and proangiogenic cells, was observed on monocytes isolated from the infarcted hearts of LV/mSCF-transduced mice. Our data suggest a model of neonatal gene delivery that leads to sustained mSCF expression during adulthood to aid recovery from MI and prevent heart failure. PMID:22998370

  12. Plant Species and Functional Group Combinations Affect Green Roof Ecosystem Functions

    PubMed Central

    Lundholm, Jeremy; MacIvor, J. Scott; MacDougall, Zachary; Ranalli, Melissa

    2010-01-01

    Background Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. Methodology/Principal Findings We used a replicated modular extensive (shallow growing- medium) green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. Conclusions/Significance Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or facilitation as mechanisms

  13. Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5

    PubMed Central

    Jia, Haibo; King, Isabelle N.; Chopra, Sameer S.; Wan, Haiyan; Ni, Terri T.; Jiang, Charlie; Guan, Xiaoqun; Wells, Sam; Srivastava, Deepak; Zhong, Tao P.

    2007-01-01

    Embryonic organs attain their final dimensions through the generation of proper cell number and size, but the control mechanisms remain obscure. Here, we establish Gridlock (Grl), a Hairy-related basic helix–loop–helix (bHLH) transcription factor, as a negative regulator of cardiomyocyte proliferative growth in zebrafish embryos. Mutations in grl cause an increase in expression of a group of immediate-early growth genes, myocardial genes, and development of hyperplastic hearts. Conversely, cardiomyocytes with augmented Grl activity have diminished cell volume and fail to divide, resulting in a marked reduction in heart size. Both bHLH domain and carboxyl region are required for Grl negative control of myocardial proliferative growth. These Grl-induced cardiac effects are counterbalanced by the transcriptional activator Gata5 but not Gata4, which promotes cardiomyocyte expansion in the embryo. Biochemical analyses show that Grl forms a complex with Gata5 through the carboxyl region and can repress Gata5-mediated transcription via the bHLH domain. Hence, our studies suggest that Grl regulates embryonic heart growth via opposing Gata5, at least in part through their protein interactions in modulating gene expression. PMID:17715064

  14. Effect of a Tibetan herbal mixture on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation.

    PubMed

    Schäfer, Daniela; Lambrecht, Julia; Radtke, Thomas; Wilhelm, Matthias; Saner, Hugo

    2015-08-01

    In this 6-week prospective, randomized, placebo-controlled and double-blind study, we investigated the effects of a natural herbal remedy based on a recipe from Tibet (Padma® 28), on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation in 80 coronary artery disease (CAD) patients (age 66 ± 8 years) on guideline-based medication for secondary prevention. We found no significant effects of Padma 28 and conclude that the addition of Padma 28 to guideline-based secondary prevention treatment of CAD did not lead to significant effects on important surrogate markers in elderly male CAD patients. PMID:25208904

  15. Plant sterols: factors affecting their efficacy and safety as functional food ingredients

    PubMed Central

    Berger, Alvin; Jones, Peter JH; Abumweis, Suhad S

    2004-01-01

    Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status. PMID:15070410

  16. Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development

    PubMed Central

    Van Laarhoven, Peter M.; Neitzel, Leif R.; Quintana, Anita M; Geiger, Elizabeth A.; Zackai, Elaine H.; Clouthier, David E.; Artinger, Kristin B.; Ming, Jeffrey E.; Shaikh, Tamim H.

    2015-01-01

    Kabuki syndrome (KS) is a rare multiple congenital anomaly syndrome characterized by distinctive facial features, global developmental delay, intellectual disability and cardiovascular and musculoskeletal abnormalities. While mutations in KMT2D have been identified in a majority of KS patients, a few patients have mutations in KDM6A. We analyzed 40 individuals clinically diagnosed with KS for mutations in KMT2D and KDM6A. Mutations were detected in KMT2D in 12 and KDM6A in 4 cases, respectively. Observed mutations included single-nucleotide variations and indels leading to frame shifts, nonsense, missense or splice-site alterations. In two cases, we discovered overlapping chromosome X microdeletions containing KDM6A. To further elucidate the functional roles of KMT2D and KDM6A, we knocked down the expression of their orthologs in zebrafish. Following knockdown of kmt2d and the two zebrafish paralogs kdm6a and kdm6al, we analyzed morphants for developmental abnormalities in tissues that are affected in individuals with KS, including craniofacial structures, heart and brain. The kmt2d morphants exhibited severe abnormalities in all tissues examined. Although the kdm6a and kdm6al morphants had similar brain abnormalities, kdm6a morphants exhibited craniofacial phenotypes, whereas kdm6al morphants had prominent defects in heart development. Our results provide further support for the similar roles of KMT2D and KDM6A in the etiology of KS by using a vertebrate model organism to provide direct evidence of their roles in the development of organs and tissues affected in KS patients. PMID:25972376

  17. Proposal for a functional classification system of heart failure in patients with end-stage renal disease: proceedings of the acute dialysis quality initiative (ADQI) XI workgroup.

    PubMed

    Chawla, Lakhmir S; Herzog, Charles A; Costanzo, Maria Rosa; Tumlin, James; Kellum, John A; McCullough, Peter A; Ronco, Claudio

    2014-04-01

    Structural heart disease is highly prevalent in patients with chronic kidney disease requiring dialysis. More than 80% of patients with end-stage renal disease (ESRD) are reported to have cardiovascular disease. This observation has enormous clinical relevance because the leading causes of death for patients with ESRD are of cardiovascular disease etiology, including heart failure, myocardial infarction, and sudden cardiac death. The 2 systems most commonly used to classify the severity of heart failure are the New York Heart Association (NYHA) functional classification and the American Heart Association (AHA)/American College of Cardiology (ACC) staging system. With rare exceptions, patients with ESRD who do not receive renal replacement therapy (RRT) develop signs and symptoms of heart failure, including dyspnea and edema due to inability of the severely diseased kidneys to excrete sodium and water. Thus, by definition, nearly all patients with ESRD develop a symptomatology consistent with heart failure if fluid removal by RRT is delayed. Neither the AHA/ACC heart failure staging nor the NYHA functional classification system identifies the variable symptomatology that patients with ESRD experience depending upon whether evaluation occurs before or after fluid removal by RRT. Consequently, the incidence, severity, and outcomes of heart failure in patients with ESRD are poorly characterized. The 11th Acute Dialysis Quality Initiative has identified this issue as a critical unmet need for the proper evaluation and treatment of heart failure in patients with ESRD. We propose a classification schema based on patient-reported dyspnea assessed both pre- and post-ultrafiltration, in conjunction with echocardiography. PMID:24530671

  18. Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

    PubMed Central

    Saito, Saho; Saito, Wataru; Saito, Michiyuki; Hashimoto, Yuki; Mori, Shohei; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2015-01-01

    Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients. PMID:25919689

  19. Contributions of Comorbid Diabetes to Sleep Characteristics, Daytime Symptoms, and Physical Function among Patients with Stable Heart Failure

    PubMed Central

    Fritschi, Cynthia; Redeker, Nancy S.

    2014-01-01

    Background Diabetes (DM) and heart failure (HF) are often comorbid. Sleep disturbances, poor physical functioning, and high levels of daytime symptoms are prevalent and contribute to poor quality of life in both populations. However, little is known about the independent and additive effects of comorbid DM on sleep, physical function, and daytime symptoms among patients with HF. Objective To investigate the extent to which comorbid DM confers independent and additive effects on sleep disturbance, physical functioning, and symptoms among patients with stable HF. Methods This secondary analysis was conducted on a sample of 173 stable Class II-IV HF patients. Self-report and polysomnography were used to measure sleep quality, objective sleep characteristics, and sleep disordered breathing. Physical function measures included wrist actigraphy, the six minute walk test, and the SF-36 Physical Component Summary Score. Fatigue, sleepiness, and depression were also measured. Univariate analyses and hierarchical regression models were computed. Results The sample included 173 (n = 119/68% HF and n = 54/32% HF plus DM) patients (age 60.4 ± 16.1 years). In analyses adjusted for age, gender, BMI, and NY Heart Association classification, HF patients with DM had longer sleep latency and spent a greater percentage of time awake after sleep onset (WASO %] than the HF patients who did not have DM (all p < .05). There were no statistically significant differences in respiratory disturbance index (RDI) or self-reported sleep quality. Sleep duration was low in both groups. Patients with DM had shorter 6MWT distance, lower ratio of daytime to nighttime activity, and lower general health and self-reported physical function. Hierarchical regression models revealed that age and DM were the only significant correlates of the sleep variables, while age, gender, NYHA class, and DM were all associated with 6MWT distance. Conclusions Comorbid DM contributes independent and additive effects on

  20. Simple Measures of Function and Symptoms in Hospitalized Heart Failure Patients Predict Short-Term Cardiac Event-Free Survival

    PubMed Central

    Cataldo, Janine; Mackin, Lynda

    2014-01-01

    Background. Heart failure (HF) is a prevalent chronic condition where patients experience numerous uncomfortable symptoms, low functional status, and high mortality rates. Objective. To determine whether function and/or symptoms predict cardiac event-free survival in hospitalized HF patients within 90 days of hospital discharge. Methods. Inpatients (N = 32) had HF symptoms assessed with 4 yes/no questions. Function was determined with NYHA Classification, Katz Index of Activities of Daily Living (ADLs), and directly with the short physical performance battery (SPPB). Survival was analyzed with time to the first postdischarge cardiac event with events defined as cardiac rehospitalization, heart transplantation, or death. Results. Mean age was 58.2 ± 13.6 years. Patient reported ADL function was nearly independent (5.6 ± 1.1) while direct measure (SPPB) showed moderate functional limitation (6.4 ± 3.1). Within 90 days, 40.6% patients had a cardiac event. At discharge, each increase in NYHA Classification was associated with a 3.4-fold higher risk of cardiac events (95% CI 1.4–8.5). Patients reporting symptoms of dyspnea, fatigue, and orthopnea before discharge had a 4.0-fold, 9.7-fold, and 12.8-fold, respectively, greater risk of cardiac events (95% CI 1.2–13.2; 1.2–75.1; 1.7–99.7). Conclusions. Simple assessments of function and symptoms easily performed at discharge may predict short-term cardiac outcomes in hospitalized HF patients. PMID:24672717

  1. Ramp Study Hemodynamics, Functional Capacity, and Outcome in Heart Failure Patients with Continuous-Flow Left Ventricular Assist Devices.

    PubMed

    Jung, Mette H; Gustafsson, Finn; Houston, Brian; Russell, Stuart D

    2016-01-01

    Ramp studies-measuring changes in cardiac parameters as a function of serial pump speed changes (revolutions per minute [rpm])-are increasingly used to evaluate function and malfunction of continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that ramp studies can predict functional capacity, quality of life (QOL), and survival in CF-LVAD patients. Hemodynamic changes per Δrpm were measured at a minimum of CF-LVAD support, at baseline pump speed, and at maximal tolerable pump speed. Subsequently functional capacity and QOL were assessed. Eighty ramp tests were performed in 44 patients (HeartMate II, Thoratec Corporation, Pleasanton, CA). Functional status was evaluated in 70% (31/44); average 6 minute walk test (6MWT) was 312 ± 220 min, New York Heart Association (NYHA) I-II/III-IV (70/30%) and activity scores very low-low/moderate-very high (55/45%). Decrease in pulmonary capillary wedge pressure per Δrpm was related to better NYHA classification; NYHA I-II vs. III-IV, -0.29 ± 0.15 vs. -0.09 ± 0.16 mm Hg/rpm * 10 (p = 0.007) as well as to activity score; very low-low vs. moderate-very high, -0.16 ± 0.16 vs. -0.31 ± 0.16 mm Hg/rpm * 10 (p = 0.02). Cardiac output change per Δrpm was correlated to measures of QOL. Ramp tests did not predict survival. In conclusion, hemodynamic changes during ramp studies are associated with measures of functional capacity and QOL. Hence, such tests could potentially identify patients in risk of failure to thrive during CF-LVAD support. PMID:27195741

  2. Peripheral chemoreceptor control of cardiovascular function at rest and during exercise in heart failure patients.

    PubMed

    Edgell, Heather; McMurtry, M Sean; Haykowsky, Mark J; Paterson, Ian; Ezekowitz, Justin A; Dyck, Jason R B; Stickland, Michael K

    2015-04-01

    Peripheral chemoreceptor activity/sensitivity is enhanced in chronic heart failure (HF), and sensitivity is linked to greater mortality. This study aimed to determine the role of the peripheral chemoreceptor in cardiovascular control at rest and during exercise in HF patients and controls. Clinically stable HF patients (n = 11; ejection fraction: 39 ± 5%) and risk-matched controls (n = 10; ejection fraction: 65 ± 2%) performed randomized trials with or without dopamine infusion (2 μg·min(-1)·kg(-1)) at rest and during 40% maximal voluntary contraction handgrip (HG) exercise, and a resting trial of 2 min of inspired 100% oxygen. Both dopamine and hyperoxia were used to inhibit the peripheral chemoreceptor. At rest in HF patients, dopamine decreased ventilation (P = 0.02), decreased total peripheral resistance index (P = 0.003), and increased cardiac and stroke indexes (P ≤ 0.01), yet there was no effect of dopamine on these variables in controls (P ≥ 0.7). Hyperoxia lowered ventilation in HF (P = 0.01), but not in controls (P = 0.9), indicating suppression of the peripheral chemoreceptors in HF. However, no decrease of total peripheral resistance index was observed in HF. As expected, HG increased heart rate, ventilation, and brachial conductance of the nonexercising arm in controls and HF patients. During dopamine infusion, there were no changes in mean arterial pressure, heart rate, or ventilation responses to HG in either group (P ≥ 0.26); however, brachial conductance increased with dopamine in the control group (P = 0.004), but decreased in HF (P = 0.02). Our findings indicate that the peripheral chemoreceptor contributes to cardiovascular control at rest in HF patients and during exercise in risk-matched controls. PMID:25614600

  3. Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    McMahon, Camilla M.; Henderson, Heather A.; Newell, Lisa; Jaime, Mark; Mundy, Peter

    2016-01-01

    Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical…

  4. Automatic Processing of Emotional Faces in High-Functioning Pervasive Developmental Disorders: An Affective Priming Study

    ERIC Educational Resources Information Center

    Kamio, Yoko; Wolf, Julie; Fein, Deborah

    2006-01-01

    This study examined automatic processing of emotional faces in individuals with high-functioning Pervasive Developmental Disorders (HFPDD) using an affective priming paradigm. Sixteen participants (HFPDD and matched controls) were presented with happy faces, fearful faces or objects in both subliminal and supraliminal exposure conditions, followed…

  5. Handgrip Strength, Positive Affect, and Perceived Health Are Prospectively Associated with Fewer Functional Limitations among Centenarians

    ERIC Educational Resources Information Center

    Franke, Warren D.; Margrett, Jennifer A.; Heinz, Melinda; Martin, Peter

    2012-01-01

    This study assessed the association between perceived health, fatigue, positive and negative affect, handgrip strength, objectively measured physical activity, body mass index, and self-reported functional limitations, assessed 6 months later, among 11 centenarians (age = 102 plus or minus 1). Activities of daily living, assessed 6 months prior to…

  6. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  7. Chronic treatment with Carvedilol improves ventricular function and reduces myocyte apoptosis in an animal model of heart failure

    PubMed Central

    Okafor, Chukwuka C; Perreault-Micale, Cynthia; Hajjar, Roger J; Lebeche, Djamel; Skiroman, Klara; Jabbour, George; Doye, Angelia A; Lee, Michael X; Laste, Nancy; Gwathmey, Judith K

    2003-01-01

    Background β-blocker treatment has emerged as an effective treatment modality for heart failure. Interestingly, β-blockers can activate both pro-apoptotic and anti-apoptotic pathways. Nevertheless, the mechanism for improved cardiac function seen with β-blocker treatment remains largely unknown. Carvedilol is a non-selective β-blocker with α-receptor blockade and antioxidant properties. We therefore studied the impact of the effects of carvedilol in an animal model of end-stage heart failure. Results To test whether chronic treatment with β-blockade decreases apoptosis, we treated myopathic turkeys with two dosages of carvedilol, 1 mg/kg (DCM1) and 20 mg/kg (DCM20), for four weeks and compared them to non-treated DCM animals (DCM0) and to control turkeys (CON). Echocardiographic measurements showed that non-treated DCM animals had a significantly lower fractional shortening (FS) when compared to CON (68.73 ± 1.37 vs. 18.76 ± 0.59%, p < 0.001). Both doses of carvedilol significantly improved FS (33.83 ± 10.11 and 27.73 ± 6.18% vs. 18.76 ± 0.59 % for untreated DCM, p < 0.001). DCM left ventricles were characterized by a higher percentage of apoptotic nuclei when compared to CON (5.64 ± 0.49 vs. 1.72 ± 0.12%, respectively p < 0.001). Both doses of carvedilol significantly reduced the number of apoptotic nuclei (2.32 ± 0.23% and 2.36 ± 0.26% 1 mg and 20 mg/kg respectively). Conclusions Carvedilol improves ventricular function. Furthermore, treatment with carvedilol decreased the incidence of apoptosis in cardiac myocytes from failing hearts at both doses. These data suggest that the inhibition of apoptosis with carvedilol may lead to improvement in ventricular function and may underlie a beneficial effect of β-blockade independent of heart rate lowering effects. PMID:12873352

  8. Automatic facial responses to affective stimuli in high-functioning adults with autism spectrum disorder.

    PubMed

    Mathersul, Danielle; McDonald, Skye; Rushby, Jacqueline A

    2013-01-17

    Individuals with autism spectrum disorder (ASD) demonstrate atypical behavioural responses to affective stimuli, although the underlying mechanisms remain unclear. Investigating automatic responses to these stimuli may help elucidate these mechanisms. 18 high-functioning adults with ASDs and 18 typically developing controls viewed 54 extreme pleasant (erotica), extreme unpleasant (mutilations), and non-social neutral images from the International Affective Picture System (IAPS). Two-thirds of images received an acoustic startle probe 3s post-picture onset. Facial electromyography (EMG) activity (orbicularis, zygomaticus, corrugator), skin conductance (SCR) and cardiac responses were recorded. The adults with ASDs demonstrated typical affective startle modulation and automatic facial EMG responses but atypical autonomic (SCRs and cardiac) responses, suggesting a failure to orient to, or a deliberate effort to disconnect from, socially relevant stimuli (erotica, mutilations). These results have implications for neural systems known to underlie affective processes, including the orbitofrontal cortex and amygdala. PMID:23142408

  9. Interventricular heterogeneity in rat heart responses to hypoxia: the tuning of glucose metabolism, ion gradients, and function.

    PubMed

    Komniski, Milena Segato; Yakushev, Sergej; Bogdanov, Nikolai; Gassmann, Max; Bogdanova, Anna

    2011-05-01

    The matching of energy supply and demand under hypoxic conditions is critical for sustaining myocardial function. Numerous reports indicate that basal energy requirements and ion handling may differ between the ventricles. We hypothesized that ventricular response to hypoxia shows interventricular differences caused by the heterogeneity in glucose metabolism and expression and activity of ion transporters. Thus we assessed glucose utilization rate, ATP, sodium and potassium concentrations, Na, K-ATPase activity, and tissue reduced:oxidized glutathione (GSH/GSSG) content in the right and left ventricles before and after the exposure of either the whole animals or isolated blood-perfused hearts to hypoxia. The hypoxia-induced boost in glucose utilization was more pronounced in the left ventricle compared with the right one. ATP levels in the right ventricle of hypoxic heart were lower than those in the left ventricle. Left ventricular sodium content was higher, and hydrolytic Na, K-ATPase activity was reduced compared with the right ventricle. Administration of the Na, K-ATPase blocker ouabain caused rapid increase in the right ventricular Na(+) and elimination of the interventricular Na(+) gradients. Exposure of the hearts to hypoxia made the interventricular heterogeneity in the Na(+) distribution even more pronounced. Furthermore, systemic hypoxia caused oxidative stress that was more pronounced in the right ventricle as revealed by GSH/GSSG ratios. On the basis of these findings, we suggest that the right ventricle is more prone to hypoxic damage, as it is less efficient in recruiting glucose as an alternative fuel and is particularly dependent on the efficient Na, K-ATPase function. PMID:21398597

  10. Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association.

    PubMed

    Pennell, Dudley J; Udelson, James E; Arai, Andrew E; Bozkurt, Biykem; Cohen, Alan R; Galanello, Renzo; Hoffman, Timothy M; Kiernan, Michael S; Lerakis, Stamatios; Piga, Antonio; Porter, John B; Walker, John Malcolm; Wood, John

    2013-07-16

    This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non-cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a

  11. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function

    PubMed Central

    Shi, Xiao; Walter, Nicole A. R.; Harkness, John H.; Neve, Kim A.; Williams, Robert W.; Lu, Lu; Belknap, John K.; Eshleman, Amy J.; Phillips, Tamara J.; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30–40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options. PMID:27031617

  12. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function.

    PubMed

    Shi, Xiao; Walter, Nicole A R; Harkness, John H; Neve, Kim A; Williams, Robert W; Lu, Lu; Belknap, John K; Eshleman, Amy J; Phillips, Tamara J; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30-40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options. PMID:27031617

  13. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE PAGESBeta

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; et al

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  14. Application for the wearable heart activity monitoring system: analysis of the autonomic function of HRV.

    PubMed

    Yang, Heui-Kyung; Lee, Jeong-Whan; Lee, Kang-Hwi; Lee, Young-Jae; Kim, Kyeong-Seop; Choi, Hee-Jung; Kim, Dong-Jun

    2008-01-01

    The wearable patch-style heart activity monitoring system (HAMS) which was used for recording ECG signal in this study is self-developed. This electrode design helps the non-restricted, non-aware and non-invasive ECG measurement. The modified bipolar electrode is convenient in use because it is designed for easy attachment and detachment with ECG measuring module by snap button. Besides, it minimizes EMI by removing the cables. In the same subjects who were exposed under stress and non-stress, the questionnaire was given out, the amount of the stress hormone was measured by blood test and the ECG signal was recorded. Through the analysis of ECG signal which is measured with wearable patch-style HAMS, the parameter highly related with mental stress were extracted from frequency and time domain. These parameters were certified as the meaningful factor after correlation analysis on the results from questionnaire and stress hormone test. Also, it is proved that the availability of wearable patch-style heart monitoring system is efficient as health monitoring system in any places and occasion. PMID:19162895

  15. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    SciTech Connect

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; May, Dalit; Johnson, Rory; Dauvillier, Jérôme; Pennacchio, Len A.; Pedrazzini, Thierry

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

  16. Form Follows Function: Advances in Trilayered Structure Replication for Aortic Heart Valve Tissue Engineering

    PubMed Central

    Simionescu, Dan T.; Chen, Joseph; Jaeggli, Michael; Wang, Bo; Liao, Jun

    2013-01-01

    Tissue engineering the aortic heart valve is a challenging endeavor because of the particular hemodynamic and biologic conditions present in the native aortic heart valve. The backbone of an ideal valve substitute should be a scaffold that is strong enough to withstand billions of repetitive bending, flexing and stretching cycles, while also being slowly degradable to allow for remodeling. In this review we highlight three overlooked aspects that might influence the long term durability of tissue engineered valves: replication of the native valve trilayered histoarchitecture, duplication of the three-dimensional shape of the valve and cell integration efforts focused on getting the right number and type of cells to the right place within the valve structure and driving them towards homeostatic maintenance of the valve matrix. We propose that the trilayered structure in the native aortic valve that includes a middle spongiosa layer cushioning the motions of the two external fibrous layers should be our template for creation of novel scaffolds with improved mechanical durability. Furthermore, since cells adapt to micro-loads within the valve structure, we believe that interstitial cell remodeling of the valvular matrix will depend on the accurate replication of the structures and loads, resulting in successful regeneration of the valve tissue and extended durability. PMID:23355946

  17. Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure.

    PubMed

    Fukui, Miho; Goda, Akiko; Komamura, Kazuo; Nakabo, Ayumi; Masaki, Mitsuru; Yoshida, Chikako; Hirotani, Shinichi; Lee-Kawabata, Masaaki; Tsujino, Takeshi; Mano, Toshiaki; Masuyama, Tohru

    2016-02-01

    While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = -0.33, p < 0.05; r = -0.28, p < 0.05, respectively), and HR (r = -0.31, p < 0.05; r = -0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction. PMID:25351137

  18. Diastolic function is associated with quality of life and exercise capacity in stable heart failure patients with reduced ejection fraction

    PubMed Central

    Bussoni, M.F.; Guirado, G.N.; Roscani, M.G.; Polegato, B.F.; Matsubara, L.S.; Bazan, S.G.Z.; Matsubara, B.B.

    2013-01-01

    Exercise capacity and quality of life (QOL) are important outcome predictors in patients with systolic heart failure (HF), independent of left ventricular (LV) ejection fraction (LVEF). LV diastolic function has been shown to be a better predictor of aerobic exercise capacity in patients with systolic dysfunction and a New York Heart Association (NYHA) classification ≥II. We hypothesized that the currently used index of diastolic function E/e' is associated with exercise capacity and QOL, even in optimally treated HF patients with reduced LVEF. This prospective study included 44 consecutive patients aged 55±11 years (27 men and 17 women), with LVEF<0.50 and NYHA functional class I-III, receiving optimal pharmacological treatment and in a stable clinical condition, as shown by the absence of dyspnea exacerbation for at least 3 months. All patients had conventional transthoracic echocardiography and answered the Minnesota Living with HF Questionnaire, followed by the 6-min walk test (6MWT). In a multivariable model with 6MWT as the dependent variable, age and E/e' explained 27% of the walked distance in 6MWT (P=0.002; multivariate regression analysis). No association was found between walk distance and LVEF or mitral annulus systolic velocity. Only normalized left atrium volume, a sensitive index of diastolic function, was associated with decreased QOL. Despite the small number of patients included, this study offers evidence that diastolic function is associated with physical capacity and QOL and should be considered along with ejection fraction in patients with compensated systolic HF. PMID:24036912

  19. Evaluation of daclizumab to reduce delayed graft function in non-heart-beating renal transplantation: a prospective, randomized trial.

    PubMed

    Wilson, C; Brook, N R; Gok, M A; Gupta, A; Asher, J F; Nicholson, M L; Talbot, D

    2005-05-01

    Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Pat